PL160793B1 - Fungicide of synergetic action - Google Patents

Abstract

PURPOSE:To obtain the subject composition having high safety and useful for the control of a wide variety of plant blights by using a thiazole derivative in combination with either one of a dithiocarbamate fungicide, an N- haloalkylthioimide fungicide, an inorganic copper fungicide, etc., as active components. CONSTITUTION:The objective composition contains (A) a compound of formula (R<1> and R<2> are H or lower alkyl; R<3> is alkyl, alkenyl, phenyl, furyl or thienyl) [e.g., 2-(2,4-dimethylthiazol-5-ylcarbonylamino)-4-methyl-3-pentenenitrile] and (B) a fungicide selected from a dithiocarbamate fungicide, an N- haloalkylthioimide fungicide, an inorganic copper fungicide, tetrachloroisophthalonitrile and dichlofluanid at a ratio of 1:(2-25). Plural blights are simultaneously controlled by the use of the composition and an excellent effect can be attained at a low concentration and low rate of application.

Description

The subject of the invention is a fungicide with a synergistic effect, used in particular in agriculture and horticulture, and containing as an active ingredient a new amide derivative of the general formula I, in which one of the symbols Y and X represents a sulfur atom and the other represents a carbon atom, Z represents a nitrile group. or thioamide, each R1 and R2 is a hydrogen atom, a halogen atom, an alkyl group of 1-6 carbon atoms, a halomethyl group or a phenyl group, and R3 is an alkenyl group of 2-6 carbon atoms, a haloalkenyl group of 2-4 carbon atoms, furyl group, thienyl group, alkoxy group with 1-4 carbon atoms, alkylthio group with 1-4 carbon atoms, alkynyloxy group with 3-5 carbon atoms, alkynylthio group

3-5 carbon atoms, a pyrazolyl group or an unsubstituted or halogen-substituted phenyl group as the first active ingredient and as the second fungicidal ingredient N-haloalkylthioimide, the active ingredients content being 0.5-90% by weight, and the first and second active ingredients being in ratio 1: 1 to 1: 30.

Until now, compounds of various chemical structures have been used as agricultural and horticultural fungicides. They contributed to the control of plant diseases and consequently to the development of agriculture. But these traditional chemical fungicides have not been proven to be sufficiently destructive and safe. For example, some dithiocarbamate fungicides such as ethylene bis / dithiocarbamate / zinc (zineb), ethylene bis / dithiocarbamate / manganese (maneb), ethylene bis / dithiocarbamate / manganese and ethylene bis / dithiocarbamate / zinc (dimethyl dithiocarbamate / ethylene dithiocarbamate / mancosethyb) complex zinc (polycarbamate), N-haloalkylthioimide fungicides such as N-trichloromethylthio-4-cyclohexane-1,2-dicarbonimide (captan), N-Γ, 1 ', 2', 2'-tetrachloroethylthio-4-cyclohexane-1,2 -dicarbonimide (captafol) and N-trichloromethylthiophthalimide (folpet), inorganic copper fungicides such as copper sulfate, basic copper sulfate, basic cupric chloride and copper hydroxide, tetrachloroisophthalonitrile (TPN) and 3-chloro-N- / 3-chloro-3-chloro-3-chloro -2-pyridyl / -2,6-dmitro-4-trifluoromethylamine (dichlorofluamde) show outstanding efficacy in the control of plant diseases such as fruit trees and vegetables and are widely used as horticultural and garden fungicides. However, the mentioned chemical compounds mainly have a therapeutic effect. Hence, they have the serious drawback that when a plant disease occurs, these chemicals are not expected to be sufficiently effective. When the use of chemicals to combat plant diseases is considered in a given situation, these compounds are sprayed to a greater or lesser extent after

160 793 when symptoms of a plant disease occur, and therefore complete disease control is difficult to expect. Moreover, the concentrations of these compounds in which they exhibit control activity are very high to be safe for use, and some of these chemicals have significant toxicity to fish.

In order to eliminate the above disadvantages, extensive research has been undertaken to find new fungicides. For example, acylalanine fungicides such as N- (2,6-dimethylphenyl) -N- (2'-methoxyacetyl) alanine (metalaxyl) methyl ester, N- (2,6-dimethylphenyl) -N- (2-) methyl ester have been developed. furooyl (furalaxyl), N (2,6-dimethylphenyl) -N-phenylacetyl) alanine (benalaxyl) methyl ester, (2-chloro) -N-2,6-dimethylphenyl / N- (tetrahydro-2-keto) 3-furanyl / acetamide (ofurace) and 2-methoxy-N- (2,6-dimethylphenyl) -N / 2-keto-1,3-oxazolidinyl-3- / acetamide (oxadixyl) as plant disease control agents caused by Oomycetes which also have excellent healing effects and have entered into practical use all over the world. But it has already been found that strains resistant to these chemicals have emerged and their damaging effects have decreased as a result.

Many active benzylamide compounds have been invented and used as herbicides or fungicides. For example, known substituted benzamide derivatives include ethyl N-benzoyl-N- (3,4-dichlorophenyl) -2-aminopropionate (benzylpropethyl) as a herbicide and N- (3-isopropoxyphenyl) -2-methylbenzamide (mepronil) as a fungicide.

Great Britain Patent Specifications No. 2,094,786, No. 2,095,237 and No. 2,107,308 disclose a herbicide and fungicide containing a substituted benzylamide derivative containing a 4-pyridylcarbonyl, 2-furylcarbonyl, 2-thienylcarbonyl or 2-benzofurylcarbonyl group, but is still a problem.

The object of the present invention was to obtain a composition free from the above-mentioned drawbacks of the known compounds and having excellent properties as an agricultural and horticultural fungicide.

In order to achieve the above goal, extensive work has been undertaken on acylamide derivatives and it has been found that amide derivatives having a thiazole or isothiazole ring have a biological effect that could not be predicted from the above-mentioned compounds and an excellent action against a wide range of plant diseases, and that especially these derivatives amide compounds have both preventive and healing properties in the fight against various crop plant diseases, such as potato blight and powdery mildew.

More particularly, the invention relates to a fungicide containing the novel compound which has a preventive and curative effect on a wide range of plant diseases such as fruit tree diseases and vegetables, has an excellent killing effect on resistant fungi, has a wide range of utility and has a long residual effect, has no phytotoxicity to crops and has a very low toxicity to warm-blooded animals and fish, in combination with the fungicidal N-haloalkylthioImide.

The new amide derivatives are represented by the general formula, in which the symbols have the meanings given above.

In the amide derivative of general formula 1, examples of alkyl group for R and R ² are methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, t-butyl, n-pentyl and n- hexyl. Examples of a chloromethyl group are chloromethyl and trifluromethyl. An alkenyl group of R3 is, for example, vinyl, allyl, propen-1-yl, 2-methyl-propen-1-yl, 1-methyl-propen-1-yl, 1,2-d-dimethyl-trimethyl-1-yl,

2-ethyl-propen-1-yl or 2-m-propyl-propen-1-yl. A haloalkenyl group is for example 2-chloroethenyl, 2-chloropropen-1-yl, or 1-methyl-2-chloropen-1-yl. Examples of an alkoxy group are methoxy, ethoxy, n-propoxy, isopropoxy, n-butoxy, Q-butoxy and t-butoxy. Examples of alkylthio groups are methylthio, ethylthio, n-propylthio, isopropylthio, n-butylthio, isobutylthio, Il-tert-butylthio and t-butylthio. Exemplary alkynyloxy groups are propyne-2-yloxy, 3-methylpropin-2-yloxy and 3-ethylpropin-2-yloxy. Examples of alkynylthio groups are propyne-2-ylthio, 3-methylpropyn-2-ylthio, 3-ethylpropin-2-ylthio. Halogen atoms can be, for example, fluorine, chlorine, bromine or iodine.

