BR102017023300A2 - INNOVATIVE CRYSTALINE FORM OF CHLORFENAPIR, PROCESS FOR THEIR PREPARATION AND USE - Google Patents

Abstract

Innovative crystalline form of chlorphenapyr, a process for its preparation and use. The present invention describes the crystalline form of chlorphenapyr of formula (I), the crystal preparation process and crystal analyzes by various analytical methods and the use of crystal to prepare a stable agrochemical formulation. The invention also describes the use of various solvents in relation to the conditions of preparation of crystalline form.

Description

(54) Title: INNOVATIVE CRYSTALLINE FORM OF CHLORFENAPIR, PROCESS FOR ITS PREPARATION AND USE OF THE SAME (51) Int. CL: A01N 43/36; C07D 207/09 (52) CPC: A01N 43/36, C07D 207/09 (30) Unionist Priority: 16/11/2016 AU 2016259360 (73) Holder (s): ROTAM AGROCHEM INTERNATIONAL COMPANY LIMITED (72) Inventor (s) ): JAMES TIMOTHY BRISTOW (74) Attorney (s): VIEIRA DE MELLO ADVOGADOS (57) Abstract: INNOVATIVE CRYSTALLINE FORM OF CHLORFENAPIR, PROCESS FOR ITS PREPARATION AND USE. The present invention describes the crystalline form of chlorfenapyr of formula (I), the process of preparing the crystal and analyzing the crystal using various analytical methods and using the crystal to prepare a stable agrochemical formulation. The invention also describes the use of various solvents in relation to the preparation conditions in a crystalline form.

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1/27

INNOVATIVE CRYSTALLINE FORM OF CHLORFENAPIR, PROCESS FOR ITS PREPARATION AND USE OF THE SAME

Field of the Invention [001] The present invention relates to a crystalline form of 4-bromo-2- (4-chlorophenyl) -1-ethoxymethyl5-trifluoromethyl-1H-pyrrole-3-carbonitrile (chlorfenapyr), its processes preparation and its use in agrochemical preparations.

Description of the Related Art [002] 4-bromo-2- (4-chlorophenyl) -1-ethoxymethyl5-trifluoromethyl-1H-pyrrol-3-carbonitrile (chlorfenapyr) is a potent insecticide and acaricide. It is an acaricide developed by Cyanamid (currently BASF) under the code AC 303630. Clorfenapir is based on the natural product dioxapyrrolomycin and was originally isolated from a fermentation broth of Streptomyces. The product is effective in the control of spider mites, cotton weevils, white flies and many species of Lepidoptera. Chlorfenapyr was registered in Japan as Kotetsu (Nippon Soda) for use in fruits and vegetables, and entered the ranks of the top ten insecticides (the 7 position) in the country in 1996. Kotetsu is also sold by Mitsubishi Chemical in Japan, and is a of its main products. In Australia, chlorfenapyr was approved for use on cotton under the trade name Intrepid, and for use on brassicas, peaches and pears under the trade name Secure in late 1998.

[003] Chlorfenapyr has molecular formula

Ci5HnBrClF3N2O. Its chemical structure is:

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2/27

[004] Commercially available chlorfenapyr, which is normally manufactured by the process described in U.S. Patent No. 5,359,090, is present in an amorphous state. It has been found that chlorfenapyr, in an amorphous state, is not suitable for use in an economic formulation due to its high tendency to aggregate, in particular, after prolonged storage. Therefore, there is a need to provide an innovative form of chlorfenapyr that exhibits improved properties, such as, for example, improved storage stability.

Summary of the Invention [005] In an attempt to solve some or all of the problems with the existing amorphous form of chlorfenapyr, a new and stable crystalline form of chlorfenapyr has been prepared.

[006] In a first aspect, the present invention provides a crystalline modification I of 4-bromo-2 (4-chlorophenyl) -1-ethoxymethyl-5-trifluoromethyl-1H-pyrrole-3carbonitrile (chlorfenapyr), called crystalline modification I, which exhibits at least three of the following reflections, in any combination, as 2Θ ± 0.20 degrees in a powder X-ray diffractogram (X-RPD) recorded using Cu — Koí radiation at 25 ° C:

2Θ = 7.73 ± 0.20 (1)

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3/27

2Θ = 9.25 ± C 1.20 (2) 2Θ = 10.87 ± 0.20 (3) 2Θ = 12.07 ± 0.20 (4) 2Θ = 12.77 ± 0.20 (5) 2Θ = 13.25 ± 0.20 (6) 2Θ = 14.21 ± 0.20 (7) 2Θ = 14.95 ± 0.20 (8) 2Θ = 15.32 ± 0.20 (9) 2Θ = 16.30 ± 0.20 (10) 2Θ = 19, 60 ± 0.20 (11) 2Θ = 20.27 ± 0.20 (12) 2Θ = 20.75 ± 0.20 (13) 2Θ = 21.47 ± 0.20 (14) 2Θ = 21.73 ± 0.20 (15) 2Θ = 23.11 ± 0.20 (16) 2Θ = 23.56 ± 0.20 (17) 2Θ = 23, 92 ± 0.20 (18) 2Θ = 24.29 ± 0.20 (19) 2Θ = 24.67 ± 0.20 (20) 2Θ = 25, 47 ± 0.20 (21) 2Θ = 25, 91 ± 0.20 (22) 2Θ = 26, 69 ± 0.20 (23) 2Θ = 26, 89 ± 0.20 (24) 2Θ = 27.25 ± 0.20 (25) 2Θ = 27.72 ± 0.20 (26) 2Θ = 28.26 ± 0.20 (27) 2Θ = 29, 83 ± 0.20 (28) 2Θ = 30.91 ± 0.20 (29)

