KR100295818B1 - 1-amino pyrrolidine derivatives and agricultural and hortic ultural resticide composition comprising same - Google Patents

Abstract

The present invention relates to a 1-amino pyrrolidine derivative represented by the following general formula (I) having excellent bactericidal power against plant pathogens and having a broad antibacterial spectrum, and an agricultural and horticultural fungicide composition comprising the same.

(I)

Where

R ¹ is a hydrogen atom or C ₁ -C ₃ alkyl,

R ² and R ³ are each independently a hydrogen atom, a halogen atom or C ₁ -C ₃ alkyl,

Q is or to be

Wherein R ⁴ is C ₁ -C ₃ alkyl,

R ⁵ and R ⁶ are each independently hydrogen atom, halogen atom, phenoxy, benzyloxy, or benzyloxy substituted with halogen atom, C ₁ -C ₃ alkyl or C ₁ -C ₃ alkoxy,

R ⁷ is C ₁ -C ₃ alkyl,

X is oxygen or sulfur atom,

Y is an oxygen atom or S (O) _n ,

n is 0, 1 or 2).

Description

1-amino pyrrolidine derivative and agricultural horticultural fungicide composition comprising the same

The present invention relates to a 1-amino pyrrolidine derivative having excellent bactericidal activity against plant pathogens, specifically 1-phenylamino-pyrrolidine-2,5-dione and 1-phenylamino-1,3-dihydro It relates to a pyrrole-2-one derivative and agrohorticultural germicide composition comprising the same.

Conventionally, 1-phenylamino-3-phenyl-pyrrolidine-2,5-dione derivatives have been reported to have an anticonvulsant effect [MJ Kornet, J. of Phermaceutical Science , 73 , 405 (1984)]. There is no mention of bactericidal activity against pathogens.

On the other hand, a number of triazoles or imidazole derivatives are known to have bactericidal or antifungal action, and Korean Patent Application No. 97-14844 discloses 3-aryl-2- (1,2,4-triazol-1-yl). -Quinoline with 3-aryl-2- (1,3-imidazol-1-yl) -quinoline, 3-aryl-2- (1,2,4-triazol-1-yl) -1H-quinoline-4 -One and 3-aryl-2- (1,3-imidazol-1-yl) -1H-quinolin-4-one are disclosed.

However, the bactericidal action of the compound is not yet sufficient, and compounds with better activity are still needed.

It is an object of the present invention to provide 1-amino pyrrolidine derivatives which are excellent in bactericidal activity against plant pathogens.

It is another object of the present invention to provide a horticultural fungicide composition comprising the compound.

In accordance with the above object, the present invention provides a 1-amino pyrrolidine derivative represented by the following general formula (I).

Formula 1

(I)

Where

R ¹ is a hydrogen atom or C ₁ -C ₃ alkyl,

R ² and R ³ are each independently a hydrogen atom, a halogen atom or C ₁ -C ₃ alkyl,

Q is or to be

Wherein R ⁴ is C ₁ -C ₃ alkyl,

R ⁵ and R ⁶ are each independently hydrogen atom, halogen atom, phenoxy, benzyloxy, or benzyloxy substituted with halogen atom, C ₁ -C ₃ alkyl or C ₁ -C ₃ alkoxy,

R ⁷ is C ₁ -C ₃ alkyl,

X is oxygen or sulfur atom,

Y is an oxygen atom or S (O) _n ,

n is 0, 1 or 2).

In another aspect, the present invention provides a horticultural germicide composition comprising a compound bactericidal effective amount of the general formula (I) and a pharmaceutically acceptable solid or liquid carrier.

Hereinafter, the present invention will be described in detail.

Q in the compound of formula (I) according to the invention Examples of phosphorus 1-phenylamino-pyrrolidine-2,5-dione derivatives are shown in Table 1 below.

compound R ¹ R ² R ³ R ⁴ R ⁵ R ⁶ X mp ( ^o C) One H H 2'-F Me H H O 2 H H 2'-F Me H H S 3 H H 4'-F Me H H O 4 H H 4'-F Me H H S 5 H H 2'-Me Me H H O 6 H H 2'-Me Me H H S 7 H 2'-Me 4'-Cl Me H H O 8 H 2'-Me 4'-Cl Me H H S 9 H H H Me H 4-F O 10 H H H Me H 4-F S 11 Me H H Me H 4-F O 12 Me H H Me H 4-F S 13 H H H Me H 4-Cl O 118-119 14 H H H Me H 4-Cl S oil 15 Me H H Me H 4-Cl O oil 16 H H 4'-Cl Me H 4-Cl O 17 H H H Me H 4-Br O 18 H H H Me H 4-Br S oil 19 Me H H Me H 4-Br O oil 20 Me H H Me H 4-Br S oil 21 H H H Me H 4-OPh O oil 22 H H H Me H 4-OPh S oil 23 Me H H Me H 4-OPh O oil 24 Me H H Me H 4-OPh S oil 25 H H H Me H 4-OCH ₂ Ph O oil 26 H H H Me H 4-OCH ₂ Ph S oil 27 Me H H Me H 4-OCH ₂ Ph O 152-153 28 Me H H Me H 4-OCH ₂ Ph S oil 29 H H H Me H 4-OCH ₂ Ph (4-F) O oil 30 H H H Me H 4-OCH ₂ Ph (4-F) S oil 31 Me H H Me H 4-OCH ₂ Ph (4-F) O oil 32 Me H H Me H 4-OCH ₂ Ph (4-F) S oil 33 H H H Me H 4-OCH ₂ Ph (2-Cl) O 131-132 34 H H H Me H 4-OCH ₂ Ph (2-Cl) S oil

