KR840002201B1 - Process for preparing isoxazolylcarboxanilides - Google Patents

Abstract

1,2-Isoxazolylcarboxanilides(I) used as a bactericide are prepared from aniline derivative(II) by means of reaction with isoxazolylcarboxylic acid derivative(III), where R1 = methyl, ethyl, or chlorine; R2 = hydrogen, methyl, ethyl, fluorine, chlorine, or bromine; R3 = methyl or ethyl; R4 = hydrogen, methyl, or ethyl; and A = substitutive nucleophilic group. (I) has an asymmetric center in propionic acid ester radical. Reaction temp. is 0 - 120≰C, and an inorganic or organic based can be used as well as a reaction accelerator.

Description

Method for producing isooxazolylcarbox anilide

The present invention relates to a method for producing isoxazolylcarbox anilide.

Heterocyclic carboxanilides which are effective as fungicides are known. (DE-OS 2,513,732 and DE-OS 2,513,788) The heterocyclic groups for these compounds are pyridyl, pyrimidinyl, dihydro-pyranyl, dihydro-1,4-thiynyl, thienyl and furyl. The action of these compounds on Downy mildew is not satisfactory.

In the present invention, it was found that the 1,2-isooxazolylcarbox annilides of the following general formula (1) have a superior bactericidal action than the previously known heterocyclic carbox anilides, especially for molds.

Wherein R ¹ is methyl, ethyl, or a business, R ² is hydrogen, methyl, ethyl, fluorine, chlorine, or bromine, R ³ is methyl or ethyl, and R ⁴ is hydrogen, methyl or ethyl.

Ixoxacyclylcarboxidelides of the general formula (I) have an asymmetric center in the propionic acid ester group. Optically pure left and right phase crystals can be made by conventional methods. Not only mixtures (usually obtained by synthesis) but also pure interphase crystals (within the scope of the present invention) all have effective bactericidal action.

The isooxazolylcarbox anilide of general formula (I) is obtained by reacting the aniline derivative of the following general formula (II) with the isooxazolyl carboxylic acid derivative of the following general formula (III), in which the temperature range is 0. Inorganic base or organic base may be used within ℃ -120 °, and reaction accelerator may be used.

In the above formula, R ¹ , R ² , R ³ are as mentioned above.

Wherein R ⁴ represents hydrogen, methyl or ethyl and A is a nucleophilic substitutable leaving group.

Examples of A in the compound of formula III include halogens such as chlorine and bromine, alkoxycarbonyloxy groups such as methoxycarbonyloxy and ethoxycarbonyloxys, and azolyl groups such as imidazolyl or triazolyl Or benzyloxycarbonyloxy and the like.

The above reaction may be carried out in the presence of a diluent or a solvent. Suitable solvents or diluents include halohydrocarbons such as methane, chloroform, 1,2-dichloroethane and chlorobenzene, cyclohexane, petroleum ether, benzene, toluene, and aspirated or aromatic hydrocarbons of xylene-dong, and esters such as ethyl acetate. And nitriles such as acetonitrile, sulfoxides such as dimethyl sulfoxide, ketones such as acetone or methyl ethyl ketone, ethers such as diethyl ether, tetrahydrofuran or dioxane, or mixtures of these solvents.

The amount of solvent or diluent is 100-2000% by weight, preferentially 100-1000% by weight, based on the starting materials of general formula (II) or (III).

As the acid binder, hydrates of alkali metal carbonates such as calcium carbonate or sodium carbonate, alkali metal hydrides such as sodium hydride, trimethylamine, triethylamine, N, N- in suitable inorganic or organic bases which can be added to the reaction mixture if desired. Tertiary amines such as dimethylanilide, NN-dimethylcyclonuxylamine, N-methylpiperidine, and pyridine, and azoles such as 1,2,4-triazole or imidazole. However, other commonly used bases can also be used.

Examples of suitable reaction accelerators include halides of metals such as sodium bromide and potassium iodide, azoles such as imidazole or 1,2,4-triazole, pyridines such as 4-dimethylaminopyridine, or mixtures thereof. have. Economically, 0.9-1.3 mole of acid derivative of general formula (III) and, if desired, 0.5-2 mole of base and 0.01-0.1 mole of reaction accelerator are used for 1 mole of aniline derivatives of general formula (II).

