KR900002057B1 - 5-hydroxa pyrazole derivatives having pysiological active property - Google Patents

Abstract

R1=H, halogen; R2=lower alkyl; R3=alkoxy, lower alkylthio, phenoxy, halogen-, nitrosubstd. phenoxy, thiophenoxy; R4=H, lower alkyl, substd. phenyl; X=O,S) to prevent rice insect and acarid are prepd. Thus 1.0g 1-methyl-3-trifloro methyl-5-hydroxy pyrazole, 1.24g diethyl chlorophosphate and 0.72g triethyl amine in 10ml methylene chloride are stirred for 2 hr. The reactant are filtered with the mixt. of hexane and ethyl acetate (4:1) to give 1.6g I (R1=H; R2=Et; R3=OET; R4=Me; X=O).

Description

Novel 5-hydroxypyrazole Derivatives with Biological Activity

The present invention relates to a novel 5-hydroxy pyrazole derivative having physiological activity, and particularly relates to a pyrazole derivative represented by the following general formula (I) which is useful as an insecticide.

Wherein R ¹ is hydrogen or a halogen atom, R ² is a lower alkyl group, R ³ is an alkoxy or lower alkylthio group, a phenoxy group, or a phenoxy group or thiophenoxy optionally having one or more halogen or nitrosubstituted groups And R ⁴ is hydrogen, a lower alkyl group, or a phenyl group having a substituent, X is oxygen or sulfur. In this case, the halogen element refers to bromine, chlorine or iodine, and the lower alkyl group refers to a linear or pulverized alkyl group having 1 to 6 carbon atoms.

Conventionally, a compound in which a phosphate ester is substituted at the 3 position of a pyrazole ring as a pyrazole derivative having an insecticidal and acaricidal effect has been introduced in Korean Patent Publication No. 255 (Taken), but the compound has very good physiological activity. However, the insecticidal effect on some pests such as rice planthopper and aphid was difficult to expect a complete insecticidal effect, so the present inventors have excellent physiological activity, and in particular, selectively for rice pests and aphids. As a result of research efforts to develop a compound exhibiting an excellent pesticidal effect, the present invention has been achieved.

The present invention provides a novel 5-hydroxy pyrazole derivative which is excellent in physiological activity, exhibits excellent insecticidal action against hygienic pests and phytoparasites, in particular rice pests and aphids, and which can be industrially advantageously produced. There is a purpose.

Hereinafter, the present invention will be described in detail.

The present invention is a 5-hydroxy pyrazole derivative represented by the following general formula (I) and a pesticide and acaricide containing the same as an active ingredient.

Wherein R ¹ , R ² , R ³ , R ⁴ and X are the same as described above.

Hereinafter, the present invention will be described in more detail according to the method for preparing 5-hydroxypyrazole derivatives according to the present invention.

The compound of formula (I) according to the present invention is mixed with 5-hydroxy pyrazole or a salt thereof represented by the following formula (II) with an organic solvent and an acid binder, and the mixture is represented by the following formula (III) It can be prepared by esterifying the pyrazole compound in addition to the compound represented.

In the above formula, R ¹ , R ² , R ³ , and R ⁴ are the same as described above, and Hal represents a halogen atom.

In this case, as the organic solvent, for example, acetonitrile, cyclohexane, benzene, toluene, xylene, acetone, methylene chloride, methyl ethyl ketone, diethyl ether, dioxane, tetrahydrofuran, and the like can be used. As examples, hydroxides, oxides, carbonates, bicarbonates, alkali metal alcoholates, tertiary amines and the like of alkali metals and alkaline earth metals can be used.

In addition, in carrying out the esterification reaction, when the general formula (III) compound is exhausted, the reaction is completed. Such a reaction can be easily confirmed by TLC or GC, and thus after the reaction is completed. The desired compound can be obtained by various methods from the reaction mixture produced. For example, the target compound of the present invention may be obtained by filtration of the reaction solution, washing the filtrate with water, and then removing the solvent. If necessary, the target compound may be prepared by re-distillation, recrystallization, chromatography, or the like. It can also be separated and purified.

