KR100232856B1 - Novel amino acid amide derivatives - Google Patents

Abstract

The present invention relates to a novel amino acid amide derivative represented by the following general formula (I), a method for preparing the same, and a composition for inhibiting the onset by plant pathogens, comprising the compound of the general formula (I) as an active ingredient. .

Wherein X ₁ and X ₂ each independently represent hydrogen, halogen, methyl or methoxy, R ₁ represents hydrogen, phenyl or —CHR ₂ R ₃ (where R ₂ represents hydrogen or methyl, and R ₃ is Hydrogen, C ₁ -C ₃ alkyl, hydroxy, thiol, C ₁ -C ₂ alkylthiomethyl, phenyl or hydroxy phenyl), R ₄ represents hydrogen or propylene with R ₁ , R ₅ represents C ₁ -C ₃ alkyl or aryl unsubstituted or substituted by methyl, halogen or halogen substituted methyl.

Description

New Amino Acid Amide Derivatives

The present invention relates to a novel amino acid amide derivative represented by the following general formula (I) and a method for producing the same.

Wherein X ₁ and X ₂ each independently represent hydrogen, halogen, methyl or methoxy, R ₁ represents hydrogen, phenyl or —CHR ₂ R ₃ (where R ₂ represents hydrogen or methyl, and R ₃ is Hydrogen, C ₁ -C ₃ alkyl, hydroxy, thiol, C ₁ -C ₂ alkylthiomethyl, phenyl or hydroxy phenyl), R ₄ represents hydrogen or propylene with R ₁ , R ₅ represents C ₁ -C ₃ alkyl or aryl unsubstituted or substituted by methyl, halogen or halogen substituted methyl.

The compound of general formula (I) according to the present invention shows an excellent effect in inhibiting the onset by phytopathogens, in particular fungi phytopathogens. Plant diseases in which the compounds of the present invention are effective include Pyricularia grisea, Rhizoctonia solani, Tomato blight (Phytophthora infestans), Plasmopara viticola, Cucumber gray mold (Botrytis cinerea) , Puccinia recondita, Erysiphe graminis, Venturia inequalis, etc., as well as powdery mildew, rust, or incomplete rot fungi (Deuterom-ycete) Plant diseases caused by Ascomycete or Basidiomycete may be mentioned. Therefore, the present invention also relates to a composition for inhibiting the onset by phytopathogens, which comprises the compound of the general formula (I) as an active ingredient.

Late blight, Downy mildew and Asymptomatic fungi have a rapid onset of resistance, and resistance to existing drugs is currently a problem. Therefore, development of inhibitors of pathogenesis by a new plant phytopathogen having high activity and low toxicity is required. . In this regard, it has already been reported that derivatives containing amino acids in the molecule have an effect on the control of late blight, Downy mildew (DE 4203084 A1, DE 3936296 A1, EP 0398072 A2, EP 0493683 A1). However, these existing amino acid derivatives showed excellent bactericidal activity against late blight and downy mildew, whereas gray mold disease could not be controlled.

Therefore, the present inventors have been able to control late blight and fungal disease, and at the same time can control gray mold, and especially to develop a fungicide that can be usefully used for gray mold, and as a result has excellent bactericidal activity. Compounds represented by the following general formula (A) each having a methoxy group substituted in the benzyl position (see Korean Patent Application No. 96-5863) and the following general formula including a t-butoxycarbonylamide group substituted with an oxime ether group in the benzyl position An amino acid amide derivative such as the compound of formula (B) (see Korean Patent Application No. 96-31437) has been filed.

을 나타내며, 여기서 R₄는 사이클로프로필, 2-클로로메틸, C₁-C₄알킬, C₁-C₄알콕시, C₁-C₃할로알콕시, 알릴옥시, 아릴옥시 또는 벤질옥시를 나타낸다.Wherein X ₁ and X ₂ each independently represent hydrogen, methoxy, methyl or halogen, or when X ₁ and X ₂ are attached to adjacent carbon atoms on a benzene ring, they are bonded to each other to form a methylenedioxy group And R ₁ represents hydrogen, methyl, 2-propyl, 2-methylpropyl, 2-butyl, phenyl or benzyl, R ₂ represents propylene with hydrogen or R ₁ and R ₃ represents hydrogen or

Wherein R ₄ represents cyclopropyl, 2-chloromethyl, C ₁ -C ₄ alkyl, C ₁ -C ₄ alkoxy, C ₁ -C ₃ haloalkoxy, allyloxy, aryloxy or benzyloxy.

