WO2025233793A1 - A mixture comprising florpyrauxifen and a safener - Google Patents

Abstract

The present invention provides: a) a mixture comprising: (i) florpyrauxifen in the form of an ester thereof as an herbicide; and (ii) an acylsulfonamide as a safener; b) a composition comprising said mixture and agriculturally acceptable carrier; and c) methods of use.

Description

A MIXTURE COMPRISING FLORPYRAUXIFEN AND A SAFENER

TECHNICAL FIELD

[0001] The present invention provides mixtures comprising florpyrauxifen, e.g., florpyrauxifen-benzyl, and an acylsulfonamide as a safener, e.g., cyprosulfamide; compositions comprising said mixtures; and their use in controlling weeds.

BACKGROUND ART

[0002] Herbicide safeners are a group of agrochemicals that protect monocotyledonous crops against injury from herbicides without reducing chemical control in target weed species, thus improving selectivity (Cataneo etal., 2013). The majority of herbicide safeners are active in cereal crops, such as maize (com), wheat, rice and sorghum.

[0003] The ability of safeners to protect crops from herbicides, thereby enhancing selectivity between crop and weed, provide many potential applications such as using higher herbicide doses to achieve more effective weed control, providing greater flexibility in crop choice; affording the possibility of providing weed control options for minor crops which are not generally targeted for development of new herbicide compounds because of their small market value; using herbicides under environmental conditions likely to cause some crop damage; extending the usage patterns of commercial herbicides; and developing molecules with desirable toxicological profiles, despite showing poor selectivity.

[0004] Safeners are known to inhibit the phytotoxicity of partner herbicides, but this may be mediated by a variety of effects. One explanation for safener mode of action, is that safeners inhibit the uptake or translocation of herbicides, such that they cannot reach the site of action This could occur through competition for the uptake active site, or through effects on membrane permeability. Alternatively, safeners may act indirectly on herbicide transport via effects on cuticular integrity (Davies and Caseley, 1999).

[0005] Another hypothesis proposed that safeners may antagonise herbicides by acting as competitive inhibitors at the site of action.

[0006] The safener mode of action theory with the most support is that safeners enhance the metabolism of herbicides to less active metabolites, thereby reducing the concentration of herbicide at its site of action (Kraehmer et al., 2014). This could occur through an increased expression of xenome enzymes, or through increased production of vital xenome cofactors, such as the tripeptide glutathione (GSH) required for glutathione conjugation. [0007] An increase in GSH content by safeners has been considered in many studies to be involved in the safening effect, with many safeners causing an elevation in GSH in maize, sorghum, tobacco (Nicotiana sp.) and rice.

[0008] The hypothesis that safening occurs through enhanced expression of xenome enzymes involved in herbicide detoxification, has gained considerable support. Xenome enzymes have been shown to be induced by safeners within a few hours of safener application (Hatzios and Burgos, 2004).

[0009] Therefore, finding a safener for a particular class of herbicides remains a difficult task since the exact mechanisms by which a safener reduces the harmful action of herbicides are not entirely clear. The fact that a compound in combination with a particular herbicide acts as a safener allows no conclusions as to whether such a compound would also show a safener action with other classes of herbicides. Thus, when using safeners for protecting the useful plants from adverse effects of herbicides, it has emerged that many of the safeners may still exhibit certain disadvantages such as reducing the action of the herbicides against the harmful plants; the useful-plant-protecting properties are not sufficient, in combination with a given herbicide; the spectrum of the useful plants in which the safener/herbicide is to be applied is not sufficiently wide; and a given safener cannot always be combined with a sufficiently large number of herbicides. Therefore, individual safeners are paired for use in specific crops and often in partnership with specific herbicides.

[0010] Florpyrauxifen (4-amino-3-chloro-6-(4-chloro-2-fluoro-3-methoxyphenyl)-5- fluoropyridine-2-carboxylic acid) is a herbicide, which is known to mimic the plant growth hormone auxin, thus causing uncontrolled and disorganized growth leading to plant death in susceptible species (auxin mimic).

