CN109803970B - Novel form of penoxsulam, process for its preparation and use thereof - Google Patents
Novel form of penoxsulam, process for its preparation and use thereof Download PDFInfo
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- CN109803970B CN109803970B CN201780056601.6A CN201780056601A CN109803970B CN 109803970 B CN109803970 B CN 109803970B CN 201780056601 A CN201780056601 A CN 201780056601A CN 109803970 B CN109803970 B CN 109803970B
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- C07D487/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00
- C07D487/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00 in which the condensed system contains two hetero rings
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- 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
- A01N43/90—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having two or more relevant hetero rings, condensed among themselves or with a common carbocyclic ring system
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Abstract
The present invention describes a crystalline form of penoxsulam of formula (I), a method for preparing the crystal, analysis of the crystal by various analytical methods, and the use of the crystal for preparing a stable agrochemical formulation. The present invention also describes the use of various solvents for the crystalline form preparation conditions.
Description
Cross Reference to Related Applications
The present application claims priority from UK patent application no 1618734.6 entitled "new form of penoxsulam, process for its preparation and its use" filed on UK intellectual property office (UK) at 11/7/2016, the entire contents of which are incorporated herein by reference.
Technical Field
The invention relates to crystalline forms of 3- (2, 2-difluoroethoxy) -N- (5, 8-dimethoxy [1, 2, 4] triazolo [1, 5-c ] pyrimidin-2-yl) -alpha, alpha-trifluorotoluene-2-sulfonamide (penoxsulam), methods for their preparation, and their use in agrochemical formulations.
Background
3- (2, 2-difluoroethoxy) -N- (5, 8-dimethoxy [1, 2, 4] triazolo [1, 5-c ] pyrimidin-2-yl) - α, α, α -trifluorotoluene-2-sulfonamide (penoxsulam) is a herbicide from the triazolopyrimidine sulfonanilide family. It is a selective and highly active herbicide for controlling grasses, broadleaf weeds and sedges on rice. It is applied over the entire field or leaf using a suitably formulated product and is absorbed by the roots or leaves of the plant, respectively.
Penoxsulam has a molecular formula C 16 H 14 F 5 N 5 O 5 And S. It has the chemical structure as follows:
commercially available penoxsulam exists in an amorphous state, which is typically made by the process described in U.S. patent No. 5858924, which is incorporated herein by reference for all purposes. It has been found that amorphous penoxsulam is not suitable for the preparation of compositions or formulations because it is very susceptible to hydrolysis due to its unstable nature. When dissolved or dispersed in water, it undergoes significant hydrolysis. Hydrolysis may even occur during storage, particularly when the compound is exposed to moisture. Thus, the stability of penoxsulam is of high concern for commercially available formulations. Accordingly, there is a need to provide new forms of penoxsulam with increased stability in the formulation.
Disclosure of Invention
To address some or all of the problems with the existing amorphous forms of penoxsulam, new stable crystalline forms of penoxsulam have been prepared.
Aspects of the invention relate to crystalline modifications of 3- (2, 2-difluoroethoxy) -N- (5, 8-dimethoxy [1, 2, 4] triazolo [1, 5-c ] pyrimidin-2-yl) - α, α, α -trifluorotoluene-2-sulfonamide (penoxsulam).
In a first aspect, the present invention provides a new crystalline form of 3- (2, 2-difluoroethoxy) -N- (5, 8-dimethoxy [1, 2, 4] triazolo [1, 5-c ] pyrimidin-2-yl) - α, α, α -trifluorotoluene-2-sulfonamide (penoxsulam), referred to as "crystalline modification I", which exhibits in any combination at least 4 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＝6.19±0.2 (1)
2θ＝10.70±0.2 (2)
2θ＝11.05±0.2 (3)
2θ＝11.47±0.2 (4)
2θ＝17.21±0.2 (5)
2θ＝18.75±0.2 (6)
2θ＝20.28±0.2 (7)
2θ＝23.38±0.2 (8)
2θ＝23.59±0.2 (9)
2θ＝24.50±0.2 (10)
2θ＝24.66±0.2 (11)
2θ＝25.10±0.2 (12)
2θ＝27.57±0.2 (13)
2θ＝29.65±0.2 (14)
in an embodiment, the crystalline modification according to the first aspect of the invention exhibits at least 4, 5, 6, 7, 8 or all of the reflections from:
2θ＝6.19±0.2 (1)
2θ＝11.47±0.2 (4)
2θ＝18.75±0.2 (6)
2θ＝20.28±0.2 (7)
2θ＝24.50±0.2 (10)
2θ＝24.66±0.2 (11)
2θ＝27.57±0.2 (13)
2θ＝29.65±0.2 (14)
in a second aspect, the present invention provides pentafluorosulphur optionally in accordance with the first aspect of the inventionCrystal modification I of oxamine, which is presented at 3360.72, 2925.19, 1637.23 and 1534.23cm -1 (iii) an Infrared (IR) spectrum having a characteristic functional group vibration peak at a wave number (cm-1, ± 0.2%) of (a).
In a third aspect, the present invention provides a crystalline modification I of penoxsulam, optionally according to the first or second aspects of the invention, which exhibits a melting point of 227 ℃ to 232 ℃.
