JP3030498B2 - Indole-2-carboxylic acid ester derivatives and fungicides for agricultural and horticultural use containing the derivatives as active ingredients - Google Patents

Description

DETAILED DESCRIPTION OF THE INVENTION

[0001]

TECHNICAL FIELD The present invention relates to an indole-2-carboxylic acid ester derivative and a fungicide for agricultural and horticultural use containing the derivative as an active ingredient.

[0002]

2. Description of the Related Art In the cultivation of agricultural and horticultural crops, many control agents are used against crop diseases, but the control effect is insufficient or the effect is limited by the emergence of drug-resistant bacteria. However, it is not always a satisfactory fungicide because it causes phytotoxicity and contamination of plants, or is highly toxic to humans and fishes. Therefore, there is a strong demand for a drug which has few such disadvantages and can be used safely.

[0003] To date, several compounds related to the indole-2-carboxylic acid ester derivatives of the present invention are known. For example, WO 94/13637 describes the following compounds (A) and (B), and discloses that these compounds are useful as medicaments.

[0004]

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[0005]

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[0006] WO 95/13266 describes the following compound (C) and discloses that the compound is useful as a medicament.

[0007]

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[0008] However, there has been no report on the agricultural and horticultural fungicidal activity of these compounds themselves.

[0009]

Problems to be Solved by the Invention Methyl 1- (butylcarbamoyl) benzimidazol-2-ylcarbamate [trade name: benomyl], 2- (2-furyl) benzimidazole [trade name: fveridazole], 2- (4) −
Thiazolyl) benzimidazole [trade name: thiabendazole], methyl benzimidazole-2-ylcarbamate [trade name: carbendazim], 1,2-bis [3-methoxycarbonyl-2-thioureido) benzene [trade name: thiophanate methyl] And benzimidazoles such as 1,2-bis (ethoxycarbonyl-2-thioureido) benzene [trade name: thiophanate]
The thiophanate fungicide has an excellent control effect on various pathogens parasitic on agricultural and horticultural crops, and has been widely used as an agricultural and horticultural fungicide since about 1970, and has greatly contributed to increasing crop production. However, when these fungicides are continuously applied to crops, the control effect of the fungicides is reduced, and it often happens that the fungicides cannot be practically used. If the expected control effect is not obtained even if the fungicide is applied, and the occurrence of disease cannot be suppressed,
Damage to drug users such as farmers is enormous. Further, it is known that bacteria exhibiting resistance to any one of the benzimidazole / thiophanate fungicides also become resistant to other fungicides in this group, and exhibit so-called cross-resistance. Therefore, for example, in a field where the control effect is not recognized even if benomyl is applied, the control effect cannot be expected even if other benzimidazole / thiophanate fungicides are applied. The use of benzimidazole / thiophanate fungicides must be stopped in fields where drug-resistant bacteria are widespread, but there are many known cases in which the density of drug-resistant bacteria does not decrease even after the use is stopped. When resistant bacteria develop, they will be affected for a long time. In such a field, the drug-resistant bacterium sprays a fungicide of another strain that does not show cross-resistance to control the disease, but a fungicide that exhibits the same control effect as the benzimidazole thiophanate fungicide. Is extremely low, making precise control difficult.

[0010]

Means for Solving the Problems In consideration of the above circumstances, the present inventors can expect that a fungicide having a bactericidal effect against drug-resistant bacteria can be expected to have a high disease control effect in a field where drug-resistant bacteria are generated. As a result of intensive efforts to develop a fungicide having such properties, it was found that the indole-2-carboxylic acid ester derivative represented by the following general formula (1) exhibits a high fungicidal effect on drug-resistant bacteria. We have found and completed the present invention here.

That is, the present invention provides a compound represented by the general formula

[0012]

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[Wherein R ¹ represents a C _1-4 alkoxycarbonyl group, a carbamoyl group, a mono (C _1-4 alkylamino) carbonyl group or a cyano group. R ² is a hydrogen atom or C
_{1-4 represents} an alkyl group. R ³ and R ⁴ are the same or different and each represents a hydrogen atom, a C _1-4 alkyl group, a halogen atom,
_{1-4 represents an} alkoxy group. Indole-2 represented by
-It relates to a fungicide for agricultural and horticultural use containing a carboxylic acid ester derivative as an active ingredient.

The compound of the present invention represented by the above general formula (1) exerts a high bactericidal effect on drug-resistant bacteria as evident from the test examples described later, and thus is effective against diseases caused by drug-resistant bacteria. Thus, an excellent control effect can be exhibited.

