KR930009819B1 - Novel compounds of 2-quinoline derivatives - Google Patents

Abstract

2-Quinolinone derivs. of formula (I) are prepd. by a cyclization of ketene dithio acetal -anilide cpds. at 140-250 deg.C. In the formula (I), R1,R2,R3 and R4 are each H, halogen, alkyl, alkoxy, thioalkoxy, halogenated lower alkyl, nitro, cyano, aryl, aryloxy, arylsulfone, alkoxycarbonyl, carboxylic or heterocyclic; R5 is alkyl or aryl; R6 is R7 or R8; R7 is alkyl or H, alkyl or haloalkyl substd. benzyl; R8 is aryl or H, halogen, alkyl or haloalkyl substd. benzyl; n = 0 or 1. The cpds. (I) have antibacterial activities.

Description

[Name of invention]

Novel 2-quinolinone derivatives

Detailed description of the invention

The present invention relates to a novel 2-quinolinone derivative represented by the following general formula (I) having a strong bacteriostatic activity.

Wherein, R ₁ , R ₂ , R ₃ , and R ₄ are the same or different and each is a hydrogen atom, a halogen atom, an alkyl group, an alkoxy group, a thioalkoxy group, a halo lower alkyl group, a nitro group, a cyano group, an aryl group, an aryl An oxy group, an aryl sulfone group, an alkoxycarbonyl, a carboxylic acid, or a heterocyclic group, R ₅ represents an alkyl group or an aryl group, R ₆ represents R ₇ or R ₈ , R ₇ represents an alkyl group or a hydrogen atom or a halogen atom , A benzyl group substituted with an alkyl or halo lower alkyl group, and n represents 0 or 1.

Here, the alkyl group means a straight chain of C ₁ -C ₆ or alkyl of C ₃ -C ₄ side chain; Alkoxy groups are C ₁ -C ₃ alkoxy or C ₁ -C ₃ haloalkoxy groups; The thioalkoxy group may be a C ₁ -C ₃ thioalkoxy group or a C ₁ -C ₃ halothioalkoxy group; The haloloweralkyl group may represent C ₁ -C ₃ haloalkyl.

And aryl is a hydrogen atom, a halogen atom, a straight chain of C ₁ -C ₄ , a straight chain of C ₃ -C ₄ or an alkyl of C ₃ -C ₄ side chain, or C ₁ -C ₃ haloalkyl, C ₁ -C ₃ Alkoxy or C ₁ -C ₃ haloalkyl, C ₁ -C ₃ alkoxy or C ₁ -C ₃ haloalkoxy or phenyl or substituted phenyl, cyano group and nitro group may represent a substituted phenyl group Heterocyclic may refer to a heterocyclic group such as morpholine containing nitrogen.

As a horticultural fungicide, synthetic compounds having various chemical structures have been used to play an enormous role in controlling plant diseases and consequently contribute greatly to the development of agriculture. However, some of these compounds have never been satisfactory in controlling the chemical composition and stability. In particular, as the fungicides known to date have become resistant, development of a fungicide with a new structure is expected.

Accordingly, the present invention aims to provide novel 2-quinolinone derivatives having novel bactericidal properties against plant pathogens, some of which also have insecticidal and acaricidal properties.

Hereinafter, the present invention will be described in detail.

The present invention relates to a novel 2-quinolinone derivative represented by the general formula (I).

The compound of formula (I) according to the present invention can be prepared with 4-alkylthio-2-quinolinone of formula (Ia) by heat cyclization of the compound of formula (II) The compound of formula (Ia) can be oxidized to prepare 4-alkylsuloxy-2-quinolinone of the general formula (Ib).

Wherein R ₁ , R ₂ , R ₃ , R ₄ , R ₅ , R ₇ are the same as defined above.

Further, according to the present invention, when the compound of the general formula (Ib) is substituted with the mercaptan of the following general formula (III), the compound of the following general formula (Ia ') is obtained and oxidized again, the following general formula (Ib') The compounds of are obtained as one kind of the above general formula (I) compounds.

In the above formulas, R ₁ , R ₂ , R ₃ , R ₄ , R ₅ and R ₈ are as described above.

Looking at the preparation method of the novel compound of the general formula (I) as described above, the ketenedithio acetal α-anilide of the general formula (II) is cyclized by heating in the presence or absence of a solvent.

The solvent that can be used at this time is a hydrocarbon solvent such as paraffin oil, benzene such as xylene, dichlorobenzene; Amides such as dimethylformamide and dimethyl acetamide; N, N-dialkyl anilines such as N, N-dimethyl aniline, N, N-diethyl aniline and the like; Ethers such as diphenyl ether and the like or mixtures thereof.

Heating reaction temperature according to the present invention is made at 140 ~ 250 ℃, preferably cyclization reaction occurs at 160 ~ 200 ℃ well. In this case, the reaction proceeds too slowly at a temperature lower than 140 ° C., and the mercaptan (R ₇ SH) generated as a by-product is broken at a temperature higher than 250 ° C., which is dangerous.

In the above general formulas (Ia ') and (Ib'), when R ₈ is aryl or genyl, the compound of the general formula (Ia) is 4-alkyl sulfoxy quinolinone (Ib) and thiophenol or substituted thiophenols, or Genzylmercaptans (HSR ₈ ) can be obtained by a substitution reaction by heating with or without a solvent, and oxidizing it yields a compound of formula (Ib ').

At this time, the solvent used is hydrocarbons such as paraffin oil, such as solvent when cyclizing; Benzenes such as xylene and dichlorobenzene; Amides such as dimethylformamide and dimethylacetamide; N, N-dialkyl anilines, such as N, N- dimethylaniline, N, N- dieth aniline, etc .; Ethers such as diphenyl ether and the like or mixtures thereof can be used. At this time, the reaction temperature is made at 140 ~ 250 ℃, preferably the substitution reaction occurs well at 160 ~ 200 ℃. If the reaction temperature is too low, the reaction time is long, and if too high, the yield is low.

