TWI778954B - A novel form of amicarbazone, a process for its preparation and use of the same - Google Patents

Abstract

The present invention describes the crystalline form of amicarbazone of formula (I), the crystal preparation process, the analyses of the crystal through various analytical methods and using the crystal to prepare stable agrochemical formulation. The invention also describes the use of various solvents towards the crystalline form preparation conditions.

Description

A new form of amfentrazone, its preparation method and use

This disclosure relates to 4-amino-N-tertiary butyl-4,5-dihydro-3-isopropyl-5-oxo-1H-1,2,4-triazole-1-formamide Crystalline form of (Amifentrazone), with respect to its preparation process and with respect to its use in agrochemicals.

類和三

酮類的除草劑在於其提供對光合電子傳遞的有效抑制，誘導葉綠素螢光並且藉由結合到具有燃盡活性(burn-down activity)的光系統II(PSII)的Qb域來中斷氧釋放。胺唑草酮經由雜草的根吸收，並被運輸到生長的尖端和葉，在該等部位光合作用的抑制導致黃化、生長停滯、組織壞死和死亡。在芽前和芽後均可以將其施用於作物(如甘蔗和玉米)上來對抗各種雜草。 Amenzazone (4-amino-N-tertiary butyl-4,5-dihydro-3-isopropyl-5-oxo-1H-1,2,4-triazole-1-formyl Amine) is a new triazolinone-related herbicide with broad-spectrum weed control with good selectivity and high potency. The activity of this new triazolinone herbicide is similar to that of three

class and three

Ketones are herbicides in that they provide potent inhibition of photosynthetic electron transport, induce chlorophyll fluorescence and interrupt oxygen release by binding to the Qb domain of photosystem II (PSII) with burn-down activity. Amfentrazone is taken up by weed roots and transported to growing tips and leaves where inhibition of photosynthesis leads to yellowing, growth arrest, tissue necrosis and death. It can be applied to crops such as sugar cane and corn both pre- and post-emergence to combat various weeds.

Amenzazone has the molecular formula C ₁₀ H ₁₉ N ₅ O ₂ . Its chemical structure is

Commercially available amfentrazone, which is generally prepared by the method described in US Pat. No. 5,194,085, exists in an amorphous state with a melting point of about 108°C. It has been found that amfentrazone, which is amorphous, is not suitable for preparation as a composition or formulation because the residue formed after dilution of the formulated product can easily clog spray filters. Therefore, there is a high demand for the development of new and stable crystalline forms of amfentrazone suitable for preparation into commercial formulations.

In order to solve some or all of the problems with the existing amorphous forms of amfentrale, new and stable crystalline forms of amfentrale have been prepared.

In a first aspect, the present invention provides 4-amino-N-tertiary butyl-4,5-dihydro-3-isopropyl-5-oxo-1H-1,2,4-triazole- Novel crystalline form of 1-formamide (amfentrazone), termed "Crystal Modification I", in X-ray powder diffraction patterns (X-RPD) recorded at 25°C using Cu-Kα radiation Present in any combination at least 3 of the following reflections, recorded as 2θ ± 0.2 degrees: 2θ = 11.0 ± 0.2 (1)

2θ=12.2±0.2 (2)

2θ=13.1±0.2 (3)

2θ=18.2±0.2 (4)

2θ=19.4±0.2 (5)

2θ=20.5±0.2 (6)

2θ=21.5±0.2 (7)

2θ=22.2±0.2 (8)

2θ=23.5±0.2 (9)

2θ=24.0±0.2 (10)

2θ=27.4±0.2 (11)

2θ=28.2±0.2 (12)

2θ=29.2±0.2 (13)

2θ=31.3±0.2 (14)

In one embodiment, the crystalline modification I of amfentrazone according to the first aspect of the invention exhibits in any combination the following reflections in an X-ray powder diffraction pattern recorded with Cu-Kα radiation at 25° C. At least 3, recorded as 2θ±0.2 degrees: 2θ=11.0±0.2 (1)

2θ=13.1±0.2 (3)

2θ=18.2±0.2 (4)

2θ=19.4±0.2 (5)

2θ=20.5±0.2 (6)

2θ=27.4±0.2 (11)

2θ=28.2±0.2 (12)

In a second aspect, the present invention provides crystalline modification I of amafentrazone, optionally according to the first aspect of the present invention, exhibiting a crystalline modification I having a concentration at wavenumbers (cm ⁻¹ , ±0.2%) of 3315.4, 3209.4 and 2970.4 Infrared (IR) spectra of characteristic functional group vibrational peaks at cm-1.

