WO2003006463A1 - Acaricide - Google Patents

Abstract

An excellent acaricide which contains as the active ingredient a mixture of the optical isomers of a thiadiazole compound. The acaricide contains a mixture of the optical isomers of a thiadiazole compound represented by the following general formula (I): (I) (wherein R1 represents halogeno or lower haloalkyl and R2 represents lower alkyl), and is characterized in that the thiadiazole compound has an enantiomer excess of 60% or higher.

Description

 Specification

Acaricide

Acaricide

<Technical field>

 The present invention relates to an acaricide containing, as an active ingredient, a mixture of optical isomers of a thiadiazole compound in which the absolute configuration of the asymmetric carbon is in the R configuration and the enantiomeric excess is higher than 60%. Background technology>

 Conventionally, insecticides and acaricides for the control of two kinds of spiders have been developed and put to practical use.

 However, repeated use of these drugs has resulted in emergence of pests that have acquired resistance to various drugs. In particular, the ascidians are resistant to drugs such as a high number of eggs due to a large number of eggs laid and a short period of development, as well as a high mutation rate, low mobility, and easy inbreeding. It has the property of making it easy to develop. Due to this property, Namihadani, Kanzahadada, and Mikanhadani have acquired resistance to some extent to almost all existing drugs. Therefore, in cases where the damage by the two species is important, the development of new drugs that are highly effective against the two species that have acquired resistance to conventional dust killers has always been desired.

 On the other hand, Japanese Patent Publication No. 7-116183 (corresponding to U.S. Pat. No. 4,877,804) discloses that a thiadiazol derivative having a certain substituent has acaricidal activity. However, the publication only mentions the racemic thiadiazole derivative, and there is no specific description about the optically active form.

An object of the present invention is to provide an acaricide having a low dose and a high activity against the two kinds of clams that have hitherto been in the above-mentioned state. <Disclosure of Invention>

 The present inventors have made intensive studies on the thiadiazole derivative described in Japanese Patent Publication No. 7-116183 (corresponding to U.S. Pat. No. 4,877,804) in order to solve the above-mentioned problems. As a result, in the case of a compound having a specific structure therein, in which the absolute configuration of the asymmetric carbon is the R configuration, the acaricide is higher than the corresponding racemic form in the case of the optical isomer mixture having a specific enantiomeric excess or higher. The present inventors have found that they exhibit activity, and have reached the present invention. That is, the gist of the present invention is represented by the following general formula (I)

[Wherein, R ¹ represents a halogen atom or a lower haloalkyl group, and R ² represents a lower alkyl group. Wherein the enantiomer excess of the thiadiazole compound represented by the formula (1) is higher than 60%, and a mixture of an optical isomer of the thiadiazole compound and an acaricide containing the same as an active ingredient.

<Best mode for carrying out the invention>

 Hereinafter, the present invention will be described in detail.

 The present invention relates to an optical isomer mixture in which the enantiomeric excess of the optically active thiadiazole compound represented by the general formula (I) is higher than 60%.

In the general formula (I), R ¹ is a halogen atom such as a fluorine atom, a chlorine atom or a bromine atom; a CLCA haloalkyl group such as a fluoromethyl group, a difluoromethyl group, a trifluoromethyl group, a fluoroethyl group, Among them, a chlorine atom or a trifluoromethyl group is preferable, and a trifluoromethyl group is particularly preferable. The substitution position is preferably at the 5-position.

R ² represents an alkyl group of CL C, of which an alkyl group of CL CS is preferred. And an ethyl group is particularly preferred.

 Preferred examples of the compound represented by the above formula (I) include those in which the above-mentioned preferred substituents are combined, among which those having an enantiomeric excess of 70% or more are more preferred, and particularly preferred. More than 80%. The upper limit of the enantiomer excess is preferably 99.5%, more preferably 99.0%, further preferably 98%, and particularly preferably 97. Most preferably it is 95%.

 The enantiomer-excess optical isomer mixture of the present invention has the following general formula (π)

[Wherein, R ¹ and R ² have the same meaning as described above. ] Can be obtained by optically resolving a racemic thiazole compound represented by the formula [1] by force column chromatography using an optically active filler.

