KR820000055B1 - Process for the preparation of urea or thiourea compounds - Google Patents

Abstract

Fungicidal title compds. (I; R1 = C5-8 cycloalkyl; R2 = C1-8 alkyl, C5-8 cycloalkyl, Ph; X = O, S; Y = halogen, C1-8 alkyl, cyano, nitro) were prepd. by reaction of N-benzyl-N-cycloalkylamine (II) and isocyanate or isothiocyanate (III). Thus, 14 g III(R2 = Ph; X = S) in 50 ml C6H6 was reacted with 19 g II(R1 = cyclopentyl; R2 = Ph; X = S; Y = Me) (m.p.; 109-111≰C).

Description

Process for preparing urea or thiourea compound

The present invention relates to a process for the preparation of the urea and thiourea compounds of the following structural formula (I) effective as fungicides.

In the above formula, R ¹ is cycloalkyl having 5 to 8 carbon atoms in the ring may be optionally substituted by alkyl having 1 to 8 carbon atoms, R ² is alkyl having 1 to 8 carbon atoms, cycloalkyl having 5 to 8 carbon atoms in the ring or Phenyl, X is oxygen or sulfur, and Y is halogen, alkyl having 1 to 8 carbons, cyano or nitro.

It is disclosed in the specification of Japanese Patent Application No. 29252/1969 that the compound of the following formula (VI) has insecticidal, acaricide, sterilization and scavenging action.

In the above formula, R ₁ to R ₁₀ should not be the same, and hydrogen, halogen, lower alkyl, lower alkoxy or NO under the condition that at least two of R ₁ to R ₅ and at least two of R ₆ to R ₁₀ are not hydrogen, respectively. ₂ , R ₁₁ is linear alkylene, R ₁₂ and R ₁₃ are each hydrogen or lower alkyl and X is oxygen or sulfur.

The compound of formula (I) has an excellent bactericidal action.

R ₁ is optionally substituted cycloalkyl having 5 to 7 carbon atoms of the ring (especially cyclopentyl or cyclohexyl) by alkyl having 1 to 4 carbon atoms (especially methyl); R ² is ethyl, n-propyl, n-butyl, secondary-butyl, amyl, cyclopentyl, cyclohexyl, cycloheptyl or phenyl; It is preferable that Y is chlorine, bromine, cyano, nitro or alkyl having 1 to 4 carbon atoms (particularly methyl), and it is particularly preferable that Y is located in the 4-position.

According to the present invention, the urea or thiourea compound of formula (I) may be reacted with (a) N-benzyl-N-cycloalkylamine of formula (II) with an isocyanate or isothiocyanate of formula (III) Or (b) reacting an N-benzyl-N-cycloalkyl carbamoyl (or thiocarbamoyl) halide of the following formula (IV) with an amine of the following formula (V).

Wherein R ¹ , R ² , X and Y are as described above and Hal is halogen, in particular chlorine or bromine.

Examples of N-benzyl-N-cycloalkylamines of the above formula (II) to be used as starting materials for the reaction process (a) are: N-4-methylbenzyl-N-cyclopentyl-amine, N-4-methyl Benzyl N-3 -methylcyclopentylamine, N-4 -methylbenzyl-N-cyclohexylamine, N-4 -methylbenzyl-N-2 -methyl cyclohexylamine, N-4 -chlorobenzyl-N-cyclobenzyl -N-cyclopentylamine, N-4-chlorobenzyl-N-3-methylcyclopentylamine, N-4-chlorobenzyl-N-cyclohexylamine, N-4-chlorobenzyl-N-2-methyl-cyclo Hexylamine, N-4-bromobenzyl-N-cyclopentylamine, N-4-bromobenzyl-N-2-methylcyclohexylamine, N-4-cyanobenzyl-N-cyclopentylamine, and N- 4-nitrobenzyl-N-chloropentylamine.

