JPH09194465A - Cyclopropanecarboxylic amide derivative and microbicidal agent for agricultural and horticultural purposes - Google Patents

Abstract

PROBLEM TO BE SOLVED: To obtain a cyclopropanecarboxylic amide derivative which has a wide range of microbicidal spectrum, particularly manifests very excellent microbicidal activity against rice blast disease without injury to useful crop plants and is useful as an active ingredient for microbicidal agent for agricultural and horticultural purposes. SOLUTION: This cyclopropanecarboxylic amide derivative is represented by formula I [R<1> -R<5> are each H, an alkyl, cyano, a halogen; R<6> is H, an alkyl; R<7> is H, methyl; X is H, an alkyl, a halogen, an alkoxy, cyano, nitro, trifluoromethyl; (m) and (n) are each an integer of 1 or 2; A is O atom, S atom, group NR<8> (R<8> is H, an alkyl, an acyl), typically 2,2-dichloro-1-ethyl-N-[(R)-1-(6- fluoro-2-benzothiazolyl)-ethyl]-3-methylcyclopropanecarboxylic amide. The compound of formula I is prepared, for example, by reaction of a compound of formula II (Q is a halogen, hydroxyl) with an amine of formula III, when necessary, in the presence of a base or a condensing agent.

Description

Detailed Description of the Invention

[0001]

TECHNICAL FIELD The present invention relates to a cyclopropanecarboxylic acid amide derivative and an agricultural and horticultural fungicide containing the same as an active ingredient.

[0002]

2. Description of the Prior Art It is already known that N-aralkylcyclopropanecarboxylic acid amide derivatives and N-heteroarylalkylcyclopropanecarboxylic acid amide derivatives have bactericidal activity. (JP-A 61-15867, JP-A 61-18751, JP-A 62-201855, JP-A 63-5)
However, there is no description of a cyclopropanecarboxylic acid amide derivative having a condensed heterocycle such as benzothiazole, benzoxazole, or benzimidazole in the amine part.

[0003]

SUMMARY OF THE INVENTION It is an object of the present invention to provide a novel fungicide having excellent bactericidal activity.

[0004]

[Means for Solving the Problems] The present inventors synthesized various cyclopropanecarboxylic acid amide derivatives and examined their physiological activities. The compounds of the present invention have a broad bactericidal spectrum, and especially in rice blast disease. On the other hand, they have an extremely excellent bactericidal activity and have found no harm to useful crops, and thus completed the present invention. That is,
The present invention provides a compound represented by the general formula [I]:

[0005]

Embedded image [In the formula, R ¹ , R ² , R ³ , R ⁴ and R ⁵ each represent a hydrogen atom, an alkyl group, a cyano group or a halogen atom, R ⁶ represents a hydrogen atom or an alkyl group, and R ⁷ represents a hydrogen atom. Or a methyl group, X is a hydrogen atom, an alkyl group,
Represents a halogen atom, an alkoxy group, a cyano group, a nitro group, a trifluoromethyl group, an alkoxyalkyl group or an acyl group, m and n each represent an integer of 1 or 2,
A represents an oxygen atom, a sulfur atom or a group> NR ⁸ (R ⁸ represents a hydrogen atom, an alkyl group, an alkoxyalkyl group or an acyl group). ] A cyclopropanecarboxylic acid amide derivative represented by the following, and an agricultural and horticultural germicide containing these cyclopropanecarboxylic acid amide derivatives as active ingredients.

The definitions of terms used in this specification are shown below.

The alkyl group refers to an alkyl group having a straight or branched chain having 1 to 6 carbon atoms, and examples thereof include a methyl group, an ethyl group, a propyl group, an isopropyl group, a butyl group, an isobutyl group and a sec-butyl group. Group, tert-butyl group, pentyl group, 1-methylbutyl group, 2-methylbutyl group, 3-methylbutyl group, 2,2-dimethylpropyl group, 1,1-dimethylpropyl group, 1-ethylpropyl group, hexyl group, Examples thereof include an isohexyl group.

The halogen atom means a fluorine atom, a chlorine atom, a bromine atom or an iodine atom.