[007] In one embodiment, the crystalline I of chlorfenapyr, according to modification the first

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4/27 aspect of the invention, exhibits at least 3, 4, 5, 6, 7, 8 or all of the following reflections, in any combination, such as 2Θ ± 0.20 degree on a powder X-ray diffractogram recorded with use of Cu — Koí radiation at 25 ° C:

2Θ = 7.73 ± 0.20 d) 2Θ = 9.25: ± 0 , 20 (2) 2Θ = 16.30 ± 0.20 (10) 2Θ = 20.27 ± 0.20 (12) 2Θ = 21.73 ± 0.20 (15) 2Θ = 23.11 ± 0.20 (16) 2Θ = 23.56 ± 0.20 (17) 2Θ = 23, 92 ± 0.20 (18) 2Θ = 24.29 ± 0.20 (19) 2Θ = 25, 47 ± 0.20 (21) 2Θ = 26, 69 ± 0.20 (23) 2Θ = 27.25 ± 0.20 (25) 2Θ = 27.72 ± 0.20 (26) 2Θ = 29, 83 ± 0.20 (28) 2Θ = 30.91 ± 0.20 (29) [008] In one second

In this respect, the present invention provides a crystalline modification I of chlorfenapyr, optionally according to the first aspect of the invention, which exhibits an infrared (IR) with characteristic functional group vibration peaks in wave numbers (cm ^-1 , ± 0, 2%) of 2,984.22, 2,230.69 and 1,977.91cm ^_1 .

[009] In a third aspect, the present invention provides a crystalline modification I of chlorfenapyr, optionally according to any one of the first to second aspects of the invention, characterized by a substantially powder X-ray diffraction pattern

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5/27 as shown in Figure 2 and / or characterized by an IR spectrum substantially as shown in Figure 1.

[0010] In a fourth aspect, the present invention provides a crystalline modification I of chlorfenapyr, optionally according to any one of the first to third aspects of the invention, obtainable by the process substantially as described in Example 2 or 3.

[0011] In a fifth aspect, the present invention provides a crystalline modification I of chlorfenapyr, optionally according to any one of the first to fourth aspects of the invention, obtainable by the process of the sixth aspect of the invention.

[0012] It was found that the present crystalline modification I of chlorfenapyr can show a significant improvement in its storage stability, which can significantly reduce the aggregation problem found with the current commercially available formulations. In addition, it has been found that the crystalline modification I of chlorfenapyr can exhibit a high degree of stability when formulated compared to amorphous chlorfenapyr prepared according to the disclosure of U.S. Patent No. 5,359,090. In particular, the crystalline modification may exhibit a very low tendency to aggregate when formulated. This can allow the preparation of commercial formulations, such as suspension concentrates (SC). Additionally, because of the good stability properties, the crystalline modification I of chlorfenapyr can provide a desirable long storage period for formulations.

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6/27 [0013] Methods for preparing amorphous chlorfenapyr are well known in the art. Amorphous clofernapyr is manufactured and made available on a commercial scale. A particularly suitable method for preparing amorphous chlorfenapyr is described in U.S. Patent No. 5,359,090.

[0014] In a sixth aspect, the present invention provides a process for preparing a crystalline modification I of chlorfenapyr which comprises the steps of:

i) dissolving chlorfenapyr in a solvent or mixture of solvents;

ii) precipitating the dissolved compound in the crystalline modification I of chlorfenapyr; and iii) isolating the precipitated crystalline modification I.

[0015] In an embodiment of the sixth aspect of the invention, chlorfenapyr in step i) is amorphous chlorfenapyr.

[0016] In an embodiment of the sixth aspect of the invention, the solvent is selected from the group consisting of halogenated hydrocarbons (for example, trifluoro methyl benzene, chlorobenzene, bromobenzene, dichlorobenzene, chlorotoluene and trichlorobenzene), ethers (for example, ethyl ether propyl, n-butyl ether, anisol, phenethol, cyclohexyl methyl ether, dimethyl ether, diethyl ether, dimethyl glycol, diphenyl ether, dipropyl ether, diisopropyl ether, di-n-butyl ether, diisobutyl ether, ether diisopropyl ether, ethylene glycol dimethyl ether, isopropyl ethyl ether, tert-butyl methyl ether, methyl tetrahydrofuran, dioxane, dichlorodiethyl ether, ethylene oxide and / or propylene oxide polyethers, nitrated hydrocarbons (for example,

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Ί / 2.Ί nitromethane, nitroethane, nitropropane, nitrobenzene, chloronitrobenzene and o-nitrotoluene), aliphatic, cycloaliphatic or aromatic hydrocarbons (eg, pentane, n-octane, nonane, ethyl benzene, mesitylene), cymene, oil fractions that have a boiling range of 70 ° C to 190 ° C, petroleum ether, lingroin, octane, benzene, esters (eg, malonates, acetic acid n-butyl ester (n-butyl acetate), methyl acetate, isobutyl acetate, dimethyl carbonate, diethyl carbonate, dibutyl carbonate and ethylene carbonate), methyl ethyl ketone and aliphatic alcohols (for example, isopropyl alcohol, n-propanol, n-butanol and tert-amyl alcohol) and mixtures of the themselves.

