EP3924346A1 - Nouvelle forme de metconazole, son procédé de préparation et son utilisation - Google Patents

Nouvelle forme de metconazole, son procédé de préparation et son utilisation

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Publication number
EP3924346A1
EP3924346A1 EP19914791.9A EP19914791A EP3924346A1 EP 3924346 A1 EP3924346 A1 EP 3924346A1 EP 19914791 A EP19914791 A EP 19914791A EP 3924346 A1 EP3924346 A1 EP 3924346A1
Authority
EP
European Patent Office
Prior art keywords
metconazole
crystalline modification
crystalline
composition
plant
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Withdrawn
Application number
EP19914791.9A
Other languages
German (de)
English (en)
Other versions
EP3924346A4 (fr
Inventor
James Timothy Bristow
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Jiangsu Rotam Chemical Co Ltd
Original Assignee
Jiangsu Rotam Chemical Co Ltd
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Jiangsu Rotam Chemical Co Ltd filed Critical Jiangsu Rotam Chemical Co Ltd
Publication of EP3924346A1 publication Critical patent/EP3924346A1/fr
Publication of EP3924346A4 publication Critical patent/EP3924346A4/fr
Withdrawn legal-status Critical Current

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Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D249/00—Heterocyclic compounds containing five-membered rings having three nitrogen atoms as the only ring hetero atoms
    • C07D249/02—Heterocyclic compounds containing five-membered rings having three nitrogen atoms as the only ring hetero atoms not condensed with other rings
    • C07D249/08—1,2,4-Triazoles; Hydrogenated 1,2,4-triazoles
    • A—HUMAN NECESSITIES
    • A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
    • A01N—PRESERVATION OF BODIES OF HUMANS OR ANIMALS OR PLANTS OR PARTS THEREOF; BIOCIDES, e.g. AS DISINFECTANTS, AS PESTICIDES OR AS HERBICIDES; PEST REPELLANTS OR ATTRACTANTS; PLANT GROWTH REGULATORS
    • A01N43/00—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds
    • A01N43/64—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having rings with three nitrogen atoms as the only ring hetero atoms
    • A01N43/647—Triazoles; Hydrogenated triazoles
    • A01N43/653—1,2,4-Triazoles; Hydrogenated 1,2,4-triazoles

