MXPA97001519A - Tifluzamide with stabilized effectiveness - Google Patents

Abstract

The disclosed invention is thifluzamide with an altered crystalline form, prepared by heat melting and then cooling, and chemical compositions for agriculture comprising said trifluzamine, which acts as an effective ingredient.

Description

TIFLUZAMIDE WITH STABILIZED EFFICACY The present invention relates to carboxyamide N- (2,6-dibromo-4-trifluoromethoxyphenyl) -2-methyl-4-trifluoromethyl-5-thiazole (common name: trifluzamide) with an altered crystalline form, its method of preparation and the chemical composition for agriculture that contains the tifluzamide, which acts as its effective ingredient.

Brief Description of the Drawings Figure 1 - X-ray diffraction pattern for a-crystalline tifluzamide powder, obtained in the Reference Example. Figure 2 - X-ray diffraction pattern for ß-crystalline tifluzamide powder, obtained in Example 1. Tifluzamide is a compound having a high pesticidal activity against scorching disease of rice leaf spots. Because the right moment to use a chemical against the scorching disease of rice leaf stains, in the rice plant crop, is when the rice field is covered with a smaller amount of water, the Index of release / diffusion of the effective ingredient significantly affects the extermination effect. However, because the water solubility of the tifluzamide is extremely slow, approximately 1.6 mg./l (20 ° C), it is desired to develop a method that can increase the rate of its release into the water and stabilize its effectiveness. We have discovered that the tifluzamide synthesized by the ordinary method of preparation changes its crystalline form, when it is fused by heat and then cooled, and that the release of the tifluzamide in water can be improved. As a result, pesticidal efficacy can be stabilized by preparing a chemical composition for agriculture that uses tifluzamide with an altered crystalline form. Based on this discovery, the present invention was perfected.

Therefore, this invention is a process for preparing tifluzamide with an altered crystalline form, comprising heat-melted thifluzamide at a temperature above the melting point, preferably 180 ° C at 250 ° C, more preferably 180 ° C to 200 ° C and then cooling to a temperature below the melting point. Another embodiment of the present invention is the tifluzamide which shows to have an endothermic peak of 175 ° C to 180 ° C by means of the differential ray calorimeter, and which has no other peak lower than said temperature. A third embodiment of this invention is the tifluzamide which shows a peak at 20 = 17.68, 20.04, 23.04, 28.88 and 29.52 by X-ray powder diffraction analysis.

Another embodiment of this invention is a chemical composition for agriculture, comprising tifluzamide with an altered crystalline form, which acts as an effective ingredient. It is known that the melting point of the tifluzamide is from 177.9 ° C to 178.6 ° C (Pesticide Manual, 1994). However, the tifluzamide synthesized in the Reference Example, shown below, shows an endothermic peak in the vicinity of 178 ° C by means of a differential scanning calorimeter (DSC), and shows an additional endothermic peak of 2.0 to 2.5 cal./gr. in the vicinity of 161 ° C. And, in the powder X-ray diffraction analysis, it shows a diffraction pattern similar to that of Figure 1. From now on, the tifluzamide with said crystalline form will be called "crystal a". The tifluzamide of this invention, which has an altered crystalline form, has a crystal structure different from that of a-crystal by X-ray powder diffraction analysis and the DSC, as illustrated by the tifluzamide obtained in the Example 1 that will be shown later. Specifically, it shows an endothermic peak only in the vicinity of 178 ° C by DSC and does not show a lower endothermic peak at that temperature. In the powder X-ray diffraction analysis, it shows a diffraction model like the one in Figure 2 and shows a peak at 2? = 17.68, 20.04, 23.04, 28.88 and 29.52. From now on, the tifluzamide which has said crystalline form will be called "crystal ß". The ß-crystalline tifluzamide of this invention is prepared by the following method. After heat-melting the α-crystalline tifluzamide at a temperature higher than the normal melting point, preferably 180 to 250 ° C, more preferably 180 to 200 ° C, it is cooled to a point less than the melting point and it crystallizes again. Although the cooling rate is not critical, in this case, the cooling rate in terms of the time required to crystallize is 190 ° C, preferably 0.01 second to 20 minutes, more preferably 0.01 to 20 seconds. The ß-crystalline tifluzamide of the present invention can be easily prepared by transferring the α-crystalline tifluzamide, which is melted at a temperature higher than its melting point, in a heating device such as a dryer to an environment having a temperature lower than its melting point, such as the ambient temperature. It can also be easily prepared by adding, by drip or spraying, the fused crystalline tifluzamide into a liquid such as water, which is inert to the trifluzamide and substantially does not dissolve thereto, or by spraying the trifluzamide into a gas such as air. , which is inert to the tifluzamide. Although there is no particular restriction in relation to the form of the chemical composition for the agricultural composition of the present invention, where the β-crystalline trifluzamide is used as the effective ingredient, powder, hydrates, pills can be mentioned as examples. , tablets, granular hydrates, suspension and others. Each of these can be prepared by ordinary methods known to those skilled in the art of chemical formulations for agriculture. In addition, there is no particular restriction on additives other than ß-crystalline tifluzamide, which will be added to the chemical composition for agriculture of this invention. Also, other effective ingredients than β-crystalline thifluzamide can be added as effective ingredients of the agricultural chemical composition of the present invention. We have discovered that the pesticidal efficacy and releasability of tifluzamide, which is extracted by leaching into water from the chemical composition for agriculture, wherein the ß-crystalline tifluzamide obtained according to the present invention serves as the effective ingredient, they have been improved compared to when a-crystalline tifluzamide was used.