Wherein X ₁ and X ₂ each independently represent hydrogen, a halogen, a methyl group or a methoxy group, R ₁ represents hydrogen, an alkyl group which is (C _1-4 ), a phenyl group or a benzyl group, and R ₂ represents hydrogen or R ₁ And a propylene group together.

The present invention has been made as a result of continuing research from this prior invention, the compound of formula (I) is late blight, downy mildew, gray mold, as well as blast (Pricularia grisea), rice leaf blight (Rhizoctonia solani), etc. The present invention was completed by confirming the fact that it shows good efficacy.

Hereinafter, the configuration of the present invention will be described in detail.

An object of the present invention is to provide a novel amino acid amide derivative represented by the following general formula (I).

Wherein X ₁ and X ₂ each independently represent hydrogen, halogen, methyl or methoxy, R ₁ represents hydrogen, phenyl or —CHR ₂ R ₃ (where R ₂ represents hydrogen or methyl, and R ₃ is Hydrogen, C ₁ -C ₃ alkyl, hydroxy, thiol, C ₁ -C ₂ alkylthiomethyl, phenyl or hydroxyphenyl), R ₄ represents hydrogen or propylene together with R ₁ , R ₅ represents C ₁ -C ₃ alkyl or aryl unsubstituted or substituted by methyl, halogen or halogen substituted methyl.

Among the compounds of the general formula (I) which show excellent effects in the fight against plant pathogens, preferred compounds are each independently X ₁ and X ₂ represent hydrogen or chloro, and R 1 represents water, phenyl or -CHR ₂ R ₃ (wherein R 2 represents hydrogen or methyl, R ₃ represents hydrogen, methyl, ethyl, isopropyl, hydroxy, thiol, methylthiomethyl, phenyl, or hydroxyphenyl), and R ₄ represents hydrogen or R Propylene is shown together with _1, and R ₅ is a compound representing methyl.

Since the compound of formula (I) contains a double bond between carbon and nitrogen, it may exist in two geometric isomeric forms such as (E) and (Z) -isomers. In the compound of formula (I), when R ₁ is not a hydrogen atom, the carbon atom substituted with R ₁ forms an asymmetric carbon, so the compound of formula (I) is an enantiomer such as R or S form or It may be present in the form of a mixture. Accordingly, the scope of the present invention includes such geometric isomers, stereoisomers or mixtures thereof.

On the other hand, the compound of the general formula (I) according to the present invention, the amino acid derivative of the general formula (II) to the general formula (III) in the presence of a base and a coupling agent in a solvent, It can be prepared by condensation with 2- (N-methoxyimino) -2-phenyl-ethylamine.

Scheme 1

In the above scheme, X ₁ , X ₂ , R ₁ , R ₄ and R ₅ are as defined above.

In the reaction, examples of the solvent include aromatic hydrocarbons such as benzene, toluene and xylene, halogenated hydrocarbons such as dichloromethane, 1,2-dichloroethane and chloroform, diethyl ether, dioxane, 1,2-dimethoxyethane, Ethers such as tetrahydrofuran, acetone, methyl ethyl ketone, ketones such as cyclohexanone, nitriles such as acetonitrile, propionitrile, esters such as methyl acetate, ethyl acetate, N, N-dimethylformamide, N One or more selected from polar solvents such as, N-dimethylacetamide and dimethyl sulfoxide may be used, and the base may be pyridine, 4-dimethylaminopyridine, triethylamine, N, N-dimethylaniline, tributylamine And one or more selected from organic bases such as N-methylmorpholine can be used, and as a coupling agent, dicyclohexylcarbodiimide (DCC), 1-ethyl-3- (3-dimethylamime One or more selected from carbodiimides such as nopropyl) carbodiimide (EDC) and inorganic dehydrating agents such as silicon tetrachloride can be used in a mixed state with 1-hydroxybenzotriazole. In particular, 1-hydroxybenzotriazole is necessary to maintain the chirality of amino acid derivatives used as starting materials. The reaction proceeds for 10 minutes to 24 hours at a temperature of -30 to 70 ° C, preferably at a temperature of -10 to 30 ° C.

On the other hand, the amino acid derivative of formula (II) used as a starting material in the reaction can be prepared and used according to the method described in the literature (see JACS Vol. 106, 1095, 1984). In addition, 2- (N-methoxyimino) -2-phenyl-ethylamine of the general formula (III) used as the reactant may be prepared and used according to the method of Scheme 2 below.

Scheme 2

In the above scheme, X ₁ and X ₂ are as defined above.

