WO2018090787A1

WO2018090787A1 - Novel crystalline form of chlorfenapyr, process for its preparation and use

Info

Publication number: WO2018090787A1
Application number: PCT/CN2017/107247
Authority: WO
Inventors: James Timothy Bristow
Original assignee: Jiangsu Rotam Chemistry Co., Ltd
Priority date: 2016-11-16
Filing date: 2017-10-23
Publication date: 2018-05-24
Also published as: AU2016102018A4; CN109071431A; BR102017023300A2; AU2016259360B1

Abstract

Provided herein are the crystalline form of chlorfenapyr of formula (I), the crystal preparation process, the analyses of the crystal through various analytical methods, using the crystal to prepare stable agrochemical formulation, and the use of various solvents towards the crystalline form preparation conditions.

Description

[Title established by the ISA under Rule 37.2] NOVEL CRYSTALLINE FORM OF CHLORFENAPYR, PROCESS FOR ITS PREPARATION AND USE

CROSS REFERENCE TO RELATED APPLICATION

This application claims priority to Australian Patent Application No. 2016259360, titled “A NOVEL CRYSTALLINE FORM OF CHLORFENAPYR, A PROCESS FOR ITS PREPARATION AND USE OF THE SAME” , filed with IP Australia on November 16, 2016, the entire contents of which are incorporated herein by reference.

FIELD

The present invention relates to a crystalline form of 4-bromo-2- (4-chlorophenyl) -1-ethoxymethyl-5-trifluoromethyl-1H-pyrrole-3-carbonitrile (chlorfenapyr) , to its preparation processes and to its use in agrochemical preparations.

BACKGROUND

4-bromo-2- (4-chlorophenyl) -1-ethoxymethyl-5-trifluoromethyl-1H-pyrrole-3-carbonitrile (chlorfenapyr) is a potent insecticide and acaricide. It is an acaricide developed by Cyanamid (now BASF) under the code AC 303630. Chlorfenapyr is based on the natural product dioxapyrrolomycin and was originally isolated from a Streptomyces fermentation broth. The product is effective in controlling spider mites, boll weevils, whitefly and many species of Lepidoptera. Chlorfenapyr was registered in Japan as Kotetsu (Nippon Soda) for use on fruit and vegetables, and entered the top-ten insecticide rankings (at number 7) in the country in 1996. Kotetsu is also sold by Mitsubishi Chemical in Japan, and is one of its leading 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.

Chlorfenapyr has a molecular formula of C₁₅H₁₁BrClF₃N₂O. Its chemical structure is:

The commercially available chlorfenapyr, which is usually manufactured by the process described in US PAT. NO. 5,359,090, is present in an amorphous state. It has been found that chlorfenapyr in an amorphous state is not suitable for being used in an economical formulation due to its high tendency to aggregate, in particular after prolonged storage. Therefore, there is a need to provide a novel form of chlorfenapyr exhibiting improved properties, such as, for example, improved storage stability.

SUMMARY

In attempt to resolve some or all of the problems with existing amorphous form of chlorfenapyr, a new and stable crystalline form of chlorfenapyr has been prepared.

In a first aspect, the present invention provides a crystalline modification I of 4-bromo-2- (4-chlorophenyl) -1-ethoxymethyl-5-trifluoromethyl-1H-pyrrole-3-carbonitrile (chlorfenapyr) , termed “crystalline modification I” , exhibiting at least three of the following reflexes, in any combination, as 2θ±0.20 degree in an X-ray powder diffractogram (X-RPD) recorded using Cu—Kα radiation at 25℃:

2θ ＝ 7.73 ± 0.20 (1)

2θ ＝ 9.25 ± 0.20 (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)

In an embodiment, the crystalline modification I of chlorfenapyr according to the first aspect of the invention, exhibiting at least 3, 4, 5, 6, 7, 8 or all of the following reflexes, in any combination, as 2θ±0.20 degree in an X-ray powder diffractogram recorded using Cu—Kα radiation at 25℃:

2θ ＝ 7.73 ± 0.20 (1)

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)

In a second aspect, the present invention provides a crystalline modification I of chlorfenapyr, optionally according to the first aspect of the invention, exhibiting an infrared (IR) with characteristic functional group vibration peaks at wavenumbers (cm^-1, ±0.2％) of 2984.22, 2230.69 and 1977.91cm^-1.