The alkoxyalkyl group has a carbon number of 2 to
6 represents an alkoxyalkyl group having a straight chain or a branched chain of 6, for example, methoxymethyl group, ethoxymethyl group, propoxymethyl group, isopropoxymethyl group, butoxymethyl group, isobutoxymethyl group, sec-butoxymethyl group, methoxy. Examples thereof include ethyl group and ethoxyethyl group.

The acyl group means an acetyl group, a benzoyl group and the like.

In the general formula [I], preferred compounds include R ¹ , R ² , R ³ , R ⁴ and R ⁵ being hydrogen atoms,
Represents a methyl group, an ethyl group or a chlorine atom, R ⁶ represents a methyl group, R ⁷ represents a hydrogen atom, X represents a fluorine atom, m represents 1, n represents 1, and A represents a sulfur atom. And a compound represented by.

The compound of the present invention represented by the general formula [I] is
Some have two or more asymmetric carbons in the molecule, and these compounds have various enantiomers and diastereomers. These can be split in any suitable way. The present invention includes these individual enantiomers, diastereomers and mixtures thereof.

[0013]

BEST MODE FOR CARRYING OUT THE INVENTION Specific examples of the compound of the present invention represented by the general formula [I] are shown in Tables 1 to 3. However, the compounds of the present invention are not limited to these compounds. The compound numbers will be referred to in the following description. In addition, compound 6 and compound 17, compound 8 and compound 9, compound 10 and compound 11, compound 12 and compound 1
3, compound 26 and compound 27, compound 28 and compound 6
3, compound 32 and compound 65, compound 33 and compound 66
Compound 70 and compound 71 are corresponding diastereomers. In addition, compound 20 is a diastereomer alone separated from compound 57, which is a corresponding mixture of diastereomers. The steric configuration in the table means the steric configuration at the 1-position of the amine moiety.

[0014]

[Table 1]

[0015]

[Table 2]

[0016]

[Table 3]

The compound of the present invention represented by the general formula [I] is
For example, it can be manufactured according to the following manufacturing method.

[0018]

Embedded image

(Wherein R ¹ , R ² , R ³ , R ⁴ , R ⁵ ,
R ⁶ , R ⁷ , A, X, m and n have the same meanings as described above, and Q represents a halogen atom or a hydroxyl group. ) The compound [I] of the present invention is obtained by reacting the cyclopropanecarboxylic acid derivative represented by the general formula [II] with the amine represented by the general formula [III], if necessary, in the presence of a base or a condensing agent. Can be manufactured by.

This reaction is usually carried out in a solvent, and any solvent can be used as long as it does not inhibit the reaction, and examples thereof include pentane, hexane, heptane, cyclohexane,
Hydrocarbons such as petroleum ether, ligroin, benzene, toluene and xylene, halogenated hydrocarbons such as dichloromethane, dichloroethane, chloroform, carbon tetrachloride, chlorobenzene and dichlorobenzene, diethyl ether, diisopropyl ether, ethylene glycol dimethyl ether, tetrahydrofuran, Ethers such as dioxane, acetone, methyl ethyl ketone, methyl isopropyl ketone, ketones such as methyl isobutyl ketone, methyl acetate, esters such as ethyl acetate, acetonitrile, propionitrile, nitriles such as benzonitrile, and further dimethyl sulfoxide, An aprotic polar solvent such as N, N-dimethylformamide or sulfolane and a mixed solvent obtained by combining a solvent selected from these can be used.

Examples of the base include alkali metal hydroxides such as sodium hydroxide and potassium hydroxide, alkaline earth metal hydroxides such as calcium hydroxide, and alkali metal carbonates such as sodium carbonate and potassium carbonate. , Sodium tert-butoxide, potassium tert
-Alkali metal alkoxides such as butoxide, and further triethylamine, trimethylamine, dimethylaniline, pyridine, N-methylpiperidine, 1,5-diazabicyclo [4.3.0] non-5-ene (DBN),
1,8-diazabicyclo [5.4.0] undec-7-
Examples thereof include amines such as ene (DBU).

