CS268690B2 - Fungicide - Google Patents

Abstract

FUNGICIDAL PYRIDYL CYCLOPROPANE CARBOXAMIDES Novel fungicidal pyridyl cyclopropane carboxamides having the general structural formula <IMG> in which R is selected from the group halogen C1-C3 alkoxy and C1-C3 haloalkoxy, R1 is selected from the group of -H and -C?N; and R2 is selected from the group of -H, -CH3 and 2-CH3; X is O or S; and fungicidally acceptable organic and inorganic salts thereof. These compounds provide excellent control of fungal growth.

Description

The invention relates to a fungicidal composition.

fungicidal infections of crops such as barley, rice, tomato, wheat, beans, roses, grapevines and other important crops can cause severe losses in both quantity and quality of agricultural products. It is therefore extremely important to have a means of preventing, suppressing or eliminating fungal growth. Preventive spraying with commercially available fungicides has been widely used to prevent infection of important agricultural crops and fungal growth on these crops. It would also be desirable to have a medicinal fungicide capable of destroying the fungus and eliminating its deleterious effects when detecting fungal infestation. Such a fungicide would be applied after infestation as a medicinal spray.

We have now found novel fungicidal compounds which are the pyridyl cyclopropanecarboxamides of the general formula

where

R is halogen such as chlorine, fluorine and bromine, preferably chlorine or C1 -C3 alkoxy such as propoxy, ethoxy, and methoxy, preferably methoxy;

R- | is hydrogen or cyano;

R 2 represents methyl or hydrogen e

X represents oxygen or sulfur, and their fungicidally acceptable salts of organic and inorganic acids. These novel fungicides are highly effective and are useful both as preventive and as medicinal fungicides.

As used herein, fungicide is a compound which inhibits fungal growth. The term '‘suppression' refers to the prevention, destruction and inhibition of fungal growth. The term "medicinal" or "curative" is used in connection with the application of a fungicide after infection, which results in the suppression of a fungal infection and which prevents the development of adverse effects on the host crop.

The present invention provides a fungicidal composition comprising as an active ingredient a fungicidally effective amount of a compound of formula (1)

where it is halogen or (C1-C3) alkoxy,

R ₂ is hydrogen, a nobo nitryl group, and R ₂ is hydrogen, a 1-methyl- or 2-methyl- group, and oxygenates the sulfur,

CS 260 690 02 or a fungicidally acceptable salt thereof 8 with organic or inorganic acids and additionally enriches the inert diluent or solvent for this elenenicin.

The term "halogen" refers to bromine, fluorine and chlorine.

The term "a-alkoxy-C 1 -C 3 -carbon" means a methoxy, ethoxy, propoxy, and propoxy group.

Compounds which are the active ingredient of the fungicidal compositions of the present invention can generally be prepared by reacting a suitable substituted 5-aminopyridine with a suitable substituted cyclopropenecarboxylic acid chloride in a polar solvent such as dichloromethane which is carried out in a suitable reactor. An acid binding agent such as pyridine is expediently present in the reaction vessel. The reaction is usually carried out at ambient temperature, but may be carried out in a temperature range of from -30 to 60 ° C, depending on the substituents present on the amlriopyridine and cyclopropene carboxylic acid chloride. The reaction is usually complete in 1 to 3 hours. The resulting product is isolated in a conventional manner by conventional techniques such as washing with an alkaline solution, such as sodium hydroxide solution with water, solution using conventional solvents such as magnesium sulfate, and crystallization from hexane. The thionocarboxamides of the invention are also effective. These compounds ae are generally prepared by reacting the corresponding amide ae with phosphorus sulphide in a neutral solvent such as benzene, toluene, chloroform, methyl chloride or pyridine. The product is soluble in strong alkali and can be isolated from the reaction mixture by virtue of this property, i.e. by adjusting the pH of the extract to the neutral zone. Salts of various pyridyl cyclopropanecarboxamides can generally be prepared by reacting at least a molar amount of the lewls acid 8 with carboxamide. The reaction is preferably carried out in a kerboxamide solvent, if necessary, with heating. The prepared gel is isolated from the reaction mixture by conventional techniques.

