Crystalline form of oxamyl process for its preparation and use of the same

Abstract

A crystalline form of oxamyl is provided. The crystalline form of oxamyl is of formula (I): ##STR00001## A crystal preparation process, the analyses of the crystal through various analytical methods, and using the crystalline form to prepare a stable agrochemical formulation is also provided. The use of various solvents towards the crystalline form preparation conditions is also provided.

Claims

1. A crystalline modification I of (EZ)-N,N-dimethyl-2-methylcarbamoyloxyimino-2-(methylthio)acetamide (oxamyl), exhibiting the following reflexes, as 2θ±0.20 degree in X-ray powder diffractogram (X-RPD) recorded using Cu-Kα radiation at 25° C.:
2θ=12.72±0.20   (1)
2θ=16.17±0.20   (2)
2θ=16.60±0.20   (3)
2θ=19.26±0.20   (5)
2θ=21.04±0.20   (7)
2θ=22.87±0.20   (8)
2θ=25.04±0.20   (10)
2θ=25.57±0.20   (11)
2θ=31.14±0.20   (16).

2. The crystalline modification I of oxamyl according to claim 1, exhibiting an IR spectrum with characteristic functional group vibration peaks at wavenumbers (cm.sup.−1, ±0.2%) of one or more of about 3325, 2935, 2161, 1713 and 1659 cm.sup.−1.

3. The crystalline modification I of oxamyl according to claim 1, exhibiting a melting point of 100° C. to 104° C.

4. The crystalline modification I of oxamyl according to claim 1, exhibiting a differential scanning calorimetry (DSC) profile having an endothermic melting peak at 102° C.

5. A process for the preparation of a crystalline modification I of oxamyl according to claim 1, comprising: i) dissolving oxamyl in a solvent, or mixture of solvents; ii) precipitating the dissolved compound into crystalline modification I of oxamyl; and iii) isolating the precipitated crystalline modification I.

6. The process according to claim 5, where the oxamyl in step i) is amorphous oxamyl.

7. The process according to claim 5, wherein the solvent is selected from the group consisting of nitrobenzene, toluene, xylene, chlorobenzene, dichlorobenzene, trifluoro methyl benzene, mesitylene, ether, ethyl acetate or a mixtures thereof.

8. The process according to claim 5, where the solvent is selected from the group consisting of ethyl acetate and/or nitrobenzene or a mixture thereof.

9. The process according to claim 5, wherein step ii) comprises concentrating the solution and/or by cooling and/or by the addition of a solubility reducing solvent and/or by adding a seed crystal of the crystalline modification I of oxamyl.

10. The process according to claim 9, wherein step ii) is effected by cooling to about 0° C. to 20° C.

11. The crystalline modification I of oxamyl according to claim 1, obtainable by the process of i) dissolving oxamyl in a solvent, or mixture of solvents; ii) precipitating the dissolved compound into crystalline modification I of oxamyl; and iii) isolating the precipitated crystalline modification I.

12. A crystalline modification I of oxamyl obtained by a process according to claim 5 and having a content of crystalline modification I of oxamyl of at least 98% by weight.

13. A composition comprising the crystalline modification I of oxamyl according to claim 1 and at least one auxiliary.

14. The composition according to claim 13, wherein the auxiliary is selected from one or more of a surfactant, a liquid diluent, a solid diluent, a wetting agent, a dispersant, a thickening agent, an antifreezing agent and a biocide.

15. The composition according to claim 14, wherein the other formulation ingredients can be are dyes and drying agents.

16. The composition according to claim 13, which is in form of a suspension concentrate (SC), an oil-based suspension concentrate (OD), an soluble concentrate (SL), a water-soluble granule (SG), a dispersible concentrate (DC), an emulsifiable concentrate (EC), an emulsion seed dressing, a suspension seed dressing, a granule (GR), a microgranule (MG), a suspoemulsion (SE) or a water-dispersible granule (WG).

17. The composition according to claim 16, which is in form of a suspension concentrate (SC) or a granule (GR).

18. The composition according to claim 13, which comprises crystalline modification I of oxamyl in an amount of less than 75% by weight.

19. The composition according to claim 13, which comprises crystalline modification I of oxamyl in an amount of 42% by weight.

20. The composition according to claim 13, which comprises crystalline modification I of oxamyl in an amount of 24% by weight.