In a fourth aspect, the present invention provides crystalline modification I of penoxsulam, optionally according to any one of the first to third aspects of the invention, which exhibits a Differential Scanning Calorimetry (DSC) curve with an endothermic melting peak starting at 228 ℃ and a peak maximum at 229 ℃, further optionally having a melting enthalpy of 80J/g.
In a fifth aspect, the present invention provides crystalline modification I of penoxsulam, optionally according to any one of the first to fourth aspects of the invention, characterized by an X-ray powder diffraction pattern substantially as shown in figure 2, and/or by an IR spectrum substantially as shown in figure 1, and/or by a DSC thermogram substantially as shown in figure 3.
In a sixth aspect, the present invention provides a crystalline variant I of penoxsulam, optionally according to any of the first to fifth aspects of the invention, obtainable by a process substantially as described in example 2 or 3.
In a seventh aspect, the present invention provides a crystalline modification I of penoxsulam optionally according to any one of the first to sixth aspects of the invention obtainable by the process of the eighth aspect of the invention.
It has been found that the hydrolytic stability of crystalline modification I of penoxsulam of the present invention is significantly increased, which significantly reduces the hydrolysis problems encountered in currently commercially available formulations. In addition, it was found that crystalline modification I of penoxsulam was easier to crush or grind than amorphous penoxsulam prepared according to the disclosure of U.S. patent No. 5,858,924. Furthermore, this crystalline modification I has a lower tendency to hydrolyze after exposure to moisture than the amorphous state described in U.S. patent No. 5,858,924. This allows the preparation of commercial formulations such as Suspension Concentrates (SC), oil-based suspension concentrates (OD), water dispersible granules (WG) and Soluble Granules (SG). The crystalline modification I of penoxsulam gives the formulations thereof the desired long shelf life due to its high hydrolytic stability. Thus, any formulation of the crystalline modification I of penoxsulam which will be disclosed hereinafter may be prepared.
In an eighth aspect, the present invention provides a process for preparing crystalline modification I of penoxsulam comprising the steps of:
i) dissolving penoxsulam in a solvent or a mixture of solvents;
ii) precipitating the dissolved compound as crystalline modification I of penoxsulam; and
iii) isolating the precipitated crystalline modification I.
In an embodiment of the eighth aspect of the present invention, the penoxsulam in step i) is amorphous penoxsulam.
Methods for preparing amorphous penoxsulam are well known in the art. Amorphous penoxsulam is manufactured and available on a commercial scale. A particularly suitable process for the preparation of amorphous penoxsulam is described in US 5858924.
In one embodiment of the eighth aspect of the present invention, the solvent is selected from halogenated hydrocarbons (e.g., chlorobenzene, bromobenzene, dichlorobenzene, chlorotoluene and trichlorobenzene); ethers (e.g., polyethers of ethyl propyl ether, n-butyl ether, anisole, phenetole, cyclohexylmethyl 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, tetrahydrofuran, methyl tetrahydrofuran, dioxane, dichlorodiethyl ether, methyl-tetrahydrofuran, ethylene oxide, and/or propylene oxide); nitrated hydrocarbons (e.g., nitromethane, nitroethane, nitropropane, nitrobenzene, chloronitrobenzene, and o-nitrotoluene); aliphatic, alicyclic or aromatic hydrocarbons (e.g., pentane, n-hexane, n-heptane, n-octane, nonane); cymene; a petroleum fraction having a boiling range of from 70 ℃ to 190 ℃; cyclohexane; methylcyclohexane; petroleum ether; light petroleum oil; octane; benzene; toluene and xylene; esters (e.g., malonic ester, n-butyl acetate (n-butyl acetate), methyl acetate, ethyl acetate, isobutyl acetate, dimethyl carbonate, diethyl carbonate, dibutyl carbonate, and ethylene carbonate); and aliphatic alcohols (e.g., methanol, isopropanol, ethanol, n-propanol, isopropanol, n-butanol, and t-amyl alcohol); mesitylene; diethyl ketone; methyl ethyl ketone and mixtures thereof.
In an embodiment of the eighth aspect of the present invention, the solvent is selected from the group consisting of nitrobenzene, toluene, xylene, benzene, chlorobenzene, dichlorobenzene, ethylbenzene, trifluorotoluene, mesitylene, ether, methyl ethyl ketone.
In an embodiment of the eighth aspect of the present invention, the solvent is selected from methyl ethyl ketone or xylene or a mixture thereof.
According to an embodiment of the eighth aspect of the present invention, crystalline modification I of penoxsulam is prepared by: dissolving amorphous penoxsulam in a solvent or solvent mixture into a concentrated solution by heating from ambient temperature to or below the reflux temperature of the solvent or solvent mixture. Optionally, the concentrated solution may be prepared at the reflux temperature of the solvent. The concentration of the solution depends on the solubility of penoxsulam in the corresponding solvent or solvent mixture.
In one embodiment of the eighth aspect of the present invention, the concentrated homogeneous solution thus prepared in step (i) is cooled to room temperature or a temperature of about 0 ℃ to 20 ℃ to crystallize the desired crystalline form from the solvent. Crystalline modification I of penoxsulam can also be crystallized by concentrating the homogeneous solution by removing the solvent or the solvent mixture to an amount with or without the application of vacuum and cooling to below the reflux temperature of the solvent or the solvent mixture.
