Derivatives of n-sulfanilimide and their acid additive salt and fungicidal agent based on them

 

(57) Abstract:

The invention relates to derivatives of N-sulfanilimide formula I, where R1and R2denote hydrogen, halogen, C1-4alkyl, C1-4alkoxycarbonyl or phenyl which can be substituted one to three times, equal or different residues from the group comprising halogen, C1-4alkyl, trifluoromethyl; R3- halogen, cyano, trifluoromethyl; R4- 4-isoxazolyl, pyrazolyl, which may be substituted with halogen, C1-4the alkyl, amino group, cycloalkyl, as well as their acid additive salt. Due to the fungicidal activity of the compounds of formula I, it is also an object of the invention is a fungicidal agent used to combat fungi, plant diseases. 2 C. p. F.-ly, 3 tables.

The invention relates to novel nitrogen heterocyclic compounds with pesticidal activity, in particular to derivatives of N-sulfanilimide and their acid additive salts and fungicidal tool based on them.

Known derivatives of N-sulfanilimide possessing fungicidal activity (see application EP N 0298196, class C 07 D 233/90, A 61 K 31/415, 11.01.1989 year).

Object of the invention is the extension of the problem is solved by the proposed derivative N-sulfanilimide General formula (I)

< / BR>
where R1and R2independently of one another denote hydrogen, halogen, C1-4alkyl, C1-4alkoxycarbonyl or phenyl which can be substituted one to three times, equal or different residues from the group comprising halogen, C1-4alkyl, trifluoromethyl;

R3- halogen, cyano, trifluoromethyl;

R4means 4-isoxazolyl, pyrazolyl, unsubstituted or substituted from one to three identical or different residues from the group comprising halogen, C1-4alkyl, amino, cycloalkyl, and their acid additive salts.

Derivatives of N-sulfanilimide General formula (I) can be obtained by ways of peers, for example, due to the fact that the imidazole derivatives of General formula (II)

< / BR>
where R1and R2have the above values, and

R5halogen, cyano or trifluoromethyl,

subjected to interaction with the compound of General formula (III)

R4-SO2-X (III)

where R4has the above value,

X represents halogen,

if necessary, in the presence of acid binding agents and, if necessary, in the presence of a diluent.

The target product is isolated in free form or in the form of predpochtitelno halogen acids, such as, for example, hydrochloric acid and Hydrobromic acid, in particular hydrochloric acid, and also phosphoric acid, sulfuric acid, nitric acid, mono - and bifunctional carboxylic, hydroxycarbonate acid, such as, for example, acetic acid, maleic acid, succinic acid, fumaric acid, tartaric acid, citric acid, salicylic acid, sorbic acid and lactic acid, and sulfonic acids, such as, for example, p-toluensulfonate, 1,5-naphthalenedisulfonate, saccharin and tishrin.

If the parent compounds to use 2,4,5-tribromoimidazole and furan-2-sulphonylchloride, the reaction course can be represented by the scheme shown in the end of the description.

The imidazoles of General formula (II) are known or can be obtained by known methods (see Chem. Ber. (1877) 10. page 1370; J. Heterocycl. Chem. (1967) 4 page 399; Chem. Ber. (1976) 109, page 1625 application DE N 2634053; application DE N 2646192; J. Chem. Soc. (1910) 97, page 1824; J. Chem. Soc. Perkin Trans. 1 (1989) pp. 95-99; ACS Symp. Ser. (1955), 584 (Synthesis and Chemistry of Agrochemicals IV), pp. 375-83; Tetrahedron (1994), 50(19), page 5741-52; application EP N 0390506: Synlett (1990), (5), pp. 277-8; application WO 95-17390; the aforementioned application EP N 0298196).

The halides of formula (III) are known or can be obtained by known acid binding substances. As such substances can be called all commonly used inorganic and organic bases. Preferably used hydrides, hydroxides, amides, alcoholate, acetates, carbonates or bicarbonates of alkali metals or alkaline earth metals, such as, for example, sodium hydride, sodium amide, sodium methylate, sodium ethylate, tert.butyl potassium, sodium hydroxide, potassium hydroxide, sodium acetate, potassium acetate, calcium acetate, sodium carbonate, potassium carbonate, potassium bicarbonate or sodium bicarbonate, and ammonium compounds such as, for example, ammonium hydroxide, ammonium acetate or ammonium carbonate, and also tertiary amines, such as, for example, trimethylamine, triethylamine, tributylamine, N,N-dimethylaniline, N,N-dimethylbenzylamine, pyridine, N-methylpiperidine, N-methylmorpholine, N, N-dimethylaminopyridine, diazabicyclo, diazabicyclo or databaseconnect.

