KR100613690B1 - 4-quinolinone derivative and fungicidal composition for agriculture and horticulture comprising same - Google Patents

Abstract

The present invention relates to a novel 4-quinolinone derivative of formula (I), which is useful as an agricultural horticultural fungicide, which selectively shows a high bactericidal effect against a wide range of plant pathogens. In addition, agricultural and horticultural fungicide compositions comprising the compound as a active ingredient and a pharmaceutically acceptable carrier can be used against a wide range of plant pathogens.

Where

R ₁ to R ₄ are hydrogen, halogen, C _1-10 linear or branched alkyl group, C _1-6 linear or branched haloalkyl group, C _1-10 linear or branched alkoxy group, phenyl group, phenoxy group, Benzyl, nitro or cyano groups (except where R ₁ to R ₄ are all hydrogen);

R ₅ is a C _1-6 linear or branched alkyl group;

, NHZAr 또는

이고;X is NHR ₆ ,

, NHZAr or

ego;

R ₆ is a substituted or unsubstituted C _1-15 linear or branched alkyl group, a substituted or unsubstituted C _3-10 cycloalkyl group, piperidine group, piperazine group or aryl group;

Y is (CH-R ₇ ) n or an oxygen atom, where n is 0 or 1 and when n is 1, R ₇ is a piperidine group;

Z is a substituted or unsubstituted C _1-6 linear or branched alkyl group;

Ar is an aryl group, a heteroaryl group, or a pyrrolidine group.

Description

4-quinolinone derivative and agricultural horticultural fungicide composition comprising the same {4-QUINOLINONE DERIVATIVE AND FUNGICIDAL COMPOSITION FOR AGRICULTURE AND HORTICULTURE COMPRISING SAME}

The present invention relates to a novel 4-quinolinone derivative having a good bactericidal effect against plant pathogens and agrohorticultural fungicide composition comprising the same.

As a horticultural fungicide for preventing plant diseases, synthetic compounds having various chemical structures have been used, which has contributed greatly to the development of agriculture. However, some of the existing fungicide compounds have been limited in their use due to weakness or environmental pollution, or they have never been satisfactory in the control of activity and stability, especially in the fungicides known to date, as their resistance has developed. The development of fungicides is required.

Accordingly, it is an object of the present invention to provide a 4-quinolinone derivative compound of a novel structure which has stronger sterilization or insecticidal properties than the conventional one, without fear of environmental pollution.

In order to achieve the above object, the present invention provides a novel 4-quinolinone derivative of the formula (1) useful as an agricultural or horticultural fungicide or insecticide:

Formula 1

Where

R ₁ to R ₄ are hydrogen, halogen, C _1-10 linear or branched alkyl group, C _1-6 linear or branched haloalkyl group, C _1-10 linear or branched alkoxy group, phenyl group, phenoxy group, Benzyl, nitro or cyano groups (except where R ₁ to R ₄ are all hydrogen);

R ₅ is a C _1-6 linear or branched alkyl group;

, NHZAr 또는

이고;X is NHR ₆ ,

, NHZAr or

ego;

R ₆ is a substituted or unsubstituted C _1-15 linear or branched alkyl group, a substituted or unsubstituted C _3-10 cycloalkyl group, piperidine group, piperazine group or aryl group;

Y is (CH-R ₇ ) n or an oxygen atom, where n is 0 or 1 and when n is 1, R ₇ is a piperidine group;

Z is a substituted or unsubstituted C _1-6 linear or branched alkyl group;

Ar is an aryl group, a heteroaryl group, or a pyrrolidine group.

In addition, the present invention provides a horticultural fungicide or insecticide composition comprising a quinolinone derivative of Formula 1 and a pharmaceutically acceptable carrier as an active ingredient.

Hereinafter, the present invention will be described in more detail.

In the 4-quinolinone derivatives according to the invention, preferred examples of R ₆ are linear or branched alkyl groups which may or may not be substituted with halogen, C _1-3 alkoxy groups, C _1-3 alkoxycarbonyl groups or C _3-6 cycloalkyl groups ; C _3-6 cycloalkyl group unsubstituted or substituted with a C _1-3 alkyl group or a phenyl group; A piperidine group unsubstituted or substituted with one or more C _1-3 alkyl groups or ethoxycarbonyl groups; Piperazine group substituted with a C _1-3 alkyl group; Halogen, a C _1-4 linear or branched alkyl, alkoxy or haloalkyl group, or a phenyl group, substituted or unsubstituted by one or more cyano groups.

In the 4-quinolinone derivative of the present invention, a preferable example of Z is a linear or branched alkyl group, hydroxymethyl group, or a phenyl group or substituted phenyl group substituted or unsubstituted C _1-3 linear or have a C _1-3 of It is a topographic alkyl group.

In the 4-quinolinone derivatives according to the invention, preferred examples of Ar are halogen, C _1-4 linear or branched alkyl, alkoxy or haloalkyl groups, nitro groups, amino groups, phenyl groups unsubstituted or substituted with one or more groups ; A pyrrolidine group substituted or unsubstituted with a C _1-3 linear or branched alkyl group; Or a pyridine group unsubstituted or substituted with a C _1-3 linear or branched alkyl group.

