CS262676B2 - Fungicide - Google Patents

Abstract

Pyrazoleoxime derivs. of formula (I) are new. In (I) R is H, lower alkyl or phenyl; R1, R2 are each H, lower alkyl, lower haloalkyl or aryl; each X is H, halogen, lower alkyl, lower alkoxy, lower haloalkyl, lower alkoxycarbonyl or methylenedioxy; n = 1 or 2. Prepn. of (I) comprises reacting pyrazole deriv. of formula (II) with hydroxyamine.

Description

Solution .se a fungicidal composition for agricultural or horticultural use which contains as active ingredient pyrazoloximový derivative of the formula I wherein R is hydrogen, C | _ ₅ alkyl or phenyl, R 11a and R 2 independently of one another denote hydrogen, С) _ ₅ а1ку1, C ₂ _ ₅ haloalkyl or aryl selected from the group consisting of [enyl, tolyl, xylyl or naphthyl, X can independently be hydrogen, halogen, C ^ alkyl, C ^ alkoxy, CjMialogenalkyl _C; _ ₇ alkoxycarbonyl or methylenedioxy, n is an integer of 1 to 2

The pyrazoloxime derivatives of formula (I) are prepared by reacting a pyrazole derivative of formula (II) wherein R, R 1, R 2, X and n are, as mentioned above, with hydroxylamine.

The present invention relates to a process for the preparation of pyrazoloxime derivatives of the general formula I

wherein R is hydrogen, C 1 -C 5 alkyl or phenyl, R 1 and R 2 independently of each other are hydrogen, C 1 -C 5 alkyl, C 1 -C 5 haloalkyl or aryl selected from from the group consisting of phenyl, tolyl, xylyl or naphthyl, X may independently of one another be hydrogen, halogen, C 1 -C 5 alkyl, C 1 -C 5 alkoxy, C 1 -C 5 haloalkyl; , C 2 -C 7 alkoxycarbonyl or methylenedioxy and n is from 1 to 2.

It is an object of the present invention to provide a process for the preparation of the pyrazoloxime derivatives of formula (I) which are novel compounds which have not been previously reported in any publication. These compounds are useful as intermediates in medicine and for agricultural chemicals or are useful directly for application due to their fungicidal activity.

It is another object of the present invention to provide compositions which contain said pyrazoloxime derivatives as an active ingredient and which are useful as an agricultural and horticultural fungicide.

The process for the preparation of the pyrazolo oxime derivatives of the formula I according to the invention is shown in the following reaction scheme:

(II)

(l)

wherein R is hydrogen, C 1 -C 5 lower alkyl or phenyl, R 1 and R 2 independently of each other are hydrogen, lower. C 1 -C 5 alkyl, C 1 -C 5 lower haloalkyl or aryl, X may independently be hydrogen, halogen, C 1 -C 5 lower alkyl, C 1 -C 5 lower alkoxy carbon atoms, lower haloalkyl of 1 to 5 carbon atoms, lower alkoxycarbonyl of 2 to 7 carbon atoms or methylenedioxy and n is a number from 1 to 2.

The above reaction can be carried out in the presence of a base and a solvent, provided that the pyrazole derivative of the general formula II is reacted with a hydroxylamine salt. The reaction can also be carried out in the presence of a solvent, if the hydroxylamine is prepared in a known manner and then directly reacted with the pyrazole derivative of the general formula II.

Examples of hydroxylamine useful herein include hydroxylamine and its salts with inorganic acids (e.g., hydrochloride, sulfate). All of these compounds are prepared by known methods.

As the solvent useful in the present invention, any solvent that does not interfere with the reaction may be used. Examples include alcohols (e.g. methanol, ethanol, isopropanol, diethylene glycol), ethers (e.g. diethyl ether, diisopropyl ether, tetrahydrofuran, dioxane, monoglyme, diglyme), halogenated hydrocarbons (e.g. dichloroethane, chloroform, tetrachloroethane), aromatic hydrocarbons (e.g. benzene, monochlorobenzene, toluene), nitriles (e.g. acetonitrile), dimethylsulfoxide, dimethylformamide, water and their respective mixtures.

If the reaction is carried out in two phases in a solvent mixture, a phase transfer catalyst such as triethylbenzylammonium chloride, trioctylmethylammonium chloride or the like can also be used.