In an embodiment of the eighth aspect of the present invention, crystalline modification I of penoxsulam may also be produced by adding seed crystals of the desired crystalline form, which may promote or accelerate crystallization, to the solution prepared in step (I) during crystallization.
The amount of seed crystals added to the concentrated solution in step (i) is typically from 0.001% to 10% by weight, optionally from 0.001% to 2.5% by weight, further optionally from 0.005% to 0.5% by weight, based on the weight of penoxsulam used to prepare the concentrated solution in step (i). Optionally, seed crystals are added to the concentrated solution at a temperature below the boiling point of the corresponding solvent or solvent mixture.
In one embodiment of the eighth aspect of the present invention, the precipitated crystalline modification I of penoxsulam obtained from step (ii) is separated from the solution by common solid component separation techniques, such as filtration, centrifugation or decantation. The isolated solid is then washed one or more times with a solvent. Optionally, as described above, the solvent used in the washing stage consists of one or more components of the solvent or solvent mixture used to prepare the concentrated solution in step (i). Methyl ethyl ketone and xylene are particularly suitable solvents for washing the recovered penoxsulam solids. The washing is usually carried out between room temperature and 0 ℃ using the corresponding solvent or solvent mixture, the temperature depending on the solubility of the crystals in order to avoid as far as possible a loss of crystals in the corresponding washing solvent.
In one embodiment of the eighth aspect of the present invention, crystalline modification I of penoxsulam is dissolved and recrystallized. The wash liquor and/or crystallization solvent in any of the processes can be concentrated to yield a solid penoxsulam that can be recycled.
In a ninth aspect, the present invention provides a crystalline modification I of penoxsulam obtained according to the eighth aspect of the invention, having a crystalline penoxsulam content of at least 98% by weight.
In a tenth aspect, the present invention provides a composition comprising the crystalline modification I of penoxsulam according to any one of the first to seventh and ninth aspects of the invention and at least one adjuvant.
In an eleventh aspect, the present invention provides the use of a crystalline modification I of penoxsulam according to any one of the first to seventh and ninth aspects of the present invention, or a composition according to the tenth aspect of the present invention, for weed control.
In an embodiment of the tenth aspect of the invention, the amount of crystalline modification I of penoxsulam is less than 75% by weight of the composition, optionally less than 50% by weight of the composition, further optionally less than 30% by weight of the composition, still further optionally about 10% to 25% by weight of the composition.
The use of amorphous penoxsulam as a herbicide is known in the art and is used on a commercial scale. It has been found that crystalline modification I of penoxsulam is also effective in controlling undesirable plant growth (such as weeds). Thus, the formulation and application techniques known in the art for penoxsulam to amorphous penoxsulam (such as disclosed in the prior art documents discussed above) can also be applied in a similar manner to penoxsulam in crystalline modification I of the present invention.
Accordingly, the present invention provides a herbicidal composition comprising penoxsulam in crystalline variant I as defined above.
In addition, the present invention provides a method for preparing a composition for controlling undesired plants (such as weeds) using crystalline modification I of penoxsulam.
The present invention also provides a method for controlling undesired plant growth, which comprises applying to a plant, plant part or the environment surrounding the plant a herbicidally effective amount of a crystalline variant I of penoxsulam according to any of the first to seventh and ninth aspects of the invention, or a composition according to the tenth aspect of the invention. Accordingly, this provides for the control of undesired plants in a plant, plant part, and/or its surroundings, comprising applying to the leaves or fruit of the plant, plant part, or surroundings of the plant a herbicidally effective amount of crystalline variant I of penoxsulam.
In one embodiment of the tenth aspect of the invention, the composition is in the form of: suspension Concentrates (SC), oil-based suspension concentrates (OD), Soluble Granules (SG), Dispersible Concentrates (DC), Emulsifiable Concentrates (EC), emulsion seed dressings, suspension seed dressings, Granules (GR), Microgranules (MG), Suspoemulsions (SE) or water dispersible granules (WG). The crystalline modification I of penoxsulam may be included in these conventional formulations in a known manner using suitable adjuvants, carriers and solvents and the like.
In one embodiment of the tenth aspect of the invention, the composition is in the form of an oil-based suspending agent (OD), Soluble Granule (SG) or water dispersible granule (WG).
In one embodiment of the tenth aspect of the invention, the crystalline modification I of penoxsulam may be present in a concentration sufficient to achieve the required dosage when applied to the plant or locus thereof, desirably in a concentration of about 0.1% to 70% by weight of the total mixture. The formulations are prepared, for example, by expanding the crystal modification I of penoxsulam with water, solvent and carrier, if appropriate with the use of emulsifiers and/or dispersants and/or other auxiliaries.
These formulations are prepared by mixing the crystalline modification I of penoxsulam with the usual additives (e.g. one or more of liquid diluents, solid diluents, wetting agents, dispersing agents, thickeners, anti-freeze agents, anti-foaming agents, biocides and any necessary adjuvants and other formulation ingredients).
