EP0000376B1 - Ureas and thioureas, processes for their preparation and their use as fungicides - Google Patents

Description

The invention relates to new urea and thiourea compounds, a process for their preparation and their use as fungicides.

worin R₁-R₁₀, die gleich oder verschieden sein können, jeweils Wasserstoff, Halogen, Niederalkyl, Niederalkoxy oder N0₂ bedeuten, mit der Maßgabe, daß wenigstens zwei der Substituenten R,-R₅ und wenigstens zwei der Substituenten R₆―R₁₀ nicht Wasserstoff bedeuten, R₁₁ geradkettiges Alkylen bedeutet, R₁₂ und R₁₃ jeweils Wasserstoff oder Niederalkyl darstellen und X für Sauerstoff oder Schwefel steht, insektizide, akarizide, fungizide und herbizide Wirksamkeit besitzen.In Japanese Patent Publication No. 29252/1969 it is described that compounds of the general formula

wherein R ₁ -R ₁₀ , which may be the same or different, each represent hydrogen, halogen, lower alkyl, lower alkoxy or N0 ₂ , with the proviso that at least two of the substituents R, -R ₅ and at least two of the substituents R ₆ ―R _{10 is} not hydrogen, R _{11 is} straight-chain alkylene, R ₁₂ and R _{13 are} each hydrogen or lower alkyl and X is oxygen or sulfur, have insecticidal, acaricidal, fungicidal and herbicidal activity.

geschaffen, worin R¹ Cycloalkyl mit 5-8 C-Atomen im Ring bedeutet, das gegebenenfalls durch Alkyl mit 1-8 C-Atomen substituiert ist, R² Alkyl mit 1-8 C-Atomen, Cycloalkyl mit 5-8 C-Atomen im Ring oder Phenyl bedeutet, X für Sauerstoff oder Schwefel steht und Y Halogen, Alkyl mit 1-8 C-Atomen, Cyan oder Nitro darstellt.According to the invention, new urea and thiorurea compounds of the general formula

created, wherein R ^{1 is} cycloalkyl with 5-8 C atoms in the ring, which is optionally substituted by alkyl with 1-8 C atoms, R ² alkyl with 1-8 C atoms, cycloalkyl with 5-8 C atoms in the ring or phenyl means, X represents oxygen or sulfur and Y represents halogen, alkyl having 1-8 C atoms, cyan or nitro.

The compounds of formula (I) have been found to have excellent fungicidal activity.

R 'is preferably a cycloalkyl optionally substituted by alkyl having 1-4 C atoms, in particular methyl, having 5-7 C atoms in the ring, in particular cyclopentyl or cyclohexyl; R ² stands for ethyl, n-propyl, n-butyl, sec-butyl, amyl, cyclopentyl, cyclohexyl, cycloheptyl or phenyl and Y means chlorine, bromine, cyano, nitro or alkyl with 1-4 C atoms, especially methyl. The radical Y is particularly preferably in the 4-position.

• a) ein N-Benzyl-IL-cycloatkylämin der allgemeinen Formel
  
  worin R¹ und Y die oben angeführte Bedeutung besitzen, mit einem Isocyanat oder Isothiocyanat der allgemeinen Formel
  
  worin R² und X die oben angeführte Bedeutung besitzen, oder
• b) ein N-Benzyl-N-cycloalkylcarbamoyl(oder -thiocarbamoyl)-halogenid der allgemeinen Formel
  
  worin R¹, X und Y die oben angeführte bedeutung haben und Hal Halogen, insbesondere Chlor oder Brom, bedeutet, mit einem Amin der allgemeinen Formel
  
  umgesetzt wird, worin R² die oben angeführte Bedeutung besitzt.

The invention further relates to a process for the preparation of new urea or thiourea compounds of the formula (1), which is characterized in that.

• a) an N-benzyl-IL-cycloatkylamine of the general formula
  
  wherein R ¹ and Y have the meaning given above, with an isocyanate or isothiocyanate of the general formula
  
  wherein R ² and X have the meaning given above, or
• b) an N-benzyl-N-cycloalkylcarbamoyl (or -thiocarbamoyl) halide of the general formula
  
  wherein R ¹ , X and Y have the meaning given above and Hal means halogen, in particular chlorine or bromine, with an amine of the general formula
  
  is implemented, wherein R ^{2 has} the meaning given above.