Inorganic or organic bases can be used as bases. The inorganic base includes, for example, alkali metal or alkaline earth metal carbonates (e.g. sodium carbonate, potassium carbonate, calcium carbonate, sodium bicarbonate) and alkali or alkaline earth metal hydroxides or hydrides (e.g. sodium hydroxide, potassium hydroxide,

calcium hydroxide, sodium hydride, lithium hydride). Organic bases include, for example, diethylamine, triethylamine, pyridine and 4-dimethylaminopyridine.

The base may be used in an equimolar amount relative to the hydroxylamine salt, but an excess of the base may also be used. The temperature of the reaction mixture is appropriately selected from temperatures ranging from room temperature to the boiling point of the solvent. The reaction time varies from one minute to 48 hours depending on the reaction temperature and the amount of reactants. The amount of the reactants may be selected such that the amount is equimolar to each other since the reaction of the invention is equimolar. However, any reactant may be used in excess. After completion of the reaction, the desired product can be separated by conventional means. If necessary, it is further purified by recrystallization, distillation or the like.

The compound of formula (II) used according to the invention can be produced, for example, by the process illustrated by the following reaction scheme:

(JV)

Wherein R, Rt, R 5, X and n are as defined above, Hal is a halogen atom and M is a hydrogen atom or an alkali metal atom. That is, the pyrazole derivative of formula (IV) is reacted with a phenol derivative of formula (III) in the presence of an appropriate solvent to form a compound of formula (II).

The compound of formula (IV) may be prepared by a known method [for example, as described in Chemical Abstracts 73, 3844W (1970)].

Typical examples of compounds of formula I are shown in Table 1. However, the compound is not limited to these examples.

TABLE 1

(AND)

H H H H H H H H H H H H H H H H H H H H H

H

H H H

H

СНз C? H5

Ri Иг F Хп Physical properties СНз Н Н oil СНз СНз Н mp 133.8 ° C СНз СНз 2-С1 mp 177.4 ° C СНз СНз 3-С1 mp 166.0 ° C СНз СНз 4-С1 mp 158.2 ° C СНз СНз 4-Вг mp 169.0 ° C СНз СНз 2-F mp 214.5 ° C СНз СНз 3-F mp 146.0 ° C СНз СНз 4-F mp 167.6 ^Q C СНз СНз 4-СНз mp 143.1 ^C C СНз СНз З-С2Н4 mp 108.5-109.3 ° C СНз СНз 4-С2Н5 mp 105.0-105.6 ° C СНз СНз 4-tert mp 138.9 ° C СНз СНз 2-ОСНз mp 170.6 ° C СНз СНз 3-ОСНз mp 150.2 ° C СНз СНз 4-ОСНз mp 123.4 ° C СНз СНз 4-ОС2Н5 mp 131.8-133.0 ⁿ C СНз СНз 3-CFs mp 158.8 ° C СНз СНз 4-СООСзН7 mp 149.8 ° C СНз СНз 2.4-С12 mp 179.0 ° C СНз СНз 3.4-С12 mp 210.6 ° C СНз СНз 3,5- (ОСНз) 2 mp 179.3 ° C СНз СНз 3,4- СНг '—О mp 152.4-154.7 ° C СНз СгН5 н mp 112.3 ° C СНз ÍS0C3H7 н mp 164.6 ° C СНз CF3 н oil СНз <2> 4-С1 mp 177.8 ° C О СНз Н mp 191.2 ° C СНз СНз Н mp 23.2 ° C СНз СНз Н mp 107.3 ° C СНз СНз Н mp 196-199.8 ° C

Table 2 shows the NMR data of Compound # 1 and # 26 whose physical properties in the respective column of Table 1 are described as "oil".

TABLE 2

Compound NMR data (CDCl 3, TMS) [ppm] No.

3.6 (singlet, 3 H),

6.7 to 7.5 (multiplet, 5H)

7.6 (singlet 11-1)

7.9 (singlet, 1 H),

9.6 (singlet, III)

3.6 (singlet, 311);

6.7 to 7.4 (ninIletlet, 5H),

7.9 (singlet, 1H), 'TU (broad singlet, IИ)

This invention is further illustrated by the following examples.

2 g (0.009 25 mol) of 5-phenoxy-4-formyl-1,3-dimethylpyrazole are dissolved in 60 ml of methanol. To this solution was added 0.8 g (0.01142 mol) of hydroxylaroin hydrochloride. The reaction mixture was stirred. To this solution is added an aqueous solution containing 0.75 g (0.01142 mol) of potassium hydroxide dissolved in 10 ml of water. The mixture was allowed to react for one hour at 60 ^° C. After the reaction was complete, methanol was distilled off from the reaction mixture. The resulting crystals were filtered and washed with water. The desired product was obtained in a yield of 2 g (93%). Melting point: 133.8 ^C.