Definitions

  • the present invention relates to a novel form of 5- (4-chlorobenzyl) -2, 2-dimethyl-1- (1H-1, 2, 4-triazol-1-ylmethyl) cyclopentanol (metconazole) , in particular to a novel crystalline form of metconazole.
  • the present invention further relates to a method for the preparation of the novel form of metconazole and, still further to the use of the novel form of metconazole in agrochemical preparations and in the control of fungicidal infestations.
  • 5- (4-chlorobenzyl) -2, 2-dimethyl-1- (1H-1, 2, 4-triazol-1-ylmethyl) cyclopentanol belongs to the chemical class of azoles exhibiting a broad spectrum of fungicidal activity.
  • Metconazole has a molecular formula of C 17 H 22 ClN 3 O and has the following structure:
  • Metconazole is a chiral molecule existing as a mixture of two pairs of diastereomers, cis-and trans-isomers. Metconazole is a systemic fungicide with a mode of action preventing spore formation and inhibiting mycelial growth. Metconazole is taken up into plant leaves and exhibits penetrant, local and acropetal systemicity. Metconazole exhibits both curative and protectant properties and has demonstrated long term activity in the control of plant disease organisms.
  • EP 0 329 397 discloses a process for producing azolylmethylcyclopentanol derivatives. Metconazole is included in the derivatives that may be formed by the process.
  • metconazole which is usually manufactured by the process described in EP 0 329 397, is present in an amorphous state.
  • metconazole in an amorphous state is not suitable for being formulated into fungicidal compositions.
  • metconazole in an amorphous state has a high tendency to aggregate, in turn blocking filters and the nozzles of the spray apparatus used in the formulation process. Therefore, there is a need to reduce the tendency for metconazole to aggregate, and thereby improve the processes for its formulation.
  • metconazole when present in a crystalline form, herein referred to as “crystalline modification I” , exhibits little to no tendency to aggregate, in turn significantly improving the processes for formulating fungicidal compositions.
  • the invention provides a crystalline form of 5- (4-chlorobenzyl) -2, 2-dimethyl-1- (1H-1, 2, 4-triazol-1-ylmethyl) cyclopentanol (metconazole) exhibiting at least 3 of the following reflexes, in any combination, as 2 ⁇ ⁇ 0.2 degree in an X-ray powder diffractogram (X-RPD) recorded using Cu-K ⁇ radiation at 25 °C:
  • the crystalline modification according to the first aspect of the invention exhibits at least 3, more preferably 4 or all of the reflexes, in any combination from the following:
  • the crystalline modification according to the first aspect of the invention exhibits an X-ray powder diffraction pattern substantially as shown in Figure 1.
  • the present invention provides a crystalline form of 5- (4-chlorobenzyl) -2, 2-dimethyl-1- (1H-1, 2, 4-triazol-1-ylmethyl) cyclopentanol (metconazole) exhibiting an infrared (IR) spectrum with characteristic functional group vibration peaks at wavenumbers (cm -1 , ⁇ 0.2%) of one or more of 3337, 2963, 2871, 1508, 1492, 1425, 1406, 1385, 1271, 1137 and 1013 cm -1 as shown in Figure 2.
  • IR infrared
  • the crystalline modification according to the second aspect of the invention exhibits an IR spectrum substantially as shown in Figure 2.
  • the crystalline form of metconazole of the second aspect of the present invention further comprises the features hereinbefore described as characterizing the crystalline form of metconazole of the first aspect of the present invention.
  • the present invention provides a crystalline form of 5- (4-chlorobenzyl) -2, 2-dimethyl-1- (1H-1, 2, 4-triazol-1-ylmethyl) cyclopentanol (metconazole) exhibiting a melting point of from about 112 to about 114°C.
  • the crystalline form of metconazole of the third aspect of the present invention further comprises the features hereinbefore described as characterizing the crystalline form of metconazole of one or both of the first and second aspects of the present invention.
  • the present invention provides a crystalline form of 5- (4-chlorobenzyl) -2, 2-dimethyl-1- (1H-1, 2, 4-triazol-1-ylmethyl) cyclopentanol (metconazole) exhibiting a differential scanning calorimetry (DSC) profile having an endothermic melting peak maximum of about 113.3°C.
  • the crystalline modification according to the fourth aspect of the invention exhibits a DSC thermogram substantially as shown in Figure 3.
  • the crystalline form of metconazole of the fourth aspect of the present invention further comprises the features hereinbefore described as characterizing the crystalline form of metconazole of one or more of the first, second and third aspects of the present invention.
  • the crystalline modification I of metconazole exhibits a significant increase in its anti-aggregation properties, which significantly reduces the aggregation problem encountered in current commercially available formulations.
  • the crystalline modification I of metconazole is easier to comminute or grind, compared with amorphous metconazole prepared in accordance with known and commonly applied procedures, such as the method disclosed in EP 0329397. This allows metconazole to used in the preparation of commercial formulations such as suspension concentrates (SC) , oil-based suspension concentrates (OD) , water-dispersible granules (WG) and water-soluble granules (SG) .
  • SC suspension concentrates
  • OD oil-based suspension concentrates
  • WG water-dispersible granules
  • SG water-soluble granules
  • the present invention provides a method for preparing the crystalline modification I of metconazole, the method comprising the steps of:
  • the metconazole starting material used in step i) of the method may be any suitable metconazole material.
  • the metconazole employed in step i) of the method is amorphous metconazole.
  • Methods for preparing amorphous metconazole are known in the art. Amorphous metconazole is manufactured and available on a commercial scale. A particularly suitable method for preparing amorphous metconazole is described in EP 0 329 397.
  • step i) of the method metconazole is dissolved in a solvent system.
