CN115244027A - Novel forms of metrafenone, process for their preparation and their use - Google Patents
Novel forms of metrafenone, process for their preparation and their use Download PDFInfo
- Publication number
- CN115244027A CN115244027A CN202180018590.9A CN202180018590A CN115244027A CN 115244027 A CN115244027 A CN 115244027A CN 202180018590 A CN202180018590 A CN 202180018590A CN 115244027 A CN115244027 A CN 115244027A
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- CN
- China
- Prior art keywords
- metrafenone
- crystalline
- crystalline modification
- modification
- solvent system
- Prior art date
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- 239000005810 Metrafenone Substances 0.000 title claims abstract description 169
- 238000000034 method Methods 0.000 title claims abstract description 44
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- BZLVMXJERCGZMT-UHFFFAOYSA-N Methyl tert-butyl ether Chemical compound COC(C)(C)C BZLVMXJERCGZMT-UHFFFAOYSA-N 0.000 claims description 14
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- A—HUMAN NECESSITIES
- A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
- A01P—BIOCIDAL, PEST REPELLANT, PEST ATTRACTANT OR PLANT GROWTH REGULATORY ACTIVITY OF CHEMICAL COMPOUNDS OR PREPARATIONS
- A01P3/00—Fungicides
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- 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
- A01N35/00—Biocides, pest repellants or attractants, or plant growth regulators containing organic compounds containing a carbon atom having two bonds to hetero atoms with at the most one bond to halogen, e.g. aldehyde radical
- A01N35/04—Biocides, pest repellants or attractants, or plant growth regulators containing organic compounds containing a carbon atom having two bonds to hetero atoms with at the most one bond to halogen, e.g. aldehyde radical containing aldehyde or keto groups, or thio analogues thereof, directly attached to an aromatic ring system, e.g. acetophenone; Derivatives thereof, e.g. acetals
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- Agronomy & Crop Science (AREA)
- General Health & Medical Sciences (AREA)
- Dentistry (AREA)
- Health & Medical Sciences (AREA)
- General Chemical & Material Sciences (AREA)
- Microbiology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Chemical & Material Sciences (AREA)
- Pest Control & Pesticides (AREA)
- Mycology (AREA)
- Agricultural Chemicals And Associated Chemicals (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Abstract
A crystalline modification I of (3-bromo-6-methoxy-2-methylphenyl) (2, 3, 4-trimethoxy-6-methylphenyl) methanone (metrafenone) is provided. Also provided are processes for preparing the crystal modification I, compositions comprising the crystal modification I and their use in controlling fungal infestation.
Description
Cross Reference to Related Applications
The present application claims priority from GB 2003282.7 entitled "novel forms of metrafenone, methods for its preparation and its use" filed on 6/10/2020, the disclosure of which is incorporated herein by reference.
Technical Field
The present invention relates to novel forms of (3-bromo-6-methoxy-2-methylphenyl) (2, 3, 4-trimethoxy-6-methylphenyl) methanone (metrafenone), particularly novel crystalline forms of metrafenone. The invention further relates to a process for the preparation of the novel forms of metrafenone. Still further, the present invention relates to the use of the novel forms of metrafenone in agrochemical formulations and in controlling fungal infestation.
Background
3-bromo-6-methoxy-2-methylphenyl- (2, 3, 4-trimethoxy-6-methylphenyl) methanone, commonly known as metrafenone, belongs to the chemical class of benzophenones and exhibits broad spectrum fungicidal activity. The molecular formula of the metrafenone is C 19 H 21 BrO 5 And has the following structure:
metrafenone is a new fungicide and is particularly useful for controlling powdery mildew oomycetes produced by leptospirillum viniferum (Uncinula necator) in all commercial varieties of grapevines. Metrafenone is used with excellent selectivity for the control and prevention of downy mildew and late blight and can be applied to inhibit all stages of fungal development.
The biochemical mode of action of metrafenone is unknown. However, it has been proposed that the mode of action of metrafenone is through the disruption of actin, a structural protein that regulates cell division and function. According to morphological observations, metrafenone appears to inhibit the growth of mycelium on the leaf surface, leaf penetration and the formation of haustoria and spores. Opalski et al's ' Metrafenone: students on the mode of action of a novel cereal powder variant ', pest Management Science, volume 62, issue 5, may 2006, pages 393 to 401[ Metrafenone: the study of the mode of action of novel cereal powdery mildew fungicides, science of pest management, vol.62, phase 5, month 5 2006, pages 393 to 401 discusses the mode of action of metrafenone.
Metrafenone may be used to control and prevent infections caused by a variety of powdery mildews (Podosphaera xanthothia) or powdery mildews (Erysiphe necator) on a range of crops, including grapes, potatoes, tomatoes and other solanaceae, cucurbits, leafy and fruiting vegetables, corm vegetables, brassica plants, hops and ornamentals.
EP0897904 relates to certain benzophenone compounds and discloses compounds having the following general formula (I).
The compounds of formula (I) include metrafenone.
EP0897904 discloses a process for the production of benzophenones, including 2-methoxybenzophenone derivatives, having the general formula (I). Metrafenone is included in the derivatives that can be formed by the methods disclosed in EP 0897904.
Commercially available metrafenone is usually manufactured by the process described in EP0897904 and is present in amorphous form with a melting point in the range from 89 ℃ to 91 ℃.
Reference herein to "residue" is to a trace amount of a compound remaining in or on the soil after a specified time. Excess fungicide or its harmful derivatives remaining in the soil may pose a threat to the environment. This is particularly true for fungicidal compounds having a long half-life. In particular, fungicide residues can reduce the microbiological and biochemical activity of the soil and lead to a reduction in yield. Fungicide residues can also contaminate groundwater. In view of this, proper management of the fungicide residues is very important in order to maintain the optimum functioning of the soil ecosystem and to preserve our environment.
It has been found that commercially available metrafenone, when used to control fungal infestation, for example as outlined above, produces a residue in the soil after field application. This commercially available form of metrafenone has a significant half-life in soil of over 120 days after application. In particular, the persistence of metrafenone in soil is discussed in the following documents: "compatibility reporting the peer review of the pesticide risk assessment of the active sub-pesticide refined: 13 January 2006", EFSA Scientific Report (2006) 58, pages 1 to 72[ Conclusion of peer review on pesticide risk assessment of the finally determined active substance metrafenone, 13.2006, EFSA Scientific Report (2006) 58, pages 1 to 72]. It was shown that metrafenone has a high persistence in the soil under aerobic conditions (DT at 20 ℃ in the laboratory) 50 182 to 365 days). Further study results are reported, where degradation proceeds at a slower rate, with 82% of the AR remaining parental after 120 days (extrapolated DT) 50 693 days). Thus, metrafenone remains active in the soil for a considerable period of time after application to the plant or locus being treated.