Formulas (Ia) and (Ia ') prepared by the above method can be prepared by the following method (Ib) and (Ib').

That is, the compounds of the general formulas (Ib) and (Ib ') in the compounds of the general formulas (Ia) and (Ia') (n is 0 in the general formula (I)) When oxidized to 1), suitable oxidizing agents used include peroxy compounds such as hydrogen peroxide, organic hydroperoxides such as 3-tert-butyl hydroperoxide, aromatic or aliphatic percarboxylic acids (e.g. m-chloro peroxy benzoic acid, Organic peroxides such as peroxy acetic acid or permono phthalic acid, heavy metal oxides, or inorganic oxide oxyacids.

At this time, the solvent used in the oxidation reaction from the general formula (Ia) and (Ia ') to the general formula (Ib) and (Ib') is water; Halogenated hydrocarbons such as dichloromethane, chloroform, carbon tetrachloride, chlorobenzene and the like; Fatty acids such as acetic acid, propionic acid and the like; Alcohols such as methyl alcohol, ethyl alcohol and the like can be used.

At this time, the reaction temperature is carried out at 0 ℃ to 130 ℃ and more preferably the reaction is carried out at 20 ℃ to 60 ℃, if the reaction temperature is too low, there is a problem that the reaction time is long, if too high the solvent boils over There is. The amount of oxidant used can usually be used 1.2 times or more than the same amount of the compound used of general formula (Ia), and there is no particular limitation thereto.

The thioquinolinone derivatives of the general formulas (Ia) and (Ia ') obtained by the above reaction and the sulfoxy-2-quinolinone derivatives of the general formulas (Ib) and (Ib') may be recrystallized or chromatographic if necessary. It may also be purified by.

-아닐리드는 다음과 같은 방법에 의해서 β-케토 아닐리드로부터 제조될 수 있다.On the other hand, the starting material used in the present invention is curtain dithio acetal of formula (II)

Anilide can be prepared from β-keto anilide by the following method.

Wherein R ₁ , R ₂ , R ₃ , R ₄ , R ₅ , R ₇ are as described above and Y represents chlorine, bromine, iodine or alkyl or arylsulfonate.

As such, the objective compounds of the present invention are novel 4-alkyl and arylthio-2-quinolinones (Ia) and (Ia '), and novel 4-alkyl and arylsuloxy-2-quinolinones (Ib) and oxidized thereof. Obtained as (Ib ') derivative.

On the other hand, the compound according to the present invention has a control effect against a wide range of plant diseases including heat diseases, paperback disease, gray mold disease, late blight, etc., which is a major factor of economic loss, and has a resistance to conventional fungicides Insecticides and acaricides are effective, as well as providing new agricultural and horticultural fungicides that have long lasting effects, as well as insecticides and insecticides such as cabbage moth and spotted mite. Useful as

In actual use, the compound of general formula (I) may be used alone, but in order to easily use as an inhibitor, one or two or more kinds of the compound (I) may be dissolved or dispersed in a carrier depending on the purpose of use, or The mixture may be mixed with or adsorbed onto a suitable solid carrier to prepare a formulation such as an emulsion, a hydrate, a powder, a granule, or a spray. If necessary, emulsifiers, suspending agents, electrodeposition agents, penetrants, wetting agents, store agents, stabilizers and the like may be added to these formulations.

Examples of such specific compounds according to the present invention are shown in Table 1 below.

TABLE 1a

TABLE 1b

TABLE 1c

TABLE 1d

TABLE 1d

TABLE 1e

Hereinafter, the present invention will be described in detail with reference to Examples, in this embodiment, the percentage is based on weight. These examples are intended to illustrate the present invention in more detail, but the present invention is not limited thereto.

Example 1

Synthesis of 3-acetyl-4-methylthio-2-quinolinone (1)

When N-phenyl-α- (bismethylthioylidene) acetoacetamide (28.1 g, 0.1 mol) is heated in a 300 ml solvent of 0-dichlorobenzene and refluxed for 2 hours, a pyrolysis reaction occurs with generation of methyl mercaptan gas. . After confirming the completion of the reaction from the thin layer chromatography, the reaction solution was cooled to precipitate crystals and filtered to obtain 19.1 g (82%) of the product.

¹ H NMR (DMSO-d ₆ ) δ: 10.7 (s, 1H), 8.2 ~ 7.15 (m, 4H), 2.65 (s, 3H), 2.53 (s,

H).

Example 2

Synthesis of 3-acetyl-7-methoxy-4-methylthio-2-quinolinone (2).

-(비스메칠티오일리덴)아세토아세트아미드(3.1g, 0.001몰)로부터 실시예 1과 동일한 반응을 진행하여 원하는 생성물을 2.1g(82%)의 수율로 얻었다.N- (m-anisyl)-

The reaction was carried out in the same manner as in Example 1 from-(bismethylthioylidene) acetoacetamide (3.1 g, 0.001 mol) to obtain a desired product in 2.1 g (82%) yield.

_{^{1 H NMR (CDCl l3) δ}} : 10.49 (s, 1H), 8.18 ~ 6.68 (s, 3H), 3.8 (s, 3H), 2.64 (s, 3H), 2.53 (s, 3H).

Example 3

Synthesis of 3-acetyl-7-chloro-methylthio-2-quinolinone (3).

The reaction was proceeded from N- (2-chlorophenyl) -α- (bismethylthioylidene) acetoacetamide (3.2 g, 0.01 mol) in the same manner as in Example 1 to yield 2.2 g (86%) of the desired product. Got it.

¹ H NMR (DMSO-d ₆ ) δ: 8.2-7.25 (m, 3H), 4.5-3.0 (brs), 2.67 (s, 3H), 2.59 (s, 3H).

