KR100373705B1 - 1-phenyl 4-azolyl pyrazole derivatives, method of preparing the same and antifungal composition comprising the same for agriculture - Google Patents

Abstract

The present invention relates to a novel 1-phenyl 4-azolyl pyrazole derivative useful as an agricultural and horticultural fungicide, wherein the 1-phenyl 4-azolyl pyrazole derivative has the following formula (1). This compound has a wide range of bactericidal effects against plant pathogens including resistant bacteria, and is excellent in preventing as well as invasive effects. In addition, agrohorticultural fungicide compositions containing an effective amount of this compound as an active ingredient can be used against a wide range of plant pathogens along with other ingredients.

[Formula 1]

(Wherein

n represents 0-2,

X is 1 to 3 C ₁ -C ₃ alkyl group, 1 to 3 chloro group, 1 to 3 fluoro group, 1 to 3 C _1-3 alkoxy group, nitro group, trihaloalkyl group, 3,4 -An ethylenedioxy group or a phenyl group or a phenoxy group,

Y is hydrogen, 1 to 3 C ₁ -C ₃ alkyl group, 1 to 3 chloro group, 1 to 3 fluoro group, 1 to 3 C _1-3 alkoxy group, nitro group, trihaloalkyl group or phenyl group Is,

Z is CH or N.)

Description

1-Phenyl 4-azolyl pyrazole derivatives, a method for producing the same, and a agricultural horticultural fungicide composition comprising the same

[Industrial use]

The present invention relates to a 1-phenyl 4-azolyl pyrazole derivative, a method for preparing the same, and an agricultural / horticultural germicide composition comprising the same, and more particularly, to a 1-phenyl 4-azolyl pyrazole derivative having an excellent bactericidal effect. .

[Prior art]

Looking at the recent development of pesticides worldwide, the development of low-dose, high selectivity, low toxicity and low pollution pesticides is mainstream due to concerns about toxicity to humans or organisms and pollution to the environment. Therefore, while inorganic and organometallic, organophosphorus compound fungicides, etc. are showing stagnation and reduction, penetration-transmitting fungicides such as azoles and benzenoids continue to grow. However, with the use of a large amount of these fungicides, resistant bacteria that are resistant to them are also rapidly expressed. Therefore, in order to reduce the expression of resistant bacteria, not only the penetration effect due to the derivation of a fungicide having a new mechanism of action, but also prevention and treatment There is an urgent need for the development of effective drugs.

EP 508527 describes pyrazole compounds of formula A having bactericidal activity.

[Formula A]

(Wherein

Ar is an unsubstituted phenyl group, a substituted or unsubstituted C ₁ -C ₄ alkyl group, a halogen, a cyano group and a C ₁ -C ₄ alkoxy group substituted, or three halogen groups substituted phenyl group,

R is an alkyl group of C ₁ -C ₁₂ ,

R ₁ is an alkyl group of C ₁ -C ₄ ,

Y is CH or N.)

However, the above-mentioned compounds not only have a narrow sterilization range but also require a high amount of a drug to obtain a sterilizing effect. Therefore, the need for research on compounds having a bactericidal effect of the new structure is emerging.

It is an object of the present invention to provide a 1-phenyl 4-azolyl pyrazole derivative having a wide range of bactericidal effects against plant pathogens including resistant bacteria.

Another object of the present invention is to provide a method for preparing the 1-phenyl 4-azolyl pyrazole derivative.

Still another object of the present invention is to provide a fungicide composition comprising the 1-phenyl 4-azolyl pyrazole derivative.

In order to achieve the above object, the present invention provides a 1-phenyl 4-azolyl pyrazole derivative of the following Chemical Formula 1.

[Formula 1]

(Wherein

n represents 0-2,

X is 1 to 3 C ₁ -C ₃ alkyl group, 1 to 3 chloro group, 1 to 3 fluoro group, 1 to 3 C _1-3 alkoxy group, nitro group, trihaloalkyl group, 3,4 -An ethylenedioxy group or a phenyl group or a phenoxy group,

Y is hydrogen, 1 to 3 C ₁ -C ₃ alkyl group, 1 to 3 chloro group, 1 to 3 fluoro group, 1 to 3 C _1-3 alkoxy group, nitro group, trihaloalkyl group or phenyl group Is,

Z is CH or N.)

The present invention also provides a methyl sulfanyl substituted 1-phenyl 4-azolyl pyrazole derivative of Formula 1a comprising reacting azolyl α-oxo ketendithioacetal of Formula 2 with phenylhydrazine of Formula 3 It provides a method for producing.

[Formula 1a]

[Formula 2]

[Formula 3]

(Wherein

X, Y and Z are the same as defined in the formula (1).)

Methyl sulfanyl substituted 1-phenyl 4-azolyl pyrazole derivatives prepared by the above-described method were oxidized to prepare methyl sulfinyl or methyl sulfonyl substituted 1-phenyl 4-azolyl pyrazole derivatives of the general formula 1b. You may.

[Formula 1b]

(Wherein

X, Y and Z are the same as defined in the formula (1), n is 1-2.)

The present invention also provides a horticultural germicide composition comprising the 1-phenyl 4-azolyl pyrazole derivative of Formula 1 as an active ingredient.

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

The present invention relates to a 1-phenyl 4-azolyl pyrazole derivative of Formula 1, which is a novel compound having a new framework structure and having a wide range of bactericidal effects against plant pathogens including resistant bacteria.

The preparation method of the 1-phenyl 4-azolyl pyrazole derivative of Chemical Formula 1 of the present invention may be classified into a case in which n is 0 and a case in which n is 1-2.

1) Manufacturing method when n is 0 in Formula 1

As shown in Scheme 1, a compound of Formula 1a in which n is 0 in Formula 1 may be prepared by reacting azolyl α-oxo ketendithioacetal of Formula 2 with phenylhydrazine of Formula 3 .

Scheme 1

(In Scheme 1, X, Y and Z are the same as the definition in Formula 1.)

In the above reaction, the compound of Formula 1a represents the following two isomers of Formulas 1a-1 and 1a-2.

[Formula 1a-1]

[Formula 1a-2]

(Wherein X, Y and Z are as defined above)

In the above reaction, the compound of Formula 3 is used in the amount of 1 to 1.2 equivalents based on the compound of Formula 2.

When the compound of the formula (3) is an acid addition salt, trialkylamines such as triethylamine as the acid remover; And inorganic salts such as sodium hydrogen carbonate, potassium carbonate and caustic soda may be added in an amount of 1 to 2 equivalents based on the compound of Formula 2.

In addition, examples of the solvent used in the reaction include ethers such as diethyl ether, diisopropyl ether, tetrahydrofuran, dioxane and diphenyl ether; Halogenated hydrocarbons such as dichloroethane, chloroform and carbon tetrachloride; Alcohols such as methanol, ethanol and isopropanol; And trialkylamines such as triethylamine, tributylamine, or steric hindrance amines such as diisopropylamine, and the like. Preferably, trialkylamines are suitable, and these may be used alone or in combination of one or more.

In addition, the reaction temperature is 50 to 150 ℃, the reaction time depends on the reaction temperature, but usually 1 to 24 hours is preferred. If the reaction temperature is less than 50 ℃ reaction does not proceed well, if the 150 ℃ ℃ the reaction proceeds sufficiently, there is no need to increase any more.