Examples of the cyanate and isothiocyanate of the above formula (III), which is another starting material of the reaction process (a), for example, phenyl isocyanate, phenyl isothiocyanate, cyclopentyl isocyanate, cyclopentyl isothiocyanate, cyclohexyl Isocyanate, cyclohexyl isothiocyanate, cycloheptyl isocyanate, cycloheptyl isothiocyanate, ethyl isocyanate, ethyl isothiocyanate, propyl isocyanate, propyl isothiocyanate, butyl isocyanate, butyl isothiocyanate, secondary Butyl isocyanate, secondary-butyl isothiocyanate, amyl isocyanate and amyl isothiocyanate.

If N-4-methylbenzyl-N-cyclopentylamine and phenyl isocyanate are used as starting materials of the reaction process (a), the reaction formula is as follows.

Examples of N-benzyl-N-cycloalkyl carbamoyl (and thiocarbamoyl) halides of the above formula (IV) to be used as starting materials for the reaction process (b) include 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 -methyl cyclopentyl, N -4-chlorobenzyl -N -cyclohexyl-, N -4-chlorobenzyl -N-2-methylcyclohexyl- , N4-bromobenzyl-N-cyclopentyl-, N-4-bromobenzyl-N-2-methylcyclohexyl-, N-4-cyanobenzyl-N-cyclopentyl-, and N-4 -Nitrobenzyl-N-cyclopentyl-carbamoyl (or thiocarbamoyl) chloride and the corresponding bromide.

Examples of the amine of the above formula (V) which is another starting material of the reaction process (b) include aniline, cyclopentylamine, cyclohexylamine, cyclohexylamine, ethylamine, propylamine, butylamine, secondary-butylamine and Amylamine.

If N-4 -chlorobenzyl-N-cyclopentyl carbamoyl chloride and cyclohexylamine are used as starting materials for the reaction process (b), the reaction is as follows.

Reaction process (b) is carried out in the presence of an acid binder. Typical acid acceptors used for this purpose are tertiary organic bases such as alkali metal hydroxides, alkali metal carbonates, alkali metal bicarbonates, alkali metal alcoholates or triethylamine, dimethylaniline or pyridine.

Reaction processes (a) and (b) according to the present invention are preferably all performed using a solvent or a diluent.

Examples of suitable inert solvents or diluents are aliphatic, cycloaliphatic and aromatic, such as water and hexane, cyclohexane, petroleum ether, ligroin, benzene, toluene, xylene, methylene chloride, chloroform, carbon tetrachloride, ethylene chloride, trichloroethylene and chlorobenzene hydrocarbon; Ethers such as diethyl ether, methyl ethyl ether, diisopropyl ether, dibutyl ether, propylene oxide, dioxane and tetrahydrofuran; Ketones such as acetone, methyl ethyl ketone, methyl isopropyl ketone, and methyl isobutyl ketone; Nitriles such as acetonitrile, propionitrile and acrylonitrile; Alcohols such as methanol, ethanol, isopropanol, butanol and ethylene glycol; Acid amides such as dimethylformamide and dimethylacetamide; Sulfones and sulfoxides such as dimethyl sulfoxide and dimethyl sulfone; It is an inert organic solvent selected from organic bases, such as pyridine.

Reaction processes (a) and (b) according to the present invention are carried out over a wide temperature range. It is generally carried out at a temperature between −20 ° C. and the boiling point of the reaction mixture, with temperatures in particular between 0 ° and 100 ° C. being preferred. The reaction can also be carried out under pressure or reduced pressure, but preferably under atmospheric pressure.

The compound of formula (I) has excellent insecticidal and growth control effects against plant pathogens, and is used for the control and eradication of diseases caused by various plant pathogens. In particular, it has strong action on basidiomycetes causing rice paper diseases, and also against parasitic fungi infecting the ground part of plants, fungi causing catheter phlegm on plants through soil, germs parasitic on seeds, and germs on soil. do.

These active compounds are used as pesticides against fungal diseases of plants because they are harmless to crops at low concentrations, have low toxicity to warm-blooded animals and have potent action on higher plants.