  • the solvent system may comprise a single solvent or a mixture of two or more solvents. Any suitable solvent that yields the crystalline modification I of metconazole may be employed in the solvent system.
  • the solvent system comprises one or more solvents selected from ethers, aliphatic and aromatic hydrocarbons.
  • Preferred ethers for use in the solvent system include, for example, methyl t-butyl ether, 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, dichlorodiethyl ether, polyethers of ethylene oxide and/or propylene oxide. Petroleum ether is also a particularly suitable solvent.
  • Preferred aliphatic hydrocarbons include, for example, aliphatic hydrocarbons having from 1 to 20 carbon atoms, preferably from 2 to 15 carbon atoms, more preferably from 4 to 12 carbon atoms, such as pentane, hexane, heptane, octane, and nonane.
  • the aliphatic hydrocarbons may be straight chain or branched, with straight chain aliphatic hydrocarbons being preferred, such as n-hexane, n-heptane and n-octane.
  • Preferred aromatic hydrocarbon solvents include benzene and alkyl-substituted benzene, preferably C 1 to C 4 alkyl-substituted benzene, provided that in the case of C 1 alkyl substituents, two or more alkyl substituents are present, more preferably C 1 to C 3 alkyl-substituted benzene, such as ethyl benzene, xylene, mesitylene and cymene. Petroleum fractions within a boiling range of from 70°C to 190°C and ligroin are also suitable as solvents.
  • the solvent system does not include cyclohexane, methylcyclohexane, toluene, tetrahydrofuran and dioxane.
  • the solvent system comprises one or more solvents selected from aromatic hydrocarbons, ether and mixtures thereof.
  • Particularly preferred solvents are xylene, methyl t-butyl ether and mixtures thereof.
  • the crystalline modification I of metconazole is prepared by dissolving metconazole in a solvent system to form as solution.
  • the dissolution of metconazole may be performed at ambient temperature.
  • the solvent system may be heated, preferably to a temperature at or below the reflux temperature of the solvent system.
  • the solution of metconazole is prepared at the reflux temperature of the solvent system. The concentration of the solution depends on such factors as the solubility of metconazole in the solvent system employed.
  • the metconazole solution prepared in step i) of the method is then used to produce the crystalline modification I of metconazole. This is achieved by crystallization. Any suitable technique may be employed to crystallize metconazole from solution in the solvent system.
  • the solution may be cooled, for example to room temperature or to a temperature of from about 0°C to about 20°C to crystallize the desired crystalline form from the solvent.
  • the crystalline modification I of metconazole may also be crystallized out of solution by concentrating the solution by removing the solvent system.
  • the solvent system may be removed by techniques known in the art, for example by evaporation with or without applying a vacuum, optionally with cooling to below the reflux temperature of the solvent system.
  • Production of the crystalline modification I of metconazole from the solution can also be effected or aided by adding seed crystals to the solution, preferably seed crystals of metconazole, more preferably seed crystals of the desired crystalline form.
  • seed crystals acts to promote or accelerate the crystallization.
  • the amount of seed crystals added to the metconazole solution may be any suitable amount required to promote or accelerate crystallization and is typically in the range of 0.001%to 10%by weight based on the weight of metconazole used to prepare the solution, preferably from 0.001%to 2.5%by weight, more preferably from 0.005 to 0.5%by weight based on the weight of metconazole used for the preparation of the solution in step (i) .
  • the seed crystals, if employed, are added to the concentrated solution at the temperature below the boiling point of the solvent system.
  • Crystallization of the crystalline modification I of metconazole from the solution formed in step i) may be carried out batchwise, semi-continuously or continuously.
  • the precipitated crystalline modification I of metconazole obtained from step ii) of the method may be isolated and revered by solid component separation techniques known in the art, such as filtration, centrifugation and/or decantation.
  • the isolated solid is preferably washed with a solvent one or more times.
  • the solvent employed in the washing stage consists of or at least comprises one or more components of the solvent system employed for preparation of metconazole solution in step i) of the method, as described above.
  • the washing step is preferably carried out using the solvent at a temperature from 0°C to room temperature, depending on the solubility of the crystalline metconazole in the solvent system being employed, in order to minimize or avoid the loss of crystalline material.
  • the crystalline modification I of metconazole is dissolved and recrystallized.
  • the washings and/or the solvent system used for crystallization in any of the method steps may be concentrated to obtain solid metconazole, which may then be recycled for use in step i) of the method.
  • the present invention provides a crystalline modification I of metconazole obtainable by the method hereinbefore described.
  • the crystalline metconazole material has a content of the crystalline modification I of metconazole of at least 98%by weight.
  • the present invention provides a fungicidal composition
  • a fungicidal composition comprising the crystalline modification I of metconazole as hereinbefore described and at least one auxiliary.
  • the composition may comprise the crystalline modification I of metconazole in any suitable amount to provide the desired fungicidal effects.
  • the amount of the crystalline modification I of metconazole in the composition is less than 90%by weight of the composition, more preferably less than 75%by weight of the composition, still more preferably less than 60%by weight of the composition, more preferably still in many embodiments less than 50%by weight of the composition.