compound R ¹ R ² R ³ R ⁴ R ⁵ R ⁶ X mp ( ^o C) 35 Me H H Me H 4-OCH ₂ Ph (2-Cl) O 67-68 36 Me H H Me H 4-OCH ₂ Ph (2-Cl) S oil 37 H H H Me H 4-OCH ₂ Ph (2-Br) O 38 H H H Me H 4-OCH ₂ Ph (2-Br) S oil 39 Me H H Me H 4-OCH ₂ Ph (2-Br) O oil 40 Me H H Me H 4-OCH ₂ Ph (2-Br) S oil 41 H H H Me H 4-OCH ₂ Ph (2-Me) O oil 42 H H H Me H 4-OCH ₂ Ph (2-Me) S oil 43 Me H H Me H 4-OCH ₂ Ph (2-Me) O oil 44 Me H H Me H 4-OCH ₂ Ph (2-Me) S oil 45 H H H Me H 4-OCH ₂ Ph (3-Me) O 46 H H H Me H 4-OCH ₂ Ph (3-Me) S oil 47 Me H H Me H 4-OCH ₂ Ph (3-Me) O 48 Me H H Me H 4-OCH ₂ Ph (3-Me) S 49 H H H Me H 4-OCH ₂ Ph (3-OMe) O oil 50 H H H Me H 4-OCH ₂ Ph (3-OMe) S oil 51 Me H H Me H 4-OCH ₂ Ph (3-OMe) O oil 52 Me H H Me H 4-OCH ₂ Ph (3-OMe) S oil 53 H H H Me 2-Cl 4-Cl O oil 54 H H H Me 2-Cl 4-Cl S oil 55 Me H H Me 2-Cl 4-Cl O oil 56 Me H H Me 2-Cl 4-Cl S oil

In addition, Q in the compound of general formula (I) Examples of phosphorus 1-phenylamino-1,3-dihydro-pyrrole-2-one derivatives are shown in Table 2 below.

compound R ¹ R ² R ³ R ⁴ R ⁵ R ⁶ R ⁷ Y mp ( ^o C) 57 H H H Me H 4-Cl Me S 58 Me H H Me H 4-Cl Me S 59 Me H H Me H 4-Cl Me SO ₂ 60 H H H Me H 4-Br Me S 61 Me H H Me H 4-Br Me S 62 Me H H Me H 4-OPh Me S 63 H H H Me H 4-OCH ₂ Ph (2-Me) Me S 64 Me H H Me H 4-OCH ₂ Ph (2-Me) Me S 65 Me H H Me H 4-OCH ₂ Ph (3-OMe) Me S 66 Me H H Me 2-Cl 4-Cl Me S

Compound (I) of the present invention can be prepared according to the following reaction scheme.

Where

R ¹ , R ² , R ³ , R ⁴ , R ⁵ , R ⁶ and R ⁷ are as defined above and m is 1 or 2.

Referring to the preparation method of the compound of the general formula (I) step by step.

(Step 1)

The phenylacetate derivative (II) is alkylated with an alkyl halide in the presence of a base to give compound (III). At this time, sodium hydride, potassium t-butoxide, lithium bistrimethylsilylamide, lithium diisopropylamide, etc. may be used as a base, and as a reaction solvent, dimethylformamide, tetrahydrofuran, ethyl ether, dimethyl sulfoxide Etc. can be used, Preferably it is dimethylformamide, and reaction temperature is 0-40 degreeC. Yield is 90-98%.

(Step 2)

Compound (III) is alkylated with methylbromoacetate in the presence of a base to give compound (IV). At this time, the reaction conditions such as base, reaction solvent and reaction temperature are the same as in step 1, the yield is 40 to 60%.

(Step 3)

Compound (IV) is hydrolyzed under basic conditions to give compound (V). At this time, potassium hydroxide, sodium hydroxide, etc. may be used as the base, water or alcohol may be used as the reaction solvent, and the reaction solution may be refluxed to obtain a compound (V) in high yield.

(Step 4)

Compound (V) can be directly refluxed in an organic acid such as acetic acid or propionic acid or aromatic organic solvent such as xylene or dichlorobenzene in the presence of phenylhydrazine to directly obtain compound (Ia) of the present invention.

Alternatively, compound (I) of the present invention may be obtained by two steps of refluxing compound (V) in acetyl chloride to obtain a furandione compound and then refluxing in acetic acid solvent in the presence of phenylhydrazine.

(Step 5)

Compound (Ia) is refluxed in an aromatic organic solvent such as benzene and toluene together with a Lawson reagent to obtain compound (Ib) of the present invention in which the oxygen atom is substituted with a sulfur atom in high yield.

(Step 6)

Compound (Ia) is alkylated with an alkyl halide in the presence of a base to give compound (Ic) of the present invention. In this case, sodium hydride, potassium t-butoxide, butyl lithium, etc. may be used as the base, dimethylformamide, tetrahydrofuran, etc. may be used as the reaction solvent, and the reaction temperature is -20 to 40 ° C.