21. The composition according to claim 13, which comprises crystalline modification I of oxamyl in an amount of 10% by weight.

22. A method for the control of insects and nematodes, comprising applying the crystalline modification I of oxamyl according to claim 1 to a plant, a plant part, or surroundings of a plant.

23. The method according to claim 22, wherein the insects and nematodes are selected from the group consisting of Boll weevil, Flea hopper, Tarnished plant bug, Cotton leaf perforator, Pink bollworm, Aphids, Flea beetle, Potato leafhopper, Tarnished plant bug and Citrus thrips.

24. The method according to claim 22, wherein the insects and nematodes are insects and nematodes on cotton and potato.

25. The crystalline modification I of oxamyl according to claim 1, characterized by X-ray powder diffraction pattern as shown in FIG. 2, and/or characterized by an IR spectrum as shown in FIG. 1, and/or characterized by a DSC thermogram as shown in FIG. 3.

Description

BRIEF DESCRIPTION OF DRAWINGS

(1) Various features and aspects of the embodiments of the invention disclosed herein can be more clearly understood by reference to the drawings, which are intended to exemplify and illustrate, but not to limit, the scope of the invention, and wherein:

(2) FIG. 1 is an infrared (IR) spectrum of an embodiment of crystalline modification I of oxamyl.

(3) FIG. 2 is a X-ray powder diffractogram (X-RPD) of the crystalline modification I of oxamyl.

(4) FIG. 3 is a Differential Scanning calorimetry (DSC) thermogram of crystalline modification I of oxamyl.

(5) FIG. 4 is a X-ray powder diffractogram of amorphous oxamyl.

DETAILED DESCRIPTION

(6) The present invention will now be described by the following examples, and in which the following measurement techniques have been employed, and which the examples are provided for illustrative purposes only, and not intended to limit the scope of the disclosure.

(7) All X-ray diffractograms were determined using powder diffractometer in reflection geometry at 25° C., using the following acquisition parameters:

(8) TABLE-US-00001 X'Pert Pro MPD from PANalytical B.V. Theta compensating slit and graphite monochromator Copper (K-alpha) radiation, 40 kV, 40 mA Step size: 0.03 degree 2-theta Count time: 1.0 second Maximum peak intensity: 1705 counts per second Scan range: 3-60 degrees 2-theta

(9) The IR spectrum was measured with the resolution of 4 cm.sup.−1 and with the number of scans of 16 for the crystallized samples. The crystalline modification I of oxamyl can be identified by its characteristic functional group vibration peaks at wavenumbers (cm.sup.−1, ±0.2%) of one or more of 3325.05, 2934.51, 2161.00, 1712.88 and 1659.10 cm.sup.−1 as shown in FIG. 1.

(10) All IR spectra were obtained using the following acquisition parameters:

(11) TABLE-US-00002 FT-IR spectrometer Nicolet ™ iS 5 Diamond ATR unit Thermo Scientific ™ iD5 ATR Wavelength range 550-4000 cm.sup.−1 Resolution 4 cm.sup.−1 Number of scans 16

(12) All DSC thermograms were obtained using the following acquisition parameters:

(13) TABLE-US-00003 Differential Scanning DSC 214 Polyma from Calorimeter NETZSCH-Gerätebau GmbH Range 60° C./1.0 (K/min)/160° C. Sample car./TC DSC 214 Corona sensor/E Segments 1/1 Crucible Pan Al, closed Atmosphere N.sub.2, 50.0 ml/min/N.sub.2, 70.0 ml/min Corr/m. range 000/5000 μV

EXAMPLES

Example 1: Preparation of Amorphous Oxamyl in Accordance with the Disclosure of U.S. Pat. No. 5,284,962, Example 2

(14) A two-stage, co-currently fed, continuous reactor system was used to react MIC (methyl isocyanate) and the oxime, methyl 2-(dimethylamino)-N-hydroxy-2-oxoethanimidothioate, to produce methyl 2-(dimethylamino)-N-[[(methylamino)carbonyl]oxy]-2-oxoethanimidothioate (oxamyl). The reactors were maintained at approximately 42° C. During steady state operation, methyl isocyanate (MIC) was fed at a rate of 1.2 g/min and vaporized and mixed with nitrogen which was fed at approximately 2200 mL/min. The oxime was fed at a rate of 7.9 g/min as a 40% slurry in water containing 0.2% TEA. Conversion of the oxime in the first reactor was about 93%. The composition of the product solution from the second reactor was approximately 47% title product, 0.9% oxime and 0.8% DMU (dimethyl urea). This composition corresponded to 97% conversion of the oxime and 8% of the original MIC as DMU. The vent stream from the second reactor contained about 0.2% MIC corresponding to removal of greater than 99% from the gas stream.