Generally, the reaction takes place at 0 ° -12 Q ° C. over 1-60 hours at atmospheric or higher pressure.

In a better process according to the invention, the acid derivative of formula (III) and, if desired, a reaction accelerator are added to the starting material of formula (II) mixed with a base or diluent together and the reaction mixture is brought to a temperature of 0 ° -120 ° C. At 0.5-12 h, preferentially 1-6 h.

To isolate the new compound, remove the diluent, dissolve the remainder in a suitable solvent, and first rinse the solution with dilute acid, then with dilute alkaline aqueous solution and water to give excess base and unreacted starting material (II). Remove (III).

The product remaining after distilling off the solvent generally does not need to be further purified, but can be further purified by recrystallization, extraction, or chromatography if necessary.

Aniline derivatives of formula (II) and their preparation are described in German Patent Publication Nos. DE-OS 2,802,211 and J.Org. Chem 30,4101-4101 (1965) and Tetrahedron, 487-493 (1965).

Certain isoxazolylcarboxylic acid derivatives used as starting materials are already known or can be made by conventional methods from isoxazolylcarboxylic acids such as general formula (IV).

R ⁴ refers to hydrogen, methyl or ethyl.

The process for preparing the isooxazolylcarboxylic acid of the general formula (IV) from the corresponding carbinols by oxidation is specified below with 3-ethylisooxazolyl-5-carboxylic acid.

At a temperature of 15 ° -20 ° C., a mixture of 750 ml of water, 164 g of Na ₂ Cr ₂ O ₇ · 2H ₂ O, and 124 ml of sulfuric acid was added to 63.5 g of 3-ethyl-5-hydroxy methylisoxazole in 250 ml of diethyl ether. Drop the drops in the middle. The mixture is stirred well at 20 ° -25 ° C. for 12 hours, then the organic phase is separated off and dried over sodium sulfide. Removal of all solvents yields 59 g of 3-ethylisoxazolyl-5-carboxylic acid having a melting point of 194 占 폚.

C ₆ H ₇ NO ₃ (141)

C H N

Calculation: 51.1 5.0 9.9

Found: 51.9 5.2 10.7

The following table shows the melting points of some carboxylic acids of formula (IV).

In the following example is shown the manufacturing process of the isoxoxazolyl carbooks anilide of the general formula (I). The relationship between the weight part and the volume part is the same between the kilogram and the liter.

EXAMPLE

A solution of 15.2 parts by volume of triethylamine and 16 parts by weight of 3-methylisoxazolyl-5-carboxylic acid chloride dissolved in 30 parts of toluene was added to N- (1-methoxycarb) in 100 parts of toluene. A drop of 20.7 parts by weight of carbonyl) -2 ', 6'-dimethylaniline is dropped into the dissolved solution. At this time, the temperature of the reaction mixture reaches up to 64 ° C. The reaction mixture is stirred for 2 hours at room temperature and then 50 moles of mole are added. The organic phase is separated off, washed three times with 50 parts of water each time, and then concentrated to dryness. The remaining oil is distilled off under high pressure.

24.1 parts by weight of 3-methylisoxazolyl-5-carboxylic acid-N- (1′-methoxycarbonylethyl)-(2 ′, 6 ”at a temperature of 170 ° C.-174 ° C. and a pressure of 0.005 mbar. -Dimethyl) -anilide is obtained.

C ₁₇ H ₂₀ O ₄ N ₂ (316.3)

C H N

Calculation 64.5 6.4 8.9

Found 64.6 6.3 8.9

For example, the following compounds having general formula (I) are obtained in a similar manner.

The active ingredient according to the present invention has a strong bactericidal action. At the concentrations needed to kill mold and bacteria, the ingredients do no harm to crops. For these reasons, the ingredients are suitable for use as crop protection against bacteria.