The compound of formula I is particularly effective against late blight and powdery mildew of various crops caused by Oomycetes. The main diseases it fights are plague

160 793 potato on potatoes (Phytophtora infestans). potato blight on tomatoes (Phytophtora infestans), blackening of tobacco stalks (Phytophthora nicotiana var. nicotiana), reddening of strawberry core (Phytophthora sp). root and stalk of soybean (Phytophthora megasporna var.sojae), grape mildew (Plasmopara viticola), cucumber mildew (Pseudopenospora cubensis), hop mildew (Pseudoperonospora humuli), spinach mildew (Peronospora lube) and various spinach plants (Peronospora) aphanomyces, Pythium etc. Another advantage of the agent according to the invention is the very low phytotoxicity when applied to crops, as can be seen from the other amide derivatives.

The compositions according to the invention are used in suitable form for seed coating, leaf spraying, soil treatment, etc. They show a sufficient effectiveness when used in conventional methods. The dose of the compounds employed and the concentration at which the agent is applied may vary depending on the crop and disease treated, the degree of disease onset, the formulation with which the compound is applied, the mode of application, and various environmental circumstances. When spraying, the amount of active ingredients is suitably 50-5000 g / ha, preferably K00-2 (00) g / ha. When the formulation is in the form of a wettable powder or an emulsifiable concentrate it is diluted with water and sprayed on - the dilution ratio is preferably 200 to 100,000, preferably 500-5,000.

The agent of the invention can be used as such, but preferably in the form of a composition with a carrier as well as with a solid or liquid diluent. A carrier as used herein is a synthetic or natural inorganic or organic substance which is included to aid the entry of the active ingredient to the site to be treated and to facilitate storage, transport and handling of the compounds as an active ingredient.

Suitable solid carriers include, for example, clays such as montmorillonite and kaolinite, inorganic substances such as diatomaceous earth, terra alba, talc, vermiculite, gypsum, calcium carbonate, silica gel and ammonium sulphate, vegetable organic substances such as soybean meal, sawdust, wheat flour and urea.

Suitable liquid carriers include, for example, aromatic hydrocarbons such as toluene, xylene and cumene, paraffinic hydrocarbons such as kerosene and mineral oils, halogenated hydrocarbons such as carbon tetrachloride, chloroform and dichloroethane, ketones such as acetone and methyl methyl ketone. ethyl, ethers such as dioxane and tetrahydrofuran, alcohols such as methanol, ethanol, propanol and ethylene glycol, dimethylformamide, dimethyl sulfoxide, and water.

In order to increase the effectiveness of the compositions according to the invention, the excipients described below can be used individually or in a composition depending on the type of preparation, the application situation, etc.

For the purposes of emulsifying, dispersing, spraying, wetting, combining, and fixing, for example, anionic surfactants such as lignin sulfonates, alkylbenzenesulfonates, salts of alkyl sulfur esters, polyoxyalkylene alkyl sulfates and polyoxyalkylene alkyl phosphoric ester salts can be used; non-ionic surfactants such as ethers, polyoxyalkylenealkyl ethers, polyoxyalkylenealkylaryl ethers, polyoxyalkylenealkylamines, polyoxyalkylenealkylamides, polyoxyalkylenealkylthioethers, polyoxyalkylene fatty acid esters, glycerin fatty acid esters, sorbitan fatty acid sorbitan esters / polyoxyethylene fatty acid esters, polyoxyethylene fatty acid esters, polyoxyethylene fatty acid esters calcium stearate and waxes; stabilizers such as propyl hydrogen phosphate and methyl cellulose, carboxymethyl cellulose, casein, and acacia. These ingredients are not limited to the specific examples given above.

Typically, the amount of active ingredients of the agent according to the invention is 0.5 to 20% by weight for dusts, 5 to 20% by weight for emulsifiable concentrates, 10 to 90% by weight for wettable powders, 0.1 to 20% by weight for granules and 10 to 90% by weight. % by weight for liquid agents. The amount of carrier is usually 50-99% by weight for dusts, 60-95% by weight for emulsifiable concentrates, 10-90% by weight for wettable powders, 80-90% by weight for granules and 10-90% by weight for liquid agents. The amount of excipient is usually 0.1-20% by weight for dusts, 1-20% by weight for emulsifiable concentrates,

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0.1-20% by weight for wettable powders, 0.1-20% by weight for granules and 0.1-20% by weight for liquid agents.

The composition of the invention has both preventive and curative activity against a wide range of diseases of fruit trees and vegetables, and shows excellent activity against those plant diseases in which the pathogenic fungus has acquired resistance against traditional fungicidal compounds. Moreover, the agent according to the invention has a sufficiently long residual action and is not phytotoxic. It also has remarkably low toxicity to warm-blooded animals and fish.

In the form of an agro-horticultural fungicide, the composition according to the invention shows activity against a wide range of plant diseases. Examples of plant diseases against which the agent of the invention has an excellent effect are bitter rot (Glomerella cingulata), anthracnose (Elsinoe ampelina), gray mold (Uncinula necator), rust (Phacospora ampelopsidis) and grape downy mildew (Plasmopara viticola), grape rust ( Gymnosporangium yemadae), alternanose leaf blotch (Alternaria mali), fruit blotch (Mycosphaerella pomi), scab (Ventuna tnaequalid) and mildew (Podosphaera leucotricha) apple, anthracnose (Colletotnchum lageniscańum), Spara melothelaa mali ), powdery mildew (Pseudoperonospora cubensis), phytophthora rot (Phytophthora melonis), scab (Clandosponum cucumerinum) and bacterial blotch (Pseudomonas lachrymans) of pumpkin, dry spot (Altenaria solani), leaf roll (Cladosporium, rotilisia caps) (Phytophthora infestans) and tomato mildew (Erysiphe cichoracearum), alternanosis (Alternari a japonica), white spot (cerosporella brassicae) and powdery mildew, rust (Puccinia alli) and mildew (Peronospora destructor) of green onions, mildew (Peronospora spinacinae) of spinach, scab (Elsinoe glycinae), red spot (Cerconospora kikikniakii) manshurica) soybeans, anthracnose (Colletotrichum lindemuthianum) and rust (Uromnyces appendiculatus) beans, mildew (Peronospora vicinae) field beans, blackening of pedicels (Phytophthora cinotians var. nicotiana) of tobacco, dry spot (Alternaria solani) and potato blight (Phytophthora infestans) of potatoes, downy mildew (Pseudoperonospora humuli) of hops, pineapple root rot (Phytophthora cinnamonii) pineapple, green pepper blight (Phytophthora humakici) core (Phytophthora fragaria) of strawberries, gray mold (Borytis cinerea) sclerosis disease (Sclerotonia sclerotium) and rot of various crops caused by Pythium, etc.

The compositions according to the invention can be used or formulated together with other agriculturally acceptable chemicals, such as fungicides, insecticides, plant growth regulators or fertilizers. The following examples illustrate the effectiveness of the new compounds in admixture with known compounds as agro-horticultural fungicides according to the invention. The compounds used in the examples are numbered as given in Table 3 and A is N-haloalkylthioimide in the form N-r112222'ttetrachloroetic: thiic-4-c: yklohexene-1,2-dicarbonamide (captafol).

Example 1. Tests for controlling powdery mildew on cucumbers (healing effect and residual effect).

Pseudoperonospora cebunis was collected from lesioned cucumber leaves (cucumber variety "Sagami Hanjiro", third main leaf stage of development) grown in pots in a greenhouse, and spore suspension of the fungus was prepared with deionized water. The spore suspension was contaminated by spraying the cucumber plant. The pots with the contaminated plants were kept for 24 hours in a greenhouse and sprayed with a fixed concentration agent (obtained by making a wettable powder and diluting to a fixed concentration) at a dose of 50 ml into 3 pots using a sprayer (1.0 kg / cm ² ) and air dried . The pots were then transferred to a greenhouse at 18-27 ° C and the lesions were assessed 10 and 18 days later. The results are presented in Table 1.