In a third aspect, the present invention provides crystalline modification I of amfentrazone, optionally according to the first or second aspect of the invention, exhibiting a melting point of 127°C-131°C, optionally 128°C-130°C °C, further depending on the circumstances, it is 129 °C. In a fourth aspect, the present invention provides crystalline modification I of amenzazone, optionally according to any one of the first to third aspects of the present invention, which exhibits an endothermic melting peak starting at 124°C and a peak maximum at Differential Scanning Calorimetry (DSC) profile at 129°C, further optionally with fusion enthalpy of 77 J/g.

In a fifth aspect, the present invention provides crystalline modification I of amafenzazone, optionally according to any one of the first to fourth aspects of the invention, by essentially Characterized by a powder X-ray diffraction pattern as shown in Figure 2, and/or by an IR spectrum substantially as shown in Figure 1, and/or by a DSC thermal spectrum substantially as shown in Figure 3 Analyze graphs to characterize.

In a sixth aspect, the present invention provides a crystallization of amafentrazone, optionally according to any one of the first to fifth aspects of the invention, obtainable by a method substantially as described in Example 2 or 3. Body I.

In a seventh aspect, the present invention provides crystalline modification I of amenzazone, optionally according to any one of the first to sixth aspects of the invention, obtainable by the method of the eighth aspect of the invention.

It has been found that the crystalline modification I of amafentrazone has a marked improvement in its stability, ie no residue after dilution. Furthermore, it has been found that the crystalline modification I is easier to pulverize or grind than the amorphous amifenzazone prepared according to the disclosure of U.S. Patent No. 5,194,085, and that formulations prepared using this It is also stable after storage. This allows the preparation of aqueous suspensions (SC), oily aqueous suspensions (OD), water dispersible granules (WG) and water soluble granules (SG). Furthermore, crystalline modification I has a lower tendency to aggregate and/or form residues after dilution compared to the amorphous phase described in US Pat. No. 5,194,085. For these reasons, crystalline modification I is more suitable for the preparation of commercial formulations. By virtue of its stability, crystalline modification I confers the desired long shelf life of its formulations. Thus, crystalline modification I can be used to prepare formulations of amfentrazone with excellent solution stability, as disclosed below.

In an eighth aspect, the present invention provides a process for the preparation of crystalline modification I of amfentrazone, the process comprising the steps of: i) dissolving amfentrazone in a solvent or a mixture of solvents; ii ) precipitating the dissolved compound as crystalline modification I of amafentrazone; and iii) isolating the precipitated crystalline modification I.

In one embodiment of the eighth aspect of the present invention, the amenzazone in step i) is amorphous amenzazone.

Methods for the preparation of amorphous amafenzazone are known in the art. Amorphous amafenzazone can be manufactured and obtained on a commercial scale. Especially suitable for preparing Methods for amorphous amfentrazone are described in US Pat. No. 5,194,085.

、二氯二乙醚、甲基-四氫呋喃、環氧乙烷和/或環氧丙烷的聚醚)、硝化烴(例如，硝基甲烷、硝基乙烷、硝基丙烷、硝基苯、氯硝基苯、乙苯和鄰硝基甲苯)、脂族、脂環族或芳族烴(例如，戊烷、正己烷、正庚烷、正辛烷、壬烷)，異丙基甲苯，具有從70℃至190℃的沸程的石油餾分，環己烷，甲基環己烷，石油醚，石油英，辛烷，苯)、酯(例如，丙二酸酯、乙酸正丁酯(醋酸正丁酯)、乙酸異丁酯、碳酸二甲酯、碳酸二乙酯、碳酸二丁酯和碳酸伸乙酯)、均三甲苯、甲基醚酮及其混合物。 In an embodiment of the eighth aspect of the present invention, the solvent is selected from the group consisting of halogenated hydrocarbons (for example, chlorobenzene, bromobenzene, dichlorobenzene, chlorotoluene, trifluoromethylbenzene and trichlorobenzene) benzene), ethers (for example, diethyl ether, ethyl propyl ether, n-butyl ether, anisole, phenetole, cyclohexyl methyl ether, dimethyl ether, dimethyl glycol, diphenyl ether, dipropyl ether, Diisopropyl ether, di-n-butyl ether, diisobutyl ether, diisoamyl ether, ethylene glycol dimethyl ether, isopropyl ethyl ether, methyl tertiary butyl ether, tetrahydrofuran, methyl tetrahydrofuran, di