Meanwhile, in the 5-hydroxy pyrazole of the general formula (II) used as the reaction starting material of the present invention, a compound in which R ¹ is hydrogen is a known compound 1, 3-dimethyl-5-hydroxy pyrazole (1 , 3-dimethyl-2-pyrazolin-5-one), but can be synthesized using ethyl acetoacetate (Reference: ARKatritzky and FWMaine, Tetrahedron, 20,299 (1964), R ¹ is halogen Substituted compounds can be synthesized from the above compounds wherein R ¹ is hydrogen using common halogenation reagents.

Examples of 5-hydroxypyrazole derivatives that can be prepared according to the present invention are shown in Table 1 below for each substituent.

TABLE 1

In order to use the compound (I) as a pesticidal and acaricide composition, one or two or more types of general pesticides can be taken, that is, dissolved or dispersed in a liquid carrier according to the purpose of use, or It can be used by mixing or adsorbing into a suitable solid carrier in the form of emulsion, hydrating agent, powder, granule, spray. If necessary, emulsifiers, suspending agents, electrodeposition agents, penetrants, wetting agents, store agents, stabilizers and the like may be added to these formulations.

The 5-hydroxypyrazole derivatives of the general formula (I) according to the present invention are useful for the control of hygiene pests, plant parasites, mites, in particular, rice worms and aphids, and a few selected compounds (I) Is more effective against several pests than the world's leading drugs (eg, BRMC ^R , which is used for exterminating pests, and Metasystox ^R , which is used for controlling aphids). It has the advantage of salvation.

The drug efficacy test for the insecticidal and acaricide activity of some representative compounds (I) of the present invention is described in the following test examples. All the test insects used in these test examples were artificially bred in the laboratory. However, since pests actually parasitic in crops are already expressing resistance to the conventional representative drugs as described above, the emergence of new pesticidal compounds is urgently required. Therefore, the significance of the present invention is greater. will be.

Hereinafter, the present invention will be described in more detail according to an embodiment of the present invention.

Example 1

Preparation of 4-chloro-1-methyl-3-trifluoromethyl-5-hydroxypyrazole (in the above formula (II), wherein R ¹ is -CL and R ⁴ is -CH _3. )

To 30 ml of chloroform, 16.5 g (0.1 mol) of 1-methyl-3-trifluoro methyl-5-hydroxy pyrazole and 14.6 g (0.11 mol) of N-chlororesinamide were added and refluxed for 2 hours. After the reaction is completed, the mixture is cooled to room temperature, and the resulting precipitate is filtered. Subsequently, the solvent was removed from the filtrate under reduced pressure, and then 10 ml of ethyl ether was added thereto to remove the solids (lysineamide) formed, and the filtrate was concentrated to give 18.2 g (91% yield) of the target compound having a purity of 96% or more. Is obtained.

At this time, the pure analytical compound is obtained using chromatography.

mp 155-156 ° C., m / e 200.05 ¹ H NMR (CDCl ₃ ) δ8.8 (broad s, 1H), 3.6 (s, 3H)

Example 2

Preparation of 0, 0-diethyl-0- (1-methyl-3-trifluoromethyl-5-pyrazoyl) phosphate ester (Identification No. of Compound; 9).

1.0 g of 1-methyl-3-trifluoromethyl-5-hydroxy pyrazole, 1.24 g of diethyl chlorophosphate and 0.72 g of triethylamine were added to 10 ml of methylene chloride, which was stirred at room temperature for 2 hours. After the reaction is completed, the reaction product is filtered and the solvent is removed in vacuo to give an oily liquid.