Therefore, there is a need for a method to reduce the length of time that metrafenone residues remain active in the soil after application to plants and their locus.
Disclosure of Invention
A new crystalline form of metrafenone, herein referred to as "crystal modification I", has now been found. Most advantageously, it has been found that the amount of metrafenone residues present in the soil is significantly reduced after application of metrafenone in this new crystalline modification I. Herein, the term "crystal modification" has the same meaning as the term "crystal form".
Another problem in the prior art is the increasing resistance of fungal species to fungicides. It has also been found that the fungal species have a significantly reduced resistance to metrafenone in this new crystalline modification I.
In a first aspect, the present invention provides (3-bromo-6-methoxy-2-methylphenyl) (2, 3, 4-trimethoxy-6-methylphenyl) methanone (metrafenone) crystal modification I exhibiting, in any combination, at least 3, more preferably 4,5, 6, 7, 8, 9, 10, 11 or more of the following reflections as 2 Θ ± 0.2 degrees in an X-ray powder diffraction pattern (X-RPD) recorded at 25 ℃ using Cu-K α radiation:
2θ=8.6±0.2 (1)
2θ=10.0±0.2 (2)
2θ=10.6±0.2 (3)
2θ=11.5±0.2 (4)
2θ=12.2±0.2 (5)
2θ=15.6±0.2 (6)
2θ=17.3±0.2 (7)
2θ=20.5±0.2 (8)
2θ=21.7±0.2 (9)
2θ=22.6±0.2 (10)
2θ=25.0±0.2 (11)
2θ=25.6±0.2 (12)
2θ=25.7±0.2 (13)
2θ=27.3±0.2 (14)
2θ=28.4±0.2 (15)
2θ=28.9±0.2 (16)
2θ=32.1±0.2 (17)。
in a preferred embodiment, the metrafenone crystalline modification I according to the first aspect of the invention exhibits, in any combination, at least 3, more preferably 4,5, 6, 7, 8, 9, 10, 11 or more, still more preferably all, of the reflections from:
2θ=8.6±0.2 (1)
2θ=10.0±0.2 (2)
2θ=10.6±0.2 (3)
2θ=11.5±0.2 (4)
2θ=12.2±0.2 (5)
2θ=15.6±0.2 (6)
2θ=17.3±0.2 (7)
2θ=20.5±0.2 (8)
2θ=21.7±0.2 (9)
2θ=22.6±0.2 (10)
2θ=25.0±0.2 (11)
2θ=27.3±0.2 (14)
2θ=32.1±0.2 (17)。
in a preferred embodiment, the metrafenone crystalline modification I according to the first aspect of the invention exhibits the following reflection:
2θ=8.6±0.2 (1)
2θ=11.5±0.2 (4)
2θ=25.0±0.2 (11)。
in a preferred embodiment, metrafenone crystalline modification I according to the first aspect of the invention exhibits the following reflection:
2θ=8.6±0.2 (1)
2θ=11.5±0.2 (4)
2θ=22.6±0.2 (10)
2θ=25.0±0.2 (11)。
in a preferred embodiment, the metrafenone crystalline modification I according to the first aspect of the invention exhibits the following reflection:
2θ=8.6±0.2 (1)
2θ=11.5±0.2 (4)
2θ=17.3±0.2 (7)
2θ=20.5±0.2 (8)
2θ=22.6±0.2 (10)
2θ=25.0±0.2 (11)。
in a preferred embodiment, the metrafenone crystalline modification I according to the first aspect of the invention exhibits the following reflection:
2θ=8.6±0.2 (1)
2θ=10.0±0.2 (2)
2θ=11.5±0.2 (4)
2θ=17.3±0.2 (7)
2θ=20.5±0.2 (8)
2θ=22.6±0.2 (10)
2θ=25.0±0.2 (11)。
in a preferred embodiment, the metrafenone crystalline modification I according to the first aspect of the invention exhibits an X-ray powder diffraction pattern substantially as shown in figure 1.
In a second aspect, the present invention provides (3-bromo-6-methoxy-2-methylphenyl) (2, 3, 4-trimethoxy-6-methylphenyl) methanone (metrafenone) crystal modification I, which exhibits the properties at 3386, 3259, 3133, 1660, 1635, 1574, 1527, 1503, 1461, 1436, 1383, 1343, 1300, 1265, 1202, 1077, 1061, 1041,1028, 928, 762, 639 and 562cm -1 More preferably 2,3,4, 5, 6, 7 or more, still more preferably the total wave number (cm) -1 ± 0.2%) of the peak characteristic of the functional group oscillation.
In a preferred embodiment, metrafenone crystal modification I according to the second aspect of the invention exhibits an IR spectrum substantially as shown in figure 2.
In a preferred embodiment, the metrafenone crystalline modification I of the second aspect of the invention further comprises the features described above characterizing the metrafenone crystalline form of the first aspect of the invention.
In a third aspect, the present invention provides a metrafenone crystalline modification I exhibiting a Differential Scanning Calorimetry (DSC) curve with an endothermic melting peak with an onset at 97.7 ℃ and a peak maximum at 99.5 ℃, further optionally with a melting enthalpy of 68.38J/g.
In a preferred embodiment, the crystalline modification according to the third aspect of the present invention exhibits a DSC thermogram substantially as shown in figure 3.
In a preferred embodiment, the crystalline form of metrafenone according to the third aspect of the invention further comprises the features described hereinbefore which characterize the crystalline form of metrafenone according to one or both of the first and second aspects of the invention.
It has been found that the metrafenone crystalline modification I exhibits a significant improvement in residue control in soil, in particular resulting in a significant reduction of metrafenone residues in soil after application, which significantly increases environmental safety.
In another aspect, the present invention provides a process for the preparation of metrafenone crystalline modification I comprising the steps of:
i) Dissolving metrafenone in a solvent system comprising one or more solvents;
ii) precipitating the dissolved metrafenone from solution in the solvent system to obtain the metrafenone crystalline modification I; and
iii) Isolating the precipitated crystalline modification I of metrafenone.