, dichlorodiethyl ether, methyl-tetrahydrofuran, polyethers of ethylene oxide and/or propylene oxide), nitrated hydrocarbons (for example, nitromethane, nitroethane, nitropropane, nitrobenzene, chloronitro benzene, ethylbenzene and o-nitrotoluene), aliphatic, cycloaliphatic or aromatic hydrocarbons (for example, pentane, n-hexane, n-heptane, n-octane, nonane), isopropyltoluene, with Petroleum fractions with a boiling range of 70°C to 190°C, cyclohexane, methylcyclohexane, petroleum ether, petrolatum, octane, benzene), esters (for example, malonate, n-butyl acetate (n-butyl acetate) butyl), isobutyl acetate, dimethyl carbonate, diethyl carbonate, dibutyl carbonate and ethylene carbonate), mesitylene, methyl ether ketone and mixtures thereof.

In an embodiment of the eighth aspect of the present invention, the solvent is selected from the group consisting of: methyl ethyl ketone, benzene, chlorobenzene, dichlorobenzene, ethylbenzene, trifluoromethylbenzene, homo Mixtures of mesitylene, nitrobenzene, THF-hexane, ethyl acetate-hexane, dichloromethane-hexane, dichloromethane-methanol, THF-water and methanol-water. In one embodiment of the eighth aspect of the present invention, the solvent is selected from the group consisting of methyl ethyl ketone, nitrobenzene or mixtures thereof.

According to an embodiment of the eighth aspect of the present invention, step ii) is achieved by concentrating the solvent and/or cooling and/or adding a solubility-reducing solvent and/or adding seeds of crystal modification I of amfentrazone.

According to one embodiment of the eighth aspect of the present invention, the crystalline modification I of amfentrazone is prepared by dissolving amorphous amfentrazone in a solvent or solvent mixture, by heating from ambient temperature to the The reflux temperature of the solvent or the solvent mixture is at or below the reflux temperature to form a concentrated solution. Optionally, concentrated solutions can be prepared at the reflux temperature of the solvent. The concentration of the solution depends on the concentration of amfentrazone in the corresponding solvent or solubility in the solvent mixture.

In one embodiment of the eighth aspect of the invention, the concentrated homogeneous solution prepared in step (i) is then cooled to ambient temperature or to about 0°C to 20°C to crystallize the desired crystalline form from the solvent . The crystalline modification I of amafentrazone can also be crystallized by removing the solvent or solvent mixture to volume with or without the application of vacuum and cooling below the reflux temperature of the solvent or the solvent mixture to concentrate the homogeneous solution.

In one embodiment of the eighth aspect of the present invention, the crystallization of crystalline modification I of amfentrazone may also be carried out by adding seeds with the desired crystalline form to the solution prepared in step (i) during the crystallization It can promote or accelerate crystallization.

The amount of seed crystals added to the concentrated solution is usually in the range of 0.001% to 10% by weight, more specifically 0.005% by weight, based on the weight of amfentrazone used to prepare the concentrated solution in step (i). % to 0.5% range. Seed crystals are added to the concentrated solution at a temperature below the boiling point of the corresponding solvent or solvent mixture, as appropriate.

In one embodiment of the eighth aspect of the present invention, the precipitated amafenzazone obtained from step (ii) is isolated from the solution by common solid component separation techniques such as filtration, centrifugation or decantation Crystal Modification I. The isolated solid is then washed one or more times with solvent. Optionally, the solvent used in the washing stage consists of one or more components of the solvent or solvent mixture used to prepare the concentrated solution in step (i), as described above. The washing is generally carried out between room temperature and 0° C., depending on the solubility of the crystals, with the corresponding solvent or solvent mixture, in order to avoid as little loss of crystals as possible in the corresponding washing solvent. In one embodiment of the eighth aspect of the present invention, crystalline modification I of amafentrazone is dissolved and recrystallized. The crystallization washes and/or solvents in any process can be concentrated to obtain recyclable solid amafenzazone.

In a ninth aspect, the present invention provides the crystalline modification I of amfentrazone obtained according to the eighth aspect of the present invention, which has a content by weight of amfentrazone of at least 98% crystalline modification I.

In a tenth aspect, the present invention provides a composition comprising the crystalline modification I of amafentrazone according to any one of the first to seventh and ninth aspects of the present invention and at least one adjuvant.

In the eleventh aspect, the present invention provides the crystalline modification I of amafenzazone according to any one of the first to seventh and ninth aspects of the present invention or the composition according to the tenth aspect of the present invention for use in Use for weed control.