As a diluent for the reaction can be called all of the commonly used inert organic solvents. Preferably use not halogenated or halogenated aliphatic, alicyclic or aromatic hydrocarbons, such as, for example, petroleum ether, giarmata, chloroform, carbon tetrachloride, dichloroethane or trichloroethane; ethers, such as, for example, a simple diethyl ether, simple diisopropyl ether, simple tert.butyl ether, simple tert.amyl ether, dioxane, tetrahydrofuran, 1,2-dimethoxyethane, 1,2-diethoxyethane or anisole; ketones, such as, for example, acetone, butanone, methyl-isobutylketone or cyclohexanone; NITRILES, such as, for example, acetonitrile, propionitrile, n - or ISO-butyronitrile or benzonitrile; amides, such as, for example, N,N-dimethylformamide, N,N-dimethylacetamide, N-methylformamide, N is an organic or triamide hexamethylphosphoric acid; esters, such as, for example, methyl ester of acetic acid or complex ethyl ester of acetic acid; sulfoxidov, such as dimethyl sulfoxide; sulfones, such as, for example, sulfolane, or amines, such as pyridine.

The reaction temperature may vary within wide limits. Typically operate at temperatures from 0oC to 150oC, preferably from 20oC to 120oC, and at atmospheric pressure. You can, however, also be operated at reduced or increased pressure.

On mol imidazole derivative of the formula (II) is usually used the testing carried out by the usual methods. The reaction mixture is usually diluted with water, and then extracted with slightly soluble in water with an organic solvent, the combined organic phases are dried and concentrated under reduced pressure. Usageprice product is purified, if necessary, from possible contamination by conventional methods such as recrystallization or chromatography. If the reaction is carried out in a water-soluble organic solvent, upon dilution of the reaction mixture with water, the desired product is sometimes obtained as a solid. In this case, the extraction disappears. The solid is separated and optionally purified by conventional methods.

Due to the fungicidal activity of derivatives of N-sulfanilimide additional object of the invention is a fungicidal agent containing as active substance a compound of General formula (Ia)

< / BR>
where R1'and R2'independently of one another denote halogen, C1-4alkyl or phenyl, substituted C1-4the alkyl,

R3'- halogen or trifluoromethyl,

R4'- 4-isoxazolyl, unsubstituted or substituted twice the same or different residues from the group including1-4alkyl, and what with fungi, such as plasmodiophoromycota, oomycetes, they, zygomycete, records of Ascomycetes, basidiomycetes, deuteromycetes.

Good tolerance of plants compounds of formula (Ia) (hereinafter "the active compounds") when necessary to combat plant diseases concentrations allows for processing ground parts of plants, seedlings, seeds and soil.

The active substance with great success used to combat diseases of fruits and vegetables, as, for example, types of Venturia, Podosphaera, Phytophtora and Plasmopara. With good success, they are used to fight diseases of rice, for example, Pyricularia species.

Active substances depending on their physical and/or chemical properties may be converted in the usual formulation, for example, solutions, emulsions, suspensions, powders, foams, pastes, granules, aerosols, nonconception in polymeric substances form and enclosed in a shell mass for seed, as well as in the preparations for ultradiscrete spraying cold and hot way.

These compounds get in a known manner, for example by mixing the active substances with extenders, i.e. liquid solvents, are TV, i.e. emulsifiers and/or dispersants and/or foam. In the case of using water as a filler can also be used as an aid in organic solvents. As liquid solvents are mainly used aromatic hydrocarbons, such as xylene, toluene or alkylnaphthalenes, chlorinated aromatic or chlorinated aliphatic hydrocarbons, such as chlorobenzene, ethylene chloride or methylene chloride, aliphatic hydrocarbons, e.g. cyclohexane or paraffins, for example petroleum fractions, alcohols, such as butanol or glycol and also their ethers and esters, ketones, such as acetone, methyl ethyl ketone, methyl isobutyl ketone or cyclohexanone, highly polar solvents such as dimethylformamide and dimethylsulfoxide, and water. Under liquefied gaseous extenders or carriers understand such liquids at normal temperature and normal pressure are gaseous, for example, working gases for aerosols, for example, halogenated hydrocarbons as well as butane, propane, nitrogen and carbon dioxide. As solid carriers use the grinding of natural rocks, for example, the Koala the x rocks for example, highly dispersed silicic acid, alumina and silicates. As solid carriers for granules are used crushed and fractionated natural rocks such as calcite, marble, pumice, thick, dolomite, and also synthetic granules of inorganic and organic grinding, and also granules of organic material such as sawdust, coconut husk, corn cobs and stalks of tobacco. As emulsifying and foaming means is used, for example, nonionic and anionic emulsifiers, for example, esters of polyoxyethylene and fatty acids, ethers of polyoxyethylene and fatty alcohols, for example, alkylarylsulphonates simple ether, alkyl sulphonates, alkyl sulphates, arylsulfonate and protein hydrolysates. As a dispersant is used, for example, ligninolytic liquor and methylcellulose.