Further, the compound of the present invention represented by the above general formula (1) does not cause phytotoxicity or pollution to plants, and has low toxicity to humans, livestock and fishes.

The indole represented by the above general formula (1)
Among the 2-carboxylic acid ester derivatives, the following general formula (1)
The indole-2-carboxylic acid ester derivative represented by a) is a novel compound not described in any literature.

[0017]

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[In the formula, R ¹ represents a C _1-4 alkoxycarbonyl group, a carbamoyl group, a mono (C _1-4 alkylamino) carbonyl group or a cyano group. R ² is a hydrogen atom or C
_{1-4 represents} an alkyl group. R ³ and R ⁴ are the same or different and each represents a hydrogen atom, a C _1-4 alkyl group, a halogen atom,
_{1-4 represents an} alkoxy group. However, when R ³ and R ⁴ are not both hydrogen atoms, and one of R ³ and R ⁴ is a C _1-4 alkoxy group and the other is a hydrogen atom, the alkoxy group is located at the 5-position of the indole skeleton. Must not be bonded, and when R ³ and R ⁴ are both chlorine atoms, these chlorine atoms must not be bonded to the 4- and 6-positions of the indole skeleton. ]

[0019]

BEST MODE FOR CARRYING OUT THE INVENTION Specific examples of each group represented by the above general formula (1) are as follows.

The C _1-4 alkoxycarbonyl group includes
For example, a methoxycarbonyl group, an ethoxycarbonyl group,
n-propoxycarbonyl group, iso-propoxycarbonyl group, n-butoxycarbonyl group, iso-butoxycarbonyl group, sec-butoxycarbonyl group, te
rt-butoxycarbonyl group and the like.

Examples of the mono (C _1-4 alkylamino) carbonyl group include a monomethylaminocarbonyl group, a monoethylaminocarbonyl group, a mono-n-propylaminocarbonyl group, a mono-iso-propylaminocarbonyl group and a mono-n -Butylaminocarbonyl group, mono-
Examples thereof include an iso-butylaminocarbonyl group, a mono-sec-butylaminocarbonyl group, and a mono-tert-butylaminocarbonyl group.

Examples of the C _1-4 alkyl group include a methyl group, an ethyl group, an n-propyl group, an isopropyl group,
Examples thereof include an n-butyl group, a sec-butyl group, and a tert-butyl group.

Examples of the halogen atom include a fluorine atom,
Examples include a chlorine atom, a bromine atom and an iodine atom.

Examples of the C _1-4 alkoxy group include a methoxy group, an ethoxy group, an n-propoxy group, an iso-propoxy group, an n-butoxy group, an iso-butoxy group, a se
c-butoxy group, tert-butoxy group and the like.

The compound of the present invention represented by the above general formula (1) is effective for controlling a drug-resistant bacterium in a field which is expected to appear by using a benzimidazole / thiophanate fungicide or a field in which it appears. Can be used. The compound of the present invention is, for example, a powdery mildew fungus (Podo) of apple.
sphaera leucotricha), apple scab (Venturia inaequalis),
Apple black spot fungus (Mycosphaerella po
mi), Apple brown spot fungus (Marssonina ma)
li), apple monilia disease fungus (Selerotinia)
mali), oyster powdery mildew (Phyllactin)
ia kicola), oyster anthracnose (Gloeo)
sporium kaki), Peach gray rot (Sele)
rotinia cinerea, peach scab (C)
ladosporium carpophilum),
Phomopsis rot fungus (Phomopsis s)
p. ), Grape gray mold fungus (Botrytis ci)
nerea), grape brown spot fungus (Cercospora)
viticola), Grape powdery mildew (Unci)
nula necrotor, grape black rot fungus (El)
sinoe ampelina, grape late-rot fungus (G
lomerella singulata, sugar beet brown spot fungus (Cercospora beticol)
a), peanut brown spot fungus (Cercospora a
rachidicola, peanut black rot (Cer)
cospola personata), barley powdery mildew (Erysiphe graminis), barley eye spot disease (Cercosporella herp)
otrichoides), barley red snow rot fungus (F
usarium nivale, wheat powdery mildew (Erysiphe graminis), cucumber powdery mildew (Sphaerotheca fuligi)
nae), Cucumber vine wilt (Mycosphaer)
ella melonis), Cucumber sclerotium fungus (So
lerotinia sclerotiorum, cucumber gray mold fungus (Botrytis cinere)
a), Cucumber scab (Cladosporium c)
ucumerum, tomato leaf mold fungus (Clad)
osporium fuvum), tomato gray mold (Botrytis cinerea), eggplant black mold (Corynespora melongenae),
Strawberry powdery mildew (Sphaerotheca hu)
muli), Fusarium ox
ysporum), onion gray rot fungus (Botry)
tis alli), Lettuce sclerotium (Sclerot)
inia sclerotiorum, celery spot rot (Cercospora apii), kidney bean spot rot (Phaeoisariopsis griseo)
la), kidney bean sclerotium (Sclerotinia)
sclerotiorum), hop gray mold (B)
otrytis cinerea), tobacco powdery mildew (Erysiphe cicholaceau)
m), rose scab (Diplocarpon ros)
ae), citrus scab (Elsinoe fwc)
etti), Citrus blue mold (Penicilliu)
m. italicum), Citrus green mold (Peni)
For example, various fungi such as C. digitatum, which are resistant to a drug such as a benzimidazole / thiophanate fungicide, can be suitably used for controlling bacteria.

