JPH07118236A - Sulfonylisoquinoline derivative and agricultural and horticultural germicide - Google Patents

Abstract

PURPOSE:To obtain a new sulfonylisoquinoline derivative capable of manifesting high activities as an agricultural and horticultural germicide. CONSTITUTION:This sulfonylisoquinoline derivative is expressed by formula 1 (R<1> is a lower alkyl, a lower alkenyl, a lower alkynyl, a lower alkylcarbonyl, a lower alkoxycarbonyl, a lower alkenyloxycarbonyl, a lower alkynyloxycarbonyl, benzyl or benzoyl; R<2> is a lower alkyl), e.g. 1,2-dihydro-2- benzyl-4-methanesulfonylisoquinoline. The compound expressed by formula 1 is obtained by reacting, e.g. a new 4-alkylsulfonylisoquinoline expressed by formula 2 with halides expressed by formula 3, providing a quaternary salt expressed by formula 4 as an intermediate and subsequently reducing the resultant compound expressed by formula 4. The compound expressed by formula 1 is capable of manifesting high controlling effects on downy mildew, late blight, etc., which are serious disease injuries of fruit trees and vegetables.

Description

Detailed Description of the Invention

[0001]

[Object of the Invention]

TECHNICAL FIELD The present invention relates to a novel sulfonylisoquinoline derivative. More specifically, 1,2-dihydro-2-substituted-4- represented by the following general formula (1)
The present invention relates to an alkylsulfonylisoquinoline derivative and an agricultural / horticultural fungicide containing the derivative as an active ingredient. Therefore, the present invention is useful in the chemical industry and the agricultural and horticultural fields, especially in the agrochemical manufacturing field.

[0002]

2. Description of the Related Art Heretofore, some compounds which are similar in chemical structure to the compound of the present invention are known. For example, regarding the methanesulfonylisoquinoline derivative, Vol. 90, No. 5, p. 594 to p. 600 (1970).
Describes that 1-methanesulfonylisoquinoline is obtained by oxidation of 1-methylthioisoquinoline with potassium permanganate. However, a 1,2-dihydro-2-substituted-4-alkylsulfonylisoquinoline derivative represented by the following general formula (1) of the present invention is not known.

[0003]

The known 1-methanesulfonylisoquinoline has no bactericidal activity against diseases in the field of agriculture and horticulture, as shown in the test examples below. On the other hand, various drugs have been used so far for downy mildew, epidemic, etc., which are important diseases of fruit trees and vegetables, but either drug is resistant to bacteria and cannot be used or its use is restricted. ing. Therefore, in these fields, the emergence of new fungicides having a skeleton different from that of conventional drugs is desired.
It is an object of the present invention to provide a germicide that meets these needs.

[0004]

[Constitution of the invention]

[Means for Solving the Problems] The inventors of the present invention have synthesized many compounds in order to achieve the above-mentioned object, and have diligently studied their usefulness. As a result, they have found that the sulfonylisoquinoline derivative represented by the following general formula (1) has high activity as an agricultural and horticultural fungicide.

Therefore, the gist of the first aspect of the present invention lies in the following general formula (1)

[Chemical 3] (In the formula, R ¹ represents a lower alkyl group, a lower alkenyl group, a lower alkynyl group, a lower alkylcarbonyl group, a lower alkoxycarbonyl group, a lower alkenyloxycarbonyl group or a lower alkynyloxycarbonyl group,
A benzyl group or a benzoyl group which may be substituted with a halogen atom, a lower alkyl group, a lower haloalkyl group or a lower alkoxy group, and R ² represents a lower alkyl group).

The second aspect of the present invention is an agricultural and horticultural fungicide characterized by containing the sulfonylisoquinoline derivative of the general formula (1) as an active ingredient. In the compound represented by the general formula (1),
Of the definitions of R ¹ and R ² , the lower alkyl group, lower alkenyl group and lower alkynyl group may be linear or branched. The term "lower" as used herein means one having 1 to 6 carbon atoms.

Next, Table 1 shows specific examples of the compound of the present invention represented by the general formula (1). The compound No. is also referred to in the following examples and test examples.

[0008]

[Table 1]

[Action] The compound of the general formula (1) of the present invention is a novel compound. Then, the compound of the general formula (1) acts as an active ingredient of the agricultural and horticultural fungicide.

[0010]

【Example】

(Method for producing compound of the present invention) General formula (1) according to the present invention
The compound (1) can be produced by either of the following two methods, that is, method [A] and method [B].

Method [A]: 4-in the formula (2)
An alkylsulfonylisoquinoline is reacted with a halide represented by the general formula (3) to give an intermediate represented by the general formula (4)
It can be produced by a method via a quaternary salt represented by. The method is applied when the halides are especially alkyl halides.