In addition to the β-crystalline tifluzamide, the agricultural chemical composition of the present invention also includes the situation where both the α-crystals and β-crystals of the trifluzamides are used as a mixture, but the mixing index of the β-form -crystalline is preferably from 20 to 100%, more preferably from 50 to 100%, from the viewpoint of improving solubility in water. This invention is explained by means of Reference Examples, Examples and Examples of Tests, which are illustrated below. However, this invention is not limited only to said examples. Incidentally, the "parts" in the following Examples and Comparative Examples mean "parts by weight". And the DSC and powder X-ray diffraction analysis, which are shown in the Reference Examples and Examples, were carried out under the test conditions illustrated below.

DSC determination (in air) Equipment DSC-3100, manufactured by Mac Science Co. Weight of the sample 3 mg. sample container Aluminum sampling rate 1.0 seconds Proportion of temperature rise 5.0 ° C / minute X-ray diffraction analysis for dust Equipment JDX-8200T, manufactured by Nippon Denshi K.K. Objective Cu 2T = 5o - 50 ° Stage angle 0.04 ° Counting time 0.5 seconds Tube voltage 30.0kV Tube current 100.0 A Reference example - Synthesis of a-crystalline tifluzamide. 6.47 gr. of thiazole 2-methyl-4-trifluoromethyl-5-chlorocarbonyl and 8.91 g. of aniline 2, 6-dibromo-4-trifluoromethoxy were added to 16.8 ml. of acetonitrile, and heated for 6.5 hours for the reflection. The solvent was removed from the reaction mixture by distillation under reduced pressure and then 420 gr. of ethyl acetate and 300 ml. of water and they stirred. After standing at rest, the ethyl acetate layer was collected and washed with 300 ml. of water, of saturated sodium bicarbonate solution and water, successively. Then, after drying over anhydrous sodium sulfate, the solvent was removed by distillation under reduced pressure to obtain 13.9 g. of tifluzamide.