Assessment standards and disease index data were calculated as shown below.

160 793

The proportions of the lesion area were observed and evaluated for each leaf and the disease severity index (disease index) was determined. For each study area, the lesion index was calculated according to the following equation.

I ⁿ d ^e k ^sc h ^oro b ^y = ⁴ⁿ⁴ + ³ⁿ³ + ^{2nz + lni} + ^Ono

N

The following assessment standard has been adopted:

Disease index% lesion area

0%

1-5%

6 - 25%

26 - 50%

51% or more no - number of leaves with a disease index of 0; ni - number of leaves with a disease index of 1; n2 number of leaves with a disease index of 2; n3 - number of leaves with a disease index of 3; n4 - number of leaves with a disease index of 4; N = no + ni + n2 + n3 + n4.

Example II. Attempt to combat potato blight on tomatoes (healing effect and residual effect).

A zoospore suspension of Phytophthora infestans grown on a potato slice for 7 days was prepared and sprayed inoculated with tomatoes (cultivar "Sahaiichi", plant height 20 cm) grown in pots in the greenhouse. The pots with the contaminated plants were kept for 24 hours in a humid chamber at 16 ° C and the fixed concentration agent (prepared by making a wettable powder and diluting with water to the specified concentration) was sprayed onto the plants at a dose of 50 ml per 3 pots with a sprayer (1.0 kg / cm ² ) and then air-dried. The pots were transferred to a greenhouse (temperature 10-20 ° C) and lesions were assessed 10 and 11 days later. The results are presented in Table 2.

Assessment standards and methods for calculating the disease index are shown in Example 1.

The novel compounds of the formula I show a preventive effect at significantly lower doses than the known killer agents. Accordingly, the compositions of the invention can show a good control effect even when applied to crops after being infected with these diseases. It can therefore significantly change the disease control system in agricultural and horticultural crops and will obviously contribute to large labor savings on the part of the producer. Since these agents have a good controlling effect when applied by watering the soil, they enable the agent to be applied to a part of the plant that cannot be reached by spraying alone in order to protect it from disease.

The results given in Tables 1 and 2 show that the agro-horticultural fungicidal composition according to the invention shows a significantly superior effect at lower doses than with the known agents.

A synergistic effect is evident when the components are mixed and the residual effect is greatly enhanced. This means that in the cultivation of crops, the use of an agro-horticultural fungicide according to the invention can combat many simultaneous plant diseases which would be difficult to control simultaneously with known fungicidal compounds.

It should be especially taken into account that the agro-horticultural composition according to the invention shows a much better control effect at lower doses than when using a single compound. This clearly shows a synergistic effect as a result of the mixing of the two main active ingredients of the agent according to the invention.

160 793

Table I.

Test with powdery mildew on cucumbers

Test compound no Concentration active ingredient (PPm) Disease index 10 days later 18 days later 2 100 0 0.7 50 0 1.0 3 1 (00 0 1.0 50 0 1.3 4 100 0 0.7 50 0 1.0 5 100 0 1.0 50 0 1.0 6 100 0 1.0 50 0 1.5 17 1100 0 0.8 50 0 0.8 18 100 0 0.6 50 0 0.7 AND 500 2.7 2.8 2 + A 100 + 500 0 0 50 + 500 0 0 17 + A 100 + 500 0 0 50 + 500 0 0 18 + A 100 + 500 0 0 50 + 500 0 0 Control sample - 3.7 3.7

A - Captafol

Table 2

Attempt to combat potato blight on tomatoes

Test compound no Concentration active ingredient (ppm) Disease index 10 days later 18 days later 1 2 3 4 2 100 0 0 50 0 0 6 100 0 0 50 0 0 12 100 0 0 50 0 0 13 100 0 0.6 50 0 0.9 50 100 0 1.0 50 0 1.0 54 100 0 1.0 50 0 1.8 AND 500 3.5 3.6

δ

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1 2 1 4 6 + A 100 + 500 0 0 50 + 500 0 0 50 + A 100 + 500 0 0 50+ 500 0 0 2 + A 100 + 500 0 0 50 + 500 0 0 Control sample - 3.6 3.8

A - Captafol

The methods for the preparation of the new amide derivatives of general formula I used as active ingredients of the agent according to the invention are illustrated by the following synthetic examples.

Example III. Synthesis of N- (alpha-cyanofurfuryl) -2-chloro-4-methylthiazole-5-carboxamide (compound No. 37).

8.8 g of lactic acid was suspended in 7 ml of thionyl thionyl and 1 drop of N, N-dimethylformamide was added. The mixture was heated under reflux for 1 hour, then excess thionyl chloride was evaporated under reduced pressure. 10 ml of benzene was added and the mixture was evaporated under reduced pressure. This procedure was repeated three times to obtain 9.7 g of 2-chloror4-methyl-thiazole-5-carboxylic acid chloride, which was used in the following reaction without purification.

2-Chloro-4-methyl-thiazolor-5-carboxylic acid chloride (1.6 g) was suspended in 30 ml of pyridine and 1.3 g of alpha-furyl / -alpha-aminoacetomtril hydrochloride was added. The mixture was stirred at room temperature for 2 hours. After the reaction, the reaction mixture was filtered. The filtrate was concentrated, and the residue was purified by silica gel column chromatography. Elution with hexane with ethyl acetate gave 1.79 g (75.2% yield) of the desired N- (alpha-cyanofurfurfoyl) -2-chloΓO-4-methylthIazole-5-carboxylic acid amide.

Example IV. Synthesis of N- (alpha-cyanofurfuryl) -2,4-dimethyltlazole-5-carboxylic acid amide (compound No. 2).

9.30 g of 2, <4-dimethylorizole-5-carboxylate in <93 ml of totaene and added

15.0g of phosphorus pentachloride. The mixture was refluxed for 1 hour. The obtained phosphorus oxychloride and toluene were evaporated under reduced pressure to give the acid chloride

2,4-dimethylthiazole-5-carboxylic acid which was used in the following reaction without purification.

6.2 g of alpha- (2-furyl) -affa-aminoacstonitrile and 6.0 g of triethylamine were dissolved in 120 ml of ethyl acetate, and 2,4-dimethylthiazole-5-carboxylic acid chloride was added dropwise to the solution while stirring. The mixture was stirred at room temperature for 1 hour. 150 ml of water was added and the precipitated triethylamine hydrochloride was dissolved. The ethyl acetate layer was separated, washed with water, dried over sodium sulfate. The dried ethyl acetate layer was distilled off under reduced pressure to remove the solvent. The residue was recrystallized from isopropyl ether to obtain 11.65 g (90.0% yield) of the desired N- (alpha-cyanofurfuryl) -2,4-dlm-methyltlazole-5-carboxylate amide.

EXAMPLE 5 Synthesis of N (alpha-cyanofurfuryl) N -diethylthiazole-carboxylic acid amide (compound No. 12).

The method described in Example 4 was followed by reacting 2,4-diethylthiazole-5-carboxylic acid and phosphorus pentachloride to give 2,4-dlethylthiazole-5-carboxylic acid chloride quantitatively. 2,4-Diethyltlazole-5-carboxylic acid chloride was used in the following reaction without purification.

2.80 g of alpha- (2-furyl) -alpha-aminoacstomtril and 6.0 g of triethylamine were dissolved in 50 ml of ethyl acetate, and 2.1 of 2,4-diethylthiazole-5-carboxylic acid chloride was added dropwise with stirring. The mixture was stirred at room temperature for 1 hour. 150 ml of water was added and the precipitated triethylamine hydrochloride was dissolved. The ethyl acetate layer was separated, washed with water and dried over sodium sulfate. The dried ethyl acetate layer was evaporated under reduced pressure to remove the solvent. The residue was recrystallized from n-hexane

160,793 to give 2.41 g (80.0% yield) of the desired N- (alpha-cyanofurfuroyl) -2,4-diethylthiazole-5-carboxylic acid amide.