Liquid diluents include, but are not limited to, water, N-dimethylamide, dimethyl sulfoxide, N-alkylpyrrolidones, ethylene glycol, polypropylene glycol, propylene carbonate, dibasic esters, paraffin, 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 (such as cyclohexanone, 2-heptanone, isophorone, and 4-hydroxy-4-methyl-2-pentanone), acetates (such as hexyl acetate, heptyl acetate, and octyl acetate), alcohols (such as methanol, cyclohexanol, decanol, benzyl, and tetrahydrofurfuryl alcohol), and mixtures thereof.
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, alumina, 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 alkylnaphthalenesulfonates are particularly useful in the compositions of the present invention.
Dispersants include, but are not limited to, sodium, calcium and ammonium salts of lignosulfonic acid (optionally polyethoxylated); sodium and ammonium salts of maleic anhydride copolymers; sodium salts of condensed phenolsulfonic acids; and naphthalene sulfonate-formaldehyde condensates. Of note are compositions containing up to 10% by weight of a dispersant. Lignosulfonates such as sodium lignosulfonate, naphthalene sulfonic acid-formaldehyde condensates such as sodium naphthalene sulfonate formaldehyde polycondensates are particularly useful for the compositions of the present invention.
Thickeners include, but are not limited to: guar gum, pectin, casein, carrageenan, xanthan gum, silica, alginates, methyl cellulose, hydroxyethyl cellulose, hydroxypropyl cellulose, and carboxymethyl cellulose. Synthetic thickeners include the derivatives of the preceding classes, and also polyvinyl alcohols, polyacrylamides, polyvinyl pyrrolidones, various polyethers, copolymers thereof as well as polyacrylic acids and salts thereof. Silica is particularly useful for the compositions of the present invention.
Suitable antifreeze agents are liquid polyols, such as ethylene glycol, propylene glycol or glycerol. The amount of antifreeze 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.
Defoamers include all substances which can generally be used for this purpose in agrochemical compositions. 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 available from GE or Compton (Compton).
Biocides may also be added to the compositions according to the invention. Suitable biocides are those based on isothiazolones, for example from ICI
Or from Sol chemical company (Thor Chemie)
RS or from Rohm and Haas company&Haas) of
MK. The amount of biocide is typically 0.05% to 0.5% by weight, based on the total weight of the composition.
Other formulation ingredients may also be used in the present invention, such as dyes, drying agents, and the like. These ingredients are known to those skilled in the art.
In one embodiment of the tenth aspect of the invention, the crystalline modification I of penoxsulam can be present both as formulations and in the use forms thereof prepared from these formulations, as well as in mixtures with other active compounds (for example insecticides, attractants, disinfectants, bactericides, acaricides, nematicides, fungicides, growth-regulating substances, herbicides, safeners, fertilizers and semiochemicals) or with agents for improving plant performance.
Preferred mixed compatibilisers of the crystal modification I of penoxsulam include cyhalofop-butyl, substituted triazolopyrimidine sulfonamide compounds such as diclosulam, cloransulam-methyl, flumetsulam (flumetsulam). Other herbicides, such as acifluorfen (acifluorfen), bentazon (bentazon), chlorimuron (chlorimuron), clomazone (clomazone), lactofen (lactofen), carfentrazone-methyl (carfentrazone-methyl), furopyrac, fluometuron (fluometuron), fomesafen (fomesafen), imazaquin (imazaquin), imazethapyr (imazethapyr), linuron (lihuron), metribuzin (metribuzin), fluroxypyr (fluazifop), haloxyfop (haloxyfop), glyphosate (glufosinate), glufosinate (glufosinate), 2, 4-D, acetochlor (acetochlor), metolachlor (metolachlor), sulfosulfuron (sulfosulfuron-methyl), sulfosulfuron (sulfosulfuron), sulfosulfuron-methyl (sulfosulfuron), sulfosulfuron (sulfosulfuron-methyl), sulfosulfuron (sulfosulfuron), sulfosulfuron) (sulfofluroxypyr), sulfosulfuron) (sulfofluroxypyr), sulfosulfuron) (sulfofluroxyphos) (sulfosulfuron) (sulfofluroxyphos) (sulfosulfuron), sulfosulfuron) (sulfoflurben) (sulfoflurbenflurbenflurbenflurbenflurbenflurbenfluroxyphos) (sulfosulfuron), sulfosulfuron) (sulfoflurbenflurbenflurbenflur) (sulfosulfuron) (sulfoflurbenflurbenflurbenflurbenflur), sulfosulfuron) (sulfoflurbenflurbenflurbenflurbenflurbenflurbenflurbenflur) (sulfoflur) (sulfosulfuron) (sulfoflur) (sulfoflurbenflur), sulfoflurbenflurbenflur) (sulfoflur), sulfosulfuron) (sulfoflurbenflurbenflurbenflurbenflurbenflur) (sulfoflurbenflurbenflur) (sulfoflur) (sulfosulfuron) (sulfoflur) (sulfoflurbenflur) (sulfoflurbenflurbenflur) (sulfoflurbenflur), sulfoflur), sulfoflurbenflurbenflurbenflurbenflur) (sulfoflur), sulfoflurbenflur) (sulfoflurbenflur), sulfoflurbenflurbenflur) (benflurbenflur, Mesosulfuron-methyl, iodosulfuron-methyl-sodium, rimsulfuron, halosulfuron-methyl, trifloxysulfuron-sodium and chlorsulfuron may also be used. It is generally preferred to use these compounds in combination with other herbicides having similar crop selectivity. It is further generally preferred to apply these herbicides simultaneously as a combined preparation or tank mix. A particularly preferred combination partner is cyhalofop-butyl. All plants and plant parts can be treated according to the invention. In this 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 may be plants which may 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 plant breeders' rights. Plant parts are understood to mean all parts and organs of plants above and below the ground, such as shoots, leaves, needles, stems, stalks, 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, are also included.