Examples of the N-benzyl-N-cycloalkylamines of the general formula (II) to be used as starting materials according to process variant a) are: N - 4 - methylbenzyl - N - cyclopentylamine, N - 4 - methylbenzyl - N - 3 - methylcyclopentylamine, N - 4 - methylbenzyl - N - cyclohexylamine, N - 4 - methylbenzyl - N - 2 - methylcyclohexylamine, N - 4 - chlorobenzyl - N - cyclopentylamine, N - 4 - chlorobenzyl - N - 3 - methylcyclopentylamine, N - 4 - chlorobenzyl - N - cyclohexylamine , N - 4 - chlorobenzyl - N - 2 - methylcyclohexylamine, N - 4 - bromobenzyl - N - cyclopentylamine, N - 4 - bromobenzyl - N - 2 - methylcyclohexylamine, N - 4 - cyanbenzyl - N - cyclopentylamine and N 4 - nitrobenzyl - N - chloropentylamine. .

Examples of the isocyanates and isothiocyanates of the general formula (III) which are also suitable as starting materials according to process variant (a) are: phenyl isocyanate, phenyl isothiocyanate, cyclopentyl isocyanate, cyclohexyl isocyanate, cyclohexyl isothiocyanate, cycloheptyl isocyanate, cycloheptyl isothiothiocyanate, aethiocyanate, sec-butyl isocyanate, sec-butyl isothiocyanate, amyl isocyanate and amyl isothiocyanate.

If N-4-methylbenzyl-N-cyclopentylamine and phenyl isocyanate are used as starting materials according to process variant a), the reaction can be illustrated by the following scheme:

Examples of the N-benzyl-N-cydoalkylcarbamoyl (and thiocarbamoyl) halides of the general formula (IV) to be used as starting materials according to process variant b) are N-4-methylbenzyl-N-cyclopentyl-, N-4-methylbenzyl-N - 3 - methylcyclopentyl -, N - 4 - methylbenzyl - N - cyclohexyl, N - 4 - methylbenzyl - N - 2 - methylcyclohexyl-, N - 4 - chlorobenzyl - N - cyclopentyl-, N - 4 - chlorobenzyl - N - 3 - methylcyclopentyl-, N - 4 - chlorobenzyl - N - cyclohexyl-, N - 4 - chlorobenzyl - N - 2 - methylcyclohexyl-, N - 4 - bromobenzyl - N - cyclopentyl-, N - 4 - bromobenzyl - N - 2 - methylcyclohexyl- , N - 4 - Cyanbenzyl - N - cyclopentyl -, and N - 4 - Nitrobenzyl - N - cyclopentyl - carbamoyl - (or -thiocarbamoyl) - chloride and the corresponding bromides.

Examples of the amines of the general formula (V), which are also suitable for use as starting materials according to process variant b), are aniline, cyclopentylamine, cyclohexylamine, cycloheptylamine, ethylamine, propylamine, butylamine, sec-butylamine and amylamine.

If 4-N-chlorobenzyl-N-cyclopentyl-carbamoyl chloride and cyclohexylamine are used as starting materials according to process variant b), the reaction can be illustrated by the following scheme:

The reaction according to process variant b) can be carried out in the presence of an acid binder. For this purpose, any conventional acid acceptor, e.g. Alkali hydroxide, alkali carbonate, alkali bicarbonate, alkali alcoholate or tertiary organic bases, e.g. Triethylamine, dimethylaniline or pyridine.

Variants a) and b) of the process according to the invention are preferably carried out in the presence of a solvent and / or diluent. Examples of suitable inert solvents or diluents are water and inert organic solvents from the group of the aliphatic, alicyclic and aromatic hydrocarbons, which may optionally be chlorinated, such as e.g. Hexane, cyclohexane, petroleum ether, liqroin, benzene, toluene, xylene, methylene chloride, chloroform, carbon tetrachloride, ethylene chloride, trichlorethylene and chlorobenzene, ether, such as e.g. Diethyl ether, methyl ethyl ether, diisopropyl ether, dibutyl ether, propylene oxide, dioxane and tetrahydrofuran, ketones such as e.g. Acetone, methyl ethyl ketone, methyl isopropyl ketone and methyl isobutyl ketone, nitriles such as e.g. Acetonitrile, propionitrile and acrylonitrile, alcohols such as e.g. Methanol, ethanol, isopropanol, butanol and ethylene glycol, esters such as e.g. Ethyl acetate and amyl acetate, acid amides such as e.g. Dimethylformamide and dimethylacetamide, sulfones and sulfoxides such as e.g. Dimethyl sulfoxide and dimethyl sulfone as well as organic bases such as e.g. Pyridine.