[0017] In an embodiment of the sixth aspect of the invention, the solvent is selected from the group consisting of nitrobenzene, benzene, chlorobenzene, dichlorobenzene, ethyl benzene, trifluoro methyl benzene, mesitylene, ether, methyl ethyl ketone or a mixture thereof.

[0018] In an embodiment of the sixth aspect of the invention, the solvent is selected from the group consisting of methyl ethyl ketone or nitrobenzene, or a mixture thereof.

[0019] According to an embodiment of the sixth aspect of the present invention, step ii) is carried out by solvent concentration and / or by cooling and / or by the addition of a solubility-reducing solvent and / or by the addition of a crystal of inoculation of crystalline modification I of chlorfenapyr.

[0020] According to a modality of the sixth

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As an aspect of the present invention, the crystalline modification I of chlorfenapyr is prepared by dissolving amorphous chlorfenapyr in a solvent or a mixture of solvents as a concentrated solution by heating from room temperature to a temperature at or below the reflux temperature of the solvent or solvent mixture. Optionally, the concentrated solutions can be prepared at the reflux temperature of the solvents. The concentration of the solution depends on the solubility of chlorfenapyr in the corresponding solvent or mixture of solvents.

[0021] In an embodiment of the sixth aspect of the invention, the concentrated homogeneous solution prepared in this way, as in step (i), is then cooled to room temperature or cooled to about 0 to 20 ° C to crystallize the form desired crystalline solvent. The crystalline modification I of chlorfenapyr can also be crystallized by concentrating the homogeneous solution by removing the solvent or mixture of solvents to a certain volume, with or without the application of vacuum and cooling to below the reflux temperature of the solvent or mixture of solvents.

[0022] In an embodiment of the sixth aspect of the invention, crystallization of the crystalline modification I of chlorfenapyr can also be obtained by adding inoculation crystals of the desired crystalline form during crystallization in the solution prepared in step (i), which can promote or accelerate crystallization.

[0023] The amount of inoculation crystal added to the concentrated solution is typically in the range of 0.001% to 10% by weight, more particularly, in the range of

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9/27

0.005% to 0.5% by weight based on the weight of chlorfenapyr used for the preparation of the concentrated solution in step (i). Optionally, the inoculation crystals are added to the concentrated solution at a temperature below the boiling point of the corresponding solvent or solvent mixture.

[0024] In an embodiment of the sixth aspect of the invention, the precipitated crystalline modification I of chlorfenapyr obtained from step (ii) is isolated by the techniques for separating the usual solid components from the solutions, such as filtration, centrifugation or decantation. Then, the isolated solid will be washed with solvent one or more times. Optionally, the solvent used in the washing stage consists of one or more components of the solvent or mixture of solvents used for the preparation of the concentrated solution in step (i), as previously described in this document. The washing is normally carried out using the corresponding solvent or solvent mixture between room temperature and 0 ° C, depending on the solubility of the crystal, in order to avoid the loss of crystal as much as possible in the corresponding washing solvent.

[0025] In an embodiment of the sixth aspect of the invention, the crystalline modification I of chlorfenapyr is dissolved and recrystallized. The washes and / or the crystallization solvent in either method can be concentrated to obtain solid chlorfenapyr, which can be recycled.

[0026] In a seventh aspect, the present invention provides a crystalline modification I of

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10/27 chlorfenapyr, obtained according to the sixth aspect of the invention, which has a crystalline modification content of chlorfenapyr I of at least 98% by weight.

[0027] In an eighth aspect, the present invention provides an insecticidal / acaricidal composition comprising the crystalline modification I of chlorfenapyr, according to any one of the first to the fifth and seventh aspects of the invention, and at least one auxiliary.

[0028] In a ninth aspect, the present invention provides a use of the crystalline modification I of chlorfenapyr according to any one of the first to the fifth and seventh aspects of the invention, or a composition according to the eighth aspect of the invention for the control of unwanted insects and mites.

[0029] In an embodiment of the eighth aspect of the invention, the amount of the crystalline modification I of chlorfenapyr is less than 75% by weight of the composition, preferably less than 50% by weight of the composition, more preferably, less than 30% by weight of the composition, even more preferably, about 24% by weight of the composition.

[0030] The use of chlorfenapyr as an insecticide and acaricide is well known in the art, and is used on a commercial scale. The crystalline modification I of chlorfenapyr is also active in the control of insects and mites. As a result, the techniques for formulating and applying chlorfenapyr known in the art for amorphous chlorfenapyr, for example, as disclosed in the prior art documents discussed earlier in this document, can also be applied in a manner analogous to chlorfenapyr in the modification

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11/27 crystalline I of the present invention.