(Step 7)

The alkylation reaction was carried out in the same manner as in Step 6 except that Compound (Ib) was used instead of Compound (Ia), to obtain Compound (Id) of the present invention.

(Step 8)

Compound (Id) is oxidized in an organic solvent containing an oxidizing agent to obtain compound (Ie) of the present invention. In this case, as the oxidizing agent, conventional oxidizing agents such as hydrogen peroxide, acetic acid peroxide, benzoic acid peroxide, oxone, and the like may be used, and as the organic solvent, halogen solvents such as dichloromethane and chloroform, alcohols such as methanol and ethanol, acetic acid and the like may be used , Reaction temperature is 0-110 degreeC.

Compounds of formula (I) of the present invention can be converted to acid addition salts according to conventional methods. Examples of such acid addition salts include acid acceptable salts of preparations such as inorganic acids such as hydrochloric acid, sulfuric acid, nitric acid and hydrobromic acid, or organic acids such as acetic acid, oxalic acid, fumaric acid, maleic acid and citric acid.

The compound of general formula (I) has a superior bactericidal action against various plant pathogens, and can be used for suppression and eradication of diseases caused by this pathogen. In particular, the compound of formula (I) has a remarkable effect on rice, Rhizoctonia solani and Pyricularia oryzae , which are serious diseases of rice, and have the following crop diseases: Corticium centrifugum , Rice white leaf blight ( Xanthomonas oryzae ), Chinese cabbage soft rot ( Erwinia aroideae ), ulcer disease ( Xanthomonas citri ), rice hoebi ( Cochliobolus miyabeanus ), banana spot ( Mycosphaerella musicola ), cucumber and strawberry gray fungus ( Botrytis cinerea ) Plasmopara viticola , Glomella cingulata of grapes, apples, and pears, Sclerotinia sclerotiorum of vegetables, Colletotrichum lagenarium , Diaporthe citri , and Podosphaera such leucotricha), cucumber mildew (Sphaerotheca fuliginea), apples spot (Alternaria mali) and folds, such as potatoes rounded blotch (Alternaria solani) and fold heukban (Alternaria kikuchiana) Half, and Apple is also effective as heukseongbyeong (Venturia inaequalis) and pears heukseongbyeong heukseongbyeong.

Accordingly, the present invention provides agrohorticultural fungicide compositions comprising an effective amount of a compound of formula (I) and a pharmaceutically acceptable salt thereof and a pharmaceutically acceptable solid or liquid carrier.

The bactericidal active compound (I) according to the present invention is a solution, emulsion, wetting agent, suspension, powder, powder, foaming agent, pasta, solvent powder, granule, aerosol, emulsion, powder for seed treatment, natural saturated with active compound and It can be used by converting it into a composition used in heating devices such as synthetic materials, very fine capsules in polymerized materials, seed coating compositions, and fumigation cartridges, fumigation cans, fumigation coils, and ULV cold misting and warming agents. . Such formulations may be prepared by known methods for mixing the active compound with a weighting agent such as liquid or liquefied gas or solid diluents or carriers, and optionally surfactants such as emulsifiers and dispersants or foaming agents may be used. In addition, when water is used as a weighting agent, an organic solvent may be used as an auxiliary solvent. Compound (I) of the present invention may be used in an amount of 0.1 to 95% depending on the formulation.

Hereinafter, the present invention will be described in more detail with reference to Preparation Examples and Examples, but the present invention is not limited thereto.

Preparation Example 1 Preparation of Methyl 2- (4-chlorophenyl) propanoate

Under nitrogen atmosphere, 13.1 g (328 mmol) of 60% sodium hydride was added to 500 ml of anhydrous dimethylformamide, cooled to 0 ° C., and 50 g (271 mmol) of methyl 2- (4-chlorophenyl) acetate was added dropwise while stirring. Stirred at room temperature for 1 hour. The reaction was then cooled to 0 ° C. and then 42.3 g (328 mmol) of iodine methane were added dropwise and stirred at room temperature for 1 hour. The reaction was added to 1000 ml of ice water and extracted twice with 200 ml of dichloromethane. The organic layer was dried over anhydrous sodium sulfate, filtered and concentrated. The product was purified by column chromatography (eluent, n-hexane: ethyl acetate = 6: 1) to give 50.0 g (yield 93%) of the title compound.

Preparation Example 2 Preparation of Dimethyl 2- (4-Chlorophenyl) -2-methyl Succinate

In a nitrogen atmosphere, 10.7 g (267 mmol) of sodium hydride was added to 500 ml of 60% anhydrous dimethylformamide, cooled to 0 ° C., and 52.4 g (264 mmol) of the compound obtained in Preparation Example 1 was added dropwise with stirring, followed by 18 at room temperature. Stir for hours. The reaction was then cooled to 0 ° C. and then 40.7 g (267 mmol) of methylbromoacetate was added dropwise and stirred at room temperature for 1 hour. The reaction was added to 1000 ml of ice water and extracted twice with 200 ml of dichloromethane. The organic layer was dried over anhydrous sodium sulfate, filtered and concentrated. The product was purified by column chromatography (eluent, n-hexane: ethyl acetate = 3: 1) to give 50.7 g (71% yield) of the title compound.