[0011] Cyprosulfamide is an arylsulfonyl-benzamide which was developed for both pre- and post-emergence applications in maize (Zea mays /.. ) and is very effective in protecting the crop from damage by acetolactate synthase (ALS) or 4-hydroxyphenylpyruvate dioxygenase (4-HPPD) active herbicides. In particular, cyprosulfamide was co-developed with the ALS-inhibiting herbicide thiencarbazone-methyl to control perennial grasses and other problem weeds in maize. According to the literature, the protection against thiencarbazone-methyl injury by cyprosulfamide is linked to enhanced herbicide metabolism (Giannakopoulos et al., 2020). [0012] In view of the above, combining a given safener with an herbicide that will provide reduced phytotoxicity of said herbicide, in an efficient way, when applied to a particular crop is not straightforward in most cases.

[0013] IN202011040680 A discloses a synergistic herbicidal composition of (A) a herbicide florpyrauxifen benzyl; (B) a one or more herbicide(s) selected from the group of various class of compounds for control of broad leaved weeds and grassy weeds and sedges in economical crops or mixture thereof; and (C) an insecticide selected from the class of diamide, metadiamide or isoxazoline as safener for reducing phytotoxicity in crops treated with a herbicide or mixture thereof.

[0014] WO 2010/060581 A2 discloses long list of possible combinations of florpyrauxifen-based compounds and various safeners.

[0015] WO 2014/150740 Al discloses a safened herbicidal composition for use in corn (maize) comprising a herbicidally effective amount of (a) florpyrauxifen or an agriculturally acceptable salt or ester thereof and (b) a safener or a compatible herbicide capable of safening. Possible such safeners include AD67, benzenesulfonamide, benoxacor, N- (aminocarbonyl)-2-chlorobenzenesulfonamide, daimuron, dichlormid, dichloroacetamide, dicyclonon, fenchlorazole-ethyl, fenclorim, fluxofenim, furilazole, isoxadifen-ethyl, mefenpyr-diethyl, naphthopyranone, naphthalic anhydride, oxabetrinil, oxime, phenylpyrimidine, phenylurea, a chemical from the quinolinyloxyacetate family of chemicals, or agriculturally acceptable salts, esters, or mixtures thereof.

[0016] WO 2014/018358 Al discloses safened herbicidal compositions for use in rice comprising a herbicidally effective amount of (a) florpyrauxifen or an agriculturally acceptable salt or ester of thereof, and (b) a safener or a compatible herbicide capable of safening such as bispyribac-sodium, carfentrazone- ethyl, a chemical from the quinolinyloxyacetate family of chemicals, cyhalofop-butyl, daimuron, dichlormid, dicyclonon, dimepiperate, fenclorim, fluxofenim, furilazole, halosulfuron-methyl, isoxadifen-ethyl, mefenpyr-diethyl, napthalic anhydride, norflurazon, oxabetrinil, pyriclor, sulcotrione, AD67, or agriculturally acceptable salts, esters, or mixtures thereof.

[0017] There is a need to provide a solution for reducing, in the most efficient way, the phytotoxicity of the herbicide florpyrauxifen or a salt, an ester, or a combination thereof, such as florpyrauxifen-benzyl, when applied to a crop such as maize (corn). SUMMARY OF INVENTION

[0018] It has now been found, in accordance with the present invention, that a mixture comprising florpyrauxifen, more specifically florpyrauxifen-benzyl, and an acyl sulfonamide, more specifically cyprosulfamide, was surprisingly less phytotoxic when applied on a plant, more specifically com (maize), as compared to a similar mixture comprising isoxadifen-ethyl as a safener.

