JPH0489478A - Maleimide derivative and agricultural/horticultural bactericide containing the same as active ingredient - Google Patents

Abstract

NEW MATERIAL:A compound of formula I [X is H, halogen or trifluoromethyl; R is OR<1> (R<1> is 1-5C alkyl, aryl or benzyl) or NR<2>R<3> (R<2> and R<3> are each H, 1-5C alkyl, phenyl, benzyl or heterocyclic group)]. EXAMPLE:3,4-Dichloro-2,5-dihydro-2,5-dioxo-beta-(4-chlorophenyl)-1H-py rrole-1- propionic methyl ester. USE:An agricultural/horticultural bactericide. PREPARATION:In accordance with the reaction formulas, a cinnamic acid derivative of formula II is allowed to react with hydroxylamine in an organic solvent such as ethanol at room temperature to a temperature close to the boiling point of the solvent to obtain a compound of formula III. This compound is then made to react with a compound of formula IV in a solvent such as acetic acid to obtain a compound of formula V, which is then esterified or put to amidation by a conventional method, thus obtaining the objective compound of the formula I.

Description

Detailed Description of the Invention [Industrial Application Field] The present invention relates to the general formula (I): [In the formula, X is a hydrogen atom, a halogen atom or a trifluoromethyl group, and R is a group -0R1 (in the formula , R1 is a linear or branched alkyl group having 1 to 4 carbon atoms, an optionally substituted aryl group, an optionally substituted benzyl group),
or a group -NR"R' (in the formula, Rz and R3 are each independently a hydrogen atom, a straight chain or branched chain having 1 to 5 carbon atoms;
represents a lower alkyl group, an optionally substituted phenyl group, an optionally substituted benzyl group, or a heterocyclic group]
The present invention relates to an agricultural and horticultural fungicide containing a maleimide derivative represented by as an active ingredient.

In general formula (1), the halogen atom of the substituent X typically includes a chlorine atom and a fluorine atom, and the linear or branched alkyl group having 1 to 5 carbon atoms in the substituent R is typically Examples include methyl group, ethyl group, n-propyl group, isopropyl group, n-butyl group, 5ec-butyl group, and isobutyl group, and typical examples of the aryl group that may be substituted include phenyl, chlorophenyl, etc. Examples of the halogen-substituted phenyl group, lower alkyl-substituted phenyl groups such as tolyl, heterocyclic groups include nitrogen-containing ring groups such as pyridyl group, and examples of the optionally substituted benzyl group include benzyl group, and halogen-substituted benzyl groups such as chlorobenzyl groups.

[Prior Art] It is known that dichloromaleimide derivatives having an amino acid skeleton have bactericidal activity (for example, Patent No. 3738591 of the Federal Republic of Germany or Japanese Unexamined Patent Publication No. 160956/1999).
(see publication). However, in these literatures, β-
There is no description of dichloromaleimide derivatives having a phenylalanine skeleton.

The problem that C invention tries to solve! ! The purpose of the present invention is to develop a new compound having a novel skeleton and having preventive or therapeutic effects on various plant diseases, and an agricultural and horticultural fungicide containing the compound.

[Means to solve the problem]

According to the present invention, there are provided a novel compound of the general formula (1) and an agricultural and horticultural fungicide containing the same as an active ingredient.

The maleimide derivative represented by the general formula (I) can be produced, for example, using cinnamic acid as a starting material according to the following reaction route.

(II) (III) (Wherein, X and R are as defined in general formula (I).) That is, Be1lsteins Handbuch
der Organischen Chemie, 14
．． According to the method described on page 493J94, general formula (II)
By reacting the cinnamic acid derivative (geometric isomer mixture) represented by the general formula (I
A compound represented by II) can be obtained. Then,
The obtained β-phenylalanine derivative (III) is reacted with dichloromaleic anhydride (IV) in a solvent such as acetic acid at a temperature ranging from room temperature to the boiling point of the solvent to obtain a compound represented by general formula (V) as a product. be able to. The carboxylic acid (V) thus obtained is converted into alcohol or amine (R
-H) by a conventional method to produce the desired compound (I).

The compound of the present invention represented by the general formula (I) obtained by the above method exhibits therapeutic and protective effects against plant diseases when applied to soil or foliage as an agricultural and horticultural fungicide. It is particularly effective against rice blast, wheat rust, late blight of tomatoes, etc., and cucumber rot.