Subsequently, when the oily liquid is purified by column chromatography on silica gel using a mixture of hexane and ethyl acetate (4: 1) as a solvent, 1.6 g of a pale yellow pure target compound is obtained.

¹ H NMR (CDCl ₃ ) δ1.2 (t, OH), 3.6 (s, 3H), 3.9 (q, 4H), 6.3 (s, 1H), M / S 302.1

Example 3

Preparation of 0, 0-diethyl-0- (1-methyl-3-trifluoromethyl) -5-pyrazoyl) thiophosphate ester (property number of compound; 13)

0.9 g of 1-methyl-3-trifluoromethyl-2-hydroxy pyrazole, 1.02 g of dimethyl chlorophosphate, and 0.70 g of triethylamine were added to methylene chloride and stirred at room temperature for 4 hours. The following operations were carried out in the same manner as in Example 2, whereby 1.14 g of a colorless target compound was obtained.

¹ H NMR (CDCl ₃ ) δ1.3 (t, 6H), 3.6 (s, 3H), 4.0 (q, 4H), 6.3 (s, 1H), M / S 318.1

Example 4

Preparation of 0, 0-diethyl-0- (4-chloro-1-methyl-3-trifluoromethyl-5-pyrazoyl) -phosphate ester (property number of the compound; 18).

From 2.0 g of 4-chloro-1-methyl-3-trifluoromethyl-5-hydroxy pyrazole, the reaction was carried out according to the method of Example 2 to obtain 3.2 g of the pure target compound.

¹ H NMR (CDCl ₃ ) δ 4.30 (t, 4H), 3.85 (s, 3H), 1.36 (t, 6H), M / S 332.6

Next, the insecticidal and acaricide activity of each of the 5-hydroxyperazole derivatives prepared as described above was measured according to the following test method (test example). At this time, the drug used in the test was dissolved 25 mg of the pyrazole derivative in 5 ml of acetone, mixed with 45 ml of trion-X-100 100 ppm aqueous solution of a surfactant, and then adjusted to a concentration of 500 ppm using a blank reagent solution do.

[Test Example 1]

Insecticidal effect test on brown planthopper.

Caterpillars of age-sensitive larvae (Nilaparvata lugens stal), bred indoors without pesticides, are housed in acrylic cages (26 cm wide, 29 cm wide and 20 cm high), with a final age of approximately 500 larvae per cage. Livestock was bred indoors using Dongjin rice in a constant temperature room (temperature: 27 ± 1 ℃, relative humidity: 50 ± 5%, light conditions: 16 females, 8 females).

In the insecticidal test, first, 6 seedlings (variety: dongjin) with 5 to 7 cm in height are rolled with cotton wool, inserted into a test tube (3 cm in diameter and 15 cm in height), and 20 adults are inoculated therein.

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 is sprayed twice.

On the other hand, the control group was treated with acetone-surfactant-distilled aqueous solution containing no test agent, but the test group and the control group were treated three times each. 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). When irritated with acupuncture, no reflexes are determined as death.

[Test Example 2]

Insecticidal test against 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 pesticide test, first, 50ml of the test drug with 500ppm concentration and 9cm diameter tobacco leaf (type: NC-82) were immersed for 30 seconds, air dried for 30 minutes, and placed in a 9cm petri dish. .

On the other hand, the control group was treated with acetone-surfactant-distilled aqueous solution, and treated three times with respect to the test group and the control group three times, and 20 insecticidal insects were inoculated into each treated tobacco leaf, followed by a constant temperature room (temperature The mortality rate was examined after 24 hours and 48 hours, stored at 21 ± 1 ℃, relative humidity 50 ± 5%, and light conditions (16 patients, 8 cancers). When irritated with a thin brush tip, no reflexes are considered death.

