DD283323A5 - FUNGICIDE COMPOSITION FOR AGRICULTURE AND GARDENING - Google Patents

Abstract

The invention relates to a fungicidal composition for agriculture and horticulture. According to the invention, amide derivatives of general formula (IV) are prepared in which the substituents have the meaning given in the description. The compounds of the present invention are used as active ingredient in fungicides or in fungicidal compositions together with a second active ingredient selected from acylalanine fungicides having control activity with respect to plant diseases caused by oomycetes, dithiocarbamate fungicides, N-haloalkylthioimide fungicides, inorganic copper fungicides , Tetrachloroisophthalonitrile, dichlofluanid and fluazinam. The compositions and compositions of the present invention are eminently suitable for horticulture and agriculture for the prevention and cure of plant diseases. Formula (IV) {fungicidal action; preventive and healing effects on plant diseases; Application in horticulture and agriculture}

Description

Field of application of the invention:

The invention relates to ''; Process for the preparation of an amide derivative of the following general formula (I)

R ²

ONHCH 'N

833 2 3

wherein one of X and Y represents a sulfur atom and the other represents a carbon atom, Z represents a nitrile or thioamide group, each of R and R represents a hydrogen atom, a halogen atom, an alkyl group having 1 to 6 carbon atoms, a halomethyl group or a phenyl group and R is an alkenyl group having 2 to 6 carbon atoms, a HaIoalkenylgruppe with? .. to 4 carbon atoms, a furyl group, a thienyl group, an alkoxy group having 1 to 4 carbon atoms, an alkylthio group having 1 to

4 carbon atoms, an alkinyloxy group with 3 to

5 carbon atoms, an alkynylthio group having 3 to

5 represents carbon atoms, a pi-tazolyl group or an unsubstituted or halo-substituted phenyl group;

Agricultural and horticultural fungicides containing the amide derivative as active ingredient; and a fungicidal composition for agriculture and horticulture containing the amide derivative of the general formula (I) as the first active ingredient and at least one component selected from the acylalanine fungicides with effect on the control of plant diseases caused by ooaiycetes, dithiocarbamate fungicides, N-haloalkylthioimide fungicides, inorganic copper fungicides, tetrachloroisophthalonitrile, dichlofluanid and fluazinam.

Characteristic de «; known, 5/0 * & $ * f '<«4 /» * Vc

Heretofore compounds having different chemical structures have been used as fungicides for agriculture and horticulture and contributed greatly to the control of plant diseases and, consequently, to the development of agriculture. However, these conventional fungicidal chemicals proved to be insufficient.

3 2 S 3 3 2 3

concerning their controlling activity and safety. For example, some dithiocarbamate fungicides such as zinc ethylene bis (dithiocarbamate) [zineb], manganese ethylene bis (dithiocarbamate) [maneb], a complex of manganese ethylene bis-cdithiocarbamate) and zinc ethylenebis (dithiocarbamate) [mancozeb] and diz : n-bis (dimethyldithiocarbamate) ethylene bis (dithiocarbamate) [polycarbamate], N-haloalkylthioimide fungicides such as N-trichloroethylthio-4-cyclohexene-i, 2-dicarboximide [captan], N-1 ', 1 ', 2 ", 2'-tetrachloroethylthio-4-cyclohexene-i, 2-dicarboximide [captofol] and N-trichloromethylthiophthalimide [folpet], inorganic copper fungicides such as cuprisulfate, basic cuprisulfate, basic cupric chloride and cupric hydroxide, tetrachloroisophthalonitrile [TPN ], N- (dichlorofluoromethylthio) -N ', N-dimethyl-N-phenylsulfamide [Dichlofluanide] and 3-chloro-N- (3-chloro-5-trifluoromethyl-2-pyridyl) -2,6-dinitro-4- trifluoromethylaniline [fluazinam], an excellent control efficacy for diseases in plants such as fruit trees and vegetables, and are becoming large Scope used as fungicides for agriculture and horticulture. However, these chemicals are predominantly preventive and are not expected to have a healing effect. Therefore, they have the serious shortcoming that when observing the occurrence of plant diseases, one can not expect sufficient efficacy from these chemicals. Considering, in a given situation, the use of chemicals to control plant diseases, these chemicals are sprayed more or less after the onset of symptoms of the plant disease and the above chemicals are difficult for complete control of the diseases. Furthermore, the concentrations of these chemicals, in which they have a controlling effect, are very high, so that they are difficult to safely attack.

and some of these chemicals have a non-negligible toxicity to fish.

To remedy this deficiency, extensive research has been carried out on new controlling agents. For example, acylalanine fungicides such as N- (2,6-dimethylphenyl) -N- (2'-methoxyacetyl) -alanine methyl ester [metalaxyl], N- (2,6-dimethylphenyI) -N- (2- furoyl) alanine methyl ester [Furalaxyl], N- (2,6-dimethylphenyl) -N- (phenylaoetyl) alanine methyl ester [benalaxyl], .2-chloro-N- (2,6-diraethylphenyl) -N- (tetrahydro-2-oxo-3-furanyl) -acetamide [Ofurace] and 2-methoxy-N- (2,6-dimethylphenyl) -N- (2-OXO-1,3-oxazolidin-3-yl) -acetamide [Oxadixyl], as a means of controlling plant diseases caused by Oomycetes, which also have an excellent curative effect and have been put into practical use worldwide. It has already been stated that these chemicals were resistant to strains and their control effect consequently decreased.

Numerous active benzylamide compounds have been found and used as herbicides or fungicides. For example, known substituted benzamide derivatives include ethyl N-benzoyl-N- (3,4-dichlorophenyl) -2-aminopropionate [benzoylpropyl ethyl] as a herbicide and N- (3-isopropoxyphenyl) -2-methylbenzyl [mepronil] as a fungicide ,

BP-2094786, BP-2095237 and BP-2107308 disclose a herbicide and a fungicide comprising a substituted benzylamide derivative having a 4-pyridylcarbonyl, 2-furylcarbonyl, 2-thienylcarbonyl or 2-benzofurylcarbonyl group, but its phytotoxicity a problem with crops.

2 8.1 3 2 3

Object of the invention:

The object of the invention is to provide processes for the preparation of a compound which is free from the above-mentioned deficiencies of the prior art and has excellent properties as a fungicide for agriculture and horticulture, as well as a fungicide for agriculture and horticulture, the compound as an active ingredient and a fungicidal composition for agriculture and horticulture, which contains the compound as the first active ingredient and a specific, known, fungicidal compound as the second active ingredient. In particular, the invention relates to a simple process for producing a compound in high yield, which has a preventive and curative effect on a wide range of plant diseases, such as diseases of fruit trees and vegetables, an excellent control effect against resistant fungi, a wide range of applicability, and the like has long residual activity, no phytotoxicity to crops and shows very low toxicity to warm-blooded animals and fish; a fungicide for agriculture and horticulture containing the compound as an active ingredient; and a fungicidal composition for agriculture and horticulture containing the compound as a first ingredient and a specific, known, fungicidal compound as a second ingredient.

Explanation of the essence of the invention:

The inventors intensively worked on acylamide derivatives to achieve the above object, and found that amide derivatives having a thiazole or isothiazole ring have a biological activity which was by no means foreseeable due to the compounds exemplified above, and an excellent control over a broad range to have plant diseases; and in particular that diose derivatives have both a preventive and a healing effect with regard to

the control of various crop diseases, such as late blight and downy mildew possess.

The amide derivatives prepared by the processes of the invention have the following general formula (I)

R ²

ONHCH

(D

in which one of the radicals X and Y represents a sulfur atom and the other represents a carbon atom, Z represents a nitrile radical

1 2 or thioamide group, each of R and R represents a hydrogen atom, a halogen atom, an alkyl group having 1 to 6 carbon atoms, a halomethyl group or a phenyl group, and R 1 represents an alkenyl group having 2 to 6 carbon atoms, a haloalkenyl group having 2 to 4 carbon atoms, a furyl group, a thienyl group, an alkoxy group having 1 to 4 carbon atoms, an alkylthio group having 1 to 4 carbon atoms, an alkynyloxy group having 3 to 5 carbon atoms, an alkynylthio group having 3 to 5 carbon atoms, a pyrazolyl group or an unsubstituted or halo-substituted one Phenyl group stands.

In the amide derivatives of the general formula (i) are

Examples of the alkyl group of R and R are methyl, ethyl, n-propyl, isopropyl, η-butyl, isobutyl, sec-butyl, tert-butyl, n-pentyl and n hexyl groups. Examples of the halomethyl group are chloromethyl and trifluoromethyl groups. The alkenyl group of R 1 is, for example, a vinyl, allyl, propen-1-yl, 2-methyl-propene-1-yl, 1-methyl-propen-1-yl, 1,2-dimethyl-propene-1-yl , 2-Etbylpropen-1-yl or 2-n-propylproper.-1-ylgruppe. The haloalkenyl group is e.g. a 2-chloroethene

3323

nyl, 2-chloropropenyl "1-yl or 1-methyl-2-chloropropenyl-iyl group. Examples of the alkoxy group are methoxy, ethoxy, n-propoxy, isopropoxy, n-butoxy, sec-butoxy and tert-butoxy groups. Examples of the alkylthio group are methylthio, ethylthio, n-propylthio, isopropylthio, n-butylthio, isobutylthio, sec-butylthio and tert-butylthio groups. Examples of the alkinyloxy group are propyn-2-yloxy, 3-methylprop-2-yloxy and 3-ethyl-2-propynyloxy groups. Examples of the alkynyltliio groups are propin-2-ylthio, 3-methylpropin-2-ylthio, 3-ethylprop-2-yl-thio groups. The halogen atom may be e.g. to act fluorine, chlorine, bromine or iodine.

The compounds of general formula (I) are new.

The present invention relates to a process for the preparation of an amide derivative of the general formula (IV)

R ¹ "R ^{2 Λ}

wherein one of X and Y represents a sulfur atom and the other represents a carbon atom, each of

1 2

R and R represents a hydrogen atom, a halogen atom, an alkyl group having 1 to 6 carbon atoms, a halomethyl group or a phenyl group, and R represents an alkenyl group having 2 to 6 carbon atoms, a haloalkenyl group having 2 to 4 carbon atoms, a furyl group, a thienyl group, a Alkoxy group having 1 to 4 carbon atoms _{f is} an alkylthio group having 1 to 4 carbon atoms, an alkynyloxy group having 3 to 5 carbon atoms, an alkynylthio group having 3 to 5 carbon atoms, a pyrazolyl group or an unsaturated

is substituted or halogen-substituted phenyl group,

the reaction of a heterocyclic, 5-membered carboxylic acid of the general formula (II)

(II)

Wherein X, Y, R and R have the above meaning, or a reactive derivative thereof with an aminoacetonitrile of the following general formula (III)

CN

H ₉ N.CN C (HI)

R ³ χ

wherein R is as defined above or with its salt;

a process for producing an amide derivative of the following general formula (IV)

R ¹ "R ^{2 X}

.CK (IV) R ³

wherein one of X and Y represents a sulfur atom and the other represents a carbon atom, each of the radicals

1 2 R and R represents a Yfesserstoffatom, a halogen atom, an alkyl group having 1 to 6 carbon atoms, a halomethyl group or a phenyl group and R ^ is an alkoxy group having 1 to 4 carbon atoms, an alkylthio group having 1 to 4 carbon atoms, an alkinyloxy group having 3 to 5 carbon atoms, an alkynylthio group having 3 to 5 carbon atoms or a pyrazolyl group,

the halogenation of an N-cyanomethylcarboxylic acid amide of the following general formula (V)

χ ^D

 vw, z (V)

Wherein X, Y, R and R are as defined above to form an intermediate of the following general formula (VI)

shark

In which X, Y, R and R are as defined above and Hai is a halogen atom, and the subsequent reaction of the compound of the general formula (VI) with a compound of the following general formula (VII)

HR ³ (VII)

wherein Rr is as defined above; and

A process for producing a compound of the following general formula (VIII)

R ¹ R ²

where X and Y represent a sulfur or carbon atom

Each of R and R represents a hydrogen atom, a halogen atom, an alkyl group having 1 to 6 carbon atoms, a halomethyl group or a phenyl group, and R 1 represents an alkenyl group having 2 to 6 carbon atoms, a haloalkenyl group having 2 to 4 carbon atoms, a furyl group, a thienyl group

8.13 2 3

10 ° ^C

is an alkoxy group having 1 to 4 carbon atoms, an alkylthio group having 1 to 4 carbon atoms, an alkynyloxy group having 3 to 5 carbon atoms, an alkynylthio group having 3 to 5 carbon atoms, a pyrazolyl group or an unsubstituted or halogen-substituted phenyl group,

which involves subjecting a compound of the following general formula (IV)

CN J-CONHCH _x

'Ν' ^R

Wherein X, Y, R, R and R '' are as defined above, an addition reaction with hydrogen sulfide.

The processes according to the invention for the preparation of the amide derivatives are represented by the following reaction schemes (a) to (c).

scheme (A) χ ^r2 ♦ H ₂ NCH ^ R ³ R ¹ reactive hereof deriva- (III ) (II) or vate R ^> Y v ^r2 ONHCH ^ CN R ³

In this scheme, the amide derivatives of general formula (IV) can be prepared by reacting the heterocyclic, 5-membered carboxylic acid of general formula (II) or its reactive derivative (such as an acid chloride

2 8.1 3 2 3

or an acid anhydride) with the aminoacetonitrile of the general formula (III) or its salt. Various methods are available for carrying out the reaction according to scheme (a) and are described below with reference to the following reaction schemes (a) -1 to (a) -5.

Tapering scheme (a) -1

Process comprising the conversion of the carboxylic acid to a chloride and its reaction with aminoacetonitrile:

R ¹ R ²

SOCl

N (II)

H N.CN _λ

¹ VR ¹ R (III) N

> - Y (3-J _x

^N (IV)

Usually, the carboxylic acid derivative (II) is heated in an excess of thionyl chloride. After the reaction, excess thionyl chloride is evaporated off to obtain the acid chloride. Sometimes the reaction in thionyl chloride does not go well. In such a case, the carboxylic acid (II) is treated with an almost weight equivalent amount of phosphorus pentachloride in an inert solvent. This makes the reaction smooth. After the reaction, low boiling materials are evaporated to give the acid chloride. The resulting acid chloride is reacted in an inert solvent with the aminoacetonitrile (III) or its salt in the presence of a weight-equivalent amount or a slight excess of a base to the amide derivative (IV)

easy way to surrender. If the salt of the aminoacetonitrile is used, the base is additionally supplied in an amount which is necessary for the neutralization of the salt. The inert solvent is inert to the chloride and the aminoacetonitrile. Specific examples are ethers such as diethyl ether, diisopropyl ether, tetrahydrofuran and dioxane, hydrocarbons such as benzene, toluene, xylene and ligroin, halogenated hydrocarbons such as dichloromethane, chloroform and carbon tetrachloride, esters such as ethyl acetate and ethyl propionate, and aprotic polar solvents such as N , N-dimethylformamide, dimethylsulfoxide and 1,3- = dimethylimidazolidinone. Pyridine can be used as the base and solvent. Examples of the base may include organic bases such as triethylamine, dimethylaniline, pyridine and DBU, and inorganic bases such as ammonia, potassium hydrogencarbonate, potassium carbonate, sodium carbonate, sodium hydrogencarbonate, sodium hydroxide and ammonium carbonate, although these examples are not limitative. It is undesirable to carry out this reaction at too high a temperature because the thermal stability of the aminoacetonitrile derivative intermediate (III) is low. Preferred reaction temperatures are 10 to 50 ^° C. After the dropwise addition of the aminoacetonitrile derivative (III), the mixture is continuously stirred at room temperature to complete the reaction. The reaction time, which varies depending on the reaction temperature, is usually 0.5 to 4 hours. After the reaction, the crude reaction product is obtained by a conventional method. The resulting desired amide derivative can be easily isolated and purified by a conventional method such as recrystallization or column chromatography.