Immediately after completion of the reaction, the solvent is distilled off or water is added to the reaction mixture, followed by extraction with an organic solvent that is insoluble in water such as dichloroethane, dichloromethane, chloroform and ethyl acetate. A crude product of the azolyl pyrazole derivative is obtained. This crude product may be an alcohol solvent such as methanol and ethanol; Esters of organic acids such as ethyl acetate and methyl acetate; Hydrocarbons such as pentane and hexane; Ethers such as ethyl ether and tetrahydrofuran; And recrystallized from a solvent selected from the mixtures thereof, or can be easily separated and purified by column chromatography.

On the other hand, the azolyl α-oxo ketene dithioacetal of the formula (2) can be prepared by a known method (see European Patent No. 508527).

2) Method for the case in which n is 1-2 in Formula 1

The following Chemical Formula 1b may be prepared by oxidizing the Chemical Formula 1a.

Scheme 2

(In Reaction Scheme 2, X, Y and Z are the same as defined in Formula 1, n is 1-2.)

In the above reaction, the compound of Formula 1b represents two isomers of the following Formulas 1b-1 and 1b-2.

[Formula 1b-1]

[Formula 1b-2]

(Wherein X, Y and Z are as defined above and n is 1-2).

Suitable oxidizing agents used in the above oxidation reactions include peroxy compounds such as hydrogen peroxide, organic hydroperoxides such as 3-tert butylhydro peroxide, aromatic or aliphatic percarboxylic acids (e.g. m-chloro peroxy benzoic acid, peroxy acetic acid or Organic peroxide metal oxides such as permono phthalic acid) and inorganic oxyacids. The amount of oxidant used is usually 1 equivalent of the oxidizing agent when n is 1 and 2 to 3 equivalents of oxidizing agent with respect to the used compound of formula (1a-1) or (1a-2). use.

At this time, the solvent used for the oxidation reaction is water; Halogen-hydrocarbons such as dichloromethane, chloroform, chlorobenzene and the like; Fatty acids such as acetic acid, propionic acid and the like; Alcohols such as methyl alcohol and the like can be used.

The reaction temperature at this time is carried out at 0 to 130 ℃ and more preferably between 20 ℃ to the boiling point of the solvent.

Derivatives of formula (1b-1) or (1b-2) obtained by the above reaction may be purified by recrystallization or column chromatography if necessary.

The novel 1-phenyl 4-azolyl pyrazole derivatives of formula 1 according to the present invention, prepared by the above method, exhibit high therapeutic and prophylactic antibacterial properties against a broad spectrum of plant pathogens. Examples of these bacteria include Piricularia oryzae of rice, Rhizoctonia solani of rice, Botrytis cinerea of cucumber, Sphaerotheca fuliginea of cucumber, and Pseudoperonospora cube of cucumber. ), downy mildew of grape fungus (Plasmopora viticola), Station pathogens of tomato (Phytophthora infestans), kkaessi pattern germs (Cochliobolus miyabeanus), brown pattern germs of peanut (Cercopora arachidicola), powdery mildew fungus of barley (Erysiphe graminis), wheat red rust ( Puccinia recondita ) and Puccinis graminis of wheat, which show excellent bactericidal effects against rice blast, tomato late blight, wheat red rust, and barley powdery mildew.

As such, the compound of formula 1 of the present invention has a bactericidal effect, and thus may be used as an active ingredient in a bactericide composition. The fungicide composition comprises from about 0.01 to 90% by weight of the compound of formula 1 of the present invention as an active ingredient. The fungicide compositions of the present invention may also be formulated into agricultural fungicide compositions by mixing with suitable adjuvants such as solid or liquid carriers, surfactants, diluents, electrodeposition agents, synergists, adhesives and dispersants, and the like.

Solid carriers usable in formulating compositions in the present invention include talc, clay, bentonite, pyrophyllite, kaolin, diatomaceous earth, silica and the like, and liquid carriers include water, methanol, ethanol, acetone, dimethylformamide, ether , Benzene, xylene, toluene and naphthalene, and the like, and nonionic surfactants such as polyoxyethylene alkylphenylether and polyoxyethylene fatty acid esters and anionic surfactants such as alkylbenzenesulfonates, Lignin sulfonate, dinaphthyl methanesulfonate), and the like. In addition, polyvinyl alcohol, carboxymethyl cellulose, gum arabic and the like can be used as the adhesive.

According to the present invention, the fungicide composition containing the compound of formula 1 of the present invention may be prepared as a powder or a hydrated powder, granules, emulsion concentrates, suspensions, fumigants, gases and pastes, and the like, as well as agricultural products, seedlings and Used to sterilize seeds and the like. For example, the compound of formula 1 may be uniformly dissolved in a hydrocarbon, acetone or alcohol with a suitable surfactant to prepare an emulsion concentrate or solution, or mixed with an inorganic powder and a suitable surface active agent, Hydrated powder can be prepared by grinding and homogenizing as much as possible. The composition thus prepared may be diluted with water to a desired concentration, or mixed with inorganic powder, crushed and mixed homogeneously and used as dust.

In addition, according to the present invention, the disinfectant composition diluted to contain an effective amount of the compound of Formula 1 of the present invention may be used in admixture with other agrochemicals such as insecticides, fungicides, herbicides, plant growth regulators and acaricides, and nutritional substances. Can be.

Examples of the novel 1-phenyl 4-azolyl pyrazole derivatives of the general formula 1 according to the present invention are shown in Tables 1 to 25 below. In Tables 1-25, No. numbers each compound for the purpose of understanding.

[Formula 1]

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

1- [1-phenyl-3- (2,4-deployment phenyl) -5-methylsulfanyl-- 1H -4- pyrazolyl] - 1H - imidazole (Compound 1)

0.64 g (2.00 mmol) of 3,3-di (methylsulfanyl) -1- (2,4-difluorophenyl) -2- ( 1H - 1 -imidazolyl) -2-propen-1-one 0.28 g (2.60 mmol) of phenylhydrazine and 15 ml of triethylamine were placed in a reactor and refluxed.

After reflux reaction was confirmed by thin layer chromatography (hexane: ethyl acetate = 1: 1), the reaction was distilled under reduced pressure to remove triethylamine, and purified by silica gel column chromatography to obtain 465 mg (63%) of brown solid. (Compound 1) was obtained.

Compound 1: ¹ HNMR (200MHz) 7.71-6.82 (m, 11H), 2.00 (s, 3H)

Example 2

1- [1- (4-Chlorophenyl) -5- (2,4-difluorophenyl) -3-methylsulfanyl- 1H -4-pyrazolyl]- 1H Imidazole (compound 3) and 1- [1- (4-chlorophenyl) -3- (2,4-difluorophenyl) -5-methylsulfanyl- 1H -4-pyrazolyl]- 1H Imidazole (compound 4)

3,3-di (methylsulfanyl) -1- (2,4-difluorophenyl) -2- ( 1H - 1 -imidazolyl) -2-propen-1-one 0.50 g (1.534 mmol) 0.35 g (1.955 mmol) of 4-chlorophenylhydrazine hydrochloride and 15 ml of triethylamine were added to a reactor and refluxed.