Example 4

Synthesis of 3-acetyl-5,8-dichloro-4-methylthio-2-quinolinone (4).

The same reaction as in Example 1 was carried out from N- (2,5-dichlorophenyl) -α- (bismethylthioylidene) acetoacetamide (3.5 g, 0.01 mol) to give 2.0 g (68%) of the desired product. Obtained in the yield.

¹ H NMR (DMSO-d ₆ + CDC _l3 ) δ: 7.7 (d, j = 9.0,1H), 7.27 (d, j = 9.0,1H), 2.64 (s, 3H), 2.52 (s, 3H).

Example 5

Synthesis of 3-acetyl-6-methoxy-4-methylthio-2-quinolinone (5).

The same reaction as in Example 1 was carried out from N- (p-anisyl) -α- (bismethylthioylidene) acetoacetamide (3.1 g, 0.01 mol) to obtain the desired product in a yield of 1.9 g (74%). Got it.

¹ H NMR (DMSO-d ₆ ) δ: 10.68 (s, 1H), 7.93-6.95 (s, 3H), 3.83 (s, 3H), 2.63 (s, 3H), 2.59 (s, 3H).

Example 6

Synthesis of 3-acetyl-6-fluoro-4-methylthio-2-quinolinone (7).

The same reaction as in Example 1 was carried out from N- (4-fluorophenyl) -α- (bismethylthioylidene) acetoacetamide (3.0 g, 0.01 mol) to give the desired product in a yield of 2.3 g (95%). Got it.

¹ H NMR (DMSO-d ₆ + CDC _l3 ) δ: 8.1 to 7.2 (m, 3H), 2.62 to (s, 3H), 2.55 (s, 3H).

Example 7

Synthesis of 3-acetyl-8-fluoro-4-methylthio-2-quinolinone (8).

The reaction of N- (2-fluorophenyl) -α- (bismethylthioylidene) butyrylacetamide (3.0 g, 0.01 mol) in the same manner as in Example 1 was carried out to yield the desired product in 2.0 g (85%) yield. Got it.

¹ H NMR (DMSO-d ₆ + CDC _l3 ) δ: 6.13 to 7.1 (m, 3H), 2.65 to (s, 3H), 2.55 (s, 3H).

Example 8

Synthesis of 3-butyryl-8-chloro-4-methylthio-2-quinolinone (9).

The reaction was proceeded in the same manner as in Example 1 from N- (2-chlorophenyl) -α- (bismethylthioylidene) butylylacetamide (3.4 g, 0.01 mol) to give 2.5 g (89%) of the desired product. Got it.

¹ H NMR (CDCl ₃ ) δ: 8.7 (s, 1H), 8.52 ~ 8.05 (m, 1H), 7.47 ~ 6.75 (m, 3H), 2.76 (t, j = 7.0,2H), 2.45 (s, 6H ), 1.72 (m, 2H), 2.45 (s, 6H), 1.72 (m, 2H), 0.95 (t, j = 7.0, 3H).

Example 9

Synthesis of 3-acetyl-8-methyl-4-methylthio-2-quinolinone (11).

The same reaction as in Example 1 was carried out from N- (o-tolyl) -α- (bismethylthioylidene) acetoacetamide (3.0 g, 0.01 mol) to obtain the desired product in 2.1 g (88%) yield. .

¹ H NMR (DMSO-d ₆ ) δ: 15.6 (s, 1H), 8.06-7.3 (m, 3H), 2.93 (s, 3H), 2.69 (s, 3H), 2.65 (s, 3H).

Example 10

Synthesis of 3-benzoyl-8-chloro-4-methylthio-2-quinolinone (12).

The same reaction as in Example 1 was carried out from N- (2-chlorophenyl) -α- (bismethylthioylidene) benzoylacetamide (3.8 g, 0.01 mol) to give the desired product in 2.6 g (81%) yield. Got it.

¹ H NMR (DMSO-d ₆ + CDCl ₃ ) δ: 8.3 to 7.2 (m, 8H), 2.65 (s, 3H).

Example 11

Synthesis of 3-acetyl-6-chloro-8-trifluoromethyl-4-methylthio-2-quinolinone (13).

From N- (4-chloro) -2- (trifluoromethylphenyl) -a- (bismethylthioylidene) acetoacetamide (3.8 g, 0.01 mol), the same reaction as in Example 1 was carried out to give the desired product, 2.3. Obtained in g (71%).

¹ H NMR (CDCl ₃ + DMSO-d ₆ ) δ: 8.3 (s, 1H), 8.12 to (s, 3H), 2.67 (s, 3H).

Example 12

Synthesis of 3-acetyl-8-methoxycarbonyl-4-methylthio-2-quinolinone (16).

The same reaction as in Example 1 was carried out from N- (2-methoxycarbonylphenyl) -α- (bismethylthioylidene) acetoacetamide (3.4 g, 0.01 mol) to give 2.8 g (99%) of the desired product. Obtained in the yield.

¹ H NMR (DMSO-d ₆ + CDCl ₃ ) δ: 2.6 (s, 3H), 3.27 (s, 3H), 4.03 (s, 3H), 7.4-8.6 (m, 3H

).

Example 13

Synthesis of 3-acetyl-6-nitro-4-methylthio-2-quinolinone (20).

The same reaction as in Example 1 was carried out from N- (4-nitrophenyl) -α- (bismethylthioylidene) acetoacetamide (3.3 g, 0.01 mol) to give the desired product in a yield of 2.1 g (80%). Got it.

¹ H NMR (DMSO-d ₆ + CDCl ₃ ) δ: 2.57 (s, 3H), 2.66 (s, 3H), 8.0-8.9 (m, 4H).

Example 14

Synthesis of 3-acetyl-6-chloro-7-nitro-4-methylthio-2-quinolinone (21).