The metrafenone starting material used in step i) of the process may be any suitable metrafenone material. In one embodiment, the metrafenone used in step I) of the process is a metrafenone crystal modification different from the metrafenone crystal modification I, e.g. a known crystal form of metrafenone, e.g. commercially available metrafenone. Methods for preparing suitable metrafenone starting materials are known in the art. Commercial metrafenone can be manufactured and obtained on a commercial scale. A particularly suitable process for preparing metrafenone for use in step i) of the above process is described in EP 0897904.
As mentioned above, in step i) of the process, metrafenone 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 which yields the crystalline modification I of metrafenone upon crystallization from solution may be used in the solvent system. In a preferred embodiment, the solvent system comprises one or more solvents selected from the group consisting of ethers, aromatic hydrocarbons, and mixtures thereof.
In one embodiment, the solvent system comprises a compound having the formula R-O-R 1 Wherein R and R 1 Independently represent an alkyl group, preferably a lower alkyl group having 1 to 8 carbon atoms, more preferably 1 to 6 carbon atoms, still more preferably 1 to 4 carbon atoms. The alkyl group may beLinear or branched.
In one embodiment, the ether in the solvent system is a glycol ether.
Preferred ethers for use in the solvent system include, for example, methyl tert-butyl ether, ethyl propyl ether, n-butyl ether, anisole, phenetole, cyclohexyl methyl ether, dimethyl ether, diethyl ether, dimethyl glycol, diphenyl ether, di-n-butyl ether, diisobutyl ether, diisoamyl ether, ethylene glycol dimethyl ether, methyl tert-butyl ether, and dichlorodiethyl ether.
Another example of an ether is a polyether, including polyethers of ethylene oxide and/or propylene oxide.
Preferred aromatic hydrocarbon solvents include benzene and alkyl-substituted benzenes, preferably C 1 To C 4 Alkyl-substituted benzene derivatives, with the proviso that in C 1 In the case of alkyl substituents, two or more alkyl substituents are present, more preferably C 1 To C 3 Alkyl-substituted benzene derivatives, such as ethylbenzene, xylene, mesitylene and cymene.
Ligroin and petroleum fractions with a boiling range of 70 ℃ to 190 ℃ are also suitable as solvents.
In a preferred embodiment, the solvent system comprises one or more solvents selected from the group consisting of aromatic hydrocarbons, ethers, and mixtures thereof. Particularly preferred solvents are xylene, methyl tert-butyl ether and mixtures thereof.
In step I) of the process of the present invention, the metrafenone crystalline modification I is prepared by dissolving metrafenone in a solvent system to form a metrafenone solution. The dissolution of metrafenone may be carried out at ambient temperature. Alternatively, the solvent system may be heated, preferably to a temperature at or below the reflux temperature of the solvent system. In one embodiment, the metrafenone solution is prepared at the reflux temperature of the solvent system. The concentration of the metrafenone solution depends on factors such as the solubility of metrafenone in the solvent system used.
The metrafenone solution prepared in step I) of the process is then used for producing the metrafenone crystal modification I. This is achieved by crystallization. Any suitable technique or combination of techniques can be used to crystallize metrafenone crystalline modification I from solution in a solvent system.
For example, the solution may be cooled, e.g., to room temperature or to a temperature of about 0 ℃ to about 20 ℃, to crystallize the desired crystalline form from the solvent.
Alternatively, or in addition, the metrafenone crystalline modification I may be crystallized from solution by concentrating the solution by removing the solvent system. The solvent system may be removed by techniques known in the art, such as evaporation by optionally cooling below the reflux temperature of the solvent system with or without the application of vacuum.
The production of the metrafenone crystal modification I from solution can also be achieved or assisted by: to the solution is added seed crystals, preferably seed crystals of metrafenone, more preferably seed crystals of the desired crystalline form, namely metrafenone crystalline modification I. The addition of seed crystals serves to promote or accelerate crystallization.
The amount of seed crystals added to the metrafenone 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 metrafenone used to prepare the solution, preferably 0.001 to 2.5% by weight, more preferably 0.005 to 0.5% by weight based on the weight of metrafenone used to prepare the solution in step (i). Preferably, if seed crystals are used, the seed crystals are added to the concentrated solution at a temperature below the boiling point of the solvent system.
The crystallization of the metrafenone crystal modification I from the solution formed in step I) can be carried out batchwise, semicontinuously or continuously.
The precipitated crystalline modification I of metrafenone obtained from step ii) of the process may be separated and recovered by solid component separation techniques known in the art, such as filtration, centrifugation and/or decantation.
Thereafter, the isolated solid is washed, preferably one or more times, with a solvent. Preferably, the solvent used in this washing stage consists of or at least comprises: one or more components of the solvent system used for preparing the metrafenone solution in step i) of the process as described above. The washing step is preferably carried out at a temperature of from 0 ℃ to room temperature using a solvent, depending on the solubility of the crystalline metrafenone in the solvent system used, in order to minimize or avoid loss of crystalline material.
In one embodiment of the process of the invention, the metrafenone crystalline modification I is dissolved and recrystallized. The wash liquor and/or solvent system used for crystallization in any process step may be concentrated to obtain solid metrafenone, which may then be recycled for use in step i) of the process.
In another aspect, the present invention provides a metrafenone crystalline modification I obtainable by the process as described above.
In the present invention, it is preferred that the crystalline metrafenone material has a content of metrafenone crystal modification I of at least 97.5% by weight.
In another aspect, the present invention provides a fungicidal composition comprising the metrafenone crystal modification I as described above and at least one auxiliary agent.
The composition may comprise any suitable amount of metrafenone crystalline modification I to provide the desired fungicidal effect. Preferably, the amount of metrafenone crystal modification I in the composition is less than 75% by weight of the composition, more preferably less than 50% by weight of the composition, still more preferably less than 40% by weight of the composition, and still more preferably in many embodiments less than 25% by weight of the composition. Preferably, the amount of metrafenone crystal modification I 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, yet more preferably greater than 10% by weight of the composition in many embodiments, such as greater than 25% by weight. In many embodiments, metrafenone crystalline modification I is present in the composition in an amount of about 50% by weight.
The use of metrafenone as a fungicide is well known in the art and metrafenone is used on a commercial scale. The metrafenone crystalline modification I is active in preventing, treating and controlling fungal infestation in plants and plant parts. Techniques for formulating and administering metrafenone are known in the art. The metrafenone crystalline modification I may be formulated and administered in a manner similar to that known and employed in the art for the known forms of metrafenone.