Starting materials, thiazole 2-methyl-4-trifluoromethyl-5-chlorocarbonyl and 2,6-dibromo-4-trifluoromethoxy aniline, were synthesized by means of the procedures described in Example 1 of the Japanese Kokai patent no. 184680/1990. The crystal thus obtained showed an endothermic peak of 2.1 cal / g. in the vicinity of 161 ° C and another endothermic peak of 9.0 cal / gr. in the vicinity of 178 ° C by DSC. And by means of X-ray powder diffraction analysis, as illustrated in Figure 1, the relative intensity of the peak at 20 = 17.7 ° was I / Io = 12 and at 2? = 23.0 ° was I / Io = ll. The crystal obtained in this Reference Example was called "crystal a". The 200 gr. of a-crystalline tifluzamide which were obtained in the Reference Example were placed in a glass Petri dish with a diameter of 3 cm. After the disc was placed in a dryer at 190 ° C to completely melt the tifluzamide, it was taken out of the dryer and then placed at room temperature to re-crystallize. In this case, the time required for the tifluzamide, which was taken out of the dryer at 190 ° C, to fully crystallize, was 20 seconds. The crystal thus acquired showed an endothermic peak of 9. 5 cal / gr. in the vicinity of 178 ° C by DSC, but did not show a peak in the vicinity of 161 ° C. By means of powder X-ray diffraction analysis, as illustrated in Figure 2, it showed a peak at 2? = 17.68, 20.04, 23.04, 28.88 and 29.52 and the relative intensity of peak at 2? = 17.6 was of I / Io = 100 and the relative intensity of peak at 20 = 23.0 ° was I / Io = 59 and, therefore, its crystalline form was different from that of a-crystal. The crystal obtained in this Example was called "β-crystal". Example 2 - Pill 1 (ß-crystal). The ß-crystalline tifluzamide obtained in Example 1 was fractured with a jet grinder (A-0 Jet Mili, manufactured by Seishin Kigyo K.K.). These 2.0 parts of fractured material, 5.0 parts of sodium lignin sulfonate, 0.5 parts of alkylbenzene sulfonic acid, 1.0 parts of sodium polyacrylate, 2.0 parts of sodium tripolyphosphate, 40 parts of bentonite, 49.5 parts of calcium carbonate and 16 parts of water were mixed in an Almighty Mixer (manufactured by Dalton K.K.), said mixture was converted into pills by means of a machine for manufacturing expulsion-type pills, equipped with a screen with 0.8 mm openings. (BR-200, manufactured by Fuji Po dal K.K.). This pill was dried at 50 ° C to obtain a pill 1 (crystal β). Example 3 - Pill 2 (mixture of the crystals a and β) The 35 parts of tifluzamide (crystal a) obtained in the Reference Example and the 65 parts of tifluzamide (crystal β) obtained in Example 1 were mixed in a jet crusher (A-0 Jet Mili). This mixed / fractured tifluzamide showed an endothermic peak of 0.71 cal / gr. in the vicinity of 161 ° C and another endothermic peak of 9.1 cal / gr. in the vicinity of 178 ° C by DSC. And X-ray diffraction analysis confirmed that it was a mixture of crystal a and crystal ß. 2.0 parts of the mixed / fractured tifluzamide (crystal a: crystal β = 35: 65) were processed as in Example 2, to obtain a pill 2 (mixture of a + β crystals). Comparative Example - crystal a The procedure of Example 2 was applied in 2.0 parts of the fractured tifluzamide (crystal a), obtained in the Reference Example, to obtain a comparative pill (crystal a). Example of Test 1 - Test of dissolution of the pills. Forty-five milligrams of each of the pills 1 and 2 and the comparative pill in a cooking container containing 100 ml were added. of strong water (hardness = 10 °) and were kept at water temperature of 30 ° C. After maintaining the above mixture at rest for 7 days, a portion of the solution was taken from the central part of the container and the content of the tifluzamide was analyzed. The percent of the tifluzamide that was released was calculated by means of the following equation. % released = A x 100 / B A: Amount (mg.) of tifluzamide released in water B: Content (mg.) of tifluzamide in the pill, which was added to the cooking vessel. The results are presented in Table 1. Example of Test 2 - Proof of the biological effect. A container (area size 1/10000) containing the rice plants in its eight leaf stage was treated with the pill obtained in Example 2 and the Comparative Example, in a dose of 300 g / area. Seven days after the treatment, the scorching stain on the leaves of the rice (Hydpochuns sasaki), which was cultivated before the time in the rice husking medium, was wrapped in a thin leaf and inserted between the rice plants. in the cooking bowl of 1/10000 area, to inoculate the plague. After inoculation, the rice plants in the 1/10000 area container were stored in a green housing at 25 ° C and 100% humidity. Seven days after the inoculation, the size of the highest spot reached by the plague to cause the disease was measured from the inoculation spot, and this was used to calculate the extermination value. The results are shown in Table 1. Table 1 Tifluzamide Value of extermination released, in that of disease 7o. day (%) scorching stains on rice leaves. (%) Pill 1 (crystal ß) 100 80 Pill 2 (crystals a + ß) 80 - Comparative Pill 58 60 (crystal a) The proportion of the release of the tifluzamide in water can be increased and the efficacy as a chemical for agriculture can be stabilized using the tifluzamide, which has been converted to the crystalline form of the present invention, as the active ingredient of the chemical for agriculture.

Claims (6)

1. CLAIMS 1. A process for preparing tifluzamide with an altered crystalline form, comprising the heat-melted tifluzamide at a temperature above the melting point and then cooling it to a temperature below the melting point.
2. 2. The tifluzamide that shows having an endothermic peak at 175 - 180 ° C by means of the differential scanning calorimeter and not having any other peak below that temperature.
3. 3. The tifluzamide showing a peak at 20 = 17.68, 20.04, 23.04, 28.88 and 29.52 by X-ray powder diffraction analysis.
4. 4. A chemical composition for agriculture, comprising tifluzamide with an altered crystalline form, which acts as an effective ingredient.
5. The process according to claim 1, wherein the trifluzamide is melted by heat at a temperature of 180 ° C to 250 ° C.
6. 6. The process according to claim 1, wherein the trifluzamide is melted by heat at a temperature of 180 ° C to 200 ° C.