Compound (6) is obtained by carrying out an oxime etherification reaction with respect to starting compound (7). In this case, inorganic bases such as sodium hydroxide, potassium hydroxide, sodium carbonate, potassium carbonate, sodium hydrogen carbonate, potassium hydrogen carbonate, sodium hydride and potassium hydride may be used. Particularly, metal hydrides such as sodium hydride and potassium hydride are preferable. Examples of the solvent include ethers such as diethyl ether, dioxane, 1,2-dimethoxyethane and tetrahydrofuran, ketones such as acetone, methyl ethyl ketone and cyclohexanone, and nitriles such as acetonitrile and propionitrile. Alcohols such as methanol, ethanol or polar solvents such as N, N-dimethylformamide, N, N-dimethylacetamide, and dimethyl sulfoxide may be used, but preferably, polar solvents of alcohols or amides are used.

Compound (5) can be prepared by carrying out bromination reaction with respect to compound (6) obtained above. As bromination reagent, bromine, hydrobromic acid, N-bromosuccinimide, copper bromide (II) can be used, and as a solvent, aromatic hydrocarbons such as benzene, toluene, xylene, dichloromethane, 1,2-dichloroethane , Halogenated hydrocarbons such as chloroform, carbon tetrachloride, and one or more selected from esters such as methyl acetate and ethyl acetate may be used, and the reaction is performed at a temperature of 0 to 100 ° C. according to the type of brominated reagent selected.

Imino azido compound (4) is obtained by performing an azido reaction on compound (5). The azidolation reaction is carried out at 0 to 30 ° C. using sodium azide in an excess of 5 equivalents or more in polar solvents such as N, N-dimethylformamide, N, N-dimethylacetamide, and dimethyl sulfoxide. In addition, the reduction of carbonyl is performed by using sodium borohydride, lithium aluminum hydride, boron hydride, or the like as a reducing agent, or by carrying out catalytic hydrogenation, and as a solvent, diethyl ether, dioxane, 1.2-dimethoxyethane, tetra Ethers such as hydrofuran are preferably used, and the reaction can be carried out at a temperature in the range of 0 to 80 ° C.

In the reduction reaction of the imino azido compound (4) to the primary amine compound (IIIa) or (IIIb), the reaction is carried out using lithium aluminum hydride, triphenylphosphine, hydrogen sulfide, or the like as a reducing agent, or a catalytic hydrogenation reaction, zinc, or the like. Reduction reaction using a metal is used. In this case, at least one selected from halogenated hydrocarbons such as dichloromethane, 1,2-dichloroethane and chloroform, ethers such as diethyl ether, dioxane, 1.2-dimethoxyethane and tetrahydrofuran may be used. It is also possible to add water as needed. Hydrolysis of the resulting phosphonium-added product in the presence of a base in a solvent yields a mixture of compounds of the general formulas (IIIa) and (IIIb), which is separated by silica gel column chromatography to obtain 2- (N- The (E) and (Z) -isomers of methoxyimino) -2-phenyl-ethylamine can be separated, respectively.

The preparation methods described above will be described in more detail based on the following examples, and typical examples of the compound of general formula (I) synthesized according to these methods are shown in Table 1 below.

TABLE 1

The compound of general formula (I) finally obtained according to the preparation method according to the present invention exhibits excellent efficacy in suppressing the onset by various phytopathogens as mentioned above. Therefore, according to the present invention, there is provided a composition for inhibiting the onset by phytopathogens, which comprises a compound of formula (I) as an active ingredient together with a carrier commonly used in the pesticide field.

In the preparation of the composition of the present invention, as a carrier usable, one or more selected from kaolin, bentonite, talc and xylene may be mentioned, and the formulation of the composition prepared with such a carrier may include a hydrate, emulsion, powder and powder. Mention may be made of weakening or granulating agents.

In addition, in suppressing the onset by phytopathogens, the composition according to the present invention is preferably applied in the range of 250 to 500 g / ha based on the active compound.

Hereinafter, the present invention will be described in more detail based on the following Preparation Examples and Examples. However, this is only for better understanding of the present invention, and the scope of the present invention is not limited to these examples in any sense.

Preparation Example 1: Synthesis of 2-amino-1- (2,4-dichloro-phenyl) -ethanone O-methyloxime

[Step 1: Preparation of 1- (2,4-dichloro-phenyl) -ethanone O-methyloxime]

18.7 g of 2,4-dichloroacetophenone, 9.07 g of methoxyamine hydrochloride and 68.2 g of potassium carbonate were added to 250 ml of methanol, stirred at reflux for 12 hours, cooled, and the methanol was evaporated under reduced pressure. Water was added to the reaction mixture, followed by extraction with ethyl acetate, followed by drying over anhydrous magnesium sulfate and evaporation to give 18.6 g (yield 86%) of the title compound as a white solid.