As the condensing agent, N, N'-dicyclohexylcarbodiimide, carbonyldiimidazole,
1-ethyl-3- (3-dimethylaminopropyl) hydrochloride
Carbodiimide, 2-chloro-1,3-dimethylimidazolium chloride and the like can be mentioned. Reaction temperature is -20 ℃
To 80 ° C, preferably 0 ° C to 50 ° C.

Various methods are conceivable for producing the compound [II] and the compound [III] as starting materials. Compound [II] can be obtained, for example, from The Journal of Organic Chemistry (J. Org. Chem.) No. 2
Volume 8, page 1404 (1963)
It can be produced from methyl acrylate and dichlorocarbene. Compound [III] is commercially available from, for example, Journal of the American Chemical Society (JA
mer. Chem. Soc. ) According to the method described in Vol. 93, page 2897 (1971), an acetyl group can be converted into a 1-aminoethyl group for production. Also,
Compound [III] can be produced from 2-amino (thio) phenols and an amino acid derivative according to the method described in the specification of Japanese Patent Application No. 7-97990, for example.

[0024]

EXAMPLES Next, the production method, formulation method and use of the compound of the present invention will be specifically described with reference to examples.

Production Example 1 2,2-Dichloro-1-ethyl-N-[(R) -1- (6-fluoro-2-benzothiazolyl) ethyl] -3-methylcyclopropanecarboxylic acid amide (Compound No. 2) Manufacturing method of (R) -1- (6-fluoro-2-benzothiazolyl) ethylamine 0.4 g and N in 30 ml of diethyl ether.
0.3 g of methylpiperidine was dissolved. 0.5 g of 2,2-dichloro-1-ethyl-3-methylcyclopropanecarbonyl chloride dissolved in 5 ml of diethyl ether was added dropwise to this solution under ice cooling. After stirring at room temperature for 2 hours, the reaction mixture was poured into 50 ml of water, and after liquid separation, the organic layer was washed with 10% hydrochloric acid, saturated aqueous sodium hydrogen carbonate solution and water in this order, and dried over magnesium sulfate. The solvent was concentrated under reduced pressure, and the obtained residue was subjected to silica gel column chromatography (eluting solvent: hexane / ethyl acetate = 4 /
Purification in 1) yielded 0.2 g (yield 22%) of the desired product as a colorless glassy substance.

¹ H-NMR (CDCl ₃ ) δ: 1.02
(3H, t), 1.25 (3H, d), 1.63 (1
H, m), 1.72 (3H, m), 2.06 (1H,
m), 2.27 (1H, q), 5.53 (1H, m),
6.65 (1H, dd), 7.21 to 7.97 (3H,
m) ppm

Production Example 2 N-[(R) -1- (2-benzothiazolyl) ethyl] -2,2-dichloro-1,3
Method for producing 3-trimethylcyclopropanecarboxylic acid amide (Compound No. 8 and Compound No. 9) 0.4 g of (R) -1- (2-benzothiazolyl) ethylamine and 0.3 g of N-methylpiperidine were dissolved in 30 ml of diethyl ether. . 2,2-Dichloro-1, dissolved in 5 ml of diethyl ether, was added to this solution under ice cooling.
0.5 g of 3,3-trimethylcyclopropanecarbonyl chloride was added dropwise. After stirring at room temperature for 2 hours, the reaction mixture was poured into 50 ml of water and the organic layer was separated by 10%.
Wash hydrochloric acid, saturated aqueous sodium hydrogen carbonate solution, and water in this order,
Dried over magnesium sulfate. The solvent is concentrated under reduced pressure,
The obtained residue was purified by silica gel column chromatography (eluting solvent: hexane / ethyl acetate = 4/1) and separated into two fractions. 0.2 g of the target substance as a white powder having a melting point of 125 to 126 ° C.
(Compound No. 8 yield 25%), melting point 159-from the other
0.3 g (compound No. 9 yield 38%) of the target substance of white powder showing 161 ° C. was obtained.