In an embodiment of the tenth aspect of the present invention, the amount of crystal modification I of amfentrazone is less than 90% by weight of the composition, and less than 80% by weight of the composition as the case may be, and further according to the composition as the case may be. less than 75% by weight of the composition, and further optionally about 70% by weight of the composition.

The use of amorphous amfentrazone as a herbicide is known in the art and is used on a commercial scale. It has been found that the crystalline modification I of amfentrazone is also effective in controlling undesired plant growth such as weeds. Therefore, with respect to amorphous amfentrazone, the formulation and application techniques of amfentrazone known in the art (such as those disclosed in the prior art documents discussed above) can also be compared with the crystalline transformation of the present invention. Amfentrazone in body I was administered in a similar manner.

Accordingly, the present invention provides a herbicidal composition comprising amfentrazone in crystalline modification I as defined above.

The present invention further provides a process for the preparation of a composition for controlling weeds using the crystalline modification I of amfentrazone.

In one embodiment of the tenth aspect of the present invention, the composition is in the following form: water suspension (SC), oil-based water suspension (OD), water-soluble granule (SG), water-dispersible emulsion (DC) ), emulsion (EC), emulsified seed dressing, suspension seed dressing, granule (GR), microgranule (MG), suspoemulsion (SE) or water dispersible granule (WG). The crystalline modification I of amafentrazone can be included in these customary formulations in a known manner using suitable adjuvants, carriers, solvents and the like.

In one embodiment of the tenth aspect of the present invention, the composition is in the form of water-dispersible granules (WG).

In one embodiment of the tenth aspect of the present invention, when applied to plants or their locus, the crystalline modification I of amafenzazone may be present in a concentration sufficient to achieve the desired dosage, desirably by weight of the total mixture It is present at a concentration of about 70%. The formulations are prepared, for example, by incorporating water, solvents and carriers, if appropriate, using emulsifiers and/or dispersants and/or other auxiliaries, into the crystalline modification I of amfentrazone.

The formulations are prepared by mixing the crystalline modification I of amfentrazone with customary additives, such as one or more of wetting agents, dispersants, antifoams and other formulation ingredients.

Wetting agents include, but are not limited to: Sodium Lauryl Sulfate, Alkyl Sulfosuccinate, Laurates, Alkyl Sulfates, Phosphates, Alkyne Diols, Ethoxylated Fluorinated Alcohols, Ethoxylated Silicone, Alkylphenol Ethoxylate, Benzene Sulfonate, Alkyl-Substituted Benzene Sulfonate, Alkyl Alpha-Olefin Sulfonate, Naphthalene Sulfonate, Alkyl-Substituted Naphthalene Sulfonate , naphthalenesulfonates and condensates of alkyl-substituted naphthalenesulfonates with formaldehyde, and alcohol ethoxylates, and mixtures thereof. Sodium lauryl sulfate is particularly useful for the compositions of the present invention.

Dispersants include, but are not limited to: sodium, calcium and ammonium salts of lignosulfonic acid (optionally polyethoxylated); sodium and ammonium salts of maleic anhydride copolymers; sodium salts of condensed phenolsulfonic acid ; and naphthalenesulfonate-formaldehyde condensates. Lignosulfonates such as sodium lignosulfonate are particularly useful for the compositions of the present invention.

Other formulation ingredients may also be used in the present invention, such as fillers, carriers, defoamers, dyes, desiccants, and the like. Such ingredients are known to those skilled in the art.

In one embodiment of the tenth aspect of the present invention, the crystalline modification I of amfentrazone may exist in formulations and in other forms prepared from such formulations, and in combination with other active compounds (such as insecticides, attractants, bactericides, bactericides, acaricides, nematicides, fungicides, growth-regulating substances, herbicides, safeners, fertilizers and signal compounds) or as a mixture with agents for improving plant traits.

In one embodiment of the tenth aspect of the present invention, when used as a herbicide The crystalline modification I of amafentrazone may further exist in formulations and in other forms prepared from such formulations, and in combination with the reduction of the activity of the active compound when used in the plant environment, on the surface of plant parts or Inhibitors of degradation after application in plant tissue are present as mixtures.

All plants and plant parts can be treated with the crystalline modification I of amfentrazone according to any aspect or embodiment of the invention. In this context, plants are understood to mean all plants and plant populations, such as desired and undesired wild plants or crop plants (including naturally occurring crop plants). Crop plants may be plants obtainable by conventional breeding and optimization methods, by biotechnological and genetic engineering methods, or by a combination of these methods, including transgenic plants and plants that may or may not be protected by plant breeder's rights cultivars. Plant parts are understood to mean all above-ground and underground parts and organs of plants, such as buds, leaves, needles, stalks, stems, flowers, fruiting bodies, fruits, seeds, roots, tubers and rhizomes. Also included are harvested material, and vegetative and reproductive propagation material, such as cuttings, tubers, meristems, rhizomes, runners, seeds, single and multiple plant cells and any other plant tissue.