The compositions can also be used binders, for example carboxymethylcellulose, natural and synthetic powdered, granular or latex polymers, such as gum Arabic, polyvinyl alcohol, polyvinyl acetate, and also natural phospholipids, such as Catalina and lecithins, and synthetic phospholipids. Friend, the such as inorganic pigments, for example iron oxide, titanium oxide, ferrocyanide blue, and organic dyes, for example, alizarin, azo and metallophthalocyanine dyes, and trace elements in the form of salts of iron, manganese, boron, copper, cobalt, molybdenum and zinc.

The compositions usually contain from 0.1 to 95 wt.% the active substance, preferably from 0.5 to 90%.

Compounds according to the invention can be used in plant protection as such or in the form of compounds in a mixture with known fungicides, bactericides, acaricides, nematicides or insecticides, in order to widen the spectrum of action or to prevent the development of resistance. In many cases get Energeticheskie effects, i.e. the activity of the mixture exceeds the activity of the individual compounds.

The active substance can be applied as such, in the form of compounds or in the form of cooked of these forms for applications, such as ready-to-use solutions, suspensions, powders for spraying, pastes, soluble powders, preparations for dusting and pellets. The application in the normal way, for example by watering, spraying, spreading, spraying, smearing, etc. Also the active ingredient incorporated into the soil. You can also process the seed.

When processing parts of plants the concentration of the active substance in a form ready for use, vary in a wide interval: usually, they range from 1 to 0.0001 wt.%, preferably from 0.5 to 0.001 wt.%.

When the seed treatment, the amount of active substance is usually from 0.001 to 50 g per kg of seed, preferably from 0.01 to 10 g

During cultivation, the concentration of active substance in the applications is from 0.00001 to 0.1 wt.%, preferably from 0.0001 to 0.02 wt.%.

Obtaining compounds of formula (I) is illustrated by the following examples.

Example 1

< / BR>
To a solution of 2.5 g (15 mmol) of a compound ethyl ester 2-cyanimide-4-carboxylic acid in 40 ml of absolute tetrahydrofuran is added 0.6 g (15 mmol) of sodium hydride (60% emulsion in mineral oil) and stirred at 20oC for 10 minutes. Then add 3.0 g (15 mmol) of 3,5-dimethylisoxazol-4-sulphonylchloride and stirred at room temperature for further 20 hours. After the reaction mixture is diluted with 150 ml of water. The resulting mixture is extracted several times complex ethyl ester acetic acid, taken the impression. The residue is subjected to chromatography on silica gel using as eluent dichloromethane. After separation of the eluate under reduced pressure to obtain 1.4 g (32% of theory) of a compound ethyl ester 2-cyan-1-(3,5-dimethyl-isoxazol-4-yl-sulfonyl)-imidazole-4 - carboxylic acid as a colorless solid with a melting point 150-153oC.

Example 2

< / BR>
To a solution of 3.0 g (5 mmol) of 2,4,5-dibromomethane in 30 ml of acetonitrile was added 2.0 g (15 mmol) of potassium carbonate and stirred at 20oC for 10 minutes. Then add to 1.9 g (10 mmol) of 3,5-dimethylisoxazol-4-sulphonylchloride and stirred at 20oC for further 20 hours. The reaction mixture is poured on 100 ml of water. The resulting precipitate is filtered off and dried.

Obtain 2.7 g (58% of theory) of 1-(3,5-dimethylisoxazol-4-yl - sulfonyl)-2,4,5-tribromoimidazole as a yellow solid with a melting point of 165-170oC.

Example 3

< / BR>
To a solution of 2.2 g (10 mmol) 4-chloro-5-(4-tolyl)-imidazole in 30 ml of acetonitrile was added 2.0 g (15 mmol) of potassium carbonate and stirred at 20oC for 10 minutes. Then added to the mixture of 1.9 g (10 mmol) of 3,5-dimethylisoxazol-4-sulphonylchloride and stirred at 20oC techou acid, taken in a quantity of 50 ml the combined organic phases are dried over sodium sulfate, and then concentrated under reduced pressure. The residue is subjected to chromatography on silica gel using as eluent methylene chloride. Through evaporation of the eluate under reduced pressure to obtain 1.8 g (50% of theory) of 4-chloro-1-(3,5-dimethyl-isoxazol-4-yl-sulfonyl)-5-(4-tolyl)-imidazole-2 - carbonitrile as a colorless solid with a melting point 103-108oC.