[Test Example 3]

Insecticidal test against bean bug

Riptortus clavatus thunberg collected in the open air was raised in a constant temperature room (temperature 25 ± 1 ℃, relative humidity 50 ± 5%, light conditions of 16 people, 8 cancers) for more than 1 year without any prey to insecticides. Used as

In the insecticidal test, first, three soybean seedlings (5-7 seedlings, roots 4-5cm) germinated in the water-containing vermiculite medium were immersed in an air medicine for 30 seconds, and then air dried. Place it in a cm clear polyethylene container, and inoculate 10 larvae of Larvae.

On the other hand, the control group is treated with acetone-surfactant-distilled water solution containing no test drug. Repeat the test and control groups three times each, and then cover the container and store it in a constant temperature room (temperature 25 ± 1 ℃, relative humidity 50 ± 5%, light conditions 16 people 8 cancer) after 24 hours and 48 hours. Examine the mortality rate. When irritated with fine needles, no reflexes are caused by death.

[Test Example 4]

Insecticidal effect test on diamond-back moth.

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

Insecticidal test, first cut the cabbage leaf into a 9cm diameter circle and soaked for 30 seconds in a 500ppm test specimen, and then air-dried for 30 minutes. On the other hand, the control group is treated with acetone-surfactant-distilled water solution containing no test drug. The leaves thus treated are placed in a Petri dish with a diameter of 9 cm, and 10 larvae are inoculated therein.

After repeating the 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 ° C, relative humidity 50 ± 5%, light conditions of 16 people, 8 cancers) for 24 hours and 48 hours. Examine the mortality rate after time. Anything that does not show reflexes when touched with a thin brush tip is considered dead.

[Test Example 5]

Insecticidal effect test on two-spotted spider mite

Tetranychus urticae koch of insecticide susceptible strains is bred indoors using Gangnam leaves in a constant temperature room (temperature 23 ± 1 ℃, relative humidity 50 ± 5%, light conditions of 16 people, 8 cancers), and the adult is disclosed. . Insecticidal test, first, agar (0.5% agar content) was poured into Shaye to the depth of about 1cm, the Gangnam bean leaves were fixed on it, and 40 adults were inoculated there, and the concentration was 500ppm Spray 3 ml of the test drug.

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 ° C., 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 to be alive.

The mortality rate was calculated according to the following equation for the experimental results obtained in Test Examples 1 to 4, which are shown in Table 2 below.

TABLE 2

As can be seen in Table 2, the 5-hydroxy pyrazole derivatives of the present invention shows an excellent insecticidal effect, especially against rice pests and aphids, BPMC ^R and Metasystox ^R which are the world's leading agents against the pests, The compound (I) of the invention was quantitatively compared (at this time, the test method is based on Test Examples 1 and 2), and the results are shown in Table 3 and Table 4 below.

TABLE 3

(Test on the Lighthopper)

* According to the results of Table 3, the effect of BPMC ^R is superior to the compounds (9 and 13) of the present invention under laboratory conditions. However, in the case of actually using the BPMC ^R for crops, the rice bran was already added to the BPMC ^R. Since it is resistant to, the same effect can be obtained only by using a concentration of several tens to several hundred times higher than the above experimental value.

TABLE 4

Claims (2)

The novel 5-hydroxypyrazole derivatives having a physiological activity characterized by the following general formula (I).

Wherein R ¹ is hydrogen or a halogen atom, R ² is a lower alkyl group, R ³ is an alkoxy or lower alkylthio group, a phenoxy group, or a phenoxy group or thiophenoxy optionally having one or more halogen or nitrosubstituent groups And R ⁴ is hydrogen, a lower alkyl group, or a phenyl group having a substituent, X is oxygen or sulfur. In this case, the halogen element refers to bromine, chlorine or iodine, and the lower alkyl group refers to a linear or pulverized alkyl group having 1 to 6 carbon atoms. Insecticide and acaricide comprising the 5-hydroxypyrazole derivative represented by the following general formula (I) as an active ingredient.

Wherein R ¹ , R ² , R ³ , R ⁴ and X are the same as defined in claim ¹ .