Therefore, the present compound is effective as a fungicide for the control of diseases caused by various plant pathogens such as Archimycetes, crude fungi, asymptomatic fungi, basidiomycetes and insecure fungi.

In particular, the compound has a prominent effect on rice, a fungus caused by fungi, such as Pellicularia sasakii and Pleicularia filamentosa, and the following crop diseases: Corticium centrifugum, Pyricularia oryzae, and rice. White leaf blight (Xanthomonas oryzae), Chinese cabbage rot (Erwinia aroideae), ulcer disease (Xanthomonas citri), rice hoe bean disease (Cochliobolus miyabeanus), banana spots (Myc osphaerella musicola), strawberry gray fungus (Botrytis cinerea) (Plasm opara viticola), Glomella cingulata of grapes, apples and pears, S clerotinia sclerotiorum of vegetables, Colletotrichum lagenarium, Diapa orthe citri, Podosphaera leucotricha ), Black spots such as Sphaerotheca fuliginea, apple spots (Alternaria mali) and potato leaf round encephalopathy (Alternaria solani) and pear plaque (Alternaria kikuchiana) It is also effective in black diseases, such as venereal inaequalis and emphysema.

Since the active compound according to the present invention has an excellent bactericidal action as described above, it can be used for diseases caused by plant pathogens, in which fungicides containing heavy metals such as arsenic or mercury which are toxic to humans and livestock should be used.

The active compounds are solutions, emulsions, hydrating agents, suspensions, powders, powders, foaming agents, pasta preparations, solvent powders, granules, aerosols, emulsions, seed treatment powders, natural and synthetic substances saturated with active compounds, and polymerized substances. Very fine capsules, seed coating compositions, and fumigation cartridges, fumigation cans, fumigation coils and ULV cold and warm preparations can be converted into formulations used as heating devices. Such formulations may be prepared by known methods of mixing the active compounds with extenders such as liquids or liquefied gases or solid diluents or carriers, optionally with surfactants such as emulsifiers and / or dispersants and / or foaming agents. When water is used as a weighting agent, an organic solvent may be used as a cosolvent.

Liquid solvent diluents or carriers, especially solvents, are mainly aromatic hydrocarbons such as xylene, toluene or alkyl naphthalene, chlorinated aromatic or chlorinated aliphatic hydrocarbons such as chlorobenzene, chloroethylene or methylene chloride, cyclohexane or paraffin (e.g. mineral oil). Alcohols such as aliphatic or alicyclic or hydrocarbons, butanol or glycol, ethers and esters thereof, ketones such as acetone, methyl ethyl ketone, methyl isobutyl ketone or cyclohexanone, or dimethylformamide, dimethyl sulfoxide and Strong polar solvents such as water are suitable.

Liquefied gas diluents or carriers refer to liquids that are gaseous at room temperature and atmospheric pressure, such as, for example, aerosol blowing agents such as butane, propane, nitrogen, carbon dioxide, and halogenated hydrocarbons.

Solid carriers include ground natural minerals such as kaolin, clay, talc, choke, quartz, attapulgite, montmorillonite or diatomaceous earth and ground synthetics such as highly dispersed silicic acid, alumina and silicates Mineral materials and the like are preferably used. Granular solid carriers can be used for the pulverized natural stone, such as calcite, marble, pumice, calculi and dolomite, as well as synthetic granules of inorganic and organic substances and granules of organic substances such as sawdust, coconut shells, corn cores and tobacco stems. Can be.

Emulsifiers and foaming agents include nonionic and anionic emulsifiers, such as polyoxyethylene fatty acid esters, polyoxyethylene fatty alcohol ethers, such as alkylarylpolyglycol ethers, alkylsulfonates, alkylsulfates, arylsulfonates And albumin hydrolysates can be used. As dispersants, additives such as lignin, powder, granules, lattice-shaped natural and synthetic polymers, such as gum arabic, polyvinyl alcohol and polyvinyl acetate, and carboxy methylcellulose, can be used in such formulations.