4-quinolinone derivatives of the general formula (1) according to the present invention, as can be seen in the following reaction formula 1, by reacting a compound of formula (III) with 2-alkyl sulfoxy-4-quinolinone of formula (II) Can be manufactured:

Wherein R ₁ , R ₂ , R ₃ , R ₄ , R ₅ and X are as defined in Formula 1, and R ₈ is an alkyl group of C _1-3 .

The reaction is an inert solvent such as ethers such as diethyl ether, isopropyl ether, tetrahydrofuran, dioxane and diphenyl ether; Hydrocarbons such as benzene, toluene, xylene, ligroin; Halogenated hydrocarbons such as dichloroethane, chloroform and carbon tetrachloride; Esters such as ethyl acetate, ethyl propionate and the like; Chlorobenzenes such as monochlorobenzene and dichlorobenzene; And aprotic polar solvents such as N, N-dimethylform amide, diethylsulfoxide and the like. In addition, pyridine or trialkylamine can be used in the reaction as a base and a solvent.

The reaction may be carried out at 0 to 260 ° C, but is preferably carried out at room temperature to the boiling point of the solvent, the reaction time depends on the reaction temperature, 0.5 to 8 hours is preferred.

Compounds of the above formula (II) may be prepared by hydrogen peroxide, acetic acid, or the like, and the sulfide synthesized by a known method (see RC Anand & AK Sinha, India Journal of Chemistry, 1991, 30B, 560; and Korean Patent No. 295819). Or oxidizing agents such as m-chloroperoxide.

On the other hand, when the amine compound of the formula (III) is used in the form of an acid addition salt, it is used after being treated with 1 to 2 equivalents of an inorganic base such as trialkylamine, potassium carbonate, sodium hydroxide and the like for acid removal.

After the completion of the reaction, when the amine compound of the formula (III) is used in a form other than an acid addition salt, the crude product can be directly obtained by distilling the solvent under reduced pressure, and in the case of using the acid addition salt, the solvent is distilled under reduced pressure. Next, water is added to dissolve the resulting salt, extracted with an organic solvent such as methylene chloride, chloroform or ethyl acetate, and then the solvent is distilled under reduced pressure to obtain a crude product.

The crude product obtained is an alcohol such as methanol or ethanol; Esters of organic acids such as ethyl acetate or methyl acetate; Hydrocarbons such as pentane or hexane; Solvents, such as ether, such as ethyl ether or tetrahydrofuran, may be recrystallized by using alone or in combination, or may be easily separated and purified by a method such as column chromatography.

The quinolinone derivatives of the formula (1) according to the present invention, prepared by the above method, have excellent bactericidal effects against various plant pathogens, and have high therapeutic and prophylactic antibacterial properties against diseases caused by plant pathogens. An example of such a pathogen is rice blast fungus in rice (Piricularia oryzae), sheath blight fungus of rice (Rhizoctonia solani), cucumber gray mold pathogen (Botrytis cinerea), powdery mildew of cucumber fungus (Sphaerotheca fuligiIlea), downy mildew fungus of cucumber (Pseudoperonospora cubensis ), downy mildew of grape fungus (Plasmopora viticola), Station pathogens of tomato (Phytophthora infestans), kkaessi pattern germs (Cochliobolus miyabeanus), brown pattern germs of peanut (Cercopora arachidcola), powdery mildew fungus of barley (Erysiphe graminis), wheat red rust ( Puccinia recondita ) and wheat stem rust fungus ( Puccinis graminis ).

In addition, the quinolinone derivatives of the formula (1) according to the present invention are sanitary pests such as flies, mosquitoes, and wheels, agricultural pests, for example, Laodelphax striatellus Fallen , Nilapanata lugens stal , and Sogatella furcifera Horvath. ), Stink bugs such as Nephotettix cincticeps Uhler , Trialeurodes vaporariorum , and Pygmy Black Aphid ( Myzus persicae Sulzer ), Phyllonorycter ringoneella Matsumura , Chinese Cabbage Lepidoptera pests such as moth ( Plutella xylostella Curtis ), moth ( Pseudaletia separata Walker ), thief moth ( Hamestra brassicae Linne ), tobacco moth ( Spodoptera litura Fablicus ) and cabbage butterfly ( Pieris rapacerucivora Boisduval ) (Oulema oryzae Kuwayama) and rice weevil roots Coleoptera pests, such as termites and bow a little and home (Echirnocnemus squameus Billberg) Are effective for the charge, in particular it shows an excellent insecticidal effect against Lepidoptera insects such as moths and some T. urticae cabbage.

According to the present invention, the compound of formula 1 of the present invention contains about 0.01 to 90% by weight, preferably about 0.01 to 40% by weight, based on the weight of the composition, as an active ingredient, suitable solid or liquid carriers and surfactants, diluents It can be formulated into agricultural compositions by mixing with other suitable auxiliaries such as electrodeposition agents, synergists, adhesives, dispersants and the like, which can be prepared as emulsions, wetting agents, powders, granules, powders and the like.