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 powder X-ray diffraction pattern substantially as shown in Figure 2, and/or characterized by an IR spectrum substantially as shown in Figure 1.

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.

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.

It has been found that the present crystalline modification I of chlorfenapyr may show a significant improvement in its storage stability, which may significantly reduce the aggregation problem encountered with current commercially available formulations. In addition, it has been found that the crystalline modification I of chlorfenapyr may exhibit a high degree of stability when formulated compared to amorphous chlorfenapyr prepared in accordance with the disclosure of US PAT. NO. 5,359,090. In particular, the crystalline modification may exhibit a very low tendency to aggregate when formulated. This may allow the preparation of commercial formulations such as suspension concentrates (SC) . Further, by virtue of good stability properties, the crystalline modification I of chlorfenapyr may provide a desirable long storage period for formulations.

Methods for preparing amorphous chlorfenapyr are well known in the art. Amorphous chlorfenapyr is manufactured and available on a commercial scale. A particularly suitable method for preparing amorphous chlorfenapyr is described in US PAT. NO. 5,359,090.

In a sixth aspect, the present invention provides a process for preparing a crystalline modification I of chlorfenapyr comprising the steps of:

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

ii) precipitating the dissolved compound into crystalline modification I of chlorfenapyr； and

iii) isolating the precipitated crystalline modification I.

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

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 propyl ether, n-butyl ether, anisole, phenetole, cyclohexyl methyl ether, dimethyl ether, diethyl 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 tert-butyl ether, methyltetrahydrofuran, dioxane, dichlorodiethyl ether, polyethers of ethylene oxide and/or propylene oxide) , nitrated hydrocarbons (for example, nitromethane, nitroethane, nitropropane, nitrobenzene, chloronitrobenzene and o-nitrotoluene) , aliphatic, cycloaliphatic or aromatic hydrocarbons (for example, pentane, n-octane, nonane, ethyl benzene, mesitylene) , cymene, petroleum fractions having a boiling range of from 70℃ to 190℃, petroleum ether, ligroin, octane, benzene, esters (for example, 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 thereof.

In an embodiment of the sixth aspect of the nvention, 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.

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.

According to an embodiment of the sixth aspect of the present invention, step ii) is effected by concentration of the solvent 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 chlorfenapyr.

According to an embodiment of the sixth aspect of the present invention, crystalline modification I of chlorfenapyr is prepared by dissolving the amorphous chlorfenapyr in a solvent or a solvent mixture as a concentrated solution by heating from ambient temperature to a temperature at or below the reflux temperature of the solvent or the 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 solvent mixture.

In an embodiment of the sixth aspect of the invention, the concentrated homogeneous solution thus prepared as in step (i) is then cooled to ambient temperature or cooled to about 0 to 20℃ to crystallize the desired crystalline form from the solvent. The crystalline modification I of chlorfenapyr can also be crystallized out by concentrating the homogeneous solution by removing the solvent or solvent mixture to a certain volume, with or without applying vacuum, and cooling to below the reflux temperature of the solvent or the solvent mixture.

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

The seed crystal amount added to the concentrated solution is typically in the range of 0.001％to 10％by weight, more particularly in the range of 0.005％to 0.5％by weight, based on the weight of chlorfenapyr used for the preparation of concentrated solution in step (i) . Optionally, the seed crystals are added to the concentrated solution at a temperature below the boiling point of the corresponding solvent or the solvent mixture.

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 usual solid component separating techniques from solutions, such as filtration, centrifugation or decantation. Then, the isolated solid will be washed with solvent one or more times. Optionally, the solvent employed in the washing stage consists of one or more components of the solvent or solvent mixture employed for the preparation of concentrated solution in step (i) , as described hereinbefore. The washing is usually carried out using the corresponding solvent or solvent mixture between room temperature and 0℃, depending on the solubility of the crystal in order to avoid the loss of crystal as far as possible in the corresponding washing solvent.

In an embodiment of the sixth aspect of the invention, crystalline modification I of chlorfenapyr is dissolved and recrystallized. The washings and/or the solvent of crystallization in any of the methods may be concentrated to obtain solid chlorfenapyr which may be recycled.

In a seventh aspect, the present invention provides a crystalline modification I of chlorfenapyr obtained according to the sixth aspect of the invention, having a crystalline modification I of chlorfenapyr content of at least 98％by weight.

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 fifth and seventh aspects of the invention, and at least one auxiliary.