The metrafenone crystalline modification I may be formulated into any suitable composition. Such formulations and their preparation are known in the art. Preferably, the composition is in the form of: suspension (SC), oil Dispersion (OD), soluble Granules (SG), dispersible Concentrate (DC), emulsifiable Concentrate (EC), emulsion seed coating, suspension seed coating, granules (GR), microgranules (MG), suspoemulsion (SE) or water dispersible granules (WG). In a preferred embodiment, the composition is in the form of a suspending agent (SC).
The preparation containing the crystalline modification I of metrafenone may be prepared using techniques known in the art, for example by expanding the crystalline modification I of metrafenone with water, solvents and carriers, if appropriate with the use of emulsifiers and/or dispersants, and/or other auxiliaries.
The compositions are prepared by combining metrafenone crystalline modification I with one or more agriculturally acceptable adjuvants. The adjuvants used in the compositions and the amounts thereof will depend on the type of formulation and/or the manner in which the end user will administer the formulation. Suitable auxiliaries are the customary formulation auxiliaries or components, such as dispersants, wetting agents, emulsifiers, extenders, carriers, solvents, surfactants, stabilizers, antifoams, antifreeze agents, preservatives, antioxidants, colorants, thickeners, biocides, solid binders and inert fillers. Such adjuvants are known in the art and are commercially available. Their use in the formulation of the compositions of the present invention will be apparent to those of ordinary skill in the art.
The surfactant may be an emulsifier, dispersant or wetting agent of ionic or non-ionic type.
Examples that may be used include, but are not limited to, salts of polyacrylic acids, salts of lignosulfonic acids, salts of benzenesulfonic or naphthalenesulfonic acids, polycondensates of ethylene oxide with fatty alcohols or with fatty acids or with fatty amines, substituted phenols (especially alkylphenols), sulfosuccinate salts, taurine derivatives (especially alkyl taurates) or phosphoric esters of polyethoxylated phenols or alcohols.
Liquid diluents include, but are not limited to, water, N-dimethylamide, dimethylsulfoxide, N-alkylpyrrolidones, ethylene glycol, polypropylene glycol, propylene carbonate, dibasic esters, paraffins, alkylbenzenes, alkylnaphthalenes, glycerol, triacetin, olive oil, castor oil, linseed oil, sesame oil, corn oil, peanut oil, cottonseed oil, soybean oil, rapeseed oil, and coconut oil, ketones (e.g., cyclohexanone, 2-heptanone, isophorone, and 4-hydroxy-4-methyl-2-pentanone), acetates (e.g., hexyl acetate, heptyl acetate, and octyl acetate), and alcohols (e.g., methanol, cyclohexanol, decanol, benzyl alcohol, and tetrahydrofurfuryl alcohol), and mixtures thereof.
The composition may further comprise one or more polymeric stabilizers. Suitable polymeric stabilizers that may be used in the present invention include, but are not limited to, polypropylene, polyisobutylene, polyisoprene, copolymers of mono-and diolefins, polyacrylates, polystyrene, polyvinyl acetate, polyurethanes, or polyamides. Suitable stabilizers are known in the art and are commercially available.
The composition may further comprise one or more defoamers. Suitable anti-foaming agents include those which may be conventionally used in agrochemical compositions for this purpose and which will be apparent to those skilled in the art. Suitable defoamers are known in the art and are commercially available. Particularly preferred defoamers are mixtures of polydimethylsiloxanes and perfluoroalkylphosphonic acids, such as silicone defoamers (e.g., commercially available from GE or Compton group (Compton)). Other examples of antifoaming agents are fatty acids, tallow, and sodium salts.
The composition may further comprise one or more preservatives. Suitable preservatives include those which may be conventionally employed in agrochemical compositions of this type for this purpose and which are likewise well known in the art. Suitable examples that may be mentioned include(commercially available from Bayer AG) and(can be selected fromCommercially available from bayer).
The composition may further comprise one or more antioxidants. Suitable antioxidants are the substances known in the art which can be used in agrochemical compositions generally for this purpose. Such as butylated hydroxytoluene are preferred.
The composition may further comprise one or more solid attachment agents. Such adhesives are known in the art and are commercially available. Suitable solid attachment agents include organic binders, including tackifiers such as cellulose, e.g., substituted cellulose, natural and synthetic polymers in the form of powders, granules, or latexes, and inorganic binders such as gypsum, silica, or cement.
The composition may further comprise one or more inert fillers. Such inert fillers are known in the art and are commercially available. Suitable fillers include, for example, natural ground minerals such as kaolin, alumina, talc, chalk, quartz, attapulgite, montmorillonite, and diatomaceous earth; or synthetic ground minerals such as highly dispersed silicic acid, alumina, silicates, and calcium hydrogenphosphates. Suitable inert fillers for granules include, for example, ground and classified natural minerals (e.g., calcite, marble, pumice, sepiolite, and dolomite), or synthetic granules of inorganic and organic abrasive materials, as well as granules of organic materials (e.g., sawdust, coconut shells, corn cobs, and tobacco stalks). Examples of inert fillers also include sodium tripolyphosphate and sucrose.
The solid diluent may 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 metal phosphates, sulphates 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 silicas and diatomaceous earths, calcium and magnesium silicates, titanium dioxide, aluminum oxide, calcium and zinc oxides and mixtures thereof.
Wetting agents include, but are not limited to: alkyl sulfosuccinates, laurates, alkyl sulfates, phosphates, acetylenic diols, ethoxylated fluorinated alcohols, ethoxylated silicones, alkylphenol ethoxylates, benzenesulfonates, alkyl-substituted benzenesulfonates, alkyl alpha-olefin sulfonates, naphthalene sulfonates, alkyl-substituted naphthalene sulfonates, condensates of naphthalene sulfonates and alkyl-substituted naphthalene sulfonates with formaldehyde, and alcohol ethoxylates, and mixtures thereof. Sodium salts of alkylnaphthalenesulfonic acids are particularly useful in the compositions of the present invention.