N- (3-nitro-4-chlorophenyl) -α- (bismethylthioylidene) acetoacetamide (3.6 g, 0.01 mol) was subjected to the same reaction as in Example 1 to 1.8 g (61%) of the desired product. ) In the yield.

¹ H NMR (DMSO-d ₆ + CDCl ₃ ) δ: 2.43 (s, 3H), 2.7 (s, 3H), 7.73-8.13 (m, 2H), 11.4 (s, 1H).

Example 15

Synthesis of 3-acetyl-8-cyano-4-methylthio-2-quinolinone (22).

The reaction of N- (2-cyanophenyl) -α- (bismethylthioylidene) acetoacetamide (3.1 g, 0.01 mol) in the same manner as in Example 1 was carried out to yield 1.8 g (73%) of the desired product. Got it.

¹ H NMR (DMSO-d ₆ + CDCl ₃ ) δ: 2.13 (s, 3H), 2.7 (s, 3H), 7.6-8.7 (m, 3H).

Example 16

Synthesis of 3-acetyl-6-chloro-8-trifluoromethyl-4- (t-butylbenzylthio) -2-quinolinone (23).

The same reaction as in Example 1 was carried out from N- (4-chloro-2-trifluoromethylphenyldene) -α- [bis- (t-butylbenzylthio) ylidene] -acetoacetamide (6.3 g, 0.01 mol). Proceed to yield the desired product in 2.5 g (54%) yield.

¹ H NMR (DMSO-d ₆ + CDCl ₃ ) δ: 1.27 (s, 9H), 2.73 (s, 3H), 4.6 (s, 2H), 7.35 (s, 4H), 7.95 (d, 1H), 8.52 (d, 1 H).

Example 17

Synthesis of 3-acetyl-6-t-butyl-4-methylthio-2-quinolinone (24).

The reaction was proceeded in the same manner as in Example 1 from N- (4-t-butylphenyl) -α- (bismethythiolidene) -acetoacetamide (3.4 g, 0.01 mol) to give 2.3 g (84%) of the desired product. Obtained in yield.

¹ H NMR (DMSO-d ₆ + CDCl ₃ ) δ: 1.37 (s, 9H), 2.6 (s, 3H), 2.63 (s, 3H), 7.73 (s, 2H), 8.23 (s, 1H), 10.83 (s, 1 H).

Example 18

Synthesis of 3-acetyl-5,6,7,8-tetrachloro-4-methylthio-2-quinolinone (27).

-(비스메칠티오일리덴)-아세토아세트아미드(3.5g, 0.01몰)로부터 실시예 1과 동일한 반응을 진행하여 원하는 생성물을 2.6g(74%)의 수율로 얻었다.N- (2,3,4,5-tetrachlorophenyl)-

The reaction was carried out in the same manner as in Example 1 from-(bismethylthioylidene) -acetoacetamide (3.5 g, 0.01 mol) to give the desired product in 2.6 g (74%) yield.

¹ H NMR (DMSO-d ₆ + CDCl ₃ ) δ: 2.43 (s, 3H), 2.66 (s, 3H), 7.96 (s, 1H).

Example 19

Synthesis of 3-acetyl-8-trifluoromethyl-4-methylthio-2-quinolinone (27).

The same reaction as in Example 1 was carried out from N- (2-trifluoromethylphenyl) -α- (bismethylthioylidene) -acetoacetamide (3.5 g, 0.01 mol) to yield 1.96 g (65%) of the desired product. Obtained in the yield.

¹ H NMR (DMSO-d ₆ + CDCl ₃ ) δ: 2.6 (s, 3H), 2.7 (s, 3H), 8.06 (m, 1H), 8.63 (m, 1H).

Example 20

Synthesis of 3-acetyl-6-fluoro-8-trifluoromethyl-4-methylthio-2-quinolinone (33).

The reaction was proceeded in the same manner as in Example 1 from N- (4-fluoro-2-trifluoromethylphenyl) -α- (bismethylthioylidene) -acetoacetamide (3.7 g, 0.01 mol) to give 2.5 g of the desired product. Obtained in a yield of (83%).

¹ H NMR (CDCl ₃ ) δ: 2.7 (s, 3H), 2.97 (s, 3H), 7.73-8.16 (m, 1H), 15.63 (s, 1H).

Example 21

Synthesis of 3-acetyl-7-fluoro-8-trifluoromethyl-4-methylthio-2-quinolinone (34).

The same reaction as in Example 1 was carried out from N- (2-trifluoromethyl-3-fluorophenyl) -α- (bismethylthioylidene) -acetoacetamide (3.7 g, 0.01 mol) to give 2.2 g of the desired product. Obtained (73%).

¹ H NMR (CDCl ₃ ) δ: 2.72 (s, 3H), 2.93 (s, 3H), 7.71˜7.68 (m, 1H), 7.83 ~ 8.1 (m, 2H).

Example 22

Synthesis of 3-acetyl-6-bromo-8-trifluoromethyl-4-methylthio-2-quinolinone (35).

From N- (4-bromo-2-trifluoromethylphenyl) -α- (bismethylthioylidene) -acetoacetamide (4.3 g, 0.01 mol), the same reaction as in Example 1 was carried out to obtain the desired product. Obtained in g (67%).

¹ H NMR (CDCl ₃ ) δ: 2.7 (s, 3H), 2.93 (s, 3H), 8.1 (s, 1H), 8.53 (s, 1H), 15.6 (m, 2H).

Example 23

Synthesis of 3-acetyl-6-chloro-7-trifluoromethyl-4-methylthio-2-quinolinone (36).

The same reaction as in Example 1 was carried out from N- (3-trifluoromethyl) -α- (bismethylthioylidene) -acetoacetamide (3.8 g, 0.01 mol) to give 1.7 g (52%) of the desired product. Obtained in yield.

¹ H NMR (CDCl ₃ ) δ: 2.7 (s, 3H), 2.92 (s, 3H), 8.1-8.3 (m, 2H), 15.57 (s, 1H).