Solid carriers that can be used in the present invention include talc, clay, bentonite, pyrophyllite, kaolin, diatomaceous earth, silica and the like; Liquid carriers include water, methanol, ethanol, acetone, diethylformamide, ether, benzene, xylene, toluene, naphtha and the like; Surfactants include nonionic surfactants such as polyoxyethylene alkylphenyl ethers and polyoxyethylene fatty acid esters, anionic surfactants such as alkylbenzenesulfonates, lignin sulfonates and dynaphthylmethanesulfonic acid salts; Adhesives include polyvinyl alcohol, CMC, gum arabic, and the like.

In addition, the composition according to the present invention can be used in combination with other pesticides, fungicides, herbicides, plant growth regulators, acaricides and the like or agrochemicals and nutritional substances.

Specific examples of 4-quinolinone derivatives of formula 1 according to the present invention are shown in Table 1 below:

Hereinafter, the present invention will be described in more detail based on the following examples. However, the following examples are not intended to limit the invention only.

Example 1: Synthesis of 3-acetyl-6-chloro-8-trifluoromethyl-2- (2-phenylethylamino) -4-quinolinone (Compound 1)

50 ml of tetrahydrofuran solvent of 3-acetyl-6-chloro-8-trifluoromethyl-4-methyl sulfoxy-2-quinolinone (3.5 g, 0.01 mol) and 2-phenylethylamine (1.21 g, 0.01 mol) Heated to reflux for 4 h. After completion of the reaction, the solvent was distilled off under reduced pressure, and the remaining solid was dissolved in 10 ml of ethyl acetate while heating. Then, 30 ml of hexane was added and recrystallized to obtain the title product in a yield of 2.57 g (63%).

¹ H NMR (CDCl ₃ ): δ 11.78 (brs, 1H), 8.47 (d, J = 2.0, 1H), 7.75 (d, J = 2.0, 1H), 7.75 (brs, 1H), 7.33 (s, 5H ), 3.55 (m, 2H), 3.08 (m, 2H), 2.7 (s, 3H)

Example 2: Synthesis of 3-acetyl-6-chloro-8-trifluoromethyl-2-isopropylamino-4-quinolinone (Compound 2)

The same reaction as in Example 1 was carried out from 3-acetyl-6-chloro-8-trifluoroethyl-4-methyl sulfoxy-2-quinolinone (3.5 g, 0.01 mol) and isopropylamine (0.6 g, 0.01 mol). The title product was obtained in 2.52 g (73%) yield.

¹ H NMR (CDCl ₃ ): δ 11.7 (s, 1H), 8.58 (m, 1H), 7.87 (m, 1H), 3.77 (m, J = 6.5, 1H), 2.93 (s, 3H), 1.47 ( d, J = 6.5, 6H)

Example 3: Synthesis of 3-acetyl-6-chloro-8-trifluoroethyl-2-cyclopentylamino-4-quinolinone (Compound 5)

The same reaction as in Example 1 from 3-acetyl-6-chloro-8-trifluoromethyl-2-methylsuloxy-4-quinolinone (3,5 g, 0.01 mol) and cyclopentylamine (0.86 g, 0.01 mol) The title product was obtained in 2.5 g (67%) yield.

¹ H NMR (CDCl ₃ ): δ 11.8 (brs, 1H), 8.47 (m, 1H), 7.83 (brs, 1H), 7.77 (m, 1H), 3.85 (brs, 1H), 2.73 (s, 3H) , 2.47 to 1.38 (m, 8H)

Example 4: Synthesis of 3-propionyl-8-chloro-2-isopropylamino-4-quinolinone (Compound 7)

The title product was obtained by the same reaction as in Example 1 from 3-propionyl-8-chloro-2-ethyl sulfoxy-4-quinolinone (2.97 g, 0.01 mol) and isopropylamine (0.6 g, 0.01 mol). Obtained in a yield of 2.93 g (71%).

¹ H NMR (CDCl ₃ ): δ 11.78 (br, 1H), 8.4 to 6.97 (m, 4H), 3.87 (m, J = 7.0, 1H), 3.27 (q, J = 8.0, 2H), 1.65 (d , J = 7.0, 6H), 1.17 (t, J = 8.0, 3H)

Example 5: Synthesis of 3-acetyl-8-methyl-2-isopropylamino-4-quinolinone (Compound 8)

The title product was obtained in the same manner as in Example 1 from 3-acetyl-8-methyl-2-methylsuloxy-4-quinolinone (2.63 g, 0.01 mol) and isopropylamine (0.6 g, 0.01 mol) to give the title product 2.59. Obtained in g (68%).