[0012]

[Chemical 4] (In the formula, R ¹ and R ² are the same as above, and X represents a halogen atom).

The reaction for producing the compound of formula (4) is usually carried out in an organic solvent. As the solvent that can be used, hydrocarbons such as toluene and hexane, halogenated hydrocarbons such as chloroform and chlorobenzene, ethers such as ethyl ether, dioxane, and tetrahydrofuran, nitriles such as acetonitrile and propionitrile, acetone, Examples thereof include ketones such as methyl isobutyl ketone, alcohols such as methanol and ethanol, amides such as dimethylformamide and dimethylacetamide, and dimethyl sulfoxide.

The reaction proceeds even at room temperature, but the reaction time can be shortened by heating within the range up to the boiling point of the solvent. After completion of the reaction, the solvent is distilled off to obtain the compound of formula (4)
The compound can be obtained. It can also be obtained by adding water and an organic solvent such as benzene, toluene, tetrahydrofuran or chloroform to fractionate the compound of the formula (4) and distilling off the solvent.

Further, the reduction reaction of the compound of formula (4) is
It is usually carried out in an organic solvent using a reducing agent such as BH ₄ , KBH ₄ and LiAlH ₄ . Usable solvents include ethers such as ethyl ether, dioxane and tetrahydrofuran, alcohols such as methanol and ethanol.

Although the reaction proceeds even at room temperature, the reaction time can be shortened by heating within the range up to the boiling point of the solvent. After completion of the reaction, the compound of the present invention can be obtained by adding water and an organic solvent such as benzene, toluene, tetrahydrofuran, chloroform and the like to separate the target product and distill off the solvent.

Method [B]: 4-in the formula (2)
It can be produced by a method of reacting an alkylsulfonylisoquinoline with a halide represented by the general formula (3) in the presence of a reducing agent. This method is applied especially when the halides are acyl halides.

[0018]

[Chemical 5]

This production reaction is usually carried out in an organic solvent. Solvents that can be used include hydrocarbons such as toluene and hexane, halogenated hydrocarbons such as dichloromethane, chloroform and chlorobenzene.

Bu ₃ SnH is used as the reducing agent. Although the reaction proceeds from a low temperature of −50 ° C. to room temperature, the reaction time can be shortened by heating in the range up to the boiling point of the solvent. After completion of the reaction, the compound of the present invention can be obtained by adding water and an organic solvent such as benzene, toluene, tetrahydrofuran, chloroform and the like to separate the target product and distill off the solvent.

Examples of production of the compound of the present invention by this method are shown in Examples 1 and 2. The compound of formula (2), which is a starting material, is a novel compound, and can be obtained by reacting 4-bromoisoquinoline, which is a known compound, with a sodium salt of alkylthiol and then oxidizing the mixture with hydrogen peroxide solution. Production examples of the compound of the formula (2) are shown in Reference Production Examples. The compound of formula (3) is a known compound.

Example 1 Production of 1,2-dihydro-2-benzyl-4-methanesulfonylisoquinoline (Compound No. 10) (Method [A]) 4-methanesulfonylisoquinoline was placed in a 500 ml four-necked flask. 20.7 g, benzyl bromide 17.1
g and 200 ml of ethanol were added and the mixture was refluxed for 4 hours. After cooling, the solvent was distilled off under reduced pressure, and the obtained crystals were recrystallized with toluene to give white crystals (yield 28.3 g), melting point 92.5-9.
An intermediate at 5 ° C (decomposition) was obtained.

Furthermore, 18.9 g of the obtained intermediate, 1.9 g of NaBH ₄ and 100 ml of methanol were placed in a _four- necked flask having a capacity of 300 ml, and the mixture was stirred at room temperature for 2 hours. After the solvent was distilled off under reduced pressure, ice water was added and the mixture was extracted with dichloromethane. The organic layer was washed with water and dried over anhydrous sodium sulfate. Then, the solvent was distilled off under reduced pressure, and the residue was purified by silica gel column chromatography using a toluene-ethyl acetate mixed solvent to give the title compound 1 as a colorless oil.
1.0 g (yield 74%, n _D ²³ = 1.5053) was obtained.

Example 2 Production of 1,2-dihydro-2- (3'-trifluoromethylbenzoyl) -4-methanesulfonylisoquinoline (Compound No. 16) (Method [B]) Four 500 ml volumes In a neck flask, 20.7 g of 4-methanesulfonylisoquinoline, 208 g of 3-trifluoromethylbenzoyl chloride and 200 of dichloromethane.
ml was added and cooled to -50 ° C. Under cooling and further Bu ₃ S
29.1 g of nH was added, and the mixture was stirred at room temperature for 1 hour. Ice water was added, the organic layer was separated and dried over anhydrous sodium sulfate. Then, the solvent was distilled off under reduced pressure, and the residue was diluted with toluene-
Purification by silica gel column chromatography using ethyl acetate mixed solvent gave 22.8 g of the title compound as colorless crystals (yield 60%, mp. 117.5-120).
C) was obtained.