The treatment of plants and plant parts with the compositions or formulations according to the invention can be carried out directly or by allowing the compositions or formulations to act on their surroundings, habitat or storage space by customary treatment methods. Examples of such customary treatment methods include dipping, spraying, vaporizing, atomizing, broadcasting, spreading (in the case of propagation material) and applying one or more coatings (especially in the case of seeds).

The composition of the present invention can be used, for example, to control one or more of the following plants (weeds): Monocotyledonous weeds including the following genera: Aegilops, Agropyron, Agrostis , Alopecurus, Apera, Avena, Brachiaria, Bromus, Cenchrus, Commelina (Commelina), Cynodon, Cyperus, Dactyloctenium, Digitaria, Echinochloa, Water Water Eleocharis, Eleusine, Eragrostis, Eriochloa, Festuca, Fimbristylis, Heteranthera, Imperata Imperata, Ischaemum, Leptochloa, Lolium, Monochoria, Panicum, Paspalum, Paspalum (Phalaris), Phleum, Poa, Rottboellia, Sagittaria, Scirpus, Setaria, Sorghum. Dicotyledonous weeds include the following genera: Abutilon, Amaranthus, Ambrosia, Anoda, Anthemis, Aphanes, Aphanes Atriplex, Bellis, Bidens, Capsella, Carduus, Cassia, Centaurea, Chenopodium , Cirsium, Convolvulus, Croton, Datura, Desmodium, Emex (Emex), Erysimum , Euphorbia, Galeopsis, Galinsoga, Galium, Hibiscus, Ipomoea, Kochia ), Lamium, Lepidium, Lindernia, Matricaria, Mentha, Mercurialis, Merremia , Momordica, Mullugo, Myosotis, Papaver, Pharbitis, Plantago, Polygonum, Portulaca ), Ranunculus, Raphanus, Ricinus, Rorippa, Rotala, Rumex, Salsola, Senecio, Sesbania, Sida, Sinapis, Solanum, Sonchus, Sphenoclea, Stellaria, Stizolobium, Taraxacum, Thlaspi, Trifolium, Urtica, Papa (Veronica), Viola (Viola), Xanthium (Xanthium).

When applying herbicidal compositions to kill growing crops of useful plants (such as sugar cane, corn, cereals, rice, maize, sorghum, cotton, canola, turf, barley, potato, sweet potato, sunflower, rye, oats, wheat The benefits of the present invention are most pronounced when weeds in , soybean, soybean, sugar beet, tobacco, safflower, tomato, alfalfa, pineapple, cucurbit, cassava and pasture grass. In one embodiment of the invention, sugar cane and corn are particularly suitable for treatment.

Throughout the specification and claims of this specification, the word "comprise" and variations of that word (such as "comprising and comprises") means "including but not limited to" and does not exclude Other parts, additives, components, integers or steps. Furthermore, the singular encompasses the plural unless the context requires otherwise: in particular, where an indefinite article is used, the specification should be read to contemplate the plural as well as the singular unless the context otherwise requires.

Preferred features of each aspect of the invention may be as described in conjunction with any other aspect. Other features of the invention will become apparent from the following examples. In general, the invention extends to any novel one or any novel combination of features disclosed in this specification (including any accompanying claims and drawings). Accordingly, unless incompatible with each other, features, integers, properties, compounds, chemical moieties or groups described in particular aspects of the invention, embodiments or examples of the invention should be understood to also apply to any Other aspects, embodiments or examples. Furthermore, unless stated otherwise, any feature disclosed herein may be replaced by an alternative feature serving the same or a similar purpose.

When upper and lower limits are recited for a property, a range of values defined by any combination of any upper limit and any lower limit can also be implied.

In this specification, unless otherwise stated, properties refer to properties measured under ambient conditions, ie at atmospheric pressure and at a temperature of about 20°C.

As used herein, the term "about or around" when used in conjunction with a numerical amount or range means slightly greater than or slightly less than the stated numerical amount or range, and for example deviates from the stated numerical amount or range. ±10% of endpoint.

As used herein, "surrounding environment" refers to a place where a plant grows, a place where the plant propagation material of the plant is sown, or a place where the plant propagation material of the plant will be sown.