[Step 2: Preparation of 2-bromo-1- (2,4-dichloro-phenyl) -ethanone O-methyloxime]

15.7 g of 1- (2,4-dichloro-phenyl) -ethanone O-methyloxime and 12.8 g of N-bromosuccinimide obtained in Step 1 were added to 200 ml of carbon tetrachloride, stirred at reflux for 10 hours, and then cooled. Carbon tetrachloride was evaporated under reduced pressure. Water was added to the reaction mixture, followed by extraction with ethyl acetate. The reaction solution was dried over anhydrous magnesium sulfate and evaporated to give 15.0 g (yield 70%) of the title compound as a yellow liquid.

[Step 3: Preparation of 2-azido-1- (2,4-dichloro-phenyl) -ethanone O-methyloxime]

9.01 g of 2-bromo-1- (2,4-dichloro-phenyl) -ethanone O-methyloxime obtained in step 2 was dissolved in 100 ml of dimethylformamide, and then 9.86 g of sodium azide was added to 0. It was added at ℃ and stirred for 1 hour at the same temperature. Poured a large amount of water into the reaction solution, extracted with ethyl acetate, dried over anhydrous magnesium sulfate and evaporated to give 7.8g (yield 99%) of the title compound in a yellow liquid.

[Step 4: Preparation of 2-amino-1- (2,4-dichloro-phenyl) -ethanone O-methyloxime]

6.11 g of 2-azido-1- (2,4-dichloro-phenyl) -ethanone O-methyloxime obtained in step 3 was dissolved in 100 ml of tetrahydrofuran, and then 1 to 2 drops of water were added thereto. 6.80 g of triphenylphosphine was added thereto, followed by stirring for about 8 hours, and 30 ml of 2N aqueous sodium hydroxide solution was added thereto, followed by stirring for 2 hours while refluxing. The reaction solution was cooled, tetrahydrofuran was removed under reduced pressure, diethyl ether was poured out, and extracted with 2N hydrochloric acid solution. The aqueous layer was basified to pH 11 with sodium hydroxide, extracted again with diethyl ether, dried over anhydrous sodium sulfate and evaporated. The residue was subjected to silica gel column chromatography (eluent: hexane / ethyl acetate / triethylamine = 5/2 / 0.5, v / v / v) to separate the E and Z isomers, respectively. The solvent was evaporated under reduced pressure to give 2.48 g (yield 45%) of the yellow liquid Z-form title compound and 2.03 g (37% yield) of the E-form title compound.

E-form ¹ H-NMR (CDCl ₃ ) δ 7.44 (s, 1H), 7.30 (s, 2H), 3.99 (s, 3H), 3.82 (s, 2H), 1.50 (br, 2H)

Z-form ¹ H-NMR (CDCl ₃ ) δ 7.45 (d, 1H), 7.32-7.28 (m, 1H), 7.08 (d, 1H), 3.85 (s, 3H), 3.65 (s, 2H), 1.49 (br, 2H)

Preparation Example 2 Synthesis of 2-amino-1-phenyl-ethanone O-methyloxime

Except for using 20 g of acetophenone instead of 2,4-dichloroacetophenone as starting materials, the procedure was the same as in Preparation Example 1, and 3.28 g of Z-form title compound (total yield 12δ) and E-form title compound were obtained. 3.61 g (13% total yield) of each were obtained.

E-form ¹ H-NMR (CDCl ₃ ) δ 7.60-7.40 (m, 5H), 4.02 (s, 5H), 3.84 (s, 2H), 1.53 (br, 2H)

Z-form ¹ H-NMR (CDCl ₃ ) δ 7.65-7.42 (m, 5H), 3.91 (s, 3H), 3.60 (s, 2H), 1.47 (br, 2H)

Example 1 Synthesis of (E, L) -2-methanesulfonylamino-N- [2-methoxyimino-2-phenyl-ethyl] -3-methyl-butyramide (1)

0.131 g of N-methanesulfonyl L-valine, 0.128 g of 1- (3-dimethylaminopropyl) -3-ethylcarbodiimide hydrochloride, 0.091 g of 1-hydroxybenzotriazole hydrate and 0.093 ml of triethylamine were dimethylform To 5 ml of amide was added and stirred at 0 ° C for 10 minutes. 0.100 g of E-2-amino-1-phenyl-ethanone O-methyloxime was added to the reaction solution, and the mixture was stirred for 2 hours. Poured a large amount of water, extracted with ethyl acetate, dried over anhydrous magnesium sulfate and evaporated to give 0.164g (yield 79%) of the title compound.