[0031] Accordingly, the present invention mites crystalline I, provides an insecticidal composition and comprises chlorfenapyr in the modification as defined earlier in this document.

Accordingly, the present invention further provides the processes for preparing compositions for controlling insects and mites using the crystalline modification I of chlorfenapyr.

[0033] In an embodiment of the eighth aspect of the invention, the crystalline modification I of chlorfenapyr is in the form of suspension concentrates (SC), oil-based suspension concentrates (OD), water-soluble granules (SG), dispersible concentrates (DC), emulsifiable concentrates (EC), emulsion inoculation coatings, suspension inoculation coatings, granules (GR), microgranules (MG), suspoemulsions (SE) and water dispersible granules (WG). The crystalline modification I of chlorfenapyr can be included in these common formulations in a known manner, with the use of suitable auxiliaries, carriers and solvents and the like.

[0034] In an embodiment of the eighth aspect of the invention, the composition is in the form of water-dispersible granules (SC).

[0035] In an embodiment of the eighth aspect of the invention, the crystalline modification I of chlorfenapyr may be present in a concentration sufficient to achieve the required dosage when applied to plants or to their loci, desirably at a concentration of about 0.1 about 75% by weight of the total mixture.

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12/27 [0036] These formulations are prepared in a known manner by mixing crystalline modification I of chlorfenapyr with common additives, for example, liquid diluents, solid diluents, wetting agents, dispersing agents, thickening agent, antifreeze agents, biocide and any adjuvants needed and other formulation ingredients.

[0037] Liquid diluents include, but are not limited to, water, N, N-dimethylamide, dimethylsulfoxide, Nalkylpyrrolidone, ethylene glycol, polypropylene glycol, propylene carbonate, dibasic esters, paraffins, alkylbenzenes, alkyl naphthalenes, glycerin, oils, triacetiva , castor, linseed, sesame, corn, peanut, inoculation of cotton, soy, rapeseed and coconut inoculation, ketones, such as 2-heptanone, isophorone and 4-hydroxy-4-methyl-2-pentanone, acetates, such as hexyl acetate, acetate of heptyl and octyl acetate, water and alcohols, such as cyclohexanol, decanol, benzyl alcohol and tetrahydrofurfuryl alcohol.

[0038] Solid diluents can be soluble in water or insoluble in water. Solid water-soluble diluents include, but are not limited to, salts such as alkali metal phosphates (eg sodium dihydrogen phosphate), alkaline earth metal phosphate, sodium, potassium, magnesium and zinc, sodium and potassium chloride, acetate sodium, sodium carbonate and sodium benzoate, and sugars and sugar derivatives such as sorbitol, lactose, sucrose and mannitol. Examples of water-insoluble solid diluents include, but are not limited to, clays, synthetic silica and diatoms,

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13/27 calcium and magnesium silicates, titanium dioxide, aluminum, calcium oxide and zinc.

[0039] Wetting agents include, but are not limited to, alkyl sulfosuccinates, laureates, alkyl sulfates, phosphate esters, acetylenic diols, ethoxy fluorinated alcohols, ethoxylated silicones, alkylene phenol ethoxylates, benzenesulfonates, alkenesulfonates, alkylsulfonates, alkylsulfonates naphthalenesulfonates, substituted naphthalenesulfonates, condensed naphthalenesulfonates and naphthalenesulfonates that have been substituted with formaldehyde and alcohol ethoxylates. The polyalkylene glycol ether is particularly useful for the composition of the invention.

[0040] Dispersing agents include, but are not limited to, sodium, calcium and ammonium salts of lignosulfonates (optionally polyethoxylates); sodium and ammonium salts of maleic anhydride copolymers; sodium salts of condensed phenolsulfonic acid; and naphthalene sulfonate-formaldehyde condensates. Compositions are observed which comprise up to 10% by weight of dispersant. Lignosulfonates, like sodium lignosulfonates, are particularly useful for the composition of the invention. The condensate of sodium alkylnaphthalenesulfonate-formaldehyde is particularly useful for the composition of the invention.

[0041] Thickeners include, but are not limited to, guar gum, pectin, casein, carrageenan, xanthan gum, alginates, methylcellulose, hydroxyethylcellulose, hydroxypropylcellulose and carboxymethylcellulose. Synthetic thickeners include derivatives from the previous categories and also polyvinyl alcohols, polyacrylamides,

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14/27 polyvinylpyrrolidones, various polyethers, their copolymers and polyacrylic acids and their salts. Xanthan gum is particularly useful for the composition of the invention.

[0042] Suitable antifreeze agents are liquid polyols, for example, ethylene glycol, propylene glycol or glycerol. The amount of antifreeze agents is generally from about 1% to about 20% by weight, in particular, from about 5 to about 10% by weight based on the total weight of the composition.