Example VI. Synthesis of N- (alpha-cyanofurfuryl) -2,4-dimethylthiazole-5-carboxylic acid amide (compound No. 2) by using a mixed acid anhydride.

4.71 g of 2, β-dimethylthiazole-5-carboxylic acid was suspended in 70 ml of tetrahydrofuran and 6.67 g of triethylamine was added. The mixture was stirred. While cooling to -10 to -5 ° C, 4.10 g of n-butylchloroformate was added and the mixture was stirred at this temperature for 30 minutes, and then 4.03 g of alpha- (2-furyl) -alpha-aminoacetonitrile hydrochloride was added. The mixture was stirred at room temperature for 5 hours and then allowed to stand overnight. The resulting precipitate was filtered off and distilled under reduced pressure to remove the solvent. The residue was purified by silica gel column chromatography. Elution with hexane / ethyl acetate gave 4.20 g (53.6% yield) of the desired N- (alpha-cyanofurfuryl) -2,4-dimethyl-thiazole-5-carboxylic acid amide.

Example VII. Synthesis of N- (alpha-cyanofurfuryl) -2,4-dimethylthiazole-5-carboxylic acid amide (compound No. 2) by CDI method.

4.0 g of alpha / 2-fur yl ^ / ^/ s ^ fa ^ -aminoacetonitrylu and the mixture 3.70 g of 50% aqueous NaOH, 150 ml of isopropyl ether was stirred at 40 ° C for 1 hour under nitrogen. The isopropyl ether layer was separated. Separately while mixing

4.71 g of 2 / 4dime ey Io thiazole ο-5-carboxylic acid and 4.88 g of carbonyldiimidazole (CD I) in 50 ml of methylene chloride while cooling on ice, alpha- (2-furyl) -alpha-aminoacetonitrile in ether was added dropwise isopropyl. The mixture was allowed to stand overnight at room temperature and distilled under reduced pressure to remove the solvent. The residue was dissolved in ethyl acetate, separated, washed with water and dried over sodium sulfate. The ethyl acetate layer was distilled under reduced pressure to remove the solvent. The residue was recrystallized from isopropyl ether to obtain 5.51 g (70.4% yield) of the desired N- (alpha-cyanofurfoyl) -2,4-dimethyl-3-azole-5-carboxylic acid amide.

Example VIII. Synthesis of N- (alpha-cyanofurfuryl) -2,4-dimethylthiazole-5-carboxylic acid amide (compound No. 2) by DCC.

3.0 g of alpha- (2-furyl) H'-aminoacetonitrile hydrochloride and a mixture of 70 g of 50% aqueous NaOH solution in 30 ml of methylene chloride was stirred at 40 ° C for 1 hour under nitrogen atmosphere. Then the methylene chloride layer was separated. Separately, while stirring, 2.50 g of 2,4-dimethylthiazole-5-carboxylic acid and 3.10 g of dicyclohexylcarbodiimide (DCC) in 50 ml of methylene chloride were added, dropwise alpha- (2-furyl) -alpha-aminoacetonitrile while cooling with ice water over a period of 1 hour. After the addition, the mixture was stirred with ice cooling, left overnight at room temperature, and the solvent was distilled off under reduced pressure. The residue was dissolved in ethyl acetate, separated, washed with water and dried over sodium sulfate. The ethyl acetate layer was distilled under reduced pressure to remove the solvent. The residue was purified by silica gel column chromatography. Elution with hexane / ethyl acetate provided 1.85 g (47.3% yield) of the desired N- (alpha-cyanofurfuryl) -2,4-dimethylthiazole-5-carboxylic acid amide.

Example IX. Synthesis of N- (alpha-cyanofurfuryl) -3- (methylisothiazole-4-carboxylic acid amide) (compound No. 32).

1.2 g of alpha- (2-furyl) -alpha-aminoacetonitrile hydrochloride was dissolved in 10 ml of pyridine, and 1.1 g of 3-methylisothiazole-3-carboxylic acid chloride was added dropwise while stirring at room temperature. After completion of dropwise addition, the mixture was stirred for 1 hour, and pyridine was distilled off under reduced pressure. The residue was dissolved in ethyl acetate, separated, washed with water and dried over sodium sulfate. The ethyl acetate layer was distilled off under reduced pressure to remove the solvent. The residue was purified by silica gel column chromatography. Elution with benzene / ethyl acetate gave 1.2 g (70% yield) of the desired N- (alpha-cyanofurfuroyl) -3-methylisothiazole-4-carboxylic acid amide.

Example X. Synthesis of N- (alpha-cyanofurfuryl) -3-methylisothiazole-5-carboxylic acid amide (compound No. 34).

160 793

5.0 g of alpha- (2-furyl) -alpha-aminoacetonitrile hydrochloride, dehydrochloride with sodium hydroxide in ethyl acetate as described in Example 5, 2.5 g of pyridine was added, and then 4.0 ethylacetate solution of 3-methylisothiazole-5-carboxylic acid chloride was added dropwise. . After the addition, the mixture was stirred for 1 hour. The reaction mixture was washed with water, dilute hydrochloric acid, and dilute aqueous sodium bicarbonate solution. Sodium sulfate and activated carbon were added to dehydrate and discolor the reaction mixture. The solvent was removed under reduced pressure and the residue was washed with diethyl ether to give 4.5 g (74% yield) of the desired N- (alpha-cyanofurfuryl) -3-methylisothiazole-5-carboxylic acid amide.

Example XI. Synthesis of N- (1-cyano-3-methyl-2-butenyl) -3-methylisothiazole-5-carboxylic acid amide (compound No. 36).

To a mixture of 30 ml of water and 30 ml of diethyl ether were added 3 ml of 28% gaseous ammonia, 2.0 g of sodium cyanide, 4.5 g of ammonium chloride and 0.5 g of triethylbenzyl ammonium chloride and the mixture was cooled to 5 ° C. While the solution was stirred, 2.8 g of 3-methyl-2-butenal were added dropwise. After the dropwise addition, the mixture was continuously stirred at 15-20 ° C for 5 hours. The ether layer was separated, washed with water, and dried over sodium sulfate to give an ether solution of 1-cyano-3-methyl-2-butenylamine. 1.0 g of triethylamine was added to the solution, and a solution of 1.1 g of 3-methylisothiazole-5-carboxylic acid chloride in ethyl acetate was added dropwise with stirring at room temperature. After the addition was complete, the mixture was stirred for 1 hour, washed with water, and the solvent was distilled off under reduced pressure. The residue was purified by silica gel column chromatography. Elution with benzene / ethyl acetate afforded 1.0 g (63% yield) of the desired N-Zcyano-1-methyl-1 -butenyl) 3-methylisothiazole-5-carboxylic acid amide.

Example XII. Synthesis of the amide of N- (α, β, β, β-cyanoben, β-α-β), β - 2 ^ m (compound No. 35)

1.2 g of cc ^ 11 ^ c ^ ^ ^ ^ ^ Cl ^ and ^ 11 ^ u was suspended in 20 ml of ethyl occan and 7 ml of 10% NaOH was added dropwise at a temperature below 10 ° C. The mixture was stirred at this temperature for 10 minutes and then a solution of 0.8 g of 3-methylisothiazole-5l carboxylic acid chloride in ethyl acetate was added dropwise at 0 ° C. After completion of the dropwise addition, the mixture was stirred for 30 minutes. The ethyl acetate layer was washed with water, and the solvent was distilled off under reduced pressure. The residue was purified by silica gel column chromatography. Elution with benzene / acetate afforded 1.0 g (77% yield) of the desired N- (alpha-cyanobenzyl) 3-methylisothiazole -15lcarboxylic acid amide.

Example XIII. Synthesis of N - [(alpha-cyano (1-piaazolyl) methyl-3-methylisothiazole'-carboxylic acid amide (compound No. 46).