Example 2 Synthesis of (E, L) -N- [2- (2,4-Dichloro-phenyl) -2-methoxyimino-ethyl] -2-methanesulfonylamino-acetamide (2)

0.072 g of N-methanesulfonyl L-glycine, 0.090 g of 1- (3-dimethylaminopropyl) -3-ethylcarbodiimide hydrochloride, 0.064 g of 1-hydroxybenzotriazole hydrate and 0.066 ml of triethylamine are dimethylform To 5 ml of amide was added and stirred at 0 ° C for 10 minutes. 0.100 g of E-2-amino-1- (2,4-dichloro-phenyl) -ethanone O-methyloxime was added to the reaction solution, and the mixture was stirred for 2 hours. Poured a large amount of water, extracted with ethyl acetate, dried over anhydrous magnesium sulfate and evaporated to give 0.126g (yield 80%) of the title compound.

Example 3: Synthesis of (E, L) -N- [2- (2,4-dichloro-phenyl) -2-methoxyimino-ethyl] -2-methanesulfonylamino-propionamide (3)

0.126 g (yield 77%) of the title compound were obtained in the same manner as in Example 2, except that 0.079 g of N-methanesulfonyl L-alanine was used instead of N-methanesulfonyl L-glycine.

Example 4 (E, L) -N- [2- (2,4-Dichloro-phenyl) -2-methoxyimino-ethyl] -2-methanesulfonylamino-3-methyl-butyrylamide 4) Synthesis]

0.137 g (yield 78%) of the title compound were obtained in the same manner as in Example 2, except that 0.092 g of N-methanesulfonyl L-valine was used instead of N-methanesulfonyl L-glycine.

Example 5 (E, L) -2-methanesulfonylamino-4-methyl-pentanoic acid [2- (2,4-dichloro-phenyl) -2-methoxyimino-ethyl] -amide (5) Synthesis of

0.146 g (yield 80%) of the title compound were obtained in the same manner as in Example 2, except that 0.099 g of N-methanesulfonyl L-leucine was used instead of N-methanesulfonyl L-glycine.

Example 6 (E, L) -2-methanesulfonylamino-3-methyl-pentanoic acid [2- (2,4-dichloro-phenyl) -2-methoxyimino-ethyl] -amide (6) Synthesis of

0.142 g (yield 78%) of the title compound were obtained in the same manner as in Example 2, except that 0.099 g of N-methanesulfonyl L-isoleucine was used instead of N-methanesulfonyl L-glycine. .

Example 7 (E, L) -N- [2- (2,4-Dichloro-phenyl) -2-methoxyimino-ethyl] -2-methanesulfonylamino-3-phenyl-propionamide (7 Synthesis of)

0.157 g (yield 80%) of the title compound were obtained in the same manner as in Example 2, except that 0.115 g of N-methanesulfonyl L-phenylalanine was used instead of N-methanesulfonyl L-glycine.

Example 8 (E, L) -1-Methanesulfonyl-pyrrolidine-2-carboxylic acid [2- (2,4-dichloro-phenyl) -2-methoxyimino-ethyl] -amide ( 8) Synthesis of

0.13 g (yield 76%) of the title compound were obtained in the same manner as in Example 2, except that 0.091 g of N-methanesulfonyl L-proline was used instead of N-methanesulfonyl L-glycine.

Example 9 (E, L) -N- [2- (2,4-Dichloro-phenyl) -2-methoxyimino-ethyl] -2-methanesulfonylamino-2-phenyl-acetamide (9 Synthesis of)

0.151 g of the title compound in the same manner as in Example 2, except that 0.108 g of N-methanesulfonyl L- (s)-(2) -phenylglycine was used instead of N-methanesulfonyl L-glycine. (Yield 79%) was obtained.

Example 10 (E, L) -N- [2- (2,4-dichloro-phenyl) -2-methoxymethoxy-ethyl] -3-hydroxy-2-methanesulfonylamino-propionamide ( 10) Synthesis]

0.128 g (yield 75%) of the title compound were obtained in the same manner as in Example 2, except that 0.086 g of N-methanesulfonyl L-serine was used instead of N-methanesulfonyl L-glycine.

Example 11 (E, L) -N- [2- (2,4-Dichloro-phenyl) -2-methoxymethoxy-ethyl] -3-hydroxy-2-methanesulfonylamino-butyramide Synthesis of 11]

0.127 g (yield 72%) of the title compound were obtained in the same manner as in Example 2, except that 0.093 g of N-methanesulfonyl L-threonine was used instead of N-methanesulfonyl L-glycine.

