KR810000201B1 - Preparing process for 1-cyclo alkyl carbonyl-3-(3,5-dihalophenyl) imidazolindin-2,4-dione - Google Patents

Abstract

Bactericidal title compds. (I; R1 = C3-6 cycloalkyl, tetramethyl cyclopropyl, 2,2-dimethy1-3-isobutenyl cyclopropyl, 2,2-dimethyl-3-dichlorovinyl cyclopropyl ; R2, R3 = H, Me; X=Cl, Br) were prepd. by reaction of II and III(Y = halogen, cycloalkylcarboxyl anhydride) or IV. Thus, 0.05mol II(R2,R3 = H; X = Cl) and 0.06mol Et3N 150ml were reacted with 0.06 mol III(R1 = cyclopropyl; Y = Cl) to give I(R1 - cyclopropyl; R2, R3 = H; X = Cl), or 0.05mol II and 0.15mol IV (R1 = C6H11) in 15ml C6H5Me were reacted to give I (R1 = C6H11; R2, R3 = Me; X = Cl).

Description

Method for preparing 1-cycloalkyl carbonyl-3- (3,5-dihalophenyl) imidazolidine-2,4-dione

The present invention is of general formula (I)

1-cyclo alkyl carbonyl-3- (3,5-di halophenyl) imidazolidine-2,4-dione (hereinafter referred to as 1-cyclo alkyl carbonyl imidazolidine dione) X is an atom of chlorine or bromine, R ₁ is C ₃ -C ₆ cycloalkyl, ratta methyl cyclopropyl, 2,2-dimethyl-3-isobutenyl cyclopropyl, 2,2-dimethyl-3-dichlorovinyl cyclo Propyl group, and R ₂ and R ₃ are each a hydrogen atom or a methyl group.

Several 3- (3,5-di halofenyl imidazolidine-2,4-dione derivatives, which are substituted by selecting the positions 1 and 5 with various substituents, have bactericidal activity against several microorganisms (US Pat. 3,716,552).

As a result of various studies, the above-mentioned chemicals (I) having a cycloalkyl carbonyl group at the 1-position show a remarkable superiority to the widely used bactericidal action and their homologues, and other harmful to plants. And the low toxicity of mammals.

The compound 1-cycloalkyl carbonyl imidazolidine dione [I] described above is used as an algae of Alternaria mali and tomato. It is particularly effective for controlling various diseases of agricultural and horticultural plants caused by phytopathological bacteria belonging to the genus Alternaria, such as (Alternaria solani).

In addition to the above-mentioned diseases, some crop diseases causing serious damage to farming and horticulture are effectively controlled by the use of 1-cycloalkyl carbonyl amidazolidine dione [I].

These diseases are the brown rot of the peach tree (Sclerotinia cinerea), the citrus tree spot disease (Diaporthe citri), the citrus fruit green mold disease (Penicillium digitatum), the citrus fruit blue mold disease, and the grape bean head gray mold disease (Botrytiscinerea) , Soybean and vegetable gray mold and Sclerotinia rot (Botrytis cinerea and Sclerotinia Sclerotiorum).

In recent years, the emergence of plant pathogens resistant to fungicides is sometimes found in the field, and the use of fungicides is becoming an important practical issue for crop protection.

Then, it was found that 1-cycloalkyl carbonyl amidazolidine dione [I] exhibits strong antibacterial activity against these drug resistant bacteria.

For example, they are poly oxin germs of Alternaria kikuchiana and thiophanate-methyl [1,2-bis (3-methoxycarbonyl-2-thioureido)- Benzene] have the same antimicrobial activity as that against their own wild bacteria (susceptible bacteria) against Botrytis cinerea pathogens resistant to.

Therefore, 1-cycloalkyl carbonyl imidazolidine dione [I] can be expected to have a significant effect on the control of plant diseases in drug-resistant bacteria.

In addition, 1-cycloalkyl carbocarbonyl imidazolidine dione [I] has properties that affect the whole plant.

These compounds penetrate the leaf tissue at the leaf surface and are absorbed by the roots and propagate throughout the leaves.

Due to this property, in addition to protecting the plant from transmission, it can effectively suppress the propagation of pathogens that invade the leaf tissue.

Although 1-cycloalkyl carbonyl imidazolidine dione [I] of the present invention is structurally related to several compounds disclosed in US Pat. No. 3,716,552, the efficiency of controlling the above-mentioned diseases is superior to that of the latter compound and 1 Cycloalkyl carbonyl imidazolidine diones are also effective for use in small amounts. This is a significant increase in their antimicrobial activity by substitution of cycloalkyl carbonyl groups at the 1-position of 3- (3,5-di halophenyl) imidazolidine-2,4-dione derivatives.