Production Example 3 N-[(R) -1- (2-benzothiazolyl) ethyl] -2,2,3,3-tetramethylcyclopropanecarboxylic acid amide (Compound No. 15)
Manufacturing method of 2,2,3,3-tetramethylcyclopropanecarboxylic acid 0.5 g was dissolved in 30 ml of chloroform, and hydrochloric acid 1-
0.8 g of ethyl-3- (3-dimethylaminopropyl) carbodiimide was added, and the mixture was stirred at room temperature for 30 minutes. (R) -1-dissolved in 5 ml of chloroform in this solution
0.7 g of (2-benzothiazolyl) ethylamine was added dropwise. After stirring at room temperature for 2 hours, the reaction mixture was mixed with 50 m of water.
After pouring into 1 l and separating the layers, the organic layer was washed with 10% hydrochloric acid, saturated aqueous sodium hydrogen carbonate solution and water in this order, and dried over magnesium sulfate. The solvent was concentrated under reduced pressure, and the obtained residue was purified by silica gel column chromatography (eluting solvent: hexane / ethyl acetate = 4/1), melting point 86-87.
As a result, 0.2 g (yield 20%) of the target product was obtained as a white powder having a temperature of 0 ° C.

Production Example 4 N-[(RS) -1- (2-benzoxazolyl) ethyl] -2,2-dichloro-1-
Method for producing ethyl-3-methylcyclopropanecarboxylic acid amide (Compound No. 26 and Compound No. 27) In 30 ml of diethyl ether, 0.5 g of (RS) -1- (2-benzoxazolyl) ethylamine and 0 of N-methylpiperidine. 0.4 g was dissolved. 2,2-Dichloro-1 dissolved in 5 ml of diethyl ether was added to this solution under ice cooling.
0.5 g of -ethyl-3-methylcyclopropanecarbonyl chloride was added dropwise. After stirring at room temperature for 2 hours, the reaction mixture was poured into 50 ml of water, and the organic layer was separated by 10 layers.
% Hydrochloric acid, saturated aqueous sodium hydrogen carbonate solution, and water in this order, and dried over magnesium sulfate. The solvent was concentrated under reduced pressure, the obtained residue was purified by silica gel column chromatography (eluting solvent: hexane / ethyl acetate = 4/1), and further, high performance liquid chromatography (YMC-0).
63-15, elution solvent: hexane / ethyl acetate = 1 /
In 1), two fractions were separated. 0.3 g of a white powder target product having a melting point of 138 to 139 ° C.
(Compound No. 26, yield 30%), melting point 157 from the other
0.4 g (compound No. 27, yield 40%) of a white powder having a temperature of ˜158 ° C. was obtained.

Production Example 5 2,2-Dichloro-1-ethyl-3-methyl-N-[(R) -1- (6-methyl-2-
Method for producing benzothiazolyl) ethyl] cyclopropanecarboxylic acid amide (Compound Nos. 20 and 57) 20 ml of toluene was charged with 0.74 g of (R) -1- (6-methyl-2-benzothiazolyl) ethylamine and 0.35 g of N-methylpiperidine. Dissolved. To this solution, 2,2-dichloro-1-ethyl-3-methylcyclopropanecarbonyl chloride dissolved in 5 ml of toluene under ice cooling was added.
80 g was added dropwise. After stirring at room temperature for 2 hours, the reaction mixture was poured into 50 ml of water, and after liquid separation, the organic layer was washed with 10% hydrochloric acid, saturated aqueous sodium hydrogen carbonate solution and water in this order, and dried over magnesium sulfate. The solvent was concentrated under reduced pressure, the obtained crude crystals were washed with hexane / diisopropyl ether, and 0.14 g (compound No. 57) of a flesh-colored target product which is one of the diastereomers showing a melting point of 151 to 154 ° C.
Yield 10%) was obtained. Further, the filtrate was concentrated under reduced pressure,
Crystallized with hexane / diisopropyl ether, 0.33 g (compound No. 20, yield 2) of a white powder of a diastereomer mixture having a melting point of 120 to 122 ° C.
4%).