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

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, still more preferably about 24％by weight of the composition.

The use of chlorfenapyr as an insecticide and acaricidal is well known in the art and is used on a commercial scale. The crystalline modification I of chlorfenapyr is also active in controlling insects and mites. As a result, the techniques of formulating and applying chlorfenapyr known in the art for amorphous chlorfenapyr, for example as disclosed in the prior art documents discussed hereinbefore, can also be applied in an analogous manner to chlorfenapyr in the crystalline modification I of the present invention.

Accordingly, the present invention provides an insecticidal and acaricidal composition comprising chlorfenapyr in the crystalline modification I as defined hereinbefore.

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

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 seed dressings, suspension seed dressings, granules (GR) , microgranules (MG) , suspoemulsions (SE) and water-dispersible granules (WG) . The crystalline modification I of chlorfenapyr can be included into these customary formulations in a known manner using suitable auxiliaries, carriers and solvents and the like.

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

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 the loci thereof, desirably in a concentration of from about 0.1 to about 75％by weight of the total mixture.

These formulations are prepared in a known manner by mixing the crystalline modification I of chlorfenapyr with customary additives, for example, liquid diluents, solid diluents, wetting agents, dispersing agents, thickening agent, antifreeze agents, biocide and any necessary adjuvants and other formulation ingredients.

Liquid diluents include, but are not limited to, water, N, N-dimethylmamide, dimethyl sulfoxide, N-alkylpyrrolidone, ethylene glycol, polypropylene glycol, propylene carbonate, dibasic esters, paraffines, alkylbenzenes, alkyl naphthalenes, glycerine, triacetine, oils of olive, castor, linseed, sesame, corn, peanut, cotton-seed, soybean, rape-seed and coconut, ketones such as 2-heptanone, isophorone and 4-hydroxy-4-methyl-2-pentanone, acetates such as hexyl acetate, heptyl acetate and octyl acetate, water and alcohols such cyclohexanol, decanol, benzyl and tetrahydrofurfuryl alcohol.

Solid diluents can be water-soluble or water-insoluble. Water-soluble solid diluents include, but are not limited to, salts such as alkali metal phosphates (e.g., sodium dihydrogen phosphate) , alkaline earth phosphates, sulfates of sodium, potassium, magnesium and zinc, sodium and potassium chloride, sodium acetate, 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 and diatomaceous silicas, calcium and magnesium silicates, titanium dioxide, aluminum, calcium and zinc oxide.

Wetting agents include, but are not limited to, alkyl sulfosuccinates, laureates, alkyl sulfates, phosphate esters, acetylenic diols, ethoxyfluornated alcohols, ethoxylated silicones, alkyl phenol ethyoxylates, benzene sulfonates, alkyl-substituted benzene sulfonates, alkyl a-olefin sulfonates, naphthalene sulfonates, alkyl-substituted napthalene sulfonates, condensates of naphthalene sulfonates and alkyl-substituted naphthalene sulfonates with formaldehyde, and alcohol ethoxylates. Polyalkylene glycol ether is particularly useful for the composition of the invention.

Dispersing agents include, but are not limited to, sodium, calcium and ammonium salts of ligninsulfonates (optionally polyethoxylated) ； sodium and ammonium salts of maleic anhydride copolymers； sodium salts of condensed phenolsulfonic acid； and naphthalene sulfonate-formaldehyde condensates. Of note are compositions comprising up to 10％by weight of dispersant. Ligninsulfonates such as sodium ligninsulfonates are particularly useful for the composition of the invention. Sodium alkyl naphthalene sulfonate-formaldehyde condensate is particularly useful for the composition of the invention.

Thickening agents include, but are not limited to, guar gum, pectin, casein, carrageenan, xanthan gum, alginates, methylcellulose, hydroxyethylcellulose, hydroxypropylcellulose, and carboxymethylcellulose. Synthetic thickeners include derivatives of the former categories, and also polyvinyl alcohols, polyacrylamides, polyvinylpyrrolidones, various polyethers, their copolymers as well as polyacrylic acids and their salts. Xanthan gum is particularly useful for the composition of the invention.

Suitable antifreezing 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.

Biocides may also be added to the composition according to the invention. Suitable biocides are those based on isothiazolones, for example

from ICI or

RS from Thor Chemie or

MK from Rohm &Haas. The amount of biocides is typically from 0.05％to 0.5％by weight, based on the total weight of composition.