Variants a) and b) of the method according to the invention can be carried out within a wide temperature range. In general, the process is carried out within a temperature range from -20 ° C. and the boiling point of the reaction mixture, preferably at temperatures from 0 to 100 ° C. The reaction is preferably carried out at atmospheric pressure, but it can also be carried out at elevated or reduced pressure.

The compounds of the formula (I) have excellent fungicidal activity and growth-inhibiting activity against phytopathogenic fungi; they can be used for combating and eradicating various diseases caused by phytopathogenic fungi. They are particularly effective against phytopathogenic fungi from the class of the Basidiomycetes, which e.g. Cause leaf sheath blight in rice plants. The active compounds according to the invention can be used against parasitic fungi which attack the part of the plants lying above the ground, against pathogenic fungi which attack the plants in the soil and cause tracheomycosis, and also pathogenic fungi carried by seeds and soil.

The active compounds according to the invention are advantageously used as agricultural and horticultural chemicals in combating fungal diseases on plants, since they have only low toxicity to warm-blooded animals and excellent tolerance to higher plants, i.e. that they have no adverse effect on crop plants when used in conventional concentrations.

The compounds of the invention can therefore be used with great success as fungicides in the control of various pathogenic fungi, such as e.g. Diseases caused by Archimycetes, Phycomycetes, Ascomycetes, Basidiomycetes and Fungi tmperfecti can be used.

The active substances are particularly effective against fungi which cause dry rot or fire (Pellicularia sasakii) and seedling rot (Pellicularia filamentosa), both serious diseases of rice plants. The active ingredients are also useful for combating the following diseases in crops: sclerotic blight (Corticium centrifugum), meltau (Pyricularia oryzae), bacterial blight (Xanthomonas oryzae) on the leaves of rice plants, bacterial soft blight in Chinese cabbage (Erwinia aroideas), citrus cancer (Rust) (Xanthomonas citri), blight (Helmintusporium) (Cochliobolus miyabeanus) in rice plants, banana leaf-infested Grind rot (Mycosphaerella musicola), strawberry-infested gray mold (Botrytis cinerea), meitau on vine sticks (Plasmopara) (Black burner) (Glomella cingulata), sclerotic rot (Sclerotinia sclerotiorum) affecting wine, apple and pear trees, vegetables, anthracnosis in melons (Colletotrichum lagenarium), melanosis (Diaporthe citri) in citrus trees, powder meltau in apple leucotilla (Pod Cucumbers (Sphaerotheca fuliginea), cork stains on apples from Alternaria mali, early rot of potato plants caused by Alternaria solani, black rot on pears due to Alternaria kikuchiana, apple scab (Venturia inaequalis) and pear scab (Venturia pirina).

Because of the excellent fungicidal properties mentioned above, the active compounds according to the invention can be used with good success in combating diseases caused by phytopathogenic fungi which have hitherto been combated with fungicides which contain heavy metals, arsenic or mercury and are harmful to humans and animals.

The active compounds according to the invention can be in the customary formulations, such as solutions, emulsions, wettable powders, suspensions, powders, dusts, foams, pastes, soluble powders, granules, aerosols, concentrated suspensions and emulsions, seed treatment powders, natural and synthetic, impregnated with the active compound materials, very fine capsules in polymeric substances, and coating compositions for use on seed, and formulations for use by Räucherausrüstungen such as Verräucherungspatronen, canisters and -schlangen, as well as in ultra-low-volume ^- (ULV) -Kaltnebel mist and warm mist formulations be transferred.

The formulations can be prepared by known methods such as e.g. by mixing the active ingredient with excipients, i.e. liquid or liquefied gaseous or solid diluents or carriers, optionally using surfactants, i.e. Emulsifiers and / or dispersants and / or foaming agents are produced. If water is used as an extender, organic solvents can be used as auxiliaries.