The compound of the present invention represented by the above general formula (1) can be produced by various methods. A typical production method is described below.

[0027]

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Wherein R ³ and R ⁴ are as defined above. R ^{2 ′} represents a C _1-4 alkyl group. R ⁵ represents a C _1-4 alkyl group. X represents a halogen atom or a leaving group such as toluenesulfonic acid ester. According to Reaction Formula-1, the compound (1-1) of the present invention in which R ¹ represents a C _1-4 alkoxycarbonyl group and R ² represents a C _1-4 alkyl group is represented by the general formula (2) Indole-2 represented
3-formylindole-2-carboxylic acid ester represented by the general formula (3) obtained by formylating a carboxylic acid ester is converted to a compound represented by the general formula (4) in an appropriate solvent such as ethanol in the presence of a base. Hydroxylamine-O
Produced by reacting with an alkyl ether or a hydrochloride thereof.

Compounds of the general formula (2) are described, for example, in the Journal of the American Chemical Society (J. Amer. Chem. Soc.), 90 , 286.
9 (1968), Synthesis (Synthesis),
186 (1985).

The compound (1-2) of the present invention wherein R ¹ represents a C _1-4 alkoxycarbonyl group and R ² represents a hydrogen atom.
Is produced by subjecting 3-formylindole-2-carboxylic acid ester represented by the above general formula (3) to a condensation reaction with hydroxylamine or a hydrochloride thereof in the presence of a base.

The compound (1-1) of the present invention, wherein R ¹ represents a C _1-4 alkoxycarbonyl group and R ² represents a C _1-4 alkyl group, is a compound represented by the general formula (1-2) It is produced by reacting a compound with an alkylating agent represented by the general formula (5) in the presence of a base. Here, as the alkylating agent of the general formula (5), for example, alkyl halide, alkyl toluenesulfonate and the like can be exemplified.

Examples of the base used in each of the above reactions include pyridine, potassium carbonate, sodium hydride and the like.

[0033]

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Wherein R ² , R ³ , R ⁴ and R ⁵ are as defined above. R ⁶ and R ⁷ represent a C _1-4 alkyl group. According to the reaction formula-2, the compound (6) in which R ¹ represents a carboxyl group is produced by hydrolyzing the compound of the present invention represented by the general formula (1-3). The hydrolysis is
For example, it is carried out in a suitable alkali or acidic aqueous solution.

The compound (1-4) of the present invention in which R ¹ represents a C _1-4 alkoxycarbonyl group can be produced by esterifying the compound of the general formula (6) obtained above.

The esterification of the compound represented by the general formula (6) is carried out according to a method commonly used in the art.
For example, the compound of the general formula (1-) is reacted with an alcohol in an inert solvent in the presence of a condensing agent such as dicyclohexylcarbodiimide (DCC) in an inert solvent.
The compound of 4) can be produced. Alternatively, a carboxylic acid halide obtained by reacting a compound of the general formula (6) with a halogenating agent such as thionyl chloride or phosphorus trichloride is reacted with an alcohol in the presence of an acid binder to obtain a compound of the general formula (1) -4) can be produced. Further, by reacting the compound of the general formula (6) with a diazoalkane such as diazomethane, the compound of the general formula (1-
The compound of 4) can be produced.