Example 1 (1.

Example 2 548-muxy-4-hydroxyimino-m-ethyl-1,3- (1-methylbenzyl) pyrazole (compound number 2)

Synthesis of 5- (2-chlorophenoxy) -4-liydroxyimino-methyl-1,3-dimethylpyrazole (Compound No. 3)

Dissolve 2 grams (0.00769 mole) of 5- (2-chlorophenoxy) -4-formyl-1,3-diniethylpyrazole in 50 ml of ethanol. To this solution was added 0.66 g (0.009 55 mol) of hydroxyl hydrochloride hydrochloride and the mixture was stirred. An aqueous solution was added to this swab, which was obtained by dissolving 1.26 g (0.009 55 mol) of potassium carbonate in 5 ml of water. The mixture was allowed to react for two hours at room temperature. After completion of the reaction, ethanol was distilled off. The resulting crystals were filtered off, washed with water and recrystallized from ethyl acetate. 1.9 g of the expected product are obtained. Yield 90%. Melting point 177.4 ^° C.

Example 3

Synthesis of 5- (3-Trifluoromethylphenoxy) -4-hydroxyin) inomethyl-1,3-dimethylpyrazole (Compound No. 18)

262876

3 grams (0.010 5 mol) of 5- (3-trifluoromethylphenoxy) -4-formyl-1,3-dimethylpyrazole are dissolved in 70 ml of ethanol. To this solution was added 0.88 g (0.012 6 mol) of hydroxylamine hydrochloride. The mixture was stirred and 1.33 g (0.0126 mol) of sodium carbonate and 10 ml of water were added. The mixture was allowed to react for three hours by distilling off. The resulting crystals were filtered and washed with water. 3 g of the expected product are obtained, yield 96%, melting point 158.8 ° C.

Example 4

Synthesis of 5-phenoxy-4- [1-hydroxyiminoethyl] -1,3-dimethylpyrazole (Compound No. 29)

5 g (0.0217 mol) of 5-phenoxy-4-acetyl-1,3'-dimethylpyrazole are dissolved in a solvent mixture consisting of 100 ml of acetonitrile and 20 ml of water. To this solution was added 1.82 g (0.26 mol) of hydroxylamine hydrochloride and the mixture was stirred. Triethylamine (3 g, 0.03 mol) was added dropwise to the reaction mixture. The reaction mixture was allowed to react at 60 ° C for three hours. After completion of the reaction, the solvent was removed by distillation. The resulting crystals were recrystallized from methanol. 4.5 g of the expected product are obtained. Yield: 85%. Melting point: 223.2 ° C.

These pyrazoloxime derivatives are able to control various diseases caused by fungi attacking valuable crops growing in paddy fields, upland fields, gardens and similar places such as rice gangrene caused by Pyricylaria oryzae, barley mildew and wheat caused by Erysiphe graminis, rust in oats caused by Puccinia coconata, brown spots in rice caused by Cochliobolus miyabeanus, purple spots (cercosporiasis) in soybeans caused by Cercospora kikuchi, false powdery mildew in cucumbers caused by Pseudoperenosphora cubensis.

For the application of the compounds of the invention as fungicides, the compounds are prepared in a suitable form for use according to conventional methods of preparing agricultural chemicals. That is, the compounds of the invention are mixed with suitable inert carriers and, if necessary, adjuvants, in a suitable ratio. By distillation, dispersion, suspension, mechanical mixing, impregnation, adsorption or sticking, a suitable form of the preparation is prepared, for example, a suspension, emulsifiable concentrate, solutions, wettable powders, dusts, granules or tablets.