[0043] Biocides can also be added to the composition according to the invention. Suitable biocides are those based on isothiazolones, for example, Proxel® from ICI or Acticide® RS from Thor Chemie or Kathon® MK from Rohm & Haas. The amount of biocides is typically 0.05% to 0.5% by weight based on the total weight of the composition.

[0044] Other formulation ingredients can also be used in the present invention, such as dyes, defoaming agents, drying agents and the like. These ingredients are known to a person skilled in the art.

[0045] In an embodiment of the eighth aspect of the invention, the crystalline modification I of chlorfenapyr may be present in its commercially available formulations and in their forms of use, prepared from these formulations and as a mixture with other active compounds (such as insecticides, attractive, sterilizing agents, bactericides, acaricides, nematicides, fungicides, growth regulating substances, herbicides, protectors, fertilizers and semi-chemicals) or with agents

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15/21 to improve the properties of the plant.

[0046] In an embodiment of the eighth aspect of the invention, when used as an insecticide and acaricide, the crystalline modification I of chlorfenapyr according to the invention may be additionally present in formulations and their forms of use, prepared from these formulations, and as a mixture with inhibitors that reduce the degradation of the active compounds after their use in the plant environment, on the surface of plant parts or in plant tissues.

[0047] Clorfenapir, which is an active ingredient in the insecticidal and acaricidal composition of the invention, is known to be effective against insects such as Hemiptera pests, such as leafhoppers (Doltocephalidae), Lepidoptera pests, as crucifer moths (Plutella xilostella), defoliating caterpillar (Spodoptera litura) and apple leaf miner (Phyllonorycter ringoniella); Thysanoptera pests, such as melon tripods (Thrips palmi) and yellow tea tripods (Spirtothrips dorsalis); agri-horticultural pests, such as mites, such as striped spider mites (Tetranychus urticae koch), kanzawa mite (Tetranychus kanzawai kishida) and Aculops pelekassi.

[0048] The benefits of the present invention are seen mainly when the insecticidal and acaricidal composition is applied to exterminate insects and mites in useful growing plant cultures: such as cotton, garlic, potato, papaya, dried beans, onions and chrysanthemums.

[0049] All plants and plant parts can be treated according to the invention. In the present context, plants should be understood as all the

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16/27 plants and plant populations, such as desired and unwanted wild plants or crop plants (including naturally occurring crop plants). Crop plants can be plants that can be obtained by conventional breeding and optimization methods, biotechnological or genetic manipulation methods, or combinations of these methods, including transgenic plants and plant cultivars that may or may not be protected by plant breeders. Plant parts should be understood as all plant parts and organs above and below the ground, such as bud, leaves, tips, stems, stems, flowers, carpophores, fruits, seeds, roots, tubers and rhizomes. The harvested materials, and materials of vegetative and generative propagation, for example, cut, tubers, meristem tissue, rhizomes, beginnings, seeds, single or multiple plant cells and any other plant tissues are also included.

[0050] The treatment according to the invention of plants and plant parts with the compositions or formulations of the inventions is carried out directly or allowing the compositions or formulations to act in their surroundings, habitat or storage space by the usual treatment methods. Examples of such usual treatment methods include dipping, spraying, vaporizing, nebulizing, diffusing, painting in the case of propagating material and applying one or more coatings particularly in the case of inoculation.

[0051] Throughout the description and claims of this specification, the words understand and

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17/27 variations of words, for example, which understands and understands, mean including, but not limited to, and do not exclude other chemical portions, additives, components, whole numbers or steps. In addition, the singular encompasses the plural, unless the context requires otherwise: in particular, when the indefinite article is used, the specification should be understood as contemplating the plurality, as well as the singularity, unless the context require otherwise.

[0052] The preferred features of each aspect of the invention can be as described together with any of the other aspects. Other features of the invention will become apparent from the following examples. In general, the invention extends to any innovative feature or any innovative combination of the features revealed in this specification (including any claims and attached drawings). Accordingly, the resources, integers, characteristics, compounds, chemical moieties or groups described in combination with a particular aspect, modality or example of the invention should be understood as applicable to any other aspect, modality or example described in this document, unless that are incompatible with them. In addition, unless otherwise stated, any resource disclosed in this document may be replaced by an alternative resource that has an equal or similar purpose.

[0053] When the upper and lower limits are quoted for a property, then a range of values defined by a combination of any of the upper limits with any of the limits

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Lower 18/27 can also be implicated.

[0054] In this specification, references to properties are - unless otherwise stated - properties measured under ambient conditions, that is, under atmospheric pressure and at a temperature of around 20 ° C.

[0055] As used in this document, the term about or around, when used in conjunction with a quantity or numerical range, means slightly more or slightly less than the indicated quantity or numerical range and, for example, up to a deviation of ± 10% from the indicated amount or numeric end point of the range.

[0056] Adjacencies, as used in this document, refer to the place where the plants grow, the place where the plant propagating material of the plants are sown or the place where the plant propagating material of the plants will be sown .

[0057] Precipitation, as used in this document, refers to the sedimentation of a solid material (a precipitate), including the sedimentation of a crystalline material, of a liquid solution in which the solid material is present in quantities greater than its solubility in amount of liquid solution.