0.7 g of N- (cyanomethyl) -3-methylisothiazolyl-5-carboxylic acid amide was dissolved in 30 ml of ethyl acetate. 0.8 g of bromine was added and the mixture was stirred for 30 minutes, then cooled in an ice bath. A mixture of 0.3 g of pyrazole, 1.0 g of triethylamine and 5 ml of ethyl acetate was added to the reaction mixture while stirring. The mixture was stirred for 30 minutes. The ethyl acetate layer was washed with water, and the solvent was distilled off under reduced pressure. The residue was purified by silica gel column chromatography eluting with benzene / ethyl acetate. 0.75 g (78% yield) of the desired N- [alpha-cyanoalpha / 1-piaazolyl / methyl-3-methyltlazole-5-carboxylic acid amide was obtained.

Example XIV. Synthesis of the amide N - [&lt; 3 &gt; alpha-cyano-alpha- (1- {3 [mu] g; ^: [alpha] ^ oilc ^^ n ^ ^ ^ ^ ^ -2,4-dimethyltlacol-5lcarboxylic acid amide (compound No. 38).

(1) Synthesis of N-cyanomethyl-2,4-dlmethylthiazole Cl5-carboxylic acid amide

A mixture of 10 g of 2,4-dimethylthiazol.15-1carboxylic acid, 13.6 g of thionyl chloride and 70 ml of toluene with ice is added 8.4 g of Ν, Ν-dimethylformamide with stirring. The mixture was stirred for 3 hours at 3-5 ° C and then for 1 hour at 20 ° C and 200 ml of toluene and 37 g of triethylamine were added. Acetyl acetate solution of aminoacetonitrile with ethyl acetate and gradually added NaOH to the mixture cooled with ice. The mixture was stirred at room temperature for 1 hour. The reaction mixture was poured into water and

160,793 were extracted with ethyl acetate. The ethyl acetate layer was washed with water, dried, and the solvent was distilled off under reduced pressure to remove the solvent. The residue was purified by column chromatography with silica gel eluting with hexane / ethyl acetate. 6.6 g (63% yield) of N-cyanomethyl-2,4-diethylthiazole-5-carboxylic acid amide were obtained.

(2) Synthesis of the acid amide N- [al ^^^ (^; ^ jj ^ r ^ (^ - ^ lf ^ / l-pii ^^ zolyl / ^/ -n ^^ only)] - ^ 2,4- dimethylthiazole-5-carboxylic acid.

1.0 g of N-cyanomethyl-2,4-dimethylthiazole-5-carboxylic acid amide was dissolved in 30 ml of ethyl acetate. 0.3 ml of bromine was added and the mixture was refluxed until the dark brown color with bromine disappeared. The reaction mixture was cooled in an ice bath, and at this temperature 0.5 g of pyrazole, 2.0 g of triethylamine and 10 ml of ethyl acetate were added. The mixture was stirred at room temperature for 2 hours, poured into water and extracted with ethyl acetate. The ethyl acetate layer was washed with water, dried, and the solvent was distilled off under reduced pressure. The residue was purified by column chromatography on silica gel eluting with hexane / ethyl acetate. 0.74 g (54.9% yield) of N- [alpha-cytan-alpha / 1-pIrazoIιlo / methyl-2,4-dimethylthiazole-5-carboxylic acid amide was obtained.

Example XV. Synthesis of N- (alpha-cyano-ethoxymethyl) -2,4-dimethylthiazole-5-carboxylic acid amide (compound No. 39).

1.0 g of N-cyanomethyl-2,4-dimethylthiazole-5-carboxylic acid amide was dissolved in 30 ml of ethyl acetate. 0.3 ml of bromine was added and the mixture was refluxed until the dark brown color with bromine disappeared. The reaction mixture was cooled in an ice bath, and at this temperature 1.0 g of ethanol, 2.0 g of triethylamine and 10 ml of ethyl acetate were added. The reaction mixture was poured into water and extracted with ethyl acetate. The ethyl acetate layer was washed with water, dried, and the solvent was distilled off under reduced pressure. The residue was purified by column chromatography eluting with hexane / ethyl acetate. 0.53 g (43.1% yield) of the desired N- (alpha-cyano-alpha-ethoxyethyl) -2,4-dimethylthiazole-5-carboxylic acid amide was obtained.

Example XVI. Synthesis of N - [(alpha-thiocarbamoyl) furfuyl] -3-methylisothiazole-5-carboxylic acid amide (compound 47).

1.0 g of N- (alpha-cyanofurfuryl) -3-methylisothiazole-5-carboxylic acid amide was dissolved in 30 ml of tetrahydrofuran and 0.6 ml of triethylamine was added. While stirring at room temperature, hydrogen sulfide gas was introduced into the mixture. 5 hours later, the solvent was evaporated from the reaction mixture under reduced pressure. Water was added to the residue. The precipitated crystals were collected by filtration to obtain 1.1 g of the desired N - [(alpha-thiocarbamoyl) furfuΓ-o] -3-methylisothiazole-5-carboxylic acid amide.

Typical examples of the new amide derivatives of general formula I used as one of the active ingredients of the agent of the invention are shown in Table 3 below.

Table 3

Relationship no Substituent Melting point ° C NMR (100MHz, 4) formula 11 group R ³ WITH 1 2 3 4 5 5 1 pattern 2 pattern 4 CN Oil (CDCla) 2.72 (3H, s), 6.24-6.66 (3H, tn), 7.34-7.49 (1H, m), 7.97 (1H, br d), J = 7Hz), 8.04 (1H, s) 2 pattern 3 pattern 4 CN 100 5-101.5 (CDCla) 2.61 (3H, s), 2.64 (3H, s), 6.34 (1H, d, J = 8.0 Hz), 6.40 (1H, ra), 6.58 ( 1H, m), 7.4 "(1H, m), 7.96 (1H, d, J = 8.0Hz) 3 pattern 3 pattern 5 CN 99-100 (CDCla) 1.85 (6H, s), 2.71 (6H, s), 5.34 (1H, d.

J = 8.0 Hz), 5.68 (1H, t, J = 8.0 Hz), 6.16 (1H, d, J = 8.0 Hz)