The pyridylcarboxamides of the invention are basic. The nitrogen atom of the proton-free pyridine ring can be protonated with an acid, whether organic or inorganic. Representative examples of inorganic acids include hydrochloric, nitric, hydrobromic, sulfuric, amidoeulfonic, and phosphoric acid. Representative examples of organic acids include acetic, trifluoroacetic acid, benzoic, benzenesulfonic, p-toluenesulfonic, naphthalenesulfonic, phenylphosphonic and organophoaphonic acids. The resulting aolls are also fungicidally effective.

Example!

Preparation of N- (2-methyl-5-piperidinyl) -cyclopropanecarboxamide

In a reaction vessel, 5-omino-2-methoxy pyridine (32.4 g, 0.10 mol) and 10 mL of pyridine in 200 mL of dichloromethane were mixed. 9.1 ml (0.10 mol) of cyclopropanecarboxylic acid chloride were added to the reaction mixture over 2 minutes. The reaction is exothermic and the temperature rises to 34 ° C. The reaction mixture was allowed to stand for one hour at room temperature and then the reaction amphis was washed with 200 ml of sodium hydroxide solution and 100 ml of water. The resulting organic phase is separated and dried over anhydrous magnesium sulfate. Crystals formed, and therefore the mixture was filtered and the residue washed with 300 ml of acetone. the ritrate * was evaporated in vacuo to give a solid which was triturated with hexane. After drying, 16.7 g of product are obtained. The resulting product was identified by infrared and NMR spectroscopy as the title olefin. Melting point: 130-131 ° C. In the following description, this compound is referred to as compound 1.

CS 268 690 B2

Example 2

Preparation of N- (2-methoxy-5-pyridyl) -cyclopropanecarboxamide dodecanoic acid salt g (0.016 mol) of the compound of Example 1 is dissolved in 100 ml of acetone in a 300 ml single-necked round-bottomed flask. Dissolution is aided by swirling movement. 3.2 g (0.016 mol) of dodecanoic acid are added and the solution is dissolved. The resulting solution was evaporated in a rotary evaporator to give 6.2 g of a white solid, m.p. 92-96 ° C, which was identified as the title compound by nuclear magnetic resonance spectroscopy. Hereinafter, this compound is referred to as Compound No. 7.

Example 3

Preparation of N- (2-methoxy-5-pyridyl) -cyclopropanethiocarboxamide

A solution of 5.0 g of N- (2-methoxy-5-pyridyl) -cyclopropanecarboxamide (0.026 mol) in methylene chloride (100 ml) was refluxed with stirring 8 6.1 g of phosphorus pentasulfide (0.03 mol). Cool to room temperature, dilute with chloroform (100 mL) and wash with saturated sodium bicarbonate solution (200 mL). The organic phase was extracted with 55N sodium hydroxide solution (2 x 100 ml). The extract was acidified with concentrated hydrochloric acid to pH 7 and extracted with chloroform (3 x 100 mL). The chloroform extract was dried over magnesium sulfate and evaporated in vacuo. 0.6 g of the expected product is obtained, m.p. 79-83 ° C.

Representative compounds of the invention and their physical properties are shown in Table I.

-Cl -OCH ₃ -OCH ₃ -CH ₃ salt of hydrochloric acid and compound No. 1 acid salt acid salt and compound salt of chloromethylphosphonic acid salt and compound 1

1-CH 3

-2! -CH

167.0 04 _f 0 70.0 66.0 169.0

92.0

74.0

70.0 dodecane and 2-naphthalenesulfonic acid No 1 acetic and 1 benzoic and 1 compounds

144.0-146.0 92.0 - 96.0

90.0 - 96.0

T12.0 - 120.0

78.0 - 85.0

110.0 - 118.0

CS 268 690 02

compound no. R 1 is R 2 X nj ^ nobo melting temperature (° C) 12 hydrochloric acid salt and compound 2 134,0 - 136.0 13 .-Вг -H -H 0 172,0 - 175.0 14 phenylphosphonic acid salt and compound 1 108,0 - 115.0 15 Dec amido sulphonic acid salt and compound 1 131,0 - 136.0 16 trifluoroacetic acid salt and compound 1 89,0 - 93.0 17 nitric acid salt and compounds 1 144,0 - 14 5,0 18 -OCH 3 -H -II WITH 79,0 - B3.0 19 Dec -F -Η -II 0 116,0 - 117.0 Example 3 Evaluation of molar equivalent preventive effects spraying Powdery mildew (Erysiphe graminis (EG) per barley:

The Northrup King Sunbar 401 barley seeds are sown (after 12 seeds in a 5 cm pot) in sand loam soil 7 days prior to testing. The test compound is diluted with a 50/50 acetone / water solution to a concentration that gradually decreases from 0.004 molar concentration. The test solution is then sprayed onto the barley plants using a sprayer.