The inert carriers used in the compositions can be either solids or liquids. Examples of acceptable solid carriers include vegetable powders such as soybean meal, cereal flour, wood flour, bark flour, sawdust, powdered tobacco stems, powdered nut husks, bran, pulverized cellulose and plant extract residues, fibrous materials such as paper, cardboard and waste materials, synthetic polymers such as powdered synthetic resins, inorganic or mineral products such as clays [eg kaolin, bentonite and acid clays], talc (eg talc and pyrophyllite), silicate substances [eg diatomaceous earth , silica sand, mica and 'white coal' (highly dispersed synthetic silica, also sometimes called finely ground hydrated silica or hydrated silica; some commercial products contain hydrated silica as the main component), actively carbon, powdered sulfur, pumice, calcined diatomaceous earth, ground brick, fly ash, ps, calcium carbonate, calcium phosphate, chemical fertilizers such as ammonium sulfate, ammonium nitrate, urea and ammonium chloride, and Farmer manure. These materials are used alone or in combination with each other. Materials which are used as liquid carriers are selected from those which are solvents of the active ingredients and those which are not solvents, but which can disperse the active compounds with an adjuvant. For example, the following materials may be used alone or in combination: water, alcohols (e.g. methanol, ethanol, isopropanol, butanol, ethylene glycol), ketones (e.g. acetone, methylethylketone, methylisobutylketone, diisobutylketone and cyclohexanone), ethers (e.g. ethyl ether, dioxane, wholeolts, dipropyl11

262876 ether and tetrahydrofuran), aliphatic hydrocarbons (e.g. petrol and mineral oils), aromatic hydrocarbons (e.g. benzene, toluene, xylene, solvent gasoline and alkylbr. Halenes), halogenated hydrocarbons (e.g. dichloroethane, chlorinated benzenes, chloroform and carbon tetrachloride), esters (e.g. ethyl acetate, dibutyl phthalate, diisopropyl phthalate and dioctyl phthalate), acid amides (e.g. dimethylformamide, dibutylformamide and dimethylacetamide), nitriles (e.g. -acetonitrile) and dimethylsulfoxide.

Adjuvants, examples of which are given below, are used according to individual purposes, in some cases combined with each other. In some cases, no adjuvant is used at all.

Surfactants such as polyoxyethylene alkylaryl ethers, polyoxyethylene alkyl ethers, polyoxyethylene higher fatty acid esters, polyoxyethylene resins, polyoxyethylene sorbitan monolaurate, polyoxyethylene sulfonate sulfonates, alkyl sulfonate sulfonates, alkyl olefin sulfonate sulfonates, alkyl olefin sulfonate sulfonates, alkyl olefin sulfonate sulfonates, alkyl olefin sulfonate sulfonates, alkylene sulfonate sulfonates, alkyl olefin sulfonates are present. For example, casein, gelatin, starch, amino acid, methylcellulose, carboxymethylcellulose, acacia, acacia, turpentine oil, rice bran oil, bentonite and lignin sulphonates can be used to stabilize the dispersion, improve tack and / or agglomerate the active compounds.

Waxes, stearates or alkyl phosphates are recommended to improve the liquid properties of the solid composition.

It is recommended to use naphthalenesulfonic acid condensation products and polyphosphates as the peptizing agent of the dispersed compositions. Anti-foaming agents such as silicone oil may also be added.

The content of the active ingredient is adjusted according to the needs. In the preparation of powdered or granulated products, the active ingredient content is usually 0.5 to 20% by weight. In the preparation of emulsifiable concentrates or wettable powdered products, a content of 0.1 to 50% by weight is desirable.

In regulating various fungi, inhibiting their growth or protecting certain useful plants against fungal damage, a dose (which is capable of regulating and / or inhibiting fungi and thereby protecting useful plants) of a fungicidal composition for agricultural and horticultural use is applied either directly as such or after dilution or suspension in water or other suitable medium on the soil or foliage of the crop to be protected from the action of the fungus.

The amount of fungicide of the invention to be used depends on various factors, such as the purpose of application, crop growth stage, weather conditions, ambient conditions, form of fungicidal composition, method of application, type of field treated in this manner and the like.

When administering the fungicidal composition of the invention alone, it is desirable that the selected dose of active compound of the invention be in the range of 5 to 500 g per 0.1 ha. It will also be appreciated that when combined with other fungicides, the optimum dose is often lower than with a single compound. Thus, the fungicide of the present invention may be used in lower than the above amounts when used in combination with another type of fungicide.

Further, the compounds of the invention are blended with other fungicides, insecticides, fertilizers and plant growth regulators when these products can be taken together with them. Illustrative examples of fungicides used in conjunction with the compounds of this invention include isoprothiolane, pyrocellilone, edifenphos, captan, chlorthalonil, captafol, thiophanate-methyl, benomyl, zineb, maneb, and the like. Illustrative examples of insecticides that are used in conjunction with a compound of the present invention include acephat, malathion, feuitrothion, BPMC and similar insecticides.