As examples of liquid diluents or carriers, especially solvents, aromatic hydrocarbons such as e.g. Xylene, toluene or alkylnaphthalenes, chlorinated aromatic or chlorinated aliphatic hydrocarbons, e.g. Chlorobenzenes, chloroethylene or methylene chloride, aliphatic or alicyclic hydrocarbons, e.g. Cyclohexane, or paraffins, e.g. Petroleum fractions alcohols, e.g. Butanol or glycol and their ethers and esters, ketones, e.g. Acetone, methyl ethyl ketone, methyl isobutyl ketone or cyclohexanone, or strongly polar solvents such as e.g. To name dimethylformamide and dimethyl sulfoxide and water.

Liquefied gaseous diluents or carriers are to be understood as liquids which are gaseous at normal temperatures and formal pressures, e.g. Aerosol propellants, e.g. halogenated hydrocarbons, and butane, propane, nitrogen and carbon dioxide.

Ground solid minerals such as e.g. Kaolins, clays, talc, chalk, quartz, attapulgite, montmorillonite or kieselguhr and ground synthetic minerals, e.g. highly disperse silica, aluminum oxide and silicates. Crushed and fractionated natural rocks such as e.g. Calcite, marble, pumice, sepiolite and dolomite, as well as synthetic granules from inorganic and organic flours and granules from organic materials such as Sawdust or sawdust, coconut shells, corn cobs and tobacco stalks can be used.

Examples of suitable emulsifiers and / or foaming agents are nonionic and anionic emulsifiers, such as e.g. Polyoxyethylene fatty acid esters, polyoxyethylene fatty alcohol ethers, e.g. Alkylaryl polyglycol ethers, alkyl sulfonates, alkyl sulfates, aryl sulfonates and albumin hydrolysis products. Suitable lignin sulfite liquors and methyl cellulose can be mentioned as suitable dispersants.

In the formulations, adhesives such as carboxymethyl cellulose and natural and synthetic polymers in the form of powders, granules or latices, e.g. Gum arabic, polyvinyl alcohol and polyvinyl acetate can be used.

Colorants such as e.g. inorganic pigments, e.g. Iron oxide, titanium oxide and Prussian blue and organic dyes such as e.g. Alizarin dyes, azo dyes or metal; phthalcyanine dyes and trace nutrients such as the salts of iron, manganese, boron, copper, cobalt, molybdenum and zinc can be used.

The active compounds according to the invention can be mixed in the formulations with other active compounds, e.g. Fungicides, insecticides, acaricides, nematocides, herbicides, bird deterrents, growth regulators, plant nutrients and soil structure improvers are used.

The formulations in general contain from 0.1 to 95 wt .-%, preferably 0.5-90 wt -9 ₆ of active ingredient.

The active compounds can be used as they are or in the form of ready-to-use solutions, emulsions, suspensions, powders, pastes and granules prepared from the formulations by further dilution. Their application can also be carried out in the usual way e.g. by watering, spraying, atomizing, dusting, scattering, dry pickling, wet pickling and wet pickling, sludge pickling or incrusting.

The active substance concentrations in the use forms can be varied within a wide range. They are generally between 0.0001 and 20% by weight, preferably between 0.005 and 10% by weight.

In general, 0.03-10 kg, preferably 0.3-6 kg, of active ingredient are used per hectare of soil.

The present invention also provides a fungicidal composition which, as an active ingredient, mixes a compound (I) according to the invention with a solid or liquefied, gaseous Ver contains a diluent or carrier or mixed with a liquid diluent or carrier containing a surfactant.

The invention further relates to the use of the compounds of the formula for combating fungi; a compound according to the invention is applied to the fungi or their habitat alone or in the form of a composition which contains a compound according to the invention mixed with a diluent or carrier as active ingredient.

Agricultural and horticultural products can be protected from fungal attack by growing them in areas to which a compound of the general formula (I) according to the invention, alone or mixed with a diluent or carrier, was applied immediately before and / or during the growth of the plants is.

The current methods of harvesting crops from horticultural and horticultural products can be improved by the present invention.

The invention is illustrated by the examples below. The compounds according to the invention are each designated by the number of the corresponding preparation example. Parts mean parts by weight.