After 24 hours and the test solutions are placed in an inoculation chamber equipped with a circulation chamber equipped with a circulation blower. Barley plants heavily damaged by sporulating fungi Erysiphe graminis are placed in front of the blower to release and dietribulate spores. After two minutes, the blower is turned off and the chamber ae is left closed for five minutes to allow the spores to settle. The inoculated plants are then placed in a greenhouse shelf and automatically supplied with water from below.

Results ae are recorded 7 days after inoculation as a percentage of disease control based on the percentage reduction of the damaged area of the plants compared to the untreated control plants. From the dose / dilution ae curves, the concentrations of the compound giving 90% disease control (CO 90) are determined.

Cut Pucks in i a recondita (PR) on sheets

In 5 cm ae pots, 5 Anza wheat seeds are sown in loamy soil 12 days prior to testing. Test compound ee is diluted with a 50/50 acetone / water solution to a concentration that decreases from the original 0.004 molar concentration. 12 ml of the test solution are sprayed onto wheat plants using a sprayer.

Prepare a suspension of urediospores of Puccinia recondita by aspirating spores of 8 leaves of wheat and uredium puatules and diluting them to a suspension containing 10 µl of spore / ml deionized water containing 0.5% polyoxyethylene sorbitan monolaurate (Tween ( ^R ) 20). The plants are inoculated 24 hours before treatment by spraying the spore suspension until dripping, after which the plants are. · Grind into a dark cloud chamber. After 48 hours in the fog, the plants are transferred to greenhouse shelves and under irrigation.

CS 268 690 B2

The results are recorded 10 days after inoculation as a percentage of disease control based on a percentage reduction in the damaged area of the plants compared to the untreated control plants. From the dose / dilution curves, the concentration of compound giving 90% disease control (CO 90) was determined.

Mold Fits On Petals (BC)

Two white rose petals were placed in a petri dish lined with moist filter paper. The test compound is diluted with 50/50 acetone / water to a concentration that decreases gradually from 0.004 molar. Spray 0.5 ml of the test solution on the petals and allow the coating to dry.

The inoculum is prepared by adding a 5 mm disc from a two week old culture of Botrytis cinerea on Elliot V-θ agar to 10 ml of sterile distilled water with 0.5% grape juice. A 20 µl drop of suspension of this inoculum is placed on each petal. Petri dishes with inoculated petals are placed in sealed plastic boxes to keep them in a saturated humidity environment.

Results are read 4 days after inoculation as a percentage reduction in necrotic area compared to controls treated with acetone / water only. The concentration of the compounds giving 90? Disease control (ЕС 90) is determined from the curve / dilution curves.

The molar equivalent of 0.004 used as the initial dilution in these evaluation procedures is equivalent to 750 ppm amides. The concentration of all test salts was set to 0.004 molar in solution, corresponding to 750 ppm of the amide from which the salts were formed.

The results are shown in Table II as approximate values of ЕС 90. The value (750) means partial suppression at 750 ppm.

Table II Compound No.

EG PR

BC

1 200 200 20 May 2 250 750 25 3 (750) 500 • 25 4 ’ > 750 > 750 750 5 (750) 200 200 6 200 200 70 7 200 200 20 May 8 200 200 20 May 9 200 200 20 May 10 200 200 20 May 1 1 200 200 20 May 12 - - 80 13 (750) (750) (750) 14  200 200 20 May 15 Dec - - 20 May 16 • - - 20 May 17 - - 20 May 18 (750) (750) 20 May 19 Dec (750) 250 80

CS 268 690 B2

Evaluation of the post-infectious fungicidal effect

Example 4

Apple scab (Venturia inaequalis) VE

Apple seedling ее is inoculated by spraying Venturia inaequalis (24 h) on their leaves using standard procedures. After inoculation, the test compound is applied in solution as a spray to the air at 160 ml / L. The results ее determined after the development of symptoms from the reduction of the affected area compared to untreated control plants.

Rice disease Piricularia oryzae (PO) days after inoculation and rice seedlings with aqueous solution containing 50 mg test compound per liter of soil. Inoculation of Piricularia oryzae is performed using standard procedures. Results ae determine after symptom development based on the reduction of lesion area in comparison and untreated control plants.