Reaction Chart (a) -2

A process comprising reacting an anhydride of the carboxylic acid with the aminoacetonitrile.

y ra-j-co

"N

(II)

CN

(III)

κ ¹ χ. ^r2

.CN

onhch;

(IV)

The amide derivative (IV) can be obtained by carrying out the same reaction as in Reaction Scheme (a) -1 except that the acid anhydride is used in place of the acid chloride.

Reaction scheme (a) -3

A process comprising reacting a mixed acid anhydride of the carboxylic acid with the aminoacetonitrile.

ClCO ₂ R

(II)

C-O-C-OR

CN

(III)

(IV)

(In the above scheme, R represents a lower alkyl group.)

The carboxylic acid derivative (II) is dissolved in an organic solvent, and in the presence of a base, a chloroformate ester is added to form a mixed acid anhydride. L \ e addition of the aminoacetonitrile (III) to the mixed acid anhydride gives the amide derivative (IV). The organic solvent and the base may be the same as in the reaction scheme (a) -1. The reaction temperature is -50 to 20 ⁰ C, preferably -10 to 10 ⁰ C, for the reaction of the carboxylic acid with chloroformate and 0 to 50 ⁰ C, preferably 10 to 30 ⁰ C, for the reaction of the mixed anhydride with the aminoacetonitrile. The isolation and purification of the final product can be carried out simply according to a conventional method, as in the case of reaction scheme (a) -1.

Reaction scheme (a) -4

Process comprising the use of carbonyldiimidazole (CDI).

F) -C-Nj (cdi:

^{r1 r2} ο o

η η η

" / ι

C-O-C-Nl

(III)

CN

, CN

ONHCHC (IV)

2 3.Vl 2 3

The carboxylic acid derivative (II) is dissolved in an organic solvent and carbonyldiimldazole is added. This is followed at 0 to 50 ⁰ C, preferably 0 to 30 ⁰ C, the addition of aminoacetonitrile (III) to give the amide derivative (IV). The organic solvent used was the same as that used in the reaction of Reaction Scheme (a) -1. The isolation and purification of the final product can be readily accomplished in conventional manner in the same manner as described for the reaction in Reaction Scheme (a) -1.

Reaction scheme (a) 5

Process comprising the use of dicyclohexylcarbodiimide (DCC).

N (II)

* x. « ²

(DCC)

X) -O-C

NH

CN

(III)

Y. C-

ONHCH; (IV)

The carboxylic acid derivative (II) is dissolved in an organic solvent and dicyclohexylcarbodiimide is added to the solution. While cooling the solution with ice-water, the aminoacetonitrile (III) is added to obtain the amide derivative. The organic used in this reaction

813 2 3

Typical solvents may be the same as those exemplified in reaction scheme (a) -1. The isolation and purification of the final product can be done easily by a conventional method.

In addition to the reaction schemes (a) -1. to (a) -5, for the preparation of the amide derivatives of the invention, methods commonly used in the art of peptide synthesis may be employed.

When R 1 in the general formula (IV) is an alkoxy, alkylthio, alkynyloxy, alkynylthio or pyrazolyl group, the amide derivative (IV) can be prepared by the following process (b).

Method (b)

\ / ^x

N (V)

-CONHCH ₂ N

Bromine and ethyl acetate as solvent;

N (VI)

ONHCH-CN

br

HR ^O (VII)

triethylamine

γ C-H-conhch; ^ N (IV)

CN

E ii ?. N-cyanomethylcarboxyamide (V) corresponding to the formula (TV) in which R * represents a hydrogen atom is used as a synthesis intermediate for a compound of the general formula (IV) in which B? an alkyloxy, alkylthio, alkynyloxy, alkynylthio or pyrazolyl group is very important.

Treatment of the N-cyanomethylcarboxyamide (V) with a>> m halogenating agent in a suitable solvent gives a halogenated intermediate (VI). Bromine or N-bromosuccinoniQ.id can be used as a halogenating agent. Examples of solvents are aliphatic halogenated hydrocarbons such as dichloromethane, chloroform, carbon tetrachloride and 1,4-dichloroethane, and aliphatic carboxylic acid esters such as methyl acetate, ethyl acetate, isopropyl acetate and ethyl propionate. The reaction temperature is 20 to 80 ^° C., preferably 30 to 50 ^° C. This reaction can be carried out in an inert gas atmosphere. Since the halogenation intermediate (VI) is unstable, it is immediately reacted with HR ⁵ (VII). This reaction takes place in the presence of an acid acceptor. Examples of the acid acceptor are tertiary amines such as triethylamine and dimethylaniline, although they are not limitative. It is desirable that this reaction be carried out in a solvent or diluent. It is desirable to avoid high temperatures in carrying out this reaction because the thermal stability of the intermediate is low. Desirably, it is done under cooling because it is exothermic. The desired amide derivative (IV) can be purified in a conventional manner by recrystallization, column chromatography, etc.

A compound of the formula (VIII) corresponding to a compound (I) in which Z represents a thioamide group can be prepared by the following method (c).

Method (c)

R R R

CSNH

^RX N. ^R

(IV) (VIII)

The thioamide derivative (VIII) can be obtained by reacting the compound (IV) with gaseous hydrogen sulfide in the presence of a mono-, catalytically effective amount of a tertiary amine in an inert solvent, e.g. aliphatic, halogenated hydrocarbons, such as dichloromethane, chloroform, carbon tetrachloride and 1,4-dichloroethane, or alipha ti carboxylic esters ^ such as methyl acetate, ethyl acetate, isopropyl acetate and ethyl propionate treated. The isolation and purification of the desired product can be easily carried out in a conventional manner by recrystallization, column chromatography, etc.

Methods of synthesizing the heterocyclic 5-membered carboxylic acid (II) used in the invention as starting material are described below with reference to citations.

(1) Thiazole-4-carboxylic acids (Journal of Chemical Society, 1946, page 87) S 0

R ¹ -C -NH

2 ^lv "'2 ^v ^ 2 ^ 2" 5 24 h reflux'

in benzene

(2) Thiazole-5-carboxylic acids (Chemical Abstracts, Volume 40, page 4056)

s o

R ³ -C -NH ₂ + R ² -C-CH-CO ₂ C ₂ H ₅ > -

Hal

9 2

R R

^C0 2 ^H

19

813 2 3

This is the so-called Hantzsch reaction.

(3) Isothiazolecarboxylic acids (Journal of Chemical Society, 1959, page 3061)

Sandmeyer reaction

CuCN _s

N>

NaOH _v

I ^

: o ₂ h

(4) 2-Halothiazole-5-carboxylic acids (Journal of Heterocyclic Chemistry, Volume 22, page 1621, 1985)

Cl

(HNO ₉ + CuCi ₉ ) or (HNO ₉ + Cu ₉ CI ₉ ) or (HNO ^ + NaJ)

^WH 2 <

H ₉ OH

Hal

R "

CO ₂ C ₉ H

CO ₂ C ₂ H

CO ₂ H

The aminoacetonitrile (III) can be easily obtained by the so-called Strecker reaction as shown below.

2 83.1 2 3

20

CH NH

IT-CHO> HO-CH ^ ^

, MCN R-CN

(IX) H ₉ N -CHQ.

(X) ^ IT

(III)

(In the above scheme, Hai means a halogen atom.)

Specifically, it can be obtained by reacting an aldehyde of the general formula (IX) with hydrogen cyanide [(X), M = H] or an alkali metal cyanide [(X), M = alkali metal] and ammonia or ammonium chloride in water or in a bilayer , consisting of water and an organic solvent system. The order of addition of the aldehyde (IX), the cyanide (X) and the ammonia or ammonium chloride is arbitrary. In any case, this reaction proceeds more efficiently in the presence of a phase transfer catalyst. The resulting aminoacetonitrile is desirably immediately subjected to the next step because it is unstable. However, when converted to a mineral acid salt, it becomes a stable solid and can be stored for a long period of time.

The present invention further relates to a fungicide for agriculture and horticulture which comprises a diluent or a carrier and / or an adjuvant and, as active ingredient, an effective amount of at least one amide derivative of the following general formula (I)

R ¹ .. R ²

wherein one of X and Y represents a sulfur atom and the other represents a carbon atom, Z represents a nitrile or thioamide group, each of the radicals

1 2 R and R represent a hydrogen atom, a halogen atom, an alkyl group having 1 to 6 carbon atoms, a halomethyl group or a phenyl group, and R 1 represents an alkenyl group having 2 to 6 carbon atoms, a haloalkenyl group having 2 to 4 carbon atoms, a furyl group, a thienyl group, an alkoxy group having 1 to 4 carbon atoms, an alkylthio group having 1 to

4 carbon atoms, an alkinyloxy group with 3 to

5 carbon atoms, an alkynylthio group having 3 to

5 carbon atoms, a pyrazolyl group or an unsubstituted or halo-substituted phenyl group.

When used as a fungicide for agriculture and horticulture, the compound of the invention exhibits excellent control over a wide range of plant diseases. It is particularly effective against late blight and downy mildew of various crops caused by oomycetes. The major diseases to be controlled are potato herb rot (Phytophthora infestans), tomato herb rot (Phytophthora infestans), tobacco black rot (Phytophthora nicotiana var.nicotiana), strawberry red rot (Phytophthora sp.), Soybean stem and root rot (Phytophthora megasperma var.sojae), more incorrect Mildew of the grape (Plasmopara viticola), cucumber downy mildew (Pseudoperonospora cubensis), false hop powdery mildew (Pseudoperonospora humuli), false spinach powdery mildew (Peronospora spinaciae) and putrefaction or seedling mildew or rot of various crops caused by Aphanomyces, Pythium, etc. Another , essential feature of the amide derivatives of the invention

2 8 'U 2 3

It is well known that when applied to crops they show little phytotoxicity observed with other amide derivatives.

The compounds prepared by the process according to the invention are applied, for example, by seed dressing, spraying on the foliage, soil treatment, etc. The compounds prepared by the methods of the invention exhibit sufficient activity when applied by methods commonly used by those skilled in the art. The rate of application of the compound of the invention and the concentration in which it is applied may depend on the crop and the disease being treated, the extent of the disease's appearance, the formulation of the compound, the method of application and various environmental conditions. When sprayed, the suitable amount of the compound as the active ingredient is 50 to 5,000 g / ha, preferably 100 to 2,000 g / ha. When the formulation is diluted and sprayed with water as a wettable powder or as an emulsifiable concentrate, the dilution ratio is preferably 200 to 10,000, preferably 500 to 5,000.

The fungicidal composition according to the invention for agriculture and horticulture can be used or formulated together with another chemical for agriculture, such as another fungicide, an insecticide or a plant growth regulator, a soil conditioner or a fertilizer substance,

The compound prepared according to the invention may be used as such, but preferably in the form of a composition comprising a carrier (which may be a solid or liquid composition).

diluent should also be included), applied. The carrier used herein means a synthetic or natural, inorganic or organic substance which is incorporated to aid in the contact of the active ingredient at the site to be treated and to facilitate the storage, transport and handling of the compound as an active ingredient.

Suitable solid carriers include z "B. Clays such as montmorillonite and kaolinite, inorganic substances such as diatomaceous earth, terra alba, talc, silica, gypsum, calcium carbonate, silica gel and ammonium sulfate, vegetable organic substances such as soybean meal, sawdust and wheat flour, and urea.

Suitable liquid carriers include e.g. aromatic hydrocarbons, such as toluene, xylene and cumene, paraffinic hydrocarbons, such as kerosene and mineral oils, halo genated hydrocarbons, such as carbon tetrachloride, chloroform and dichloroethane, ketones, w.1 .-. S acetone and methyl ethyl ketone, 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 potency of the compounds prepared according to the invention, the adjuvants described below may be used singly or in combination, depending on the type of formulation, the situation of use, etc.

For purposes of emulsification, dispersion, distribution, wetting, binding and stabilization, e.g. anionic surfactants, such as lignosulfonates, alkylbenzenesulfonates, alkylsulfuric ester salts, polyoxyalkylene alkyl sulfates and polyoxyalkylene alkyl phosphorus

28.1323

24 *

säureestersalze; nonionic surfactants such as polyoxyalkylene alkyl ethers, polyoxyalkylene alkylaryl ethers, polyene-alkylalkylenealkylamines, polyoxyalkylenealkylamides, polyoxyalkylene alkylthioethers, polyoxyalkylene fatty acid esters, glycerin acid esters, sorbitan fatty acid esters, polyoxyalkylene sorbitan fatty acid esters, and polyoxypropylene / polyoxyethylene block copolymerisates; Lubricants, such as calcium stearate and waxes; Stabilizers, such as isopropyl hydrogen phosphate and methyl cellulose, carboxymethyl cellulose, casein and gum arabic, are used. These components should not be limited to the specific examples given above.

Usually, the amount of the active ingredient in the composition of the present invention is 0.5 to 20% by weight for a dust, 5 to 20% by weight for an emulsifiable concentrate, 10 to 90% by weight for a wettable powder, 0.1 to 20% by weight % for granules and 10 to 90% by weight for a flowable agent. The amount of the carrier in the formulation is usually 50 to 99% by weight for a dust, 60 to 959 ° for an emulsifiable concentrate, 10 to 90% by weight for a wettable powder, 80 to 99% by weight for granules and 10 to 90% by weight with a flowable agent. The amount of adjuvant usually amounts to 0.1 to 20 wt.% In a dust, 1 to 20 wt.% For an emulsifiable concentrate, 0.1 to 20 wt.% In a wettable powder, 0.1 to 20 Ge \ r .% Granules and 0.1 to 20 wt.% For a flowable agent.