The new active ingredients have a potent bactericidal activity against bacteria that cause plant diseases. The new compounds are, for example, against erythrophiles in cereals, erythropoie polygons of legumes, phytophthora layers of potatoes and tomatoes, and phytoprora paracities in strawberries, and grapes of sporathecoccicias of apples. And per phytotoracitol, cucumber pheronosporacubensis, hops pheronospora humulley, onion phytonospora pest, rose pheronosporatpart, tobacco pheronosporatabakina, grapes Plasmopata Vitcola, Plasmophora Halsteady of sunflower, Sclerospora Macrospora of Indian corn, Bremia lactuque of lettuce, Fruit mucom mucedo, Tizopus snigrican of beet, Unusual of grape It is suitable for treating the locators and the sparotcapanosa of the rose.

Its use depends on the type of effect desired, using 0.1-5 kg of active ingredient per hectare. Some of the active ingredients have properties that heal the disease and can be used on plants infected with germs, and the effect is successful. Many new compounds also have a penetrating effect, which means that by treating the roots of plants, the outer parts of the plant can be protected.

The new compounds can also be used to treat bacteria that cause diseases such as tegyuminose and obscured phyticol and apanomyces. In this case, 10-200 g of active ingredient per 100 kg of seeds is used as seed income system.

When using the compounds, the plants are sprayed and sprayed with the active ingredients or the seeds are treated with the active ingredient. It is effective both before and after the plant or its seeds are infected with bacteria.

The active ingredients according to the invention can be modified in the form of conventional materials, i.e. solutions, emulsions, suspensions, powders, particles, doughs and the like. The form used depends entirely on the purpose of using the component. In either case, the active ingredients should be finely and evenly distributed. The types of materials used are made by conventional methods, such as diluting the active ingredients with solvents and media, in which case emulsifiers and dispersants are added during dilution and organic aids are used when diluting water. . Among the suitable auxiliaries are solvents selected from aromatics such as xylene and benzene, chloro aromatics such as chlorobenzene, paraffin, alcohols such as methanol and ethanol, amines such as ethanol amine and dimethyl formamide, natural compounds such as kaolin, alumina, talc, and limestone. Non-ionic and anionic emulsifiers, such as polyoxyethylene fatty alcohols, alkylsulfonates, and arylsulfonates, mobile media using rock powders, highly ground silica and synthetic rock powders such as silicate, grig lignin, sulfite Treatment liquids and dispersants such as methyl cellulose.

The fungicide contains 0.1-95% by weight of active ingredient, preferably 0.5-90% by weight.

Agents and those in usable forms obtained therefrom, such as solvents, emulsions, suspensions, powders, dusts, or particles, are used by conventional methods such as spraying, spraying, seeding, or irrigation. Examples of such formulations are shown below.

I. Mix 90 parts by weight of compound 1 with 10 parts of N-methyl-α-pyrrolidone. This gives a mixture suitable for use in the form of very fine droplets.

II. 20 parts by weight of Compound 1 are made up of 80 parts by weight of xylene, 10 parts by weight of 1 mole of oleic acid-N-monoethanolamide and 8-10 moles of ethylene oxide precursor, 5 parts by weight of calcium salt of dodecylbenzenesulfonic acid, and 1 mole. It is dissolved in a mixture of castor oil and 5 parts by weight of 40 mol of ethylene oxide precursor. The solution is poured into 100,000 parts by weight of water and distributed uniformly to give an aqueous dispersion containing 0.02% by weight of active ingredient.

III. 20 parts by weight of compound 4 are dissolved in a mixture of 40 parts by weight of cyclohexanone, 30 parts by weight of isobutanol, 1 mole of isooctyl phenol and 10 parts by weight of 7 moles of ethylene oxide precursor. The solution was placed in 100,000 parts by weight of water and dispersed to obtain a dispersion containing 0.02% by weight of the active ingredient.

IV. 20 parts by weight of Compound 2 are dissolved in a mixture of 25 parts by weight of cyclohexanol, 65 parts by weight of mineral oil having a boiling point of 210 ° -280 ° C., and 1 part of castor oil and 10 parts by weight of a 40 mol molar of ethylene oxide. Let's do it. The solution is poured into 100,000 parts by weight of water and distributed evenly to give a dispersion containing 0.02% by weight of active ingredient.