After reflux reaction was confirmed by thin layer chromatography (hexane: ethyl acetate = 1: 1), the reaction was distilled under reduced pressure to remove triethylamine and purified by silica gel column chromatography to give 250 mg (42%) of brown liquid. (Compound 3) and 130 mg (22%) of yellow liquid (Compound 4) were obtained.

Compound 3: ¹ HNMR (200 MHz) δ 7.49 (s, 1 H), 7.32 (d, J = 8.75 Hz, 2H), 7.21 (d, J = 8.75 Hz, 2H), 7.11 (s, 1H), 7.07- 6.97 (m, 1H), 6.96 (s, 1H), 6.90-6.76 (m, 2H), 2.53 (s, 3H)

Compound 4: ¹ HNMR (200 MHz) δ7.68-7.38 (m, 6H), 7.17 (s, 1H), 7.02 (s, 1H), 6.96-6.76 (m, 2H), 2.00 (s, 3H)

Example 3

1- [3- (2,4-Difluorophenyl) -1- (4-methoxyphenyl) -5-methylsulfanyl- 1H -4-pyrazolyl]- 1H Imidazole (compound 5)

0.46 g (1.341 mmol) of 3,3-di (methylsulfanyl) -1- (2,4-difluorophenyl) -2- ( 1H - 1 -imidazolyl) -2-propen-1-one , 0.26 g (1.489 mmol) of 4-methoxyphenylhydrazine hydrochloride and 15 ml of triethylamine were placed in a reactor and refluxed.

After the reflux reaction was confirmed by thin layer chromatography (hexane: ethyl acetate = 1: 1), the reaction was distilled under reduced pressure to remove triethylamine, and purified by silica gel column chromatography to obtain 190 mg (48%) of a yellow solid. (Compound 5) was obtained.

Compound 5: ¹ HNMR (200 MHz) 7.58 (s, 1 H), 7.57 (d, J = 8.95 Hz, 2H), 7.52-7.41 (m, 1 H), 7.17 (s, 1 H), 7.04 (d, J = 8.95 Hz, 2H), 7.03 (s, 1H), 6.96-6.75 (m, 2H), 3.87 (s, 3H), 1.99 (s, 3H)

Example 4

1- [1-(-4-methoxyphenyl) -3- (4-methoxyphenyl) -5-methylsulfanyl- 1H -4-pyrazolyl]- 1H Imidazole and 1- [1- (4-methoxyphenyl) -5- (4-methoxyphenyl) -3-methylsulfanyl- 1H -4-pyrazolyl]- 1H Imidazole (compound 25)

2- ( 1H - 1 -imidazolyl) -1- (4-methoxyphenyl) -3,3-di (methylsulfanyl) -2-propen-1-one 0.73 g (2.281 mmol), 4- 0.60 g (3.436 mmol) of methoxyphenylhydrazine hydrochloride and 0.64 ml (4.529 mmol) of triethylamine were placed in a reactor and refluxed.

After the reflux reaction was confirmed by thin layer chromatography (hexane: ethyl acetate = 1: 1), the reaction was distilled under reduced pressure to remove triethylamine, and purified by silica gel column chromatography to obtain 600 mg of an isomer mixture of 1: 1.6. 67%) of yellow liquid (Compound 25) was obtained.

Compound 25: ¹ HNMR (200 MHz) δ7.66-6.75 (m, 22H), 3.90 (s, 3H), 3.82 (s, 3H), 3.80 (s, 3H), 3.77 (s, 3H), 2.51 (s , 3H), 2.01 (s, 3H)

Example 5

5- (3,4-Dichlorophenyl) -1- [1- (2,5-dimethylphenyl) -3-methylsulfanyl- 1H -4-pyrazolyl]- 1H Imidazole (compound 53)

1- (3,4-dichlorophenyl) -3,3-di (methylsulfanyl) -2- ( 1H - 1 -imidazolyl) -2-propen-1-one 0.80 g (2.228 mmol), 2 0.50 g (2.896 mmol) of, 5-dimethylphenylhydrazine hydrochloride and 20 ml of triethylamine were placed in a reactor and refluxed.

After the reflux reaction was confirmed by thin layer chromatography (hexane: ethyl acetate = 2: 1), the reaction was distilled under reduced pressure to remove triethylamine, and purified by silica gel column chromatography to obtain 420 mg (44%) of a yellow liquid. (Compound 53) was obtained.

Compound 53: ¹ HNMR (200 MHz) δ 7.49 (m, 1H), 7.25-6.92 (m, 7H), 6.68 (m, 1H), 2.48 (s, 3H), 2.30 (s, 3H), 1.95 (s , 3H)

Example 6

1- [1- (3,5-Dichlorophenyl) -5- (4-fluorophenyl) -3-methylsulfanyl- 1H -4-pyrazolyl]- 1H -1,2,4-triazole (compound 76)

3,3-di (methylsulfanyl) -1- (4-fluorophenyl) -2- ( 1H -1,2,4-triazol-1-yl) -2-propene-1-one 0.70 g (2.265 mmol), 0.58 g (2.717 mmol) of 3,5-dichlorophenylhydrazine hydrochloride, and 15 ml of triethylamine were placed in a reactor and refluxed.

After reflux reaction was confirmed by thin layer chromatography (hexane: methylene chloride: ethyl acetate = 5: 5: 1), the reaction product was distilled under reduced pressure to remove triethylamine, and purified by silica gel column chromatography to obtain 320 mg (34). %) Of a white solid (Compound 76) was obtained.

Compound 76: ¹ HNMR (200 MHz) δ 8.08 (m, 2H), 7.31 (m, 1H), 7.18-6.99 (m, 6H), 2.56 (s, 3H)

Example 7

1- [1- (3,5-Dichlorophenyl) -5- (4-fluorophenyl) -3-methylsulfinyl- 1H -4-pyrazolyl]- 1H -1,2,4-triazole (compound 77)

1- [1- (3,5-dichlorophenyl) -5- (4-Floro-phenyl) -3-methylsulfanyl-- 1H -4- pyrazolyl] - 1H -1,2,4- triazole (Compound 76) 0.10 g (0.238 mmol), hydrogen peroxide (35%) 0.07 g (0.714 mmol), and acetic acid 15 ml were placed in a reactor and stirred at room temperature.

After the reaction was stirred, the reaction was confirmed by thin layer chromatography (hexane: ethyl acetate = 1: 1), and 30 ml of water was added to the product, followed by extraction three times with 30 ml of ethyl acetate to obtain an organic solvent layer. The organic solvent layer was washed with water, dried over magnesium sulfate and concentrated. The concentrate was purified by silica gel column chromatography to yield 90 mg (87%) of a white solid (Compound 77).

Compound 77: ¹ HNMR (200 MHz) δ 8.24 (s, 1H), 8.10 (s, 1H), 7.39 (m, 1H), 7.22-7.03 (m, 6H), 3.04 (s, 3H)

Example 8

1- [1- (3,5-Dichlorophenyl) -5- (4-fluorophenyl) -3-methylsulfonyl- 1H -4-pyrazolyl]- 1H -1,2,4-triazole (compound 78)

1- [1- (3,5-dichlorophenyl) -5- (4-Floro-phenyl) -3-methylsulfanyl-- 1H -4- pyrazolyl] - 1H -1,2,4- triazole (Compound 76) 0.07 g (0.167 mmol), hydrogen peroxide (35%) 0.05 g (0.515 mmol), and acetic acid 15 ml were put in a reactor and refluxed.