The present inventors point out for the first time that there was such an unexpected effect.

The primary object of the present invention is to prepare novel 1-cycloalkyl carbonyl imidazolidine diones [I] which are useful as fungicides. Another object of the present invention is to provide a method for preparing such 1-cyclo alkyl carbonyl imidazolidine dione [I].

Another object of the present invention is to provide a sterile compound containing 1-cyclo alkyl carbonyl imidazolidine dione [I].

The above and other objects and advantages of the present invention will become apparent from the foregoing and further description below.

1-cycloalkyl carbonyl imidazolidine dione [I] is prepared by reacting the corresponding 1-unsubstituted compound of the following general formula.

In this formula, X, R ₂ and R ₃ have the cycloalkyl carboxylic acid of the following general formula and are as defined above, respectively.

In which R ₁ is as defined above or a reactive derivative thereof.

Usually this reaction is carried out between the 1-unsubstituted compound [II] described above and the cycloalkane carbonyl halide of the following general formula.

Wherein R ₁ is as defined above and Y is a halogen atom or a cycloalkyl carboxylic anhydride of the general formula:

In this formula, R ₁ is as defined above.

An example of the typical process which implements the manufacturing method which made it possible to obtain the target object 1-cycloalkyl carbonyl imidazolidine dione [I] in a favorable yield is as follows.

[Step A]

1-unsubstituted compound [II], which is a raw material, in the presence or ratio of a suitable solvent (e.g., tetrahydrofuran, methyl isobutyl ketone, benzene, toluene, xylene, chlorobenzene, chloroform, carbon tetrachloride, nitrobenzene) In the presence of an equivalent or excess of cycloalkyl carbonyl halide [IV] at room temperature (0-35 [deg.] C.) and, if necessary, a dehydrohalogenating agent (e.g. triethyl amine, N-methyl morpholine , Pyridine, dimethylaniline, diethyl aniline) and / or until heated to reflux) to form 1-cycloalkyl carbonyl imizazolidine dione [I].

[Process B]

1-Non-substituted compound (2) as a raw material is cycloalkyl carbon in the presence or absence of a suitable solvent (e.g., chloroform, carbon tetrachloride, benzene, toluene, xylene, ligroin) (0-35 ° C) Reaction is carried out in an equivalent molar amount of carboxylic anhydride [V], and if necessary, heating to form 1-cycloalkyl carbonyl imidazolidine dione [I].

The 1-cyclo alkyl carbonyl imidazolidine dione [I] thus prepared is purified by its usual process such as recrystallization in a suitable solvent if necessary.

The 1-unsubstituted compound [III] which is a raw material can be obtained, for example, by the method described in US Pat. No. 3,668,217.

In practical use as a disinfectant, 1-cycloalkyl carbonyl imidazolidine dione [I] may be mixed with other components such as carriers and diluents alone or in an easy to use solid carrier such as talc, clay isotropic. B) it may be mixed with diluents or liquid carriers or diluents such as organic solvents.

This bactericidal compound may be formed into any commonly used shape such as, for example, powders, wet powders, oil sprays, aerosols, tablets, emulsified concentrates and particulates.

The products described above generally contain from 0.1 to 95.O% by weight of active ingredient, and from 0.2 to 90.0 (by mixing other ingredients), suitably by weight.

The suitable amount of the product to be used is generally 10g to 1000g / 10, and the concentration of the product to be used is preferably within the range of 0.001 to 0.1% by weight.

However, since the amount and concentration vary depending on the shape of the product, the time of use, the method of use, the place of use, the disease and the crop, the amount and concentration can be increased or decreased appropriately regardless of the above range.