Other formulation ingredients can also be used in the present invention, such as dyes, antifoaming agents, drying agents, and the like. These ingredients are known to one skilled in the art.

In an embodiment of the eighth aspect of the invention, the crystalline modification I of chlorfenapyr can be present in its commercially available formulations and in its use forms, prepared from these formulations, and as a mixture with other active compounds (such as insecticides, attractants, sterilizing agents, bactericides, acaricides, nematicides, fungicides, growth-regulating substances, herbicides, safeners, fertilizers and semiochemicals) or with agents for improving plant properties.

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

Chlorfenapyr, which is an active ingredient of 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 such as diamond back moth (Plutella xylostella) , common cutworm (Spodoptera litura) , and apple leafminer (Phyllonorycter ringoniella) ； Thysanoptera pests such as melon thrips (Thrips palmi) and yellow tea thrips (Spirtothrips dorsalis) ； agrohorticultural pests such as mites such as two-spotted spider mite (Tetranychus urticae koch) , kanzawa spider mite (Tetranychus kanzawai kishida) and Aculops pelekassi.

The benefits of the present invention are seen most when the insecticidal and acaricidal composition is applied to kill insects and mites in growing crops of useful plants: such as cotton, garlic, potato, papaya, dry bean, onion and chrysanthemum.

All plants and plant parts can be treated in accordance with the invention. In the present context, plants are to be understood as meaning all plants and plant populations such as desired and undesired wild plants or crop plants (including naturally occurring crop plants) . Crop plants can be plants which can be obtained by conventional breeding and optimization methods, by biotechnological and genetic engineering methods, or by combinations of these methods, including the transgenic plants and the plant cultivars which can or cannot be protected by plant breeders' rights. Plant parts are to be understood as meaning all parts and organs of plants above and below the ground, such as shoot, leaves, needles, stalks, stems, flowers, fruit bodies, fruits, seeds, roots, tubers and rhizomes. Harvested materials, and vegetative and generative propagation materials, for example, cutting, tubers, meristem tissue, rhizomes, offsets, seeds, single and multiple plant cells and any other plant tissues, are also included.

Treatment according to the invention of the plants and plant parts with the compositions or formulations of the inventions is carried out directly or by allowing the compositions or formulations to act on their surroundings, habitat or storage space by the customary treatment methods. Examples of these customary treatment methods include dipping, spraying, vaporizing, fogging, broadcasting, painting on in the case of propagation material, and applying one or more coats particularly in the case of seed.

Throughout the description and claims of this specification, the words “comprise” and variations of the words, for example “comprising” and “comprises” , mean “including but not limited to” , and do not exclude other moieties, additives, components, integers or steps. Moreover, the singular encompasses the plural unless the context otherwise requires: in particular, where the indefinite article is used, the specification is to be understood as contemplating plurality as well as singularity, unless the context requires otherwise.

Preferred features of each aspect of the invention may be as described in connection with any of the other aspects. Other features of the invention will become apparent from the following examples. Generally speaking, the invention extends to any novel one, or any novel combination, of the features disclosed in this specification (including any accompanying claims and drawings) . Thus features, integers, characteristics, compounds, chemical moieties or groups described in conjunction with a particular aspect, embodiment or example of the invention are to be understood to be applicable to any other aspect, embodiment or example described herein unless incompatible therewith. Moreover, unless stated otherwise, any feature disclosed herein may be replaced by an alternative feature serving the same or a similar purpose.

Where 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 lower limits may also be implied.

In this specification, references to properties are –unless stated otherwise –to properties measured under ambient conditions, i.e. at atmospheric pressure and at a temperature of about 20℃.

As used herein, the term “about” or "around" when used in connection with a numerical amount or range, means somewhat more or somewhat less than the stated numerical amount or range, and for example to a deviation of ± 10％of the stated numerical amount or endpoint of the range.

“Surrounding, ” as used herein, refers to the place on which the plants are growing, the place on which the plant propagation materials of the plants are sown or the place on which the plant propagation materials of the plants will be sown.

"Precipitation" as used herein, refers to the sedimentation of a solid material (aprecipitate) , including the sedimentation of a crystalline material, from a liquid solution in which the solid material is present in amounts greater than its solubility in the amount of liquid solution.

All percentages are given in weight ％unless otherwise indicated.