¹ H NMR (DMSO-d ₆ ): δ 11.5 (br.d, 1H), 8.33 to 7.33 (m, 4H), 3.8 (m, J = 7.0, 1H), 2.77 (s, 3H), 2.4 (s , 3H), 1.45 (d, J = 7.0, 6H)

Example 6: 3-acetyl-6-chloro-8-trifluoromethyl-2- (p-fluorophenethylamino) -4-quinolinone (Compound 25) Synthesis

3-acetyl-6-chloro-8-trifluoromethyl-2-methylsulfoxy-4-quinolinone (3.5 g, 0.01 mol) with p-fluorophenethylamine hydrochloride (1.76 g, 0.01 mol) and triethylamine After carrying out the same reaction as in Example 1 from (1.1 g, 0.01 mol), the solvent was distilled off under reduced pressure. The remaining solid was dissolved in 50 ml of ethyl acetate, washed with 50 ml of water, dried over anhydrous magnesium sulfate, and the solvent was distilled off under reduced pressure. Again, the remaining solid was dissolved in 10 ml of ethyl acetate and recrystallized by adding 30 ml of hexane to give the title product in a yield of 2.25 g (53%).

¹ H NMR (CDCl ₃ ): δ 2.7 (s, 3H), 2.97 to 3.16 (t, J = 6.4, 2H), 3.47 to 3.77 (m, 2H), 6.93 to 8.47 (m, 7H), 11.73 (s , 1H)

Example 7: Synthesis of 3-acetyl-8-fluoro-2- (1-methoxy-2-propylamino) -4-quinolinone (Compound 27)

The same reaction as in Example 1 was carried out from 3-acetyl-8-fluoro-2-methylsuloxy-4-quinolinone (2.67 g, 0.01 mol) and 1-methoxy-2-propylamine (0.88 g, 0.01 mol). The title product was obtained in 2.53 g (87%) yield.

¹ H NMR (CDCl ₃ ): δ 1.5 (d, 3H), 2.8 (s, 3H), 3.7-3.9 (m, 3H), 3.6 (s, 3H), 7.2-8.3 (m, 4H)

Example 8: Synthesis of 3-acetyl-6-chloro-8-trifluoromethyl-2-ethylamino-4-quinolinone (Compound 29)

Example 1 from 3-acetyl-6-chloro-8-trifluoromethyl-2-methylsulfoxy-4-quinolinone (3.5 g, 0.01 mol) and ethylamine (70 wt% aqueous solution: 0.65 g, 0.01 mol) The reaction was carried out to give the title product in a yield of 2.52 g (76%).

¹ H NMR (CDCl ₃ ): δ 1.37-1.6 (t, j = 8, 3H), 2.73 (s, 3H), 3.23-3.67 (m, 2H), 7.77-8.47 (m, 3H), 11.57 (s , 1H)

Example 9: Synthesis of 3-acetyl-8-fluoro-2- (2-methylcyclohexylamino) -4-quinolinone (Compound 34)

The same reaction as in Example 1 was carried out from 3-acetyl-8-fluoro-2-methylsuloxy-4-quinolinone (2.67 g, 0.01 mole) and 2-methylcyclohexylamine (1.13 g, 0.01 mole). The product was obtained in a yield of 2.1 g (66%).

¹ H NMR (CDCl ₃ ): δ 1.0 to 1.5 (m, 12H), 2.6 (s, 3H), 3.9 (m, 1H), 7.l to 8.4 (m, 3H)

Example 10 Synthesis of 3-acetyl-8-trifluoromethyl-2- (α-methylbenzylamino) -4-quinolinone (Compound 38)

The same reaction as in Example 1 was carried out from 3-acetyl-8-trifluoromethyl-4-ethyl sulfoxy-2-quinolinone (3.17 g, 0.01 mol) and α-methylbenzylamine (1.21 g, 0.01 mol). The title product was obtained in a yield of 2.43 g (65%).

¹ H NMR (CDCl ₃ ): δ 1.63-1.83 (d, J = 7, 3H), 2.8 (s, 3H), 4.57-4.77 (m, lH), 7.23-8.6 (m, 9H), 12.2 (s , 1H)

Example 11: Synthesis of 3-acetyl-5-nitro-8-chloro-2- (p-chlorobenzylamino) -4-quinolinone (Compound 86)

The same reaction as in Example 1 was carried out from 3-acetyl-5-nitro-8-chloro-2-methylsuloxy-4-quinolinone (3.28 g, 0.01 mol) and p-chlorobenzylamine (1.42 g, 0.01 mol). The title product was obtained in 2.32 g (57%) yield.

¹ H NMR (DMSO-d ₆ ): δ 11.9 (m, 1H), 8.43 (brs, 1H), 7.8 (d, J = 9.0, 1H), 7.5 (s, 4H), 7.3 (d, J = 9.0 , 1H), 4.9 (d, J = 6.0, 2H), 2.7 (s, 3H)

Example 12 Synthesis of 3-acetyl-6,8-dichloro-2- (2-methylcyclolexylamino) -4-quinolinone (Compound 89)

The same reaction as in Example 1 was carried out from 3-acetyl-6,8-dichloro-2-methylsuloxy-4-quinolinone (3.18 g, 0.01 mol) and 2-methylcyclohexylamine (1.13 g, 0.01 mol). The title product was obtained in 2.68 g (73%) yield.