V. 20 parts by weight of compound 5 are well mixed with 3 parts by weight of sodium salt of diisobutylnaphthalene-α-sulfonic acid, 17 parts by weight of sodium salt of lignin-sulfonic acid obtained from the sulfite treatment solution, and 60 parts by weight of powdered silica gel. The mixture is made into a powder, and the mixture is evenly dispersed in 20,000 parts by weight of water to obtain a molecular liquid containing 0.1% by weight of active ingredient.

VI. Mix 3 parts by weight of compound 3 with 97 parts by weight of special kaolin. Then the powder containing 3% by weight of the active ingredient is lingual.

VII. 30 parts by weight of compound 4 are mixed well with 92 parts by weight of powdered silica gel and 8 parts by weight of paraffin oil sprayed onto the silica gel. This results in an active ingredient formulation with good adhesion.

VIII. 40 parts by weight of compound 2 are mixed well with a mixture of 10 parts of sodium salt of phenolsulfonic acid-urea-formaldehyde concentrate, 2 parts of silica gel and 48 parts of water. Dilution with 100,000 parts by weight of water gives a dispersion containing 0.04% of the active ingredient.

IX. 20 parts of compound 4 잘 Mix well with 2 parts of calcium salt of dodecyl bunsensulfonic acid, 2 parts of fatty alcohol polyglycol ether, 2 parts of sodium salt of phenolsulfonic acid-urea-formaldehyde concentrate, and 68 parts of paraffinic mineral oil. A stable acid oil dispersion is obtained.

The active ingredients according to the invention can be mixed with other active ingredients such as herbicides, insecticides, growth regulators and other fungicides or can be mixed with fertilizers. Mixing with other fungicides may extend the scope of the bactericidal action.

The fungicides listed below are those which can be bound together with the compounds according to the invention for the purpose of illustration and do not limit the scope of their binding possibilities. Fungicides that can be combined with the compounds of the present invention include the following. That is, dithiocarbamates and their derivatives, polar iron (III) dimethyl dithiocarbamate, zinc dimethyldithiocarbamate, manganese N, N-ethylin-bis-dithiocarbamate, manganese zinc N, N -Ethylenediamine-bis-dithiocarbamate, zinc N, N-ethylene -bis-dithiocarbamate, tetramethylmethyl uramdi sulfide complex and zinc N, N /- Ammonia complexes of propylene-bis-dithiocarbamate and NN / -polypropylene-bis- (thiocarbamoyl) -disulfide,

Nitrile derivatives, i.e., dinitro- (I-methylheptyl) -phenylchlorobiate, 2-sec.-butyl-4,6-dinitrophenyl 3,3-dimethyl-acrylate and 2-sec. -Butyl-4,6-dinitropenyl isopropyl carbonate,

Heterocyclic compounds, i.e., N-trichloromethyl thiodetrahadroframidide, N-trifluoromethyl thi-phthalimide, 2-heptadecyl-2--2-imidazoline ace Tight, 2,4-dichloro-6- (0-chloroanilino) -S--triazine, 5-amino-1- (bis- (dimethylamino) -phosphinyl)- 3-phenyl-1,2,4-triazole, 5-ethoxy-3-trichloromethyl-1,2,4-thiadiazole, 2,3-dicyano-I, 4-dithiaanthraquinone -Methyl 1- (butylcarbadoyl) -2-benzimidazle-carbamate, 2-methoxy carbonylamino-benzimidazle, 4- (2-chlorophenylyldrazono) -3-meth Tyl-5-isoxozoline, pyridine-2-thio-1-waside, 8-hydroxyquinoline and its copper salt, 2,3-dihydro-5-carboxanilide-6-methyl-I , 4-oxacin-4,4-dioxide, 2,3-dihydro-5-carboxanili do-6-methyl-I, 4-oxacin, 2-fur-2-yl- Burnsimidazole, piperazine-I, 4-diyl--bis-1- (2 , 2,2-trichloroethyl) -formamide), 5-butyl-2-dimethylamino-4-hydroxy-6-methyl-pyridinedine, bis- (P- Chlorofeureido) -benzene, and a variety of fungicides, extremely dodecurianidineacetate, 3- (2- (3,5-dimethyl-2-hydroxycyclohexyl) 2-hydroxyethyl) -glutarmidide, hexachlorobenzene, N-dichlorofluoromethyl thio-N /, N'- dimethyl-N-phenyl-sulfuric acid amide, 2,5-Dimethyl-furan-3-carboxylic acid anhydride, 2,5-dimethazol-1'-yl)-[1- (4 / -chlorophenoxy)]-3,3-di Methyl-butan-2-one, 1- (1 ', 2, 4'-triazol-1'-yl) [-1- (4'-chlorophenoxy)]-3,3-dimethylbutane-2 -Ol, N- (n-propyl) -N- (2,4,6-trchlorochlorooxy) -N-imidazolyl urea, N-cyclohexyl-N-methoxy-2 , 5-methoxymethyl-5-methyl-3- (3,5-dichlorophenyl) -2,4-dioxo-1,3-oxazolidine and N- [3- (tert-butyl Pentyl) -2-methyl Propyl] -cis-2,6-dimethylmorpholine.