In addition, 1-cycloalkyl carbonyl imizazolidine dione [I] is, for example, N- (3,5-dichlorophenyl) -1,2-dimethyl cyclopropane-1,2-dicarboximide, Sn-butyl -S'-P-tertbutyl benzyl N-3-pyridyl dithio carbon imitate, 0,0-dimethyl-0-2,6-dichloro-4-methyl phenyl phosphoro thioate, methyl N-benz Imidazol-2-yl-N- (butyl carbamoyl) carbamate, N-trichloromethyl thio-4-cyclo hexene-1,2-dicarboximide, cis-N- (1,1, 2,2-tetrachloroethyl thio) -4-cyclo hexene-1,2-dicarboximide, polyoxine, streptomycin, zinc ethylene-bis (dithiocarbamate), zinc dimethyl thiocarbamate , Manganese ethylene-bis (dithio carbamate), bis (dimethyl methyl carbamoyl) di sulfite, ketrachlor isophthalonitrile, 8-hydroxy quinoline, dodecyl quinidine acetate, 5,6 Dehydro 2-methyl-1,4-oxathiin-3-carbox anilide, N'-dichloro fluoro methyl thio-N, N-dimethyl-N'-phenyl sulfamide, 1- (4-chloro phenoxy ) -3,3-Dimethyl-1- (1,2,4-triazol-1-yl) -2-butanone, 1,2-bis (3-methoxy carbonyl-2-thioureido) It is used in admixture with other fungicides such as benzene isotropic, and 1-cycloalkyl carbonyl imidazolidine dione [I] is, for example, 0,0-dimethyl-0- (4-nitro-m-tolyl) phosphorothio , 0-P-cyanophenyl-0-ethylphenyl phosphono thioate, 0,0-dimethyl-5- (N-methyl carbamoyl methyl) -phospho di thioate, 2-methoxy-4- 1,3,2-benzo dioxa phosphorin-2-sulfide, 0,0-dimethyl-S '-(1-ethoxy carbonyl-1-phenyl methyl) phosphoro dithioate, α-cyano- 3-phenoxy benzyl-2- (4-chlorophenyl) iso valerate, 3-phenoxy benzyl-2,2-dimethyl-3- (2,2-dichlorovinyl) cyclopropane carboxylate, 3- It is used in combination with insecticides such as phenoxy benzyl chrysanthate isokin, in which case the inhibitory effect of the respective chemicals is not diminished.

Therefore, simultaneous control of two or more parasites and harmful insects is possible.

In addition, it can be used in admixture with agricultural chemical products such as nematode control agent and wall repellent control agent and various fertilizers.

Substantial and presently suitable shapes of the invention are set forth in the various examples below.

In these examples, parts and percentages are expressed by weight.

Example 1

Process for preparing 1-cyclo alkyl carbonyl imidazolidine dione (I)

[Step A]

0.O5 mol of 3- (3,5-dihalophenyl) imidazolidine-2,4-dione derivative of the general formula [II] and 0.06 mol of triethyl amine are dissolved in 150 ml of toluene, and a general formula [ 0.06 mol of hydrochloric acid [IV] is slowly added dropwise to room temperature with stirring.

The stock is thus added and the mixture is heated to reflux for 7 hours.

The reaction mixture is filtered and the filtrate is concentrated under reduced pressure. The resulting residue is washed well with water, and the part which is not dissolved in water is recovered by filtration and dried to obtain 1-cycloalkyl carbonyl-3- (3,5-dihalophenyl) imide of the general formula [I]. Zolidine-2,4-dione derivatives are obtained in high yield.

This crude product is recrystallized from ethanol to obtain a purified product.

[Process B]

0.05 mol of 3- (3,5-dihalophenyl) imidazolidine-2,4-dione derivative of the general formula [II] and 0.15 mol of anhydrous acid of the general formula [V] are dissolved in 15 ml of toluene. .

The mixture is heated to reflux for 15 hours.

After the reaction is completed, the reaction solution is cooled to room temperature, poured into water saturated with sodium bicarbonate and stirred for a while.

The solid material thus obtained was filtered, washed several times with water and dried to obtain 1-cycloalkyl carbonyl-3- (3,5-di halophenyl) imidazolidine-2,4-dione of the general formula [I]. The derivative is obtained in high yield.

This crude product is recrystallized from ethanol to obtain a purified product. By any of the above-described processes, 1-cycloalkyl carbonyl imidazolidine dione [I] shown in Table 1 is prepared.

Example 2

Formulation Example

a) powder

2 parts (8) compound and 98 parts of clay were thoroughly mixed and mixed to obtain a powder containing 2% of the active ingredient. It is sprayed in the usual way.

b) powder

Three parts (4) of the compound and 97 parts of talc were thoroughly mixed and mixed to obtain a powder containing 3% of the active ingredient. It is sprayed in the usual way.

c) hydration

50 parts of (1) compound, an alkyl benzenesulfonate system which is a 5 parts humectant, and 45 parts of diatomaceous earth were completely ground and mixed to obtain a hydrating agent containing 50% of the active ingredient.

Dilute with water and spray when using.

d) emulsions

10 parts of (2) compound, 40 parts of dimethyl sulfoxide, 40 parts of xylene and 10 parts of polyoxyethylene dodecyl phenol ether emulsifier were mixed to obtain an emulsion containing 10% of the active ingredient.

When used, dilute this emulsion with water and spray.

e) standing

5 parts of (10) compound, 93.5 parts of clay, and 1.5 parts of polyvinyl alcohol-based binder are thoroughly ground and mixed, kneaded with water, dried to a granule and dried to contain 5% of the active ingredient. Got it.

The following examples show some representative test data that support the superior action of 1-cyclo alkyl carbonyl imidazolidine dione [I].