Preparation Example 3 Preparation of Dimethyl 2- (4-Chlorophenyl) -2-methyl Succinic Acid

30.7 g (113 mmol) of the compound obtained in Preparation Example 3 was dissolved in 300 ml of methanol, and a solution of 22.5 g (340 mmol) of 85% potassium hydroxide in 50 ml of water was added dropwise, followed by stirring at reflux at 100 to 120 ° C. for 4 hours. It was. The product was concentrated to about 100 ml, 500 ml of ice water was added, and 10% hydrochloric acid was added to pH 5 to obtain a white solid product. The product was filtered under reduced pressure and dried to give 23.6 g (yield 86%) of the title compound.

Example 1 Preparation of 1-phenylamino-3- (4-chlorophenyl) -3-methyl-pyrrolidine-2,5-dione (compound 13 in Table 1)

10 ml of acetyl chloride was added to 5.00 g (20.6 mmol) of the compound obtained in Preparation Example 3 under a nitrogen atmosphere, and the mixture was refluxed at 50 to 60 ° C. for 1 hour while stirring. The reaction was then distilled under reduced pressure to remove acetyl chloride, and the resulting 3- (4-chlorophenyl) -3-methyltetrahydro-2,5-furan dione compound was used directly without further purification.

4.7 g of the obtained 3- (4-chlorophenyl) -3-methyltetrahydro-2,5-furandione compound was added to 50 ml of acetic acid and 2.45 g (22.7 mmol) of phenylhydrazine was added, followed by 1 hour at a temperature of 120 to 140 ° C. At reflux. The reaction was distilled under reduced pressure to remove acetic acid, xylene was added and then distilled briefly. The product was subjected to column chromatography (eluent, n-hexane: ethyl acetate = 3: 1) without further treatment to give 5.38 g (yield 83%) of the title compound.

¹ H NMR (200 MHz, CDCl 3) δ 7.33 (s, 4H, aromatic), 7.28-7.16 (m, 2H, aromatic), 6.99-6.90 (m, 1H, aromatic), 6.72-6.67 (m, 2H, aromatic) , 2.95 (dd, J = 50.6, 18.8 Hz, 2H, CH ₂ ), 1.60 (s, 3H, Me).

Example 2: Preparation of 1-phenylamino-3- (4-chlorophenyl) -3-methyl-5-thioxo-pyrrolidin-2-one (Compound 14)

Under nitrogen atmosphere, 15 ml of anhydrous benzene was added to 1.50 g (4.76 mmol) of the compound obtained in Example 1 and 2.12 g (5.24 mmol) of Lawson reagent, followed by reflux for 4 hours with stirring. Directly performing column chromatography (eluent, n-hexane: ethyl acetate = 3: 1) on the reaction product was carried out to obtain 1.43 g (yield 91%) of the title compound.

¹ H NMR (200MHz, CDCl3) δ 7.35 (s, 4H, aromatic), 7.30-7.17 (m, 2H, aromatic), 7.03-6.95 (m, 1H, aromatic), 6.77-6.73 (m, 2H, aromatic) , 2.99 (ddd, J = 56.2, 19.2, 1.0 Hz, 2H, CH ₂ ), 1.76 (s, 3H, Me).

Example 3 of 3- (4-chlorophenyl) -3-methyl-1- (methyl-phenyl-amino) -5-methylsulfanyl-2,3-dihydro-pyrrol-2-one (compound 59) Produce

725 mg (18.1 mmol) of 60% sodium hydride was added to 30 ml of anhydrous dimethylformamide in a nitrogen atmosphere, cooled to 0 ° C., and 3.00 g (9.06 mmol) of the compound obtained in Example 2 was added dropwise with stirring to room temperature. Stir for hours. After the reaction was cooled to 0 ° C., 2.55 g (18.1 mmol) of iodine methane was added thereto, and the resultant was stirred at room temperature for 1 hour. The product was added to 200 ml of ice water and extracted with dichloromethane. The extract was dehydrated and concentrated with anhydrous sodium sulfate, and then purified by column chromatography (eluent, n-hexane: ethyl acetate = 2: 1) to obtain 1.76 g (54% yield) of the title compound.

¹ H NMR (200 MHz, CDCl 3) δ 7.54-7.11 (m, 5H, aromatic), 6.98-6.67 (m, 4H, aromatic), 5.16 (s, 1H), 5.13 (s, 1H), 3.26 (d, J = 11 Hz, 3H, N-Me), 2.31 (s, 3H, S-Me), 1.62 (s, 3H, Me)

Example 4 of 3- (4-chlorophenyl) -3-methyl-1- (methyl-phenyl-amino) -5-methylsulfonyl-2,3-dihydro-pyrrol-2-one (compound 60) Produce

0.81 g (2.0 mmol) of the compound obtained in Example 3 was added to 10 ml of methanol in which 1.23 g (2.0 mmol) of oxone was dissolved, followed by stirring at room temperature for 3 hours. The reaction was added to 20 g of ice water and extracted twice with 30 ml of dichloromethane. The organic layer was washed with 100 ml of water and then dried over anhydrous sodium sulfate, filtered and concentrated. The product was purified by column chromatography (eluent, n-hexane: ethyl acetate = 3: 1) to give 0.77 g (yield 92%) of the title compound.