Example 24

Synthesis of 3-acetyl-6-hexyl-4-methylthio-2-quinolinone (37).

The reaction was proceeded from N- (4-hexylphenyl) -α- (bismethylthioylidene) -acetoacetamide (3.7 g, 0.01 mol) in the same manner as in Example 1 to give 2.5 g (82%) of the desired product. Got it.

¹ H NMR (CDCl ₃ ) δ: 0.78-0.97 (m, 3H), 1.16 ~ 1.8 (m, 10H), 2.67 (s, 3H), 2.83 (s, 3H

), 7.57 ~ 8.07 (m, 3H)

Example 25

Synthesis of 3-acetyl-6,7,8-trifluoro-4-methylthio-2-quinolinone (38).

From N- (2,3,4-triorphenyl) -α- (bismethylthioylidene) -acetoacetamide (3.4 g, 0.01 mole), the same reaction as in Example 1 was carried out to obtain 1.8 g of the desired product. 67%).

¹ H NMR (CDCl ₃ ) δ: 2.73 (s, 3H), 2.97 (s, 3H), 7.6-7.93 (m, 1H), 15.73 (s, 1H).

Example 26

Synthesis of 3-acetyl-6-chloro-8-trifluoromethyl-4- (2,4-dichlorobenzylthio) -2-quinolinone (39).

Same as Example 1 from N- (4-chloro-2-trifluoromethylphenyl) -α- [bis (2,4, -dichlorobenzylthio) ylidene] acetoacetamide (6.0 g, 0.01 mol) The reaction was carried out to obtain the desired product in 2.4 g (51%) yield.

¹ H NMR (CDCl ₃ ) δ: 15.68 (s, 1H), 8.57 (m, 1H), 7.67 ~ 7.03 (m, 4H), 4.87 (s, 2H), 2.97 (s, 3H).

Example 27

Synthesis of 3-acetyl-8-chloro-4-methylsulfoxy-2-quinolinone (91).

3-acetyl-8-chloro-4-methylthio-2-quinolinone (26.7 g, 0.01 mol) (3) was added to 200 ml of ethanol, and magnesium monooxy phthalate (29.7 g, 0.1 mol) was dissolved in 150 ml of water. The solution is slowly added dropwise at room temperature. After dropping, the reaction temperature was raised to 50 ° C and allowed to react at the same temperature for 2 hours. At the end of the reaction, the ethyl alcohol was distilled off, removed, 500 ml of water was added, and the produced solid was filtered to recrystallize the ethyl alcohol from 100 ml to obtain 23.2 (82%) of the product.

¹ H NMR (CDCl ₃ ) δ: 8.3-7.5 (m, 3H), 3.1 (s, 3H), 2.8 (s, 3H).

Example 28

Synthesis of 3-acetyl-6-methoxy-4-methylsuloxy-2-quinolinone (92).

Hydrogen peroxide (30% aqueous solution 2.83 g, 0.025 mol) while 3-acetyl-6-methoxy-4-methylthio-2-quinolinone (2.6 g, 0.01 mol) (5) was added to 10 ml of acetic acid and maintained at 80 ° C. Is added dropwise and stirring is continued at 80 to 30 minutes. After the reaction was cooled, the mixture was put into 500 g of ice water, and the precipitated solid was filtered and dried to synthesize 2.3 g (85%) of the desired product in a yield.

¹ H NMR (CDCl ₃ ) δ: 7.9 to 7.3 (m, 3H), 3.9 (s, 3H), 3.0 (s, 3H), 2.8 (s, 3H).

Example 29

Synthesis of 3-acetyl-5,8-dichloro-4-methylsuloxy-2-quinolinone (93).

The reaction was carried out as in Example 27 from 3-acetyl-5,8-dichloro-4-methylthio-2-quinolinone (3.0 g, 0.01 mol) (4) to give 2.4 g (78%) of the desired product. Got it.

¹ H NMR (CDCl ₃ ) δ: 8.0 to 7.0 (m, 2H), 3.1 (s, 3H), 2.75 (s, 3H).

Example 30

Synthesis of 3-acetyl-8-fluoro-4-methylsulfoxy-2-quinolinone (97).

The same reaction as in Example 28 was carried out from 3-acetyl-8-fluoro-4-methylthio-2-quinolinone (2.5 g, 0.01 mol) (8) to obtain the desired product in a yield of 2.0 g (79%). .

¹ H NMR (CDCl ₃ ) δ: 8.3-7 (m, 4H), 3.05 (s, 3H), 2.82 (s, 3H).

Example 31

Synthesis of 3-acetyl-6-chloro-8-trifluoromethyl-4-methylsulfoxy-2-quinolinone (98).

The same reaction as in Example 27 was carried out from 3-acetyl-6-chloro-8-trifluoromethyl-4-methylthio-2-quinolinone (3.4 g, 0.01 mol) (13) to give 2.9 g (85) of the desired product. %) Yield.

¹ H NMR (CDCl ₃ ) δ: 2.75 (s, 3H), 3.0 (s, 3H), 8.6 (d, 1H), 8.0 (d, 1H), 11.25 (s, 1H).

Example 32

Synthesis of 3-acetyl-8-fluoro-4-benzylsulfoxy-2-quinolinone (100).

The reaction was carried out as in Example 27 from 3-acetyl-8-fluoro-4-benzylthio-2-quinolinone (3.2 g, 0.01 mol) (15) to obtain the desired product in a yield of 2.9 g (87%). .

¹ H NMR (CDCl ₃ ) δ: 2.86 (s, 3H), 4.37 (s, 2H), 7.13-7.47 (m, 8H), 8.16 (s, 1H).

Example 33

Synthesis of 3-acetyl-8-trifluoromethyl-4-methylsuloxy-2-quinolinone (102).