The compound of the present invention can be mixed with a carrier and, if necessary, other adjuvants, to form a formulation commonly used as an agricultural and horticultural fungicide, such as a powder, a coarse powder, a fine granule, a granule, a wettable powder,
It is prepared and used in forms such as emulsions, suspensions, and aqueous solutions. Suitable liquid carriers include, for example, water, alcohols such as ethanol and ethylene glycol, ketones such as acetone, ethers such as dioxane and cellosolve, aliphatic hydrocarbons such as kerosene and kerosene, and aromatics such as benzene and toluene. group hydrocarbons, other organic bases such as pyridine,
Halogenated hydrocarbons such as chloroform and carbon tetrachloride,
Examples include esters such as ethyl acetate and fatty acid glycerin ester, nitriles such as acetonitrile, dimethylformamide and dimethyl sulfoxide.

Suitable solid carriers for use in the agricultural and horticultural fungicides of the present invention include, for example, vegetable powders (e.g., starch, wheat flour, etc.), mineral powders (e.g., kaolin, bentonite,
(calcium phosphate, clays, talcs, silicas, etc.), and these can be used alone or in combination of two or more.

In addition, as emulsifiers, spreading agents, penetrating agents, dispersants, etc., soaps, sulfuric esters of higher alcohols, alkyl sulfonic acids, alkylaryl sulfonic acids, quaternary ammonium salts, oxyalkylamines, fatty acid esters, polyalkylene oxides, etc. Surfactants such as surfactants and anhydrosorbitol-based surfactants are widely used, and generally contain 0.2% or more in formulations.
The content is preferably about 10% (% is weight %, the same applies hereinafter).

Further, other types of fungicides, insecticides, nematicides, herbicides, plant growth regulators, plant nutrients, fertilizers, soil conditioners, etc. may be mixed as appropriate.

The agricultural and horticultural fungicide of the present invention is the above-mentioned maleimide derivative (I
), a carrier, auxiliary ingredients, etc., by a known method or a method analogous thereto. The content ratio (wt%) of the compound in the pesticidal agent in the present invention is about 5 to 90% for emulsions, wettable powders, etc., and 0% for oils, powders, etc.
．． Appropriately it is about 1 to 20%, and for granules, about 1 to 50%. In addition, when using emulsions, hydrating agents, etc.
Furthermore, it is preferable to dilute it appropriately with water (for example, 50 to 5000 times) and then spray it.

The amount of the compound of the present invention (1) to be used, the combination of mixing with other types of drugs, and the mixing ratio thereof will depend on the growth stage of the target plant, the growth situation, the type of pathogenic bacteria, the state of disease onset, the time of application of the drug, or the time of application. Although it varies depending on the method and other conditions,
Generally, compound (1) is 10 to 300 g per 10 ares.
You just have to adjust it so that it is within the range. In addition, the concentration of compound (1) may be in the range of 10 to 11,000 pp+, and the method of use may be by spraying, dusting, irrigating, or coating seeds, which is safe for crops. The present invention is not limited to any amount, concentration, or method of use as long as it is effectively applied.

[Examples] Next, the present invention will be explained in more detail with reference to production examples, formulation examples, and test examples, but it goes without saying that the technical scope of the present invention is not limited to these examples.

Sodium metal (5.4g) was dissolved in ethanol (120d
) and stirred at room temperature to dissolve, to prepare a sodium ethoxide solution. A saturated aqueous solution of hydroxylammonium chloride (16.0 g) was added to the mixture, stirred at room temperature for 10 minutes, and precipitated common salt was filtered off. Then, p-chlorocinnamic acid (10.0 g) was added to the hydroxylamine solution obtained as a filtrate, and the mixture was stirred and refluxed for 6 hours. After the reaction was completed, the reaction solution was concentrated under reduced pressure to about half its original volume, and white crystals were precipitated. By filtering and drying this, 3-amino-3-(4-chlorophenyl)propionic acid (5.62 g/yield: 51%) was obtained.

This β-amino acid (1.8 g) and dichloromaleic anhydride (1.8 g) were dissolved in 20M1 acetic acid, and the mixture was stirred and refluxed for 1 hour. After the reaction, the reaction solution was concentrated under reduced pressure and the resulting crystals were washed with a mixed solvent of ether and n-hexane to give 3,4-dichloro-2,5-dihydro-2, 5-'; Oxo α-(
4-chlorophenyl)-IH-pyrrole-1-propionic acid (2,72 g/yield: 87%) was obtained.