The dispersant used in the formulation may be a nonionic dispersant or an anionic dispersant. Suitable nonionic dispersants for the stabilizing component of the concentrates of the present invention are known in the art and are commercially available. The nonionic dispersant is preferably an ethoxylated nonionic dispersant, especially a polyethylene oxide-polypropylene oxide block copolymer. Such compounds are commercially available, for example, from BASF a.g
Alternatively, the non-ionic dispersing agent may be a polyoxyethylene fatty acid or a polyoxyethylene alcohol. Again, such compounds are known in the art and may be prepared by alkoxylation of fatty acids, alcohols or alkylphenols having 9 to 24 carbon atoms, more preferably 12 to 22 carbon atoms, especially 14 to 20 carbon atoms. Alkoxylation is preferably carried out using ethylene oxide. The aliphatic portion of the fatty acids and alcohols may be straight chain or branched. Particularly preferred compounds of this type are alkyl ethoxylates, alkylaryl ethoxylates and alkoxyethoxylates, obtainable, for example, from Clariant GmbHAnd available from Clariant
Suitable anionic dispersants for use in the formulation are known in the art and are commercially available.The anionic dispersants are preferably ammonia, alkali metal or alkaline earth metal sulfonates, sulfates or phosphates, especially alkylnaphthalenesulfonic acid formaldehyde condensates, tristyrylphenol or distyrylphenol. Such compounds are commercially available, for example, from Akzo NobelD425 and those available from Rhodia Chemical Company
Thickeners include, but are not limited to guar gum, pectin, casein, carrageenan, xanthan gum, alginates, methyl cellulose, hydroxyethyl cellulose, hydroxypropyl cellulose, and carboxymethyl cellulose, and mixtures thereof. Synthetic thickeners include the derivatives of the foregoing classes, and also polyvinyl alcohols, polyacrylamides, polyvinyl pyrrolidones, various polyethers, copolymers thereof and polyacrylic acids and salts thereof, and mixtures thereof. Alkyl polyvinylpyrrolidones are particularly useful for the compositions of the invention.
Antifreeze agents are known in the art and are commercially available. Suitable antifreeze agents include urea, glycerol, liquid polyols, such as ethylene glycol, propylene glycol or glycerol. The amount of antifreeze agent is generally from about 1% to about 20% by weight, especially from about 5% to about 10% by weight, based on the total weight of the composition.
Biocides may also be added to the compositions according to the invention. Suitable biocides include isothiazolone-based biocides, for example from the company tornado (LONZA inc.)Or from Sol chemical company (Thor Chemie)RS or from Rohm and Haas company&Haas) ofMK. The amount of biocide is typically 0.01% to 0.04% by weight, based on the total weight of the composition.
Other formulation components may also be used in the present invention such as dyes, desiccants, and the like. These components and their use are known to those skilled in the art.
The present invention further provides a method for preventing, treating and/or controlling fungal infestation in a plant comprising applying to the plant, plant part, or the plant's surroundings a fungicidally effective amount of a metrafenone crystalline variant I as described hereinabove, or a composition as described hereinabove.
In another aspect, the present invention provides the use of a metrafenone crystalline variant I as described above, or a composition as described above, for preventing, treating and/or controlling fungal infestation in plants and/or plant parts.
The metrafenone crystal modification I can be used together with other active compounds (for example insecticides, attractants, bactericides, acaricides, nematicides, fungicides, growth-regulating substances, herbicides, safeners, fertilizers and semiochemicals) or together with plant characteristic-improving agents. Such other compounds and agents may be included in the same composition as the metrafenone crystalline modification I or used in the form of one or more separate compositions.
Preferred compounds of the metrafenone crystal modification I may be epoxiconazole, fenpropimorph, pyraclostrobin, picoxystrobin, prothioconazole, cyproconazole, azoxystrobin, tebuconazole, difenoconazole, boscalid, dimethomorph, chlorothalonil, bromuconazole, diniconazole, epoxiconazole, fenbuconazole, fluquinconazole (fuquinconazole), flusilazole (fusilazole), hexaconazole, prochloraz, propiconazole, tetraconazole, triflumizole (trifumizol), flutriafol (furiazol), myclobutanil, kresoxim-methyl, dimoxystrobin, benomyl, carbendazim, debacarb, fuberidazole (fureidazole), thiabendazole, thiophanate-methyl, benalaxyl, furalaxyl, metalaxyl and mixtures thereof.
Particularly preferred compounds are epoxiconazole and combinations of epoxiconazole and fenpropimorph.
All plants and plant parts can be treated with the crystalline modification I of metrafenone according to the invention. In the present context, plants are 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 transgenic plants and plant cultivars which may or may not be protected by the rights of the plant breeders. Plant parts are to be understood as meaning all above-and underground parts and organs of plants, such as buds, leaves, needles, stalks, stems, flowers, fruit bodies, fruits, seeds, roots, tubers and rhizomes. Harvested material, as well as vegetative and reproductive propagation material, such as cuttings, tubers, meristems, rhizomes, offsets, seeds, single and multiple plant cells and any other plant tissue, is also considered to be a plant part.
Throughout the specification and claims of this specification, the word "comprise" and variations of the word, such as "comprises" and "comprising", mean "including but not limited to", and do not exclude other moieties, additives, components, integers or steps.
Preferred features of each aspect of the invention may be as described in connection with any of the other aspects. Other features of the present invention will become apparent from the following examples. In general, 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, any feature disclosed herein may be replaced by an alternative feature serving the same or similar purpose, unless expressly stated otherwise.
Where upper and lower limits are recited for a property, a range of values bounded by a combination of any upper limit and any lower limit may also be implied.
In the present specification, unless otherwise specified, reference to a characteristic means a characteristic measured under ambient conditions, i.e., at atmospheric pressure and a temperature of about 20 ℃.
As used herein, the term "about" when used in connection with a numerical quantity or range means slightly greater than or slightly less than the numerical quantity or range and, for example, deviates from the numerical quantity or from the end point of the range by ± 10%.
As used herein, "surroundings" refers to the place where a plant is growing, the place where the plant propagation material of a plant is sown, or the place where the plant propagation material of a plant will be sown.
The treatment according to the invention of plants and plant parts with the compositions or preparations according to the invention can be carried out directly or by means of customary treatment methods to make the compositions or preparations work in their surroundings, habitat or storage space. Examples of such conventional treatment methods include dipping, spraying, vaporizing, atomizing, broadcasting, painting (in the case of propagation material) and applying one or more coatings (especially in the case of seeds).
The active ingredient metrafenone of the fungicidal composition of the present invention is known to be effective against a range of fungi such as powdery mildew.