The reflux reaction product was confirmed by completion of the reaction by thin layer chromatography (hexane: ethyl acetate = 1: 1), and 30 ml of water was added to the product, followed by extraction three times with 30 ml of ethyl acetate to obtain an organic solvent layer. The organic solvent layer was washed with water, dried over magnesium sulfate and concentrated. The concentrate was purified by silica gel column chromatography to give 70 mg (93%) of a white solid (Compound 78).

Compound 78: ¹ HNMR (200 MHz) δ 8.24 (s, 1H), 8.10 (s, 1H), 7.43 (m, 1H), 7.26 (m, 2H), 7.19-7.02 (m, 4H), 3.28 (s , 3H)

Example 9

1- [1- (2,5-Dimethylphenyl) -5- (4-fluorophenyl) -3-methylsulfanyl- 1H -4-pyrazolyl]- 1H -1,2,4-triazole (compound 80)

3,3-di (methylsulfanyl) -1- (4-fluorophenyl) -2- ( 1H -1,2,4-triazol-1-yl) -2-propene-1-one 0.70 g (2.265 mmol), 0.47 g (2.722 mmol) of 2,5-dimethylphenylhydrazine hydrochloride and 15 ml of triethylamine were placed in a reactor and refluxed.

After the reflux reaction was confirmed by thin layer chromatography (hexane: methylene chloride: ethyl acetate = 5: 5: 1), the reaction was distilled under reduced pressure to remove triethylamine, and purified by silica gel column chromatography to obtain 400 mg (47). %) To a yellow solid (Compound 80).

Compound 80: ¹ HNMR (200 MHz) δ8.12 (s, 1H), 8.11 (s, 1H), 7.11-6.83 (m, 7H), 2.51 (s, 3H), 2.30 (s, 3H), 1.95 (s , 3H)

Example 10

1- [1- (2,5-dimethylphenyl) -5- (4-fluorophenyl) -3-methylsulfinyl- 1H -4-pyrazolyl]- 1H -1,2,4-triazole (compound 81)

1- [1- (2,5-dimethylphenyl) -5- (4-Floro-phenyl) -3-methylsulfanyl-- 1H -4- pyrazolyl] - 1H -1,2,4- triazole (Compound 80) 0.10 g (0.264 mmol), 0.08 g (0.824 mmol) of hydrogen peroxide (35%) and 15 ml of acetic acid were added to a reactor and stirred at room temperature.

After the reaction was stirred, the reaction was confirmed by thin layer chromatography (hexane: ethyl acetate = 1: 1), and 30 ml of water was added to the product, followed by extraction three times with 30 ml of ethyl acetate to obtain an organic solvent layer. The organic solvent layer was washed with water, dried over magnesium sulfate and concentrated. The concentrate was purified by silica gel column chromatography to yield 100 mg (96%) of a white solid (Compound 81).

Compound 81: ¹ HNMR (200 MHz) δ8.34 (s, 1H), 8.13 (s, 1H), 7.20-6.88 (m, 7H), 3.03 (s, 3H), 2.33 (s, 3H), 1.95 (s , 3H)

Example 11

1- [1- (2,5-dimethylphenyl) -5- (4-fluorophenyl) -3-methylsulfonyl- 1H -4-pyrazolyl]- 1H -1,2,4-triazole (Compound 82)

1- [1- (2,5-dimethylphenyl) -5- (4-Floro-phenyl) -3-methylsulfanyl-- 1H -4- pyrazolyl] - 1H -1,2,4- triazole (Compound 80) 0.10 g (0.264 mmol), 0.08 g (0.824 mmol) of hydrogen peroxide (35%) and 15 ml of acetic acid were placed in a reactor and refluxed.

The reflux reaction product was confirmed by completion of the reaction by thin layer chromatography (hexane: ethyl acetate = 1: 1), and 30 ml of water was added to the product, followed by extraction three times with 30 ml of ethyl acetate to obtain an organic solvent layer. The organic solvent layer was washed with water, dried over magnesium sulfate and concentrated. The concentrate was purified by silica gel column chromatography to give 95 mg (88%) of a white solid (Compound 82).

Compound 82: ¹ HNMR (200 MHz) δ 8.28 (s, 1H), 8.13 (s, 1H), 7.20-6.88 (m, 7H), 3.29 (s, 3H), 2.33 (s, 3H), 1.95 (s , 3H)

Example 12

1- [1- (2-ethylphenyl) -3- (4-fluorophenyl) -5-methylsulfanyl- 1H -4-pyrazolyl]- 1H -1,2,4-triazole (Compound 83) and 1- [1- (2-ethylphenyl) -5- (4-fluorophenyl) -3-methylsulfanyl- 1H -4-pyrazolyl]- 1H -1,2,4-triazole (compound 84)

3,3-di (methylsulfanyl) -1- (4-fluorophenyl) -2- ( 1H -1,2,4-triazol-1-yl) -2-propene-1-one 0.70 g (2.265 mmol), 0.47 g (2.722 mmol) of 2-ethylphenylhydrazine hydrochloride and 15 ml of triethylamine were placed in a reactor and refluxed.

After reflux reaction was confirmed by thin layer chromatography (hexane: methylene chloride: ethyl acetate = 5: 5: 1), the reaction product was distilled under reduced pressure to remove triethylamine, and purified by silica gel column chromatography to obtain 70 mg (8). %) Of a brown liquid (compound 83) and 400 mg (47%) of a pale yellow solid (compound 84).

Compound 83: ¹ HNMR (200 MHz) δ8.29 (s, 1H), 8.24 (s, 1H), 7.51-7.34 (m, 6H), 7.00 (m, 2H), 2.52 (q, J = 7.53 Hz, 2H ), 2.03 (s, 3H), 1.21 (t, J = 7.53 Hz, 3H)

Compound 84: ¹ HNMR (200 MHz) δ 8.16 (s, 2H), 7.41-7.21 (m, 4H), 7.06-6.85 (m, 4H), 2.56 (s, 3H), 2.44 (q, J = 7.53 Hz , 2H), 1.12 (t, J = 7.53 Hz, 3H)

Example 13

1- [1- (2-ethylphenyl) -5- (4-fluorophenyl) -3-methylsulfinyl- 1H -4-pyrazolyl]- 1H -1,2,4-triazole (compound 85)

1- [1- (2-ethylphenyl) -5- (4-Floro-phenyl) -3-methylsulfanyl-- 1H -4- pyrazolyl] - 1H -1,2,4- triazole (Compound 84) 0.10 g (0.264 mmol), 0.08 g (0.824 mmol) of hydrogen peroxide (35%), and 15 ml of acetic acid were added to a reactor and stirred at room temperature.

After the reaction was stirred, the reaction was confirmed by thin layer chromatography (hexane: ethyl acetate = 1: 1), and 30 ml of water was added to the product, followed by extraction three times with 30 ml of ethyl acetate to obtain an organic solvent layer. The organic solvent layer was washed with water, dried over magnesium sulfate and concentrated. The concentrate was purified by silica gel column chromatography to give 88 mg (84%) of a white solid (Compound 85).