[0058] All percentages are given in% by weight, unless otherwise stated.

Brief Description of the Drawings [0059] The invention can be more clearly understood by reference to the drawings, which are described below, and are intended to exemplify and

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19/27 illustrate, but do not limit, the scope of the invention, in which:

[0060] Figure 1 is an infrared (IV) spectrogram of the crystalline modification I of chlorfenapyr;

[0061] Figure 2 is an X-ray powder diffractogram of crystalline modification I of chlorfenapyr;

[0062] Figure 3 is an X-ray diffractogram of amorphous chlorfenapyr powder.

Detailed Description [0063] The present invention will now be described by the following examples and in which the following measurement techniques have been employed, and whose examples are provided for illustrative purposes only and are not intended to limit the scope of the disclosure.

[0064] All X-ray diffractograms were determined using the powder diffractometer in reflection geometry at 25 ° C, using the following acquisition parameters:

X’Pert Pro MPD from PANalytical B.V.

Theta compensation slot and graphite monochromator

Copper radiation (K-alpha), 40 kV, 40 mA Step size: 0.03 degree 2-theta Counting time: 1.0 second Maximum peak intensity: 1,705 counts per second

Scanning range: 3 to 60 degrees 2-theta [0065] The IV spectrum was measured with a resolution of 4 cm ^-1 and with a number of scans of 16 for crystallized samples. The crystalline modification I of

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20/27 chlorfenapyr can be identified by its characteristic functional group vibration peaks in wave numbers (cm ^-1 , ± 0.2%) of 2,984.22, 2,230.69 and 1,977.91cm ^_1 , as shown in Figure 1 .

All IV spectra were obtained using the following acquisition parameters:

Spectrometer FT-IR Nicolet ™ iS 5 unity Diamond ATR Thermo Scientific ™ iD5 ATR Range length wave 550 - 4000 cm ' ¹ Resolution 4 cm ^-1 Number of sweeps 16

Examples

Example 1: Preparation of amorphous chlorfenapyr according to US Patent disclosure No. 5,359,090, Example 1 [0066] A stirred mixture of 4-bromo-2- (4chlorophenyl) -5- (trifluoromethyl) pyrrole-3-carbonitrile (17.4 g, 0.05 mol), dietoxymethane (10.4 g, 0.10 mol) and dimethylformamide (DMF) (4.6 g, 0.0625 mol) in toluene, under N ₂ , was treated in portions with phosphorous oxychloride (9.6 g, 0.0625 mol) at 35 ° C to 45 ° C for a period of 10 minutes, heated to 45 to 53 ° C for about 0.5 hour, cooled to 35 ° C and drip treated with

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21/27 triethylamine (7.25 g, 0.0715 mol) over a period of 2 hours at 35 ° C to 45 ° C. The reaction mixture was treated with water and the toluene was removed by azeotropic distillation. The remaining residue was treated with water, filtered and the filter cake was dried in vacuo at 60 ° C to generate the title product, 20.8 g, 92.7% pure, with 94.6% yield and identified by analysis HPLC.

Scheme 1. Chlorfenapyr synthesis [0067] As shown in Figure 3, the powder X-ray diffraction pattern of the resulting chlorfenapyr product had no significant signs, indicating that the chlorfenapyr product prepared according to the patent disclosure U no .S. 5,359,090 is amorphous.

Example 2: Preparation of crystalline modification I of chlorfenapyr

Crystallization from methyl ethyl ketone [0068] 10 g of amorphous chlorfenapyr sample as prepared in Example 1 were placed in a 3-neck round bottom flask together with 50 ml of methyl ethyl ketone, and the resulting slurry was heated to 65 ° C to generate a homogeneous solution. Insoluble particles, if any, were filtered and the solution was slowly cooled to 20 ° C to 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 3 ml

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22/27 methyl ethyl ketone at 20 ° C. The filtered crystals were dried in vacuo at 40 ° C. The crystalline product obtained was> 98% pure and the yield was found to be not less than 90%.

[0069] The crystals obtained were analyzed by IV spectrometry and powder X-ray diffraction, and it was found to be the crystalline modification I of chlorfenapyr, as shown in Figures 1 and 2, respectively.

[0070] Spectrum IV of crystalline modification I exhibited the characteristic group functional vibrations in wave numbers (cm ^-1 , ± 0.2%) of 2,984.22, 2,230.69 and 1,977.91 cm ^-1 , as shown in Figure 1.

[0071] The crystal powder X-ray diffractogram showed the reflections, as shown in Figure 2, and the values are summarized in Table 1.

Table 1

Crystalline Modification I 2 Θ (°) gives) 7.73 ± 0.20 11.44 ± 0.05 9.25 ± 0.20 9.56 ± 0.05 10.87 ± 0.20 8.14 ± 0.05 12.07 ± 0.20 7.34 ± 0.05 12.77 ± 0.20 6.93 ± 0.05 13.25 ± 0.20 6.68 ± 0.05 14.21 ± 0.20 6.23 ± 0.05 14.95 ± 0.20 5.93 ± 0.05 15.32 ± 0.20 5.78 ± 0.05 16.30 ± 0.20 5.44 ± 0.05 19.60 ± 0.20 4.53 ± 0.05

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The resulting heterogeneous 24/21 was stirred at 20 ° C for 2 h. Then, the slurry was filtered and washed with 3 ml of nitrobenzene. The filtered crystals were dried in vacuo at 45 ° C. The crystalline products obtained had a purity> 98% and the yield was found to be not less than 90%.