The benefits of the present invention are most apparent when fungicidal compositions are applied to prevent, treat and control fungal infestation in crops of growing useful plants, such as grapes, potatoes, tomatoes, barley, oats, peach, squash, roses, rye, wheat and other Solanaceae (Solanaceae), cucurbits, leafy and fruiting vegetables, bulb vegetables, brassica, hops and ornamentals.
As discussed above, the metrafenone crystalline modification I prepared using a solvent system comprising an aromatic hydrocarbon and/or an ether exhibits a significantly reduced half-life, particularly under aerobic conditions typically present in field soils, resulting in a significant reduction in the residual metrafenone residue in the soil after application.
Thus, in a further aspect, the present invention provides the use of a solvent system comprising a solvent selected from aromatic hydrocarbons, ethers and mixtures thereof for producing a crystalline form of metrafenone having a significantly reduced half-life.
In particular, the half-life of metrafenone may be reduced from 120 days to 7 to 14 days, more preferably 10 to 11 days, under aerobic conditions in soil at ambient conditions. In this regard, the half-life of metrafenone prepared by crystallization from the above solvent system can be reduced by 90% to 95%.
In another aspect, the present invention provides the use of a solvent system comprising a solvent selected from the group consisting of aromatic hydrocarbons, ethers and mixtures thereof for producing a crystalline form of metrafenone which exhibits reduced residue in soil.
Suitable and preferred solvents are discussed above.
Drawings
The various features and aspects of the embodiments of the invention disclosed herein may be more clearly understood by reference to the accompanying drawings, which are intended to be illustrative and explanatory, and not limiting of the scope of the invention, and in which:
FIG. 1 is an X-ray powder diffraction pattern (X-RPD) of the crystal modification I of metrafenone;
FIG. 2 is an Infrared (IR) spectrum of a metrafenone crystal modification I;
FIG. 3 is a Differential Scanning Calorimetry (DSC) thermogram of crystalline modification I of metrafenone; and is
FIG. 4 is an X-ray powder diffraction pattern (X-RPD) of amorphous metrafenone.
Detailed Description
The present invention will now be described by the following examples, and wherein the following measurement techniques have been employed, and these examples are provided for illustrative purposes only, and are not intended to limit the scope of the present disclosure.
All percentages are given in weight percent unless otherwise indicated.
Reference herein to "room temperature" is to a temperature in the range of from 20 ℃ to 25 ℃.
All X-ray powder diffraction patterns were determined using a powder diffractometer at 25 ℃ in reflection geometry using the following acquisition parameters:
x' Pert Pro MPD from PANALYTICAL B.V |
Theta compensation slit and graphite monochromator |
Copper (K-alpha) radiation, 40kV,40mA |
Step length: 0.03 degree 2-theta |
Counting time: 1.0 second |
Maximum peak intensity: 1705 times per second |
Scanning range: 3-60 degrees 2-theta |
At 4cm -1 And 16 scans were measured for the IR spectrum of the crystalline sample. Through which 3386, 3259, 3133, 1660, 1635, 1574, 1527, 1503, 1461, 1436, 1383, 1343, 1300, 1265, 1202, 1077, 1061, 1041,1028, 928, 762, 639 and 562cm as shown in fig. 2 -1 Wave number (cm) of one or more of -1 And + -0.2%) to identify the metrafenone crystal modification I.
All IR spectra were obtained using the following acquisition parameters:
FT-IR spectrometer | Nicolet TM iS 5 |
Dammond ATR unit | Thermo Scientific TM iD5 ATR |
Range of wavelengths | 550-4000cm -1 |
Resolution ratio | 4cm -1 |
Number of scans | 16 |
All DSC thermograms were obtained using the following acquisition parameters:
examples
Example 1: preparation of crystalline metrafenone according to the disclosure of EP0897904 (example 6C)
5-bromo-6-methyl-2-methoxybenzoic acid (24g, 10mmol), 3,4, 5-trimethoxytoluene (1.82g, 10mmol), and P 2 O 5 A mixture of (10.0 g) and dichloromethane (150 mL) was stirred at room temperature for 16 h. Subsequently, dichloromethane was distilled off, and the residue was diluted with ethyl acetate. The organic phase was washed with water and concentrated. The residue was purified by column chromatography (petroleum ether: ethyl acetate, 8And (4) recrystallizing in diisopropyl ether. The solid material was collected by vacuum filtration and washed with cold petroleum ether: diisopropyl ether (1.
The reaction sequence may be as shown below:
as shown in fig. 4, the X-ray powder diffraction pattern of the resulting metrafenone product is free of significant signal, indicating that the metrafenone product prepared according to the disclosure of EP0897904 is amorphous.
Example 2: preparation of metrafenone crystal modification I from xylene
Example 1 was repeated several times and the solid metrafenone obtained was combined. 4g of metrafenone from example 1 was placed in a 3-neck round bottom flask together with 25mL of xylene and the resulting slurry was heated to 65 ℃ to obtain a homogeneous solution. Insoluble particles (if any) were removed by filtration and the solution was slowly cooled to ambient temperature. Fine crystals formed during cooling and the mixture was stirred at ambient temperature for 2 hours.
Thereafter, the slurry was filtered and washed with 3mL of cooled xylene. The filtered crystals were dried at 40 ℃ under vacuum to remove traces of xylene from the crystallized product. The purity of the crystalline product thus obtained was 98%, and the yield was found to be about 90%.
The crystals were analyzed by X-RPD, IR spectroscopy and DSC, and were found to be metrafenone crystal modification I having the characteristics shown in fig. 1, fig. 2 and fig. 3, respectively.
The IR spectrum of the crystalline metrafenone exhibits the spectrum shown in FIG. 2 at 3386, 3259, 3133, 1660, 1635, 1574, 1527, 1503, 1461, 1436, 1383, 1343, 1300, 1265, 1202, 1077, 1061, 1041,1028, 928, 762, 639 and 562cm -1 A characteristic vibrational peak of the functional group at the wavenumber of one or more of.
The DSC thermogram of crystalline metrafenone exhibits an endothermic melting peak maximum at 99.5 ℃, as shown in figure 3.
The X-ray powder diffraction pattern of the metrafenone crystals reveals the reflections in fig. 1 and the values are summarized in table 1 below.
TABLE 1
Example 3: preparation of metrafenone crystalline modification I from methyl tert-butyl ether
A4 g sample of metrafenone prepared in example 1 was placed in a 3-neck round-bottom flask together with 30mL of methyl t-butyl ether, and the resulting slurry was heated to 40 ℃ to obtain a homogeneous solution. Insoluble particles (if any) were removed by filtration and the solution was slowly cooled to ambient temperature. Fine crystals formed during cooling and the mixture was stirred at ambient temperature for 2 hours.