The thus obtained carboxylic acid (1.5 g), 1(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (WSC-HCI) (1.0 g) and 4-pyrrolidinopyridine (20 ml) were dissolved in 30 ml of dichloromethane. and add methanol (0.3 wdl") to it,
The reaction was allowed to proceed at room temperature for 3 hours. After the reaction was completed, the reaction solution was concentrated under reduced pressure, the residue was dissolved in ethyl acetate, washed with water, dried over magnesium sulfate, the solvent was distilled off, and the resulting residue was subjected to silica gel chromatography (developing solvent: n-hexane). /ethyl acetate = 9/1) to obtain the title compound (850 cm/yield: 54%) as a pale yellow oil.

Furthermore, Nos. 1 to 10 were obtained by a method similar to the above method.
Compounds 19, 20.22-24.26-28.30-32 and 34-36 were obtained.

Metallic sodium (l1g) was added to ethanol (180d) and dissolved by stirring at room temperature to prepare a sodium ethoxide solution. To this was added a saturated aqueous solution of hydroxylammonium chloride (32,0g), and
The mixture was stirred for 0 minutes, and precipitated common salt was filtered off. Then, m-)lifluoromethylcinnamic acid (20.0 g) was added to the hydroxylamine solution obtained as a filtrate, and the mixture was stirred and refluxed for 6 hours. After the reaction was completed, the reaction solution was concentrated under reduced pressure to about half its original volume, and white crystals were precipitated. By filtering and drying this, 3-amino-3-(3
-trifluoromethylphenyl)propionic acid (5,1
g) was obtained. The obtained crude crystals and dichloromaleic anhydride (4.5 g) were dissolved in 100 yd of acetic acid, and the mixture was stirred and refluxed for 1 hour. After the reaction, the reaction solution was concentrated under reduced pressure and the resulting crystals were washed with a mixed solvent of ether and n-hexane to give 3,4-dichloro-2,5-dihydro-2, 5-dioxo-β-(3-
trifluoromethylphenyl)-1H-pyrrole-1-
Propionic acid (8.70 g/yield: 25%) was obtained.

The carboxylic acid thus obtained (1.5 g) and 1-(
3-Dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (WSC-HCf) (20ml 1g) was dissolved in 30d dichloromethane, and P-toluidine (5
60■) was added thereto, and the mixture was allowed to react at room temperature for 3 hours. After the reaction was completed, the reaction solution was concentrated under reduced pressure, the residue was dissolved in ethyl acetate, washed with water, dried over magnesium sulfate, and the solvent was distilled off.
The obtained residue was purified by silica gel chromatography (developing solvent: n-hexane/ethyl acetate = 8/2) to obtain the title compound as a pale yellow oil (1.30 g/yield: 69
%) was obtained.

Furthermore, by a method similar to the above method, Nα11-172
Compounds 1, 25.29 and 37-44 were obtained.

Compound Nα and physical property values of the compounds synthesized by the method of Example 1 or 2 are shown in Table 1 below. Furthermore, the abbreviations in Table 1 are as follows.

Me: methyl group, Et: ethyl group, Pr: propyl group, Bu nibutyl group, Ph: phenyl group, P
y: pyridyl group, m, p: melting point, nMS: refractive index index.

11th Engineering 2a→- Male'' 11th Engineering 2j]→- 10 parts of compound (Na2) (represents parts by weight. The same applies hereinafter),
Sodium lauryl sulfate 5 parts, sodium dinaphthylmethane disulfonate formalin condensate 2 parts and clay 83
100 parts of a wettable powder were obtained by mixing and pulverizing 100 parts of a wettable powder.

MM5 pull 1m1 [low compound (Na2) 0.2 parts, calcium stearate 0
．． 5 parts of talc, 50 parts of talc, and 493 parts of clay were mixed and ground to obtain 100 parts of a powder.

100 parts of an emulsion was obtained by mixing and dissolving ``1 sword'' LL1, 9 parts of the compound (Nα2), 10 parts of ethylene glycol, 20 parts of dimethylformamide, 10 parts of alkyl dimethyl ammonium chloride, and 51 parts of methanol.

10 parts of the compound (Nα2), 15 parts of starch, 72 parts of bentonite, and 3 parts of sodium salt of lauryl alcohol sulfate were mixed and ground to obtain 100 parts of granules.

1. Potato (test method) Thirty sprouted paddy rice grains (variety Nihonbare) were sown directly into pots and grown in a greenhouse until the 2-3 leaf stage.

A hydrating powder prepared according to the method of Formulation Example 1 was diluted with water to a predetermined concentration on the rice seedlings, and the mixture was sprayed with a spray gun.
Spray 30d per 3 pots, leave at room temperature for 1 day, and then incubate with Pyricularia oryzae.
was inoculated. The inoculum was a suspension of spores of rice blast fungus formed and grown on Inawara decoction agar medium (spore concentration 5Xl).
The seeds were inoculated by spraying using a spray gun.