[Reference Production Example] 4-Methanesulfonylisoquinoline (compound of formula (2))
Production of 4-bromoisoquinoline 20.8 g, methyl mercaptan sodium salt 70.0 g in a 500 ml four-necked flask.
g and 200 ml of dimethylsulfoxide are put at 130 ° C.
It was stirred for 1 hour. After cooling, ice water was added and the mixture was extracted with toluene. The organic layer was washed with water and dried over anhydrous sodium sulfate. Then, the solvent was distilled off under reduced pressure to obtain 4
-Methylthioisoquinoline (Yield 105.0 g, mp. 6
4-65 ° C) was obtained.

Add 4 to a 500 ml four-necked flask.
-Methylthioisoquinoline (43.7 g), 35% hydrogen peroxide solution (48.5 g), sodium tungstate (0.5 g) and acetic acid (20 ml) were added, and the mixture was stirred at 50 ° C for 3 hours. After cooling, water was added and the mixture was extracted with toluene. The layer was washed with water and dried over anhydrous sodium sulfate. After that, the solvent was distilled off under reduced pressure, and the residue was recrystallized using a toluene-ethyl acetate mixed solvent to obtain 36.7 g of the title compound as a colorless crystal (yield 7
1%, mp. 164-165 ° C) was obtained.

(Method for Formulating Agricultural and Horticultural Bactericide) The agricultural and horticultural bactericidal agent of the second invention can be used by formulating the compound of the general formula (1) by a conventional formulation. . That is, a wettable powder, an emulsion, a liquid agent, a sol agent (flowable agent), an oil agent is prepared by mixing the compound of the general formula (1) with a suitable carrier and auxiliary agent such as a surfactant, a binder and a stabilizer. , Powders, DL (driftless type) powders, fine granules, coarse powders and the like. The content of the compound of the present invention in these preparations is a wettable powder, an emulsion, a sol,
In the case of an oil agent, the range of 1 to 90% (weight%: the same applies hereinafter)
0.5 to 5 for powders, DL powders, fine powders, and coarse powders
%, And in the case of granules, it may be contained in the range of 1 to 10%.

The method of using the agricultural / horticultural germicide of the present invention is generally as follows. That is, in the case of wettable powders, liquid preparations, emulsions, sol preparations (flowable preparations) and oil preparations, the active ingredient is generally diluted to 1 to 500 times with water.
The solution is adjusted to a concentration of 10,000 ppm. Then, the diluted solution is sprayed onto the foliage at the disease occurrence site of the plant in an amount of 50 to 300 liters, usually 100 to 200 liters, per 10 ares.

Further, liquid agents, emulsions and sol agents (flowable agents) are not diluted with water and remain as a concentrated solution or with water.
Dilute to within 0 times and mainly use for microscopic spraying (LV)
As a spraying agent, ULV spraying agent) 50 per 10 are
A volume of 3000 ml is sprayed using a helicopter.

The powder, DL powder, fine powder, and coarse powder are 2 to 5 kg per 10 ares (50 to 50 in terms of active ingredient).
(About 500 g) is applied to the foliage at the disease occurrence site of the plant, the soil surface, the soil or the water surface. The method for formulating the compound of the present invention represented by the general formula (1) as an agricultural and horticultural fungicide is shown in Examples 3 to 6 below.

Example 3 (powder) 2 parts of compound No. 10, PAP (physical property improver)
1 part and 97 parts of clay are uniformly mixed and ground to obtain a dust containing 2% of active ingredient.

Example 4 (Wettable powder) 20 parts of the compound of compound No. 16, 3 parts of potassium alkylbenzene sulfonate, 5 parts of polyoxyethylene nonylphenyl ether and 72 parts of clay were uniformly mixed and pulverized. A wettable powder containing 20% of the active ingredient is obtained.

Example 5 (Emulsion) 30 parts of compound No. 6 and 40 parts of methyl ethyl ketone
Parts and polyoxyethylene nonyl phenyl ether 3
Mixing and dissolving 0 parts gives an emulsion containing 30% of active ingredient.

Example 6 (sol agent) 40 parts of compound No. 8 compound, lauryl sulfate 2
Parts, 2 parts of sodium alkylnaphthalene sulfonate, 1 part of acetoxypropyl cellulose and 55 parts of water are uniformly mixed to obtain a sol containing 40% of the active ingredient.