¹ H NMR (CDCl ₃ ): δ 12.0 (m, 1H), 8.2 (d, J = 2.0, lH), 7.9 (brs, 1H), 7.6 (d, J = 2.0, 1H), 3.0 (m, 1H ), 2.8 (s, 3H), 1.0 to 2.5 (m, 9H), 1.0 to 1.2 (m, 3H)

Example 13: Synthesis of 3-acetyl-7-t-butyl-2-cyclobutylamino-4-quinolinone (Compound 155)

The title product was subjected to the same reaction as in Example 1 from 3-acetyl-7-t-butyl-2-methylsuloxy-4-quinolinone (3.05 g, 0.01 mol) and cyclobutylamine (0.71 g, 0.01 mol). Was obtained in a yield of 2.6 g (83%).

¹ H NMR (CDCl ₃ ): δ 11.4 (m, 1H), 8.3 to 8.4 (d, 1H), 7.2 to 7.7 (m, 2H), 2.9 (s, 3H), 1.5 to 2.9 (m, 4H), 1.2 (s, 9H), 0.9 to 1.1 (m, 2H)

Example 14 Synthesis of 3-acetyl-8-ethyl-2-cyclopentylamino-4-quinolinone (Compound 178)

The title product was obtained in the same manner as in Example 1 from 3-acetyl-8-ethyl-2-methylsuloxy-4-quinolinone (2.77 g, 0.01 mol) and cyclopentylamine (0.86 g, 0.01 mol) to give the title product 2.15. Obtained in g (72%).

¹ H NMR (CDCl ₃ ): δ 11.6 (m, 1H), 8.1 (d, J = 6.0, 1H), 7.4-7.1 (m, 3H), 3.8 (m, 1H), 2.8 (s, 3H), 2.7 (m, 2H), 2.1 to 1.5 (m, 8H), 1.4 (t, J = 6.0, 3H)

Example 15 Synthesis of 3-acetyl-6-chloro-8-methyl-2- (p-fluorophenethylamino) -4-quinolinone (Compound 198)

3-acetyl-6-chloro-8-methyl-2-methylsuloxy-4-quinolinone (2.98 g, 0.01 mole) with p-fluorophenethylamine hydrochloride (1.76 g, 0.01 mole) and triethylamine (1.1 g, 0.01 mol) to give the title product in the yield of 2.9 g (71%).

¹ H NMR (DMSO-d ₆ ): δ 11.5 (m, 1H), 8.3 (s, 1H), 7.9 (s, 1H), 7.6-6.8 (m, 5H), 3.77 (m, 2H), 3.0 ( t, J = 7.0, 2H), 2.6 (s, 3H), 2.4 (s, 3H)

Example 16: Synthesis of 3-acetyl-5,8-dichloro-2- (N-morpholino) -4-quinolinone (Compound 289)

The reaction was carried out in the same manner as in Example 1 from 3-acetyl-5,8-dichloro-4-methylsuloxy-4-quinolinone (3.18 g, 0.01 mol) and morpholine (0.87 g, 0.01 mol) to give the title product. Was obtained in a yield of 2.56 g (75%).

¹ H NMR (DMSO-d ₆ ): δ 6.7-7.3 (m, 3H), 2.9-3.3 (m, 8H), 2.3 (s, 3H)

Example 17 Synthesis of 3-acetyl-5,7-dimethyl-2- (β-methylphenethylamino) -4-quinolinone (Compound 308)

Reaction was carried out as in Example 1 from 3-acetyl-5,7-diethyl-2-methylsuloxy-4-quinolinone (2.77 g, 0.01 mol) and β-methylphenethylamine (1.35 g, 0.01 mol). The title product was obtained in 2.96 g (85%) yield.

¹ H NMR (DMSO-d ₆ ): δ 11.6 (m, 1H), 7.2 (s, 5H), 6.7-7.1 (d, 2H), 3.5 (m, 2H), 3.2 (m, 1H), 2.7 ( s, 3H), 2.6 (s, 3H), 2.2 (s, 3H), 1.3 (d, 3H)

Example 18 Synthesis of 3-acetyl-8-isopropyl-2-sec-butylamino-4-quinolinone (Compound 316)

The title product was subjected to the same reaction as in Example 1 from 3-acetyl-8-isopropyl-2-methylsuloxy-4-quinolinone (2.91 g, 0.01 mol) and sec-butylamine (0.73 g, 0.01 mol). Was obtained in a yield of 2.7 g (90%).

¹ H NMR (CDCl ₃ ): δ 11.6 (m, 1H), 8.2 (d, J = 8.0, 1H), 7.7-7.1 (m, 3H), 3.5 (m, 1H), 2.9 (m, 1H), 2.8 (s, 3H), 1.7 (m, 2H), 1.4 (m, 9H), 1.1 (t, J = 6.0, 3H)

Example 19 Synthesis of 3-acetyl-8-phenyl-2- (β-methylphenethylamino) -4-quinolinone (Compound 337)

The title product was subjected to the same reaction as in Example 1 from 3-acetyl-8-phenyl-2-methylsuloxy-4-quinolinone (3.25, 0.01 mol) and β-methylphenethylamine (1.35 g, 0.01 mol). Was obtained in a yield of 3.29 g (83%).