¹ H NMR (200 MHz, CDCl 3) δ 7.69-7.17 (m, 5H, aromatic), 7.10-6.85 (m, 4H, aromatic), 5.17 (s, 1H), 5.13 (s, 1H), 3.28 (d, J = 12 Hz, 3H, N-Me), 3.12 (s, 3H, SO ₂ Me), 1.62 (s, 3H, Me).

The compounds of the present invention described in Tables 1 and 2 were synthesized in the same manner as in Examples 1 to 4, and the ¹ H NMR spectra of these compounds were shown in Tables 3 and 4, respectively.

Compound number ¹ H NMR (CDCl ₃ , 200 MHz) 9 7.12-6.89 (m, 4H), 6.80-6.72 (m, 2H), 6.68-6.60 (m, 2H), 2.89 (dd, J = 47.4, 17.8 Hz, 2H), 1.58 (s, 3H) 10 7.16-7.00 (m, 3H), 6.95-6.80 (m, 3H), 6.74-6.71 (m, 2H), 2.87 (dd, J = 56.4, 18.8 Hz, 2H), 1.63 (s, 3H) 11 7.14-7.00 (m, 3H), 6.86-6.77 (m, 3H), 6.75-6.71 (m, 2H), 2.80 (s, 3H), 2.64 (dd, J = 55.8, 16.7 Hz, 2H), 1.54 ( s, 3 H) 12 7.16-7.00 (m, 3H), 6.90-6.82 (m, 3H), 6.77-6.70 (m, 2H), 2.76 (s, 3H), 2.64 (dd, J = 45.0, 15.7 Hz, 2H), 1.61 ( s, 3 H) 13 7.33 (s, 4H), 7.28-7.16 (m, 2H), 6.99-6.90 (m, 1H), 6.72-6.67 (m, 2H), 2.95 (dd, J = 50.6, 18.8 Hz, 2H), 1.60 ( s, 3 H) 14 7.35 (s, 4H), 7.30-7.17 (m, 2H), 7.03-6.95 (m, 1H), 6.77-6.73 (m, 2H), 2.99 (ddd, J = 56.2, 19.2, 1.0 Hz, 2H), 1.76 (s, 3 H) 15 7.32 (s, 4H), 7.25-7.18 (m, 2H), 6.92-6.84 (m, 1H), 6.69-6.65 (m, 2H), 3.27 (s, 3H), 2.99 (dd, J = 49.8, 18.7 Hz, 2H), 1.68 (s, 3H) 17 7.40-7.21 (m, 4H), 7.00-6.88 (m, 2H), 6.79-6.69 (m, 3H), 3.20 (dd, J = 55.9, 18.0 Hz, 2H), 1.64 (s, 3H) 18 7.42-7.20 (m, 4H), 7.00-6.84 (m, 2H), 6.74-6.66 (m, 3H), 3.14 (dd, J = 60.5, 17.8 Hz, 2H), 1.69 (s, 3H) 19 7.50-7.15 (m, 4H), 7.02-6.90 (m, 2H), 6.82-6.71 (m, 3H), 3.70 (s, 3H), 3.18 (dd, J = 70.4, 18.8 Hz, 2H), 1.65 ( s, 3 H) 20 7.48-7.18 (m, 4H), 7.05-6.95 (m, 2H), 6.84-6.70 (m, 3H), 3.66 (s, 3H), 3.22 (dd, J = 65.2, 19.7 Hz, 2H), 1.71 ( s, 3 H) 21 7.60-7.43 (m, 2H) 7.20-7.00 (m, 4H), 6.88-6.60 (m, 4H), 3.34 (dd, J = 68.8, 19.2 Hz, 2H), 1.60 (s, 3H) 22 7.58-7.42 (m, 2H) 7.24-7.11 (m, 4H), 6.90-6.72 (m, 4H), 3.30 (dd, J = 48.58, 18.2 Hz, 2H), 1.70 (s, 3H) 23 7.50-7.20 (m, 2H), 7.12-7.00 (m, 4H), 6.90-6.82 (m, 4H), 3.68 (s, 3H), 3.38 (dd, J = 75.6, 19.0 Hz, 2H), 1.63 ( s, 3 H) 24 7.60-7.32 (m, 2H), 7.25-7.00 (m, 4H), 6.95-6.80 (m, 4H), 3.66 (s, 3H), 3.49 (dd, J = 42.4, 16.4 Hz, 2H), 1.71 ( s, 3 H) 25 7.43-7.02 (m, 9H) 6.90-6.80 (m, 5H), 4.98 (s, 2H), 3.06 (dd, J = 70.4, 18.8 Hz, 2H), 1.70 (s, 3H) 26 7.50-7.10 (m, 9H) 7.00-6.85 (m, 5H), 5.02 (s, 2H), 3.10 (dd, J = 65.0, 18.4 Hz, 2H), 1.78 (s, 3H) 27 7.49-7.12 (m, 9H) 7.04-6.82 (m, 5H), 4.99 (s, 2H), 3.30 (s, 3H), 3.04 (dd, J = 75.4, 17.8 Hz, 2H), 1.68 (s, 3H ) 28 7.60-7.25 (m, 9H) 7.12-6.92 (m, 5H), 5.00 (s, 2H), 3.46 (s, 3H), 3.08 (dd, J = 70.0, 19.4 Hz, 2H), 1.75 (s, 3H )