160 793

1 2 3 4 5 5 4 pattern 3 pattern 5 CN 115.5-118.5 (CDClb) 2.66 (6H, s), 6.42 (1H, d, J = 9.0 Hz), 6.98 (2H m). 7.34 (1H, d, J = 8.0 Hz), 7.38 (IH, d, J = 9.0 Hz) 5 pattern 3 pattern 7 CN 90- 9t (CDClb) 2.60 (6H, s), 6.18 (1H, d, J = 9.0 Hz), 6.68 IIH, d J = 9.0 Hz), 7.0-71 (1H , m), 7.28-7.44 (2H, m) pattern 3 formula 8 CN 132-135 (CDClb) 2.61 (6H, s), 6.18 (1H, d, J = 9.0 Hz), 6.81 11H. s. J = 9.0 Hz), 7.28-7.52 (5H, m) 7 pattern 4 pattern 4 CN Oil (CDClb) 2.72 (3H, s), 6.26 (1H, d, J = 8.0Hz), 6.36 (1H, m), 6.54 (broad, d, J = 4Hz) , 6.95 (1H, d, J = 8.0Hz), 7.43 (1H, broad d, J = 4Hz), 8.65 (lH.s) 8 pattern 9 formula 8 CN Oil (CDClb) 2.62 (3H, s), 6.16 (1H, d, J = 8.0 Hz), 7.2-7.5 (5H, m), 8.46 (1H, s) 9 pattern 10 pattern 4 CN 99-102 (CDClb) 1.40 (3H, t, J = 8Hz), 2.70 (3H, s), 3.00 (2H, q, J = 8Hz), 6.36 (1H, broad, d, J = 8Hz), 6.4-6.7 (2H, m), 6.78 (1H, br d, J = 8Hz), 7.42 (IH, m) 10 pattern 10 pattern 6 CN 9 ^, 5-91.6 (CDClb) 1.34 (3H, t, J = 7Hz), 2.68 (3H, s), 2.98 (2H, q, J = 7Hz), 6.41 (1H, d, J = 8Hz), 6.61 (1H, br d, J = 8Hz), 6.96-7.12 (1H, m), 7.23-7.48 (2H, m) li pattern 10 formula 8 CN Oil (CDCb) 1.36 (3H, t, J = 7Hz), 2.66 (3H, s), 2.96 (2H, q, J = 7Hz), 6.22 (1H, d, J = 8 Hz), 6, -tó (1H, broad, d, J = 8 Hz), 7.1 ^^ 7.60 (3H, m) 12 formula 11 pattern 4 CN 114.5-115.5 (CDCb) 1.30 (3H, t, J = 8Hz), 1.38 (3H, t, J = 8Hz), 2.98 (2H, q J = 8Hz), 3.09 (2H, q. J = 8Hz), 6.28 (1H, d, J = 8Hz), 6.40 (1H, m), 6.56 (2H, m), 7.48 (1H, m) 13 formula 11 pattern 6 CN 117-118 (CDClb) 1.31 (3H, t, J = 8 Hz), 1.39 (3H, t, J = 8 Hz). 2.97 (2H, q, J = 8Hz), 3.05 (2H, q, J = 8Hz), 6.29 (1H, d. J = 9Hz), 6.74 (1H, broad, d, J = 9Hz), 7.00 (1H, m), 7.2-7.4 (2H, m) 14 formula 11 formula 8 CN 79- 81 (CDCb) U ^^ (3H, t, J = 8 Hz), 1.34 (3H, t, J = 8 Hz). 2.92 (2H, q, J = 8Hz), 3.00 (2H, q, J = 8Hz), 6.21 (1H, d, J = 9Hz), 6.67 (1H, d, J = 9Hz), 7.20-7.50 (5H, broad s) 15 pattern 12 pattern 4 CN Oil (CDClb) 1.02 (3H, t, J = 7Hz), 1.80 (2H, m, J = 7Hz). 2.68 (3H, s), 2.91 (2H, t, J = 7Hz), 6.31 (1H, d, J = 8Hz), 6.42, 6.59, 7.47 (each IH, m), 6.80 (1H broad d, J = 8Hz) 16 pattern 12 pattern 6 CN Oil (CDCb) 1 (X) (3H, t, J = 7Hz), 1.78 (2H, m, J = 7Hz), 2.66 (3H, s), 2.89 (2H, i, J = 7Hz), 6.41 (1H, d, J = 8Hz), 6.62 (1H, br d, J = 8Hz), 7.0-7.4 (3H.m) 17 pattern 13 pattern 4 CN Oil (CDCb) 1.30 (3H, t, J = 7Hz), 2.69 (3H, s), 3.47 (2H, q, J = 7Hz), 6.29 (1H, d, J = 8Hz ), 6 (29-6 (72 (3H.m), 7.28-7.71 (IH, m) 18 pattern 13 pattern 6 CN 124.5-125.8 (CDCb) 1.20 (3H, t, J = 8Hz), 2.67 (3H, s), 2.96 (2H, q, J = 8Hz), 6.53 (IH, d, J = 7Hz), 7.00-7.72 (3H, m), 9.61 (IH, broad d, J = 7Hz) 19 pattern 13 pattern 6 CN 111-112 (CDCb) 1.27 (3H, t, J = 7Hz), 2.67 (3H, s), 3.03 (2H, q, J = 7Hz), 6.22 (1H, d, J = 8Hz), 6.66 (1H, br d, J = 8Hz), 7.20-7.64 (5H, s) twenty pattern 14 pattern 4 CN 117-118 (CDCb) 0.96 (3H, t, J = 8Hz), 1.74 (2H, m, 3 = 8

Hz), 2.70 (3H, s), 3.02 (2H, t, J = 8Hz), 6.32 (1H, d, J = 8Hz), 6.45, 6.60, 7, 70 (1H, m each), 6.88 (1H, br d, J = 8Hz)

160 793

1 2 3 4 5 5 21 pattern 14 pattern 6 CN 117.5-119 (CDCU) 0.96 (3H, t. J = 8 Hz), 1.54 (2H, m. J = 8 Hz), 2.68 (3H, s), 3.01 (2H. T. J = 8 Hz), 6.44 (1H, d, J = 8Hz), 6.90-7.50 (4H, m) 22 pattern 14 pattern 18 CN 93- 94 (CDCU) 0.93 (3H, t, J = 8Hz), 1.70 (2H, m J = 8Hz), 2.66 (3H, s), 2.98 (2H, t. J = 8 Hz), 6.25 (1H, d, J = 9Hz), 6.84 (1H, broad t, J = 9Hz), 7.28-7.74 (5H, m) 23 pattern 15 pattern 4 CN 105-107 (CDCU) 2.77 (3H, s), 6.23 (IH, d, J = 8Hz), 6.45 (IH, m), 6.62 (IH, m). 6.93 (1H, br d, J = 8Hz), 7.50 (1H, m) 24 pattern 15 pattern 6 CN Oil (CDCU) 2.76 (3H, s), 6.39 (1H, d, J = 8Hz), 6.90-7.13 (2H, m), 7.36-7.48 (2H, m ) 25 pattern 16 pattern 4 CN 98.5- 99.0 (CDCU) 1.34 (3H, t, J = 8Hz), 3.20 (2H, q, J = 8Hz), 6.30 (1H, d, J = 8Hz), 6.42 (1H , m), 6.60 (1H, m), 6.72 (1H, br d, J = 8Hz), 7.48 (1H, m), 7.74 (1H, s) 26 pattern 17 pattern 4 CN 147-151 (CDCU) 2.74 (3H, s), 6.26 (1H, d, J = 8Hz), 6.3-6.7 (3H, m), 7.3-7.5 (3H, m ), 7.8-7.9 (2H, m) 27 pattern 17 pattern 6 CN 162-163 (CDCla) 2.64 (3H, s), 6.26 (1H, d, J = 8Hz), 6.8 (1H, m), 7.1-7.3 (5H, m), 7.7 ( 2H, m), 9.24 (IH, br d, J = 8Hz) 28 pattern 17 formula 8 CN 138-139 (CDCU) 2.73 (3H, s), 6.25 (1H, d, J = 8Hz), 6.66 (1H, brd, J = 8Hz), 7.36-7.62 (8H , m), 7.82-7.97 (2H, m) 29 pattern 18 pattern 4 CN 233.5-234.5 (CDCU) 2.72 (3H, s), 6 "40 (1H, d, J = 8Hz), 6.45-6.68 (2H, m), 7.32-7.87 (6H, m ), 9.78 (1H, broad d, J = 8Hz) thirty pattern 18 pattern 6 CN 216.5-218.0 (CDCU) 2.73 (3H, s), 6.51 (1H, d, J = 7Hz), 6.83-7.79 (8H, m), 9.82 (1H, br d, J = 7 Hz) 31 pattern 18 formula 8 CN 220.5-221.5 (CDCU) 2.70 (3H, s), 6.25 (1H, d, J = 7Hz), 7.04-7.74 (10H, m), 9.67 (1H, br d, J = 7 Hz) 32 pattern 19 pattern 4 CN 126-127 (CDCU) 2.62 (3H, s), 6.26 (1H, d, J = 8Hz), 6.38 (1H, t, J = 2Hz), 6.54 (1H, d, J = 2Hz), 7.44 (1H, d, J = 2Hz), 7.50 (1H, d, J = 8Hz), 9.00 (3H, s) 33 pattern 19 pattern 5 CN Oil (CDCU) 1.84 (2H, s), 5.34 (1H, d, J = 8Hz), 5.70 (1H, t, J = 8Hz), 7.30 (1H, d, J = 8 Hz), 9.08 (3H, s) 34 pattern 20 pattern 5 CN 136-137 (DMSOde) 2.87 (3H, s), 6.44 (1H, d, J = 8Hz), 6.50 (1H, t, J = 2Hz), 6.62 (1H, d, J = 2 Hz), 7.74 (1H, d, J = 2Hz), 7.76 (1H, s), 10.02 (1H, d, J = 8 Hz) 35 pattern 20 formula 8 CN 129-131 (DMSOd 6) 2.54 (3H, s), 6.40 (1H, broad) 7.4-7.7 (5H, m), 7.84 (1H, s), 10.0 (1H, broad) 36 pattern 20 pattern 5 CN 123-125 (DMSOde) 1.78 (6H, d, J = 2Hz), 2.48 (3H, s), 5.3-5.8 (2H, m), 7.74 (1H, s), 9, 58 (1H, d. J = 8 Hz) 37 pattern 21 pattern 4 CN 90-91 (CDCU) 2.55 (3H, s), 6.24 (1H, d, J = 8Hz), 6.55 (2H, m), 7.52 (1H, m), 8.06 (1H, m), 8.06 (1H, d, J = 8Hz) 38 pattern 22 pattern 23 CN 14-141 (CDCU) 2.67 (3H, s), 6.30-6.40 (1H, m), 7.20 (IH, d, J = 8Hz), 7.60-7.66 (1H, m ). 7.72-7.80 (1H, m), 8.30 (lH, d, J = 8Hz) 39 pattern 22 -OCjHj CN 89- 90 (CDCU) 1.30 (3H, t, J = 7Hz), 2.70 (3H, s), 2.73