The compound (1-5) of the present invention in which R ¹ represents a mono (C _1-4 alkylamino) carbonyl group and the compound (1-6) of the present invention in which R ¹ represents a carbamoyl group are obtained as described above. It is produced by amidating a compound of the general formula (6).

The amidation of the compound of the general formula (6) can be carried out, for example, by reacting the compound of the general formula (6) with an amine in an inert solvent in the presence of a condensing agent such as dicyclohexylcarbodiimide (DCC), or The reaction is carried out by reacting a carboxylic acid halide obtained by reacting the compound of the general formula (6) with a halogenating agent such as thionyl chloride or phosphorus trichloride with an amine in the presence of an acid binder.

The dehydration reaction of the compound of the general formula (1-6)
By appropriately utilizing a known method available in the art, for example, the compound of the general formula (1-6) can be dehydrated with a dehydrating agent such as thionyl chloride or diphosphorus pentoxide in an inert solvent such as toluene or diethyl ether. This is easily done by processing.

The compound (1) of the present invention obtained by the above-mentioned various methods can be easily isolated and purified from the reaction mixture by a usual separation means, for example, a solvent extraction method, a recrystallization method and a column chromatography method.

When the compound of the present invention is used as an active ingredient of a fungicide, it may be used as it is without adding other components, but usually, it is mixed with a solid carrier, a liquid carrier, a gaseous carrier, a bait, and the like. , If necessary, surfactants and other pharmaceutical auxiliaries are added, oils, emulsions, wettable powders, flowables,
It is formulated into granules, powders, aerosols, aerosols, etc. and used.

Examples of the solid carrier used in the preparation of these preparations include clays (kaolin clay, diatomaceous earth, synthetic hydrous silicon oxide, bentonite, fubasami clay, acid clay, etc.), talcs, ceramics, and other inorganic minerals ( Fine powders or granular materials such as celite, quartz, sulfur, activated carbon, calcium carbonate, hydrated silica, etc., and chemical fertilizers (ammonium sulfate, phosphorous ammonium, ammonium nitrate, urea, salt ammonium, etc.), etc. For example, water, alcohols (methanol, ethanol, etc.), ketones (acetone, methyl ethyl ketone, etc.), aromatic hydrocarbons (benzene, toluene, xylene, ethylbenzene, methylnaphthalene, etc.), aliphatic hydrocarbons (hexane, cyclohexane, etc.) Kerosene, light oil, etc.), esters (ethyl acetate, butyl acetate, etc.), nitriles (acetonitrile Isobutyronitrile), ethers (diisopropyl ether, dioxane, etc.),
Acid amides (N, N-dimethylformamide, N, N-
Dimethylacetamide, etc.), halogenated hydrocarbons (dichloromethane, trichloroethane, carbon tetrachloride, etc.), dimethyl sulfoxide, vegetable oils such as soybean oil, cottonseed oil and the like. Examples of the gaseous carrier (propellant) include Freon gas, butane gas , LPG (liquefied petroleum gas), dimethyl ether, carbon dioxide gas and the like.

Examples of the surfactant include alkyl sulfates, alkyl sulfonates, alkyl aryl sulfonates, alkyl aryl ethers and polyoxyethylenates thereof, polyethylene glycol ethers, polyhydric alcohol esters, sugar alcohols Derivatives and the like.

As auxiliary agents for preparations such as fixatives and dispersants, for example, casein, gelatin, polysaccharides (starch,
Gum arabic, cellulose derivatives, alginic acid, etc.), lignin derivatives, bentonite, saccharides, synthetic water-soluble polymers (polyvinyl alcohol, polyvinylpyrrolidone, polyacrylic acids, etc.). Stabilizers such as PAP (isopropyl isopropyl phosphate) ), BHT (2,6-
Di-tert-butyl-4-methylphenol), BH
A (a mixture of 2-tert-butyl-4-methoxyphenol and 3-tert-butyl-4-methoxyphenol), vegetable oil, mineral oil, surfactant, fatty acid, or ester thereof.

The preparation thus obtained is used as it is or diluted with water or the like. Also, if necessary, other fungicides, insecticides, nematicides, acaricides, herbicides,
They can be used simultaneously with or without mixing with plant growth regulators, synergists, soil conditioners, animal feeds and the like.

When the compound of the present invention is used as an agricultural and horticultural fungicide, its application rate is usually 10 to 10 per 10 ares.
0 g. When the emulsion, wettable powder, flowable or the like is diluted with water and used, the application concentration is usually 10 ppm to 5 ppm.
000 ppm, and granules, powders and the like are preferably applied as they are without dilution.