Including Production Example 1 to Production Example 5, Tables 4 to 6
Examples of physical properties of the compound of the present invention are shown in.

[0032]

[Table 4]

[0033]

[Table 5]

[0034]

[Table 6]

The agricultural / horticultural germicide of the present invention comprises a cyclopropanecarboxylic acid amide derivative represented by the general formula [I] as an active ingredient. When the compound of the present invention is used as an agricultural and horticultural fungicide, the active ingredient can be used in an appropriate dosage form according to the purpose. Usually, the active ingredient is diluted with an inert liquid or solid carrier, and if necessary, a surfactant and the like are added thereto, and powders, wettable powders, emulsions,
It can be used in the form of preparations such as granules.

Suitable carriers include, for example, solid carriers such as talc, bentonite, clay, kaolin, diatomaceous earth, white carbon, vermiculite, slaked lime, silica sand, ammonium sulfate and urea, liquid carriers such as isopropyl alcohol, xylene, cyclohexanone and methylnaphthalene. Etc. As the surfactant and dispersant, for example, dinaphthyl methanesulfonate, alcohol sulfate, alkylaryl sulfonate, lignin sulfonate,
Polyoxyethylene glycol ether, polyoxyethylene alkyl aryl ether, polyoxyethylene sorbitan monoalkylate and the like can be mentioned. Examples of the auxiliary include carboxymethyl cellulose. These preparations are diluted to an appropriate concentration and then sprayed or applied directly.

The fungicide for agricultural and horticultural use of the present invention can be used by foliage application, soil application or water surface application. The compounding ratio of the active ingredient is appropriately selected according to need, but is 0.1 to 20% (by weight) in the case of powder and granules, and 5 to 80% (by weight) in the case of emulsion and wettable powder. Appropriate.

The application rate of the agricultural / horticultural fungicide of the present invention varies depending on the type of compound used, target disease, tendency of occurrence, degree of damage, environmental conditions, dosage form used and the like. For example, when used as is, such as powders and granules,
The active ingredient may be appropriately selected from the range of 0.1 g to 5 kg, preferably 1 g to 1 kg per 10 ares. When used in liquid form such as emulsions and wettable powders, 0.1
ppm to 10,000 ppm, preferably 10 to 3.0 ppm
It is better to select from the range of 00 ppm as appropriate.

The fungicide for agricultural and horticultural use according to the present invention has the above-mentioned application form.
a) genus, for example Pyricularia
oryzae) Venturia genus,
For example, Venturia inaequal
plant diseases caused by is) can be controlled.

Furthermore, the agricultural and horticultural fungicides according to the present invention may be mixed with insecticides, other fungicides, herbicides, plant growth regulators, fertilizers and the like, if necessary. Next, the formulation method will be specifically described with reference to typical formulation examples of the agricultural and horticultural germicide of the present invention. In the following description, “%” indicates weight percentage.

Formulation Example 1 Dusts 2% of the compound (2), 5% of diatomaceous earth and 93% of clay were uniformly mixed and pulverized to obtain a dust. Formulation Example 2 Wettable powder Compound (8) 50%, diatomaceous earth 45%, sodium dinaphthylmethanedisulfonate 2% and sodium ligninsulfonate 3% were uniformly mixed and ground to obtain a wettable powder. Formulation Example 3 Emulsion Compound (26) 30%, cyclohexanone 20%, polyoxyethylene alkylaryl ether 11%, calcium alkylbenzene sulfonate 4% and methylnaphthalene 35% were uniformly dissolved to obtain an emulsion. Formulation Example 4 Granules Compound (20) 5%, lauryl alcohol sulfate sodium salt 2%, sodium lignin sulfonate 5
%, Carboxymethylcellulose 2% and clay 86%
Is uniformly mixed and pulverized. To this mixture, 20% of water was added and kneaded, processed into granules of 14 to 32 mesh using an extrusion type granulator, and then dried to obtain granules.

Next, the effects of the fungicide for agricultural and horticultural use of the present invention will be specifically described with reference to test examples.