From 3-acetyl-8-trifluoromethyl-4-methylthio-2-quinolinone (3.0 g, 0.01 mole) (29), the same reaction as in Example 27 was carried out to yield 2.5 g (82%) of the desired product. Got it.

¹ H NMR (CDCl ₃ ) δ: 2.87 (s, 3H), 3.03 (s, 3H), 7.52-8.78 (m, 3H), 11.25 (s, 1H).

Example 34

Synthesis of 3-acetyl-8-cyano-4-methylsuloxy-2-quinolinone (104).

The reaction was carried out from 3-acetyl-8-cyano-4-methylthio-2-quinolinone (2.6 g, 0.01 mol) (29) as in Example 27 to give the desired product in 1.8 g (68%) yield. Got it.

¹ H NMR (CDCl ₃ ) δ: 2.67 (s, 3H), 7.6-8.67 (m, 4H).

Example 35

Synthesis of 3-acetyl-5,8-dichloro-4- (p-chlorophenyl) thio-2-quinolinone (182).

3-acetyl-5,8-dichloro-4-methylsulphoxy-2-quinolinone (3.2 g, 0.01 mol) (93) and p-chlorothiophenol (1.73 g, 0.012 mol) were stirred at 200 ° C. with 30 After reversing for a minute, slowly cooled to 100 ° C, dissolved in 15 ml of toluene, and then cooled to room temperature. The precipitated process was filtered and dried to yield the desired product in 3.3 g (83%) yield.

¹ H NMR (CDCl ₃ ) δ: 7.2 to 8.3 (m, 6H), 3.00 (s, 3H).

Example 36

Synthesis of 3-acetyl-5,8-dichloro-4- (p-chlorophenyl) sulfoxy-2-quinolinone (184).

3-acetyl-5,8-dichloro-4- (p-chlorophenyl) thio-2-quinolinone (1 g, 0.0025 mol) (182) was mixed with 5 ml of acetic acid and hydrogen peroxide (30% 0.57 g, 0.005 mol). After stirring at 100 ° C. for 30 minutes, 50 g of ice water was added, and the precipitated solid was filtered and dried to obtain 0.8 g (73%) of the desired product.

¹ H NMR (DMSO-d ₆ + CDCl ₃ ) δ: 7.2 to 8.3 (m, 6H), 3.05 (s, 3H).

Next, the bactericidal activity of the 2-quinolinone derivative of the present invention thus prepared was measured by the following test method.

At this time, 25mg of 2-quinolinone derivative (I) was dissolved in 10ml of acetone and 90ml of 250ppm aqueous solution containing Tween 20 was added to the solution to investigate the protective effect of phytopathogenic bacteria. After adjusting to 250ppm 50ml each was sprayed on the surface of the host plant of a certain size.

The plants sprayed with the drug were left at room temperature for 24 hours to volatilize the solvent and water, and then inoculated with the pathogens prepared as follows. All experiments were conducted in duplicate.

[Test Example 1]

[Sterilization effect on rice fever]

Strains of pathogens (Pyricularia oryzae) were inoculated in rice bran agar medium (Rice Polish 20g, Dextrose 10g, Ager 15g, D.W.1ℓ) and incubated for 2 weeks in a 26 ℃ incubator. The pathogen-grown medium was scraped off with a high gallbladder to remove the aerial hyphae, and spores were formed for 48 hours on a fluorescent lamp-turned shelf (25-28 ° C).

Bacterial inoculation was sprayed enough to flow down to Nakdong rice (3-4 leaves) susceptible to rice fever after making the spore suspension 106 spores / ml of a certain concentration using sterilized distilled water.

The inoculated rice was left in the dark for 24 hours, and then incubated for 5 days in a constant temperature and humidity room with a relative humidity of 90% or higher and a temperature of 26 ± 2 ° C. The disease was investigated by examining the lesion area formed on the fully developed leaf just below the top leaf of 3-4 leaf rice.

[Test Example 2]

[Sterilization Effect on Rice Leaf Pattern Blight]

Put the appropriate amount of bran into 1ℓ culture bottle, sterilize, inoculate agar pieces of pathogen (Rhizoctoniaslani) grown in potato agar medium for 3 days, and then cultivate the mycelia of cultured finely. 5 cm) was inoculated evenly incubated in a humidified room (28 ± 1 ℃) and placed in a constant temperature and humidity room with a relative humidity of 80% or more after 5 days to investigate the disease occurrence.

The incidence survey was conducted based on the ratio of disease area to diseased leaves in 2 ~ 3 leaf seedlings based on the ratio of lesion area to leaf area.

[Test Example 3]

Bactericidal Effect on Cucumber Gray Mold

Strains isolated from tomato (Botrytis cinerea) were inoculated in the sensing medium (PDA) and placed in a plate at 25 ℃ incubator for 15 days in a light dark state to form spores. The spores formed on the medium were put in 10 ml of distilled water per plate, and after scraping the spores with a brush to filter the spores and harvesting the spores, the concentration of the spores was 106 / ml and the area ratio of one leaf was examined.

[Test Example 4]

[Sterilization Effect on Tomato Blight]

Plasma (Phytophthora infestans) bacteria were placed on V-8 juice agar (V-8 juice 200ml, CaCO ₃ 4.5g, agar 15g, distilled water 800ml) medium and cultured for 14 days by 16 hours of light treatment and 20 hours of dark treatment at 20 ℃. The spores were then harvested. At this time, the plate sterilized distilled water was added and shaken to remove the jujube sac from the flora, and then the jujube sac was filtered using a 4-ply piece of cloth. The concentration of harvested saponiferous sac was adjusted to 105 / ml, and the inoculum was sprayed with tomato seedlings for 1 day at 20 ° C, and then transferred to a constant temperature and humidity chamber with a relative humidity of 80% or higher at 20 ° C for 4 days. After that, the lesion area ratio (%) of one and two leaves of tomato was examined.