These application rates and application concentrations vary depending on the type of preparation, application time, application place, application method, target disease, target crop, degree of damage, etc., and are not limited to the above ranges. It can be increased or decreased.

[0048]

Hereinafter, the present invention will be further clarified with reference to Production Examples of raw materials for producing the compound of the present invention as Reference Examples, and further to Production Examples, Formulation Examples and Test Examples of the compound of the present invention. The present invention is not limited to these examples. Hereinafter, "parts" means "parts by weight".

Reference Example 1 Synthesis of methyl 3-formyl-4-methoxy-7-methylindole-2-carboxylate 3.2 ml of anhydrous dimethylformamide was cooled to 0 ° C.
1.6 g (10.2 mmol) of phosphorus oxychloride was added dropwise over 10 minutes. After stirring for 2 hours as it was, the temperature was returned to room temperature, and methyl 4-methoxy-7-methylindole-
A solution of 2.4 g (11.0 mmol) of 2-carboxylate in 10 ml of anhydrous dimethylformamide was added dropwise over 20 minutes. After stirring at room temperature for 1 hour, the mixture was stirred at 90 ° C. for 2 hours. After dropping the reaction solution onto 30 g of ice, 1.8 g
Then, 10 ml of an aqueous solution of sodium hydroxide was added, and the mixture was stirred at 60 ° C. for 1 minute. After returning to room temperature, 100 ml of water was added, and the mixture was extracted three times with 20 ml of diethyl ether. After the diethyl ether solution was dried over anhydrous magnesium sulfate, the obtained crude product was purified by silica gel column chromatography to obtain 0.8 g of yellow crystals. Yield 29.6%.

Melting point: 192-193 ° C. ¹ H-NMR (300 MHz, CDCl ₃ -DMSO-d
_{6 /} TMS; δ ppm): 11.55 (1H, br)
s), 10.72 (1H, s), 7.03 (1H, d,
J = 8.00 Hz), 6.56 (1H, d, J = 8.0)
0 Hz), 3.99 (3H, s), 3.93 (3H,
s), 2.50 (3H, s).

Production Example 1 Methyl 4-methoxy-3-methoxyiminomethyl-7
Synthesis of -methylindole-2-carboxylate (Compound 1) 1.24 g (5.0 mmol) of methyl 3-formyl-4-methoxy-7-methylindole-2-carboxylate was dissolved in 20 ml of ethanol, and hydroxylamine was dissolved. 0.43 g of the hydrochloride salt of -O-methyl ether (5.1
(Mmol) and 0.71 g (8.63 mmol) of sodium acetate in 10 ml of an aqueous solution, and the mixture was heated under reflux for 2 hours. After returning to room temperature, ethanol was removed under reduced pressure, and the precipitated crude crystals were filtered, washed with water, and recrystallized with methanol to obtain 1.0 g of yellow crystals. Yield 72.2%.

Melting point: 131-132 ° C. ¹ H-NMR (300 MHz, CDCl ₃ / TMS; δp
pm): 8.88 (1H, brs), 8.79 (1H, br)
s), 7.30 (1H, d, J = 7.44 Hz), 6.
46 (1H, d, J = 7.44 Hz), 4.12 (3
H, s), 3.96 (3H, s), 3.91 (3H,
s), 2.42 (3H, s).

Production Example 2 Methyl 3- (hydroxyiminomethyl) -4,7-dimethylindole-2-carboxylate (Compound 2)
Synthesis of methyl 4,7-dimethylindole-2-carboxylate 0.7 g (3.03 mmol) in ethanol 15
0.43 g (5.21 mmol) of sodium acetate and 0.22 g of hydroxylamine hydrochloride
(3.075 mmol) of an aqueous solution (7.5 ml) was added, and the mixture was refluxed for 4 hours. After the ethanol was distilled off under reduced pressure, the residue was washed with water 1
Poured into 00 ml. After the crude crystals were filtered off with suction, they were dried under vacuum and dried to give 690 mg of white crystals. Yield 93%.

Melting point: 183-184 ° C. ¹ H-NMR (300 MHz, CDCl ₃ / TMS; δp
pm): 9.96 (1H, brs), 9.86 (1H, br)
s), 7.84 (1H, brs), 7.08 (1H,
d, J = 7.35 Hz), 6.99 (1H, d, J =
7.35 Hz), 4.05 (3H, s), 2.78 (3
H, s), 2.50 (3H, s).