(3Η, s), 3.71 (2H, q, J = 7Hz), 6.10 (1H, d, J = 10Hz), 6.95 (1H, d, J = 10Hz)

160 793

1 2 3 4 5 5 40 pattern 22 -OCHjC = CH CN Oil (CDCl3) 2.25-2.59 (1H, m), 2.71 (6H, s), 4.31 (2H, d, J = 3Hz). 6.31 (1H, d, J = 9Hz), 6.31 (1H, d, J = 9Hz), 7.04 (1H, d, J = 9Hz) 41 pattern 22 -SCjHs CN Oil (CDC3) 1.37 (3H, t, J = 8Hz), 2.68 (3H, s), 2.70 (3H, s), 2.87 (2H, q, J = 8Hz), 6 , 15 (1H, d, J = 9Hz), 6.96 (1H, d, J = 9Hz) 42 pattern 22 -OCjHr / n / CN Oil (CDC3) 0.93 (3H, t, J = 7Hz), 1.80 (2H, m, J = 7Hz), 2.68 (3H, s), 2.91 (2H, t, J = 7Hz), 6.31 (1H, d, J = 8Hz), 6.42, 6.59, 7.47 (1H, m each), 6.80 (1H, broad d, J = 8Hz) 43 pattern 22 OCHs CN Oil (CDC3) 2.66 (3H, s), 2.68 (3H, s), 3.38 (3H, s), 5.95 (1H, d, J = 9Hz), 7.08 (1H, d, J = 9 Hz) 44 pattern 22 SCjHr / i / CN 105-106 (CDC3) 1.36 (3H, d, J = 6Hz), 1.39 (3H. D, J = 6Hz), 2.65 (3H, s), 2.68 (3H, s), 3 . 25 (1H, m, J = 6Hz),) 6.09 (1H, d, J = 9Hz), 7.03 (1H, br d, J = 9Hz) 45 pattern 20 pattern 23 CN 134-136 (DMSOde) 2.56 (3H, s), 6.40 (1H, t, J = 2Hz), 7.64 (1H, d, J = 8Hz), 7.7O (1H, d, J = 2 Hz), 7.86 (1H, s). 7.94 (1H, d, J = 2Hz), 10.96 (1H, d, J = 8 Hz) 46 pattern 19 pattern 23 CN 176-178 (DMSOd6) 2.60 (3H, s), 6.40 (1H, t, J = 2Hz), 7.60 (1H, d, J = 8Hz), 7.66 (1H, d, J = 2 Hz), 7.96 (1H, d, J = 2 Hz), 9.62 (1H, s), 10.56 (1H, d, J = 8 Hz) 47 pattern 20 pattern 4 39 163-167 (DMSOd 6) 2.48 (3H, s), 5.92 (1H, d, J = 7.5Hz), 6.34-6.52 (2H, m), 7.62 (1H, s), 7.87 (1H, s), 9.13 (1H, d, J = 7.5Hz), 9.54 (1H, s), 9.82 (1H, s) 48 pattern 22 pattern 4 39 96.5- 99.0 (DMSOd6) 2.58 (3H, s), 2.63 (3H, s), 5.94 (1H, d, J = 8.5Hz), 6.41 (2H, s), 7.57 ( 1H, s), 8.16 (1H, d, J = 8.5Hz), 9.60 (1H, s), 9.98 (1H, s) 49 pattern 24 pattern 4 CN 1 ^^, 5 ^ 130 (CDC3) 2.70 (3H, s), 4.9 (2H, s), 6.22 (1H, d, J = 8Hz), 6.32-6.64 (2H, m), 7. 08 (1H, broad, J = 8Hz), 7.40-7.48 (1H, m) 50 pattern 25 pattern 4 CN 118, (^ 119.0 (CDC3) 1.24 (6H, d, J = 7Hz), 2.63 (3H, s), 3.63 (1H, qt, J = 7Hz), 6.16 (1H, d, J = 8Hz ), 6.16- 6.68 (2H, m), 6.55 (1H, br d, J = 8Hz), 7.16-7.39 (1H, m) 51 pattern 25 pattern 6 CN Oil (CDCl3) 1.28 (6H, d, J = 7Hz), 2.64 (3H, s), 3.72 (1H, qi, J = 7Hz), 6.33 (1H, d, J = 8Hz), 6.60 (1H, broad d, J = 8Hz), 6.75-7.22 (3H, m) 52 pattern 25 formula 8 CN 95.0- 98.0 (CDCb) 1.21 (6H, d, J = 7Hz), 2.57 (3H, s), 3.61 (1H, qt, J = 7Hz), 6.08 (1H, d, J = 8Hz), 6.61 (1H, br d, J = 8Hz), 7.10-7.24 (5H, m) 53 pattern 26 pattern 4 CN Oil (CDClb) 2.68 (3H, s), 6.23 (IH, d, J = 8Hz), 6.12-6.62 (2H, m), 7.20-7.44 (1H, m ), 7.90 (1H, br d), 8.01 (1H, s) 54 pattern 13 pattern 5 CN 90.5- 92.0 (CDCb) 1.27 (3H, t, J = 8Hz), 1.81 (6H, s), 2.65 (3H, s), 3.01 (2H, q, J = 8Hz), 5 , 47 (1H, d, J = 8Hz), 5.60 (1H, broad d, J = 8Hz), 6.48 (1H, broad d, J = 8Hz) 55 pattern 13 pattern 27 CN 113-116 (CDClb) 1.32 (3H, t, J = 8Hz), 2.75 (3H, s), 3.11 (2H, q, J = 8Hz), 6.58 (1H, d, J = 8Hz), 6.92 (1H, br d, J = 8Hz), 7.5-7.8 (8H, m), 7.88 (1H, m) 56 pattern 13 pattern 28 CN 115-119 (CDCb) 1.30 (3H, t, J = 8Hz), 2.75 (3H, s), 3.10

(2Η, t, J = 8Hz), 6.44 (lH, d, J = 8Hz), 7.2O (1H, br d, J = 8Hz), 6.62 (4H, m)