The invention also relates to a fungicidal composition for agriculture and horticulture which comprises a diluent or a carrier and / or an adjuvant and as the first active ingredient at least one amide derivative of the following general formula (I)

25

ONHCH

(D

wherein one of the radicals X and Y represents a sulfur atom and the other represents a carbon atom, Z is a nitrile or

1 ? Thioamido group, each of Reftees R and R represents a hydrogen atom, a halogen atom, an acyl group having 1 to 6 carbon atoms, a halomethyl group or a phenyl group, and R represents an alkenyl group having 2 to 6 carbon atoms, a haloalkenyl group having 2 to 4 Carbon atoms, a furyl group, a thienyl group, an alkoxy group having 1 to 4 carbon atoms, an alkylthio group having 1 to 4 carbon atoms, an alkynyloxy group having 3 to 5 carbon atoms, an alkynylthio group having 3 to 5 carbon atoms, a pyrazolyl group or an unsubstituted or halo-substituted phenyl group stands,

and at least one component selected from acylalanine fungicides having efficacy in control of oomycete-induced plant diseases, dithiocarbamate fungicides, N-haloalkylthioimide fungicides, inorganic copper fungicides, tetrachloroisophthalonitrile, dichlofluanid and fluazinam, as the second active ingredient ,

With regard to the second active ingredient used in the invention, examples of acylalanine fungicides are metalaxyl, furalaxyl, benalaxyl, ofurace, oxadixyl and cyprofuram. Examples of dithiocarbamate fungicides are zineb, maneb, mancozeb, polycarbonates and propineb. Captan, Captafol and Folpet are examples of the N-haloalkylthioimide fungicides. Examples of inorganic

Copper fungicides are Cuprisulfat, basic Cuprisulfat, basic Cuprichlorid and Cuprihydroxid.

The compound prepared in accordance with the present invention has both preventive and curative effects against a wide range of diseases in fruit trees and vegetables, and exhibits excellent control over those plant diseases in which pathogenic fungi have evolved resistance to conventional fungicidal chemicals. Furthermore, the composition according to the invention has a sufficiently long residual action and has no phytotoxicity. It also has an extremely low toxicity to warm-blooded animals and fish.

As a fungicide for agriculture and horticulture, the composition according to the invention has a controlling effect on a wide range of plant diseases. Examples of plant diseases against which the composition according to the invention exhibits an excellent control effect include maturation rot (Glomerella cingulata), anthracnose (Elsinoe ampelina), powdery mildew (Uncinula necator), rust (Phacospora ampelopsidis) and downy mildew (Plasmopara viticola) grapes; Rust (Gymnosporangium yauadae), Alternaria leaf spot (Alternaria mali), fruit spot (My.cosphaerella pomi), scab (Venturia inaequalis) and powdery mildew (Podosphaera leucotricha) of the apple; Anthracnose (Colletotrichum lagenarium), powdery mildew (Sphaerotheca fuliginea), rubbery stem rot (Mycosphaerella melonis), downy mildew (Pseudoperonospora cubensis), Phytophthora rot (Phytophthora melonis), scab (Cladosporium cucumerinum) and bacterial spots (Pseudomonas lachrymans) in squash; early rot or early mildew (Alternaria solani), foliage

8-U2

mold (Cladosporium fulvum), Phytophthora rot fPhytophthora capsici), herb rot (Phytophthora infestans) and powdery mildew (Erysiphe cichoracearum) in tomato; Alternaria leaf spots (Alternaria japonica), white spots (Cercosporella brassicae) and downy mildew in cruciferous animals; Rust (Puccinia aiii) and downy mildew (Peronospora destructor) green onion; downy mildew (Peronospora spinaciae) in spinach; Scab (Elsinoe glycines), purple spots (Cercospora kikuchii) and downy mildew (Peronospora manchurica) of soybean; Anthracnose (Colletotrichum lindemuthianum) and rust (Uromnyces appendiculatus) of the white bean; downy mildew (Peronospora viciae) in field beans; Black rot (Phytophthora nicotiana var. Nicotiana) of tobacco; Early blight (Alternaria solani) and late blight (Phytophthora infestans) in potato; downy mildew (Pseudoperonospora humuli) in hops; Phytophthora rot (Phytophthora cinnamomi) in the pineapple; Phytophthora rot of the green pepper (Phytophthora capsici); powdery mildew (Sphaerotheca humuli) and red rot (Phytophthora fragarie) of strawberry; and gray mold (Botrytis cinerea), Sclerotinis disease (Sclerotinia sclerotiorum) and putrefaction (by pythium, etc.) of various crops.

The compounds prepared according to the invention are e.g. by seed pickling, spraying on the foliage, soil treatment, etc. applied. The compounds of the invention exhibit sufficient activity when applied by methods commonly used by those skilled in the art. The rate of application of the compounds of the invention and the concentrations in which they are applied may depend on the crop and the disease being treated, the extent of occurrence of the

28 2 833 2

disease, the formulation of the compound, the method of application and various environmental conditions. When sprayed, the suitable amount of the compound as the active ingredient is 50 to 5,000 g / ha, preferably 100 to 2,000 g / ha. If it is to be sprayed on as a wettable powder or as an emulsifiable concentrate "diluted with water, the dilution ratio is preferably 200 to 10,000, preferably 500 to 5,000.

The agricultural and horticultural fungicidal composition of the present invention may be used or formulated with other agricultural chemicals such as another fungicide, insecticide or plant growth regulator, soil conditioner or fertilizer substance.

The compounds prepared according to the invention can be applied as solcu, but preferably in the form of a gel with a carrier (this also includes solid or liquid diluents). The carrier used herein means a synthetic or natural, inorganic or organic substance incorporated to assist in the contact of the active agents at the site to be treated and to facilitate the storage, transport and handling of the compound as an active ingredient.

Suitable solid carriers ur.d liquid carrier and Adjuvantier ι önnen the same? such as those given above as examples.

Usually, the amount of the active ingredients in the composition according to the invention is 0.5 to 20% by weight in the case of a dust, 5 to 20% by weight in the case of an emulsifiable concentrate,

3323

29

10 to 90% by weight of a wettable powder, 0.1 to 20 % by weight of granules and 10 to 90 % by weight of a flowable composition. The amount of the carrier in the formulation is usually 50 to 99% by weight of a dust, 60 to 95% by weight of an emulsifiable concentrate, 90% by weight of a wettable powder, 80 to 99% by weight of Granules and 10 to 90 Gew.?6 at a flowable agent. The amount of the adjuvant is usually 0.1 to 20 wt% with a dust, 1 to 20% Gew.?6 in an emulsifiable concentrate, 0.1 to 20 Ge \ r. In a wettable powder, 0.1 ms 20. % By weight in the case of granules and from 0.1 to 20% by weight in the case of a flowable agent. The ratio of the fungicide as the second active ingredient to the amide derivative of the invention can be freely changed between 0, 1, and 30.

EXAMPLES

The processes according to the invention for preparing the amide derivatives of the general formula (I) are illustrated below by the following synthesis examples.

Synthetic Example 1

Synthesis of N-ir.-cyanofurfuryl-chloro-methylthiazole

5-carboxyamide (Compound No. 37)

8.8 g of 2-chloro-4-methylthiazole-5-carboxylic acid were suspended in 7 ml of thionyl chloride and treated with 1 drop of N, N-dimethylformamide. The mixture was refluxed for one hour and then excess thionyl chloride was evaporated under reduced pressure. 10 ml of benzene were added and the mixture was evaporated under reduced pressure. This procedure was repeated three times to give 9.7 g of 2-chloro-4-methylthiazole-5-carboxylic acid chloride, which was used in the following reaction without purification.

833 2 3

The 2-chloro-4-methylthiazole-5-carboxylic acid chloride (1.6 g) was suspended in 30 ml of pyridine and treated with 1.3 g of cc- (2-furyl) -a-aminoacetonitrile hydrochloride. The mixture was stirred for 2 h at room temperature. 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 / ethyl acetate gave 1.79 g (yield 75.2%) of the desired N- (o-cyano-furfuryl) -2-chloro-4-methylthiazolo [5-carboxamide.

Synthesis Example 2

Synthesis of N- (a-cyanofurfuryl) -2,4-dimethylthiazole-5-

carboxamide (Compound No. 2) _i

9.30 g of 2,4-dimethylthiazole-5-carboxylic acid were suspended in 90 ml of toluene and mixed with 15.0 g of phosphorus pentachloride. The mixture was refluxed for 1 h. Under reduced pressure, the resulting phosphorus oxychloride and toluene were evaporated to give 2,4-dimethylthiazole-5-carboxylic acid chloride which was used in the following reaction without purification.

6.2 g of α- (2-furyl) -aminoacetonitrile and 6.0 g of triethylamine were dissolved in 120 ml of ethyl acetate, and 2,4-dimeth3'-thiazole-5-carboxylic acid chloride was added dropwise to the solution while stirring, and the mixture was stirred for 1 hour room temperature. 150 ml of water were 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 distilled under reduced pressure to remove the solvent. The residue was recrystallized from isopropyl ether to obtain 11.65 g (yield 90.0%) of desired N- (α-cyanofurofuryl) -.,., 4-dimethylthiazole-5-carboxylic acid amide.

8.13 2 3

31

Synthesis Example 3

Synthesis of N- (a-cyanofurfuryl) -2,4-diethylthiazole-5-

carboxamide (Compound No. 12)

According to the procedure of Synthetic Example 2, 2,4-diethylthiazole-5-carboxylic acid and phosphorus pentachloride were reacted to quantitatively obtain 2,4-diethylthiazole-5-carboxylic acid chloride. The 2,4-diethylthiazole-5-carboxylic acid chloride was used in the following reaction without purification.

2.80 g of α- (2-furyl) -α-aminoacetonitrile and 6.0 g of triethylamine were dissolved in 50 ml of ethyl acetate, and 2.1 g of 2,4-diethylthiazole-5-carboxylic acid chloride was added dropwise with stirring, and the mixture was stirred 1 h at room temperature. 150 ml of water were 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 η-hexane to obtain 2.41 g (yield 8O, 0-6) of desired N- (ω-cyano-fururfuryl) -2,4-dimethylthiazole-5-carboxylic acid amide.

Synthesis Example 4

Synthesis of N- (a-cyanofurfuryl) -2,4-dimethylthiazole-5-carboxylic acid amide (Compound No. 2) using a mixed acid anhydride

4.71 g of 2,4-dimethylthiazole-5-carboxylic acid were suspended in 70 ml of tetrahydrofuran and added with 6.67 g of triethylamine. The mixture was stirred. Under cooling to -10 to -5 ⁰ C was added 4.10 g of n-butyl chloroformate and the mixture was stirred for 30 min at this temperature and offset hereinafter with 4.03 g ct (2-furyl) -a-amino-

acetonitrile hydrochloride. The mixture was stirred at room temperature for 5 h and then allowed to stand overnight. The precipitate was separated by filtration 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- (o-cyanofurfuryl) -2,4-dimethylthiazole-5-carboxylic acid amide.

Synthesis Example 5

Synthesis of N- (a-cyanofurfuryl) -2,4-dimethylthiazole-5- carboxylic acid amide (Compound No. 2) by the CDI method

4.0 g of α- (2-furyl) -a-aminoacetonitrile hydrochloride and a mixture of 3.70 g of a 50% aqueous solution of NaOH and 50 ml of isopropyl ether were stirred at 40 ^° C. for 1 h under nitrogen gas. The i-propyl ether layer was separated. Separately, while 4.71 g of 2,4-dimethylthiazole-5-carboxylic acid and 4.88 g of carbonyldiimidazole (CDI) were stirred in 50 ml of methylene chloride, α- (2-furyl) -ocaminoacetonitrile in isopropyl ether was added dropwise under ice cooling. The mixture was allowed to stand at room temperature overnight 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 ureacrystallized from isopropyl ether to give 5.51 g (yield 70.4%) of desired N- (α-cyanofurfuryl) -2,4-dimethylthiazole-5-carboxylic acid amide.

Synthetic Example 6

Synthesis of N- (α-cyanofurfuryl) -2,4-aminophenylthiazole-5- carboxylic acid amide (Compound No. 2) by the DCC method

2 fm 2 3

3.0 g o .- ^ - FurylJ-oc-aminoacetonitrile hydrochloride and a mixture of 70 g of a 50% aqueous solution of NaOH and 30 ml of methylene chloride was stirred for 1 h at 40 ⁰ C under nitrogen gas. Thereafter, the methylene chloride was chi ent separated. Separately, while 2.50 g of 2,4-dimethylthiazole-5-carboxylic acid and 3.10 g of dicyclohexylocarbodiimide (DCC) were stirred in 50 ml of methylene chloride, α- (2-furyl) -a-aminoacetonitrile was cooled with ice-water added dropwise over 1 h. After the addition, the mixture was stirred for 1 hour under cooling with ice, allowed to stand at room temperature overnight, 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 purified by silica gel column chromatography. Elution with hexane / ethyl acetate gave 1.85 g (47.3% yield) of the desired N- (cc-cyanofurfuryl) -2,4-dimethylthiazole-5-carboxylic acid amide.

Synthesis example 7

Synthesis of N- (a-cyanofurfuryl) -3-methylisothiazole-4

carboxamide (Compound No. 32) ; _

1.2 g of a- (2-furyl) -a-aminoacetonitrile hydrochloride was dissolved in 10 ml of pyridine, and while stirring at room temperature, 1.1 g of 3-methylisothiazole-4-carboxylic acid chloride was added dropwise. After dropwise addition, the mixture was stirred for 1 h and distilled under reduced pressure to remove the pyridines. 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 through

8.13 2

Purified silica gel column chromatography. Elution with benzene / ethyl acetate gave 1.2 g (70% yield) of the desired N- (a-cyanofurfuryl) -3-methylisothiazole-4-carboxylic acid amide.

Synthesis Example 8

Synthesis of N- (a-cyanofurfuryl) -3-methylisothiazole-5

carboxamide (Compound No. 34)

5.0 g of α- (2-furyl) -a-aminoacetonitrile hydrochloride was subjected to hydrogen chloride elimination with sodium hydroxide in ethyl acetate by the same method as in the above Synthesis Example 6. 2.5 g of pyridine was added and further added dropwise with an ethyl acetate solution of 4.0 g of 3-methylisothiazole-5-carboxylic acid chloride. After the addition, the miscipitation was stirred for 1 h. The reaction mixture was washed with water, dilute hydrochloric acid and dilute aqueous sodium bicarbonate solution. Sodium sulfate and charcoal were added to dehydrate and decolorize the reaction mixture. The solvent was removed under reduced pressure and the residue was washed with ethyl ether to give 4.5 g (yield 74 $) of the desired N- (α-cyanofurfuryl) -3-methylisothiazole-5-carboxylic acid amide.

Synthetic Example 9

Synthesis of N- (1-cyano-3-methyl-2-butenyl) -3-methyliso-

thiazole-5-carboxylic acid amide (Compound No. 36)

To a mixture of 30 ml of water and 30 ml of ethyl ether was added 3 ml of 28% aqueous ammonia, 2.0 g of sodium cyanide, 4.5 g of ammonium chloride and 0.5 g of triethylbenzylammonium chloride, and the mixture was cooled to 5 ^° C. with stirring A solution of 2.8 g of 3-methyl-2-butenal was added dropwise. After dropwise addition, the mixture was condensed for 5 h.

stirred continuously at 15 to 20 ⁰ C. 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 treated dropwise with stirring at room temperature with an ethyl acetate solution of 1/1 g of 3-methyl-isothiazole-5-carboxylic acid chloride. After the addition, the mixture was stirred for 1 hour, washed with water and distilled under reduced pressure to remove the solvent. The residue was purified by silica gel column chromatography. Elution with benzene / ethyl acetate gave 1.0 g (63% yield) of the desired N- (i-cyano-3-methyl-2-butenyl) -3-methylisothiazole-5-carboxylic acid amide.