The benefits of the present invention are most pronounced when herbicidal compositions are applied to kill weeds in growing crops of useful plants (such as sugarcane, corn, cereals, rice, maize, sorghum, cotton, canola, turf, barley, potato, sweet potato, sunflower, rye, oats, wheat, soybean, sugar beet, tobacco, safflower, tomato, alfalfa, pineapple, cucurbits, cassava, and pasture grasses). In embodiments of the invention, rice and grains are particularly suitable for treatment.
Throughout the description and claims of this specification, the word "comprise" and variations of the word, such as "comprises" and "comprising", means "including but not limited to", and does not exclude other moieties, additives, components, integers or steps. Furthermore, 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 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, unless incompatible with each other, features, integers, properties, compounds, chemical moieties or groups described in connection with a particular aspect, embodiment or example of the invention are to be understood to also apply to any other aspect, embodiment or example described herein. Moreover, any feature disclosed herein may be replaced by alternative features serving the same or similar purpose, unless expressly stated otherwise.
Where upper and lower limits are recited for performance, a range of values defined by any combination of any upper limit and any lower limit may also be implied.
In this specification, unless otherwise indicated, properties refer to properties measured at ambient conditions, i.e. at atmospheric pressure and at a temperature of about 20 ℃.
As used herein, the term "about" when used in conjunction with a numerical quantity or range means slightly greater or slightly less than the numerical quantity or range, plus or minus 10% from the end point of the numerical quantity or range.
The term "crystal" as used herein refers to a solid state form in which molecules are arranged to form a crystal lattice comprising distinguishable unit cells. In general, crystalline materials can be identified, for example, by producing a diffraction peak when subjected to X-ray radiation and/or exhibiting an endothermic melting peak profile with a characteristic peak under Differential Scanning Calorimetry (DSC).
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 of plants and plant parts with the compositions or preparations according to the invention is carried out directly or by allowing the compositions or preparations to act on their surroundings, habitat or storage space in a conventional manner of treatment. Examples of such conventional treatment methods include dipping, spraying, vaporizing, atomizing, broadcasting, brushing (in the case of propagation material) and applying one or more coatings (especially in the case of seeds).
As used herein, "precipitation" refers to the settling of a solid material (precipitate) from a liquid solution (including the settling of a crystalline material), wherein the solid material is present in an amount greater than its solubility in the amount of liquid solution.
All percentages are given in weight percent unless otherwise indicated.
Drawings
The invention may be more clearly understood by reference to the accompanying drawings described below, which are intended to illustrate and explain, without limiting the scope of the invention, and in which:
figure 1 is an Infrared (IR) spectrum of crystalline modification I of penoxsulam;
figure 2 is an X-ray powder diffraction pattern of crystalline modification I of penoxsulam;
figure 3 is a Differential Scanning Calorimetry (DSC) thermogram of crystal modification I of penoxsulam;
figure 4 is an X-ray powder diffraction pattern of amorphous penoxsulam.
Detailed Description
Embodiments of the present invention will now be described by the following examples, and the following measurement techniques have been employed therein, and these examples are for illustrative purposes only, and are not intended to limit the scope of the present disclosure.
All X-ray diffraction patterns were determined using the following acquisition parameters in a reflection geometry at 25 ℃ using a powder diffractometer:
for the crystallized sample, 4cm was used -1 And the IR spectrum was measured with 16 scan times. Crystalline modification I of penoxsulam may be identified by its wavenumber (cm) at 3360.72, 2925.19, 1637.23, and 1534.23 as shown in figure 1 -1 And 0.2%) of the characteristic functional group.
All IR spectra were obtained using the following acquisition parameters:
all DSC thermograms were obtained using the following acquisition parameters:
examples
Example 1: amorphous penoxsulam was prepared according to the disclosure of U.S. patent No. 5,858,924 with the necessary modifications as in example 20
A mixture of 93.8mmol of 2-amino-5, 8-dimethoxy [1, 2, 4] triazolo [1, 5-c ] pyrimidine, 7.6mmol of 2- (2, 2-difluoroethoxy) -6- (trifluoromethyl) benzenesulfonyl chloride and 10mL of anhydrous acetonitrile was prepared and to this mixture was added 0.61mL (7.6mmol) of anhydrous pyridine, 43. mu.L (0.6mmol) of anhydrous dimethyl sulfoxide and a small amount of anhydrous 4A molecular sieve at ambient temperature with stirring and means to remove water from the system. The mixture was stirred for 5 days. An additional 1.0g (3.4mmol) of 2- (2, 2-difluoroethoxy) -6- (trifluoromethyl) benzenesulfonyl chloride and 0.30mL (3.5mmol) of anhydrous pyridine were added and the mixture was stirred for an additional 2 days. An additional 0.30mL (3.5mmol) of anhydrous pyridine was added and stirring was continued for an additional 4 days. The mixture was then diluted with 100mL of dichloromethane and the resulting mixture was washed with 2 × 100mL of 2N aqueous hydrochloric acid, dried over magnesium sulfate and concentrated by evaporation under reduced pressure. The tan solid residue was subjected to silica gel chromatography, eluting with a mixture of dichloromethane and ethanol, to give 54% penoxsulam.