¹ H NMR (DMSO-d ₆ ): δ 11.3 (m, 1H), 8.3 (brs, 1H), 8.3 to 8.0 (m, 1H), 7.8 to 6. 9 (m, 12H), 3.3 (m, 2H), 3.03 (m, 1H), 2.6 (s, 3H), 1.23 (d, J = 7-0, 3H)

Example 20 Synthesis of 3-acetyl-5-methyl-8-chloro-2- (p-chlorophenethylamino) -4-quinolinone (Compound 434)

Reaction as in Example 1 from 3-acetyl-5-methyl-8-chloro-2-methylsuloxy-4-quinolinone (2.97 g, 0.01 mol) and p-chlorophenethylamine (1.56 g, 0.01 mol) To give the title product in 3.11 g (80%) yield.

¹ H NMR (DMSO-d ₆ ): δ 1 l.6 (m, 1H), 8.7 (s, 1H), 7.7 (s, 4H), 7.1 to 7.9 (m, 2H), 3.9 (q, 2H), 3.2 (t, 2H), 2.9 (s, 3H), 2.7 (s, 3H)

Example 21 Synthesis of 3-acetyl-6-fluoro-8-chloro-2-isoamylamino-4-quinolinone (Compound 437)

The same reaction as in Example 1 was carried out from 3-acetyl-6-fluoro-8-chloro-2-methylsuloxy-4-quinolinone (3.02 g, 0.01 mol) and isoamylamine (0.87 g, 0.01 mol). The title product was obtained in a yield of 2.79 g (86%).

¹ H NMR (CDCl ₃ ): δ 11.6 (m, 1H), 8.0-7.8 (m, 2H), 7.4 (dd, J = 8.0, 2.0, 1H), 3.4 (m, 2H), 2.8 (s, 3H ), 1.7 (m, 3H), 0.9 (d, J = 6.0, 6H)

Example 22 Synthesis of 3-acetyl-5-trifluoromethyl-8-methoxy-2-isobutylamino-4-quinolinone (Compound 446)

The same reaction as in Example 1 from 3-acetyl-5-trifluoromethyl-8-methoxy-2-methylsuloxy-4-quinolinone (3.47 g, 0.01 mol) and isobutylamine (0.73 g, 0.01 mol) To give the title product in 2.46 g (69%) yield.

¹ H NMR (DMSO-d ₆ ): δ 11.1 (m, 1H), 8.5 (brs, 1H), 7.2 to 7.7 (m, 2H), 4.2 (s, 3H), 3.0 to 3.6 (m, 2H), 2.6 (s, 3H), 1.8 to 2.3 (m, 1H), 1.1 (d, J = 6.0, 6H)

Sterilization Effect Test Example

To investigate the protective effect against plant pathogens, 25 mg of test compound was dissolved in 10 ml of acetone, 90 ml of 250 ppm aqueous solution of Tween 20 was added to the solution, and the concentration was adjusted to 250 ppm. 50 ml of foliar spray was applied to host plants. The sprayed plants were left at room temperature for 24 hours to volatilize the solvent and water. Thus, plants (test group) and untreated plants (control group) treated with the fungicide composition were inoculated with specific plant pathogens as shown in the following test examples, and left for the same period under the same conditions (humidity and temperature), The control area (Control Value,%) was calculated as shown in Equation 1 by obtaining the disease area ratio of each leaf (obtained from the ratio of disease area ratio prepared based on the ratio of the measured disease area to the leaf area). All experiments were repeated twice, and the higher the control value, the better the sterilization effect.

Control value (%) = (1- (Length of treatment area / lesion area of control)) × 100

Test Example 1: bactericidal effect on rice fever

Strains of pathogens ( Pyricularia oryzae ) were inoculated in rice bran agar medium (Rice Polish 20g, dextrose 10g, agar 15g, distilled water 1L) and incubated for 2 weeks in a 26 ℃ incubator. The surface of the medium in which the pathogen was grown was scraped with a rubber gallbladder to remove airborne hyphae, and spores were formed for 48 hours on a shelf of 25 to 28 ° C. in which a fluorescent lamp was turned on. Germ inoculation was sprayed sufficiently to flow into the Nakdong rice (3-4 leaf stage) susceptible to rice blast, after making a spore suspension (10 ⁶ spores / ml of spores) of a certain concentration using sterile distilled water. The inoculated rice was incubated for 24 hours in a dark state, and the disease area ratio of leaves was determined by inducing the disease for 5 days in a constant temperature and humidity chamber at a relative humidity of 90% or higher and 26 ± 2 ° C. At this time, the lesion area formed on the fully developed leaf just below the top leaf of 3-4 leaf rice was measured.

Test Example 2: The bactericidal effect on the rice leaf blight blight

Put the appropriate amount of wheat bran into 1L culture bottle, sterilize, inoculate agar pieces of pathogen ( Rhizoctonia solani ) grown on potato agar medium for 3 days, and finely crush the cultured mycelium masses. (5cm) and inoculated evenly in a constant temperature and humidity room with 28 ± 1 ℃ and relative humidity of 80% or more for 5 days to determine the lesion area ratio of leaves of 2-3 leaf seedlings.