Reference Example 2 Synthesis of 4,7-dimethyl-3-methoxyiminomethylindole-2-carboxylic acid 4.5 g (17.3) of methyl 4,7-dimethyl-3-methoxyiminomethylindole-2-carboxylate
Was dissolved in 35 ml of methanol, 35 ml of a 1N aqueous sodium hydroxide solution was added, and the mixture was heated under reflux for 2 hours. After returning to room temperature, the mixture was concentrated and added dropwise to a mixed aqueous solution of 30 g of ice and 50 ml of 1N hydrochloric acid. The resulting precipitate was collected by filtration and washed with water. Drying under reduced pressure gave 4.1 g of pale yellow crystals. 96.3% yield.

Melting point: 220 ° C. (decomposition) ¹ H-NMR (300 MHz, CDCl ₃ -DMSO-d)
_{6 /} TMS; δ ppm): 13.5-12.5 (1H,
brs), 9.59 (1H, brs), 8.90 (1
H, s), 7.06 (1H, d, J = 7.23 Hz),
6.93 (1H, d, J = 7.23 Hz), 4.07
(3H, s), 2.68 (3H, s), 2.50 (3
H, s).

Production Example 3 Synthesis of ethyl 4,7-dimethyl-3-methoxyiminomethylindole-2-carboxylate (compound 3) 0.7 g of 4,7-dimethyl-3-methoxyiminomethylindole-2-carboxylic acid (2.85 mmol) was dissolved in 65 ml of anhydrous tetrahydrofuran, 0.19 ml of ethanol and 0.28 g (2.3 mmol) of 4- (N, N-dimethylamino) pyridine were added, and the mixture was cooled to 0 ° C. With vigorous stirring, 0.65 g (3.13 mmol) of 1 ', 4'-dicyclohexylcarbodiimide was added over 5 minutes, and the mixture was stirred at room temperature overnight. The generated urea derivative was removed by filtration, and the obtained solution was concentrated under reduced pressure, and then purified by silica gel column chromatography (ethyl acetate: n-hexane = 1: 4) to give 270 mg of the desired product as white crystals. Obtained. Yield 38.4%.

Melting point: 124-125 ° C. ¹ H-NMR (300 MHz, CDCl ₃ / TMS; δp
pm): 8.91 (1H, brs), 8.82 (1H, br)
s), 7.04 (1H, d, J = 7.01 Hz), 6.
88 (1H, d, J = 7.01 Hz), 4.45 (1
H, q, J = 7.14 Hz), 4.01 (3H, s),
2.68 (3H, s), 2.47 (3H, s), 1.4
4 (3H, t, J = 7.14 Hz).

Production Example 4 Synthesis of 4,7-dimethyl-3-methoxyiminomethylindole-2-N-methylcarboxamide (Compound 4) A 40% methanol solution of monomethylamine was used in place of ethanol, and 4- ( N, N-dimethylamino)
Except that pyridine was not added, the mixture was treated in the same manner as in Production Example 3 to obtain 170 mg of white crystals. Yield 21.7%.

Melting point: 202-203 ° C. ¹ H-NMR (300 MHz, CDCl ₃ / TMS; δp
pm): 9.68 (1H, brs), 8.95 (1H, br)
s), 7.26 (1H, brs), 7.23 (1H,
d, J = 7.23 Hz), 6.88 (1H, d, J =
7.23 Hz), 4.03 (3H, s), 3.06 (3
H, s), 2.68 (3H, s), 2.50 (3H,
s).

Production Example 5 Synthesis of 4,7-dimethyl-3-methoxyiminomethylindole-2-carboxamide (Compound 5) 2.0 g of 4,7-dimethyl-3-methoxyiminomethylindole-2-carboxylic acid (compound 5) 8.62 mmol) was dissolved in 25 ml of chloroform, and while stirring, 5.2 g (43.1 mmol) of thionyl chloride in chloroform solution 1
0 ml was added dropwise over 5 minutes. After heating and refluxing for 50 minutes,
After returning to room temperature, chloroform was removed under reduced pressure. The obtained solid was dissolved in benzene and dried under reduced pressure. The obtained crude crystals were dissolved in anhydrous tetrahydrofuran (30 ml), and this was added to a 25% aqueous ammonia solution cooled to 0 ° C.
It took 0 minutes and added dropwise. After stirring for 1 hour,
The solution was added dropwise to a 0.5N hydrochloric acid aqueous solution, and the precipitated crystals were collected by filtration and further washed with water. The obtained crude crystals were recrystallized from methanol-ethyl acetate to obtain 1.7 g of pale yellow crystals. 85.7% yield.