  • the amount of the crystalline modification I of metconazole in the composition is greater than 0.1%by weight of the composition, more preferably greater than 1%by weight of the composition, still more preferably greater than 5%by weight of the composition, more preferably still in many embodiments greater than 10%by weight of the composition, for example greater than 15%by weight.
  • the crystalline modification I of metconazole is present in the composition in an amount of about 40%by weight.
  • metconazole as fungicide is well known in the art and metconazole is used on a commercial scale.
  • the crystalline modification I of metconazole is active in preventing, treating and controlling fungal infestations in plants and plant parts. Techniques of formulating and applying metconazole are known in the art.
  • the crystalline modification I of metconazole can be formulated and applied in analogous manners to those known and employed in the art for metconazole.
  • the crystalline modification I of metconazole may be formulated into any suitable composition.
  • the composition is in the form of a suspension concentrate (SC) , an oil dispersion (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) or water-dispersible granules (WG) .
  • SC suspension concentrate
  • OD oil dispersion
  • SG water-soluble granules
  • DC dispersible concentrate
  • EC emulsifiable concentrate
  • emulsion seed dressing emulsion seed dressing
  • GR granules
  • MG microgranules
  • SE suspoemulsion
  • WG water-dispersible granules
  • the composition is in the form of a
  • the crystalline modification I of metconazole formulations may be prepared using techniques known in the art, for example, by extending the crystalline modification I of metconazole with water, solvents and carriers, using, if appropriate, emulsifiers and/or dispersants, and/or other auxiliaries. These formulations may be prepared in a known manner by mixing the crystalline modification I of metconazole with at least one customary additive, for example, wetting agents, dispersants, thickening agent, anti-freezing agents, biocide and any necessary adjuvants and other formulation ingredients.
  • customary additive for example, wetting agents, dispersants, thickening agent, anti-freezing agents, biocide and any necessary adjuvants and other formulation ingredients.
  • Wetting agents include, but are not limited to, alkyl sulfosuccinates, laureates, alkyl sulfates, phosphate esters, acetylenic diols, ethoxyfluornated alcohols, ethoxylated silicones, alkyl phenol ethoxylates, benzene sulfonates, alkyl-substituted benzene sulfonates, alkyl ⁇ -olefin sulfonates, naphthalene sulfonates, alkyl-substituted naphthalene sulfonates, condensates of naphthalene sulfonates and alkyl-substituted naphthalene sulfonates with formaldehyde, and alcohol ethoxylates. Alkyl naphthalene sulphonates, sodium salts are particularly useful for the composition of the invention.
  • Dispersants may be a non-ionic dispersing agent or an anionic dispersing agent.
  • Suitable non-ionic dispersing agents for use in the stabilizing component of the concentrate of the present invention are known in the art and are commercially available.
  • the non-ionic dispersing agent is preferably an ethoxylated non-ionic dispersing agent, in particular polytheyleneoxide-polypropyleneoxide block-copolymers. Such compounds are available commercially, for example available from BASF A.G.
  • the non-ionic dispersing agent may be a polyoxyethylene fatty acid or polyoxyethylene alcohol.
  • such compounds are known in the art and can be prepared by the alkoxylation of fatty acids, alcohols or alkylphenols having from 9 to 24 carbon atoms, more preferably from 12 to 22 carbon atoms, in particular from 14 to 20 carbon atoms.
  • the alkoxylation is preferably carried out using ethylene oxide.
  • the aliphatic moieties of the fatty acids and alcohols may be straight chained or branched chain.
  • Particularly preferred compounds of this class are alkylethoxylates, alkylarylethoxylates and alkyloxyethoxylates, for example available from Clariant GmbH, and available from Clariant GmbH.
  • Suitable anionic dispersing agents for use in the stabilizing component of the concentrate of the present invention are known in the art and are commercially available.
  • the anionic dispersing agent is preferably a sulfonate, sulphate or phosphate of ammonia, an alkali metal or alkaline earth metal, in particular an alkylnaphthalene sulfonic acid formaldehyde condensate, tristyrylphenols or distyrylphenols.
  • Such compounds are available commercially, for example D425, available from Akzo-Nobel, and available from Rhodia Chemical Company.
  • 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. Alkylpolyvinylpyrrolidones are particularly useful for the composition of the invention
  • Suitable anti-freezing agents are urea, glycerine, liquid polyols, for example ethylene glycol, propylene glycol or glycerol.
  • the amount of anti-freezing 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.
  • formulation ingredients can also be used in the present invention, such as dyes, anti-foaming agents, drying agents, and the like.
  • the crystalline modification I of metconazole may be formulated together with inhibitors which reduce degradation of the active compound after their application in the environment of the plant, on the surface of plant parts or in plant tissues. These ingredients are known to one skilled in the art and are commercially available.
  • the present invention further provides a method for preventing, treating and/or controlling fungal infestation of a plant, comprising applying to the plant, plant parts, or the surroundings of the plant, a fungicidally effective amount of crystalline modification I of metconazole as hereinbefore described, or a composition as hereinbefore described.
  • the present invention provides the use of the crystalline modification I of metconazole as hereinbefore described, or a composition as hereinbefore described, for preventing, treating and/or controlling fungal infestations in plants and/or plant parts.
  • the crystalline modification I of metconazole can be employed 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.
  • 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.