As used herein, "precipitation" refers to the precipitation of solid material (precipitate) from a liquid solution, including the settling of crystalline material, wherein the solid material is present in an amount greater than its solubility in that volume of liquid solution.

All percentages are given in % by weight unless otherwise stated.

The present invention can be understood more clearly by referring to the accompanying drawings described below, and the present invention is intended to illustrate and illustrate rather than limit the scope of the present invention, wherein: Figure 1 is the infrared (IR ) spectrogram; Fig. 2 is the X-ray powder diffraction diagram of the crystal modification I of amfentrazone; Fig. 3 is the differential scanning calorimetry (DSC) thermal analysis diagram of the crystal modification I of amfentrazone; Fig. 4 is an X-ray powder diffraction pattern of amorphous amafenzazone.

A detailed description

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

All X-ray diffraction patterns were determined in reflection geometry using a powder diffractometer at 25 °C using the following acquisition parameters:

The IR spectra of the crystalline samples were measured with a resolution of 4 ^cm and a scan number of 16. The crystalline modification I of amafentrazone can be identified by its characteristic functional group vibration peaks at 3315.38, 3209.42 and 2970.40 cm ^-1 (cm ^-1 , ±0.2%), as shown in Figure 1 .

All IR spectra were acquired using the following acquisition parameters:

All DSC thermograms were obtained using the following acquisition parameters:

example Example 1: Preparation of Amorphous Amenzazone according to the Disclosure in Example 2 of U.S. Pat. No. 5,194,085 Amended

Add 3.6 g (0.036 mol) of tertiary butyl isocyanate and 0.05 g to 0.1 g of 1,8-diazabicycloundecene (DBU) to 3.52 g (0.03 mol) of 4-amino-3- Isopropyl-1H-1,2,4-triazol-5-(4H)-one in 80 ml of anhydrous acetonitrile, the mixture was stirred at 20°C for 2 hours, concentrated in vacuo, and the residue was dissolved in dichloro In methane, the solution was washed with water, dried over sodium sulfate and concentrated in vacuo, and the residue was precipitated by trituration with diethyl ether as an amorphous solid with a melting point of 108°C according to US 5,194,085.

As shown in Fig. 4, the X-ray powder diffraction pattern of the obtained amfentrazone product has no significant signal, which indicates that the amfentrazone product prepared according to the disclosure in U.S. Patent No. 5,194,085 is amorphous .

Preparation of crystalline modification I of amafentrazone Example 2 - Crystallization from Methyl Ethyl Ketone

A sample of amorphous amfentrazone (10 g) prepared as in Example 1 was placed in a three-necked round bottom flask together with methyl ethyl ketone (60 ml), and the resulting slurry was heated to 35° C. to obtain a homogeneous solution . The homogeneous solution was stirred at 35°C for 2 h and insoluble particles (if any) were filtered and the solution was cooled slowly to 20°C-25°C. Upon cooling, fine crystals formed and the resulting heterogeneous mixture was stirred at 20 °C for 2 h. Then, the slurry was filtered and washed with methyl ethyl ketone (3 ml) at 20°C. The filtered crystals were dried under vacuum at 20°C. The resulting crystalline product has a purity of 98%.

The resulting crystals were analyzed by IR, X-RPD and DSC and found to be crystalline modification I of amafentrazone as shown in Figures 1, 2 and 3, respectively.

The IR spectrum of amfentrazone showed the characteristic vibrations of functional groups at wavenumbers (cm ^-1 , ±0.2%) of 3315.38, 3209.42 and 2970.40 cm ^-1 , as shown in Figure 1 .

The DSC thermogram of amfentrazone crystals presents an endothermic melting peak at 123.8°C, a peak maximum at 129.2°C, and a melting enthalpy of 76.91 J/g, as shown in FIG. 3 . The X-ray powder diffraction pattern of the crystals exhibited reflections as shown in FIG. 2 and the values are summarized in Table 1.

Example 3 - Crystallization from Nitrobenzene

A sample of amorphous amfentrazone (5 g) prepared as in Example 1 was placed in a three-neck round bottom flask with nitrobenzene (35 ml), and the resulting slurry was heated to 60° C. to obtain a homogeneous solution. The resulting hot solution was stirred at 60 °C for 2 h and insoluble particles (if any) were filtered and the solution was slowly cooled to 20 °C. Upon cooling, fine crystals formed and the resulting heterogeneous mixture was stirred at 20 °C for 2 h. The slurry was then filtered, washed with nitrobenzene (3 ml) at 20°C; and dried under vacuum at 45°C. The crystals thus obtained had a purity of 98%.