29 7.63-7.20 (m, 8H) 7.12-6.95 (m, 5H), 4.99 (s, 2H), 3.17 (dd, J = 65.4, 18.6 Hz, 2H), 1.64 (s, 3H) 30 7.59-7.15 (m, 8H) 7.07-6.92 (m, 5H), 5.00 (s, 2H), 3.20 (dd, J = 72.0, 19.8 Hz, 2H), 1.72 (s, 3H) 31 7.52-7.22 (m, 8H) 7.13-6.90 (m, 5H), 5.01 (s, 2H), 3.47 (s, 3H), 3.10 (dd, J = 45.4, 16.2 Hz, 2H), 1.60 (s, 3H ) 32 7.65-7.30 (m, 8H) 7.20-7.02 (m, 5H), 4.97 (s, 2H), 3.53 (s, 3H), 3.07 (dd, J = 52.8, 18.0.2 Hz, 2H), 1.68 (s , 3H) 33 7.54-7.47 (m, 2H) 7.32-7.14 (m, 6H), 7.03-6.89 (m, 3H), 6.80-6.64 (m, 2H), 5.12 (s, 2H), 3.04 (dd, J = 65.4, 18.6 Hz, 2H), 1.75 (s, 3H) 34 7.60-7.51 (m, 2H) 7.35-7.20 (m, 6H), 7.09-6.93 (m, 3H), 6.82-6.65 (m, 2H), 5.10 (s, 2H), 3.14 (dd, J = 70.4, 19.6 Hz, 2H), 1.78 (s, 3H) 35 7.57-7.48 (m, 2H) 7.35-7.18 (m, 6H), 7.05-6.90 (m, 3H), 6.82-6.60 (m, 2H) 4.98 (s, 2H), 3.52 (s, 3H), 3.05 ( dd, J = 70.2, 19.0 Hz, 2H), 1.62 (s, 3H) 36 7.63-7.55 (m, 2H) 7.48-7.25 (m, 6H), 7.14-6.99 (m, 3H), 6.90-6.78 (m, 2H) 5.01 (s, 2H), 3.64 (s, 3H), 3.10 ( dd, J = 55.2, 14.8 Hz, 2H), 1.69 (s, 3H) 37 7.30-7.06 (m, 8H), 7.00-6.89 (m, 3H), 6.76-6.69 (m, 2H), 5.00 (s, 2H), 3.25 (dd, J = 65.8, 17.4 Hz, 2H), 2.34 ( s, 3H), 1.60 (s, 3H) 38 7.27-7.07 (m, 8H), 6.94-6.89 (m, 3H), 6.69-6.65 (m, 2H), 4.95 (s, 2H), 3.39 (dd, J = 72.2, 19.0 Hz, 2H), 2.31 ( s, 3H), 1.65 (s, 3H) 39 7.25-7.00 (m, 8H), 6.99-6.80 (m, 3H), 6.70-6.62 (m, 2H), 4.98 (s, 2H), 3.30 (s, 3H), 3.03 (dd, J = 68.8, 19.4 Hz, 2H), 2.32 (s, 3H), 1.68 (s, 3H) 40 7.33-7.13 (m, 8H), 6.99-6.83 (m, 3H), 6.67-6.64 (m, 2H), 4.99 (s, 2H), 3.27 (s, 3H), 3.03 (dd, J = 61.8, 18.2 Hz, 2H), 2.34 (s, 3H), 1.72 (s, 3H) 41 7.35-7.20 (m, 8H), 7.10-6.85 (m, 3H), 6.67-6.60 (m, 2H), 5.01 (s, 2H), 3.40 (dd, J = 68.8, 18.6 Hz, 2H), 2.30 ( s, 3H), 1.65 (s, 3H) 42 7.38-7.21 (m, 8H), 7.18-6.91 (m, 3H), 6.73-6.70 (m, 2H), 5.00 (s, 2H), 3.45 (dd, J = 71.6, 19.2 Hz, 2H), 2.34 ( s, 3H), 1.71 (s, 3H) 43 7.35-7.12 (m, 8H), 6.99-6.87 (m, 3H), 6.72-6.65 (m, 3H), 5.04 (s, 2H), 3.31 (s, 3H), 3.07 (dd, J = 67.2, 19.8 Hz, 2H), 2.35 (s, 3H), 1.72 (s, 3H) 44 7.42-7.20 (m, 8H), 7.12-7.00 (m, 3H), 6.84-6.70 (m, 3H), 5.07 (s, 2H), 3.31 (s, 3H), 3.08 (dd, J = 45.2, 14.3 Hz, 2H), 2.40 (s, 3H), 1.80 (s, 3H) 45 7.42-7.18 (m, 8H), 7.05-6.90 (m, 3H), 6.82-6.69 (m, 2H), 5.01 (s, 2H), 3.74 (s, 3H), 3.25 (dd, J = 67.8, 17.4 Hz, 2H), 1.60 (s, 3H) 46 7.47-7.15 (m, 8H), 7.04-6.89 (m, 3H), 6.75-6.68 (m, 2H), 4.98 (s, 2H), 3.85 (s, 3H), 3.27 (dd, J = 72.8, 19.0 Hz, 2H), 1.65 (s, 3H) 47 7.43-7.20 (m, 8H), 6.99-6.76 (m, 3H), 6.70-6.62 (m, 2H), 4.98 (s, 2H), 3.78 (s, 3H), 3.03 (dd, J = 67.5, 18.4 Hz, 2H), 1.68 (s, 3H) 48 7.57-7.29 (m, 8H), 7.10-6.99 (m, 3H), 6.87-6.72 (m, 2H), 4.99 (s, 2H), 3.80 (s, 3H), 3.10 (dd, J = 60.8, 18.2 Hz, 2H), 2.44 (s, 3H), 1.72 (s, 3H) 53 7.40-7.26 (m, 3H), 7.14-6.98 (m, 3H), 6.72-6.67 (m, 2H), 2.96 (dd, J = 51.6, 19.8 Hz, 2H), 1.54 (s, 3H)