160 793

1 2 3 4 5 5 57 pattern 13 pattern 29 CN 14-148 (CDCb) 1.29 (3H, t, J = 8Hz), 2.73 (3H, s), 3.08 (2H, q, J = 8Hz), 6.40 (1H, d, J = 8 Hz), 7.08 (1H, broad d, J = 8 Hz), 7.64 (4H, s) 58 pattern 30 pattern 31 CN Oil (CDClb) 6.30 (1H, d, J = 8Hz), 6.1-6.62 (2H, m), 7.18-7.46 (1H, m), 8.14 (1H, broad d, J = 8Hz), 8.35 (1H, s), 8.86 (1H.s) 59 pattern 31 pattern 4 CN 88- 89 (CDCb) 1.28 (3H, t, J = 8Hz), 1.37 (6H, d, J = 7Hz), 3.03 (2H, q, J = 8Hz), 3.18 (1H , s, J = 7Hz), 6.24 (1H, br d, J = 7Hz), 6.33 (1H, d, J = 7Hz), 6.16-6.2 (2H, m) , 7.28-7.52 (1H, m) 60 pattern 31 pattern 6 CN 135-136 (CDCb) 1.30 (3H, t, J = 8Hz), 1.39 (6H, d, J = 7Hz), 3.06 (2H, q, J = 8Hz), 3.25 (1H , qt, J = 7Hz), 6.41 (2H, singlet like), 6.92-7.46 (3H, m) 61 pattern 31 formula 8 CN 115-116 (CDCb) 1.29 (3H, t, J = 8Hz), 1.38 (6H, d, J = 6Hz), 3.05 (2H, q, J = 8Hz), 3.32 (1H , qt, J = 6Hz), 6.25 (2H, singlet like), 7.20-7.0 (5H, m) 62 pattern 32 pattern 4 CN 108.5-109.5 (CDCb) 1.28 (3H, t, J = 7Hz), 1.43 (9H, s), 3.05 (2H, q, J = 7Hz), 6.24 (1H, d), 6 , 10-6.48 (3H, m), 7.20-7.46 (1H, m) 63 pattern 32 pattern 6 CN 145-146 (CDCb) 129 (3H, t, J = 8Hz), 1.43 (9H, s), 3.06 (2H, q, J = 8Hz), 6.39 (2H, singlet like), 6 . 90-7.44 (3H, m) 64 pattern 32 formula 8 CN 126-127 (CDCb) 1.30 (3H, t, J = 8Hz), 1.44 (9H, s), 3.08 (2H, q, J = 8Hz), 6.22 (2H, singlet like) , 7.20-7.64 (5H, m) 65 pattern 13 pattern 35 CN 118-120 (CDClb) 1.26 (3H, t, J = 7Hz), 2.65 (3H, s), 2.97 (2H, q, J = 7Hz), 6.28 (1H, d, J = 8 Hz), 6.46 (1H, broad d, J = 8 Hz), 7.0-7.6 (4H, m) 66 pattern 33 pattern 4 CN semi-permanent (CDCb) 6.28 (1H, d, J = 8Hz), 6.02-6.68 (2H, m), 7.11 (1H, br d, J = 8Hz), 7.20-7 .44 (1H, m) 67 pattern 34 pattern 4 CN 10 (6-107 (CDClb) 2.89 (3H, s), 6.36 (1H, d, J = 8Hz), 6.36-6.68 (2H, m), 7.36-7.56 (1H, m ), 8.14 (1H, br d, J = 8Hz), 8.51 (lH.s) 68 pattern 34 formula 8 CN 94 - 94.5 (CDClb) 2.88 (3H, s), 6.31 (1H, d, J = 8Hz), 7.30-7.68 (5H, m), 8.15 (1H, br d, J = 8 Hz), 8.46 (lH, s) 69 pattern 34 formula 8 CN 101-104 (CDClb) 2.86 (3H, s), 6.44 (1H, d, J = 8Hz), 6.90-7.10 (1H, m), 7.22-7.45 (2H, m ), 8.16 (1H, br d, J = 8Hz), 8.44 (1H, s) 70 pattern 36 pattern 6 CN 128.0-129.0 (CDClb) 2.65 (3H, s), 6.42 (1H, d, J = 8Hz), 6.76 (1H, d, J = 8Hz), 7.0-7.2 (2H, m), 7.4 (1H, s) 71 pattern 36 pattern 4 CN 92.5- 93.0 (CDCb) 2.70 (3H, s), 6.31 (1H, d, J = 8Hz), 6.52 (lH.dd, J = 3.0, 1.0Hz), 7.55 ( 1H, d, J = 1Hz) 72 pattern 38 pattern 6 CN 131.5-132.0 (CDClb) 2.67 (3H, s), 6.41 (1H, d, J = 8Hz), 6.77 (1H, d, J = 8Hz), 7.0-7.2 (1H, m). 7.3-7.35 (2H, tn) 73 pattern 38 pattern 4 CN 130.5-1310 (CDClb) 2.66 (3H, s), 6.35 (1H, d, J = 8Hz), 6.62 (1H, dd, J = 3Hz), 6.71 (1H, d, J = 3 Hz), 6.76 (lH, d, J = 8 Hz), 7.52 (lH, d, J = 1 Hz) 74 pattern 38 pattern 6 CN 1 ^ (^, ^^ 131.0 (CDClb) 2.63 (3H, s), 6.41 (1H, d, J = 8Hz), 6.77 (1H, d, J = 8Hz), 7.15 (1H, m), 7 , 17.5 (2H, m)

R ¹ R ²

IN CONHCH ^X N

With a '\ r3

160 793

-CH = C

CH'CH.

MODEL 1

MODEL 5

MODEL 6

N -S CH3 S

N CH S H

MODEL 7

PATTERN 2

MODEL 8

3 'Ó PATTERN

N CH3 'r ³

N., CA ^S.

CH3

PATTERN i

MODEL 9

MODEL 1

N C2H5

N ^ CH ₃

MODEL 11

MODEL 12

^{N n- C} 3 ^ 7 ch3- ~; x

MODEL U

N CF "

N CoHc {ν 'from b

MODEL 15

MODEL 16

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PATTERN 17 PATTERN 18 N% - ^h 3 CC ^{N εΗ} 3% PATTERN '9 PATTERN 20 NC ^h 3 c ^and xr ⁿ - < ^CH 3 CH3 - < _S K PATTERN 2 ' PATTERN 22 N-n <] N CH? Cl ² PATTERN 23 PATTERN 24 N '- ^C 3 ^H 7 ^CH 3 ^ _s X N CH3 - <sl PATTERN 25 PATTERN 26 CL

PATTERN 27

PATTERN 28

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Cl

MODEL 29

MODEL 30 c ₃ h ₇ - & f tC, ^H9 XX

MODEL 31

MODEL 32

S '

N Cl

Cl

N

CH,

MODEL 33

MODEL 34

-b

Cl

N CH3

PATTERN 35 pp

MODEL 36

Br

N CHr

V. '

PATTERN 37 n ^ ch ₃ χ

-C-NH

PATTERN 3Θ

MODEL 39

Publishing Department of the UP RP. Circulation of 90 copies Price PLN 10,000

Claims (1)

Patent claim A fungicide with synergistic action, used in particular in agriculture and horticulture, and containing a diluent or carrier and / or an excipient and an active ingredient, characterized in that the first active ingredient is at least one amide derivative of the general formula I, in which one of X and Y are sulfur atom and the other is carbon atom, Z is nitrile or thioamide group, R ¹ and R ² each are hydrogen, halogen, 1-6 carbon atoms, halomethyl or phenyl group, and R ³ is an alkenyl group of 2-6 carbon atoms, a haloalkenyl group of 2-4 carbon atoms, a furyl group, a thienyl group, an alkoxy group of 1-4 carbon atoms, an alkylthio group of 1 to 4 carbon atoms, an alkynyloxy group of 3-5 carbon atoms, an alkynylthio group of 3-5 carbon atoms, a pyrazolyl group or an optionally halogen-substituted phenyl group, and the second active ingredient is at least one N-haloalkylthioimide fungicide, the content of which is of the active ingredients is 0.5-90% by weight, and the first and second active ingredients are in a ratio of 1: 1 to 1: 30.