Compound 85: ¹ HNMR (200 MHz) δ 8.31 (s, 1H), 8.11 (s, 1H), 7.44-7.20 (m, 4H), 7.05-6.85 (m, 4H), 3.01 (s, 3H), 2.34 (q, J = 7.5 Hz, 2H), 1.06 (t, J = 7.5 Hz, 3H)

Example 14

1- [1- (2-ethylphenyl) -5- (4-fluorophenyl) -3-methylsulfonyl- 1H -4-pyrazolyl]- 1H -1,2,4-triazole (Compound 86)

1- [1- (2-ethylphenyl) -5- (4-Floro-phenyl) -3-methylsulfanyl-- 1H -4- pyrazolyl] - 1H -1,2,4- triazole (Compound 84) 0.10 g (0.264 mmol), 0.08 g (0.824 mmol) of hydrogen peroxide (35%) and 15 ml of acetic acid were placed in a reactor and refluxed.

The reflux reaction product was confirmed by completion of the reaction by thin layer chromatography (hexane: ethyl acetate = 1: 1), and 30 ml of water was added to the product, followed by extraction three times with 30 ml of ethyl acetate to obtain an organic solvent layer. The organic solvent layer was washed with water, dried over magnesium sulfate and concentrated. The concentrate was purified by silica gel column chromatography to give 85 mg (78%) of a white solid (Compound 86).

Compound 86: ¹ HNMR (200 MHz) δ 8.26 (s, 1H), 8.11 (s, 1H), 7.43-7.22 (m, 4H), 7.04-6.84 (m, 4H), 3.27 (s, 3H), 2.33 (q, J = 7.53 Hz, 2H), 1.06 (t, J = 7.53 Hz, 3H)

Example 15

1- [1- (4-Chlorophenyl) -3- (4-methylphenyl) -5-methylsulfanyl- 1H -4-pyrazolyl]- 1H -1,2,4-triazole (Compound 90) and 1- [1- (4-chlorophenyl) -5- (4-methylphenyl) -3-methylsulfanyl- 1H -4-pyrazolyl]- 1H -1,2,4-triazole (compound 91)

0.70 g (2.295) of 3,3-di (methylsulfanyl) -1- (4-methylphenyl) -2- ( 1H -1,2,4-triazol-1-yl) -2-propen-1-one mmol), 0.53 g (2.960 mmol) of 4-chlorophenylhydrazine hydrochloride, and 15 ml of triethylamine were added to the reactor and refluxed.

After the reflux reaction was confirmed by thin layer chromatography (hexane: ethyl acetate = 1: 1), the reaction was distilled under reduced pressure to remove triethylamine and purified by silica gel column chromatography to obtain 100 mg (11%) of white solid. (Compound 90) and 630 mg (72%) of a pale yellow solid (Compound 91) were obtained.

Compound 90: ¹ HNMR (200 MHz) δ 8.25 (s, 2H), 7.69 (d, J = 8.85 Hz, 2H), 7.53 (d, J = 8.85 Hz, 2H), 7.31 (d, J = 8.12 Hz, 2H), 7.14 (d, J = 8.12 Hz, 2H), 2.35 (s, 3H), 2.31 (s, 3H)

Compound 91: ¹ HNMR (200 MHz) δ 8.09 (s, 1H), 8.04 (s, 1H), 7.31 (d, J = 8.95 Hz, 2H), 7.23 (d, J = 8.95 Hz, 2H), 7.08 ( d, J = 8.08 Hz, 2H), 6.97 (d, J = 8.08 Hz, 2H), 2.53 (s, 3H), 2.31 (s, 3H)

Example 16

1-[-(4-chlorophenyl) -5- (4-methylphenyl) -3-methylsulfinyl- 1H -4-pyrazolyl]- 1H -1,2,4-triazole (Compound 92)

1- [1- (4-chlorophenyl) -5- (4-methylphenyl) -3-methylsulfanyl-- 1H -4- pyrazolyl] - 1H -1,2,4- triazole (Compound 91) 0.17g (0.446 mmol), 0.26 g (2.676 mmol) of hydrogen peroxide (35%), and 15 ml of acetic acid were added to a reactor and stirred at room temperature.

The reaction product obtained by stirring was subjected to thin layer chromatography (hexane: ethyl acetate = 1: 1) to confirm the completion of the reaction. Then, 30 ml of water was added to the product and extracted three times with 30 ml of ethyl acetate to obtain an organic solvent layer. The organic solvent layer was washed with water, dried over magnesium sulfate and concentrated. The concentrate was purified by silica gel column chromatography to give 175 mg (99%) of a white solid (Compound 92).

Compound 92: ¹ HNMR (200 MHz) δ 8.16 (s, 1H), 8.09 (s, 1H), 7.33 (d, J = 9.2 Hz, 2H), 7.24 (d, J = 9.2 Hz, 2H), 7.11 ( d, J = 8.1 Hz, 2H), 6.97 (d, J = 8.1 Hz, 2H), 3.04 (s, 3H), 2.32 (s, 3H)

Example 17

1-[-(4-chlorophenyl) -5- (4-methylphenyl) -3-methylsulfonyl- 1H -4-pyrazolyl]- 1H -1,2,4-triazole (Compound 93)

1- [1- (4-chlorophenyl) -5- (4-methylphenyl) -3-methylsulfanyl-- 1H -4- pyrazolyl] - 1H -1,2,4- triazole (Compound 91) 0.22g (0.577 mmol), hydrogen peroxide (35%), 0.34 g (3.500 mmol), and acetic acid 15 ml were placed in a reactor and refluxed.

The reflux reaction product was confirmed by completion of the reaction by thin layer chromatography (hexane: ethyl acetate = 1: 1), and 30 ml of water was added to the product, followed by extraction three times with 30 ml of ethyl acetate to obtain an organic solvent layer. The organic solvent layer was washed with water, dried over magnesium sulfate and concentrated. The concentrate was purified by silica gel column chromatography to give 230 mg (96%) of a white solid (Compound 93).

Compound 93: ¹ HNMR (200 MHz) δ 8.18 (s, 1H), 8.09 (s, 1H), 7.35 (d, J = 9.1 Hz, 2H), 7.27 (d, J = 9.1 Hz, 2H), 7.09 ( d, J = 8.2 Hz, 2H), 6.95 (d, J = 8.2 Hz, 2H), 3.28 (s, 3H), 2.31 (s, 3H)

Example 18

1- [1- (2-ethylphenyl) -3- (4-methylphenyl) -5-methylsulfanyl- 1H -4-pyrazolyl]- 1H -1,2,4-triazole (Compound 103) and 1- [1- (2-ethylphenyl) -5- (4-methylphenyl) -3-methylsulfanyl- 1H -4-pyrazolyl]- 1H -1,2,4-triazole (compound 104)

0.40 g (1.311) of 3,3-di (methylsulfanyl) -1- (4-methylphenyl) -2- ( 1H -1,2,4-triazol-1-yl) -2-propen-1-one mmol), 0.29 g (1.680 mmol) of 2-ethylphenylhydrazine hydrochloride, and 15 ml of triethylamine were placed in a reactor and refluxed.