[0019] In one aspect, the present invention thus provides a mixture comprising: (i) florpyrauxifen or a salt, an ester, or a combination thereof as an herbicide; and (ii) an acylsulfonamide as a safener. In certain embodiments, said florpyrauxifen is in the form of an ester thereof, such as florpyrauxifen-benzyl. In specific such embodiments, said florpyrauxifen is in the form of benzyl ester thereof; and said acyl sulfonamide is cyprosulfamide.

[0020] In another aspect, the present invention relates to a composition comprising: (i) a mixture as defined above; and (iii) agriculturally acceptable carrier.

[0021] In a further aspect, the present invention relates to a method of controlling weed comprising applying to a locus an effective amount of a mixture comprising: (i) florpyrauxifen or a salt, an ester, or a combination thereof as an herbicide; and (ii) an acylsulfonamide as a safener. In certain embodiments, said florpyrauxifen is in the form of an ester thereof, such as florpyrauxifen-benzyl.

BRIEF DESCRIPTION OF DRAWINGS

[0022] Fig. 1 shows the phytotoxicity of florpyrauxifen-benzyl and its combination with either cyprosulfamide or isoxadyfen-ethyl as compared to control, when applied to com that reached the 2-3 leaves stage, at 7 and 14 days after application (Fig 1A and Fig IB, respectively). Entries in each case are as indicated in Table 1 (Examples).

[0023] Fig. 2 shows the phytotoxicity of florpyrauxifen-benzyl and its combination with either cyprosulfamide or isoxadyfen-ethyl as compared to control, when applied to corn that reached the 4-5 leaves stage, at 7 and 14 days after application (Fig 2A and Fig 2B, respectively). Entries in each case are as indicated in Table 1 (Examples). DETAILED DESCRIPTION

[0024] In one aspect, disclosed herein is a mixture comprising a herbicide selected from florpyrauxifen or a salt, an ester, or a combination thereof, and a safener selected from an acylsulfonamide.

[0025] The term “safener” as used herein refers to a compound or a mixture of compounds which compensates for, or reduces, the phytotoxic properties of a herbicide toward useful plants without essentially reducing the herbicidal action against harmful plants.

[0026] In certain embodiments, the mixture of the invention further comprises an additional herbicide. Particular such embodiments are those wherein said additional herbicide is selected from a very long-chain fatty acid synthesis inhibitor; an acetolactate synthase inhibitor; and a hydroxyphenyl pyruvate dioxygenase inhibitor.

[0027] Non-limiting examples of very long-chain fatty acid (VLCFA) synthesis inhibitors include acetamide-based VLCFA inhibitors such as napropamide, naproanilide, and diphenamid; oxyacetamide-based VLCFA inhibitors such as flufenacet and mefenacet; chloroacetamide-based VLCFA inhibitors such as acetochlor, dimethachlor, metolachlor (including fS')-metolachlor, (A’)-metolachlor, as well as any mixture thereof such as a racemate thereof), dimethenamid (including CS')-dimethenamid, ( ’)-dimethenamid, as well as any mixture thereof such as a racemate thereof), alachlor, butachlor, butenachlor, delachlor, prynachlor, terbuchlor, allidochlor, xylachlor, 2-chloro-N,N-diethylacetamide (CDEA), diethatyl, metazachlor, pethoxamid, pretilachlor, propachlor, propisochlor, and thenylchlor; tetrazolinone-based VLCFA inhibitors such as fentrazamide, and ipfencarbazone; anilofos; cafenstrole; piperophos; pyroxasulfone; epronaz; tridiphane; indanofan; and enantiomers thereof.