Inorganic pigments such as iron oxide, titanium oxide and prussian blue cow and organic dyes such as alizarin dye, azo dye or metal phthalocyanine dye are used as colorants and salts of iron, magnesium, fluorine, copper, cobalt, molybdenum and zinc. Or the like as a micronutrient.

The active compound according to the present invention may be a formulation mixed with other active compounds such as fungicides, insecticides, acaricides, nematicides, herbicides, algal repellents, plant growth regulators and soil structure improvers.

These formulations generally contain from 0.1 to 95% by weight of active ingredient, preferably from 0.5 to 90% of active ingredient.

Degradable compounds can be used in the form of preparations or in the form of preparations which require dilution such as ready-to-use solutions, emulsions, suspensions, powders, pastas and granules. These compounds can be used by conventional methods such as spraying, spraying, spraying, scattering, powdering, and the like.

The concentration of the active compound as a commercial preparation can be varied over a wide range. These formulations are generally from 0.0001 to 20% by weight, preferably from 0.005 to 10% by weight.

Generally, the amount of active compound is used in the range of 0.03 to 10 kg per hectare of soil, preferably 0.3 to 6 kg.

The present invention also includes a sterilizing composition in which the compound of the present invention is mixed with a solid or liquefied gas diluent or carrier as an active ingredient or with a liquefied diluent or carrier containing a surfactant.

The present invention also includes a method for controlling fungus, characterized in that the compound according to the present invention is used alone or as an active ingredient in the form of a composition in which the active compound of the present invention is mixed with a diluent or a carrier.

The present invention also includes a method of protecting a crop from damage by fungi by using the compound of the present invention alone or in the form of a mixture with a diluent or a carrier before or during the growth of the crop.

It can be seen that the present invention can improve the conventional crop harvest.

A bactericidal composition according to the present invention is as follows. The active compounds according to the invention are denoted by the same numbers as the corresponding preparation examples, respectively.

Example (i)

50 parts of compound No. 1, 45 parts of a mixture of diatomaceous earth and kaolin (1: 5) and 5 parts of an emulsifier (polyoxyethylene alkylphenyl ether) are ground and mixed to prepare a hydrating agent. Dilute to 0.05% concentration with water before sparging.

Example (ii)

30 parts of compound number 3,30 parts of xylene, 30 parts of methyl naphthalene, and 10 parts of polyoxyethylene alkylphenyl ethers are stirred, and the concentrate which can be emulsified is prepared. Dilute to 0.05% concentration with water before sparging.

[Example]

A powder is prepared by grinding and mixing a mixture of talc and clay (1: 3) of 2 parts of compound No. 21 and 98 parts. Spray it and use it.

Example (iV)

A powder is prepared by grinding and mixing 1,5 parts of compound number 23, 0.5 parts of isopropyl hard drogen phosphate (PAP) and 98 parts of talc and clay mixture (1: 3).

Example (V)

10 parts of compound number 27, 10 parts of bentonite, 78 parts of talc and clay mixture (1: 3) and 2 parts of lignin sulfonate are mixed. 25 parts of water is added to the mixture, the whole is mixed, dried to 40 to 50 °, and granulated to 20 to 40 meshes using a granulator.

Example (Vi)

While rotating 95 parts of clay powder having a particle size of 0.2 to 2 mm with a rotary mixer, 5 parts of compound No. 29 in an organic solvent are sprayed onto the particles to hydrate uniformly. It granulates after drying to 40-50 degree.

Example (Vii)

0.5 part compound number 30, 20 part high boiling point aromatic compound, and 79.5 part kerosene are mixed, stirring, and an oily agent is manufactured.

The bactericidal action of the compounds according to the invention is explained as in the following bioassays.

In these tests, the active compounds according to the present invention are indicated in parentheses with the same numbers as in the corresponding preparation examples.