Scheme 1. Synthesis of penoxsulam
As shown in fig. 4, the X-ray powder diffraction pattern of the resulting penoxsulam product did not have a significant signal, indicating that the penoxsulam product prepared according to the disclosure of U.S. patent No. 5,858,924 was amorphous.
Example 2: preparation of crystalline modification I of penoxsulam
Crystallization from methyl ethyl ketone
A 10g sample of amorphous penoxsulam prepared in example 1 was taken and placed in a 3-neck round-bottom flask along with 50mL of methyl ethyl ketone and the resulting slurry was heated to 65 ℃ to give a homogeneous solution. Insoluble particles (if any) were filtered and the solution was slowly cooled to 20-25 ℃. After cooling, fine crystals formed and the resulting heterogeneous mixture was stirred at 20 ℃ for 2 hours. The slurry was then filtered and washed with 3mL of methyl ethyl ketone at 20 ℃. The filtered crystals were dried under vacuum at 40 ℃. The crystals thus obtained had a purity of > 98%, and the yield of the product recovered as crystals was found to be not less than 90%.
The crystals obtained were analyzed by DSC, IR spectroscopy and X-ray powder diffraction, and found to be crystal modification I of penoxsulam as shown in fig. 1, fig. 2 and fig. 3, respectively.
A DSC thermogram of penoxsulam exhibits an endothermic melting peak with an onset at 227.5 ℃ and a maximum peak at 229.2 ℃, further optionally having a melting enthalpy of 79.66J/g as shown in figure 3.
The IR spectrum of crystal modification I of penoxsulam showed the values at 3360.72, 2925.19, 1637.23 and 1534.23cm as shown in FIG. 1 -1 Characteristic vibrational peaks of the functional group at one or more wavenumbers.
The X-ray powder diffraction pattern of crystal modification I of penoxsulam crystals exhibits the reflections in fig. 2, and the values are summarized in table 1.
TABLE 1
Example 3: preparation of crystalline modification I of penoxsulam
Crystallization from xylene
A 5g sample of amorphous penoxsulam prepared in example 1 was taken and placed in a 3-neck round-bottom flask together with 30mL of xylene, and the resulting slurry was heated to 83 ℃ to obtain a homogeneous solution. Insoluble particles (if any) were filtered and the solution was slowly cooled to 20-25 ℃. After cooling, fine crystals formed and the resulting heterogeneous mixture was stirred at 20 ℃ for 2 hours. The slurry was then filtered and washed with 3mL of xylene at 20 ℃. The filtered crystals were dried under vacuum at 45 ℃. The crystalline product thus obtained had a purity of > 98%, and the yield of the product recovered as crystals was found to be not less than 80%.
The obtained crystals were characterized as crystal modification I of penoxsulam using IR spectroscopy, X-ray powder diffraction and DSC as described in example 2.
Example 4: preparation of oil-based suspension concentrate (OD) formulations
All the components listed in table 2 below were uniformly mixed and milled with Dyno-Mill (manufactured by Willy a. bachofen AG) to obtain an oil-based suspension.
TABLE 2
Example 5: preparation of oil-based suspension concentrate (OD) formulations
All the components listed in table 3 below were uniformly mixed and ground with Dyno-Mill (manufactured by Willy a. bachofen AG) to obtain an oil-based suspension.
TABLE 3
Example 6: preparation of Soluble Granules (SG)
All the components listed in table 4 below were mixed, blended and milled in a high speed rotary mill. Sufficient water is added to obtain an extrudable paste. The paste is extruded through a die or screen to form an extrudate. The wet extrudates were dried in a vacuum oven at 70 ℃ and then screened through a 0.71mm-2mm screen to obtain product granules.
TABLE 4
Example 7: preparation of Water dispersible granules (WG)
All the components listed in table 5 below were mixed, blended and milled in a high speed rotary mill. Sufficient water is added to obtain an extrudable paste. The paste is extruded through a die or screen to form an extrudate. The wet extrudates were dried in a vacuum oven at 70 ℃ and then screened through a 0.71mm-2mm screen to obtain product granules.
TABLE 5
Example 8: stability test
The stability of penoxsulam in the composition was determined as follows: the samples were aged in a heated oven with the same atmosphere therein, and then the penoxsulam content before and after aging was compared to determine the Relative Percent Hydrolysis (RPH). The RPH is calculated by the following equation:
the penoxsulam content is determined by measuring the composition with High Pressure Liquid Chromatography (HPLC) using a reverse phase column and an eluent.