Synthetic Example 10

Synthesis of N-ict-cyanobenzy ^^ - methylisothiazole-S-car-

bonsäureamid (Compound No. 35)

1.2 g of oc-benzyl-oc-aminoacetonitrile hydrochloride were suspended in 20 ml of ethyl acetate and 7 ml of 10% NaOH was added dropwise at a temperature below 10 ⁰ C. The mixture was stirred for 10 minutes at this temperature and an ethyl acetate solution of 0.8 g of 3-methylisothiazole-5-carboxylic acid chloride was added dropwise at ⁰ ° C. After the addition, the mixture was stirred for 30 minutes. The ethyl acetate layer was washed with water and distilled under reduced pressure to remove the solvent. The residue was purified by silica gel column chromatography. Elution with benzene / ethyl acetate gave 1.0 g ( 77% yield ) of the desired N- (o-cyanobenzyl) -3-methylisothiazole-5-carboxylic acid amide.

Syrrth example 11

Synthesis of N-toc-cyano-a-O-pyrazoly-methyl-methyl

isothiazole-5-carboxylic acid amide (Compound No. 46)

0.7 g of N- (cyanomethyl) -3-methylisothiazole-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 and then cooled over 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 with stirring. The mixture was stirred for 30 minutes. The ethyl acetate layer was washed with water and distilled under reduced pressure to remove the solvent. The residue was purified by silica gel column chromatography. Elution with benzene / ethyl acetate gave 0.75 g "( 78% yield ) of the desired N- [a-cyano-a- (1-pyrazolyl) -methyl] -3-methylthiazole-5-carboxylic acid amide.

Synthetic Example 12

Synthesis of N- [α-cyano-α- (1-pyrazolyl) methyl] -2,4-di- methylthiazole-5-carboxylic acid amide (Compound No. 38) (1) Synthesis of N-cyanomethyl ^^ - dimethylthiazole-S - carboxylic acid amide

A mixture of 10 g of 2,4-dimethyl + hiazole-5-carboxylic acid, 13.6 g of thionyl chloride and 70 ml of toluene was cooled with ice and added with stirring 8.4 g of N, N-dimethylformamide. The mixture was stirred for 3 h at 3 to 5 ⁰ C and then for 1 h at 20 ⁰ C and it was mixed with 200 ml of toluene and 37 g of triethylamine. An ethyl acetate solution of aminoacetonitrile prepared from aminoacetonitrile sulfate using ethyl acetate and NaOH was gradually added to the reaction mixture under ice-cooling. The mixture was stirred for 1 h at room temperature. The reaction mixture was poured into water and extracted with ethyl acetate. The ethyl acetate layer was washed with

37

233323

washed, dried and distilled under reduced pressure to remove the solvent. The residue was purified by silica gel column chromatography. Elution with hexane / ethyl acetate gave 6.6 g (53% yield) of N -cyanomethyl-2,4-diethylthiazole-5-carboxylic acid amide.

(2) Synthesis of N- [α-cyano-α- (1-pyrazolyl) methyl] -2,4- dimethylthlazole-5-carbonylureamide

1.0 g of N-cyanomethyl-1-dimethylthiazole-S-carboxylic acid aramid was dissolved in 30 ml of ethyl acetate. 0.3 ml of bromine was added and the mixture was refluxed until the disappearance of the dark brown color of the bromine. The reaction mixture was cooled over an ice-bath and 0.5 g of pyrazole, 2.0 g of triethylamine and 10 ml of ethyl acetate were added at the above temperature. The mixture was stirred for 2 h at room temperature. The reaction mixture was poured into water and extracted with ethyl acetate. The ethyl acetate was not washed with water, dried and distilled under reduced pressure to remove the solvent. The residue was purified by silica gel column chromatography. Elution with hexane / ethyl acetate gave 0.74 g (54.9% yield) of the desired N- [o -cano-cyano-oc-1-pyrazolyl) -methyl] -2,4-dimethylthiazole-5-carboxylic acid amide.

Synthetic Example 13

Synthesis of N- (α-cyano-a-ethoxymethyl) -2,4-dimethylethyl

thiazole-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 heated to reflux until the disappearance of the dark brown color of the bromine. The reaction mixture was cooled via e ⁿ 'nem ice bath and

1.0 g of ethanol, 2.0 g of triethylamine and 10 ml of ethyl acetate were added at the above temperature. The mixture was stirred for 2 h at room temperature. The reaction mixture was poured into water and extracted with ethyl acetate. Ethyl acetate layer was washed with water, dried and distilled under reduced pressure to remove the solvent. The residue was purified by silica gel column chromatography. Elution with hexane / ethyl acetate gave 0.53 g (43.1% yield) of the desired N- [a-cyano-a-ethoxymethyl) -2,4-dimethyl-thiazole-5-carbonamidamide.

Synthetic Example 14

Synthesis of N - [(α-thiocarbamoyl) -furfuryl] -3-methyliso-

thiazole-5-carboxylic acid amide (Compound No. 47)

1.0 g of N- (a-cyanofurfuryl) -3-methylisothiazole-5-carboxylic acid amide was dissolved in 30 ml of tetrahydrofuran and added with 0.6 ml of triethylamine. With stirring at room temperature, hydrogen sulfide was introduced into the mixture. 5 hours later, the reaction solvent was evaporated under reduced pressure. Water was added to the residue. The precipitated crystals were separated by filtration to give 1.1 g of the desired N - [(α-thiocarbamoyl) -furfuyl] -3-methylisothiazole-5-carboxylic acid amide.

Table 1 below shows typical examples of amide derivatives of general formula (I) prepared according to the invention. The terms (a), (b) and (c) in the column "Process" mean the processes (a), (b) and (c), respectively, as described above.

th - Il U) ft. ro • ro 1 = Ö H w VO · - » ft * •• co th ft. "ft • ro "-" N ^^ ft. ~ co -au CM te p ^ - ^^ ι * _ ** cn S ε cm rc υ ^ * ac ro ro · 0 ro Io ' " * - * Ία ί9 (CDC) 6.68 '(2H, 0 C ^ »^ ro Ή ac • VO * · 0 te r-I ο * cn • ε 0 • - * * w ^ H (O • * - * U m cnr * - ro * "^ 4 ft » cn · ft. · cn O. cm cn VO CO 11 te · N cn ^ {f ^ ft. χ cn Il ft. ro ^ · 33 in CM Ίΰ from r 11 ε - ^ I co 0 VO Π C VO · - * ^^ In S **** CD • -3 r-H · ^ * "* ^ 3 in £ ί VD VJ (CDC] 7.34-8.041 ^ VO N (Λ p 0 τ? a VO - · O Ό cm Σ • Xl -O «> 0 vo ^ -s cn vo VO - in S 00 * ·. · • ε ι "C. te · S gco from H cc 00 CM H3 CM CM ίπ ro 11 ν- * r-j rH r * H Il -HI CM ^ roM «a ^^ co CO CM VO Γ- » H VD rH «· • YY (CDC) 6,981 (IH, r-l · cr> :O • * - * * ^ J CM • Ό in • r » OJ O VO • VO "ST" · - BS 00 D Ίη «- r - ^ » Ίη * " co in 3 - VO ». VO ^ -> in 0 - ^ cn a: · ν te · SN * in as IO 33 cn r ··, :: r » - C VD Il ^ - 0 ^^ ^. C in O au 0 ^ H · - co · - »co from 00 ^ ri ad ^ a VO - • Il ε r • Ό CM 1-3 no Ό I Il I CM _< ^ _v jji (CDC) d, J = (IH, .-. 33 raw (CDC] (IH, 7.48 » (CDC] 6,811 in 0 " 0 r- ( I in O cn ro · cn C in CM ro 0 C r-i CM 0 _ro ^ ro Cii C X C C V (0) y · ' JJ I C CD • ω'S " 3 JJ • Η C JJ C ro (O from r3 Ind.  s >

in • ο ro \ *. - • ι ν *. CN co / ₌ CO +0 -, CO e - O e I σι 5 , ^ ^ U ⁰ ^ ^ ^- N -V 'HT O CN ν t £ J S * N cn ro • VD S <CO · 33 cn r. VO ^ -  ? O CN rt r » CTl ·. CO (Vi N • OO CN r- 23 Γ- si r ^ H Il CO r- » · * »™ H ro • S3 Il · Il · CN O - co »-Γ l" 3 SJ ^ VO CN ^{> N} ci · "VO - > "3 VO - • Ι- * VO · Il W OO W · • - -'e e 00 "n CN VJ f "3 - - Il VO O ' ri · r- YY - « S3 * 'HT Il S3 • Xf * X TJ -Ό> "3 ^ · * N · N cn VO 33 3 <- - VD ^ 3 <Sl ^ S3 Il Il • ftt. fO - ro «-» ^ -i »Cl S3 CO CN 33 CO ** Π3 22 O *  * - «» [\ | CO " tr «* ro H ^ ro Il VX) CO ro - » co io CTi .Q • Xl · • Il S3 from 33 E ro - · • ro - VD co Ία CN r-i VO CO • CTVD • CT %. rH - • Il - r-i r-i CS · 33 • 33 -3? XJ CN CN Ό 31 • ΓΟ VO VD rH ~ Ό ,-1 IO ^ S3 r ^ - 33 W N • * ~ *. CN E ^ O4 Xi CN « ro - VO nd vo m S3 - Γ "ΌΟ N - N «- * ^ e OO Γ0 rH Γ- »33 Ι N VD 33 CTi *. m in ftt CN " W · Il · ^ ¹¹ c! VO 33 - OO O 33 co ο az ~ a: OO bvooo cn Γ- 33 Γ- Il · ii Il · r- ( raw rh • Il rt I 1-3 ro ^ ^ * 3 CO * - "· CDCl .36 ( 33 - * · · »· VD O ^ vo ro «-; 4J ^ VD YY · CN rH ä VO ν it · JJ <-> · J-J «" * * " O CN ^^ j I f * ^ N VD fO VD • VO ♦ · 33 OO - -r * ^ N ^ O - 33 co - ^ • 33 M Il r. ro ^ Cu S. OO * μ CO ft. rt I cn CN IO ^^ f ~ 3 E * ~ ^ ^^ OO η H ^ ro Il .Ό • -3 »-Χ IO ^ * 3 « Il ro ^ N ^ ** * "3 ^ * - rs *-S3 ro · ^ j * - ^ ^ * ^ ro- t-3 * - ^ M SC C3 S « • O ¹ 33 E • Il VD ta CO ro - CO ro - cn S stvo ri CN ri »-3 Ό * - * ro r- Il • CT Il • vT Il - »OO ~ sTr ^ se * ~. - e • Il 1-3 ΓΤΝ · i-H ROCR • S3 U CN Ή ¹ O * -> sT ·· r- <- VO ^ * CJ O I CN 'HZ TDCD Xl - .- »-Ό mCN Ό '~ RTN v- * · fr ^ ^ Q J-S. ROCT CDCl .98 (IH, r-i * - * O H U Jn vj - CN ^ - ^ CN ^ ^- * I :O VO χι IO CN O rh IO OO C rh σ> I r-i rt CTi o \ io rh O r ~ { IO r- cn :O rh C r - C = t / = 3 O V W pn / y ν O y 3 tt) / IO rH rt I W CU CN U Xl cd I ^ ^W EH J / V, W - ⁼ JP 3 ~ CN  • ^ (3 U cn Ία ro rH rH (O

8.13 2 3

CO in * - * * • 0 O i rh • co Π3 JR> » , N \ I * I e zti ro ° .B cn ' 9 I CS - "! 1 ^w Il O (O Il co ^^ Γ l "r> (O ai VO CN cn r- ro «H rH · 0 VD r "3 • rh Ι Il CN Γ CS Ü - · \ rs VD • σ M- < rh Ι -VO • O flj ". ^ - * rh VO ro -O ^, vo in * »^ - ^ rH CN "-» JJ CT * - » U ^^ k. tl H *H ~ 0 w · ε ν · jt \ XJ rh -G VD O j ''. (O · VO *** ^ S S cn ft, ro • S N N • S - VD aT "^ ro it ii "it U -r * CS VD S CS S P "] CM • r · H - ro ^. • co C! ^ .13 «- 'w 1-3 * r 0 in O rh cn r> - OO rh C I ro ^ n ^^ IN Il tr - 0 ro 0 - OO " Il Il ^^ A- co VD P ^ ^ h VO CO ry year , , Ό 0 • " "-3 cn / ^v CS «| [PN. • Il • · rH ro '.20-7.! r-Λ CS t CN (^ Il CN * -> 0 rH -Γ- 1 ^ * t CD • Γ 1-3 xt S - - p ·. Il JJ Ό VD - ^. -CN - ^^ r "3 1 ^ tT ^ ^^ TJ ^. - ^ O 73 'S - SSr- N r- a It » e N N CN VO co co vo CD *. S • S - S C3 · ^ - Il Il · r- jj " CS S OO ΓΠ rs CO · VD N Il Il · - » U JJ (N ι ro Il rH * Il rH ii ro a: t-3 cn co χ " M T (-3 * - * η - co • fc V · » S - N • ⁼ S CN ro υ CS -in ii CS cn s CS S ro G u29-6 / - in xl -CS - · - »^ i * ^ - -S in 00 • Il jj r-i 0 O ^ yy · YY · JJ U) · s cn *. cn VD * -} CS ro vo ^ vo VO - - - Ό ro CS Il • S vi VO TTS H S-rH SS - ^ - ^ - 1-3 VD CS CO CS CS Ό ro • ro ^ - - ^ ro - ro ro ^ it cn - CM 0 TO VD vo 0 s from RTS from 0 S · • σ CS S - OO S Il ro H CNCO · it r cn r- co vj rH CS • U) VO · • • Il cn * Il • · Il Xl '"R0rH (IaIrH rh Γ = 8Ηζ), '!! Η, br rh rH 1-3 rH l ~ 3 O CN r ~ 3 ^% " r ^ 3 VO rH 8 0-0 co vo • Γ} - rH g 'red' ¹ H o cn ro '"rorj' rH 8S "" ro - »Ό Ή Η Ν - ^ CJ S - CO Q OO S OO II II rH · CS - * * t "3 - ^ VO co H in CS OO co :O S3 CN  H rh I rh rh rh cn H C I I m I :O C in rH rH rH "Z Λ: / CN rH rh rh U \ S • ^ in "it \ C C / ^ W 0th t W Ρ \ / C / ~ - 3 c / ^ 1 (Θ) O V- 1 ) W ^. Fri. Y r I "ro Y ^ JO ( C Hr-l \ D I I X) W 2 CD V ⁼ EH 1 "n Y C (O in ' co ro rH · rH - '