BRIEF DESCRIPTION OF DRAWINGS

The invention can be more clearly understood by reference to the drawings, which are described below, and are intended to exemplify and illustrate, but not to limit, the scope of the invention, wherein:

Figure 1 is a an infrared (IR) spectrograph of crystalline modification I of chlorfenapyr；

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

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

DETAILED DESCRIPTION

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.

All X-ray diffractograms were determined using powder diffractometer in reflection geometry at 25℃, using the following acquisition parameters:

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

The IR spectrum was measured with the resolution of 4cm^-1 and with the number of scans of 16 for the crystallized samples. The crystalline modification I of chlorfenapyr can be identified by its characteristic functional group vibration peaks at wavenumbers (cm^-1, ±0.2％) of 2984.22, 2230.69 and 1977.91cm^-1 as shown in Figure 1.

All IR spectra were obtained using the following acquisition parameters:

FT-IR spectrometer	Nicolet^TM iS 5
Diamond ATR unit	Thermo Scientific^TM iD5 ATR
Wavelength range	550 -4000 cm^-1
Resolution	4 cm^-1
Number of scans	16

Examples

Example 1: Preparation of amorphous chlorfenapyr in accordance with the disclosure of US PAT. NO. 5, 359, 090, Example 1

A stirred mixture of 4-bromo-2- (4-chlorophenyl) -5- (trifluoromethyl) pyrrole-3 -carbonitrile (17.4g, 0.05mole) , diethoxymethane (10.4g, 0.10mole) and dimethylformamide (DMF) (4.6g, 0.0625mole) in toluene, under N₂, was treated portion-wise with phosphorous oxychloride (9.6g, 0.0625mole) at 35℃～45℃ over a 10 minute period, heated at 45°～53℃ for about 0.5 hour, cooled to 35℃ and treated dropwise with triethylamine (7.25g, 0.0715mole) over a 2 hour period at 35℃～45℃. The reaction mixture was treated with water and the toluene is removed via azeotropic distillation. The remaining residue was treated with water, filtered and the filtercake was dried in vacuo at 60℃. to give the title product, 20.8g, 92.7％pure, 94.6％yield, identified by HPLC analysis.

As shown in Figure 3, the X-ray powder diffraction pattern of the resulting chlorfenapyr product has no significant signals, which indicates the chlorfenapyr product prepared in accordance with the disclosure of US PAT. NO. 5,359,090 is amorphous.

Example 2: Preparation of the crystalline modification I of chlorfenapyr

Crystallization from methyl ethyl ketone

10g of amorphous chlorfenapyr sample as prepared in Example 1 was taken in a 3-neck round bottom flask along with 50ml of methyl ethyl ketone and the resulting slurry was heated to 65℃ to get a homogeneous solution. The insoluble particles, if any, were filtered and the solution was slowly cooled to 20℃～25℃. Upon cooling, fine crystals were formed and the resulting heterogeneous mixture was stirred at 20℃ for 2h. Then, the slurry was filtered and washed with 3 ml of methyl ethyl ketone 20℃. The filtered crystals were dried under vacuum at 40℃. The crystalline product obtained had a purity of >98％and the yield was found to be not less than 90％.

The obtained crystals were analyzed by IR spectrometry and X-ray powder diffraction and found out to be crystalline modification I of chlorfenapyr as shown in Figure 1 and 2 respectively.

The IR spectrum of the crystalline modification I of exhibited the functional group characteristic vibrations at wavenumbers (cm^-1, ±0.2％) of 2984.22, 2230.69 and 1977.91cm^-1 as shown in Figure 1.

The X-ray powder diffractogram of crystals exhibited the reflexes as shown in Figure 2 and the values are summarized in Table 1.

Table 1

Example 3: Preparation of the crystalline modification I of chlorfenapyr

Crystallization from nitrobenzene

5g of amorphous chlorfenapyr sample as prepared in Example 1 was taken in a 3-neck round bottom flask along with 30ml of nitrobenzene and the resulting slurry was heated to 83℃ to get a homogeneous solution. The insoluble particles, if any, were filtered and the solution was slowly cooled to 20℃～25℃. Upon cooling, fine crystals were formed and the resulting heterogeneous mixture was stirred at 20℃ for 2h. Then, the slurry was filtered, washed with 3 ml of nitrobenzene. The filtered crystals were dried under vacuum at 45℃. The crystalline products obtained had a purity of >98％and the yield was found to be not less than 90％.