The samples prepared in examples 4, 5, 6 and 7 were stored at 54 ℃ for 1 week. These procedures followed CIPAC MT 46.3. The concentration of penoxsulam was measured by HPLC at the end of each storage time. The results are shown in Table 6.
TABLE 6
It was surprisingly found that crystalline modification I of penoxsulam is extremely stable after 1 week of storage at 54 ℃. It has a reduced tendency to hydrolyse compared to the amorphous form. In these tests of crystal modification I of penoxsulam, the Relative Percent Hydrolysis (RPH) was 3% or less, 2% or less, and 1% or less. In comparison, when amorphous penoxsulam is used, the corresponding RPH is not less than 45%. Reducing hydrolysis by up to about 15-fold, reducing hydrolysis by up to about 20-fold, reducing hydrolysis by up to about 25-fold, reducing hydrolysis by up to about 45-fold when using crystalline variant I of penoxsulam when compared to amorphous penoxsulam; this covers the range of about 15 to 45 fold reduction in hydrolysis produced. For these reasons, it is well suited to the preparation of commercial formulations where such hydrolysis may result in loss of production capacity.
Claims (21)
1. A crystalline modification of penoxsulam which exhibits the following reflection as 2 Θ ± 0.2 degrees in an X-ray powder diffraction pattern recorded at 25 ℃ using Cu-ka radiation:
2θ＝6.19±0.2 (1)
2θ＝11.47±0.2 (4)
2θ＝18.75±0.2 (6)
2θ＝20.28±0.2 (7)
2θ＝24.50±0.2 (10)
2θ＝24.66±0.2 (11)
2θ＝27.57±0.2 (13)
2θ＝29.65±0.2 (14)。
2. a crystalline modification of penoxsulam exhibiting the following reflections in an X-ray powder diffraction pattern recorded at 25 ℃ using Cu-ka radiation:
2θ＝6.19±0.2 (1)
2θ＝10.70±0.2 (2)
2θ＝11.05±0.2 (3)
2θ＝11.47±0.2 (4)
2θ＝17.21±0.2 (5)
2θ＝18.75±0.2 (6)
2θ＝20.28±0.2 (7)
2θ＝23.38±0.2 (8)
2θ＝23.59±0.2 (9)
2θ＝24.50±0.2 (10)
2θ＝24.66±0.2 (11)
2θ＝25.10±0.2 (12)
2θ＝27.57±0.2 (13)
2θ＝29.65±0.2 (14)。
3. the crystalline modification of penoxsulam according to claim 1 or claim 2, which exhibits a crystallinity of at least about 3360.72, 2925.19, 1637.23 and 1534.23cm -1 Has a characteristic functional group vibration peak at one or more wavenumbers.
4. The crystalline modification of penoxsulam according to claim 1 or claim 2, which exhibits a melting point of 227 ℃ to 232 ℃.
5. The crystalline variant of penoxsulam according to claim 4, which exhibits a melting point of 228 ℃ to 230 ℃.
6. The crystalline variant of penoxsulam according to claim 4, which exhibits a melting point of 229 ℃.
7. The crystalline modification of penoxsulam according to claim 1 or claim 2, which exhibits a Differential Scanning Calorimetry (DSC) curve in which an endothermic melting peak starts at 228 ℃ and the peak maximum is at 229 ℃.
8. The crystalline modification of penoxsulam according to claim 7, which exhibits a Differential Scanning Calorimetry (DSC) curve in which the endothermic melting peak has a melting enthalpy of 80J/g.
9. A crystal modification of penoxsulam according to claim 1 or claim 2, characterized by an X-ray powder diffraction pattern substantially as shown in figure 2, and/or by an IR spectrum substantially as shown in figure 1, and/or by a DSC substantially as shown in figure 3.
10. A process for preparing a crystalline modification of penoxsulam according to any one of claims 1 to 9, comprising:
i) dissolving penoxsulam in a solvent, wherein the solvent is methyl ethyl ketone or xylene or a mixture thereof;
ii) precipitating the dissolved compound as a crystalline modification of penoxsulam; and
iii) isolating the precipitated crystalline modification.
11. The process of claim 10, wherein the penoxsulam in step i) is amorphous penoxsulam.
12. The process according to claim 10 or claim 11, wherein step ii) is carried out by concentrating the solvent and/or by cooling and/or by adding a solubility-reducing solvent and/or by adding seeds of the crystalline modification of penoxsulam.
13. The process according to claim 12, wherein step ii) is carried out by cooling to 0 to 20 ℃.
14. A composition comprising a crystalline modification of penoxsulam according to any one of claims 1 to 9 and at least one adjuvant.
15. The composition of claim 14, wherein the adjuvant is selected from the group consisting of liquid diluents, solid diluents, wetting agents, dispersing agents, thickening agents, anti-freezing agents, anti-foaming agents, and biocides.
16. A composition according to claim 14 or claim 15, in the form of: suspension (SG), Dispersible (DC), Emulsifiable Concentrate (EC), emulsion seed dressing, Granules (GR) or Suspoemulsion (SE).
17. A composition according to claim 14 or claim 15, in the form of: oil-based suspension concentrates (OD), Soluble Granules (SG), suspension seed dressings, Microgranules (MG) or water dispersible granules (WG).