833 2 3

N EC - EC S .. EC · - • CO 4? - I C co E ^ i * 4J - ^ U \ ^ ³ 'S r-t ro of approx ro ό ro ό ^ r ►CN U VO Il Mr- N - - Em TJ ITt HD CS v- Il - tr Ii r » JJ v- O ro ^ ^ - · Ec ro in rh ac · ro - cn - - Il ro II in <a CS I CN VO EC r ^ w * I EC · EC S'o ^ * CS * - * »V rh V- - ri I ε ν- oo ro CS «Η CN Ό) ro ^ ε  > «Ro -S-i ro - u 3 in it -CS · ro - · «# CN ν- Il · CN v- EC · • Ό JQ ro ¹ T C in -v • N rH EC ac · r- cn * - ^ ro -CS CN VO - rh H ro ro CN VO • w · EC V ^ EC EC ~ t ~ 2 · C - Il ο vo ιΗ ro O * i-l r- UH UJ r- O - v Ό - EC cn · • £ co ΓΟ "3 * rH ν- V- EC - * ~ » r » - * N rH EC cn πτο »-ν ε EC rH ro- O O CN - Q ro - EC U · · Ή • o - ro yy ε ro II rH ν- Ν hH ^^ <ι - eg r ~. ν- vo VO - ^ EC Il - Ii η O VO H. - Q VD and EC Π · Il m »-» ι ro O \ vo vo ^ • ^ ^^ N - - ο rH ^ *. 1-3 - - Is * ~ CN 1-3 v- CN · ro EC CN ^. • from office EC EC • VO ν · ro - <r N he" rs v- - CN -vT ro yy VO * - Γ- · Il · EC CTi • in Il IO 1-3 vo ω I in VO · rH O - o in σ \ I - ^ v Il ro r- EC. , I ro 53 g cn - I ro ro γ Οϊ ul ro C * - »ro ιο-o -EC VO EC W · cn ^ v cn C ECRH Γ »CN ° P • m · ro v- EC - ο vo (N Γ0 ro - r »· ο • vo ε Ή ^ i * ~ ίτο - » CN ΓΤ "** Γ- ^ J -% ^ EC * rH I ij ro Ea Q vo ro D · ti ro £ E 'Ί CDC .90 CS "5? - CN fÖ • "Η ν- w vo -> r-v u EC in ro · cn wv fv. rH Vp rh (** " VV ₀ in O H ν :O -H rH I ίο δ ο O C • p εΓ ro O V (Q ro I (Fort J ₃ \ ^b w φ / \ H ro ΓΗ. Φ rO G ro CD rH (O S EH CN v- ro (O CS V-

833 2 3

OO VD th ro -co I 43 - κ - Γ ** · TJ U M Ö cn Ία VO VO te te te in ^ -. Γ- ^ Il - £. ro te ^ - CN VO "a ro TJ 2C M * S3 cn , S ro • 3 λ · th OO cn co ro Γ ** ^k r-i κ - O ^ - * - .TJ- Il - ro Il - Il TJ ^ ^- * ΕΠ - * -O co - aal = CN «Γ- 1-3 ~ CN H ₃ TJ • "3 in rH si n cn Il ^ co o cn _k E C CN - co S3 ^ ε Il Jj ^ *. Vj · TJ - TJ · • r Il CN - r-H I 33 vo vo • -D Il -te TJ S3 co (CDC (IH, 7.82 te VO - Cj • CN TJ CN ac - -P Π3 ^ D cn TJ - CO VO rh In - TJ Il S3 Γ ** · ^ · cn - ^ co te Γ} rH · ro rH O · rH S3 53 - - ^ r * » rH I I Tr in rH rH S3 - VO co • I J, ro * * - rH TJ CN - in ro ro VO CN VO CN ** * rc VO - CN · rh ro CO O O CN T - vo * ε te. G te · r ^ rH • in ac VO CO cn Ία * - * cn W VO · rH - - ^ *. C CN - CN "Φ vo - Mη m S - O w oo - »- in η ^ · -ro H ro N η yes r- ac · »-a (CDC 7.04 ro r » CN D3 OO ro s in 23 CN - - * I - r ~ · cn ti r ^ co • η Ii « • tj · rH Ό , ~ t-3 • "" ^ * * '^ 3 ϊ ^} VO · CN CO cn σ \ (N CN CN 2ί • r » VO - I VO -CN CN · C 'Top in • J-I Il r \ T CN 1-3 * «. ^ U roe Xt (CDC 6.45 be. (CDC 6.83 σ - r-i co "ia m O CN f> H TJ (CDC (IH, (IH, CN · - • • CN CO C (CDC 6.38 "(IH, rH CN co I vo in I CN CN VO I VO r-H VO CN CN C {r- δ C C -ρ CQ rH Ία  Ρ 9 ro - ^ U °? O ν_ ^ H Ep H ω Z \ cd EH o 15 Θ ro - * r- Ία CN - ^

83 3 2 3

a 5 \ / -r " r- • ft. ZZ ai co ο R I ro -OO a - oo OO - Il CM CO S / a ii Nr ^ - a »o I co a Il r- r- CO - »rH -Γ3 I Il r -s J- O) * · co Ό -CM JP ro co "^ Al rH O) -H in tr Ό Il * i ^ * Ö CO co - · U Q) • co η j; Γ ** in a Ό Il CM X) »J CM · ro a co χι rh X ^ O ^ Xl * »^ H "·. co ~ oo ^ Ό - -χ O 23 ^ ^ 3 EC ^ * y CO VO W ro ΗΌΗ rH a (DMSO-d (5H, m) • in - O O rh CM · a · ^ * * · »· T» » O «- * tr ο CO cn rH CO • I * * a ^ i * JwC «r ^^ • rH U) rh tr ι - '73 ro » VO »- * vo ο Λ CM ^ ο vo a co. 5 CM - CM a u) • e ro vo co from a -vo a {r- CM VO • · Il • co C Il ^ - VO Γ * "* * ~ 3 CM Il ·· VO * - ^ U) ^ - a I 1-3 U) vo U) -O - "r- CQ ^ - * · "^ Vo Ό Tr CM W · V) YY a hj Γ ** · r " -in r- ^ a · - "CM - a r ~. co r ~ a - i-i a a r-- Ii - ~ C VO * - * ro »-» «- · VO rH OO t-3 N in - ^ - N O • Sj co »-, in -" r a ro tr o CM -CM • e VO OO · co r »^> JJ Il in 'rt CM • η co * * co - ra ro " f-ft ft * CM f-3 ri in VO ^ PTM (j in eh Ci VO (DMSO-d 6.50 (IH (IH, d, (J = 8Hz) «CM rH C) - - U rH rH «-» - a CO- ^ i- { Ή .N - ^ ο a oo ρ oo ο VO-- rh rh CO (DMSO-d 5.3-5.8 cn tr f \ in I σ rh I VO CM cn I O H ro rh tr :O rh I ro C .-H C CM C O 9 iH G. 5 C V \ / ö G I H = C ο- \ / JP IQ Y Χ D = H U   ΐ> - Y \. O cn Q) H rh H Q) tr (ö C U co " P »RJ I ro " VO (O ro - ^

TJ TJ O I - N Ίλ rc * l ^^ _k • 33 VD S - 33 ro ES • r "H Il ^ - ^ "3 ^ CO CO as 1-3 VD cn "" "I - - ΪΣ · Il η Il π U) - ^ 5 * - ^ Ό * H VO t ~ 2 O "· O U) co ^ TJ "? Ή r-l - η Ν (Λ Γ- - η «-; TJ • 33 ε TJ ro ve Γ2 · EE η cn 33 - - η - CN \ O Il η ο · 33% - in * ϊ ~ 3 * - ^ as Γ »~ - VD N CO rH C3 * »Jt * U cn rh • N ^^ E3 VO · CO ^ r-i X) U) ** η CN 33 cn VD • f * 3 * ^ TJ • in X) Γ- · - Ή Il CN i-i S ^ r-l CN - II _y r ** cb _t 1 1 ^ - • • ·· - " η 33 - η __! CN - l-i-t * TS co - ^ f ^ σ ¹ Ii as co as VO CO 33 η II »" 3 * -N * co 11 cn Γ ** · AJ "^ i * • O VO (O ο * ~ 3 * ε Γ ^ ΐ 11 1-3 11 Il · CN · Il * - CN Ό ^ 3 ^ r ^ ^ 3 , ^ ^^ - (7> - -CN - * - »- . η • a. M ro 4J * - * cn OJ r TJ  »^ -P 33 r-l in N co 33 · ι-Ι cn \ d - ^ - - cn · - as W VO η η - in 33 CN 33 33 · VO as cn • cn - ιη m ^ -> rH η cn ro 11 ro CN Il ο * · m CN - * ^ - f * ^ * ^ - * * - · I "} ro · - »· IN r ^ · co vo η -cn VD VD • to vo in 33 η · cn cn .- * τ VO » * "% r-l CN r ") • CN • tn · • TJ • O) TJ * - »33 -C • I! r-l VD 0 vo CN • Η γτο N CN> -.) λ ^ - ~ 33 - # - * 33 33 53 CDCl .73 (= 10H * - ^ - row ^ -. no «-» mn r TO rW no * - * CDCl3H, = 9Hz rH - N cj co ic Q VO CO CDCl .95 ( r-l in cn r- <N ρ as cn U CN Il W- * * m ^ P ^ - CN ^ - in W. ' CN vo O -> - «1-3 VO cn O I cn • co H H H H i in S :O :O :O :O 0 r-l = C ε C Ψ = _ ^ • "cn ti ** ro ir •H  » 1 (cont G. / 5 H H ω _ - CD G H ro - CN 3 ro 3 3 O XJ

tp υ O - ro ^ o -Q to JN I r. (j Ό Tl ro ^ ^^ O γ " OO ^ n O ro S U vo VD Ό ö : -ni J. Ö / Ό N rH U ro vo 6 = r O flj • . "- * k W = U S _TM U VD · "ro V tn ^ Γ · r- »- N * - * S Q " · - CO cn "ta • vo - S S tO rH ro S Il ro I S ·· f-C JN in * -> O O ^ - * ·% - * VO rH • · CM ^ r vo U M VO Ξ S CO Il N VO «**» Γ * · S CO σ »ιΗ co cj CM ·· ^ · Cn CM · rj s cn N Il rH · • · CM Tl IO νο ro ti r » CM «ES rj «- cn in oo VO ^ • Hr ^ co •• ω · -Ϊ "*" T * t-3 ^ Il Ό · ^ * -H -r- ^ / -. ro T3 vo I ι M *, I ^ W WWW * ~ * S t "i S iS 4y jy ·. to co ro co · ' - CM r-l S * · * · W *. W O νο Ii r a Ii <- «- CM #H ^^ S 2- ΠΞ fc ^ ^ t s r »» • η rH l "3 VD E Il - CM ^ ΓΟ Η Η CM CM - * - * cn σ · · rH rj p cn ^ τρ ro r ** co • -Ό N τρ rrj C3 ^w RH O - ^ • s in vo in o \ cn ^> - p •> Η ^ p Ό νο in · - * · • «· • e N - OO VO Jf. • in - * cn <N Γ * O ^ S S Il VO - · •-CM r ^ Ή t "3 * · Γ-I .- » S CO ^ x VD - ^. · »* B ^ Γι il »- <- »- N • H rH tn · ~ ~ CM 1-3 VO ·> to ο S r ~ ν to to to ^ Ή Ό r »cm WVD - ν S W «jQ - · Il vo * - * s-in ^ ^ ^ · * Vo ^^ Ό VO Sfsh - · to C3 'S * S S S υ · ε ro te r * ro CM rH Γ0 VD - - CC * - * ». ft. co II % ^ v ^ »> ^ S * » r ^ { νο »-» Ό ***** s CUHO ONS UN in ~ O ^ rH in τρ from r ^ ro rH τρ r »in • S * ION" CM CM ·. «T · , t * - " CM Il · CM OO SG • S CM cm νο cn CM VD CO • 1-3 VO Il rH CM OO VO - CM τρ Il · from · rf- * »w ^ ro- »r ~ rH N I CJ S O Q CO τρ U Il · '"νο τρ <- »i" D cn DMSO-d .34-6. .13 (1H VO- »^ - » » * - »II -. ^ ^ TOO ¹ ε UM CM 'Ο * · CfV Q rH ^ -. VO »- vo cn TJ JM _N O in in C / 3. · K co co S Il Il ^ * ^ ^^ ** ^ W - IQ (DMSO-d (IH, d, J = 2Hz), - »-j η O O r- ro cn VO co VO C3 r-J fH ro rh cn I rh I cn in I I I ro I • O VO vo in cn • ro rh IN rH CO VO i-i rH U C B C _ r-N O U IJ Il • μ I (For τ- Η H <D , Q

833

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CN rh sT - in JP JP rh U C O • cn T Γ VO JJ "ro 53 VO G • - r-H ¹ ^ 33 V rh ** CN  <* "J ro a: • 53 r-H ro Ή ro H "! Η -O ^ σ> Oil in ~ "OJ ro Ή I in •• Ο ^. VO "rH .-" VO N · - • σ Β w σ \ in Io -O «-» Ol rh vo (O UI · OJ · 33 ^m 33 Γ * ·· O) • in - ^ OJ · C in ^ vo vo U CO -VO oi "Yes Il ·· * Π3 H3 a: ^ ro - g - 33 - ro »-» aT - ro ^ in * ^ C n: iH μ VO w w ro ^ -> * - * r- oo in ν - "^ N ^ * 53 Ό ^ «* ~ T ^ j * ^ 4 * r-al χ in 53 VO CO co co * * • CO H r- co • η • Il • in vo OJ Il ^ • Il Ol rj OJ <-3 1-3 co CN Γ5 rH ^ T ro · cn r ^ - co 33 - 33 Sr 33 • I -53 CO CO CO 53 - r \ 53 ro r- ·· (in vo ο cn ti η II '"i ** ^ CO 53 ^ Il rH v ^ Π - ^ w oi Γ ^ O ^ 3 l ™ 3 * - * £ Il H E t-3 - »Ol f "3 CO ^ J * ^ · t ~ 2 OO rj ^ ro oil O (N * »(O * · »R - -ro · OJ ^ CP'O 4J · 33 - · «a: Ό · r- r _v VD ^! VO OO 4J »·> 3 · I I - V ^ VO "- - in · »O a: ε οι 33 - OO - Ol 33 -r » ro a: oi a: ro -% · 33 -VO VO .-. · FROM * OO S3 53 ro - ^ Η cn a! T ro ^ - »· w Μ VO OO S3 VO Ol rH r »ο σ ro co in - ^ JO VO O 33 cn r ~ · OJ Il - CN · VO • Il · ro oo - • Il ~ OJ OJ H VO O • ro rH rs r-> • Il - ^ * - »· · ή in y ~ N ^ * · ^ - oo ^ 4J CO cop oo rH 73 - -co rou ti rotJ ¹ Il rH rj (CDC 6.12 bd), row ^ »- ^ r -H UN (CDC (2H, J = 8H rou Il (CDC IH, bd, (CDC (IH, bd, O -33 53 Ω S3 CO CO η η * - * ^ "* r ^ r ^ (CDC (2H, bd, O ο vo •H co Oil cn H cn ro H I O :O in :O 95th C σ C S C C O r G G r Γ -CH at ro , V X • yto G .P υ ro ta in ^ in "-