After the reflux reaction was confirmed by thin layer chromatography (hexane: methylene chloride: ethyl acetate = 8: 8: 1), the reaction was distilled under reduced pressure to remove triethylamine, and purified by silica gel column chromatography to obtain 56 mg (12). %) Of a brown liquid (compound 103) and 220 mg (44%) of a brown solid (compound 104) were obtained.

Compound 103: ¹ HNMR (200 MHz) δ 8.26 (s, 1H), 8.24 (s, 1H), 7.54-7.26 (m, 6H), 7.11 (d, J = 7.94 Hz, 2H), 2.52 (q, J = 7.63 Hz, 2H), 2.32 (s, 3H), 2.04 (s, 3H), 1.21 (t, J = 7.63 Hz, 3H)

Compound 104: ¹ HNMR (200 MHz) δ8.23 (s, 1H), 8.08 (s, 1H), 7.36-7.19 (m, 4H), 6.96 (d, J = 8.24 Hz, 2H), 6.85 (d, J = 8.24 Hz, 2H), 2.52 (s, 3H), 2.41 (q, J = 7.53 Hz, 2H), 2.23 (s, 3H), 1.08 (t, J = 7.53 Hz, 3H)

Example 19

1- [1- (2,3-dimethylphenyl) -3- (4-methylphenyl) -5-methylsulfanyl- 1H -4-pyrazolyl]- 1H -1,2,4-triazole (compound 105) and 1- [1- (2,3-dimethylphenyl) -5- (4-methylphenyl) -3-methylsulfanyl- 1H -4-pyrazolyl]- 1H -1,2,4-triazole (compound 106)

0.40 g (1.311) of 3,3-di (methylsulfanyl) -1- (4-methylphenyl) -2- ( 1H -1,2,4-triazol-1-yl) -2-propen-1-one mmol), 0.29 g (1.680 mmol) of 2-ethylphenylhydrazine hydrochloride, and 15 ml of triethylamine were placed in a reactor and refluxed.

After reflux reaction was confirmed by thin layer chromatography (hexane: methylene chloride: ethyl acetate = 8: 8: 1), the reaction product was distilled under reduced pressure to remove triethylamine, and purified by silica gel column chromatography to obtain 40 mg (8). %) Yellow solid (compound 105) and 160 mg (33%) of pale yellow solid (compound 106) were obtained.

Compound 105: ¹ HNMR (200 MHz) δ8.26 (s, 1H), 8.24 (s, 1H), 7.36-7.09 (m, 7H), 2.38 (s, 3H), 2.32 (s, 3H), 2.05 (s , 6H)

Compound 106: ¹ HNMR (200 MHz) δ8.26 (s, 1H), 8.24 (s, 1H), 7.36-7.09 (m, 7H), 2.38 (s, 3H), 2.32 (s, 3H), 2.05 (s , 6H)

Example 20

1- [3- (4-Chlorophenyl) -1- (4-fluorophenyl) -5-methylsulfanyl- 1H -4-pyrazolyl]- 1H -1,2,4-triazole and 1- [5- (4-chlorophenyl) -1- (4-fluorophenyl) -3-methylsulfanyl- 1H -4-pyrazolyl]- 1H -1,2,4-triazole (Compound 111)

0.40 g of 3,3-di (methylsulfanyl) -1- (4-chlorophenyl) -2- ( 1H -1,2,4-triazol-1-yl) -2-propen-1-one 1.229 mmol), 0.26 g (1.599 mmol) of 4-fluorophenylhydrazine hydrochloride, and 15 ml of triethylamine were placed in a reactor and refluxed.

The reflux reaction product was confirmed by completion of the reaction by thin layer chromatography (hexane: methylene chloride: ethyl acetate = 8: 8: 1), and the reaction product was distilled under reduced pressure to remove triethylamine and purified by silica gel column chromatography. 24 mg (5%) of a brown liquid (compound 111) was obtained.

Compound 111: ¹ HNMR (200 MHz) δ 8.26 (s, 1H), 8.25 (s, 1H), 8.11 (s, 1H), 8.10 (s, 1H), 7.34-7.20 (m, 8H), 7.11-7.00 (m, 8H), 2.53 (s, 3H), 2.07 (s, 3H)

Example 21

1- [5- (4-fluorophenyl) -1- (3-chloro-4-methylphenyl) -3-methylsulfanyl- 1H -4-pyrazolyl]- 1H Imidazole (Compound 143) and 1- [3- (4-fluorophenyl) -1- (3-chloro-4-methylphenyl) -5-methylsulfanyl- 1H -4-pyrazolyl]- 1H Imidazole (compound 144)

0.45 g (1.380 mmol), 3- 1- (4-fluorophenyl) -3,3-di (methylsulfanyl) -2- ( 1H - 1 -imidazolyl) -2-propen-1-one 0.41 g (2.123 mmol) of chloro-4-methylphenylhydrazine hydrochloride and 15 ml of diisopropylamine were placed in a reactor and refluxed.

The reflux reaction product was confirmed by completion of the reaction by thin layer chromatography (hexane: ethyl acetate = 1: 1), and diisopropylamine was distilled under reduced pressure and purified by silica gel column chromatography to give 320 mg (50%) of a white solid (Compound 143). And 150 mg (24%) of a pale yellow solid (Compound 144).

Compound 143: ¹ HNMR (200 MHz) δ 7.44 (m, 2H), 7.15 (m, 2H), 6.95 (m, 6H), 2.52 (s, 3H), 2.37 (s, 3H)

Compound 144: ¹ HNMR (200MHz) δ7.73 (m, 1H), 7.64 (s, 1H), 7.55-7.28 (m, 5H), 7.08-6.95 (m, 3H), 2.48 (s, 3H), 2.03 (s, 3H)

Example 22

1- [1- (4-methoxyphenyl) -3-methylsulfanyl-5- (4-nitrophenyl)- 1H -4-pyrazolyl]- 1H Imidazole (compound 146) and 1- [1- (4-methoxyphenyl) -5-methylsulfanyl-3- (4-nitrophenyl)- 1H -4-pyrazolyl]- 1H Imidazole (compound 147)

2- ( 1H - 1 -imidazolyl) -3,3-di (methylsulfanyl) -1- (4-nitrophenyl) -2-propen-1-one 0.50 g (1.492 mmol), 4-meth 0.34 g (1.940 mmol) of oxyphenylhydrazine hydrochloride and 15 ml of triethylamine were placed in a reactor and refluxed.

After reflux reaction was confirmed by thin layer chromatography (hexane: ethyl acetate = 1: 1), the reaction was distilled under reduced pressure to remove triethylamine and purified by silica gel column chromatography to obtain 140 mg (23%) of brown solid. (Compound 146) and 100 mg (16%) of a brown solid (Compound 147) were obtained.

