KR19980074124A - Stabilized Tifluzamide - Google Patents

Abstract

The present invention relates to a tifluzamide having a modified crystalline form prepared by heat-melting and cooling and to an agrochemical composition comprising such a tifluzamide as an active ingredient.

Description

Stabilized Tifluzamide

The present invention provides a modified crystalline form of N- (2,6-dibromo-4-trifluoromethoxyphenyl) -2-methyl-4-trifluoromethyl-5-thiazole carboxyamide (collectively: Tiflu Jamimid (thifluzamide), a method for producing the same and an active ingredient relates to a pesticide composition containing tifluzamide.

Tifluzamide is a compound having excellent insecticidal activity against rice leaf spot wither disease. In the case of the use of the control agent for the rice leaf spot side disease in rice cultivation field, since the paddy is covered with a small amount of water, the dissolution / diffusion rate of the active ingredient significantly affects the control effect. However, since the solubility of tifluzamide in water is very low at about 1.6 mg / l (20 ° C.), it is desired to increase the rate at which difluzamide elutes in water and stabilize its effect.

The inventors have found that when heat-melting and then cooling the synthesized tifluzamide by a conventional manufacturing method, its crystalline form changes and further improves the elution of tifluzamide to water. As a result, it is possible to stabilize the bactericidal effect by preparing a pesticide composition using tifluzamide having the modified crystalline form.

1 is a graph showing a powder X-ray diffraction pattern of α-crystalline tifluzamide obtained in Reference Example,

FIG. 2 is a graph showing a powder X-ray diffraction pattern of β-crystalline tifluzamide obtained in Example 1. FIG.

In one aspect of the invention, the deformation is achieved by heat-melting the tifluzamide at a temperature above the melting point, preferably between 180 and 250 ° C., more preferably between 180 and 200 ° C., followed by cooling to a temperature below the melting point. A method for preparing tifluzamide in crystalline form is provided.

In another aspect of the present invention, tifluzamide is provided by a differential scanning calorimeter which exhibits an endothermic peak at 175 to 180 ° C. and has no peak below the temperature.

In another aspect of the present invention, there is provided a tifluzamide showing peaks of 2θ = 17.68, 20.04, 23.04, 28.88 and 29.52 by powder X-ray diffraction analysis.

Furthermore, in another aspect of the present invention, there is provided a pesticide composition comprising tifluzamide in crystalline form modified with the active ingredient.

The melting point of tifluzamide is known to be 177.9-178.6 ° C. (Pesticide Manual, 1994). However, tifluzamide synthesized in the reference example described below shows an endothermic peak at around 178 ° C by a differential scanning calorimeter (DSC), which shows another endothermic peak at 2.0 to 2.5 cal / g at around 161 ° C. In the powder X-ray analysis, the diffraction pattern is shown in FIG. 1. Hereinafter, tifluzamide of this crystalline form is referred to as α-crystalline form.

Tifluzamide with the modified crystalline form of the present invention has a crystalline structure that is different from the α-crystalline form by powder X-ray diffraction analysis and DSC, as illustrated by the tifluzamide obtained in Example 1 below. In particular, the endothermic peak is exhibited only in the vicinity of 178 ° C by DSC, and the endothermic peak is not shown below the temperature. In powder X-ray diffraction analysis, the diffraction pattern as shown in FIG. 2 is shown, and 2θ = 17.68, 20.04, 23.04, 28.88 and 29.52 peaks are shown. Hereinafter, tifluzamide having such a crystalline form is referred to as β-crystal form.

Β-crystalline tifluzamide of the present invention is prepared by the following method. The α-crystalline tifluzamide is heat-melted at a temperature above the normal melting point, preferably at 180 to 250 ° C, more preferably at 180 to 200 ° C, and then cooled to a temperature below the melting point and recrystallized.

Although the cooling rate is not important, in this case, the cooling rate is preferably 0.01 to 20 minutes, more preferably 0.01 to 20 seconds to crystallize at 190 ℃.

Β-crystalline tifluzamide according to the present invention can be easily produced by transferring α-crystalline tiplazamide, which is melted at a temperature higher than the melting point, from a heating device such as a dryer to a temperature lower than the melting point, such as room temperature. have.