Test Example 3: bactericidal effect on tomato gray mold

Strains ( Botrytis cinerea ) isolated from tomatoes were inoculated in potato agar medium (PDA) and plated in an incubator at 25 ° C. to incubate for 15 days under light dark conditions to form spores. The spores formed on the medium were put in 10 ml of distilled water per plate, scraped with a brush, and then spores were filtered with gauze to harvest spores. The spore concentration was 10 ⁶ / ml, and then sprayed on single-leaf cucumbers. This was induced for 3 days in a 20 ℃ wet room to determine the lesion area ratio of one leaf.

Test Example 4: bactericidal effect against tomato late blight

Phytophthora infestans were placed on V-8 juice agar medium (V-8 juice 200ml, CaCO ₃ 4.5g, agar 15g, distilled water 800ml) and light treated at 20 ℃ for 16 hours and dark treated for 14 hours. Spores were harvested after incubation. At this time, sterile distilled water was added to the plate and shaken to separate the zygote sac from the flora, and then, the 4-stage piece of cloth was used to filter the stool sac. Adjust the concentration of strained sachets to 10 ⁵ pcs / ml and inoculate the inoculum to tomato seedlings for 1 day in a 20 ° C. chamber, and then transfer to a constant temperature and humidity room with a temperature of 20 ° C. and a relative humidity of 80% or more. After 1 day of onset, the lesion area ratio of one and two leaves of tomato was examined.

Test Example 5: bactericidal effect on wheat rust

The pathogen ( Puccinia recondita ) was used for direct passage to plants in the laboratory. For subculture and pharmacological investigation of strains, 15 seed grains (silver onions) were seeded in a disposable pot (diameter: 6.5 cm), and spores were inoculated by sprinkling the wheat of one leaf grown for 7 days in a greenhouse. The inoculated one-leafed wheat was incubated for one day in a 20 ° C. chamber, then transferred to a constant temperature and humidity chamber of 70% relative humidity and 20 ° C. for 10 days to induce onset, and the leaf area ratio of the leaves was determined.

Test Example 6: bactericidal effect on barley powdery mildew

The pathogen ( Erysiphe graminis f.sp.hordei ) was used by passage in the laboratory. For subculture and pharmacological investigation of strains, seeded 15 barley seeds (East barley No. 1) in a disposable pot (diameter: 6.5 cm) and seeded on barley plants grown for 7 days in a greenhouse (25 ± 5 ℃). After inoculating the powdery mildew spores, it was transferred to a constant temperature and humidity room of 50% relative humidity and 22 to 24 ° C to induce the onset for 7 days, and then the leaf area ratio of the leaves was determined.

The control value was calculated by substituting the lesion area ratios of the treated and control leaves measured in Test Examples 1 to 6, and the results are shown in Table 2 as the activity index.

Insecticidal Effect Test Example

In order to investigate the insecticidal effect of the 4-quinolinone derivative according to the present invention, 25 mg of the test compound was dissolved in 5 ml of acetone, and then mixed with 45 ml of a 100 ppm aqueous solution of Triton-X-100, a surfactant, The test drug obtained by adjusting the concentration to 250 ppm was sprayed on each adult. On the other hand, the control group was treated with acetone-surfactant-distilled water solution containing no test compound. Thus, after leaving the test group and the control group for the same period of time under the same conditions (humidity and temperature) as in the following test examples, the mortality rate (%) was calculated as shown in Equation 2 from the results obtained, all the experiments Each repeat was repeated three times.

Mortality rate (%) = (100-surviving appendix)

Test Example 7: Insecticidal effect on Nilaparvata lugens stal

Raise susceptible Nilaparvata lugens stalls bred indoors without spraying insecticides in an acrylic cage (26 cm wide, 29 cm long and 20 cm high) with the same reproductive nymphs to have a final adult density of approximately 500 per cage. Were bred indoors using Dongjin rice in a constant temperature room (temperature 27 ± 1 ℃, relative humidity 50 ± 5%, light conditions of 16 females, 8 females).

For insecticidal testing, first, 6 seedlings (cultivar: Dongjin), 5-7 cm long, are rolled with cotton wool, inserted into a test tube (31 cm in diameter, 15 cm in height), and then inoculated with 20 adult adults. The test drug prepared beforehand was sprayed twice by placing a nozzle of a micro atomizer (a single injection amount of 0.0254 ± 0.0005 ml) in the center of the inlet. Subsequently, the mortality rate was examined after 24 hours and 48 hours while the test tube was kept in a constant temperature room (temperature 25 ± 1 ° C., relative humidity 50 ± 5%, light conditions 16 people 8 cancer). At this time, when the stimulation with saliva did not show a reflex action was considered as a death.

Test Example 8: Insecticidal effect on peach aphid ( Myzus persicae sulzer )

Peach or aphid ( Myzus persicae sulzer ), which was raised for 2 years without spraying pesticides indoors, was smoked in a constant temperature room (temperature 21 ± 1 ℃, relative humidity 50 ± 5%, light conditions 16 people, 8 cancers). Indoor breeding using), and the insects were notified.