[Test Example 5]

[Sterilization Effect on Wheat Red Rust Disease]

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 on wheat of one leaf grown in a greenhouse for 7 days. The inoculated one-leaf wheat was incubated for one day at 20 ° C., and then transferred to a constant temperature and humidity room at 20 ° C. having a relative humidity of 70% to invent the invention, and examined the onset 10 days after the inoculation. The incidence was investigated 10 days after inoculation of rust spores.

[Test Example 6]

[Sterilization Effect on Barley Powder]

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 of 1-leaf barley grown for 7 days in a greenhouse (25 ± 5 ℃). Powdered spore spores were inoculated and inoculated. The inoculated plants were inoculated in the same manner as above and transferred to a constant temperature and humidity room with a relative humidity of 50% and 22-24 ° C. to induce the invention for 7 days, and then examined the lesion area ratio.

For the test results of Test Examples 1 to 6, the control value was calculated according to the following equation and shown in Table 2 below.

Table 2 Determination of bactericidal activity of 4-alkyl and arylthio-2-quinolinone derivatives (I)

Next, the insecticidal and acaricide activity of the 4-alkyl and aryl-2-quinolinone derivatives of the present invention were measured according to the following test method (test example).

In this case, the drug used in the test was dissolved 25 mg of the 4-alkyl and arylamino-2-quinolinone derivatives (I) in 5 ml of acetone, and then mixed with 45 ml of Tritonx-100 100 ppm aqueous solution, and then the concentration thereof. Use the test solution adjusted to be 250ppm.

[Test Example 7]

[Pesticide Effect Test on Brown Planthopper]

Breed susceptible Nilaparvatalugens stals bred indoors without insecticides in an acrylic cage (26cm wide, 29cm long, 20cm high), but have the same reproductive nymphs so that the final adult density per cage is approximately 500. The animals are bred indoors using Dongjin rice in a constant temperature room (27 ± 1 ℃, relative humidity 50 ± 5%, 16 conditions of 8 cancers), and the adult at 4 days after allegory is disclosed.

In the insecticidal test, first, 6 seedlings (cultiform: dongjin) of 5-7 cm in length are rolled with cotton wool, inserted into a test tube (31 cm in diameter and 15 cm in height), and 20 adult insects are inoculated there.

Subsequently, a nozzle of a microspray machine (single injection amount 0.0254 ± 0.0005 ml) is placed at the center of the inlet of the test tube, and the previously prepared blank reagent solution is sprayed twice.

On the other hand, the control group was treated with acetone-surfactant-distilled water solution containing no test agent, but was treated three times for the test group and the control group, respectively. Then, the mortality rate was examined after 24 and 48 hours while being kept in a constant temperature room (temperature 25 ± 1 ℃, relative humidity 50 ± 5%, light conditions 16 people 8 cancer). It is determined that death does not show reflex effect when stimulated with saliva.

[Test Example 8]

[Insecticidal effects on green peach aphid.]

Peach black aphid (Myzus persicae sulzer), which was raised indoors for 2 years without pesticide selection, was smoked in a constant temperature room (temperature 21 ± 1 ℃, relative humidity 50 ± 5%, light conditions of 16 people, 8 cancers). Indoor breeding using) and disclosure of insects. In the pesticidal test, first, 50 ml of the test compound having a concentration of 500 ppm and pear leaves (variety: NC-82) cut into 9 cm diameters were immersed for 30 seconds, air-dried for 30 minutes, and then placed in a 9 cm petri dish.

Meanwhile, the control group was treated with acetone-surfactant-distilled water solution, and treated three times with respect to the test group and the control group, and 20 insecticides were inoculated into tobacco leaves treated with the respective drugs, The mortality rate was examined 24 hours and 48 hours after storage at (25 ± 1 ℃, relative humidity 50 ± 5%, light conditions 16 people 8 cancer). When irritated with the tip of a brush, no reflexes are considered dead.

[Test Example 9]

[Insecticidal test on diamond-back moth]

The average density per breeding box was 500 for the Chinese cabbage moth (Plutella Xylostella Linnaeus), which was grown in a constant temperature room (temperature 27 ± 1 ℃, relative humidity 50 ± 5%, light conditions of 16 people, 8 cancers), without using pesticides. Breed as many as possible, and insect pest test 3 larvae should be disclosed.

Insecticidal experiment, first cut the cabbage leaf into a circle of 6cm diameter and soaked for 36 seconds in 500ppm of the test compound, and then air-dried for 30 minutes.

On the other hand, the control group is treated with acetone-surfactant-distilled water solution that does not contain the test drug. The leaves thus treated are placed in a Petri dish, each 6 cm in diameter, and 10 larvae of 3 larvae are inoculated therein. After repeated treatment for the test group and the control group, three times, the Petri dish was covered with a lid and kept in a constant temperature room (temperature 25 ± 1 ℃, relative humidity 50 ± 5%, light conditions 16 patients 8 cancer) for 24 hours, 48 Examine the mortality rate after time. When touched with the tip of a thin brush, it is judged to have died of showing no reflex.

[Test Example 10]

[Pesticide test on two-spotted spider mite]

Insecticide susceptible spots (Tetranychus urticae koch) are bred indoors using Kangnam bean leaves in a greenhouse (temperature 23 ± 1 ℃, relative humidity 50 ± 5%, light conditions of 16 people, 8 cancers), and the adult is disclosed. . Insecticide test, first, boiled agar solution (0.5% of agar content) is poured into the curry so that it is about 1cm deep, cooled and hardened, and then the Gangnam bean leaves are fixed on it. Then, 40 adults are inoculated here, Spray 3 ml of the test drug with 500 ppm.