[0073] The crystals were characterized as the crystalline modification I of chlorfenapyr using IV spectrometry, powder X-ray diffraction and DSC, as described in Example 2.

Formulation examples

Example 4 - Preparation of amorphous chlorfenapyr suspension concentrate (SC) [0074] All components in the 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.

Table 2

Content % by weight Occupation Amorphous clorfenapyr, 98% (prepared in example 1) 24.49 Ingredient active Propylene glycol 5 Agent anti-freeze and Formulation of polydimethylsiloxane modified (SAG 1529) 0.5 Agent defoamer Condensate of alkylnaphthalenesulfonate -sodium formaldehyde 3 Agent dispersant

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(MORWET D-425® POWDER) Ether of polyalkylene glycol (ATLAS ™ G-5000) 2 Agent humectant Xanthan gum (AG-RHO POL 23 / W) 0.2 Agent thickener 1,2-benzisothiazole-3-one (NIPACIDE BIT 20) 0.2 Biocide Water Amount enough up to 100% Diluent

Example 5 - Preparation of Chlorfenapyr Crystalline Modification Suspension Concentrate (SC) [0075] All components in the list in Table 3 below were mixed uniformly and the resulting mixture was molded with a Dyno-Mill (manufactured by Willy A. Bachofen AG) to obtain a suspension concentrate.

Table 3

Content % by weight Occupation Clorfenapir, modification crystalline I, 98% (prepared in example 2) 24.49 Ingredient active Propylene glycol 5 Agent anti-freeze and Formulation of polydimethylsiloxane 0.5 Agent defoamer

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modified (SAG 1529) Condensate of alkylnaphthalenesulfonate -sodium formaldehyde (MORWET D-425® POWDER) 3 Agent dispersant Ether of polyalkylene glycol (ATLAS ™ G-5000) 2 Agent humectant Xanthan gum (AG-RHO POL 23 / W) 0.2 Agent thickener 1,2-benzisothiazole-3-one (NIPACIDE BIT 20) 0.2 Biocide Water Amount enough up to 100% Diluent

Example 6: Comparison of storage stability [0076] The samples prepared in Examples 4 and 5 were stored at 54 ° C for 1 month, 3 months and 6 months. The procedures are followed according to CIPAC MT 4 6.3. The concentration of chlorfenapyr was tested at the end of each storage period by high performance liquid chromatography (HPLC). Aggregation was measured by observation. The original concentration of chlorfenapyr in each formulation was equal to 24%. The results are listed in Table 4.

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Table 4

Amos tra 1 month 3 months 6 months Concentration of pir chlorphen (%) Aggregates dog Concentration of pir chlorphen (%) Aggregation to Concentration of pir chlorphen (%) Aggregation to Exem peep 4 20 + 12 +++ 10 +++++ Exem peep 5 24 23 23

Note: + means small amount of aggregation. +++++ means a lot of aggregation. means no aggregation.

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Claims (17)