Melting point: 196-197 ° C. ¹ H-NMR (300 MHz, CDCl ₃ / TMS; δp
pm): 10.35 (1H, brs), 9.69 (1
H, brs), 8.96 (1H, s), 7.00 (1
H, d, J = 7.17 Hz), 6.88 (1H, d, J)
= 7.17 Hz), 6.15 (1H, brs), 4.0
0 (3H, s), 2.68 (3H, s), 2.53 (3
H, s).

Production Example 6 Synthesis of 2-cyano-4,7-dimethyl-3-methoxyiminomethylindole (Compound 6) 10 ml of phosphorus oxychloride was cooled to 0 ° C. and stirred with 4,7-dimethyl-3. 0.7 g (3.04 mmol) of -methoxyiminomethylindole-2-carboxylic acid was added to 5
After stirring for an additional minute, the mixture was stirred at room temperature for 10 minutes. After heating under reflux for 40 minutes, the mixture was cooled to room temperature. After drying under reduced pressure, the obtained solid was dissolved in 10 ml of ethyl acetate, and then added dropwise to 10 ml of ice and 15 ml of 5% aqueous sodium bicarbonate. The ethyl acetate layer was separated, and the ethyl acetate layer was further separated with a 5% aqueous sodium bicarbonate solution (15 m).
1 and 15 ml of distilled water. The ethyl acetate solution was dried over magnesium sulfate and the mixture of isomers (E / Z = 1 /
As 1), 0.4 g of pale yellow crystals was obtained. Yield 62.0
%.

Melting point: 169-170 ° C. ¹ H-NMR (300 MHz, CDCl ₃ / TMS; δp
pm): 8.79 (1H, brs), 8.60 (1H, br)
s), 7.07 (1H, d, J = 7.28 Hz), 6.
92 (1H, d, J = 7.28 Hz), 4.07 (3
H, s), 2.64 (3H, s), 2.47 (3H,
s).

Production Example 7 Synthesis of Methyl 3- (methoxyiminomethyl) -4,7-dimethylindole-2-carboxylate (Compound 7) Methyl 3- (hydroxyiminomethyl) -4,7-dimethylindole-2- 0.8 g carboxylate
(3.25 mmol), methyl iodide 0.60 g (4.2
A mixture of 3 mmol), 0.59 g (4.23 mmol) of potassium carbonate and 20 ml of acetonitrile was refluxed for 19 hours. After removing potassium carbonate by filtration, acetonitrile was distilled off under reduced pressure. The obtained residue was dissolved in ethyl acetate and washed three times with water. After drying over anhydrous magnesium sulfate,
Purified by silica gel column chromatography, 210
mg of pale yellow crystals were obtained. Yield 25%.

Melting point: 107-108 ° C. ¹ H-NMR (300 MHz, CDCl ₃ / TMS; δp
pm): 8.93 (1H, brs), 8.81 (1H, br)
s), 7.03 (1H, d, J = 7.35 Hz), 6.
88 (1H, d, J = 7.35 Hz), 4.01 (3
H, s), 3.98 (3H, s), 2.68 (3H,
s), 2.47 (3H, s).

In the same manner as in Production Examples 1 to 7, the following Tables 1 to
The compounds shown in Table 3 were obtained.

[0068]

[Table 1]

[0069]

[Table 2]

[0070]

[Table 3]

Formulation Example 1 (Emulsion) 10 parts of each of the compounds of the present invention were mixed with Solvesso 150 35
And 35 parts of N-methylpyrrolidone, and 10 parts of Solpol 3005X (emulsifier, manufactured by Toho Chemical Co., Ltd.) was added thereto, followed by stirring and mixing to obtain a 10% emulsion.

Formulation Example 2 (Wettable powder) 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. In addition, the mixture was stirred and mixed with a juice mixer to obtain a 20% wettable powder.

Formulation Example 3 (granules) To 5 parts of each of the compounds of the present invention, 2 parts of sodium dodecylbenzenesulfonate, 10 parts of bentonite and clay 83
Add and mix well with stirring. Next, an appropriate amount of water was added to the mixture, and the mixture was further stirred, granulated by a granulator, and dried by ventilation to obtain 5% granules.