Example (i) (wettable powder)

50 parts by weight of compound no. 1, 45 parts by weight of a mixture (1: 5) of diatomaceous earth and kaolin and 5 parts of an emulsifier (polyoxyethylene alkylphenyl ether) are pulverized and mixed to form a wettable powder, which is sprayed with water is diluted to a concentration of 0.05%.

Example (ii) (Emulsifiable concentrate)

30 parts of compound no. 3, 30 parts of xylene, 30 parts of methylnaphthalene and 10 parts of a polyoxyethylene alkylphenyl ether are converted with stirring into an emulsifiable concentrate which is diluted to a concentration of 0.05% with water before spraying.

Example (iii) (dust)

2 parts of compound no. 21 and 98 parts of a mixture (1: 3) of talc and clay are pulverized and mixed to a dust which is dusted.

Example (iv) (dust)

1.5 parts of compound No. 23, 0.5 part of isopropyl hydrogen phosphate and 98 parts of a mixture (1: 3) of talc and clay are pulverized and mixed to form a dust.

Example (v) (granules)

10 parts of compound no. 27, 10 parts of bentonite, 78 parts of a mixture (1: 3) of talc and clay and 2 parts of lighnine sulfonate are mixed and mixed with 25 parts of water. The thoroughly blended mixture is processed by extrusion granulator into granules with a particle size of 350-700 µm (20-40 mesh), which is dried at 40-50 ° C.

Example (vi) (granules)

95 parts of clay powder with a particle size distribution of 0.2 to 2 mm are placed in a rotary mixer. During the rotation, the particles are sprayed evenly with a solution of 5 parts of Compound No. 29 in an organic solvent. The mixture is converted into granules by drying at 40-50 ° C.

Example (vii) (Oily preparation)

0.5 part of compound No. 30, 20 parts of a high-boiling aromatic compound and 79.5 parts of kerosene are mixed with stirring to form an oily preparation.

The fungicidal activity of the compounds according to the invention can be seen from the bioassay example below.

In this example, the compounds according to the invention are each designated by the number (in parentheses) of the corresponding preparation example which follows later in the description.

The known comparison compounds are defined as follows:

• (B) = ein Polyoxinkomplex (handelsüblich)
• (C) = Bis-(dimethylthiocarbamoylthio)-methyl-arsin

(described in Japanese Patent Publication No. 29252/1969)

• (B) = a polyoxine complex (commercially available)
• (C) = bis (dimethylthiocarbamoylthio) methyl arsine

Example A

• Wirkstoff: 50 Gew.-Teile
• Trägermittel: 45 Gew.-Teile eines Gemisches (1:5) aus Kieselgur und Kaolin
• Emulgator: 5 Gew.-Teile Polyoxyäthylenalkylphenyläther

Efficacy test against pellicularia sasakii (leaf sheath dry rot), pot test. Preparation of the fungicidal composition:

• Active ingredient: 50 parts by weight
• Carrier: 45 parts by weight of a mixture (1: 5) of diatomaceous earth and kaolin
• Emulsifier: 5 parts by weight of polyoxyethylene alkylphenyl ether

The above-mentioned amounts of active ingredient, carrier and emulsifier were ground to a wettable powder, which was diluted with water to the prescribed concentration.

Test procedure:

Rice plants (variety: Kinmaze) were grown in Wagner pots (0.0002 a) under flood conditions. When the rice plant reached the early ear stage, a liquid preparation, prepared as described above and containing an active ingredient in the prescribed concentration, was applied to it in amounts of 100 ml / per 3 pots.

worin

• N die Gesamtzahl der untersuchten Pflanzenstengel,
• n_o die Zahl der nicht befallenen Stengel,
• n₁ die Zahl der Stengel, an welchen sich der Befall vom unteren Teil der Pflanze bis zum ersten Blattscheidenabschnitt erstreckt,
• n₂ die Zahl der Stengel, an welchen sich der Befall vom unteren Teil der Pflanze bis zum zweiten Blattscheidenabschnitt erstreckt und
• n₃ die Anzahl der Stengel bedeutet, an welchem sich der Befall vom unteren Teil der Pflanze bis zum dritten Blattscheidenabschnitt erstreckt.