The crystals were characterized as amfentrazone crystalline modification I using infrared spectroscopy and x-ray diffraction as described in Example 2.

Example 4: Preparation of water dispersible granules (WG)

All components listed in Table 2 below were mixed, blended and ground in a high speed rotary mill. Add enough water to obtain an extrudable paste. The paste is extruded through a die or screen to form an extrudate. The wet extrudate was dried in a vacuum oven at 70°C, and then sieved through a 0.71mm-2mm sieve to obtain product granules.

Example 5: Preparation of Suspension (SC)

Aqueous suspensions (SC) are prepared by mixing the finely ground active ingredient with the adjuvants listed in Table 3:

Example 6: Oil-based suspension (OD)

All the components listed in Table 4 below were uniformly mixed and milled with a Dyno-Mill (manufactured by Willy A. Bachofen Ag) to obtain an oil-based aqueous suspension.

Example 7: Comparison of formulation stability - wet sieve test

The WG samples prepared in Examples 4-7 were diluted with water and their residues were compared by passing through a 325 mesh (44 μm opening) wet sieve. The amount of material retained on the screen was determined by drying and weighing. The results are listed in Table 5.

It was surprisingly found that the crystalline modification I of amfentrazone is extremely stable after dilution. It has a reduced tendency to generate aggregates and residues after dilution compared to the amorphous form. In these tests for crystalline modification I of amafentrazone, residues of 0.5% or less, 0.3% or less, and 0.2% or less remained. By way of comparison, when amorphous amafenzazone was used, the corresponding residual residue was not less than 8%. when At a dilution factor of 1000, up to about 25 times less residue and up to about 35 times less residue are produced when using the crystalline modification I of amazepam compared to the amorphous form of mefentrazone , up to about 50 times less residue; this covers a range of about 25 to 50 times less than the relative residue formed. For these reasons it is well suited for the preparation of commercial formulations where such aggregates/residues may clog spray filters resulting in loss of productivity.

Claims (24)