For the insecticidal test, first, 50 ml of the test drug with a concentration of 500 ppm and tobacco leaf (variety: NC-82) cut into a circular shape of 9 cm in diameter were immersed for 30 seconds and dried in the wind for 30 minutes, followed by 9 cm petri dish. I put it. Subsequently, 20 worms were inoculated into tobacco leaves treated with the respective drugs, and then stored in a constant temperature room (temperature 25 ± 1 ° C., relative humidity 50 ± 5%, light conditions of 16 people 8 and 24 hours). The mortality rate was later examined. When irritated with a thin brush tip, no reflexes were considered dead.

Test Example 9: Insecticidal effect on Chinese cabbage moth ( Plutella Xylostella Linnaeus )

The average density per breeding box was 500 for the Chinese cabbage moth ( Plutella Xylostella Linnaeus ), which was raised using a cabbage in a constant temperature room (temperature 27 ± 1 ℃, relative humidity 50 ± 5%, 8 females in the light condition) without using insecticide. As many as three breeding, three larvae were disclosed.

For the pesticidal test, first, the cabbage leaves were cut into 6 cm diameter circles, soaked in a test drug having a concentration of 500 ppm for 36 seconds, and then dried in the wind for 30 minutes. The leaves thus treated were placed in a Petri dish each 6 cm in diameter, and then 10 larvae of 3 larvae were inoculated. Subsequently, the petri dishes were covered with a lid and stored in a constant temperature room (temperature 25 ± 1 ° C., relative humidity 50 ± 5%, light conditions of 16 patients, 8 cancers), and the mortality rate was examined after 24 and 48 hours. Death was considered to not show reflexes when stimulated with a thin brush tip.

Test Example 10: Insecticidal effect on spotted mite ( Tetranychus urticae koch )

The insecticide susceptible mite ( Tetranychus urticae koch ) was bred indoors using kidney beans in a constant temperature room (temperature 23 ± 1 ° C, relative humidity 50 ± 5%, light conditions of 16 people, 8 cancers), and their loyalty was disclosed. .

For the insecticidal test, first, the boiled agar solution (agar content of 0.5%) was poured into the chaile to a depth of about 1 cm, cooled and hardened, and then the kidney beans were fixed on it. 40 adults were inoculated and 3 ml of test drug with a concentration of 500 ppm was sprayed using a micro sprayer. Subsequently, the mortality was examined through a microscope after 24 hours and 48 hours, respectively, while keeping the saale in a constant temperature room (temperature 25 ± 1 ° C., relative humidity 50 ± 5%, light conditions of 16 people 8 cancers). Death was considered to show no reflex when stimulated.

The mortality measured from Test Examples 7 to 10 is shown in Table 3 below.

Compound number A light bulb Peach Black Aphid Chinese cabbage moth Spotting 2 10 0 100 63 19 0 0 100 0 20 0 0 80 100 23 0 0 90 100 85 0 10 100 7 182 0 0 100 100 238 0 0 100 0

As can be seen from the results of Tables 2 and 3, the composition comprising the 4-quinolinone derivatives according to the present invention not only has a wide range of bactericidal effects against plant pathogens, but also against insecticidal effects, in particular cabbage moth and spotted mite Has excellent pesticidal effect.

Claims (6)

4-quinolinone derivative of formula Formula 1

Where R ₁ to R ₄ are hydrogen, halogen, C _1-10 linear or branched alkyl group, C _1-6 linear or branched haloalkyl group, C _1-10 linear or branched alkoxy group, phenyl group, phenoxy group, Benzyl, nitro or cyano groups (except where R ₁ to R ₄ are all hydrogen); R ₅ is a C _1-6 linear or branched alkyl group; X is NHR ₆ ,

, NHZAr or

ego; In this case, R ₆ is halogen, C _1-3 alkoxy group or a C _1-3 alkoxycarbonyl group which is optionally substituted or substituted with a linear or branched alkyl group, C _1-3 alkyl, unsubstituted C ₃ to C _1-3 of _-6 cycloalkyl group, optionally substituted by C _1-3 alkyl group or an ethoxycarbonyl group piperidin dingi, substituted with a C _1-3 alkyl group or unsubstituted, and piperacillin oscillator; Y is (CH-R ₇ ) n or an oxygen atom, where n is 0 or 1 and when n is 1, R ₇ is a piperidine group; Z is a C _1-3 linear or branched alkyl group substituted or unsubstituted with a C _1-3 linear or branched alkyl group, a hydroxymethyl group or a phenyl group; Ar is a phenyl group optionally substituted with halogen, a C _1-4 linear or branched alkyl group, alkoxy group, amino group or haloalkyl. delete delete delete An agricultural and horticultural fungicide composition comprising the 4-quinolinone derivative according to claim 1 as an active ingredient and a pharmaceutically acceptable carrier. Agrohorticultural insecticide composition comprising the 4-quinolinone derivative according to claim 1 and a pharmaceutically acceptable carrier as an active ingredient.