CO υ χ. »3 - * ^ - * ) rc <ν - O Y • I e ft • e I • χ m e in I - / I e O - E CO U) Γ ** * - ^^ r •H \ £> to SC VO (N to vo oj O 's • E υ OJ H νο Τ3, N _ "· cr> I r *. cn Il · ft * • Ii Γ * · Π3 OJ - ^ 3 - Ρ "" Oj in VO 11 * » • V "3 VO ro 15 ιη - FROM Ε Il rh t ~ 2 ro VO in rc VO - CO * - ^ vo! -j • ä ^ - * - - - · ft, ro <-Ν O VD CO VO J VO OJ Γ- VO ft. Ό «j« O * - ' W · I Il CO 1 W Γ - - ft. m Ό Il ^ 3 * - E VO (O co in • ΓΟ X ^^ Γ • • E VO ». X - • οο • W N Ι e .-4 VO Il Γ e VO ro λ VD - r- '' CO VD ft. «Ta- * h ^ cn I * - »N * Ό ^^ W OJ 4J L- co Ο O ro e ** XY U] ft. J ^ 11 • cn O ^ fO ro · OJ Γ0 r ^ \ · r- co I (ΙΗ, H} ι ** ro 1 • "ET t • Il N E N ^ * • ft. rH CT • VO OJ I'D E t-t π: co ft * ^^ rh ΕΠ rh CO - CO ^ l TD e rh - E ft. Il "W H · OJ - rH K * - »Ό Ι-) Ή O ro ιη N ^ ^^ Ό • e N E OJ CoE W dB - - CO ft. ft. rh e • co ro ft. CO X -v Ό XJ ~ * - ^ CO ro Il · CS Il <-Η U) • _N ro Il • "3 ro • Il rh 1-3 - E 1 = ** S Πΐ co Γ0 t-3 ft " , fctO I ^ ** - · O - ro Il * ft. »J» **** - ^ «. ^ 1-3 vo ft. N • Η ft. OJ XY · ^ ¹ O E CO 11 CO Nft. T ^ CO JJ • VO - ro <-i OJ - Il E co - X OJ VO X - VO β * - ^ • CP Ji ro π * · * E ro ~ · VD VD ro ro ^ ^ γ- * -% "^ »~» E * - ' ft. cn N - ο) co - T ¹ T Il O CT OJ - co EC 23 • Il ~ (CDCJ 7.18- (CDC] 3.031 <-) ro • CP CN r ^ n • 33 Ή t Il ~ .- * - OO Έ -. X  H h3 VO roCP Il cn xl j 3.061 , ^ * -Η * "3 QE-D OJ · η H co I (IH, Γ I (CDC) 3.05i Γ » OCPrp : Ο co (CLXJ VO (CDCJ (2H, 7.20- CO co ro VO 1 in ^ * V i-H J cn rh C ε in V O VO a in • "τ t-H in = co δ ο ^ C O H C Ί ο η - ;? • ρ 3 / / U O > r-S (β \ tu / / in Hurry \ - "~ OJ CD CO C ιη O ' VO · rh VO

table Il 1 (cont.) CN 145-146 (CDCl ₅ ) 1.29 (3H, t, J = 8Hz), 1.43 (9H, s), 3.06 (2H, 4f J = 8Hz), 6.39 (2U, singlet similar), 6.90-7.44 (3H, m) P- .0 63 (a) N / ^C 2 ^H 5 η 126-127 (CDCl ₅ ) 1.30GH, t, J = BHz), 1.44 (9H, s), 3.08 (2H, 4, J = 8Hz), 6.22 (2H, singlet similar), 7.20-7.64 (5H, m) 64 (a) A '"Cl ti 118-120 (CDCl ₅ ) 1.26C3H, t, J = 7Hz), 2.65 (3H, s), 2.97 (2H, q, J = 7Hz) _f 6.28 (1H, d, J = 8Hz), 6.46QH, bd, J = 8Hz), 7.0-7.6 (4H, m) 65 (a) F - \ g) η semi-solid (CDCl ₅ ) 6.28 (1H, d, J = 8Hz), 6.02-6.68 (2H, m), 7.11 (1H, bd, J = 8Hz), 7.20-7.44 (111, m) 66 (a) ^s ^ cH ₃ Il 106-107 (CDCl ₅ ) 2.89GH, s), 6.36QH, d, J = 8Hz), 6.36-6.68 (2H, m), 7.36-7.56 (1H, m), 8.14 (1H, bd, J = 8Hz), 8.5 KlH, s) 67 (a) π 101-104 (CDCl ₅ ) 2.86 (3H, s), 6.44 (1H, d, J = 8Hz), 6.9O-7.1O (1H, m), 7.22-7.45 (2 !!, m), 8.16 (1H, bd, J = 8Hz), 8.44 (IH, s) 68 (a) S

VO TJ ro vo • OJ - O _i _ro 'S VO O / ~ - / - in C / l C • -TJ a _Q a in - ^ OJ f * · # * ^ · - co , r-1 VO «- * co I a ^r O. r - VO · ro ro ^^ - \ ^^ / (O O • a VO OJ • VO VO Il · Eo ¹ p • η a  k · - M • "3" · «· Ro Il Εΰ ro rH · "% - -. ro J ₄ I -in - * - * I ^ CO ^ - * (/ J S ** N Il ^ a ^ 2 N oo a - ^ ro η ro ¹ ^ e Il in Il «· Il ** fH U ro T a ro ro H a ^ j- rh cn ro TO Il ca H ro Il I ""} - a VO "-» r * 3 · • "3 -» «- · rH »-» oo TJ - Tj a - -T? S rH «- * W a ^ a in -  in ~ i * "* rH - • -π m a · * £ • rH δ ^. vo · CO £ C OJ OJ O ri VO «- * ^ - ** p ^ - rH TJ co in ο «j ro in in r • OJ ι • -in Γ0. - OJ CO vo · • OJ • from a Ol ^ ΓΤ ** 03 VO · VO rH a ro (CDC] 7.30- (IH ₇ *. ι - a2 ft. W ro Il "* σ r- O - - I - OJ - ^. ro in w · U) · <- * * "^ O -S ν in VO - a - a -oo W · w a · • TJ ro .- ^ Γ0 O Il a - a - - OJ cn In ^ - ^ · h5 o ro ro ^. I vo co r- Ii - JC a3 - ^ a ν vo ro a (CDC) 6,771 (2H, n \ • Il • * -j TJ from office VD II ro O U) OJ l "3 OJ • Il • 1-3 li a * - \ jO a OJ O OJ f "3 rh S 'HT) [DCD] (CDC] (IH, 6.83 ' πα * ^ 0O TJ * ro O 'HT) [DCD] (CDC) (IH, (IH, rh O σ I ι c * \ ι cn , • in OJ ro OJ i-H O t-i cn ro ro ro rH I I rh <- { C O in I I co OJ in in OJ cn rh O C C ro ri ro ri C C Vl • Ρ U O W j fn I (U H H O) , Ω α) H C OJ "Jo

₅₁ 2833 2

The following formulation examples illustrate the preparation of the fungicide or fungicidal composition of the invention for agriculture and horticulture according to the invention. The active compounds are represented by the compound numbers given in Table 1. All parts are by weight.

Formulation Example 1 Dust

3 parts of compound No. 5, 20 parts of diatomaceous earth, 30 parts of terra alba and 47 parts of talc were pulverized and mixed uniformly to give 100 parts of dust.

Formulation example 2 Wettable powder

Thirty parts of Compound No. 19, 47 parts of diatomaceous earth, 20 parts of terra alba, 1 part of sodium lignosulfonate and 2 parts of sodium alkylbenzenesulfonate were uniformly pulverized and mixed to give 100 parts of a wettable powder.

Formulation Example 3 Emulsifiable concentrate

20 parts of Compound No. 6, 10 parts of cyclohexane, 50 parts of xylene and 20 parts of Sorpol (trade name for a surfactant of Toho Chemical Co., Ltd.) were uniformly blended to give 100 parts of an emulsifiable concentrate.

Formulation Example 4 Granules

1 part of compound no. 2, 78 parts of bentonite, 20 parts of talc and 1 part of sodium lignosulfonate were mixed and mixed with

a moderate amount of water was added and the mixture was kneaded. The kneaded mixture was granulated by a conventional method in an extrusion granulating machine and dried to give 100 parts of granules.

Formulation Example 5 Granules

5 parts of Compound No. 11, 1 part of polyethylene glycol nonylphenyl ether, 3 parts of polyvinyl alcohol and 91 parts of clay were uniformly mixed. Water was added, and the mixture was granulated and dried to obtain 100 parts of granules.

Formulation Example 6 Dust

2 parts of Compound No. 20, 40 parts of calcium carbonate and 58 parts of clay were uniformly mixed to give 100 parts of dust.

Formulation Example 7 Wettable powder

50 parts Compound No. 37, 40 parts talc, 5 parts. Sodium lauryl phosphate and 5 parts of sodium alkylnaphthalenesulfonate were mixed to give 100 parts of wettable powder.

Formulation Example 8 Wettable powder

50 parts of Compound No. 4, 10 parts of sodium lignosulfonate, 5 parts of sodium alkylnaphthalenesulfonate, 10 parts of white carbon and 25 parts of diatomaceous earth were mixed and pulverized to give 100 parts of wettable powder.

3 23

Formulation Example 9 Flowable agent

40 parts of Compound No. 10, 3 parts of carboxymethyl cellulose, 2 parts of sodium lignosulfonate, 1 part of dioctylsulfosuccinate sodium salt and 54 parts of water by wet-pulverizing by means of a sand grinder to give 10 parts of a flowable agent.

Formulation Example 10 Dust

2 parts of Compound No. 2, 2 parts of metalaxyl, 20 parts of diatomaceous earth, 30 parts of terra alba and 45 parts of talc were mixed and pulverized to give 100 parts of dust.

Formulation Example 11 Wettable powder

15 parts of Compound No. 4, 15 parts of oxadixyl, 47 parts of diatomaceous earth, 20 parts of terra alba, 1 part of sodium lignosulfonate and 2 parts of sodium alkylbenzenesulfonate were uniformly pulverized and mixed to give 100 parts of wettable powder.

Formulation Example 12 Wettable powder

10 parts of compound No. 6, 20 parts of metalaxyl, 55 parts of talc, 3 parts of sodium lauryl phosphate and 2 parts of sodium alkylnaphthalenesulfonate are mixed to give 100 parts of wettable powder.

Formulation Example 13 Wettable Powder

5 parts compound no. 2, 15 parts ofurace, 65 parts

83 3 2 3

Diatomaceous earth, 10 parts of white carbon, 5 parts of sodium lauryl phosphate and 2 parts of sodium alkylnaphthalenesulfonate were mixed to give 100 parts of wettable powder.

Formulation Example 14 Wettable powder

20 parts of Compound No. 2, 30 parts of benalaxyl, 35 parts of talc, 10 parts of white carbon, 3 parts of sodium lauryl phosphate and 2 parts of alkylnaphthalenesulfonate were mixed to give 100 parts of wettable powder.

Formulation Example 15 Emulsifiable concentrate

7 parts of Compound No. 6, 10 parts of Metalaxyi, 50 parts of phenoxyethanol, 28 parts of xylene, 3 parts of polyoxyethylene styrylphenyl ether and 2 parts of sodium alkylnaphthalenesulfonate were mixed to give 100 parts of emulsifiable concentrate.

Formulation Example 16 Granules

3 parts of Compound No. 17, 10 parts of Metalaxyi, 84 parts of clay, 1 part of polyethylene glycol nonylphenyl ether and 2 parts of polyvinyl alcohol were uniformly mixed and kneaded by adding a moderate amount of water. The kneaded mixture was granulated by means of a conventional method using an extrusion granulator and dried to give 100 parts of granules.

833 2 3

Formulation Example 17 Denutable powder

5 parts of compound No. 4, 45 parts of mancozeb, 27 parts of diatomaceous earth, 20 parts of terra alba, 1 part of sodium lignosulfonate and 2 parts of sodium alkylbenzenesulfonate were pulverized and mixed uniformly to give 100 parts of wettable powder.

Formulation Example 18 Wettable powder

10 parts of compound No. 18, 50 parts of mancozeb, 35 parts of talc, 3 parts of sodium auric acid phosphate and 2 parts of sodium alkylnaphthalenesulfonate were uniformly pulverized and mixed to give 100 parts of wettable powder.

Formulation Example 19 Wettable Powder

5 parts of Compound Nos. 2, 50 parts of captan, 40 parts of talc, 3 parts of sodium laurylphosphate and 2 parts of sodium alkylnaphthalenesulfonate were uniformly pulverized and mixed to 100 parts of wettable powder 7, \ i arise.

Formulation Example 20 Wettable powder

Ten parts of Compound No. 2, 50 parts of captafol, 35 parts of talc, 3 parts of sodium lauryl phosphate and 2 parts of sodium alkylnaphthalenesulfonate were uniformly pulverized and mixed to give 100 parts of wettable powder.

Formulation Example 21 Wettable Powder

5 parts of compound no. 6, 50 parts of folpet, 40 parts of talc, 3 parts of sodium lauryl phosphate and 2 parts of sodium alkyl

naphthalenesulfonate were uniformly pulverized and mixed to give a wettable powder.

Formulation Example 22 Wettable powder

5 parts of compound No. 4, 50 parts of basic copper chloride, 40 parts of talc, 3 parts of sodium lauryl phosphate and

2 parts of sodium alkylnaphthalenesulfonate were uniformly pulverized and mixed to give 100 parts of wettable powder.

Formulation Example 23 Wettable powder

7 parts of Compound No. 4, 50 parts of basic copper sulfate, 38 parts of talc, 3 parts of sodium lauryl phosphate and 2 parts of sodium alkylnaphthalenesulfonate were uniformly pulverized and mixed to give 100 parts of wettable powder.

Formulation Example 24 Wettable powder

5 parts compound no. 6, 50 parts TPN, 40 parts talc,

3 parts of sodium lauryl phosphate and 2 parts of sodium alkylnaphthalenesulfonate were uniformly pulverized and mixed to give 100 parts of wettable powder.

Formulation Example 25 Wettable powder

7 parts of compound No. 2, 50 parts of zineb, 3 parts of sodium lignosulfonate, 3 parts of sodium alkylnaphthalenesulfonate, 7 parts of white carbon and 30 parts of diatomaceous earth were uniformly pulverized and mixed to give 100 parts of wettable powder.

Formulation Example 26 Wettable powder

3 parts of compound no. 2, 50 parts of mancozeb, 3 parts of sodium lignosulfonate, 3 parts of sodium alkylnaphthalenesulfonate, 5 parts of white carbon, 16 parts of terra alba and 20 parts of diatomaceous earth were uniformly pulverized and mixed to give 100 parts of wettable powder.