Test Example 1 Rice blast preventive effect test Approximately 15 rice seeds (cultivar: Aichi Asahi) were placed in a clay pot with a diameter of 7 cm.
Each seed was sown and grown in a greenhouse for 2 to 3 weeks. A wettable powder prepared according to Formulation Example 2 was diluted with water so that the active ingredient concentration became 500 ppm, and the rice seedling having the fourth leaf completely developed was sprayed with 10 ml per pot. After air-drying, a conidia suspension of rice blast fungus (Pyricularia oryzae) was spray-inoculated and immediately placed in a 25 ° C moist chamber for 24 hours. Then, it was transferred to a greenhouse, and 5 days after the inoculation, the number of lesions on the fourth leaf was counted, the control value was calculated according to the equation 1, and the evaluation was given according to the criteria in Table 7. The results are shown in Table 8.

[0044]

[Equation 1]

[0045]

[Table 7]

[0046]

[Table 8]

Test Example 2 Water blast application test for rice blast disease Into a white porcelain bowl having a diameter of 9 cm, 1.5 leaf stage paddy rice (cultivar: Aichi Asahi) seedlings were transplanted at 3 sites at 4 sites and grown in a greenhouse. The wettable powder prepared according to Formulation Example 2 at the 2.5 leaf stage was subjected to water application to a pot such that the active ingredient concentration was 300 g per 10 ares. Ten days after the treatment, a conidia spore suspension of rice blast fungus (Pyricularia oryzae) was spray-inoculated and immediately placed in a 25 ° C moist chamber for 24 hours. After that, it was transferred to a greenhouse, and 5 days after the inoculation, the number of lesions on the highest leaf at the time of inoculation was counted, and the control value was calculated according to Equation 1. The results are shown in Table 9.

[0048]

[Table 9]

Test Example 3 Test for Preventing Apple Black Blight Disease Apple seeds (variety: red ball) in a 9 cm × 9 cm PVC pot
5 seeds were sown and grown in a greenhouse for 20 days. On seedlings with four true leaves spread, a wettable powder prepared according to Formulation Example 2 was diluted with water so that the concentration of the active ingredient was 500 ppm, and 20 ml was sprayed per pot. After air-drying, a spore suspension of apple scab (Venturia inaequalis) was spray-inoculated and immediately placed in a humid chamber at 22 ° C.
I put in time. After that, it was transferred to a greenhouse, and 14 days after the inoculation, the degree of disease of each true leaf was examined according to the criteria shown in Table 10. The results are shown in Table 11. As a comparative drug, the compound shown in Chemical formula 4 (described in JP-A-6-157499) was similarly prepared and tested.

[0050]

[Table 10]

[0051]

Embedded image

[0052]

[Table 11]

 ─────────────────────────────────────────────────── ─── Continuation of the front page (72) Inventor Katsumi Furuse 1809 Kamo, Kikugawa-cho, Ogasa-gun, Shizuoka Prefecture (72) Inventor Yoshiyuki Kojima 69 Takagosho, Kakegawa City, Shizuoka Prefecture (72) Inventor Kensuke Muramatsu Kakegawa City, Shizuoka Prefecture 11 from 3-15 Katsugaoka

Claims (2)

[Claims] 1. A compound of the general formula [I] [In the formula, R ¹ , R ² , R ³ , R ⁴ and R ⁵ each represent a hydrogen atom, an alkyl group, a cyano group or a halogen atom, R ⁶ represents a hydrogen atom or an alkyl group, and R ⁷ represents a hydrogen atom. Or a methyl group, X is a hydrogen atom, an alkyl group,
Represents a halogen atom, an alkoxy group, a cyano group, a nitro group, a trifluoromethyl group, an alkoxyalkyl group or an acyl group, m and n each represent an integer of 1 or 2,
A represents an oxygen atom, a sulfur atom or a group> NR ⁸ (R ⁸ represents a hydrogen atom, an alkyl group, an alkoxyalkyl group or an acyl group). ] The cyclopropane carboxylic acid amide derivative shown by these. 2. A fungicide for agricultural and horticultural use containing the cyclopropanecarboxylic acid amide derivative according to claim 1 as an active ingredient.