The numbers of the compounds in these examples correspond to those listed in Table 1.

Example 3

Antimicrobial test against drug resistant bacteria:

10 ml of potato juice stream medium was dissolved by heating, an emulsion of the present test compound was added, the mixture was sufficiently mixed, and the mixture was introduced into a glass petri dish having a diameter of 9 cm to make an agar plate.

Drug-resistant gray fungi (Botrytis cinerea) or wild bacteria (susceptible bacteria) that are resistant to 1,2-bis (3-methoxycarbonyl-2-thioureido) benzene isolated from grapes after solidifying the agar The bacterium (Boattis cinerea) of botrytis cinerea (diameter 5 mm) was placed in the center of the agar plate and incubated at 20 ° C. for 3 days.

After cultivation, the diameter of the grown flora was measured, and the inhibition rate of bacterial growth was calculated by the following equation.

As a result, as shown in Table 2, the compound of the present invention showed strong antimicrobial activity against the drug-resistant Botrytis cinerea, similarly to that of susceptible wild bacteria Brittis cinerea.

TABLE 2

* 1) Strains resistant to 1,2-bis (3-methoxycarbonyl-2-thioureido) benzene (isolated from grapes)

2) Commercially available fungicides 1,2-bis (3-methoxy carbonyl-2-thioureido) benzene.

Example 4

Control Effect Test of Alternaria Kikuchiana of Pear Tree:

Three-year-old pears (cultivar: 20-seed) grown in pots 30 cm in diameter were used as test plants.

When 3-4 new branches were seeded from a seedling of a tree and 10-20 sheets of new leaves appeared, the emulsion of the test compound was diluted with water, and a chemical solution of a given concentration was sprayed at 30 ml per tree. After spraying, it is cultivated in a greenhouse for 7 days, and then sprinkled with condensed spores of pear tree black spot bacteria obtained by incubating with vegetable juice agar medium for 10 days and sprayed the whole seedlings. After inoculation, it was placed in a wet place for 24 hours, and again in a greenhouse for 2 days. The incidence was investigated using the incidence index (0, 1, 2, 3, 4, 5) as follows.

The incidence was calculated by the following equation.

As a result, the compound of the present invention showed superior control effect compared to the comparative control compound tested simultaneously as shown in Table 3.

TABLE 3

Note 1) Compounds disclosed in U.S. Patent 3,716,552

2) commercial sterilizer

So-called Capaptafol

Example 5

Control Effect of Kidney Bean on Sclerotinia sclerotiorum:-

Kidney beans (variety: Taisho kin rabbit) were allowed to grow in a pot of 15 cm in diameter until they had two leaves.

The emulsion form containing the test compound was diluted with water and sprayed at a rate of 100 ml per kidney bean pot.

These kidney beans were dried in air for 4 hours, and then they were inoculated with the flora of the Scletotinian scletothiogae (diameter 5 mm).

After inoculation, the test plants were developed by placing them at 20 ° C. for 4 days in a humid and dark condition.

In order to evaluate this incidence, it calculated based on the following criteria.

As a result, the compound of the present onset showed superior control effect compared to the comparative control compound tested simultaneously as shown in Table 4.

TABLE 4

Caution 1) Commercial Sterilizer

＂Dcna＂

Example 6

Control effect test of orange tree against blue fungal disease (Penicillium italicum):

Orange fruit (variety: Unshu) was washed well with water and dried naturally.

Each emulsion containing the test compound was diluted with water to the required concentration and the orange fruit dried in air was soaked in this solution for 1 minute.

Spore suspensions of penicillium italicum obtained by incubation in potato medium for 5 days were sprayed onto the orange fruit surface to inoculate. After inoculation into these fruits, they were placed in a wet room for 7 days, and the incidence was tested using the onset index (0, 1, 2, 3, 4, 5). These results were shown as the average value of the incidence index.

As a result, various compounds of the present invention had superior control effect as compared to the comparative control compound tested simultaneously as shown in Table 5.

Claims (1)

1-cycloalkyl carbonyl-3- represented by the general formula [I] by reacting the compound represented by the general formula [IV] with the compound represented by the general formula [IV] or the compound represented by the general formula [V]. Process for the preparation of (3,5-di halophenyl) imidazolidine-2,4-dione.

[Wherein X is an atom of chlorine or bromine, R ₁ is a C ₃ -C ₆ cycloalkyl group, tetra methylcyclopropyl group, 2,2-dimethyl-3-isobutenyl cyclopropyl group, 2,2-dimethyl-3- Dichloro vinylcyclopropyl group, R ₂ , R ₃ are each a hydrogen atom or a methyl group, and Y is a halogen atom or a cycloalkylcarboxyl anhydride.]