Formulation Example 4 (Powder) One part of each of the compounds of the present invention was dissolved in an appropriate amount of acetone.
To this were added 5 parts of synthetic hydrous silicon oxide fine powder, 0.3 part of acidic isopropyl phosphate (PAP) and 93.7 parts of clay, and the mixture was stirred and mixed with a juice mixer, and acetone was removed by evaporation to obtain a 1% powder. .

Formulation Example 5 (Floable agent) Water containing 20 parts of each of the compounds of the present invention, 3 parts of polyoxyethylene tristyryl phenyl ether phosphate triethanolamine, and 0.2 parts of Rhodazil 426R (silicone-based antifoaming agent) After mixing with 20 parts and wet grinding using a Dynomill, the mixture was mixed with 60 parts of water containing 8 parts of propylene glycol and 0.32 part of xanthan gum to obtain a 20% suspension in water.

Test Example 1 (Effect of controlling cucumber gray mold) Cucumber cultivated in a greenhouse for about 2 weeks (variety "Suzunari Yotsuba")
A predetermined amount (500 ppm) of a wettable powder of the compound of the present invention prepared in Formulation Example 2 was sprayed on the seedlings in a sufficient amount, and air-dried. Then, the first leaf was cut off, and placed on a potato / saccharose / agar medium at 25 ° C. Benomyl and thiophanate methyl resistant Botrytis c.
inerea) A mycelial disk in which the tip of the microflora was punched out was inoculated to the leaves, and the leaves were kept at 100% humidity and 25 ° C. for 3 days. The lesion diameter was measured, and each drug was evaluated by the following formula (control value calculation formula). The control value was calculated and the results are shown in Table 4. The test compound numbers in Table 4 correspond to the compound numbers in Production Examples. For comparison, the results obtained using commercially available fungicides benomyl and thiophanate methyl are also shown in Table 4.
Are shown together.

[0077]

(Equation 1)

[0078]

[Table 4]

From Table 4, it can be seen that the compounds of the present invention exhibit an excellent control effect against drug-resistant Botrytis cinerea.

──────────────────────────────────────────────────続 き Continuation of front page (56) References JP-A-10-17548 (JP, A) (58) Fields investigated (Int. Cl. ⁷ , DB name) C07D 209/42 A01N 43/38 CA, REGISTRY (STN)

Claims (2)

(57) [Claims] 1. A compound of the general formula [In the formula, R ¹ represents a C _1-4 alkoxycarbonyl group, a carbamoyl group, a mono (C _1-4 alkylamino) carbonyl group or a cyano group. R ² represents a hydrogen atom or a C _1-4 alkyl group. R ³ and R ⁴ are the same or different and are each a hydrogen atom,
It represents a C _1-4 alkyl group, a halogen atom or a C _1-4 alkoxy group. Provided that R ¹ is a C _1-4 alkoxycarbonyl group, R
² is a hydrogen atom or a C _1-4 alkyl group; R ³ and R ⁴ are C _1-4
When it represents an alkyl group or a halogen atom, one of R ³ and R ⁴ must not be bonded to the 4-position of the indole skeleton and the other must be bonded to the 7-position of the indole skeleton. ] A fungicide for agricultural and horticultural use, comprising the indole-2-carboxylic acid ester derivative represented by the formula (1) as an active ingredient. 2. A compound of the general formula [In the formula, R ¹ represents a C _1-4 alkoxycarbonyl group, a carbamoyl group, a mono (C _1-4 alkylamino) carbonyl group or a cyano group. R ² represents a hydrogen atom or a C _1-4 alkyl group. R ³ and R ⁴ are the same or different and are each a hydrogen atom,
It represents a C _1-4 alkyl group, a halogen atom or a C _1-4 alkoxy group. However, when R ³ and R ⁴ are not both hydrogen atoms, and one of R ³ and R ⁴ is a C _1-4 alkoxy group and the other is a hydrogen atom, the alkoxy group is located at the 5-position of the indole skeleton. Must not be bonded, and when R ³ and R ⁴ are both chlorine atoms, these chlorine atoms must not be bonded to the 4- and 6-positions of the indole skeleton. Further, R ¹ is a C _1-4 alkoxycarbonyl group, and R ² is a hydrogen atom.
Child or a C _1-4 alkyl group, when R ³ and R ⁴ represents a C _1-4 alkyl group or a halogen atom, bonded and the other indole at the 4-position of the one indole skeleton in R ³ and R ⁴ Should not be attached to position 7 of the backbone. ] An indole-2-carboxylic acid ester derivative represented by the formula: