RU2171806C2 - Derivatives of n-sulfonylimidazole and their acid-additive salts and fungicide agent based on thereof - Google Patents

Abstract

FIELD: organic chemistry, fungicides. SUBSTANCE: invention relates to derivatives of N-sulfonylimidazole of the formula (I)

where R¹ and R² mean hydrogen, halogen atoms, C_1-4-alkyl, C_1-4- - alkoxycarbonyl or phenyl that can be substituted from one to three times with similar or different residues taken among the group including halogen atom, C_1-4-alkyl, trifluoromethyl-group; R₃ is halogen atom, cyano-group, trifluoromethyl-group; R₄ is 4- isoxazolyl, pyrazolyl that can be substituted with halogen atom, C_1-4-alkyl, amino-group, cycloalkyl, and their acid- -additive salts also. These compounds exhibit fungicide activity and can be used as agents for control of fungi in plants diseases. EFFECT: fungicide activity of compounds. 2 cl, 3 tbl, 30 ex

Description

 The invention relates to new nitrogenous heterocyclic compounds having pesticidal activity, in particular to derivatives of N-sulfonylimidazole and their acid addition salts and a fungicidal agent based thereon.

 Derivatives of N-sulfonylimidazole are known to have fungicidal activity (see application EP N 0298196, class C 07 D 233/90, A 61 K 31/415, 01/11/1989).

 The objective of the invention is to expand the range of derivatives of N-sulfonylimidazole with fungicidal activity.

где R¹ и R² независимо друг от друга означают водород, галоген, C_1-4 алкил, C_1-4 алкоксикарбонил или фенил, который может быть замещен от одного до трех раз одинаковыми или различными остатками из группы, включающей галоген, C_1-4 алкил, трифторметил;
R³ - галоген, циано, трифторметил;
R⁴ означает 4-изоксазолил, пиразолил, незамещенные или замещенные от одного до трех раз одинаковыми или различными остатками из группы, включающей галоген, C_1-4 алкил, амино, циклоалкил, и их кислотно-аддитивными солями.The problem is solved by the proposed derivatives of N-sulfonylimidazole of General formula (I)

where R ¹ and R ² independently from each other mean hydrogen, halogen, C _1-4 alkyl, C _1-4 alkoxycarbonyl or phenyl, which may be substituted from one to three times by the same or different residues from the group comprising halogen, C _{1 -4} alkyl, trifluoromethyl;
R ³ is halogen, cyano, trifluoromethyl;
R ⁴ means 4-isoxazolyl, pyrazolyl, unsubstituted or substituted one to three times by the same or different residues from the group consisting of halogen, C _1-4 alkyl, amino, cycloalkyl, and their acid addition salts.

где R¹ и R² имеют вышеуказанные значения, и
R⁵ - галоген, циано или трифторметил,
подвергают взаимодействию с соединением общей формулы (III)
R⁴-SO₂-X (III)
где R⁴ имеет вышеуказанное значение,
X означает галоген,
при необходимости, в присутствии связывающего кислоту вещества и, при необходимости, в присутствии разбавителя.Derivatives of N-sulfonylimidazole of the general formula (I) can be obtained by analogous methods, for example, due to the fact that imidazole derivatives of the general formula (II)

where R ¹ and R ² have the above meanings, and
R ⁵ is halogen, cyano or trifluoromethyl,
subjected to interaction with the compound of General formula (III)
R ⁴ —SO ₂ —X (III)
where R ⁴ has the above meaning,
X is halogen
if necessary, in the presence of an acid binding agent and, if necessary, in the presence of a diluent.

 The target product is isolated in free form or in the form of an acid addition salt.

 Acids that can be used for salt formation include preferably hydrohalic acids, such as, for example, hydrochloric acid and hydrobromic acid, in particular hydrochloric acid, as well as phosphoric acid, sulfuric acid, nitric acid, mono- and bifunctional carboxylic and hydroxycarboxylic acids, such as, for example, acetic acid, maleic acid, succinic acid, fumaric acid, tartaric acid, citric acid, salicylic acid, sorbic acid and lactic acid slots as well as sulfonic acids such as, for example, p-toluenesulfonic acid, 1,5-naphthalenedisulphonic acid, saccharine and tiosaharin.

 If 2,4,5-tribromimidazole and furan-2-sulfonyl chloride are used as starting compounds, the reaction can be represented by the scheme given at the end of the description.

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

 The halides of formula (III) are known or can be obtained by known methods (see J. Heterocycl. Chem., 1981, pp. 997-1006).

 The reaction is preferably carried out in the presence of an acid binder. As such substances can be called all commonly used inorganic and organic bases. Preferably, hydrides, hydroxides, amides, alcoholates, acetates, carbonates or hydrogen carbonates of alkali metals or alkaline earth metals are used, such as, for example, sodium hydride, sodium amide, sodium methylate, sodium ethylate, potassium tert-butylate, sodium hydroxide, potassium hydroxide, sodium acetate, potassium acetate, calcium acetate, sodium carbonate, potassium carbonate, potassium hydrogen carbonate or sodium hydrogen carbonate, as well as ammonium compounds such as, for example, ammonium hydroxide, ammonium acetate or ammonium carbonate, as well as tertiary mines, such as, e.g., trimethylamine, triethylamine, tributylamine, N, N-dimethylaniline, N, N-dimethylbenzylamine, pyridine, N-methylpiperidine, N-methylmorpholine, N, N-dimethylaminopyridine, diazabicyclooctane, diazabicyclononene or diazabicycloundecene.

 As a diluent for the reaction, all commonly used inert organic solvents can be mentioned. Non-halogenated or halogenated aliphatic, alicyclic or aromatic hydrocarbons are preferably used, such as, for example, petroleum ether, hexane, heptane, cyclohexane, methylcyclohexane, benzene, toluene, xylene or decalin; chlorobenzene, dichlorobenzene, dichloromethane, chloroform, carbon tetrachloride, dichloroethane or trichloroethane; ethers, such as, for example, diethyl ether, diisopropyl ether, methyl tert-butyl ether, methyl tert-amyl ether, dioxane, tetrahydrofuran, 1,2-dimethoxyethane, 1,2-diethoxyethane or anisole ; ketones, such as, for example, acetone, butanone, methyl isobutyl ketone 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-methylformanilide, N-methylpyrrolidone or hexamethylphosphoric triamide; esters, such as, for example, acetic acid methyl ester or acetic acid ethyl ester; sulfoxides, such as dimethyl sulfoxide; sulfones, such as sulfolane, or amines, such as pyridine.

The reaction temperature can vary widely. Usually operate at temperatures from 0 ^o C to 150 ^o C, preferably from 20 ^o C to 120 ^o C, and at atmospheric pressure. You can, however, also work at low or high pressure.

 From 1 to 15 mol, preferably from 1 to 2 mol, particularly preferably from 1 to 1.3 mol of a halide of formula (III) is usually used per mole of the imidazole derivative of formula (II). Processing is carried out according to conventional methods. The reaction mixture is usually diluted with water and then extracted with a poorly soluble organic solvent in water, the combined organic phases are dried and concentrated under reduced pressure. The precipitated product is purified, if necessary, of possible contaminants by conventional methods, such as recrystallization or chromatography. If the reaction is carried out in a water-soluble organic solvent, then 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, if necessary, purified by conventional methods.

где R^1' и R^2' независимо друг от друга означают галоген, C_1-4алкил или фенил, замещенный C_1-4алкилом,
R^3' - галоген или трифторметил,
R^4' - 4-изоксазолил, незамещенный или замещенный двукратно одинаковыми или различными остатками из группы, включающей C_1-4алкил, амино, циклоалкил.Due to the fungicidal activity of N-sulfonylimidazole derivatives, an additional object of the invention is a fungicidal agent containing, as an active substance, a compound of the general formula (Ia)

where R ^{1 '} and R ^2' independently from each other mean halogen, C _1-4 alkyl or phenyl substituted with C _1-4 alkyl,
R ^{3 '} is halogen or trifluoromethyl,
R ^{4 '} - 4-isoxazolyl, unsubstituted or substituted twice by the same or different residues from the group consisting of C _1-4 alkyl, amino, cycloalkyl.

 The proposed fungicidal agent is used in plant protection to combat fungi, such as plasmodioforomycetes, oomycetes, chitridiomycetes, cygomycetes, ascomycetes, basidiomycetes, deuteromycetes.

 The good tolerance by plants of the compounds of formula (Ia) (hereinafter “active substances”) at the concentrations necessary for controlling plant diseases allows the treatment of terrestrial parts of plants, seedlings, seeds and soil.

 At the same time, active substances are used with particular success in the fight against diseases of fruits and vegetables, such as, for example, the species Venturia, Podosphaera, Phytophtora and Plasmopara. With good success, they are used to combat rice diseases, for example, with species of Pyricularia.

 Active substances, depending on their physical and / or chemical properties, can be converted into conventional formulations, for example, solutions, emulsions, suspensions, powders, foams, pastes, granules, aerosols, finely encapsulated in polymeric substances forms and in shell-encapsulated masses for seed, as well as in preparations for ultra-low volume spraying cold and hot.

 These compositions are prepared in a known manner, for example, by mixing the active substance with fillers, i.e. liquid solvents, pressurized gases and / or solid carriers, if necessary using surfactants, i.e. emulsifiers and / or dispersants and / or blowing agents. In the case of using water as a filler, organic solvents can also be used as an aid. The liquid solvent used is mainly aromatic hydrocarbons, for example, xylene, toluene or alkylnaphthalenes, chlorinated aromatic or chlorinated aliphatic hydrocarbons, for example, chlorobenzene, ethylene chloride or methylene chloride, aliphatic hydrocarbons, for example, cyclohexane or paraffins, for example, oil fractions, alcohols for example butanol or glycol, as well as their ethers and esters, ketones, for example acetone, methyl ethyl ketone, methyl isobutyl ketone or cyclohexanone, highly polar solvents for example, dimethylformamide and dimethyl sulfoxide, as well as water. By liquefied gaseous fillers or carriers are meant liquids that are gaseous at normal temperature and normal pressure, for example, working gases for aerosols, for example, halogenated hydrocarbons, as well as butane, propane, nitrogen and carbon dioxide. Solid carriers include grinding of natural rocks, for example, kaolin, alumina, talc, chalk, quartz, attapulgite, montmorillonite or diatomaceous earth and grinding of synthetic rocks, for example, finely divided silicic acid, alumina and silicates. As solid carriers for granules, crushed and fractionated natural rocks are used, for example, calcite, marble, pumice, sepiolite, dolomite, as well as synthetic granules from inorganic and organic grinding, as well as granules from organic materials, for example, sawdust, coconut husks, ears of corn and stalks of tobacco. As emulsifying and foaming agents, for example, nonionic and anionic emulsifiers are used, for example, polyoxyethylene fatty acid esters, polyoxyethylene fatty alcohol ethers, for example, alkylaryl polyglycol ether, alkyl sulfonates, alkyl sulfates, arylsulfonates and protein hydrolysates. As the dispersant used, for example, ligninsulfite liquor and methyl cellulose.

 Binders, for example, carboxymethyl cellulose, natural and synthetic powdered, granular or latex polymers, for example, gum arabic, polyvinyl alcohol, polyvinyl acetate, as well as natural phospholipids, for example, cephalins and lecithins, and synthetic phospholipids can also be used in the compositions. Other additives may include mineral and vegetable oils.

 Dyes such as inorganic pigments, for example, iron oxide, titanium oxide, ferrocyanine blue, and organic dyes, for example, alizarin, azo and metal phthalocyanine dyes, and trace elements in the form of salts of iron, manganese, boron, copper, cobalt, can also be used. molybdenum and zinc.

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

 The compounds of the invention can be used in plant protection as such or in the form of mixtures with known fungicides, bactericides, acaricides, nematicides or insecticides in order to expand the spectrum of action or to prevent the development of resistance. Moreover, in many cases synergistic effects are obtained, i.e. the activity of the mixture exceeds the activity of individual compounds.

 Active substances can be used as such, in the form of formulations or in the form of forms prepared from them for use, such as ready-to-use solutions, suspensions, spray powders, pastes, soluble powders, dusting preparations and granules. The application takes place in the usual way, for example, by watering, spraying, scattering, spraying, spreading, etc. It is also possible to apply the active substances with an ultra-low volume method, or apply a composition with an active principle or the active substance itself to the soil. You can also process seed.

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

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

 When processing the soil, the concentration of the active substance in the field of application is from 0.00001 to 0.1 wt.%, Preferably from 0.0001 to 0.02 wt.%.

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

К раствору 2,5 г (15 ммоль) сложного этилового эфира 2-цианимидазол-4-карбоновой кислоты в 40 мл абсолютного тетрагидрофурана прибавляют 0,6 г (15 ммоль) гидрида натрия (60%-ная эмульсия в минеральном масле) и перемешивают при 20^oC в течение 10 минут. Затем добавляют 3,0 г (15 ммоль) 3,5-диметилизоксазол-4-сульфонилхлорида и перемешивают при комнатной температуре в течение дальнейших 20 часов. После этого реакционную смесь разбавляют 150 мл воды. Образующуюся смесь несколько раз экстрагируют сложным этиловым эфиром уксусной кислоты, взятым в количестве по 150 мл. Объединенные органические фазы после сушки над сульфатом натрия сгущают при пониженном давлении. Остаток подвергают хроматографии на силикагеле с применением в качестве элюента дихлорметана. После сгущения элюата при пониженном давлении получают 1,4 г (32% теории) сложного этилового эфира 2-циан-1-(3,5-диметил-изоксазол-4-ил-сульфонил)-имидазол-4- карбоновой кислоты в качестве бесцветного твердого вещества с точкой плавления 150-153^oC.Example 1

To a solution of 2.5 g (15 mmol) of ethyl 2-cyanimidazole-4-carboxylic acid ethyl ester in 40 ml of absolute tetrahydrofuran was added 0.6 g (15 mmol) of sodium hydride (60% emulsion in mineral oil) and stirred at 20 ^o C for 10 minutes. Then add 3.0 g (15 mmol) of 3,5-dimethylisoxazole-4-sulfonyl chloride and stirred at room temperature for a further 20 hours. After this, the reaction mixture was diluted with 150 ml of water. The resulting mixture was extracted several times with ethyl acetate, taken in an amount of 150 ml. The combined organic phases, after drying over sodium sulfate, are concentrated under reduced pressure. The residue was subjected to silica gel chromatography using dichloromethane as an eluent. After the eluate was concentrated under reduced pressure, 1.4 g (32% of theory) of 2-cyan-1- (3,5-dimethyl-isoxazol-4-yl-sulfonyl) -imidazole-4-carboxylic acid ethyl ester was obtained as a colorless solid with a melting point of 150-153 ^o C.

К раствору 3,0 г (5 ммоль) 2,4,5-тирбромимидазола в 30 мл ацетонитрила прибавляют 2,0 г (15 ммоль) карбоната калия и перемешивают при 20^oC в течение 10 минут. Затем добавляют 1,9 г (10 ммоль) 3,5-диметилизоксазол-4-сульфонилхлорида и перемешивают при 20^oC в течение дальнейших 20 часов. Затем реакционную смесь подают на 100 мл воды. Получаемый осадок отфильтровывают и сушат.Example 2

To a solution of 3.0 g (5 mmol) of 2,4,5-tyrbromimidazole in 30 ml of acetonitrile, 2.0 g (15 mmol) of potassium carbonate was added and stirred at 20 ^° C. for 10 minutes. Then 1.9 g (10 mmol) of 3,5-dimethylisoxazole-4-sulfonyl chloride are added and stirred at 20 ^° C. for a further 20 hours. Then the reaction mixture is fed into 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-tribromimidazole as a yellow solid with a melting point of 165-170 ^o C.

К раствору 2,2 г (10 ммоль) 4-хлор-5-(4-толил)-имидазола в 30 мл ацетонитрила прибавляют 2,0 г (15 ммоль) карбоната калия и перемешивают при 20^oC в течение 10 минут. Затем к смеси добавляют 1,9 г (10 ммоль) 3,5-диметилизоксазол-4-сульфонилхлорида и перемешивают при 20^oC в течение 4 часов. После этого реакционную смесь подают на 150 мл воды и экстрагируют сложным этиловым эфиром уксусной кислоты, взятым в количестве 50 мл. Объединенные органические фазы сушат над сульфатом натрия, а затем сгущают при пониженном давлении. Остаток подвергают хроматографии на силикагеле с применением в качестве элюента хлористого метилена. Путем сгущения элюата при пониженном давлении получают 1,8 г (50% теории) 4-хлор-1-(3,5-диметил-изоксазол-4-ил-сульфонил)-5-(4-толил)-имидазол-2- карбонитрила в качестве бесцветного твердого вещества с точкой плавления 103-108^oC.Example 3

To a solution of 2.2 g (10 mmol) of 4-chloro-5- (4-tolyl) -imidazole in 30 ml of acetonitrile, 2.0 g (15 mmol) of potassium carbonate was added and stirred at 20 ^° C. for 10 minutes. Then, 1.9 g (10 mmol) of 3,5-dimethylisoxazole-4-sulfonyl chloride was added to the mixture and stirred at 20 ^° C. for 4 hours. After that, the reaction mixture was fed into 150 ml of water and extracted with ethyl acetate, taken in an amount of 50 ml. The combined organic phases are dried over sodium sulfate and then concentrated under reduced pressure. The residue was subjected to silica gel chromatography using methylene chloride as an eluent. By thickening the eluate under reduced pressure, 1.8 g (50% of theory) of 4-chloro-1- (3,5-dimethyl-isoxazol-4-yl-sulfonyl) -5- (4-tolyl) -imidazole-2- are obtained carbonitrile as a colorless solid with a melting point of 103-108 ^o C.

 Similarly receive the substances shown in table 1.

Fungicidal activity is illustrated by the following examples.
Example 27
Experience with Phytophthora (tomato) / protective effect
1 weight including the active substance is mixed with 47 weight. including acetone as a solvent and 3 weight. including simple alkyl-aryl-polyglycol ether as an emulsifier and the concentrate is diluted with water to the desired concentration.