54 7.37-7.27 (m, 3H), 7.16-6.94 (m, 3H), 6.80-6.71 (m, 2H), 2.98 (dd, J = 51.0, 19.8 Hz, 2H), 1.62 (s, 3H) 55 7.44-7.28 (m, 3H), 7.16-6.99 (m, 3H), 6.85-6.77 (m, 2H), 3.31 (s, 3H), 3.01 (dd, J = 48.8, 15.7 Hz, 2H), 1.60 ( s, 3 H) 56 7.42-7.18 (m, 3H), 7.02-6.84 (m, 3H), 6.74-6.65 (m, 2H), 3.30 (s, 3H) 3.16 (dd, J = 42.0, 19.2 Hz, 2H), 1.68 ( s, 3 H)

57 7.53-7.22 (m, 5H), 6.98-6.67 (m, 4H), 5.22 (s, 1H), 5.19 (s, 3H), 2.39 (s, 3H), 1.28 (s, 3H) 58 7.54-7.11 (m, 5H), 6.98-6.67 (m, 4H), 5.16 (s, 1H), 5.13 (s, 1H), 3.26 (d, J = 11 Hz, 3H), 2.31 (s, 3H), 1.62 (s, 3 H) 59 7.69-7.17 (m, 5H), 7.10-6.85 (m, 4H), 5.17 (s, 1H), 5.13 (s, 1H), 3.28 (d, J = 12 Hz, 3H), 3.12 (s, 3H), 1.62 (s, 3 H)

The bactericidal activity of the prepared compounds of the present invention was measured as follows. That is, to investigate the preventive effect against plant pathogens, 50 mg of the test compound was dissolved in 10 ml of acetone, and then 140 ml of 250 ppm aqueous Tween 20 solution was added to adjust the concentration to 250 ppm. 50 ml of this solution were sprayed onto the foliar of a certain size of host plant. The plants sprayed with the medicament were left at room temperature for 24 hours to volatilize the solvent and water, and then inoculated there with plant pathogens. The pathogen strains of the test examples below were taken directly from wild plants and used by pure alternation culture. All experiments were repeated twice.

Test Example 1 Bactericidal Effect on Rice Blast

Pyricularia oryzae strains of rice blast were inoculated in rice bran agar medium (rice bran 20 g, dextrose 10 g, agar 15 g, distilled water 1 L) and incubated for 2 weeks in a 26 ^o C incubator. The surface of the medium in which the pathogen was grown was scraped off with a rubber gallbladder to remove aerial hyphae and placed on a fluorescent lighted shelf (25-28 ^o C) for 48 hours to form spores. The bacterial inoculation was inoculated with pathogens by spraying the conidia to form a spore suspension of 10 ⁶ spores / ml using sterile distilled water, and then spraying enough to flow into Nakdong rice (3-4 leaves) susceptible to rice blasting. . The inoculated rice was left in the dark for 24 hours, and then placed for 5 days in a constant temperature and humidity room with a relative humidity of 90% or more and a temperature of 26 ± 2 ^o C. The incidence was investigated by examining the lesion area formed on the fully developed leaf just below the top leaf of 3-4 leafy rice, according to the standard disease area ratio comparison table.

Test Example 2: bactericidal effect on rice leaf blight blight

After the appropriate amount of bran was put into a 1L culture bottle and sterilized, agar pieces of Rhizoctonia solani ( Rhizoctonia solani ) grown in potato agar medium (PDA) for 3 days were inoculated and incubated at 25 ^o C for 10 days. . After cultivating the mycelial cultivation moderately finely, inoculate evenly into the pot (5 cm) in which Nakdong rice of 2-3 leaves was grown, and incubate in a wet room (28 ± 1 ^o C), and leave it for 5 days in a constant temperature and humidity room with a relative humidity of 80% or more. Disease occurrence was investigated. The incidence was investigated according to the comparison table of disease area ratios based on the ratio of lesion area to leaf area of leaf lesions.

Test Example 3: bactericidal effect on cucumber gray mold

Strains isolated from cucumber gray mold disease ( Botrytis cinerea ) were inoculated in potato agar medium (PDA) and incubated in a 25 ^° C. incubator for 15 days to form spores. Enough distilled water of 10 ml per plate on medium brush scratched after the spores were harvested by filtering the spores in spore gauze then a concentration of 10 ⁶ / ml and then such that the flow down to the 1 leaf stage cucumber was inoculated spray. After 3 days of wet treatment on 20 ^o C wet room, the leaf area ratio of the first leaf was investigated.