Formulation Example 27 Wettable Powder

5 parts of compound No. 10, 50 parts of dichlofulanide, 40 parts of talc, 3 parts of sodium lauryl phosphate and 2 parts of sodium alkylnaphthalenesulfonate were uniformly pulverized and mixed to give 100 parts of wettable powder.

Formulation Example 28 Granules

1 part of Compound No. 2, 2 parts of polycarbamate, 85 parts of clay, 9 parts of diatomaceous earth, 1 part of polyethylene glycol nonylphenyl ether and 2 parts of polyvinyl alcohol were uniformly mixed and further kneaded by adding a moderate amount of water. The kneaded mixture was granulated by an ordinary method in an extrusion granulator and dried to give 100 parts of granules.

Formulation Example 29 Dust

2 parts of Compound No. 4, 2.0 parts of polycarbamate, 10 parts of diatomaceous earth, 20 parts of terra alba and 48 parts of talc were uniformly pulverized and mixed to give 100 parts of dust.

83 32

58

The following test examples illustrate the effectiveness of the compounds according to the invention as a fungicide for agriculture and horticulture and the fungicidal composition for agriculture and horticulture. The compounds used in these test examples are identified by the numbers given in Table 1 or the symbols in Table 2.

Table 2

A: Complex of manganese and zinc ethylene bis (dithiocarbamates) [mancozeb]

B: Zinc ethylene bis (dithiocarbamate) [zineb]

C: N-1 ', 1', 2 ·, 2-tetrachloroethylthio-4-cyclohexene-1,2-dicarboximide [captafol]

D: basic copper chloride E: tetrachloroisophthalonitrile [TPN] '

F: 3-chloro-N- (3-chloro-5-trifluoromethyl-2-pyridyl) -2,6-dinitro-4-trifluoromethylaniline [cichlofulanide]

G: N- (2,6-dimethylphenyl) -N- (2'-methoxyacetyl) alanine methyl ester [metalaxyl]

H: N- (2,6-dimethylphenyl) -N- (2-furoyl) -alanine ethyl ester [Furalaxyl]

I: N- (2,6-dimethylphenyl) -N- (phenylacetyl) alanine methyl ester [benalaxyl]

J: 2-chloro-N- (2,6-dimethylphenyl) -N- (tetrahydro-2-0X0-3-furanyl) -acetamide [Ofurace]

K: 2-methoxy-N- (2,6-dimethylphenyl) -N- (2-oxo-1,3-oxazolidin-3-yl) -acetamide [oxadixyl]

L: 3-chloro-N- (oxoperhydro-3-furyl) -eyelopropancarboxyanilide [Cyprofuram]

M: N- (α-cyanofurfuryl) -2, o-dichloropyridine-A-carboxylic acid amide

N: N- (a-cyanofurfuryl) -furan-2-carboxylic acid amide.

59

annotation

The compounds M and N are described in the above-mentioned, published British Patent Application BP-2095237. Compounds G to L are commercially available agricultural chemicals for controlling potato herb rot and cucumber downy mildew.

Test Example 1

Test for control of potato herb rot (preventive

Effect)

A chemical (obtained by preparing a wettable powder of each test compound according to the method of Formulation Example 8 and diluting it with water to a predetermined concentration) was applied to potatoes (variety: "Danshaku"; plant height about 25 cm) in pots in a greenhouse grew up, applied at a rate of 50 ml / 3 pots using a spray gun (1.0 kg / cm) and then air dried. A zoospore suspension of Phytophthora infestans cultured on a potato disk for 7 days was sprayed on the potato plant and inoculated. The test plant was kept at a temperature of 17 to 19 ⁰ C and a humidity of more than 9596 for 6 days, and then the extent of damage formation was examined.

For each of the leaves, one observed and evaluated the proportion of the area of the lesions and determined the index of the extent of the disease (disease index). For each of the test areas, the damage index was calculated according to the following equation.

Damage ₌ H + 5n ₃ ^{+ 2} * 2 + ¹ⁿ i + ^ o index N

60

23

The evaluation standards are the following:

Disease index proportion of the area of injury

0 o

1 1 - .5

2 6-25

3 26-50

4 51 or more

Number of leaves with a disease index of: Xi ₀ : 0

η ..: 1

_# ry

XV 4

Test Example 2

Test for the control of potato herb rot (healing

DE effect) ____-__ «__ - _-.

A zoospore suspension was prepared from Phytophthora infestans cultured on a potato disk for 7 days and inoculated by spraying on potatoes (variety: "Danshaku", plant height etv / a 25 cm) grown in pots in a greenhouse. The pots were left for 20 hours at 17 to 19 ⁰ C and then the chemical with a predetermined concentration (obtained by preparing a wettable powder of each test compound in accordance with the method of the FormulierungsbeispL ice 8 and diluting it with water to the predetermined concentration) to the Potato plants in an amount of 50 ml / 3 pots sprayed using a spray gun (1.0 kg / cm) and then dried in air. The pots were kept for 6 days at a temperature of 17 to 19 ⁰ C and a humidity of

61

3 * 3

more than 95%, and then the degree of damage formation was examined. The standards for evaluation and the method of indicating the damage index were as in Test Example 1.

Test example 3

Te, to check the wrong cucumber

(preventative effect) ·

The chemical was prepared in a predetermined concentration (obtained by preparing a wettable powder of each test compound according to the method of Formulation Example 8 and diluting it with water to a predetermined concentration) on cucumbers (variety: Sagami hanöiro) at the stage where two main leaves developed were) grown in pots in a greenhouse, sprayed in an amount of 30 ml / 3 pots using a spray gun (1.0 kg / cm) and dried in air. From the damage to the mildew-infected cucumber leaves, Pseudoperonospora cubenis was obtained and a spore suspension prepared using deionized water and inoculated by spraying on the cucumbers. Immediately thereafter, the inoculated pots were left at a temperature of 18 to 20 ^° C. and a humidity of more than 95 $ for 24 hours and then transferred to a greenhouse (at 18 to 27 ^° C.). Seven days later, the degree of damage formation was examined.

The standards for evaluation and the method of displaying the injury index were as in Test Example

Test Example 4

Test to control the downy mildew in the cucumber

(healing effect)

It was as in Test Example 3, a spoi "ensuspension of Pseudoperonospcra cubenis forth and inoculated by spraying on the same cucumber as used in Test Example 3. FIG. Immediately then were inoculated pots 24 h at a temperature of 18 to 20 ^0C and a The chemical was left at a predetermined concentration (obtained by preparing a wettable powder of each test compound according to the method of Formulation Example 8 and diluting it with water to the predetermined concentration) on the cucumber in an amount of 30 ml / 3 pots using a spray gun (1.0 kg / cm) is sprayed and dried in air. the pots were then transferred to a greenhouse (at 16 to 27 ⁰ C) and 7 days later with respect to the ftrades the formation of lesions examined.

The standards for evaluation and the method of displaying the injury index were as in Test Example 1.

Test Example 5

Test for control of tomato herb rot (soil drench)

The chemical was prepared in a predetermined concentration (obtained by preparing a wettable powder of each test compound according to the method of Formulation Example 8 and diluting it with water to a predetermined concentration) by soaking in the soil near the roots of the tomato (variety: Sekaiichi; 20 cm), which grew up in pots (7.5 cm in diameter) in a greenhouse, introduced with the aid of a pipette in an amount of 2 ml / pot. The pots were then left in the greenhouse for 5 days. A zoospore suspension of phyto-

63

Phthora infestans, which had been cultivated for 7 days on a cartouche before being cultivated. The suspension was then inoculated by spraying on the chemical-treated tomato plants. The test plants were left at a temperature of 17 to 19 ⁰ C and a humidity of more than 95%, and it was investigated the degree of damage.

The standards of evaluation and the method of indicating the damage index were as in Test Example 1.

In the above Test Examples, the concentration of the active ingredients was adjusted to 100 ppm in the case of spraying and 15 g / Ar in the case of soil saturation.

The results of the above test examples are shown in Table 3.

Test Example 6

Test to control the downy mildew in the cucumber

(healing effect and remaining effect)

Pseudoperonospora cubenis was taken from the damage to cucumber leaves (variety: Sagami hanjiro, at the stage where 3 main leaves were developed) grown in pots in a greenhouse, and a spore suspension was taken from the cucumbers by using deionized water Fungus. The spore suspension was inoculated by spraying on the cucumber plants. The inoculated pots were left in the greenhouse for 24 hours, and the chemical was brought to a predetermined concentration (obtained by preparing a wettable powder of each test compound according to the test method of Formulation Example 18 or 19 and diluting it to the predetermined concentration.

in an amount of 50 ml / 3 pots using a spray gun (1.0 kg / cm) and dried in air. Thereafter, the pots were transferred to a greenhouse (18 to 27 ⁰ C) and 10 and 18 days after examined the degree of damage. The results are shown in Table 4.

The standards of evaluation and the method of indicating the damage index were as in Test Example 1.

Test Example 7

Test for control of tomato herb rot (curative effect and remaining effect)

A zoospore suspension of Phytophthora infestans cultured for 7 days on a potato disk was prepared and inoculated by spraying on tomatoes (variety: Sekaiichi, plant height 20 cm) grown in pots in a greenhouse. The inoculated pots were left in a humid chamber of 16 ^° C. for 24 hours, and a chemical was sprayed at a predetermined concentration (obtained by preparing a wettable powder of each test compound according to Formulation Example 18 or 19 and diluting it with water to the predetermined concentration ) on the plants in an amount of 50 ml / 3 pots using a spray gun (1.0 kg / cm) and dried in air. The pots were placed in a greenhouse converted (10 to 20 ⁰ C), and 10 days and 11 days later they examined the degree of formation of lesions. The results are shown in Table 5.

The standards of evaluation and the method of indicating the damage index were as in Test Example 1.

65

Test report 8

Test for control of cucumber downy mildew (effect on a strain resistant to acylalanine chemicals )

The chemical was prepared in a predetermined concentration (obtained by preparing a wettable powder of each test compound according to Formulation Example 11 or 12 and diluting it with water to the predetermined concentration) on the cucumbers (variety: Sagami hanjiro; the stage in which the three main leaves were developed were) grown in pots in a greenhouse, sprayed in an amount of 50 ml / 3 pots using a spray gun (1.0 kg / cm) and dried in air. Both the acylalanine fungicide resistant and susceptible Pseudoperonospora cubenis strain were harvested from the cucumber leaf damage infected with downy mildew. They were mixed and a spore suspension was made from the mixture. The spore suspension was then inoculated on the treated cucumber leaves by spraying. The inoculated pots were left in a humid chamber for 24 h at 20 ⁰ C and then transferred to a greenhouse (18 to 27 ⁰ C). 10 and 18 days later, the degree of damage was assessed. The damage index was determined as in Test Example 1. The results are shown in Table 6.

Test Example 9 Test for the control of early tomato rot

The chemical was applied to the tomatoes (obtained by preparing a wettable powder of each test compound according to Formulation Example 18 and diluting it with water to the determined concentration) to the tomatoes (variety:

Sekaiichi; Plant height about 20 cm) grown in pots in a greenhouse, sprayed in an amount of 50 ml / 3 pots using a spray gun (1.0 kg / cm) and dried in air. A spore suspension of Alternaria solani cultured in a PSA medium was prepared and inoculated on the tomato in the pots by spraying. The pots were placed in a greenhouse (25 to 33 ⁰ C) was transferred, and 10 days later they examined the degree of formation of lesions. The damage index was determined as in Test Example 1 and the results are shown in Table 7.

The results given in Table 3 show that the compounds of the present invention have excellent control over plant diseases caused by oomycetes, such as potato herb rot, tomato herb rot and cucumber downy mildew, when applied by spraying alone, but also by soil saturation, whereas the comparative compounds M and N, which are regarded as relatively similar to the compounds produced according to the invention, show little or no control effect in these plant diseases. Furthermore, the compounds according to the invention have a preventive effect at much lower dosages than commercially available and widely used against these plant diseases zinc ethylene bis (dithiocarbamate) and tetrachloroisophthalonitrile and have a curative effect, these two commercially available chemicals do not have. Accordingly, the compounds of the invention can show a good control effect even if they are applied after infection of the crops with these diseases. Thus, this can greatly affect the disease control system for crops in

2 83.1 2

Farming and horticulture change and obviously contribute greatly to saving labor on the part of the breeder. Since the compounds of the present invention, when applied by soil soaking, have a good control effect, they enable the part of a plant, which is believed to be unreachable by the chemical by spraying alone, to be protected from disease.

The results given in Tables 4 and 5 show that the fungicidal composition according to the invention for agriculture and horticulture has a very superior control effect at lower dosages than is the case when applying dithiocarbamates, N-haloalkylthioimides, inorganic copper fungicides, TPN or Thiazole and IsothiazoIderivaten prepared according to the invention as active ingredients. Obviously, a synergistic effect is found due to the mixing, and the remaining effect is greatly enhanced.

The results given in Table 7 show that the agricultural and horticultural fungicidal composition of the present invention has an excellent control effect on a wide range of plant diseases caused by phytopathogenic fungi, such as Alternaria solani, Pseudoperonospora cubenis and Colletotrichum lagenarium, which are taxonomic of each other are removed. This means that in the cultivation of crops, application of the agricultural and horticultural fungicidal composition can control a variety of co-occurring plant diseases which are difficult to control simultaneously with the aid of conventional fungicidal compounds.

83,323

As shown in Table 6, the fungicidal composition of the invention for agriculture and horticulture has an excellent control effect against a wide range of plant diseases caused by Oomycetes, whose resistance to fungicidal chemicals is a serious problem. In particular, the fungicidal composition of the invention for agriculture and horticulture shows a much better control effect at lower dosages than in the case of the sole use of acylalanine fungicides (such as metalaxyl, furalaxyl, benalaxyl, oxadixyl, Ofurace and Cyprofuram), thiazole derivatives and isothiazole derivatives, the active ingredients this composition. Obviously, a synergistic effect appears as a result of mixing.

8332 ₃

Table 3

Test for diseases of the potato, cucumber and tomato

Test and damage index

Binding Potato Herb Fawn Seer Flour 'iWatherkraut no. rotten dew at d.Gurke rotten

by-passing, soothing 2 0 0 0 0 0 3 0 - 0 0 0 4 0 0 0 0 0 5 0 0 0 0 0 6 0 - 0 0 0 7 0 0 0 0 0 8th 0.3 - 0.2 0 0.2 9 0 0 0 0 0 10 0 - 0 0 0 11 0 0 0 0 0 12 0 0 0 0 0 13 0 - 0 0 0 14 0 0 0 0 0 15 0 0 0 0 0 16 0 - 0 0 0 17 0 0 0 0 0 18 0 - 0 0 0 19 0 0 0 0 0 20 0 0 0 0 0

70

2833

Table 3 (cont.)