 To test the protective effect, young plants are sprayed with the preparation of the active substance in an amount of 50 g / ha, and the active substance is used in the amount indicated below. After the preparation has dried, the plants are inoculated with an aqueous suspension of Phytophthora infestans.

Plants are placed in an incubation chamber at a relative humidity of 100% and a temperature of about 20 ^o C.

 3 days after inoculation, an assessment is performed. At the same time, 0% means the degree of action that corresponds to the degree of action achieved in the control experiment, while the degree of action equal to 100% means that no lesion is observed.

 Active substances and experimental results are shown in table 2.

Example 28
Experience with Podosphaera (apple) / protective effect
1 weight including the active substance of example 3 mix 47 weight. including acetone as a solvent and 3 weight. including simple alkyl-aryl-polyglycol ether as an emulsifier and the concentrate is diluted with water to the desired concentration.

 To test the protective effect, young plants are sprayed with the preparation of the active substance, while the active substance is used in an amount of 10 g / ha. After the preparation has dried, inoculation is carried out by pollinating the plants with conidia of the powdery mildew pathogen Podosphaera leucotricha.

Plants are then placed in a greenhouse at a temperature of 23 ^o C and a relative humidity of about 70%.

 10 days after inoculation are evaluated. At the same time, 0% means the degree of action that corresponds to the degree of action achieved in the control experiment, while the degree of action equal to 100% means that no lesion is observed.

 In this experiment, the compound of example 3 shows an activity of 79%.

Example 29
Experience with Plasmopara (grape) / protective effect
1 weight including the active substance is mixed with 47 weight. including acetone as a solvent and 3 weight. including simple alkyl-aryl-polyglycol ether as an emulsifier and the concentrate is diluted with water to the desired concentration.

To test the protective effect, young plants are sprayed with the preparation of the active substance, while the active substance is used in an amount of 50 g / ha. After the preparation has dried, the plants are inoculated with an aqueous suspension of Plasmopara viticola conidia spores, after which they are placed in a humid chamber at a temperature of about 20 - 22 ^o C and a relative humidity of 100% for 24 hours. After this, the plants are visited in a greenhouse at a temperature of 21 ^o C and a relative humidity of about 90% for 24 hours.

 6 days after inoculation, an assessment is performed. At the same time, 0% means the degree of action that corresponds to the degree of action achieved in the control experiment, while the degree of action equal to 100% means that no lesion is observed.

 Active substances and experimental results are shown in table 3.

Example 30
Experience with Venturia (apple) / protective effect
1 weight. including the active substance of examples 4 and 13, respectively, are mixed with 47 weight. including acetone as a solvent and 3 weight. including simple alkyl-aryl-polyglycol ether as an emulsifier and the concentrate is diluted with water to the desired concentration.

To test the protective effect, young plants are sprayed with a preparation of the active substance, while the active substance is used in an amount of 100 g / ha. After the preparation has dried, the plants are inoculated with an aqueous suspension of conidia of the apple scab pathogen Venturia inaequalis, after which they are placed in an incubation chamber at a temperature of about 20 ^o C and a relative humidity of 100% for 24 hours.

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

 12 days after inoculation are evaluated. At the same time, 0% means the degree of action that corresponds to the degree of action achieved in the control experiment, while the degree of action equal to 100% means that no lesion is observed.

 In this experiment, the compounds of both examples exhibit 100% activity.

Claims (2)

1. Derivatives of N-sulfonylimidazole of the formula I

where R ¹ and R ² independently from each other mean hydrogen, halogen, C _1-4 alkyl, C _1-4 alkoxycarbonyl or phenyl, which may be substituted from one to three times by the same or different residues from the group comprising halogen, C _{1 -4} alkyl, trifluoromethyl;
R ³ is halogen, cyano, trifluoromethyl;
R ⁴ - 4-isoxazolyl, pyrazolyl, unsubstituted or substituted one to three times by the same or different radicals from the group consisting of halogen, C _1-4 alkyl, amino, cycloalkyl,
as well as their acid addition salts. 2. A fungicidal agent characterized by a content of an N-sulfonylimidazole derivative of the general formula Ia

where R ^{1 '} and R ^2' independently from each other mean halogen, C _1-4 alkyl or phenyl substituted with C _1-4 alkyl;
R ^{3 '} is halogen, trifluoromethyl, cyano;
R ^{4 '} - 4-isoxazolyl, unsubstituted or substituted twice by the same or different residues from the group consisting of C _1-4 alkyl, amino, cycloalkyl.

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