  • Such other compounds and agents may be included in the same composition as the crystalline modification I of metconazole or employed in the form of one or more separate compositions.
  • Preferred mixing partners of the crystalline modification I of metconazole include pyraclostrobin, picoxystrobin, prothioconazole, cyproconazole, azoxystrobin, tebuconazole, difenoconazole, boscalid, dimethomorph, chlorothalonil, bromuconazole, diniconazole, epoxiconazole, fenbuconazole, fuquinconazole, fusilazole, hexaconazole, prochloraz, propiconazole, tetraconazole, trifumizol, futriafol, myclobutanil, kresomix-methyl, dimoxystrobin, benomyl, carbendazim, debacarb, fuberidazole, thiabendazole, thiophanate-methyl, benalaxyl, ofurace, metalaxyl, furalaxyl, oxadix
  • Particularly preferred mixing partners are pyraclostrobin, picoxystrobin, azoxystrobin, difenoconazole, prothioconazole, boscalid, dimethomorph, chlorothalonil and mixtures thereof.
  • plants and plant parts may be treated with the crystalline modification I of metconazole in accordance with the present invention.
  • 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 may 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 shoots, leaves, needles, stalks, stems, flowers, fruit bodies, fruits, seeds, roots, tubers and rhizomes.
  • Harvested materials, and vegetative and generative propagation materials for example, cuttings, tubers, meristem tissue, rhizomes, offsets, seeds, single and multiple plant cells and any other plant tissues, are also considered as being plant parts.
  • references to properties are, unless stated otherwise, to properties measured under ambient conditions, that is at atmospheric pressure and at a temperature of about 20°C.
  • 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.
  • Treatment according to the invention of the plants and plant parts with the compositions or formulations of the invention may be carried out directly or by allowing the compositions or formulations to act on their surroundings, habitat or storage space by the customary treatment methods.
  • 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.
  • Metconazole which is an active ingredient of the fungicidal composition of the invention, is known to be effective against a range of fungi, such as brown rust, yellow rust, Septoria leaf spot and Fusarium.
  • the benefits of the present invention are seen most when the fungicidal composition is applied to prevent, treat and control fungal infestation in growing crops of useful plants: such as cereals, rape, soybean, rice, vine, fruit and vegetable.
  • Precipitation 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.
  • FIG. 1 is an X-ray powder diffractogram (X-RPD) of a crystalline modification I of metconazole;
  • FIG. 2 is an infrared (IR) spectrum of a crystalline modification I of metconazole.
  • FIG. 3 is a differential scanning calorimetry (DSC) thermogram of a crystalline modification I of metconazole.
  • the IR spectrum was measured with the resolution of 4 cm -1 and with the number of scans being 16 for the crystallized samples.
  • the crystalline modification I of metconazole can be identified by its characteristic functional group vibration peaks at wavenumbers (cm -1 , ⁇ 0.2%) of one or more of 3337, 2963, 2871, 1508, 1492, 1425, 1406, 1385, 1271, 1137 and 1013 cm -1 as shown in Figure 2.
  • Example 1 Preparation of amorphous metconazole in accordance with the disclosure of EP 0329397 (Example 1)
  • the oily material was purified with column chromatography using silica gel. 4.37 g of the target compound, 5- (4-chlorobenzyl) -2, 2-dimethyl-1- (1H-1, 2, 4-triazol-1-ylmethyl) cyclopentanol (metconazole) was obtained.
  • reaction sequence may be illustrated as follows:
  • the X-ray powder diffraction pattern of the resulting metconazole product has no significant signals, which indicates the metconazole product prepared in accordance with the disclosure of Example 1 of EP 0329397 is amorphous.
  • Example 2 4 g of the metconazole sample prepared in Example 1 was placed in a 3-neck round bottom flask along with 25 mL of xylene and the resulting slurry was heated to 65°C to get a homogeneous solution. The insoluble particles, if any, were filtered and the solution was slowly cooled to ambient temperature. Fine crystals were formed during the cooling and the mixture was stirred at ambient temperature for 2 hours.
  • the slurry was filtered and washed with 3 mL of xylene.
  • the filtered crystals were dried under vacuum at 40°C in order to remove the xylene traces from the crystalline product.
  • the crystalline product thus obtained had a purity of 98%and the yield was found to be about 90%.
  • the crystals were analyzed by X-RPD, IR spectrometry and DSC and found to be a crystalline modification I of metconazole having the characteristics shown in Figure 1, Figure 2 and Figure 3, respectively.
  • the IR spectrum of the crystalline metconazole exhibited the functional group characteristic vibration peaks at wavenumbers of one or more of 3337, 2963, 2871, 1508, 1492, 1425, 1406, 1385, 1271, 1137 and 1013 cm -1 as shown in Figure 2.
  • the DSC thermogram of the crystalline metconazole exhibited an endothermic melting peak maximum at 113.3 °C as shown in Figure 3.
  • Example 2 4 g of the metconazole sample prepared in Example 1 was placed in a 3-neck round bottom flask along with 30 mL of methyl t-butyl ether and the resulting slurry was heated to 40°C to get a homogeneous solution. The insoluble particles, if any, were filtered and the solution was slowly cooled to ambient temperature. Fine crystals were formed during the cooling and the mixture was stirred at ambient temperature for 2 hours.
  • the crystalline product thus obtained had a purity of 99%and the yield was found to be about 88%. Metconazole crystalline modification I was obtained.
  • compositions of Examples 4 to 6 and other comparative examples were diluted with water with a dilution factor of 50 and their residue was compared by passing through a wet sieve of 325 mesh (44 ⁇ m openings) . The residue deposit on the sieve was observed.
  • Table 5 The results are set out in Table 5 below.
  • the further comparative examples employed crystalline forms of metconazole prepared by crystallization from solution in each of methylcyclohexane, cyclohexane, tetrahydrofuran and dioxane.