On the other hand, the control group is sprayed with acetone-surfactant-distilled water solution that does not contain the test drug, but is repeated three times for the test group and the control group, respectively. Subsequently, it was stored in a constant temperature room (temperature 25 ± 1 ℃, relative humidity 50 ± 5%, light conditions of 16 people, 8 cancers), and the mortality rate was examined through a microscope after 24 hours and 48 hours, respectively. When stimulated, moving is considered alive.

For the test results obtained in Test Examples 7 to 10, the mortality rate was calculated according to the following equation, which is shown in Table 3 below.

TABLE 3 Determination of insecticidal and acaricide activity of 4-alkyl and arylamino-2-quinolinone derivatives (I)

As can be seen from the above table, the 4-alkylthio-2-quinolinone derivatives of the present invention exhibit an excellent insecticidal effect, particularly against spot mites.

Claims (17)

The novel 2-quinolinone derivative represented by following General formula (I).

Wherein R ₁ , R ₂ , R ₃ , and R ₄ are the same or different, and each represents a hydrogen atom, a halogen atom, an alkyl group, an alkoxy group, a thioalkoxy group, a halo lower alkyl group, a nitro group, a cyano group, an aryl group, or an aryl. An oxy group, an aryl sulfone group, an alkoxycarbonyl group, a carboxylic acid, or a heterocyclic group, R ₅ represents an alkyl group or an aryl group, R ₆ represents R ₇ or R ₈ , R ₇ represents an alkyl group or a hydrogen atom, a halogen atom, A benzyl group substituted with alkyl or halo lower alkyl, R ₈ represents an aryl group or a benzyl group substituted with a hydrogen atom, a halogen atom, alkyl or halo lower alkyl, and n represents 0 or 1. According to claim 1, wherein R ₁ , R ₂ , R ₃ , R ₄ are each a hydrogen atom, a halogen atom, a straight chain of C ₁ -C ₆ or an alkyl group of a C ₃ -C ₄ side chain, C ₁ -C ₃ Alkoxy or C ₁ -C ₃ haloalkoxy group, C ₁ -C ₃ thioalkoxy group or C ₁ -C ₃ halothioalkoxy group, C ₁ -C ₃ haloalkyl group, nitro group, cyano group, phenyl group Or a morpholin containing substituted phenyl group, phenoxy or substituted phenoxy group, phenyl sulfone group or substituted phenyl sulfone group, alkoxycarbonyl, carboxylic acid, or nitrogen. The 2-quinolinone derivative according to claim 1, wherein R ₅ is a C ₁ -C ₃ alkyl group or a phenyl or substituted phenyl group. The compound of claim 1, wherein R ₇ is C ₁ -C ₆ straight chain, C ₃ -C ₄ side chain alkyl or hydrogen atom, halogen atom, C ₁ -C ₄ alkyl, C ₁ -C ₃ haloalkyl 2-quinolinone derivative, characterized in that the benzyl group substituted by. The method of claim 1, wherein, R ₈ is a hydrogen atom, a halogen atom, a C ₁ -C ₄ straight chain or C ₃ -C ₄ branched chain alkyl of, C ₁ -C ₃ haloalkyl, C ₁ -C ₃ alkoxy or C ₁ -C ₃ haloalkoxy, phenyl or substituted phenyl, cyano group, nitro group and the like are one or more substituted phenyl groups or hydrogen atom, halogen atom or C ₁ -C ₄ alkyl or C ₁ -C ₃ halo 2-quinolinone derivative, characterized in that the benzyl group substituted with alkyl. A method for producing a 2-quinolinone derivative of the following general formula (Ia) by subjecting the ketenedithio acetal α-anilide represented by the following general formula (II) to heat ringing.

In the above formulas, R ₁ , R ₂ , R ₃ , R ₄ , R ₅ and R ₇ are as defined above, respectively. The method of claim 6, wherein the heat cyclization is carried out at 140 ~ 250 ℃ method of producing a 2-quinolinone derivative. A method for producing 2-quinolinone represented by the following general formula (Ib) by oxidizing the compound of the following general formula (Ia).

In the above formulas, R ₁ , R ₂ , R ₃ , R ₄ , R ₅ and R ₇ are as defined above, respectively. The method of claim 8, wherein the oxidation is carried out at 0 ~ 130 ℃ reaction method of the 2-quinolinone derivative. The method of claim 8, wherein the oxidizing agent is hydrogen peroxide, 3-tert butylhydroperoxide, chloroperoxy benzoic acid or peroxy acetic acid, or a metal oxide thereof. A method for preparing a 2-quinolinone derivative of the following general formula (Ia ') by substituting the mercaptan of the following general formula (III) with the 2-quinolinone represented by the following general formula (Ib).

In the above formula, R ₁ , R ₂ , R ₃ , R ₄ , R _5, R ₇ and R ₈ are as defined above, respectively. The method of claim 11, wherein the substitution reaction is performed at 100 to 250 ° C. 13. A method for producing 2-quinolinone represented by the following general formula (Ib ') by oxidizing a compound of the following general formula (Ia').

In the above formulas, R ₁ , R ₂ , R ₃ , R ₄ , R ₅ and R ₇ are as defined above, respectively. The method of claim 13, wherein the oxidation reaction is 20

Method for producing a 2-quinolinone derivative characterized in that the reaction at ~ 130 ℃. The method for producing 2-quinolinone according to claim 13, wherein the oxidizing agent is hydrogen peroxide, 3-tert butylhydroperoxide, chloroperoxy benzoic acid or peroxy acetic acid or metal salt oxides thereof. A fungicide comprising a 2-quinolinone derivative represented by the following general formula (I) as an active ingredient.

Wherein R ₁ , R ₂ , R ₃ , R ₄ , R ₅ and n are as defined in claim 1, respectively. A pesticide comprising a 2-quinolinone derivative represented by the following general formula (I) as an active ingredient.

Wherein R ₁ , R ₂ , R ₃ , R ₄ , R ₅ , R ₆ and n are as defined in claim 1, respectively.