(15) ##STR00003##

(16) As shown in FIG. 4, the X-ray powder diffraction pattern of the resulting oxamyl product has no significant signals, which indicates the oxamyl product prepared in accordance with the disclosure of U.S. Pat. No. 5,284,962 is amorphous.

Example 2: Preparation of the Crystalline Modification I of Oxamyl

(17) Crystallization from Ethyl Acetate

(18) 10 g of amorphous oxamyl sample prepared in Example 1 was taken in a 3 neck round bottom flask along with 50 mL of ethyl acetate and the resulting slurry was heated to 65° C. to get a homogeneous solution. The insoluble particles, if any, were filtered and the solution was slowly cooled to 20˜25° C. Upon cooling, fine crystals were formed and the resulting heterogeneous mixture was stirred at 20° C. for 2 h. Then, the slurry was filtered and washed with 3 mL of ethyl acetate at 20° C. The filtered crystals were dried under vacuum at 40° C. The crystal product obtained had a purity of >98% and the recovered product as crystal was found to be about 90% yield.

(19) The obtained crystals were analyzed by IR spectrometry, X-RPD and DSC and found out to be crystalline modification I of oxamyl as shown in FIG. 1, FIG. 2 and FIG. 3, respectively.

(20) The IR spectrum of the crystalline modification I of oxamyl is set out in FIG. 1. The IR spectrum of oxamyl exhibited the functional group characteristic vibrations peaks at wavenumbers of one or more of 3325.05, 2934.51, 2161.00, 1712.88 and 1659.10 cm.sup.−1.

(21) The DSC thermogram of oxamyl exhibited an endothermic melting peak at 102° C. as shown in FIG. 3.

(22) The X-ray powder diffractogram of the crystals exhibited the reflexes in FIG. 2 and the values are summarized in Table 1.

(23) TABLE-US-00004 TABLE 1 Crystalline Modification I 2θ(°) d(Å) 12.718 ± 0.2 8.076 ± 0.05 16.171 ± 0.2 6.360 ± 0.05 16.601 ± 0.2 6.196 ± 0.05 17.714 ± 0.2 5.809 ± 0.05 19.255 ± 0.2 5.349 ± 0.05 20.026 ± 0.2 5.145 ± 0.05 21.040 ± 0.2 4.899 ± 0.05 22.874 ± 0.2 4.511 ± 0.05 24.432 ± 0.2 4.227 ± 0.05 25.035 ± 0.2 4.127 ± 0.05 25.571 ± 0.2 4.042 ± 0.05 26.159 ± 0.2 3.953 ± 0.05 26.879 ± 0.2 3.849 ± 0.05 29.633 ± 0.2 3.498 ± 0.05 29.914 ± 0.2 3.466 ± 0.05 31.142 ± 0.2 3.332 ± 0.05

Example 3: Preparation of the Crystalline Modification I of Oxamyl

(24) Crystallization from Nitrobenzene

(25) 5 g of amorphous oxamyl sample prepared in Example 1 was taken in a 3 neck round bottom flask along with 30 mL of nitrobenzene and the resulting slurry was heated to 83° C. to get a homogeneous solution. The insoluble particles, if any, were filtered and the solution was slowly cooled to 20° C. Upon cooling, fine crystals were formed and the resulting heterogeneous mixture was stirred at 20° C. for 2 h. Then, the slurry was filtered, washed with 3 mL of nitrobenzene at 20° C. and dried under vacuum at 45° C. The crystal product thus obtained had a purity of >98% and the recovered yield was found to be about 90% yield.

(26) The crystals were characterized as being oxamyl crystalline modification I using IR spectrometry, X-ray powder diffraction and DSC, as described in Example 2.

Formulation Examples

Example 4 Preparation of Suspension Concentrate (SC), 42% Oxamyl

(27) All the components list in Table 2 below were mixed uniformly and the resulting mixture was ground with a Dyno-Mill (manufactured by Willy A. Bachofen AG) to obtain a suspension concentrate.