 The following general formula (III)

[Wherein, R ¹ and R ² have the same meaning as described above. ] Can be produced by subjecting the optically active hydrazine derivative represented by the formula [1] to cyclocondensation in the presence of a dehydrating agent. Examples of the dehydrating agent used here include concentrated sulfuric acid, phosphorus pentoxide, phosphorus pentasulfide, polyphosphoric acid, acetic anhydride, methanesulfonic acid and the like, and concentrated sulfuric acid is particularly preferred. This reaction is usually carried out without a solvent, but in some cases, aromatic hydrocarbons such as benzene, toluene, and quinone, methylene chloride, chloroform, 1,1,2,2-te The reaction can also be carried out in an inert solvent such as halogenated hydrocarbons such as trachlorethane or ethers such as ether, tetrahydrofuran and dioxane. The reaction temperature varies depending on the type of the dehydrating agent, but is usually about 110 to 200 ° C.

 In addition, typical methods for producing the optically active hydrazine derivative represented by the above general formula (III) typically include the following three production methods.

(Production method 1) The following general formula (IV)

[Wherein, R ¹ and R ² have the same meaning as described above. An optically active propionic acid derivative represented by the general formula (VI)

S 隱

H ₂ NNH'C OR 2

[Wherein, R ² has the same meaning as described above. And a thiocarbazic acid derivative represented by the formula:

 As the base, it is preferable to use sodium methoxide or sodium methoxide.

 The reaction is usually carried out in a solvent. Examples of the solvent include aromatic hydrocarbons such as benzene, toluene and xylene, amides such as formamide, N, N-dimethylformamide and ethers such as ether, tetrahydrofuran and dioxane. And alcohols such as methanol, ethanol and the like, and mixtures thereof.

The amount of the reagent used in the reaction is 1 to 3 mol, preferably 1 to 1.5 mol, of the thiocarbazic acid derivative represented by the general formula (V) per mol of the compound represented by the general formula (IV). , Sodium methoxide or sodium ethoxide is 1-3 mol, preferably Or 1 to 2 moles. The reaction temperature is usually -20 to 100 ° C, preferably 0 to 40 ° C.

(Production method 2) The following general formula (VI)

[Wherein, R ¹ has the same meaning as described above. The optically active phenoxypropionic acid chloride derivative represented by the formula [1] is reacted with a thiocarbazic acid derivative represented by the same general formula (V) as in the above production method 1 in the presence of a base.

 Examples of the base used in this reaction include inorganic bases such as sodium carbonate, potassium carbonate, sodium bicarbonate, potassium bicarbonate, and sodium hydride, and organic bases such as triethylamine, pyridine, and N, N-dimethylaniline. .

 The reaction is usually carried out in a solvent. Examples of the solvent include aromatic hydrocarbons such as benzene, toluene and xylene, ketones such as acetone and methylethylketone, esters such as ethyl formate and ethyl acetate, acetonitrile and propionyl. Inert solvents such as nitriles such as tolyl, formamide, amides such as N, N-dimethylformamide, ethers such as ether, tetrahydrofuran and dioxane, and mixtures thereof.

 The amount of the reagent used in the reaction is 1 to 3 mol, preferably 1 to 1 mol of the thiocarbazic acid derivative represented by the general formula (V) per mol of the compound represented by the general formula (VI).

5 mol, base is 1-3 mol, preferably 1-2 mol. The reaction temperature is usually 1 2

0 to L 0 ° C, preferably 0 to 40 ° C.

(Production method 3) The following general formula (VII) (VII)

[Wherein, R ¹ has the same meaning as described above. The optically active phenoxypropionic acid derivative represented by the formula [1] is reacted with a thiocarbazic acid derivative represented by the same general formula (V) as in the above production method 1 in the presence of a dehydrating condensing agent.

 Examples of the dehydrating condensing agent include dicyclohexyl c 3 -carbo isopropyl carbodiimide, N-ethyl-N '13 -dim o diimide,

 Thiolaminopropyl carbodiimide, difuunyl phosphoryl azide and the like. H The reaction is usually carried out in a solvent. Examples of the solvent include aromatic hydrocarbons such as benzene, toluene and xylene, and halogenated hydrocarbons such as methylene chloride, chloroform, and 1,1,2,2-tetrachloroethane. Or an inert solvent such as ethers such as ether, tetrahydrofuran, and dioxane, or a mixture thereof. The amount of the reagent used in the reaction is 1 to 3 mol, preferably 1 to 1.5 mol, of the thiocarbazic acid derivative represented by the general formula (V) per mol of the compound represented by the general formula (VII). The amount of the dehydrating condensing agent is 1 to 3 mol, preferably 1 to 2 mol. The reaction temperature varies depending on the type of dewatering agent, but is usually about 110 to 200 ° C.

The starting materials represented by the general formulas (IV), (VI) and (VII) used in the above Production Methods 1 to 3 can be obtained, for example, by the following reaction.