One day after application of the active ingredient, the lower parts of the plants were inoculated with the fungus pellicularia sasakii (which had been grown on a barley medium for 10 days to form sclerotia). The plants were kept in a greenhouse at 28-30 ^o C and a relative humidity of at least 95%. The degree of infestation was then assessed and the phytotoxicity of the active ingredient determined. During the assessment, the extent of the affected parts was determined from the inoculation point (at the lower part of the plants) and calculated as follows:

wherein

• N the total number of plant stems examined,
• n _o the number of unaffected stems,
• n ₁ the number of stems on which the infestation extends from the lower part of the plant to the first leaf sheath section,
• n ₂ the number of stems on which the infestation extends from the lower part of the plant to the second leaf sheath section and
• n _{3 means} the number of stems on which the infestation extends from the lower part of the plant to the third leaf sheath section.

The results are shown in Table A. The symbol "-" in the last column means that no phytotoxicity was observed.

The process for the preparation of the compounds according to the invention is explained in more detail with reference to the preparation examples below.

example 1

With cooling and stirring, a solution of 14 g of phenyl isothiocyanate in 50 ml of hexane was added dropwise to 19 g of N-4-methylbenzyl-N-cyclopentylamine in 400 ml of hexane. After the addition was complete, the temperature of the reaction mixture was gradually raised, and the solution was stirred at 40 ° C for about 5 hours. The mixture was then cooled and filtered. Recrystallization from a mixture of hexane and ethyl alcohol gave 30 g of N-4-methylbenzyl-N-cyclopentyl-N'-phenylthiourea with a melting point of 109-111 ° C.

Example 2

Analogously to the method described in Example 1, 31 g of N-4-chlorobenzyl-N-cyclopentylamine were reacted with 13 g of propyl isocyanate and 32 g of N-4-chlorobenzyl-N-cyclopentyl-N'-propylurea with a melting point of 103- Get 105 ° C.

Other compounds of the invention prepared according to the methods described in Examples 1 and 2 are listed in Table 1.

Example 17 (alternative method)

A solution of 27 g of N-4-chlorobenzyl-N-cyclopentyl-carbamoyl chloride in 100 ml of toluene was added dropwise to 20 g of cyclohexylamine in 400 ml of toluene with cooling and stirring. After the addition was complete, the temperature of the reaction mixture was gradually raised and the mixture was stirred at 70-80 ^° C for about 10 hours. After cooling, the resulting cyclohexylamine hydrochloride was filtered off. The toluene layer was washed with water, 1% aqueous sodium carbonate, 1% hydrochloric acid and water and dried over anhydrous sodium sulfate. The toluene was then distilled off and the residue was recrystallized from a mixture of hexane and ethyl alcohol, and 25 g of N-4-chlorobenzyl-N-cyclopentyl-N'-cyclohexylurea with a melting point of 99-101 ° C. were obtained.

Claims (5)

1. Urea and thiourea compounds of the general formula

in which

R' represents cycloalkyl with 5-8 carbon atoms in the ring, which may be optionally substituted by alkyl with 1-8 carbon atoms, R² represents alkyl with 1-8 carbon atoms, cycloalkyl with 5-8 carbon atoms in the ring or phenyl, X represents oxygen or sulphur, and Y represents halogen, alkyl with 1-8 carbon atoms, cyano or nitro.

2. A process for the preparation of new urea or thiourea compounds of formula (1), characterised in that a) an N-benzyl-N-cycloalkylamine of the general formula

in which

R¹ and Y have the meanings stated in claim 1, is reacted with an isocyanate or isothiocyanate of the general formula

in which

R² and X have the meanings stated in claim 1, or (b) an N-benzyl-N-cycloalkyl carbamoyl (or thiocarbamoyl) halide of the general formula

in which

R¹, X and Y have the meanings stated in claim 1, and Hal represents halogen, in particular chlorine or bromine, is reacted with an amine of the general formula

in which

R² has the meaning stated in claim 1.

3. A fungicidal composition, characterised in that it contains urea and thiourea compounds according to claim 1.

4. The use of urea and thiourea compounds according to claim 1 for combating fungi.

5. A process for the preparation of fungicidal compositions, characterized in that urea and thiourea compounds according to claim 1 are mixed with diluents and surface-active ingredients.