[0035]

INDUSTRIAL APPLICABILITY The compound of the present invention exhibits a high control effect against downy mildew, epidemic and the like, which are important diseases of fruit trees and vegetables, and is therefore useful as a fungicide for agriculture and horticulture.

Specific examples of the usefulness of the compound of the present invention are shown in Test Examples 1 and 2. [Test Example 1] Cucumber downy mildew control effect test No. 2 cultivated in a greenhouse in a clay pot with a diameter of 9 cm
20 ml of a dilute solution of a wettable powder having a predetermined concentration prepared according to Example 4 was sprayed on cucumber seedlings (variety: Sagamihanjiro) at the leaf stage.
Then, spores of cucumber downy mildew ( Pseudoperonospora cubensis ) were scraped off from the leaves affected by cucumber downy mildew with a moistened brush, and 50 ppm of a spreading agent (polyoxyethylene alkyl ether) was used.
Suspended in aqueous solution. Then, the spore concentration was adjusted to 5 × 10 ⁶ spores (pieces) / ml, and one day after spraying the drug, a spore suspension of cucumber downy mildew was spray-inoculated. Then, it was allowed to stand in a greenhouse at 20 ° C. and a humidity of 100% for 2 days to cause cucumber downy mildew. Six days after the inoculation, the lesion area ratio (%) per leaf was investigated, and the control value (%) was calculated by the following formula.

This test was carried out in a double system per leaf fluid concentration group,
The average control value (%) was calculated, and the evaluation value was calculated according to the following criteria. In addition, phytotoxicity to cucumber was investigated according to the following criteria. The results are shown in Table 2. In addition,
The evaluation value of the control effect and the investigation index of the chemical damage were similarly used in the following Test Examples 2 to 4.

[Equation 1]

[0038]

Investigation index of phytotoxicity 5: severe 4: severe 3: high 2: slight 1: slight 0: none

[0040]

[Table 2]

[Test Example 2] Tomato epidemic control effect test Prepared according to Example 4 on the 5th leaf stage seedling of tomato (cultivar: Toko K) cultivated in a greenhouse in a vinyl pot having a diameter of 9 cm. 30 ml per 3 pots was sprayed with the diluted solution of the wettable powder having a predetermined concentration, using an automatic spraying device. The day after the chemical treatment, on a potato slice sliced in advance at 20 ° C, 3
Phytophthora infestans cultivated for days:
The zoospores of Phytophthora infestans) were roughed (adjusted so that the concentration of zoospores was 10 ⁵ cells / ml) and spray-inoculated on tomatoes using a spray gun. Then, after storing in a humid chamber at 20 ° C and 100% humidity for 5 days,
About the 1st to 4th true leaves Area of disease spread of tomato disease (%)
Was investigated, the average disease area ratio was calculated, and the control value (%) was calculated by the following formula.

This test is carried out in a double system for each concentration of the chemical solution.
The average control value (%) was calculated and converted into an evaluation value. In addition, the same criteria as in Test Example 1 were used to investigate the chemical damage to tomatoes. The results are shown in Table 3.

[0043]

[Equation 2]

[0044]

[Table 3]

 ─────────────────────────────────────────────────── ─── Continuation of the front page (72) Seiichi Kutsuma 3-21-13 Sabudai, Sagamihara City, Kanagawa Prefecture Laplace Fujishin 102 No. 102 (72) Inventor Kazuyoshi Arita 2385, Toda, Atsugi, Kanagawa Prefecture Kitakogaku Dormitory (72) ) Inventor Kyoko Iwashita 533 Kamoshida-cho, Midori-ku, Yokohama-shi, Kanagawa Green Hill Kamoshida Higashi Danchi, Room 7 Room 401

Claims (2)

[Claims] 1. A general formula: (In the formula, R ¹ represents a lower alkyl group, a lower alkenyl group, a lower alkynyl group, a lower alkylcarbonyl group, a lower alkoxycarbonyl group, a lower alkenyloxycarbonyl group or a lower alkynyloxycarbonyl group,
A sulfonylisoquinoline derivative represented by a benzyl group or a benzoyl group which may be substituted with a halogen atom, a lower alkyl group, a lower haloalkyl group or a lower alkoxy group, and R ² represents a lower alkyl group). 2. A general formula: (In the formula, R ¹ represents a lower alkyl group, a lower alkenyl group, a lower alkynyl group, a lower alkylcarbonyl group, a lower alkoxycarbonyl group, a lower alkenyloxycarbonyl group or a lower alkynyloxycarbonyl group,
A sulfonylisoquinoline derivative represented by a benzyl group or a benzoyl group which may be substituted with a halogen atom, a lower alkyl group, a lower haloalkyl group or a lower alkoxy group, and R ² represents a lower alkyl group) as an active ingredient. A fungicide for agricultural and horticultural use.