After that, the slurry was filtered and washed with 3mL of methyl t-butyl ether. The filtered crystals were dried at 40 ℃ under vacuum to remove traces of methyl tert-butyl ether from the crystallized product.
The crystalline product thus obtained had a purity of 98% and a yield of about 88% was found. Crystalline modification I of metrafenone was obtained as determined using X-RPD, IR spectroscopy and DSC analysis.
Example 4: preparation of the Suspension Concentrate (SC)
The sample was prepared by uniformly mixing all the components listed in table 2 and grinding with Dyno-Mill (manufactured by Willy a. Bachofen AG) to obtain a suspension.
TABLE 2
Compositions S2 and S3 contain the metrafenone crystal modification I and are thus embodiments of the invention. Composition S1 is a comparative example.
Example 5: testing of residue in soil
140g of soil samples were collected from the field and divided into 14 different pots (6 cm diameter plastic pots). The metrafenone products obtained in examples 1 to 3 and the compositions S1, S2 and S3 prepared in example 4 were added to the soil in two pots, respectively, to provide two replicates in an amount such that the final concentration of metrafenone in the soil in the pots was 50ppm.
In addition, metrafenone prepared by recrystallization from a solvent system containing 15% by weight of ethyl acetate in heptane was also added to the soil in one pot to provide further comparison.
Untreated soil was used as a control.
All pots were kept at ambient temperature of about 20 ℃ in the greenhouse. The soil humidity in the pots was about 60%.
The amount of residual metrafenone in the soil in each pot was determined at regular intervals after treatment as follows:
a 1g soil sample was collected from each pot and added to a 10mL centrifuge tube. Deionized water (1 mL) and acetonitrile (2 mL) were added, and the mixture was subjected to mixing for 3 minutes. Thereafter, sodium chloride (1 g) was added and the resulting mixture was subjected to mixing for an additional 5 minutes. Finally, the tubes were centrifuged at 4000rpm for 5 minutes.
The supernatant was collected and filtered through a 0.2 μm membrane for analysis using chromatography as follows.
All samples were analyzed using UPLC-MS/MS under the following conditions:
the mobile phase is acetonitrile and deionized water containing 0.2 percent of formic acid;
flow rate: 0.3mL/min;
injection volume: 5 mu L of the solution;
column: acquisty UPLC HSS T3 from Waters corporation (Waters) having an inner diameter of 2.1mm, a length of 100mm, and a particle size of 1.8 μm;
the column temperature was 35 ℃.
The retention time of metrafenone in the column was 2.87 minutes.
Gradient of mobile phase:
time (minutes) | Acetonitrile | H 2 O(0.2%HCOOH) |
0 | 10 | 90 |
1.5 | 90 | 10 |
3 | 90 | 10 |
3.1 | 10 | 90 |
4 | 10 | 90 |
50.01 | Stop |
The results are shown in Table 3 below.
TABLE 3
As can be seen from the data in table 3, metrafenone (S1) prepared according to the known method of the prior art (example 1) and present in the suspension comprising it remained in the soil in significant amounts after 7 days, still remaining in significant amounts after 130 days. Similar results were obtained using crystalline metrafenone prepared using ethyl acetate/heptane as solvent.
In contrast, the metrafenone crystal modification I (examples 2 and 3) and the compositions containing it (S2 and S3) resulted in a significant reduction of the metrafenone residues present in the soil after only 7 days. The data show a significant reduction in the persistence of the metrafenone crystalline modification I compared to prior art metrafenone products.
Notably, the prior art metrafenone products exhibit a half-life in soil of about 120 days. In contrast, the metrafenone crystalline modification I according to the invention exhibits a significantly reduced half-life in soil, in particular from 7 to 14 days, more in particular from 10 to 11 days.
Claims (25)
1. A crystalline modification I of (3-bromo-6-methoxy-2-methylphenyl) (2, 3, 4-trimethoxy-6-methylphenyl) methanone (metrafenone) exhibiting, in any combination, at least 3 of the following reflections as 2 Θ ± 0.2 degrees in an X-ray powder diffraction pattern (X-RPD) recorded at 25 ℃ using Cu-ka radiation:
2θ=8.6±0.2 (1)
2θ=10.0±0.2 (2)
2θ=10.6±0.2 (3)
2θ=11.5±0.2 (4)
2θ=12.2±0.2 (5)
2θ=15.6±0.2 (6)
2θ=17.3±0.2 (7)
2θ=20.5±0.2 (8)
2θ=21.7±0.2 (9)
2θ=22.6±0.2 (10)
2θ=25.0±0.2 (11)
2θ=25.6±0.2 (12)
2θ=25.7±0.2 (13)
2θ=27.3±0.2 (14)
2θ=28.4±0.2 (15)
2θ=28.9±0.2 (16)
2θ=32.1±0.2 (17)。
2. a metrafenone crystalline modification I according to claim 1, which exhibits at least 3, more preferably 4,5, 6, 7, 8, 9, 10, 11 or more, still more preferably all, of the reflections from:
2θ=8.6±0.2 (1)
2θ=10.0±0.2 (2)
2θ=10.6±0.2 (3)
2θ=11.5±0.2 (4)
2θ=12.2±0.2 (5)
2θ=15.6±0.2 (6)
2θ=17.3±0.2 (7)
2θ=20.5±0.2 (8)
2θ=21.7±0.2 (9)
2θ=22.6±0.2 (10)
2θ=25.0±0.2 (11)
2θ=27.3±0.2 (14)
2θ=32.1±0.2 (17)。
3. crystalline modification I of metrafenone according to claim 1 or 2, characterized by an X-ray powder diffraction pattern substantially as shown in figure 1.
4. A metrafenone crystalline modification I which is represented in 3386, 3259, 3133, 1660, 1635, 1574, 1527, 1503, 1461, 1436, 1383, 1343, 1300, 1265, 1202, 1077, 1061, 1041,1028, 928, 762, 639And 562cm -1 Wave number (cm) of one or more of -1 0.2%) of the IR spectrum with characteristic functional group oscillation peaks.
5. The crystalline modification I of metrafenone according to claim 4, characterized by an IR spectrum substantially as shown in figure 2.