Known control compounds are as follows:

(Published in Japanese Patent Application No. 29252/1969)

(B) = polyoxin complex (usually useful)

(C) = bis- (dimethyl thiocarbamoylthio) -methyl-arcin

[Test Example A]

Action test on Pellicularia sasakii / spots

Preparation of Sterilizing Compositions

Active compound: 50 parts by weight

Carrier: 45 parts by weight of a mixture of diatomaceous earth and kaolin (1: 5)

Emulsifier: 5 parts polyoxyethylene alkylphenyl ether

The above-mentioned amount of the active compound, the carrier and the emulsifier are mixed and ground to prepare a hydrating agent, and then diluted with water to the concentration.

[Test Course]

Rice (Kinmaze variety) is planted in a Wagner pot (0.0002), and when sprouted, the liquid formulation containing the active compound is added to the concentration of 100 ml per three pots.

One day after the use of the active compound, the lower part of the plant is inoculated with the bacterium bacterium (grown in barley medium for 10 days). The plants are left in a greenhouse with a temperature of 28-30 ° C. and a relative humidity of at least 95%. The extent of infection is then estimated and the phytotoxicity of the active compound is described. In this calculation, the spread of injury from the inoculation site (bottom plants) is measured and the following calculation is made:

Where N is the number of all observed plant stems, n ₀ is the number of uninfected stems, n ₁ is the number of stems infected from the lower part of the plant to the first leaf area, and n ₂ is the lower part of the plant from the bottom of the plant Number of stems infected, n ₃ is the number of stems infected from the underside of the plant to the third vinegar site.

The test results are shown in Table A. "-" In the last column means no toxicity to plants.

TABLE Aa

Table Ab

[Table Ac]

[Table Ad]

The preparation method of the compound according to the present method is as follows.

Preparation Example 1

A 50 ml hexane solution containing 14 g of phenyl isothiocyanate is added dropwise to the 400 ml hexane containing 19 g of N-4-methylbenzyl-N-cyclopentylamine while cooling and stirring. After the dropwise addition, the temperature of the reaction mixture was gradually raised and stirred at 40 ° C for 5 hours. After cooling, the residue was recrystallized from a mixture of hexane and ethyl alcohol. 30 g of N-4-methylbenzyl-N-cyclopentyl-N'-phenylthiourea is obtained.

Melting Point: 109 ~ 111 ℃

Preparation Example 2

In a manner similar to Preparation Example 1, 31 g of N-4-chlorobenzyl-N-cyclopentylamine is reacted with 13 g of propyl isocyanate. 32 g of N-4-chlorobenzyl-N-cyclopentyl-N'-propylurea are obtained.

Melting Point: 103-105 ℃

Other compounds according to the invention, prepared in a similar manner to Preparation Examples 1 and 2, are listed in Table 1.

TABLE 1A

TABLE 1b

TABLE 1c

TABLE 1d

TABLE 1e

TABLE 1f

Table 1g

Production Example 17 (Other Method)

100 ml of toluene containing 27 g of N-4-chlorobenzyl-N-cyclopentyl-carbamoyl chloride was added dropwise while cooling and stirring to 400 ml of toluene containing 20 g of cyclohexylamine. After dropping, the reaction temperature is gradually raised and stirred at 70 ° C. to 80 ° C. for 10 hours. Cyclohexylamine HCl prepared after cooling is isolated by filtration. The toluene layer is washed with water, 1% aqueous sodium carbonate solution, 1% hydrochloric acid, and then again with water, and dried in the presence of anhydrous sodium sulfate. Toluene is distilled off and the residue is recrystallized from a mixture of hexane and ethyl alcohol. 25 g of N-4-chlorobenzyl-N-cyclopentyl-N-cyclohexyl urea is obtained.

Claims (1)

N-benzyl-N-cycloalkylamine of formula (II) is reacted with an isocyanate or isothiocyanate of formula (III) to form a urea or thiourea compound of formula (I) How to make

Wherein R ¹ is cycloalkyl having 5 to 8 carbon atoms in the ring and may be optionally substituted by alkyl having 1 to 8 carbon atoms, R ² is alkyl having 1 to 8 carbon atoms and cycloalkyl having 5 to 8 carbon atoms in the ring Or phenyl, X is oxygen or oil, and Y is halogen, alkyl of 1 to 8 carbon atoms, cyano or nitro.