(VIII) (IV)

(VII) [Wherein, R ¹ and R ² have the same meanings as described above, and Z represents a halogen atom, an alkylsulfonyloxy group, or an arylsulfonyloxy group. ]

 In addition, the optically active hydrazine derivative represented by the general formula (III) may be produced by the above-mentioned production method 1 to production method 3 and then recrystallized to increase not only the chemical purity but also the optical purity. It is preferable. The optical isomer mixture of the present invention has an enantiomeric excess of 60 ° /. A higher thiazazole compound exhibits particularly excellent acaricidal activity. Specifically, it has a wide range of effects on mites such as Namihadani, Kanzadahadani, Citrus abandoned, etc., Tomato sabidad, Citrus sabidad, etc., and kills not only adults but also adults. It also has an excellent egg effect.

 The optical isomer mixture of the present invention also has a bactericidal effect against various plant pathogens such as powdery mildew, late blight, and downy mildew.

 When the optical isomer mixture of the present invention is used as an acaricide, it may be used alone, but is preferably used as a composition to which a pesticide auxiliary commonly used in the art is added. Although the dosage form of the acaricide is not particularly limited, it is preferably in the form of, for example, emulsions, wettable powders, wettable powders, aqueous solvents, liquids, flowables, powders, granules and the like. One or more of the above compounds can be blended as an active ingredient.

Agrochemical auxiliaries used for producing acaricides are, for example, substances having an effect of improving, stabilizing, dispersing, etc., for example, carriers (diluents), spreading agents, emulsifiers , A wetting agent, a dispersant, a disintegrant and the like can be used. The carrier that can be used in the acaricide composition of the present invention may be either solid or liquid as long as it is commonly used for agricultural and horticultural drugs, and is not limited to a specific one. In addition to these, various adjuvants, and if necessary, stabilizers such as antioxidants and ultraviolet absorbers and coloring agents can also be used. The effective content (%) of the active ingredient of the present invention in these preparations is selected from the range of 0.1 to 99.5%, and may be appropriately determined according to various conditions such as the form of the preparation and the method of application. For example, emulsions, wettable powders, wettable powders, For water solvents, liquids and flowables, the range can be 1-90% (% by weight; the same applies hereinafter). For powders and granules, the range can be 0.5-10%.

 The acaricide of the present invention includes other fungicides, insecticides, acaricides, herbicides, insect growth regulators, fertilizers, and soil conditioners as long as the activity of the compound of the present invention as an active ingredient is not impaired. And any other active ingredients. The method of applying the agricultural and horticultural fungicide of the present invention is not particularly limited, and it can be applied by any method such as foliage application, water surface application, soil treatment, seed treatment and the like. Examples>

 Next, the present invention will be described more specifically with reference to Production Examples, Formulation Examples, and Test Examples of the compound of the present invention, but the present invention is not limited to the following examples unless it exceeds the gist thereof. Production Example 1 (R) 12-Ethoxy 5 -— [1- [4- (5-Trifnorolelomethylylpyridine-12-yloxy) phenoxy] ethyl] Production of 1,1,3,4-thiadiazole

 2-ethoxy-5- [1- [1- [5- (5-triphnoleolomethinolepyridine-1-2-inoleoxy) phenoxy] ethyl] synthesized according to Production Example 2 described in JP-B-7-116183 ] — 1,3,4-thiadiazole (melting point: 86.6 to 87 · 4 ° C) was subjected to optically active column chromatography (filler: CH I RAL PAK AS (manufactured by Daicel Chemical), developing solvent: hexane / Isopropanol)

(R) 1-2-ethoxy-5- [1-1- [4- (5-trifluoromethylpyridine-12-yloxy) phenoxy] ethyl] -11,3,4-thiadiazole (Compound No. 1) was obtained. Purity 99.5% or more (by liquid chromatography; 254 nm) ₀ Optical purity 99.5% ee or more (by optically active column liquid chromatography). 69.8-70.8 ° C.

At the same time, it is an enantiomer (S) —2-ethoxy-5— [1- [4- (5-trifluoromethylpyridine-1-21-yloxy) phenoxy] ethyl]-1, 3, I got 4-le too. Production Example 2

 The compound No. 1 and its enantiomer obtained in Production Example 1 were dissolved in a predetermined amount in ethyl acetate and concentrated to dryness under reduced pressure to give (R) -2-ethoxy-5- [1-] having the following optical purity, respectively. [4- (5-Trifluoromethylpyridine-12-yloxy) phenoxy] ethyl] -11,3,4-thiadiazone (compounds Nos. 2 to 4) were prepared.