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  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Agronomy & Crop Science (AREA)
  • Pest Control & Pesticides (AREA)
  • Plant Pathology (AREA)
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  • Engineering & Computer Science (AREA)
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  • Agricultural Chemicals And Associated Chemicals (AREA)

Abstract

L'invention concerne une modification cristalline I de 5- (4-chlorobenzyl) -2, 2-diméthyl-1-(1H -1, 2, 4-triazol-1-ylméthyl) cyclopentanol (metconazole). La modification cristalline est caractérisée, par exemple en ce qu'elle présente au moins 3 des réflexes suivants, dans n'importe quelle combinaison, en tant que 2θ ± 0,2 degré dans un diffractogramme de rayons X sur poudre (X-RPD) enregistré à l'aide d'un rayonnement Cu-Kα à 25 °C : 2θ = 10,3 ± 0,2 (1) 2θ = 15,8 ± 0,2 (4) 2θ = 20,6 ± 0,2 (5) 2θ = 22,2 ± 0,2 (6) 2θ = 23,3 ± 0,2 (7). L'invention concerne également un procédé de préparation de la modification cristalline, des compositions comprenant la modification cristalline et son utilisation dans la lutte contre des infestations fongiques.
EP19914791.9A 2019-02-11 2019-11-21 Nouvelle forme de metconazole, son procédé de préparation et son utilisation Withdrawn EP3924346A4 (fr)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
GB1901847.2A GB2581208B (en) 2019-02-11 2019-02-11 A novel form of metconazole, a process for its preperation and use of the same
PCT/CN2019/119925 WO2020164287A1 (fr) 2019-02-11 2019-11-21 Nouvelle forme de metconazole, son procédé de préparation et son utilisation

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Publication Number Publication Date
EP3924346A1 true EP3924346A1 (fr) 2021-12-22
EP3924346A4 EP3924346A4 (fr) 2022-12-21

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JPH0762001B2 (ja) * 1988-02-16 1995-07-05 呉羽化学工業株式会社 アゾリルメチルシクロアルカノール誘導体の製造法
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GB201901847D0 (en) 2019-04-03
EP3924346A4 (fr) 2022-12-21

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