6. A crystalline modification I of metrafenone exhibiting a Differential Scanning Calorimetry (DSC) curve having an endothermic melting peak with an onset at 97.7 ℃ and a peak maximum at 99.5 ℃.
7. The crystalline modification I of metrafenone according to claim 6, characterized by a DSC thermogram substantially as shown in figure 3.
8. Crystalline modification I of metrafenone according to any one of claims 1 to 3, further exhibiting an IR spectrum according to any one of claims 4 or 5, and/or a Differential Scanning Calorimetry (DSC) curve according to any one of claims 6 or 7.
9. A process for the preparation of the crystalline modification I of metrafenone according to any one of claims 1 to 8, which comprises:
i) Dissolving metrafenone in a solvent system comprising one or more solvents;
ii) precipitating the dissolved metrafenone from solution in the solvent system to obtain the metrafenone crystalline modification I; and
iii) Isolating the precipitated crystalline modification I.
10. The method according to claim 9, wherein the metrafenone in step I) is a different crystalline modification of metrafenone than said crystalline modification I of metrafenone.
11. The method of claim 9 or 10, wherein the solvent system comprises a solvent selected from the group consisting of aromatic hydrocarbons, ethers, and mixtures thereof.
12. The method of any one of claims 9 to 11, wherein the solvent system comprises a compound having the general formula R-O-R 1 Wherein R and R 1 Each independently represents a lower alkyl group.
13. The process of claim 11 or 12, wherein the solvent system comprises xylene and/or methyl tert-butyl ether.
14. The method according to any one of claims 9 to 13, wherein step ii) comprises concentrating the solution by removing solvent and/or cooling the solvent system.
15. The method according to any one of claims 9 to 14, wherein in step ii) seed crystals are added to the solution formed in step i).
16. The method of claim 15, wherein the seed crystals comprise the metrafenone crystalline modification I.
17. A crystalline material comprising the metrafenone crystalline modification I prepared by the method according to any one of claims 9 to 16.
18. A composition comprising the metrafenone crystal modification I according to any one of claims 1 to 8 or the crystalline material according to claim 17 and at least one auxiliary.
19. The composition of claim 18, wherein the adjuvant is selected from the group consisting of surfactants, dispersants, wetting agents, emulsifiers, extenders, carriers, solvents, surfactants, stabilizers, defoamers, antifreeze agents, preservatives, antioxidants, colorants, thickeners, biocides, solid attachment agents, inert fillers, and mixtures thereof.
20. The composition of claim 18 or 19, wherein the composition is in the form of: suspending agents (SC), oil Dispersions (OD), soluble Granules (SG), dispersible agents (DC), emulsifiable Concentrates (EC), emulsion seed coatings, suspension seed coatings, granules (GR), microgranules (MG), suspoemulsions (SE) or water dispersible granules (WG).
21. The composition of claim 20, wherein the composition is in the form of a Suspension Concentrate (SC).
22. A method of preventing, treating and/or controlling fungal infestation of plants comprising applying to the plant, plant part or the surroundings of the plant a fungicidally effective amount of the metrafenone crystalline variant I according to any one of claims 1 to 8 or the crystalline material according to claim 17, or the composition according to any one of claims 18 to 21.
23. Use of the crystalline modification I of metrafenone according to any one of claims 1 to 8 or the crystalline material according to claim 17 for preventing, treating and/or controlling fungal infestation in plants or plant parts.
24. Use of a solvent system comprising a solvent selected from the group consisting of aromatic hydrocarbons, ethers, and mixtures thereof, for producing a crystalline form of metrafenone with a significantly reduced half-life.
25. Use of a solvent system comprising a solvent selected from aromatic hydrocarbons, ethers and mixtures thereof for producing a crystalline form of metrafenone which exhibits reduced residue in soil.
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GB2003282.7A GB2592668B (en) | 2020-03-06 | 2020-03-06 | A novel form of metrafenone, a process for its preparation and use of the same |
PCT/CN2021/072802 WO2021175029A1 (en) | 2020-03-06 | 2021-01-20 | A novel form of metrafenone, a process for its preparation and use of the same |
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CN1217317A (en) * | 1997-08-20 | 1999-05-26 | 美国氰胺公司 | Fungus-killing compound of 2-methoxydiphenylketones |
WO2004054953A1 (en) * | 2002-12-13 | 2004-07-01 | Basf Aktiengesellschaft | Method for the production of benzophenones |
Family Cites Families (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
DE69803907T2 (en) * | 1997-08-20 | 2002-06-27 | Basf Ag | Fungicides 2-methoxybenzophenones |
AU2677201A (en) * | 2000-01-13 | 2001-07-24 | Basf Aktiengesellschaft | A process for the preparation of substituted benzophenones |
ES2374856T3 (en) * | 2007-07-06 | 2012-02-22 | Basf Se | CRYSTAL FORM OF [3- (4,5-DIHIDRO-3-ISOXALIL) -2-METHYL-4- (METILSULFONIL) PHENYL] - (5-HYDROXI-1-METHYL-1H-PIRAZOL-4-IL) METANONE. |
-
2020
- 2020-03-06 GB GB2003282.7A patent/GB2592668B/en active Active
-
2021
- 2021-01-20 WO PCT/CN2021/072802 patent/WO2021175029A1/en unknown
- 2021-01-20 CN CN202180018590.9A patent/CN115244027A/en active Pending
- 2021-01-20 EP EP21764047.3A patent/EP4114817A4/en active Pending
Patent Citations (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN1217317A (en) * | 1997-08-20 | 1999-05-26 | 美国氰胺公司 | Fungus-killing compound of 2-methoxydiphenylketones |
WO2004054953A1 (en) * | 2002-12-13 | 2004-07-01 | Basf Aktiengesellschaft | Method for the production of benzophenones |
CN1726178A (en) * | 2002-12-13 | 2006-01-25 | 巴斯福股份公司 | Method for the production of benzophenonen |
Non-Patent Citations (1)
Title |
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陈一芬;万欢;臧佳良;冀亚飞;: "苯菌酮的合成", 合成化学, no. 03, 20 June 2009 (2009-06-20), pages 390 - 391 * |
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EP4114817A1 (en) | 2023-01-11 |
GB202003282D0 (en) | 2020-04-22 |
GB2592668B (en) | 2024-08-14 |
EP4114817A4 (en) | 2024-03-27 |
GB2592668A (en) | 2021-09-08 |
WO2021175029A1 (en) | 2021-09-10 |
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