Example 12 (E, L) -N- [2- (2,4-dichloro-phenyl) -2-methoxymethoxy-ethyl] -3-mercapto-2-methanesulfonylamino-propionamide ( 12) Synthesis of

0.133 g (yield 75%) of the title compound were obtained in the same manner as in Example 2, except that 0.094 g of N-methanesulfonyl L-cysteine was used instead of N-methanesulfonyl L-glycine.

Example 13 (E, L) -N- [2- (2,4-Dichloro-phenyl) -2-methoxymethoxy-ethyl) -2-methanesulfonylamino-4-methylthio-butyrylamide Synthesis of (13)]

0.140 g (yield 74%) of the title compound were obtained in the same manner as in Example 2, except that 0.107 g of N-methanesulfonyl L-methionine was used instead of N-methanesulfonyl L-glycine.

Example 14 (E, L) -N- [2- (2,4-Dichloro-phenyl) -2-methoxyimino-ethyl] -3- (4-hydroxy-phenyl) -2-methanesulfur Synthesis of Ponylamino-Propionamide (14)]

0.144 g (yield 71%) of the title compound were obtained in the same manner as in Example 2, except that 0.122 g of N-methanesulfonyl L-tyrosine was used instead of N-methanesulfonyl L-glycine.

Example 15 Synthesis of (Z, L) -2-methanesulfonylamino-N- [2-methoxyimino-2-phenyl-ethyl] -3-methyl-butyramide (15)

0.131 g of N-methanesulfonyl L-valine, 0.128 g of 1- (3-dimethylaminopropyl) -3-ethylcarbodiimide hydrochloride, 0.091 g of 1-hydroxybenzotriazole hydrate and 0.093 ml of triethylamine were dimethylform To 5 ml of amide was added and stirred at 0 ° C for 10 minutes. 0.100 g of Z-2-amino-1-phenyl-ethanone O-methyloxime was added to the reaction solution, and the mixture was stirred for 2 hours. Poured a large amount of water, extracted with ethyl acetate, dried over anhydrous magnesium sulfate and evaporated to give 0.160g (yield 77%) of the title compound.

Example 16 Synthesis of (Z, L) -N- [2- (2,4-Dichloro-phenyl) -2-methoxymethoxy-ethyl] -2-methanesulfonylamino-acetamide (16)

0.072 g of N-methanesulfonyl L-glycine, 0.090 g of 1- (3-dimethylaminopropyl) -3-ethylcarbodiimide hydrochloride, 0.064 g of 1-hydroxybenzotriazole hydrate and 0.066 ml of triethylamine are dimethylform To 5 ml of amide was added and stirred at 0 ° C for 10 minutes. 0.100 g of Z-2-amino-1- (2,4-dichloro-phenyl) -ethanone O-methyloxime was added to the reaction solution, and the mixture was stirred for 2 hours. Poured a large amount of water, extracted with ethyl acetate, dried over anhydrous magnesium sulfate and evaporated to give 0.128g (yield 81%) of the title compound.

Example 17 Synthesis of (Z, L) -N- [2- (2,4-Dichloro-phenyl) -2-methoxymethoxy-ethyl] -2-methanesulfonylamino-propionamide (17)

0.126 g (yield 77%) of the title compound were obtained in the same manner as in Example 16, except that 0.079 g of N-methanesulfonyl L-alanine was used instead of N-methanesulfonyl L-glycine.

Example 18 (Z, L) -N- [2- (2,4-Dichloro-phenyl) -2-methoxymethoxy-ethyl] -2-methanesulfonylamino-3-methyl-butyrylamide 18) Synthesis]

0.132 g (yield 75%) of the title compound were obtained in the same manner as in Example 16, except that 0.092 g of N-methanesulfonyl L-valine was used instead of N-methanesulfonyl L-glycine.

Example 19 (Z, L) -2-methanesulfonylamino-4-methyl-pentanoic acid [2- (2,4-dichloro-phenyl) -2-methoxyimino-ethyl] -amide (19) Synthesis of

0.149 g (yield 82%) of the title compound were obtained in the same manner as in Example 16, except that 0.099 g of N-methanesulfonyl L-leucine was used instead of N-methanesulfonyl L-glycine.

Example 20 (Z, L) -2-methanesulfonylamino-3-methyl-pentanoic acid [2- (2,4-dichloro-phenyl) -2-methoxyimino-ethyl] -amide (20) Synthesis of

0.137 g (yield 75%) of the title compound were obtained in the same manner as in Example 16, except that 0.099 g of N-methanesulfonyl L-isoleucine was used instead of N-methanesulfonyl L-glycine. .