SeptoriosisB wheat (SN) ·

Two days prior to inoculation, the test elouConino was applied in a solution of nu seedlings of wheat seedlings in the form of a spray on the leaf at a concentration of 500 mg / l. Septoria nodorum is inoculated according to standard procedures. The results are determined after the development of symptoms from the reduction in the area of injury compared to 8 untreated control plants.

FusarióžB wheat (FC)

Fusarium culmonum infested wheat seed is treated at 500 mg / kg with the test compound using standard methods. The sc results determine after the development of symptoms from a reduction in the area of injury compared to untreated control plants.

• Activity is evaluated by the following steps

- zero

X - light

XX - medium

XXX - high

Table III

Disease compound no.

VE

AFTER

SN

FC

XXX X

0. X

XX

Example 5

Evaluation of therapeutic sprays

Rust Puccinie rocondita (P R)

In 5 cm diameter pots, 7 seeds of Anza wheat are sewn into loam soil on the day before testing. A urediospore suspension of Puccinia rccondita is prepared by aspiration of the spores

CS 268 690 B2 from wheat leaf with uredium pustules and diluting them to a suspension containing 10 ⁵ spores / ml deionized water containing 0.5% polyoxyethylene sorbitan monolaurate (Tweeni ^R > 20). Plants are inoculated by spraying the spore suspension until dripping, the leaves are ignited, and then the plants are sprayed again with the spore suspension until dripping and then placed in a mist chamber. After 48 hours in the fog, the plants are transferred to greenhouse shelves with underwater irrigation.

The test compound is diluted with a 50/50 acetone / water solution to a concentration that decreases from 0.075 50 hours after inoculation, the plants are placed on a rotary table and sprayed with the test solution using spray nozzles until the solution drips almost. (The inoculation time is defined when the plants are placed in a cloud chamber).

Results are recorded 10 days after inoculation as a percentage of disease control based on the percentage decrease in damaged area compared to untreated control plants.

Table IV Compound No. PR

100 ALIGN!

100 ALIGN!

100 ALIGN!

100 ALIGN!

100 ALIGN!

100 ALIGN!

100 ALIGN!

100 ALIGN!

100 ALIGN!

100 ALIGN!

100 ALIGN!

The compounds of the invention are particularly effective against Ootrytis and can be used both as preventive foliar sprays and as therapeutic foliar sprays. They are more potent than the standard commercially available compounds used in preventive and therapeutic sprays against Ootrytis. Mushrooms against which the compounds of the invention are particularly effective include Botrytis cinerea, Venturia inaequalis, Septoria nodorum, Erysiphe graminis, Fusarium culmorum, Piricularia oryzae and Puccinia graminis.

The compounds of the invention are useful as fungicides, in particular as preventive and curative fungicides, and can be applied in various ways at different concentrations. In general, these compounds and compositions based thereon may be applied directly to the crop leaves, to the soil in which the crops are grown, or to irrigation water that feeds the crop or soil. In practice, the above defined compounds are formulated as fungicidal compositions by mixing the fungicidally effective amount of the compounds with excipients and carriers normally used to facilitate dispersion of the active ingredients in agricultural applications. It should be taken into account that the type of formulation and the method of administration of the toxic substance may affect the efficacy of the substances in the application. The fungicidally active compounds may be formulated as wettable powders, emulsifiable concentrates, dusts, solutions and other known formulations, depending on the desired mode of application.

CS 268 690 82

Preferred compositions for preventive and curative fungicidal applications are wettable powders and emulsifiable concentrates. These compositions may contain from about 0.1% to about 95% or more of the active ingredient. The fungicidal effective amounts depend on the species of oenoma or plants that have 30 m / m and the application rate is in the range of about 0.056 to about 2,000 kg / ha, preferably about 0.11 to about 11.2 kg / ha.

Wettable powders are in the form of finely divided particles which readily disperse in water and other dispersants. The wettable powder is finally applied to the soil or plant either as a dry powder or as a dispersion in water or other liquid. Typical carriers for wettable powders are the Valchrida, kaolin clays, silicas and other readily wettable organic and inorganic diluents. Wettable powders are normally prepared containing from 5 to 95% of active ingredient and usually also contain small amounts of wetting, dispersing or emulsifying agents to facilitate wetting and dispersion.