Further, molten α-crystalline tifluzamide is added dropwise to or sprayed with a liquid such as water that is inert to tifluzamide and substantially does not dissolve tifluzamide, or the tifluzamide is compared to tifluzamide. It can be easily prepared by spraying on a gas such as inert air.

Although the form of the formulation of the pesticide composition according to the present invention is not particularly limited, β-crystalline tifluzamide may be used as an active ingredient, powder, hydrate, pellets, tablets, granular hydrates and suspensions. Each of these may be prepared by conventional methods known to those skilled in the agrochemical formulation art. Furthermore, the addition of β-crystalline tifluzamide to the pesticide composition of the present invention is not particularly limited. In addition, other active ingredients other than β-crystalline tifluzamide may be added as an active ingredient to the pesticide composition of the present invention.

The inventors have found that when the β-crystalline tifluzamide obtained by the present invention is used as an active ingredient of the pesticide composition, tifluzamide has water from the pesticidal composition and pesticide composition as compared to the α-crystalline tifluzamide. It was found that the elutability eluted at was improved. In addition to β-crystalline tifluzamide, a mixture of α-crystalline and β-crystalline tifluzamide may also be used in the pesticide composition according to the present invention, but the mixing ratio of β-crystalline form in relation to the improvement of solubility in water Preferably it is 20-100%, More preferably, it is 50-100%.

Hereinafter, embodiments of the present invention will be described in detail. However, the scope of the present invention is not limited to the following examples. In addition, in the following Example and a comparative example, a part means a weight part. And DSC and powder X-ray diffraction analysis shown in Reference Examples and Examples were performed under the following test conditions.

DSC measurement (in air)

DSC-3100 from Mac Science Co.

Sample weight 3 mg

Aluminum sample pan

Sampling rate 1.0 sec

Temperature rise rate 5.0 ℃ / min

Powder X-Ray Diffraction

Nippon Denshi K.K.'s JDX-8200T

Target Cu 2θ = 5 ° ~ 50 °

Step Angle 0.04 °

Counting time 0.5 seconds

Tube voltage 30.0 kV

Tube Current 100.0 mA

[Reference Example]

Synthesis of α-crystalline Tifluzamide

6.47 g of 2-methyl-4-trifluoromethyl-5-chlorocarbonyl thiazole and 8.91 g of 2,6-dibromo-4-trifluoromethoxy aniline were added to 16.8 ml of acetonitrile and heated for 6.5 hours. To reflux. After distillation under reduced pressure to remove the solvent from the reaction mixture, 420 g of ethyl acetate and 300 ml of water were added and stirred. After standing still, the ethyl acetate layer was collected and washed successively with water, saturated sodium bicarbonate solution and 300 ml of water, respectively. Then dried over anhydrous sodium sulfate and distilled under reduced pressure to remove the solvent to give 13.9 g of tifluzamide.

Starting materials 2-methyl-4-trifluoromethyl-5-chlorocarbonyl thiazole and 2,6-dibromo-4-trifluoro by the method described in Example 1 of JP Patent 184680/1990. Romethoxy aniline was synthesized.

The so-obtained crystals showed an endothermic peak of 2.1 cal / g near 161 ° C. and another endothermic peak of 9.0 cal / g near 178 ° C. by DSC. As shown in FIG. 1, the relative peak intensities at 2θ = 17.7 ° by powder X-ray diffraction analysis were I / I ₀ = 12 and I / I _o = 11 at 2θ = 23.0 °. The crystal obtained in the reference example is an α-crystalline form.

Example 1

Synthesis of β-crystalline Tifluzamide

After 200 mg of the α-crystalline tifluzamide obtained in the reference example was placed in a glass petri dish having a diameter of 3 cm, the dish was placed in a 190 ° C. drier to completely melt the tifluzamide. It was taken out of the dryer and left at room temperature to recrystallize. In this case, the time taken for the tfluzamide to be removed from the 190 ° C. drier and completely recrystallized was 20 seconds.

The crystal thus obtained showed an endothermic peak of 9.5 cal / g at around 178 ° C by DSC, but no peak at around 161 ° C. Powder X-ray diffraction analysis showed peaks at 2θ = 17.68, 20.04, 23.04, 28.88 and 29.52, as shown in FIG. 2, and the relative peak intensity at 2θ = 17.6 ° was I / I ₀ = 100 and , The relative peak intensity at 2θ = 23.0 ° was I / I ₀ = 59, and thus the crystalline form was different from that of the α-crystal. The crystal obtained in this example is called β-crystal type.