Similarly receive are shown in table 1 substances.

Fungicidal activity is illustrated by the following examples,

Example 27

Experience with Phytophthora (tomato) / protective action

1 weight. including the active substance is mixed with 47 weight. including acetone as solvent and 3 weight. including simple alkyl-aryl-polyglycolic ether as an emulsifier and the concentrate is diluted with water to the desired concentration.

For testing protective activity, young plants are sprayed with the preparation of the active substance in a quantity of 50 g/ha, the active substance is applied in the following number. After priyanie drug carry out the inoculation of the plants with an aqueous suspension of Phytophthora infestans.

Plants are placed in the incubation AI assess. 0% means the degree of action, which corresponds to the degree steps achieved in the control experiment, while the level of 100% means that the lesion is not observed.

The active substance and the results of the experiment are shown in table 2.

Example 28

Experience with Podosphaera (Apple) / protective action

1 weight. including the active substance of example 3 is mixed 47 weight. including acetone as solvent and 3 weight. including simple alkyl-aryl-polyglycolic ether as an emulsifier and the concentrate is diluted with water to the desired concentration.

For testing protective activity, young plants are sprayed with the preparation of the active substance, the active substance is used in an amount of 10 g/ha After priyanie drug carry out inoculation by dusting the plants conidine pathogen of Apple powdery mildew Podosphaera leucotricha.

The plants are then placed in a greenhouse at a temperature of 23oC and a relative humidity of about 70%.

10 days after inoculation assess. 0% means the degree of action, which corresponds to the degree steps achieved in the control experiment, while the level of 100% means that h is CLASS="ptx2">

Example 29

Experience with Plasmopara (grape) / protective action

1 weight. including the active substance is mixed with 47 weight. including acetone as solvent and 3 weight. including simple alkyl-aryl-polyglycolic ether as an emulsifier and the concentrate is diluted with water to the desired concentration.

For testing protective activity, young plants are sprayed with the preparation of the active substance, the active substance is applied in a quantity of 50 g/ha After priyanie drug plants inoculant with an aqueous suspension of conidia spores Plasmopara viticola, after which they are placed in a humid chamber at a temperature of about 20 - 22oC and a relative humidity of 100% within 24 hours. After this plant visit in the greenhouse at a temperature of 21oC and a relative humidity of about 90% within 24 hours.

6 days after inoculation assess. 0% means the degree of action, which corresponds to the degree steps achieved in the control experiment, while the level of 100% means that the lesion is not observed.

The active substance and the results of the experiment are shown in table 3.

Example 30

Experience with Venturia (Apple) / protective action

1 weight. including atprestige alkyl-aryl-polyglycolic ether as an emulsifier and the concentrate is diluted with water to the desired concentration.

For testing protective activity, young plants are sprayed with the preparation of the active substance, the active substance is applied in the amount of 100 g/ha After priyanie drug plants inoculant with an aqueous suspension of conidia of the pathogen of Apple scab Venturia inaequalis, after which they are placed in an incubation chamber at a temperature of about 20oC and a relative humidity of 100% within 24 hours.

Then the plants are placed in a greenhouse at a temperature of 20oC and a relative humidity of about 70%.

12 days after inoculation assess. 0% means the degree of action, which corresponds to the degree steps achieved in the control experiment, while the level of 100% means that the lesion is not observed.

This experience of connection both examples show 100% activity.

1. Derivatives of N-sulfanilimide formula I

< / BR>
where R1and R2independently of one another denote hydrogen, halogen, C1-4alkyl, C1-4alkoxycarbonyl or phenyl which can be substituted one to three times, equal or different residues from the group comprising halogen, C1-4alkyl, trifluoromethyl;1-4alkyl, amino, cycloalkyl,

and their acid additive salt.

2. Fungicidal agent which contains a derivative of N-sulfanilimide General formula Ia

< / BR>
where R1'and R2'independently of one another denote halogen, C1-4alkyl or phenyl, substituted C1-4by alkyl;

R3'halogen, trifluoromethyl, cyano;

R4'- 4-isoxazolyl, unsubstituted or substituted twice the same or different residues from the group including1-4alkyl, amino, cycloalkyl.

 

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