(28) TABLE-US-00005 TABLE 2 Weights % Comparative Ingredients Sample A Sample A Function Oxamyl, crystalline 42.86 0 Active modification I, 98% compound (prepared in Example 2) Amorphous oxamyl 0 42.86 Active (prepared in Example 1) compound Propylene glycol 5 5 Anti-freezing agent Modified polydimethyl- 0.5 0.5 Antifoaming siloxane formulation agent (SAG 1529) Sodium Alkylnaphthalene- 3 3 Dispersing sulfonate, formaldehyde agent condensate (MORWET D-425 ® POWDER) Polyalkylene glycol 2 2 Wetting ether (ATLAS ™ agent G-5000) Xanthan gum 0.2 0.2 Thickening (AG-RHO POL 23/W) agent 1,2-Benzisothiazol- 0.2 0.2 Biocide 3-one (NIPACIDE BIT 20) Water Balance Balance Diluent to 100% to 100%

Example 5 Preparation of Suspension Concentrate (SC) 24% Oxamyl

(29) All the components list in Table 3 below were mixed uniformly and the resulting mixture was ground with a Dyno-Mill (manufactured by Willy A. Bachofen AG) to obtain a suspension concentrate.

(30) TABLE-US-00006 TABLE 3 Weights % Comparative Ingredients Sample B Sample B Function Oxamyl, crystalline 24.49 0 Active modification I, 98% compound (prepared in Example 2) Amorphous oxamyl 0 24.49 Active (prepared in Example 1) compound Propylene glycol 5 5 Anti-freezing agent Modified polydimethyl- 0.5 0.5 Antifoaming siloxane formulation agent (SAG 1529) Sodium Alkylnaphthalene- 3 3 Dispersing sulfonate, formaldehyde agent condensate (MORWET D-425 ® POWDER) Polyalkylene glycol 2 2 Wetting ether (ATLAS ™ agent G-5000) Xanthan gum 0.2 0.2 Thickening (AG-RHO POL 23/W) agent 1,2-Benzisothiazol- 0.2 0.2 Biocide 3-one (NIPACIDE BIT 20) Water Balance Balance Diluent to 100% to 100%

Example 6: Preparation of Granules (GR), 10% Oxamyl

(31) All the components listed in Table 4 below were mixed, blended and milled in a high-speed rotary mill. Sufficient water was added to obtain an extrudable paste. The paste was extruded through a die or screen to form an extrudate. The wet extrudate was dried at 70° C. in a vacuum oven and then sifted through 0.71 mm˜2 mm screens to obtain the product granules.

(32) TABLE-US-00007 TABLE 4 Weights % Comparative Ingredients Sample C Sample C Function Oxamyl, crystalline 10.2 0 Active modification I, 98% compound (prepared in Example 2) Amorphous oxamyl 0 10.2 Active (prepared in Example 1) compound Alkyl naphthalene 1.6 1.6 Wetting sulphonate, sodium agent salt (Akzo Nobel) Lignosulfonic acid, 8 8 Dispersing sodium salt agent (REAX ® 88B) Fatty acids, tallow, 1 1 Antifoaming sodium salts agent (AGNIQUE ® SOAP L) Mannitol (Shangdong Balance Balance Filler Tianli) to 100% to 100%

Example 7: Comparison of the Storage Stability

(33) Samples prepared in Examples 4, 5 and 6 were stored in heated ovens (54° C.) having the same atmosphere for 1 month, 3 months and 6 months. The procedures are followed according to CIPAC MT 46.3. The concentration of oxamyl was tested at the end of each storage time by high pressure liquid chromatography (HPLC). The aggregation was measured by observation. The results are listed in Table 5.

(34) TABLE-US-00008 TABLE 5 1 month 3 month 6 month Original Concentration Concentration Concentration concentration, of oxamyl of oxamyl of oxamyl Sample Formulation % (%) Aggregation (%) Aggregation (%) Aggregation Sample A SC 42 42 − 42 − 42 − Comparative SC 42 38 ++ 31 +++ 20 +++++ Sample A Sample B SC 24 24 − 24 − 24 − Comparative SC 24 20 ++ 15 +++ 10 +++++ Sample B Sample C GR 10 10 − 10 − 10 − Comparative GR 10 9 + 8 ++ 5 +++ Sample C Remark: “+” means small amount of aggregation. “+++++” means a lot of aggregation. “−” means no aggregation.