Compound 146: ¹ HNMR (200 MHz) δ8.12 (s, 1H), 8.07 (s, 1H), 7.48 (m, 1H), 7.16 (m, 5H), 6.91 (m, 3H), 3.83 (s, 3H ), 2.52 (s, 3H)

Compound 147: ¹ HNMR (200 MHz) δ 8.18 (s, 1H), 8.13 (s, 1H), 7.66-7.49 (m, 5H), 7.32 (m, 1H), 7.16 (m, 3H), 3.90 (s , 3H), 2.02 (s, 3H)

Example 23

1- [1- (4-methoxyphenyl) -3-methylsulfanyl-5- (4-phenylphenyl)- 1H -4-pyrazolyl]- 1H Imidazole (compound 158) and 1- [1- (4-methoxyphenyl) -5-methylsulfanyl-3- (4-phenylphenyl)- 1H -4-pyrazolyl]- 1H Imidazole (compound 159)

3,3-di (methylsulfanyl) -1- (4-phenylphenyl) -2- ( 1H - 1 -imidazolyl) -2-propen-1-one 0.50 g (1.366 mmol), 4-meth 0.31 g (1.776 mmol) of oxyphenylhydrazine hydrochloride and 15 ml of triethylamine were placed in a reactor and refluxed.

After reflux reaction was confirmed by thin layer chromatography (hexane: ethyl acetate = 1: 1), the reaction was distilled under reduced pressure to remove triethylamine, and purified by silica gel column chromatography to obtain 65 mg (11%) of brown liquid. (Compound 158) and 70 mg (12%) of a brown solid (Compound 159) were obtained.

Compound 158: ¹ HNMR (200 MHz) δ 7.55-6.84 (m, 16H), 3.80 (s, 3H), 2.50 (s, 3H)

Compound 159: ¹ HNMR (200 MHz) δ7.67-6.79 (m, 16H), 3.87 (s, 3H), 2.00 (s, 3H)

Example 24

1- [5- (2,4-dichlorophenyl) -1- (4-methoxyphenyl) -3-methylsulfanyl- 1H -4-pyrazolyl]- 1H Imidazole (compound 285) and 1- [3- (2,4-dichlorophenyl) -1- (4-methoxyphenyl) -5-methylsulfanyl- 1H -4-pyrazolyl]- 1H -1,2,4-imidazole (Compound 286)

0.40 g (1.114 mmol) of 1- (2,4-dichlorophenyl) -3,3-di (methylsulfanyl) -2- ( 1H - 1 -imidazolyl) -2-propen-1-one, 4 0.23 g (1.317 mmol) of methoxyphenylhydrazine hydrochloride and 15 ml of triethylamine were placed in a reactor and refluxed.

After the reflux reaction was confirmed by thin layer chromatography (hexane: ethyl acetate = 1: 2), the reaction was distilled under reduced pressure to remove triethylamine, and purified by silica gel column chromatography to obtain 65 mg (14%) of red liquid. (Compound 285) and 163 mg (34%) of yellow semisolid (Compound 286) were obtained.

Compound 285: ¹ HNMR (200 MHz) δ 7.46 (s, 1H), 7.38 (m, 1H), 7.23-6.80 (m, 8H), 3.79 (s, 3H), 2.53 (s, 3H)

Compound 286: ¹ HNMR (200 MHz) δ7.60-6.97 (m, 10H), 3.88 (s, 3H), 2.00 (s, 3H)

Example 25

1- [5- (2,4-Dichlorophenyl) -1- (4-fluorophenyl) -3-methylsulfanyl- 1H -4-pyrazolyl]- 1H Imidazole and 1- [3- (2,4-dichlorophenyl) -1- (4-fluorophenyl) -5-methylsulfanyl- 1H -4-pyrazolyl]- 1H Imidazole (Compound 287)

0.40 g (1.114 mmol) of 1- (2,4-dichlorophenyl) -3,3-di (methylsulfanyl) -2- ( 1H - 1 -imidazolyl) -2-propen-1-one, 4 0.22 g (1.292 mmol) of fluorophenylhydrazine hydrochloride and 15 ml of triethylamine were placed in a reactor and refluxed.

After the reflux reaction was confirmed by thin layer chromatography (hexane: ethyl acetate = 1: 2), the reaction was distilled under reduced pressure to remove triethylamine, and purified by silica gel column chromatography to obtain 315 mg of an isomer mixture of 1: 1.7. 67%) of a yellow semisolid (Compound 287) was obtained.

Compound 287: ¹ HNMR (200 MHz) δ7.71-6.72 (m, 20H), 2.57 (s, 3H), 2.01 (s, 3H)

Example 26

1- [1- (4-Chlorophenyl) -3- (2,4-dichlorophenyl) -5-methylsulfanyl- 1H -4-pyrazolyl]- 1H Imidazole (compound 288)

0.40 g (1.114 mmol) of 1- (2,4-dichlorophenyl) -3,3-di (methylsulfanyl) -2- ( 1H - 1 -imidazolyl) -2-propen-1-one, 4 0.24 g (1.340 mmol) of chlorophenylhydrazine hydrochloride and 15 ml of triethylamine were placed in a reactor and refluxed.

After reflux reaction was confirmed by thin layer chromatography (hexane: ethyl acetate = 1: 2), the reaction was distilled under reduced pressure to remove triethylamine, and purified by silica gel column chromatography to give 30 mg (6%) of pale yellow color. Solid (Compound 288) was obtained.

Compound 288: ¹ HNMR (200 MHz) δ 7.69-7.31 (m, 8H), 7.14 (m, 1H), 6.98 (m, 1H), 2.02 (s, 3H)

Example 27

1- [5- (2,4-Dichlorophenyl) -1- (4-methylphenyl) -3-methylsulfanyl- 1H -4-pyrazolyl]- 1H Imidazole (compound 291) and 1- [3- (2,4-dichlorophenyl) -1- (4-methylphenyl) -5-methylsulfanyl- 1H -4-pyrazolyl]- 1H Imidazole (Compound 292)

0.40 g (1.114 mmol) of 1- (2,4-dichlorophenyl) -3,3-di (methylsulfanyl) -2- ( 1H - 1 -imidazolyl) -2-propen-1-one, 4 0.21 g (1.324 mmol) of methylphenylhydrazine hydrochloride and 15 ml of triethylamine were placed in a reactor and refluxed.

After reflux reaction was confirmed by thin layer chromatography (hexane: ethyl acetate = 1: 2), the reaction was distilled under reduced pressure to remove triethylamine and purified by silica gel column chromatography to give 38mg (8%) of red color. A liquid (compound 291) and 96 mg (21%) of a pale yellow solid (compound 292) were obtained.

Compound 291: ¹ HNMR (200 MHz) δ 7.46 (m, 1H), 7.38 (m, 1H), 7.23-7.07 (m, 7H), 6.95 (m, 1H), 2.54 (s, 3H), 2.33 (s , 3H)

Compound 292: ¹ HNMR (200 MHz) δ 7.55 (m, 3H), 7.42-7.26 (m, 5H), 7.13 (m, 1H), 6.99 (m, 1H), 2.45 (s, 3H), 2.00 (s , 3H)

Example 28

1- [5- (2,4-Dichlorophenyl) -1- (2-methylphenyl) -3-methylsulfanyl- 1H -4-pyrazolyl]- 1H Imidazole (compound 293) and 1- [3- (2,4-dichlorophenyl) -1- (2-methylphenyl) -5-methylsulfanyl- 1H -4-pyrazolyl]- 1H Imidazole (compound 294)

0.40 g (1.114 mmol) of 1- (2,4-dichlorophenyl) -3,3-di (methylsulfanyl) -2- ( 1H - 1 -imidazolyl) -2-propen-1-one, 2 0.21 g (1.324 mmol) of methylphenylhydrazine hydrochloride and 15 ml of triethylamine were placed in a reactor and refluxed.