After inoculation, leave in a greenhouse at 26°C for 24 hours.
Thereafter, the seedlings were grown in a greenhouse at 25°C for 7 days avoiding direct sunlight to develop the disease. After the onset of the disease, the number of lesions per pot was measured, and the control value was calculated using the following formula.

Table 2 (Continued) [Test Results] The control effect of the test chemicals was evaluated using the compound (3,4-dichloro-2,5-dihydro-2) described in JP-A-1-160956.
,5-dioxo-IH-virol-1-propionic acid p
-Toluidineamide; abbreviated as A in the table), the second
Shown in the table.

2. Tomatoes [Test method] Tomato seedlings (variety: Red Cherry) grown at the 5th to 6th leaf stage after sowing (3 replicates per section) were treated with a hydrating powder prepared according to the method of Formulation Example 1 at a predetermined concentration. Diluted with water and sprayed 30% per 3 pots using a spray gun. One day after treatment with the chemical, this was treated with Phytophthora 1nf.
estans) was inoculated. Scrape off the zoospore sacs formed on the tomato leaves and collect 1 x 10S zoospores/
After preparing the seedlings as shown in Table d, they were kept at 13°C for about 1 hour, and after confirming the indirect germination of zoospores (at least 40%), they were inoculated by spraying with a spray gun.

After inoculation, it was stored in a greenhouse at 20°C for 1 day, and then kept in a greenhouse at 25°C for 2 days. Three to four leaves per plant were examined for the lesion area ratio in 10 stages, and the control value was calculated.

〔Test results〕

The control effect of the test agent was evaluated using the compound described in JP-A-1-160956 (3,4-dichloro-2,5-dihydro-2
,5-dioxo-IH-pyrrole-1-propionic acid p
-) luidinamide; abbreviated as A in the table), the third
Shown in the table.

3 1 Rust [Test method] Wheat grown at the first leaf stage after sowing (variety: Norin No. 61) (
A hydrating powder prepared according to the method of Formulation Example 1 was diluted with water to a predetermined concentration and sprayed at 30 d per 3 pots using an automatic spraying device, and 1 day after the drug treatment, Puccinia recondita was inoculated. As an inoculum, we used summer spores obtained by shredding diseased leaves, adding water, applying ultrasound twice, and straining through four layers of gauze.
×10S pieces/xi! A spore suspension was prepared and inoculated. After inoculation, the plants were kept in a humid room at 24°C for 24 hours, and then kept in a glass greenhouse for 9 days. The disease severity was determined using the formula and the control value was calculated accordingly.

0: No disease onset, 1: Number of lesions 1-5.2: Number of lesions 6-10, 3: Number of lesions 11-20.4: Number of lesions 21- Infection degree = [Test results] of the test drug The control effect was evaluated using the compound described in JP-A-1-160956 (3,4-dichloro-2,5-dihydro-2
,5-dioxo-IH-pyrrole-1-propionic acid P
-) luidinamide; abbreviated as A in the table), the fourth
Shown in the table.

Control value = 100- (incidence)

Claims (1)

[Claims] 1. General formula (I): ▲There are mathematical formulas, chemical formulas, tables, etc.▼ [In the formula, X is a hydrogen atom, a halogen atom, or a trifluoromethyl group, and R is a group -OR^1 (In the formula, R^1 is a linear or branched alkyl group having 1 to 5 carbon atoms, an optionally substituted aryl group, an optionally substituted benzyl group), or a group -NR^2R^3 ( In the formula, R^2 and R
^3 each independently represents a hydrogen atom, a linear or branched alkyl group having 1 to 5 carbon atoms, an optionally substituted phenyl group, an optionally substituted benzyl group, or a heterocyclic group)
A maleimide derivative represented by 2. General formula (I): ▲There are mathematical formulas, chemical formulas, tables, etc.▼ [In the formula, X is a hydrogen atom, a halogen atom, or a trifluoromethyl group, and R is a group -OR^1 (in the formula, 1 is a linear or branched alkyl group having 1 to 5 carbon atoms, an optionally substituted aryl group, an optionally substituted benzyl group), or a group -NR^2R^3 (in the formula, R^2 and R
^3 each independently represents a hydrogen atom, a linear or branched alkyl group having 1 to 5 carbon atoms, an optionally substituted phenyl group, an optionally substituted benzyl group, or a heterocyclic group)
An agricultural and horticultural fungicide containing a maleimide derivative represented by the following as an active ingredient.