Example 21 (Z, L) -N- [2- (2,4-Dichloro-phenyl) -2-methoxyimino-ethyl] -2-methanesulfonylamino-3-phenyl-propionamide (21 Synthesis of)

0.155 g (yield 79%) of the title compound were obtained in the same manner as in Example 16, except that 0.115 g of N-methanesulfonyl L-phenylalanine was used instead of N-methanesulfonyl L-glycine.

[Example 22: (Z, L) -1-methanesulfonyl-pyrrolidine-2-carboxylic acid [2- (2,4-dichloro-phenyl) -2-methoxyimino-ethyl] -amide ( 22) Synthesis]

0.135 g (yield 77%) of the title compound were obtained in the same manner as in Example 16, except that 0.091 g of N-methanesulfonyl L-proline was used instead of N-methanesulfonyl L-glycine.

Example 23 (Z, L) -N- [2- (2,4-Dichloro-phenyl) -2-methoxyimino-ethyl] -2-methanesulfonylamino-2-phenyl-acetamide (23 Synthesis of)

0.158 g of the title compound in the same manner as in Example 16, except that 0.108 g of N-methanesulfonyl L- (s)-(2) -phenylglycine was used instead of N-methanesulfonyl L-glycine. (Yield 83%) was obtained.

Example 24 (Z, L) -N- [2- (2,4-Dichloro-phenyl) -2-methoxyimino-ethyl] -3-hydroxy-2-methanesulfonylamino-propionamide ( Synthesis of 24]

0.126 g (yield 74%) of the title compound were obtained in the same manner as in Example 16, except that 0.086 g of N-methanesulfonyl L-serine was used instead of N-methanesulfonyl L-glycine.

Example 25 (Z, L) -N- [2- (2,4-Dichloro-phenyl) -2-methoxymethoxy-ethyl] -3-hydroxy-2-methanesulfonylamino-butyramide Synthesis of 25]

0.126 g (yield 71%) of the title compound were obtained in the same manner as in Example 16, except that 0.093 g of N-methanesulfonyl L-threonine was used instead of N-methanesulfonyl L-glycine.

Example 26 (Z, L) -N- [2- (2,4-Dichloro-phenyl) -2-methoxymethoxy-ethyl] -3-mercapto-2-methanesulfonylamino-propionamide ( Synthesis of 26]

0.124 g (yield 70%) of the title compound were obtained in the same manner as in Example 16, except that 0.094 g of N-methanesulfonyl L-cysteine was used instead of N-methanesulfonyl L-glycine.

Example 27 (Z, L) -N- [2- (2,4-Dichloro-phenyl) -2-methoxymethoxy-ethyl] -2-methanesulfonylamino-4-methylthio-butyrylamide Synthesis of 27

0.140 g (yield 74%) of the title compound were obtained in the same manner as in Example 16, except that 0.107 g of N-methanesulfonyl L-methionine was used instead of N-methanesulfonyl L-glycine.

Example 28 (Z, L) -N- [2- (2,4-Dichloro-phenyl) -2-methoxyimino-ethyl] -3- (4-hydroxy-phenyl) -2-methanesulfur Synthesis of Ponylamino-Propionamide (28)]

0.149 g (yield 73%) of the title compound were obtained in the same manner as in Example 16, except that 0.122 g of N-methanesulfonyl L-tyrosine was used instead of N-methanesulfonyl L-glycine.

¹ H NMR data of the compounds of the general formula (I) synthesized according to the above Examples are shown in Table 2 below.

TABLE 2

Biological Experimental Example

In order to verify the control effect against the phytopathogens of the general formula (I) compound according to the present invention, the following four plant diseases were selected and the antimicrobial activity of each compound was investigated according to the method as described below. The compound of was found to exhibit excellent control effect.

Rice Leaf Blight (RLB) Pyricularia grisea

Rice Sheath Blight (RSB) Rhizoctonia solani

Cucumber gray mold (CGM) Botrytis cinerea

Tomato late blight (TLB) Phytophthora infestans

That is, after dissolving the compound in 10% acetone aqueous solution containing 250 ppm of Tween-20, 5 ml of foliar spray was applied to the host plants of a certain size, and the concentration of each compound was adjusted to 250 ppm. The plants sprayed with the medicament were left at room temperature for 24 hours to volatilize the solvent and water, and then inoculated with the prepared pathogens as described in the following experimental examples, and the plant disease prevention effect was calculated in comparison with the non-treated group. All experiments were repeated twice, and the ratings were divided according to the criteria in Table 3.