Test Example 4 bactericidal effect against tomato late blight

Phytophthora infestans strains were inoculated into V-8 juice agar medium (V-8 juice 200 ml, potassium carbonate 4.5 g, agar 15 g, distilled water 800 ml) and light treated at 20 ^o C for 16 hours and 8 hours. Spores were formed by incubation for 14 days in the dark. Sterile distilled water was added to the plate and shaken to separate the zygote sac from the flora, and then the zygote sac was harvested using a 4-ply piece of cloth. After adjusting the concentration of lactose sac to 10 ⁵ pcs / ml, it was sprayed with tomato seedlings for 1 day in a 20 ^o C chamber, then transferred to a constant temperature and humidity chamber at 20 ° C. and a relative humidity of 80% or higher, and then developed for 4 days. The lesion area (%) of one and two leaves of tomato was investigated.

Test Example 5: bactericidal effect against wheat red rust

Puccinia recondita strains of wheat red rust were used for passaging directly to plants in a laboratory. For seeding culture and investigation of efficacy, 15 seed grains (silver onions) were sown in a disposable pot (diameter: 6.5 cm), and then spores were inoculated by sprinkling one leafy wheat grown for 7 days in a greenhouse. Wheat inoculated leaf stage 1 was examined after the onset of the disease induced 10 transferred to a 20 ^o C in a wet substance of seupsil one days after treatment and a relative humidity of 70% 20 ^o C constant temperature hangseupsil inoculated days. The onset was to investigate the lesion area rate 10 days after inoculation of spores.

Test Example 6: bactericidal effect on barley flour bottle

Erysiphe graminis f.sp.hordei strain of barley powdery mildew was used by passage in the laboratory. For passaging of the strain and investigation of efficacy, 15 seeded barley seeds (East barley No. 1) were sown in a disposable pot (diameter: 6.5 cm), and grown on a single barley barley grown for 7 days in a greenhouse (25 ± 5 ° C). Powdered spore spores were inoculated and inoculated. The inoculated plants were inoculated in the same manner as above, and the relative humidity of 50% and 22-24 ℃ was transferred to a constant temperature and humidity room to induce the onset for 7 days and then the area ratio of the lesions was investigated.

From the test results of Test Examples 1 to 6, a control value was calculated according to Equation 1 below.

According to the calculated control value, the activity index (++++: 81-100% for control, +++: 61-80% for control, ++: 41-60% for control, +: 21-40% for control ,-: Control was 0-20%), and the results are shown in Table 5.

Compound number Rice fever Rice leaf pattern Cucumber gray mold Tomato plague Wheat Red Rust Wheat flour 13 - ++ +++ ++ + - 14 ++++ - + +++ ++++ + 15 ++ + ++ + ++++ + 17 - + - - - - 18 ++++ ++ + ++++ +++ - 19 - +++ - ++ +++ - 20 - + + - - - 21 ++++ ++ - ++ +++ - 22 ++++ ++ - ++ + - 23 ++ ++ - - - - 24 - + - - - - 25 - + - ++ - - 26 - + - + - - 27 - + + - - - 28 - + - - - - 29 - ++ + - - - 30 - ++ - - - - 31 - ++ + - - - 32 - + + - - - 33 - - +++ ++ - + 34 - ++ ++ + ++ ++++ 35 - ++ + ++ +++ + 36 - ++ - - - - 37 - - + - - - 38 - ++ - - + - 39 - - +++ - - - 40 + ++ - - - - 41 ++++ +++ - +++ ++++ + 42 - + - - - - 43 +++ - - + +++ - 44 ++++ +++ - +++ ++++ + 45 ++ - - ++ ++++ - 46 ++ - - + - - 47 - - - - - +++ 49 - ++ - + + - 50 - + - - - - 51 - ++ + ++++ +++ - 52 - - - - - + 53 - ++ - ++ + + 63 - + - - - -

As shown in Table 5, it can be seen that the compounds of the present invention have excellent bactericidal activity against plant pathogens and a broad antibacterial spectrum.

The novel 1-amino pyrrolidine derivatives of the general formula (I), which are the compounds of the present invention, have excellent bactericidal activity and broad antibacterial spectrum, and thus are useful as agricultural horticultural fungicides.

Claims (2)

1-amino pyrrolidine derivative represented by the following general formula (I). Formula 1 (I) Where R ¹ is a hydrogen atom or C ₁ -C ₃ alkyl, R ² and R ³ are each independently a hydrogen atom, a halogen atom or C ₁ -C ₃ alkyl, Q is or to be Wherein R ⁴ is C ₁ -C ₃ alkyl, R ⁵ and R ⁶ are each independently hydrogen atom, halogen atom, phenoxy, benzyloxy, or benzyloxy substituted with halogen atom, C ₁ -C ₃ alkyl or C ₁ -C ₃ alkoxy, R ⁷ is C ₁ -C ₃ alkyl, X is oxygen or sulfur atom, Y is an oxygen atom or S (O) _n , n is 0, 1 or 2). Rice fever, rice leaf blight, cucumber ash fungus, tomato late blight, wheat rust and barley, comprising a bactericidal effective amount of the compound of formula (I) according to claim 1 and a pharmaceutically acceptable solid or liquid carrier Agrohorticultural fungicide composition having a bactericidal effect against pathogens causing powdery mildew.