Example 2

Pellet 1 (β-crystalline)

The β-crystalline tifluzamide obtained in Example 1 was crushed with a jet crusher (A-O Jet Mill manufactured by Seishin Kigyo K.K.). 2.0 parts of this crushed material, 5.0 parts of sodium lignin sulfonate, 0.5 parts of alkylbenzene sulfonic acid, 1.0 part of sodium polyacrylate, 2.0 parts of sodium tripolyphosphate, 40 parts of bentonite, 49.5 parts of calcium carbonate and 16 parts of water Almighty Mixer (Dalton KK And pelletizer in the form of an extruder equipped with a screen with 0.8 mm openings. The pellet was dried at 50 ° C. to obtain pellet 1 (β-crystalline form).

Example 3

Pellet 2 (mixture of α + β crystalline forms)

35 parts of tifluzamide (α-crystalline) obtained in the reference example and 65 parts of tifluzamide (β-crystalline) obtained in Example 1 were mixed in a jet crusher (A-O Jet Mill). The mixed / milled tifluzamide shows an endothermic peak of 0.71 cal / g near 161 ° C. and another endothermic peak of 9.1 cal / g near 178 ° C. by DSC. And the X-ray diffraction analysis showed that the material is a mixture of α-crystalline form and β-crystalline form.

2.0 parts of the mixed / milled tifluzamide (α-crystalline form: β-crystalline form = 35:65) was treated in the same manner as in Example 2 to obtain pellet 2 (mixture of α + β crystal form).

[Comparative Example]

α-crystalline

The test method of Example 2 was applied to 2.0 parts of the jet-milled tifluzamide (α-crystalline form) obtained in the reference example to obtain a comparative pellet (α-crystalline form).

[Test Example 1]

Pellet Dissolution Test

45 mg of pellets 1 and 2 and comparative pellets each were added to a beaker containing 1000 ml of hard water (hardness = 10 °) and maintained at a water temperature of 30 ° C. After standing still for 7 days, the solution was aliquoted from the center of the beaker and the content of tifluzamide was analyzed. The percent eluted tifluzamide was calculated by the following equation.

% Elution = A × 100 / B

A: Amount of tifluzamide eluted with water (mg)

B: The amount of tifluzamide in pellets added to the beaker (mg)

The test results are shown in Table 1 below.

[Test Example 2]

Biological effect test

300 g / are of pellets obtained in Example 2 and Comparative Example were treated with a 1 / 10000-sized ar planter planted with rice, the eighth flag. 7 days after treatment. A rice leaf spot withering pest (Hydpoxhuns sasaki), which was previously cultured in a rice hull medium, was wrapped in a cheese cross and inserted between rice paddies of 1/10000 ar pollen to inoculate the worm.

After inoculation, rice of 1/10000 argon was left in a greenhouse at 25 ° C. and 100% humidity. Seven days after the inoculation, the height of the spot where the disease-causing pest reached the highest spot among the inoculated spots was measured, and the control value was measured. The test results are shown in Table 1 below.

TABLE 1

By using tifluzamide modified in the crystalline form of the present invention as the active ingredient of the pesticide, the dissolution rate of tifluzamide eluted in water is increased, and the pesticide effect is stabilized.

Claims (6)

Heat-melting the tiplazamide at a temperature above the melting point; And Then cooling to a temperature below the melting point; Tifluzamid production method having a modified crystalline form comprising a. Tifluzamide, exhibiting an endothermic peak at 175-180 ° C. and having no other peak below said temperature by a differential scanning calorimeter. Tifluzamide showing peaks at 2θ = 17.68, 20.04, 23.04, 28.88 and 29.52 by powder X-ray diffraction analysis. Agrochemical composition comprising tiplazamide having a crystalline form modified with the active ingredient. The method of claim 1, wherein the Tfluzamide is heat-melted at 180 ℃ to 250 ℃. The method of claim 1, wherein the Tfluzamide is heat-melted at 180 ℃ to 200 ℃.