The following examples illustrate the fungicidal activity and formulations of the compounds of this invention. However, the present invention is not limited to these examples.

Test - example 1

Rice brown spot control test

Young rice in Stage 5 Certain (variant: Nihonba.ro) is cultivated in plastic cups of 12 cm diameter. These plants are sufficiently sprayed with a spray gun with a chemical solution containing as active ingredient a compound of the invention at a predetermined concentration. The day after spraying, the rice was inoculated by spraying with a suspension of conidia C-ochliobolus miyabeanus. The rice is left to stand for 20 hours in a moist room. Then they are transferred to the greenhouse. On the fourth day after seeding, the lesions developed on each leaf were detected. The percent control of the compound used is calculated from the following formula:

262 ^ 76

1.3 14

Percentage control = [1 - (number of damage per sheet of processed rice group;) / (number of damage per sheet of unprocessed rice group)]

The regulatory effect of the compound is determined from the following criteria:

Criteria - A: percentage of regulation = 95 to 100%,

B: regulation percentage = 80 to 94%,

C: control percentage = 60 to 79 ° / o.

The results are shown in Table 3.

TABLE 3

Number of test compound

Concentration (ppm)

Regulatory effect of the compound

2 200 C 4 200 C 6 200 В 8 200 В 9 200 А 10 200 А 13 200 С 15 Dec 200 В 16 200 В 22nd 200 С 24 200 С 25 200 С 29 200 В

Test - example 2

Rice control regulation test

Five-leaf young rice (variant: Nihonbare) is grown in plastic cups of 10 cm diameter (10 rice in each crucible). These plants are sufficiently sprayed with a spray gun with a chemical solution containing as active ingredient a compound of the invention at a predetermined concentration. The day after spraying, the rice was inoculated by spraying a conidia suspension of Pyricularia oryzae. The rice is left to stand in a moist room for 20 hours and then transferred to a greenhouse. On the sixth day after seeding, the number of lesions developed is determined and compared to that of the rice control group (i.e., the group to which the compound has not been applied. The control value of the compound used is calculated. 1. The results are shown in Table 4.

TABLE 4

Test compound number Concentration (ppm) Regulatory effect

2 .1 000 с 5 1 000 А 6 1 000 в 8 1 000 с 9 1 000 в 10 1 ооо с 11 1 000 с 13 1 000 с 14 1 000 в 16 1 000 с 19 Dec 1000 в

Formulation - Example 1

Wettable Powder Compound No. 5 50 parts diatomaceous earth / clay mixture 45 parts polyoxyethylennonylphenyl ether 5 parts

The above materials are mixed uniformly. Grinding gives a wettable powder.

Formulation - Example 2

Emulsion Compound No. 9 20 parts tetrahydrofuran 20 parts xylene 45 parts mixture of polyoxyethylennonylphenyl ether and alkylbenzenesulfonic acid salt 15 parts

The above materials are mixed uniformly. Dissolution yields an emulsion.

Formulation - Example 3

Dust Compound No. 10 4 parts diatomaceous earth, clay and talc mixture 95 parts calcium stearate 1 part

The above materials are mixed uniformly. Grinding gives a dust.

Formulation - Example 4

Granules Compound No. 29 3 parts bentonite clay mixture 92 parts calcium ligninsulfonate 5 parts

The above materials are uniformly mixed and ground. Add the appropriate amount of water and flex the mixture. Pelletization gives granules.

Claims (2)

A fungicidal composition for agricultural and horticultural use, characterized in that the active ingredient comprises a pyrazoloxime derivative of the general formula (I): hydrogen, halogen, C 1 -C 5 -alkyl, C 1 -C 5 -alkoxy, haloalkyl C 1 -C 5, C 2 -C 7 alkoxycarbonyl, or methylenedioxy and n is from 1 to 2. 2. A process according to claim 1 for the preparation of a pyrazolo oxime derivative of the formula I, characterized in that a pyrazole derivative of the formula II is reacted in which R represents a hydrogen atom, a C1-C5 alkyl group or a phenyl group, R1 and R2 independently are hydrogen, C 1 -C 5 alkyl, C 1 -C 5 haloalkyl or aryl selected from the group consisting of phenyl, tolyl, xylyl or naphthyl, X may independently of (II) wherein R is , R1, R2, X and n are as above with hydroxylamine.