21 0 - 0 0 0 22 0 0 0 0 0 25 0 - 0 0 0 26 0 0 0 0 - 32 0 0 0 0 0 33 0 0 0 0 0 34 0 0 0 0 0 35 0 0 0 0 0 36 0 - 0 0 0 38 0 0 0 0 - 39 0 - 0 0 0 40 0 0 0 0 - 41 0 - 0 0 0 42 0.5 0.6 0.3 0.3 - 43 1.2 - 1.2 1.0 - 44 0 0 0 0 - 45 0 0 0 0 - 46 0 -. 0 0 0 47 0 0 0 0 - 48 0 0 0 0 - 50 0 0 0 0 0

833 2 3

Table 3 (cont.)

51 0 0 0 0 0 52 0 0 0 0 0 53 0 0 0 0 0 54 0 0 0 0 0 55 - - 0 0.5 - 56 - - 0.3 0.5 - 58 0 - 0 0 - 59 0 0 0 0 0 60 0 0 0 0 - 61 0 0 0 0 - 62 0 0.4 0 0 - 65 - - 0 0 - 71 - - 0 0.2 - 73 - - 0 0.2 - M 2.0 2.4 2.1 2.4 3.2 N 2.0 2.5 1.9 2.3 3.0 B 2.3 3.8 2.0 3.4 3.8 e 2.4 3.6 2.5 3.7 3.7 untreated 3.7 3.8 3.7 3.7 3.8

72

Table 4 Test for cucumber downy mildew

Test compound no.

Concentration of the active substance (ppm)

Damage index IO days 18 days later later

2 100 50 0 0 0.7 1.0 3 100 50 0 0 1.0 1.3 4 100 50 0 0 0.7 1.0 5 100 50 0 0 1.0 1.0 6 100 50 0 0 1.0 1.5 17 100 50 0 0 0.8 '0.8 18 100 50 0 0 0.6 0.7 A 500 2.9 2-9. C 500 3.0 , .3.0 D 500 3.5 3.7 e 500 3.0 3.1 F 500 2.7 2.8 2 + A 100 + 500 50 + 500 0 0 0 0 3 + A 100 + 500 50 + 500 0 0 0 0 4 + A 100 + 500 50 + 500 0 0 0 0 5 + A 100 + 500 50 + 500 0 0 0 0

73

Table 4 (cont.)

2 + C 100 + 500 50 + 500 1 0 T 0 0 6 + C 100 + 500 50 + 500 0 0 0 0 17 + C 100 + 500 50 + 500 0 0 0 0 18 + C 100 + 500 50 + 500 0 0. 0 0 3 + D 100 + 500 50 + 500 0 ö .. 0 0.5 5 + D 100 + 500 50H500 0 0 0 0.2 18 + D 100 + 500 50 + 500 ... 0 .0 0.1 0.5 2 + E 100 + 500 50 + 500 0 0 0. 0 6 + E 100 + 500 ..50 + 500 0 0 0 0 17 + E 100 + 500 50 + 500 0 0. 0 0 18 + E 100 + 500 50 + 500 0 0 0. 0 2 + F 100 + 500 50 + 500 0 o 0 0. 4 + F 100 + 500 50 + 500 0 0 0 0 5 + F 100 + 500 50 + 500 0 0 0 0 unbehin dert 3.7. 3.7

Table 5 Tomato herb rot test

test compound 2 concentration SchädiKungsindex 10 days later No. 6 of the active substance (vvm) IO days later 0.8 1.2 12 100 50 0 0 1.1 1.4 13 100 50 0 0 0.7 1.0 50 100 50 0 0 0.6 0.9 54 100 50 0 0 1.0 1.0 A 100 50 0 0 1. ¹ O 1.8 C 100 50 0 0 3.5 D 500 3.3 3.6 e 500 3.5 3.5 F 500 3.5 3.4 2 + A 500 3.0 3.0 6 + A 500 3.0 0 0 13 + A 1004500 50 + 500 0 0 0 0 54 + A 100 + 500 50 + 500 0 0 0 0 2 + C 100 + 500 50 + 500 0 0 0 0.4 ' 100 + 500 50 + 500 0 0 0: o. . 100 + 500 -50 + 500 0 o

Table 5 (cont.)

unbehan delt.

76

813

Table 6 Test for cucumber downy mildew

Test compound no.

Concentration injury index of the drug 10 days 18 days (ppm) later later

2 + G

4 + G

5 + G

6 + G

200 100

200 100

200 100

200 100

200 100

200 100

200 100

200 100

200 100

200 100

50 + 50 50 + 100

50 + 50 50 + 100

50 + 50 50 + 100

50 + 50 50 + 100

0 0

0 0

0 0

0 0.5

2.4 2.4

2.2 2.5

1.7 1.6

2.0 2.5

1.5 1.9

1.3 1.3

0 0

0 0

0 0

0 0

0.6 1.1

1.0 1.5

0.9 1.5

2.0 2.0

3-0 3.5

2.8 3.5

2.0 2.2

3.1 3.3

1.8 2.5

2.0 2.8

0 0

0 0

0 0

0 0

77

8.13 2

Table 6 (cont.)

2 + H 50 + 50 50 + 100 0 0 0 0 4 + H 50 + 50 50 + 100 0 0 0 0 5 + H 50 + 50 50 + 100 0 0 0 0 6 + H 50 + 50 50 + 100 0 0 0.2 0.2 2 + 1 50 + 50 50 + 100 0 0 0 0 4 + 1 50 + 50 50 + 100. 0 0 0 0 5 + 1 50 + 50 50 + 100 0 o 0 0 6 + 1 50 + 50 50 + 100 0 0 0.3 0.1 2 + J 50 + 50 50 + 100 0 0 0 0 4 + J 50 + 50 50 + 100 0 0 0 0 5 + J 50 + 50 50 + lCO 0 0 0 0 6 + J 50 + 50 50 + 100 0 0 0.3 0.1 2 + K 50 + 50 50 + 100 0 0 0 0 4 + K 50 + 50 50 + 100 0 0 0 0 5 + K 50 + 50 50 + 100 0 0 0 0

78

Table 6 (cont.)

6 + K 2 + L 4 + L 5 + L 6 + L

untreated

50 + 50 50 + 100

50 + 50 50 + 100

50 + 50 50 + 100

50 + 50 50 + 100

50 + 50. 50 + 100

0 0

0 0

0 0

3.4

0.3 0.2

0 0

0 0

0 0

0 0

3.5

79

Table 7 Tomato early blight test

Test concentration Concentration of the active substance no. (ppm) index

2 100 2.6 • 3 100 3.0 4 100 3.1 6 100 3.0 12 100 2.7 18 100 2.9 A 500 0.8 e 500 0.7. F 500 ... l.o 2 + A 100 + 500 0 3 + A 100 + 500 O.. 12 + A .100 + 500 0 4 + E .100 + 500 , 0 6 + E 100 + 500 0 18 + E 100 + 500 0 2 + F 100 + 500 0 3 + F 100 + 500 0 12 + F 100 + 500 0 untreated - ?

Claims (19)

80 ^ 8 3 3 claims A process for producing an amide derivative represented by the following general formula (IV) CN / _TV ONHCH ^ ^K ' wherein one of X and Y represents a sulfur atom and the other represents a carbon atom, each of the radicals 1 2
R and R represent a hydrogen atom, a halogen atom, an alkyl group having 1 to 6 carbon atoms, a halomethyl group or a phenyl group, and R represents an alkenyl group having 2 to 6 carbon atoms, a haloalkenyl group having 2 to 4 carbon atoms, a furyl group, a thienyl group, an alkoxy group with 1 to 4 carbon atoms, an alkylthio group having 1 to 4 carbon atoms, an alkynyloxy group having 3 to 5 carbon atoms, an alkynylthio group having 3 to 5 carbon atoms, a pyrazolyl group or an unsubstituted or halogen-substituted phenyl group, that is the reaction of a heterocyclic, 5-membered carboxylic acid of the following general formula (II) (II) 1 2
wherein X, Y, R and R are as defined above, or their reactive derivative with an aminoacetonitrile of the following general formula (III) 28.Ί3 23 81 CN
H ₂ N »CN (III) wherein R 1 is as defined above or a salt thereof. 2 »Process for the preparation of an amide derivative of the following general formula (IV) R ¹ " _x R ^{2 x} - ' ^ CN ^ "3 wherein one of X and Y represents a sulfur atom and the other represents a carbon atom, each of the radicals 1 2
R and R represent a hydrogen atom, a halogen atom, an alkyl group having 1 to 6 carbon atoms, a halomethyl group or a phenyl group, and R represents an alkoxy group having 1 to 4 carbon atoms, an alkyl + molar group having 1 to 4 carbon atoms, an alkynyloxy group having 3 to 5 Carbon atoms, an alkynylthio group having 3 to 5 carbon atoms or a pyrazolyl group, the halogenation of an N-cyanomethylcarboxylic acid amide of the following general formula (V) ^ N ' 1 2
wherein X, Y, R and R are as defined above to form an intermediate of the following general formula (Vl) R _χ R ² (VI) YQ 9-f-CONHCH * CNN Hai 82 1 2
wherein X, Y, R and R are as defined above and Hai is a halogen atom, and the subsequent reaction of the compound of the general formula (Vl) with a compound of the following general formula (VII) HR ³ (VII) wherein R is as defined above. 3. Process for the preparation of an amide derivative of the following general formula (VIII) R ¹ R ² f (VIII) ^R where X and Y represent a sulfur or carbon atom 1 2
each of R and P represents a hydrogen atom, a halogen atom, an alkyl group having 1 to 6 carbon atoms, a halomethyl group or a phenyl group, and R 1 represents an alkenyl group having 2 to 6 carbon atoms, a haloalkenyl group having 2 to 4 carbon atoms a furyl group, a thienyl group, an alkoxy group having 1 to 4 carbon atoms, an alkylthio group having 1 to 4 carbon atoms, an alkynyloxy group having 3 to 5 carbon atoms, an alkynylthio group having 3 to 5 carbon atoms, a pyrazolyl group or an unsubstituted or halogen-substituted phenyl group, which involves subjecting a compound of the following general formula (IV) R ¹ _χ R ² 8:13 pm 23 83 wherein X, Y, R, R and R ^ are as defined above, comprising an addition reaction with hydrogen sulfide. A fungicidal composition for agriculture and horticulture, comprising a diluent or a carrier and / or an adjuvant and as an active ingredient an effective amount of at least one amide derivative of the following general formula (I) R ¹ _χ R ² _χ
^ ^Z Y Qj) J-CONHCHC ^ ₃ in which one of the radicals X and Y represents a sulfur atom and the other represents a carbon atom, Z denotes a nitrile 1 or thioamide group, each of R and R represents a hydrogen atom, a halogen atom, an alkyl group having 1 to 6 carbon atoms, a halomethyl group or χ represents a phenyl group and R represents an alkenyl group having 2 to 6 carbon atoms, a haloalkenyl group having 2 to 4 carbon atoms, a furyl group, a thienyl group, an alkoxy group having 1 to 4 carbon atoms, an alkylthio group having 1 to 4 carbon atoms, an alkinyloxy group having 3 to 5 carbon atoms, an alkynylthio group having 3 to 5 carbon atoms, a pyrazolyl group or an unsubstituted or halo-substituted phenyl group. A fungicide for agriculture and horticulture according to claim 4, wherein the proportion of the amide derivative represented by the general formula (I) is 1 to 90% by weight. 6. A fungicidal composition for agriculture and horticulture, comprising a diluent or a carrier and / or an adjuvant and as the first active ingredient at least one amide derivative of the following general formula (i) ONHCH ^ 3 ^R in which one of the radicals X and Y represents a sulfur atom and the other represents a carbon atom, Z denotes a nitrile 1 ? or thioamido group, each of R and R represents a hydrogen atom, a halogen atom, an alkyl group having 1 to 6 carbon atoms, a halomethyl group or a phenyl group and R ^ represents an alkenyl group having 2 to 6 carbon atoms, a haloalkenyl group having 2 to 4 carbon atoms, a furyl group, a thienyl group, an alkoxy group having 1 to 4 carbon atoms, an alkylthio group having 1 to 4 carbon atoms, an alkynyloxy group having 3 to 5 carbon atoms, an alkynylthio group having 3 to 5 carbon atoms, a pyrazolyl group or an unsubstituted or halogen substituted phenyl group, and as the second active ingredient, at least one component selected from acylalanine fungicides having control activity with respect to plant diseases caused by oomycetes, dilithiocarbamate fungicides, N-haloalkylthioimide fungicides, inorganic copper fungicides, tetrachloroisophthalonitrile, dichlofluanid and fluazinam. A composition according to claim 6, in which the second active ingredient is at least one acylalanine fungicide having control activity over oomycete-induced plant diseases. 8. The composition according to claim 6, wherein the second active agent is at least one component selected from dithiocarbamate fungicides, N-Haloalkylthloimid fungicides, inorganic copper fungicides, tetrachloroisophthalonitrile, dichlofluanide and fluazinam. A composition according to claim 6, wherein the second active ingredient is a dithiocarbamate fungicide. A composition according to claim 6, wherein the second active ingredient is an N-haloalkylthioimide fungicide. A composition according to claim 6, wherein the second active ingredient is an inorganic copper fungicide. 12. The composition according to claim 6, wherein the second active ingredient is tetrachloroisophthalonitrile. 13. The composition according to claim 6, wherein the second active ingredient is dichlofluanid. 14. A composition according to claim 6, wherein the second active ingredient is fluazinam. A method of controlling plant diseases which comprises applying a compound prepared according to the method of claim 1 to plant pathogenic fungi or to its location. 16. A method of controlling plant diseases, which comprises applying the fungicide or a fungicidal composition according to any one of claims 4 to 14 to plant pathogenic fungi or their location. 17. The method according to claim 15, wherein the amide derivative of the general formula (1) is applied as active ingredient in an amount of 0.05 "to 1 kg / ha. A process according to claim 16, wherein the fungicide or fungicidal composition according to any one of claims 4 to 14 is applied in an amount of 0.2 to 5 kg / ha. ^A 2 8:13 2 Patent aaoprlioho A fungicidal composition for agriculture and horticulture, characterized in that it comprises a yden-center or a carrier and / or an adjuvant, and the active ingredient is an effective amount of at least one amino derivative of the following general formula (I) OOHHOH (X) in which one of the radicals X and Y represents a sulfur atom and the other a carbon atom, Z is a Ni tr U- • ι ρ or thioamido group, each of R and R represents a hydrogen atom, a halogen atom, an alkyl group having 1 to 6 carbon atoms, a halomethyl group or phenyl group, and Br represents an alkenyl group having 2 to 6 carbon atoms, a haloalkenyl group having 2 to 4 carbon atoms, a furyl group, a thienyl group, an alkoxy group having 1 to 4 carbon atoms, an alkylthio group having 1 to 4 carbon atoms, an alkynyloxy group having 3 to 5 carbon atoms, an alklnylthio group having 3 to 5 carbon atoms, a pyrazolyl group or an unsubstituted or halo-substituted phenyl group Fungicide for agriculture and horticulture according to Claim A »characterized in that the proportion of the amide derivatives of the general formula (I) is up to 30% by weight«