Dry bulk or water dispersible granules are agglomerated wettable powders produced either by granulation through a sieve or in a fluid bed. These compositions are finally applied to the soil or plants in the form of a dispersion in water or other liquid. The granules are free of dust and are free-flowing, yet still form homogeneous dispersions when diluted with water. Typical carriers in these types of compositions are bleaches, kaolin clays, silicas and other readily wettable organic or inorganic diluents. These compositions are normally formulated containing from 5 to 95% active ingredient and usually also contain small amounts of wetting, dispersing or emulsifying agents to facilitate wetting and dispersion. .

Emulsifiable Concentrates These are homogeneous liquid formulations which are dispersible in water and other dispersing agents. They may consist of the active compound 8 itself by addition of a liquid or solid emulsifier, or may also contain a liquid carrier such as xylene, heavy aromatic petroleum fractions, isophorone and other non-volatile organic solvents. For fungicidal application, these concentrates are dispersed in water or other liquid carrier and are usually applied to the treated area in the form of a spray. The percentage by weight of the principal active ingredient may vary depending on the intended application, but is usually in the range of 0.1 to 95% by weight of the active ingredient. .

Typical wetting, dispersing or emulsifying agents used in the production of agricultural products include, for example, alkyl and alkali metal phosphates and sulfates and their sodium salts, polyhydroxy alcohols and other types of surfactants, many of which are commercially available. When surfactants are used, their circulation in the fungicidal composition is from 0.1 to 15% by weight.

Dusts, which are free-flowing mixtures of the active ingredient, are useful compositions for many applications. 8 Finely divided solids such as talc, clay, flours and other organic and inorganic solids which act as dispersants and carriers for the toxic additive. .

For ophthalmic purposes, this is a paste which is a homogeneous suspension of finely divided solid toxic ingredients in a liquid carrier such as water or oil. These compositions are normally formulated with from 5 to 95% active ingredient and usually also contain small amounts of wetting, dispersing or emulsifying agents to facilitate wetting and dispersion. Prior to application, the pastes are usually diluted and applied to the treated area as a spray.

CS 268 690 B2

Examples of typical compositions additive oil% by weight

Compound 1 oil solvent-heavy arom. Petroleum fraction in total

100 ALIGN!

Compound 2 kerosene emulsifying agent (mixture of long-chain ethoxylated polyethers and long-chain sulfonate) total

Emulsifiable concentrate

100 ALIGN!

Emulsifiable concentrate

Compound 3 kerosene

Emulsifying agent (mixture of ethoxylated long-chain ethers and long-chain sulphate) total

100 ALIGN!

Dust and / or powders

ingredient * % wt. . wt. % wt. Compound 4 0.5 50.0 90.0 attapulgite clay powder 93.5 44.0 4.0 Sodium ligninsulfonate . ⁵ '° 3.0 3.0 sodium dioctylsulfosuccinate . 1.0 1, 0 1, 0 total 100.0 100.0 100.0 Like other useful resources pro fungicidní application may be mentioned simple roz Effectively additive flows in the disperser, ₍ in which effective the additive is completely soluble to the required concentration, as in ncetone, alkylovnných n Ofta sloth, xylene sky other organic

solvents. Pressure sprays, usually acronols, may also be used. In this case, the active ingredient is dispersed in finely divided form due to evaporation of the low boiling dispersing solvent or carrier, such as freons.

С5 260,690 В2

The fungicidal compositions of the invention are applied to the plants by a conventional procedure.

The impregnated nobo liquid eo compositions may not be applied to the plants by motor sprayers, hand or trailed sprayers and similar devices. The compositions can also be applied by air as poprofte nobo fats, since iodine is effective in small doses. '

Claims (2)

1. A fungicidal composition comprising, as an active ingredient, a fungicidally effective amount of a compound of formula (I) wherein: --------------------------- · -........ R 2 is halogen or C 1 -C 3 alkoxy, is hydrogen or nitryl; and R 2 is hydrogen, 1-methyl or 2-methyl, and. X represents oxygen or sulfur, or a fungicidally acceptable salt thereof, with organic or inorganic acids, and additionally contains an inert diluent or carrier therefor. · 2. A fungicidal composition according to claim 1, wherein the active ingredient of the formula I is a compound in which P is chlorine or a methoxy group, R1 is hydrogen or nitrile, R2 is hydrogen, 1-methyl or The 2-methyl group for X is oxygen or its fungicidally acceptable salts with organic or inorganic acids.