The following examples illustrate the biochemical action of new compounds of formula (I). The agents used in the comparison are referred to as the following fungicides: N- (1 / -methoxycarbonyl ethyl) N- (putane- (2 ')-carbonyl) -2,6-dimethyline aniline (A ) Wave N- (1 / -methoxycarbonylethyl) -N- (pyridine-3 "-carbonyl) -2-methyl-6-chloroaniline (also referred to as B).

Example A

Action on wheat fungus

Wheat germ growing in pollen was sprayed with a liquid emulsion consisting of 80% by weight of active ingredient and 20% of emulsifier. After the aliquot was dried, some fungus (Erisperum graminus) was sprinkled on the shoot leaves. The wheat thus treated was left in a greenhouse at a relative humidity of 75-80% and a temperature of 20P-22 ° C. After 0 days, the degree of mold growth was checked.

Content of active ingredient contained in the injection liquid sprayed on the active ingredient leaf

Example B

Bactericidal action on the phytotrophic layer of tomato.

On the leaves of "Professordullov" species tomato, a suspension consisting of 80% (weight%) of active ingredient and 20% of sodium lignin sulfonate was dispensed. Sprays of 0.1,0.05,0.025 and 0.012% concentrations were used, respectively. . After the sprayed liquid layer had dried, the suspension of the Fittra pests was infected with tmatri leaves. The tomatoes thus treated were left in a room saturated with steam maintained at 16 ° -18 ° C. for 5 days. After this period, the disease spread on the untreated leaves and the bactericidal activity of the compounds could be clearly confirmed.

Content of active ingredient in active ingredient spray

0; Not affected by germs.

5; Completely invaded by bacteria.

Example C

Bactericidal Activity of Plasmoparabiticola in Grapes.

Grape leaves of Multer-Turgau were sprayed with a suspension consisting of 80% active weight (% by weight) and 20% emulsifier. 0.05% and 0.012% of the spray solution was used. In order to demonstrate the active period of the active ingredient, the sprayed plants were left to dry in the greenhouse for 10 days. The leaves were then infected with a suspension of plasmogar Viterola and left for 16 hours in a room saturated with steam maintained at 24 ° C. The table was then placed in a greenhouse at 20 ° -30 ° C for 8 days. The plant was put back in the damp room for 16 hours to enhance the growth of the bacteria. The result of measuring bacterial infection is as follows.

Content of the active ingredient contained in the active ingredient spray liquid

0; Not invaded by germs.

5; Completely invaded by bacteria.

Claims (1)

A method for preparing isooxazolylcarboxanilide of the following general formula (I), wherein the aniline derivative of the following general formula (II) is reacted with an isooxacyl carboxylic acid derivative of the following general formula (III):

Wherein R ¹ is methyl, ethyl or chlorine, R ² is hydrogen, methyl, ethyl, fluorine, urethane or bromine, R ³ is methyl or ethyl, and R ⁴ is hydrogen, methyl, or ethyl, and A is nucleophilic A substitutable leaving group.