Next, preparation examples of the compound of the present invention will be shown. In the following, “parts” and “° / ₀ ” mean “parts by weight” and “% by weight”, respectively. Formulation Example 1 Emulsion

20 parts by weight of the compound of the present invention, solpol 3005 X (mixture of nonionic surfactant and anionic surfactant, Toho Chemical Industry Co., Ltd., trade name) ₁₅ parts by weight of xylene 35 Dissolved in a mixed solvent consisting of 30 parts by weight of methylacetamide and 30 parts by weight of the active ingredient, and 20 parts by weight of the active ingredient. /. Emulsion was obtained. Formulation Example 2 wettable powder

20 parts by weight of the compound of the present invention, Carplex # 80D (white carbon, Shionogi & Co., Ltd., trade name) 20 parts by weight, ST kaolin clay (Kaolinite, Tsuchiya Riki Olin Kogyo Co., Ltd.) Product name) 5 parts by weight, Lunox P65L (anionic surfactant, Toho Chemical Industry Co., Ltd., product name) 3 parts by weight, uniformly mixed and pulverized, active ingredient 2 0% by weight of wettable powder was obtained. Formulation Example 3 wettable powder for granules

 40 parts by weight of the compound of the present invention, ST kaolin clay (Kaolinite, Tsuchiya Kaolin Kogyo Co., Ltd., trade name) 52 parts by weight, Sorpol 90047 K (anionic surfactant, Toho Chemical Industries, Ltd.) 5 parts by weight, Lunox P65L (Anionic surfactant, Toho Chemical Co., Ltd., trade name) 3 parts by weight, kneaded, extruded, manufactured The granules (diameter 0.8 mm) were dried and sized to obtain 40% by weight of a water dispersible granule. Formulation Example 4 Flowable

20 parts by weight of the compound of the present invention, 5 parts by weight of Sorpol 904 K, 5 parts by weight of Sorbon T-120 (nonionic surfactant, Toho Chemical Industry Co., Ltd., trade name) 3 parts by weight, ethylene glycol 8 parts by weight of water 54 wet parts of 4 parts by weight, 1 weight of this slurry mixture. / ₀ Xanthan gum (natural polymer) Aqueous solution (10 parts by weight) was added and mixed well to obtain a flowable substance having an active ingredient of 20% by weight / ₀ . Next, the effects of the acaricide of the present invention will be described with reference to specific test examples. Test example 1 Acaricidal effect on eggs of Nami-Nada two

 On the leaf disk (3 cm in diameter) of the kidney beans, five adult females were released. After release, eggs were laid on leaf disks for 20 hours, and then female adults were removed. Using a rotary spray tower (manufactured by Mizuho Rika), 3.5 ml of a solution prepared by diluting the agricultural and horticultural acaricide of the present invention prepared according to the formulation of Preparation Example 1 to a predetermined concentration with water was placed on the above disk. Sprayed. (1 concentration, 2 replicates). Eight days after the treatment, the number of unhatched eggs and the number of hatched larvae were examined to determine the ovality (%). Table 2 shows the results.

The same evaluation was performed using the racemic compound corresponding to the compound No. 1 as Comparative Example A, and the results are shown in Table 2. Table 2

As is evident from Table 2, the acaricide containing the optical isomer mixture of the present invention as an active ingredient is different from the racemic form only when the content of the specific optical isomer (R configuration) is higher than 60% ee. It shows that it shows excellent effect, and shows higher acaricidal activity at 80 ° / oee or more. Although the present invention has been described in detail and with reference to specific embodiments, it will be apparent to those skilled in the art that various changes and modifications can be made without departing from the spirit and scope of the invention.

 This application is based on a Japanese patent application filed on July 13, 2001 (Japanese Patent Application No. 2001-213082), the contents of which are incorporated herein by reference. Industrial applicability>

 According to the present invention, an excellent mixture of optical isomers can be obtained as an acaricide for agricultural and horticultural use.

Claims

Scope of request General formula (I) below

[In the formula, R ¹ represents a nitrogen atom or a lower haloalkyl group, and R ² represents a lower alkyl group. ] An optical isomer mixture of a thiadiazole compound, wherein the thiadiazole compound represented by the formula (1) has an enantiomeric excess of more than 60%.

2. The optical isomer mixture according to claim 1, wherein the enantiomeric excess is 70% or more.

3. The optical isomer mixture according to claim 1, wherein the enantiomeric excess is 80% or more.

4. The optical isomer mixture according to any one of claims 1 to 3, wherein the substitution position of R ¹ is the 5-position.

5. An acaricide comprising the optical isomer mixture according to any one of claims 1 to 4 as an active ingredient.