After the reflux reaction was confirmed by thin layer chromatography (hexane: ethyl acetate = 1: 2), the reaction was distilled under reduced pressure to remove triethylamine and purified by silica gel column chromatography to obtain 55 mg (12%) of brown liquid. (Compound 293) and 19 mg (4%) of a pale yellow solid (Compound 294) were obtained.

Compound 293: ¹ HNMR (200 MHz) δ 7.48 (m, 1H), 7.27 (m, 3H), 7.16-6.96 (m, 6H), 2.53 (s, 3H), 2.22 (s, 3H)

Compound 294: ¹ HNMR (200 MHz) δ 7.58 (m, 1H), 7.45-7.25 (m, 7H), 7.14 (m, 1H), 7.01 (m, 1H), 2.22 (s, 3H), 2.00 (s , 3H)

The bactericidal effect of the novel 1-phenyl 4-azolyl pyrazole derivatives of the formula 1 of the present invention prepared as in Example was measured by the following test method.

Bactericidal effect test

To investigate the protective effect against plant pathogens, 25 mg or 10 mg of the test compound (compounds shown in Tables 1 to 25 above) was dissolved in 10 ml of acetone, and 90 ml of a 250 ppm aqueous solution containing Tween 20 was added to the solution. After adjusting to 250ppm or 100ppm, 50ml of foliar spray was applied to host plants of a certain size. The sprayed plants were left at room temperature for 24 hours to volatilize the solvent and water. Thus, the plants (treatment) and the untreated plants (control) treated with the disinfectant composition were inoculated with specific plant pathogens as shown in the following test examples, and left under the same conditions (humidity and temperature) for the same period of time. The control area (Control Value,%) was calculated as shown in Equation 1 by obtaining the disease area ratio (obtained from the ratio of the disease area ratio prepared based on the ratio of the measured disease area to the leaf area). The higher the control value, the better the sterilization effect.

[Equation 1]

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

Activation Index +++: Control from 81 to 100%

++: Control is 61-80%

+: Control is 41 to 60%

-: Control is 40% or less

Test Example 1

Sterilization Effect on Rice Blast

Pyricularia oryzae strains were inoculated in rice bran agar medium (Rice Polish 20g, dextrose 10g, agar 15g, distilled water 1L) and incubated in a 26 ° C. incubator for 2 weeks. The surface of the medium in which the pathogen was grown was scraped off with a rubber gallbladder to remove airborne hyphae, and spores were formed on a shelf at 25 to 28 ° C. for 48 hours with a fluorescent lamp turned on.

Germ inoculation was sprayed sufficiently to flow into Nakdong rice (3-4 leaves) susceptible to rice blast, after making a spore suspension (10 ⁶ / ml) of a certain concentration using sterilized distilled water.

The inoculated rice was incubated for 24 hours in a dark state, and the incidence of leaf area was determined by inducing the onset for 5 days in a constant temperature and humidity room of 90% relative humidity 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

Bactericidal Effect on Rice Leaf House Blight

Appropriate amount of bran was placed in a 1 L culture bottle and sterilized. Agar pieces of Rhizoctonia solani grown in potato agar medium (potato dextrose agar) for 3 days were inoculated on the sterilized bran and cultured. Subsequently, the cultured mycelium masses were finely ground and inoculated evenly in the pot (5 cm) in which 2-3 leaves of Nakdong rice were grown and induced to develop for 5 days in a constant temperature and humidity room with 28 ± 1 ° C. and a relative humidity of 80% or more. The diseased area ratio of the leaves of the bizarre seedlings was determined.

Test Example 3

Bactericidal Effect on Cucumber Gray Mold Disease

Cucumber gray fungal pathogen ( Botrytis cinerea ) isolated from tomato was inoculated in potato agar medium and placed in a plate at 25 ℃ incubator for 15 days under light dark conditions to form spores. After the spores formed on the medium into the distilled water 10㎖ per plate with a brush scraping the spores harvested by filtering them with spores gaahje and make the spore concentration to be 10 ⁶ / ㎖ was spray inoculated per leaf stage cucumber. This was induced for 3 days on a 20 ° C wet ground, and the lesion area ratio of one leaf of the main leaf was obtained.

Test Example 4

Bactericidal Effect on Tomato Blight

Phytophthora infestans of tomato was 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 8 hours. Spores were harvested after 14 days of 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 out the gestational sac. The concentration of strained strains was adjusted to 10 ⁵ / ml using sterile distilled water, and this inoculum was sprayed with tomato seedlings for 1 day in a 20 ° C. chamber, and then at a temperature of 20 ° C. and a relative humidity of 80% or more. After transferring to the humidity chamber for 4 days, the lesion area ratio of one and two leaves of the tomato was examined.

Test Example 5

Sterilization Effect against Wheat Red Rust

Puccinia recondita of wheat 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 at 20 ° C. for 1 day and then transferred to a constant temperature and humidity chamber of 70% and 20 ° C. for 10 days to induce onset, and then the leaf area ratio of the leaves was determined.

Test Example 6

Bactericidal Effect on Barley Powder Disease

Barley powdery mildew ( Erysiphe graminis f.sp.hordei ) was used by passage in the laboratory. For the subculture and pharmacological investigation of strains, seedlings of 15 barley seeds (East barley No. 1) were sown in a disposable pot (diameter: 6.5 cm), and barley was grown for 7 days in a greenhouse (25 ± 5 ^o C) for 7 days. Was inoculated with powdery mildew spores and transferred to a constant temperature and humidity room at a relative humidity of 50% and 22 to 24 ° C to induce the onset for 7 days, and then calculate the area ratio of the leaves.

The control value was calculated by substituting the lesion area ratios of the treatment and control leaves measured in Test Examples 1 to 6, and the results are shown in Table 26 as the activity index.

As shown in Table 26, the disinfectant composition comprising the compound of formula 1 of the present invention is excellent sterilization effect against rice fever, rice leaf pattern blight disease, cucumber gray mold disease, tomato blight disease, wheat red rust disease and barley flour powder Able to know. In particular, it has an excellent bactericidal effect against barley flour.

The novel 1-phenyl 4-azolyl pyrazole derivatives according to the invention have a wide range of bactericidal effects against plant pathogens, in particular against rice blasts, tomato blight, wheat red rust and barley powdery mildew. In addition, it is excellent in preventing and treating effects as well as penetration.

Claims (4)

delete delete delete Agrohorticultural fungicide composition comprising 1-phenyl 4-azolyl pyrazole derivative of formula 1 as an active ingredient. [Formula 1] (Wherein n represents 0-2, X is 1 to 3 C ₁ -C ₃ alkyl group, 1 to 3 chloro group, 1 to 3 fluoro group, 1 to 3 C _1-3 alkoxy group, nitro group, trihaloalkyl group, 3,4 -An ethylenedioxy group or a phenyl group or a phenoxy group, Y is 1 to 3 C ₁ -C ₃ alkyl groups, 1 to 3 chloro groups, 1 to 3 fluoro groups, 1 to 3 C _1-3 alkoxy groups, nitro groups, trihaloalkyl groups or phenyl groups, Z is CH or N.)