18. The composition of claim 17, in the form of: oil-based suspending agents, Soluble Granules (SG) or water dispersible granules (WG).
19. The composition of claim 14 or claim 15, comprising a crystalline variant of penoxsulam in an amount of less than 75% by weight.
20. The composition of claim 14 or claim 15, comprising a crystal modification of penoxsulam and cyhalofop-butyl.
21. Use of the crystal modification of penoxsulam according to any one of claims 1 to 9 or the composition according to any one of claims 14 to 20 for weed control.
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| PCT/CN2017/107092 WO2018082456A1 (en) | 2016-11-07 | 2017-10-20 | A novel form of penoxsulam, a process for its preparation and use of the same |
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Citations (8)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5858924A (en) * | 1996-09-24 | 1999-01-12 | Dow Agrosciences Llc | N-( 1, 2, 4! triazoloazinyl) benzenesulfonamide and pyridinesulfonamide compounds and their use as herbicides |
| WO2004080184A1 (en) * | 2003-03-13 | 2004-09-23 | Basf Aktiengesellschaft | Synergistically acting herbicidal mixtures |
| WO2005097793A1 (en) * | 2004-03-26 | 2005-10-20 | Dow Agrosciences Llc | An improved process for the preparation of n-([1,2,4]triazolopyrimidin-2-yl)aryl sulfonamides |
| CN101861867A (en) * | 2010-06-22 | 2010-10-20 | 惠州市中迅化工有限公司 | Pesticide compound containing penoxsulam and cyhalofop-butyl and application thereof |
| CN103044431A (en) * | 2012-10-22 | 2013-04-17 | 中国药科大学 | Novel preparation method of penoxsulam |
| CN103724353A (en) * | 2013-12-12 | 2014-04-16 | 江苏富鼎化学有限公司 | Improved synthesis method of penoxsulam |
| CN104402890A (en) * | 2014-11-10 | 2015-03-11 | 常州大学 | Preparation method of penoxsulam |
| CN104447756A (en) * | 2014-11-10 | 2015-03-25 | 常州大学 | Method for preparing penoxsulam midbody |
Family Cites Families (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| BR0114163A (en) * | 2000-09-26 | 2003-07-29 | Dow Agroscience Llc | Process for the preparation of 2-alkoxy-6-trifluoromethyl-n - ([1,2,4]) triazolo [1,5-c] pyrimidin-2yl-) benzenesulfonamides |
| CN104557800B (en) * | 2014-12-31 | 2017-04-26 | 常州大学 | 2-phenoxyl tetrahydrofuran (tetrahydropyrane) derivatives and application thereof in synthesis of penoxsulam |
| CN107021966B (en) * | 2017-04-11 | 2019-04-19 | 四川福思达生物技术开发有限责任公司 | The synthetic method of improved penoxsuam |
-
2016
- 2016-11-07 GB GB1618734.6A patent/GB2555635B/en active Active
-
2017
- 2017-10-20 WO PCT/CN2017/107092 patent/WO2018082456A1/en active Application Filing
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Patent Citations (8)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5858924A (en) * | 1996-09-24 | 1999-01-12 | Dow Agrosciences Llc | N-( 1, 2, 4! triazoloazinyl) benzenesulfonamide and pyridinesulfonamide compounds and their use as herbicides |
| WO2004080184A1 (en) * | 2003-03-13 | 2004-09-23 | Basf Aktiengesellschaft | Synergistically acting herbicidal mixtures |
| WO2005097793A1 (en) * | 2004-03-26 | 2005-10-20 | Dow Agrosciences Llc | An improved process for the preparation of n-([1,2,4]triazolopyrimidin-2-yl)aryl sulfonamides |
| CN101861867A (en) * | 2010-06-22 | 2010-10-20 | 惠州市中迅化工有限公司 | Pesticide compound containing penoxsulam and cyhalofop-butyl and application thereof |
| CN103044431A (en) * | 2012-10-22 | 2013-04-17 | 中国药科大学 | Novel preparation method of penoxsulam |
| CN103724353A (en) * | 2013-12-12 | 2014-04-16 | 江苏富鼎化学有限公司 | Improved synthesis method of penoxsulam |
| CN104402890A (en) * | 2014-11-10 | 2015-03-11 | 常州大学 | Preparation method of penoxsulam |
| CN104447756A (en) * | 2014-11-10 | 2015-03-25 | 常州大学 | Method for preparing penoxsulam midbody |
Non-Patent Citations (3)
| Title |
|---|
| Penoxsulam—Structure–activity relationships of triazolopyrimidine sulfonamides;Timothy C.Johnson et al.;《BIOORGANIC & MEDICINAL CHEMISTRY》;20090214;第17卷;第4233页右栏最后一段及第4235页右栏第4段 * |
| 五氟磺草胺的开发和苯甲酰基脲类似物的研究;李成坤;《中国优秀硕士学位论文全文数据库 工程科技I辑》;20141215(第12期);正文第26页 2.3.1.8节 * |
| 新型除草剂五氟磺草胺的改进合成研究;徐思田;《中国学位论文全文数据库》;20160514;正文第34页 3.3.4.6节 * |
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