1. Crystalline I modification of 4-bromo-2- (4-chlorophenyl) -1-ethoxymethyl-5-trifluoromethyl-1H-pyrrol-3carbonitrile (chlorfenapyr) characterized by exhibiting at least 3 of the following reflections, in any combination, such as 2Θ ± 0.20 degree X-ray powder diffractogram (X-RPD) recorded using Cu — Koí radiation at 25 ° C: 2Θ = 7.73: i 0 i, 20 d) 2Θ = 9.25: i 0 i, 20 (2) 2Θ = 10.87 ± 0.20 (3) 2Θ = 12.07 ± 0.20 (4) 2Θ = 12.77 ± 0.20 (5) 2Θ = 13.25 ± 0.20 (6) 2Θ = 14.21 ± 0.20 (7) 2Θ = 14.95 ± 0.20 (8) 2Θ = 15.32 ± 0.20 (9) 2Θ = 16.30 ± 0.20 (10) 2Θ = 19, 60 ± 0.20 (11) 2Θ = 20.27 ± 0.20 (12) 2Θ = 20.75 ± 0.20 (13) 2Θ = 21.47 ± 0.20 (14) 2Θ = 21.73 ± 0.20 (15) 2Θ = 23.11 ± 0.20 (16) 2Θ = 23.56 ± 0.20 (17) 2Θ = 23, 92 ± 0.20 (18) 2Θ = 24.29 ± 0.20 (19) 2Θ = 24.67 ± 0.20 (20) 2Θ = 25, 47 ± 0.20 (21) 2Θ = 25, 91 ± 0.20 (22) Petition 870170082931, of 10/27/2017, p. 31/71 2/5 2Θ = 26.69 ± 0.20 (23) 2Θ = 26.89 ± 0.20 (24) 2Θ = 27.25 ± 0.20 (25) 2Θ = 27.72 ± 0.20 (26) 2Θ = 28.26 ± 0.20 (27) 2Θ = 29.83 ± 0.20 (28) 2Θ = 30.91 ± 0.20 (29) 2. Crystalline I modification of chlorfenapyr, according to claim 1, characterized by exhibiting at least 3 of the following reflections, such as 2Θ ± 0.20 degree in a powder X-ray diffractogram recorded with the use of Cu-Koí radiation 25 ° C: 2Θ = 7.73 ± 0.20 d) 2Θ = 9.25: ± 0 , 20 (2) 2Θ = 16.30 ± 0.20 (10) 2Θ = 20.27 ± 0.20 (12) 2Θ = 21.73 ± 0.20 (15) 2Θ = 23.11 ± 0.20 (16) 2Θ = 23.56 ± 0.20 (17) 2Θ = 23, 92 ± 0.20 (18) 2Θ = 24.29 ± 0.20 (19) 2Θ = 25, 47 ± 0.20 (21) 2Θ = 26, 69 ± 0.20 (23) 2Θ = 27.25 ± 0.20 (25) 2Θ = 27.72 ± 0.20 (26) 2Θ = 29, 83 ± 0.20 (28) 2Θ = 30.91 ± 0.20 (29) 3. Crystalline modification I of chlorfenapyr, according to claim 1 or 2, characterized by an infrared (IR) spectrum with peaks of vibration of Petition 870170082931, of 10/27/2017, p. 32/71 3/5 characteristic functional groups in wave numbers (cm ¹ , ± 0.2%) of 2,984.22, 2,230.69 and 1,977.91 cm ' ¹ . Crystalline modification I of chlorfenapyr according to any one of claims 1 to 3, characterized in that the powder X-ray diffraction pattern is substantially as shown in Figure 2 and / or in which the IV spectrum is substantially as shown in Figure 1. Process for the preparation of a crystalline modification I of chlorfenapyr, as defined in any one of claims 1 to 4, characterized by comprising: i) dissolve chlorfenapyr in a solvent or an solvent mixture; ii) precipitate the compound dissolved at crystalline modification I chlorfenapyr; and iii) isolate the modification crystalline I hasty. 6. Process, according to the claim 5, characterized by chlorfenapyr in step i) is amorphous chlorfenapyr. Process according to claim 5 or 6, characterized in that the solvent is methyl ethyl ketone and / or nitrobenzene. Process according to any one of claims 5 to 7, characterized in that step ii) is carried out by concentrating the solvent and / or by cooling and / or by adding a solubility-reducing solvent and / or by adding a crystal inoculation of crystalline modification I. Petition 870170082931, of 10/27/2017, p. 33/71 4/5 Process according to any one of claims 5 to 7, characterized by step ii) being carried out by cooling to about 0 to 20 ° C. Crystalline modification I of chlorfenapyr according to any one of claims 1 to 4, characterized in that it is obtainable by the process, as defined in any one of claims 5 to 9. Crystalline modification I of chlorfenapyr characterized in that it is obtained as defined in any one of claims 5 to 9, and has a crystalline modification I content of chlorfenapyr of at least 98% by weight. Composition characterized in that it comprises the crystalline modification I of chlorfenapyr, as defined in any one of claims 1 to 4 and 11, and at least one auxiliary. 13. Composition according to claim 12, characterized in that the auxiliary is selected from one or more of a solvent, a diluent, a wetting agent, a dispersing agent, a thickening agent, an antifreeze agent and a biocide. Composition according to Claim 12 or 13, characterized in that it is in the form of a suspension concentrate (SC), an oil-based suspension concentrate (OD), water-soluble granules (SG), a dispersible concentrate (DC), an emulsifiable concentrate (EC), an emulsion inoculation coating, a suspension inoculation coating, granules (GR), microgranules (MG), a suspoemulsion (SE) and water dispersible granules (WG). Petition 870170082931, of 10/27/2017, p. 34/71 5/5 18. Use of chlorfenapyr, as Composition according to Claim 14, characterized in that it is in the form of a suspension concentrate (SC). Composition according to any one of claims 12 to 15, characterized in that it comprises the crystalline modification I of chlorfenapyr in an amount of less than 75% by weight. Composition according to any one of claims 12 to 16, characterized in that it comprises the crystalline modification I of chlorfenapyr in an amount of 24% by weight. crystalline modification I of defined in any one of claims 1 to 4, or a composition as defined in any one of claims 12 to 17, characterized in that it is for the control of insects and mites. Method for controlling insects and mites, for comprising applying the crystalline modification I of chlorfenapyr, as defined in any one of claims 1 to 4, or a composition, as defined in any one of claims 12 to 17, to grow crop plants. 20. Method, according to claim 19, characterized in that the plants are selected from cotton, garlic, potatoes, papaya, dry beans, onions and chrysanthemums. 19. featured Petition 870170082931, of 10/27/2017, p. 35/71 1/2 FIGURE 1 FIGURE 2 Petition 870170082931, of 10/27/2017, p. 36/71 2/2 FIGURE 3 Counts Petition 870170082931, of 10/27/2017, p. 37/71 1/1