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

Formulation examples

Example 4–Preparation of suspension concentrate (SC) of amorphous chlorfenapyr

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.

Table 2

Example 5–Preparation of Suspension Concentrate (SC) of chlorfenapyr crystalline modification I

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.

Table 3

Example 6: Comparison of the storage stability

Samples prepared in Examples 4, and 5 were stored at 54℃ for 1 month, 3 months and 6 months. The procedures are followed according to CIPAC MT 46.3. The concentration of chlorfenapyr was tested at the end of each storage time by high pressure liquid chromatography (HPLC) . The aggregation was measured by observation. The original concentration of chlorfenapyr in each formulation was 24％. The results are listed in Table 4.

Table 4

Remark: “+” means small amount of aggregation. “+++++” means a lot of aggregation. “-” means no aggregation.

Claims

A crystalline modification I of 4-bromo-2- (4-chlorophenyl) -1-ethoxymethyl-5-trifluoromethyl-1H-pyrrole-3-carbonitrile (chlorfenapyr) ， exhibiting at least 3 of the following reflexes， in any combination， as 2θ±0.20 degree in X-ray powder diffractogram (X-RPD) recorded using Cu-Kα radiation at 25℃：

2θ ＝ 7.73 ± 0.20                   (1)

2θ ＝ 9.25 ± 0.20                   (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) .
The crystalline modification I of chlorfenapyr according to claim 1， exhibiting at least 3 of the following reflexes， as 2θ±0.20 degree in an X-ray powder diffractogram recorded using Cu-Kα radiation at 25℃：

2θ ＝ 7.73 ± 0.20                   (1)

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) .
The crystalline modification I of chlorfenapyr according to claims 1 or 2， exhibiting an infrared (IR) spectrum with characteristic functional group vibration peaks at wavenumbers (cm^-1， ±0.2％) of 2984.22， 2230.69 and 1977.91 cm^-1.
The crystalline modification I of chlorfenapyr according to any one of claims 1 to 3， characterized by X-ray powder diffraction pattern substantially as shown in Figure 2， and/or characterized by an IR spectrum substantially as shown in Figure 1.
A process for the preparation of a crystalline modification I of chlorfenapyr according to any one of claims 1 to 4， comprising：

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

ii) precipitating the dissolved compound into crystalline modification I of chlorfenapyr； and

iii) isolating the precipitated crystalline modification I.
The process according to claim 5， where the chlorfenapyr in step i) is amorphous chlorfenapyr.
The process according to claims 5 or 6， wherein the solvent is methyl ethyl ketone and/or nitrobenzene.
The process according to any one of claims 5 to 7， wherein step ii) is effected by concentration of the solvent 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.
The process according to any one of claims 5 to 7， wherein step ii) is effected by cooling to about 0 to 20℃.
The crystalline modification I of chlorfenapyr according to any one of claims 1 to 4， obtainable by the process of any one of claims 5 to 9.
The crystalline modification I of chlorfenapyr obtained according to any one of claims 5 to 9 and having a crystalline modification I of chlorfenapyr content of at least 98％by weight.
A composition comprising the crystalline modification I of chlorfenapyr according to any one of claims 1 to 4 and 11 and at least one auxiliary.
The composition according to claim 12， wherein the auxiliary is selected from one or more of a solvent， a diluent， a wetting agent， a dispersing agents， a thickening agent， an antifreeze agent and a biocide.
The composition according to claims 12 or 13， which is in a 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 seed dressing， a suspension seed dressing， granules (GR) ， microgranules (MG) ， a suspoemulsion (SE) and a water-dispersible granule (WG) .
The composition according to claim 14， which is in a form of a suspension concentrate (SC) .
The composition according to any one of claims 12 to 15， which comprises crystalline modification I of chlorfenapyr in an amount of less than 75％by weight.
The composition according to any one of claims 12 to 16， which comprises crystalline modification I of chlorfenapyr in an amount of 24％by weight.
A use of the crystalline modification I of chlorfenapyr according to any one of claims 1 to 4 or a composition according to any one of claims 12 to 17 for the control of insects and mites.
A method of controlling insects and mites， comprising applying the crystalline modification I of chlorfenapyr according to any one of claims 1 to 4 or a composition according to any one of claims 12 to 17 to growing crop plants.
The method of claim 19， wherein the plants are selected from cotton， garlic， potato， papaya， dry bean， onion and chrysanthemum.