TABLE 3

Experimental Example 1: Antimicrobial Activity against Rice Fever

Pyricularia grisea was inoculated on oatmeal medium (Oatmeal 50g, agar 20g, 1 liter with distilled water) and incubated at 25 ° C., humidity 60%, and light conditions for 10 days. The conidia were formed into a spore suspension (10 ⁶ spores / ml) at a constant concentration using distilled water containing 250 ppm of Tween-20 (electrodeposition agent), and then flowed down to Nakdong rice (3-4 leaf stage) susceptible to rice fever. Pathogens were inoculated by sufficient spraying.

Inoculated rice was placed in a humid chamber in a dew chamber at 25 ° C. for 24 hours, placed in a constant temperature and humidity chamber at a relative humidity of 90% or higher and temperature at 25 ° C. for 5 days, and then the incidence area was calculated. At this time, the onset of disease was calculated by comparing the diseased area formed on the fully developed leaf just below the uppermost leaves of the 3-4 leafy rice to the standard disease area ratio table (compared to the diseased area rate based on the ratio of the diseased area to the total leaf area). Table 4) shows the results according to the criteria of Table 3 and grades them according to the criteria in Table 3.

Experimental Example 2: Antimicrobial Activity against Rice Leaf House Blight

A proper amount of bran was placed in a 1 L culture bottle and sterilized, and then inoculated with agar pieces of pathogen (Rhizoctonia solani AG-1) incubated for 3 days in potato agar medium. After incubating for 10 days, the mycelium mass was finely crushed, and 10 ml of Nakdong rice of 2-3 leaves was evenly inoculated in the pot, and then incubated for 48 hours in a wet room (28.0 ° C.). The incidence rate was investigated after 5 days of relative humidity at 80% relative humidity. The incidence of disease was investigated by examining the lesion area formed in the leaflets of 2 to 3 leaf seedlings according to the standard bleeding area ratio comparison table, and graded according to the criteria of Table 3, and the results are shown in Table 4.

Experimental Example 3: Antimicrobial Activity against Tomato Blight

Rhytophthora infestans were inoculated in rye B agar medium (60 g of rye, 20 g of sucrose, 50 ml of β-sitosterol, 20 g of agar, 1 liter of distilled water), and then incubated at 20 ° C. for 16 hours and for 8 hours. Incubation at 14 days induces the production of zygote sac. Sterile distilled water was added to the plate, and the spooned sachets were separated from the bacterial layer using a reagent spoon. The concentration of harvested spermatozoa was adjusted to 5 × 10 ⁴ / ml and used as the inoculum. This inoculum was sprayed with 3 ml of tomato seedlings. After inoculating plants inoculated for 5 days in a 20 ° C. wet room, the lesion area ratio (%) was investigated and graded according to the criteria of Table 3, and the results are shown in Table 4.

Experimental Example 4: Antimicrobial Activity against Cucumber Gray Mold

Pathogens isolated from tomatoes (Botrytis cinerea KC1) were inoculated in rice bran agar medium (RPA), and then condensed spores were formed by repeating 16 hours of light treatment and 8 hours of dark treatment in a 20 ° C. incubator for 10 days. Potato liquid medium (potato 200 g, dextrose 20 g, distilled water was added to 1 L) was poured into the medium, the formed spores were scraped, and then filtered with gauze to harvest spores. The spore concentration was adjusted to 1 × 10 ⁶ / ml and this was inoculated with 3 ml of single-leaf cucumber seedlings. The inoculated plants were wet treated at 20 ° C. for 4 days, and the lesion area ratio (%) of one leaf of the main leaf was examined, and then graded according to the criteria of Table 3, and the results are shown in Table 4.

TABLE 4

Claims (2)

Amino acid amide derivatives of the general formula (I) below, geometric isomers and stereoisomers thereof:

Wherein X ₁ and X ₂ each independently represent hydrogen, halogen, methyl or methoxy, R ₁ represents hydrogen, phenyl or —CHR ₂ R ₃ (where R ₂ represents hydrogen or methyl, and R ₃ is Hydrogen, C ₁ -C ₃ alkyl, hydroxy, thiol, C ₁ -C ₂ alkylthiomethyl, phenyl or hydroxy phenyl), R ₄ represents hydrogen or propylene with R ₁ , R ₅ represents C ₁ -C ₃ alkyl or aryl unsubstituted or substituted by methyl, halogen or halogen substituted methyl. The compound of claim 1, wherein X ₁ and X ₂ each independently represent hydrogen or chloro, R ₁ represents hydrogen, phenyl or —CHR ₂ R ₃ (wherein R ₂ represents hydrogen or methyl, R ₃ represents hydrogen, Methyl, ethyl, isopropyl, hydroxy, thiol, methylthiomethyl, phenyl or hydroxyphenyl), R ₄ represents hydrogen or propylene together with R ₁ and R ₅ represents methyl .