A kind of 4-amino-N-tertiary butyl-4,5-dihydro-3-isopropyl-5-oxo-1H-1,2,4-triazole-1-formamide (amine azole oxalone) which exhibits the following reflections in X-ray powder diffraction patterns (X-RPD) recorded at 25° C. with Cu-Kα radiation, denoted as 2θ ± 0.2 degrees: 2θ =11.0±0.2 (1) 2θ=13.1±0.2 (3) 2θ=18.2±0.2 (4) 2θ=19.4±0.2 (5) 2θ=20.5±0.2 (6) 2θ=27.4±0.2 (11) 2θ=28.2 ±0.2 (12). The crystalline modification I of amfentrazone as described in item 1 of the patent application, the crystalline modification I further exhibits the following reflections in the X-ray powder diffraction pattern recorded at 25°C using Cu-Kα radiation One or more, recorded as 2θ±0.2 degrees: 2θ=12.2±0.2 (2) 2θ=21.5±0.2 (7) 2θ=22.2±0.2 (8) 2θ=23.5±0.2 (9) 2θ=24.0±0.2 ( 10) 2θ=29.2±0.2 (13) 2θ=31.3±0.2 (14). The crystalline modification I of amfentrazone described in item 1 or 2 of the patent claims, the crystalline modification I exhibits wave numbers (cm ^-1 , ±0.2%) of 3315.4, 3209.4 and 2970.4 cm ^-1 Infrared (IR) spectra of the characteristic functional group vibration peaks at . As for the crystal modification I of amfentrazone described in item 1 or 2 of the patent application, the crystal modification I exhibits a melting point of 127°C-131°C. As for the crystal modification I of amfentrazone described in item 1 or 2 of the patent application, the crystal modification I exhibits a melting point of 128°C-130°C. For the crystal modification I of amfentrazone described in item 1 or 2 of the patent application, the crystal modification I exhibits a melting point of 129°C. The crystal modification I of amfentrazone as described in item 1 or 2 of the patent application, the crystal modification I exhibits a differential scanning calorimetry method with an endothermic melting peak starting at 124°C and a peak maximum at 129°C (DSC) profile, further optionally having an enthalpy of fusion of 77 J/g. The crystalline modification I of amfentrazone as described in item 1 or 2 of the scope of application is characterized by having an X-ray powder diffraction pattern substantially as shown in Figure 2, and/or by having substantially IR spectrum as shown in FIG. 1 , and/or characterized as having a DSC substantially as shown in FIG. 3 . The crystal modification I of amfentrazone as described in item 1 or 2 of the scope of the patent application, the crystal modification I can be obtained by a method comprising the following steps: (i) dissolving amorphous amfentrazone in methyl ethyl ketone to form a slurry; heat the slurry to obtain a homogeneous solution; stir the homogeneous solution and optionally filter insoluble particles; slowly cool the homogeneous solution to form fine crystals and stir the resulting heterogeneous mixture; Washing with methyl ethyl ketone to obtain crystallization; or (ii) dissolving amorphous amfenflumezone in nitrobenzene to form a slurry; heating the slurry to obtain a homogeneous solution; stirring the homogeneous solution, and optionally filtering the insoluble particles; slowly cooling the homogeneous solution to form fine crystals and stirring the resulting heterogeneous mixture; and filtering the heterogeneous mixture and washing with nitrobenzene to obtain crystals. A method for preparing the crystal modification I of amfentrazone described in any one of the claims 1 to 7, the method comprising: i) dissolving amfentrazone in a solvent or a mixture of solvents ii) precipitating the dissolved compound as crystalline modification I of amafentrazone; and iii) isolating the precipitated crystalline modification I. The method described in item 10 of the scope of the patent application, wherein the amfenflumezone in step i) is amorphous Amazepam. The method described in item 10 or 11 of the scope of patent application, wherein the solvent is selected from the group consisting of: methyl ethyl ketone, benzene, chlorobenzene, dichlorobenzene, ethyl benzene, trifluoromethyl Benzene, mesitylene, nitrobenzene, or mixtures of THF-hexane, ethyl acetate-hexane, dichloromethane-hexane, dichloromethane-methanol, THF-water, and methanol-water. The method as described in item 10 or 11 of the scope of application, wherein the solvent is methyl ethyl ketone, nitrobenzene or a mixture thereof. The method as described in claim 10 or 11, wherein step ii) is achieved by concentrating the solvent and/or cooling and/or adding a solubility-reducing solvent and/or adding seeds of crystal modification I of amafentrazone . The method as described in claim 14, wherein step ii) is achieved by cooling to about 0°C to 20°C. The crystal modification I of amfentrazone described in item 1 or 2 of the patent application, the crystal modification I can be obtained by the method described in any one of the 10th to 15th items of the patent application. A crystalline modification I of amfentrazone, which is obtained according to the method of any one of claims 10 to 15 and has a crystalline modification of amfentrazone content of at least 98% by weight I, wherein the crystalline modification I of amfentrazone exhibits the following reflection in an X-ray powder diffraction pattern (X-RPD) recorded at 25° C. using Cu-Kα radiation, denoted as 2θ±0.2 degrees: 2θ= 11.0±0.2 (1) 2θ=13.1±0.2 (3) 2θ=18.2±0.2 (4) 2θ=19.4±0.2 (5) 2θ=20.5±0.2 (6) 2θ=21.5±0.2 (7) 2θ=27.4± 0.2 (11) 2θ=28.2±0.2 (12). The crystalline modification I of amfentrazone as described in item 17 of the patent application, the crystalline modification I further exhibits the following reflections in the X-ray powder diffraction pattern recorded at 25°C using Cu-Kα radiation One or more, recorded as 2θ±0.2 degrees: 2θ=12.2±0.2 (2) 2θ=21.5±0.2 (7) 2θ=22.2±0.2 (8) 2θ=23.5±0.2 (9) 2θ=24.0±0.2 (10) 2θ=29.2±0.2 (13) 2θ= 31.3 ± 0.2 (14). A composition, comprising the crystal modification I of amafentrazone described in any one of items 1 to 9 and 17 to 18 of the patent scope of the application and at least one auxiliary agent. The composition as described in claim 19 of the patent application, wherein the additive is selected from the group consisting of wetting agent, dispersant, defoamer and other formulation components. The composition as described in item 20 of the patent application, wherein other formulation components can be fillers, dyes and desiccants. Such as the composition described in any one of the 19th to 21st items of the scope of the patent application, the composition is in the following forms: water suspension (SG), oil-based water suspension (OD), water-soluble granule (SG), Water dispersible emulsion (DC), emulsion (EC), emulsified seed dressing, suspension seed dressing, granule (GR), microgranule (MG), suspoemulsion concentrate (SE) or water dispersible granule (WG) . As the composition described in claim 22, the composition is in the form of water-dispersible granules (WG). A crystalline modification I of amafenzazone as described in any one of items 1 to 9 and 17 to 18 of the scope of application or a composition as described in any one of items 19 to 23 of the scope of application For weed control purposes.

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