[0028] Non-limiting examples of acetolactate synthase (ALS) inhibitors include imidazolinone-based ALS inhibitor such as imazethapyr, imazapic, imazamethabenz- methyl, imazapyr, imazamox, and imazaquin; triazolinones-base ALS inhibitor such as flucarb azone-Na, propoxy-carbazone-Na, and thiencarbazone-methyl; sulfonylurea-based ALS inhibitor such as ethoxysulfuron, mesosulfuron-methyl, flazasulfuron, chlorimuron- ethyl, azimsulfuron, chlorsulfuron, cinosulfuron, cyclosulfamuron, imazosulfuron bensulfuronmethyl, amidosulfuron, iodosulfuronmethyl-Na, halosulfuron-methyl, metazosulfuron, foramsulfuron, flucetosulfuron, nicosulfuron, metsulfuron-methyl ethametsulfuron-methyl, primisulfuron-methyl, propyrisulfuron, prosulfuron, pyrazosulfuronethyl, triasulfuron, tribenuron-methyl, rimsulfuron, orthosulfamuron, sulfometuron-methyl, tritosulfur, trifloxysulfuron-Na, sulfosulfuron, triflusulfuron- methyl, and thifensulfuronm ethyl; sulfonanilide-based ALS inhibitor such as pyrimisulfan and triafamone; pyrimidinyl benzoate-based ALS inhibitor such as bispyribac-Na, pyriminobacmethyl, pyribenzoxim, pyriftalid, and pyrithiobac- Na; triazolopyrimidine- based ALS inhibitor such as flumetsulam, diclosulam, cloransulammethyl, penoxsulam, pyroxsulam, and florasulam, metosulam.

[0029] Non-limiting examples of hydroxyphenyl pyruvate dioxygenase (HPPD) inhibitors include pyrazole-based HPPD inhibitor such as pyrazoxyfen, pyrazolynate, pyrasulfotole, topramezone, benzofenap, and tolpyralate; triketon-based HPPD inhibitor such as mesotrione, benzobicyclon, tembotrione, sulcotrione, bicyclopyrone, fenquinotrione, and tefuryltrione.

[0030] More particular such embodiments are those wherein said additional herbicide is at least one herbicide selected from dimethenamid, thiencarbazone-methyl, topramezone and tembotrione.

[0031] In certain embodiments, the mixture of the invention comprises florpyrauxifen or a salt, an ester, or a combination thereof, as the only herbicide; and an acylsulfonamide as the only safener, i.e., the herbicide comprised within said mixture consists or consists essentially of florpyrauxifen or a salt, an ester, or a combination thereof; and the safener comprised within said mixture consists or consists essentially of said acylsulfonamide. The term “consists of’ or “consists essentially of’ as used herein with respect to said mixture means that no other herbicide, besides florpyrauxifen or a salt, an ester, or a combination thereof, is present in said mixture; and that no other safener, besides said acylsulfonamide, is present in said mixture.

[0032] In certain embodiments, the florpyrauxifen comprised within the mixture of the invention according to any one of the embodiments above is in the form of a free acid thereof. [0033] In certain embodiments, the florpyrauxifen comprised within the mixture of the invention according to any one of the embodiments above is in the form of an ester thereof. Non-limiting examples of esters of florpyrauxifen include Ci-Cs-alkyl esters and C1-C4- alkoxy-C2-C4-alkyl esters, such as methyl esters, ethyl esters, isopropyl, butyl, hexyl, heptyl, isoheptyl, isooctyl, 2-ethylhexyl, methylheptyl (MHE; meptyl), butoxypropyl (butometyl), and butoxyethyl esters; and aryl esters such as benzyl. [0034] In particular such embodiments, the florpyrauxifen comprised within the mixture of the invention according to any one of the embodiments above is in the form of benzyl ester thereof (also referred to herein as “florpyrauxifen-benzyl”).

[0035] Non-limiting examples of acysulfonamides include: i) an N-acylsulfonamide of the formula I or a salt thereof (e.g., as disclosed in WO 1997/045016 Al):

¹ , wherein R¹ is (Ci-Ce)alkyl or (C3-Ce)cycloalkyl, wherein said alkyl or cycloalkyl is optionally substituted by one or more substituents selected from the group consisting of halogen, -O-(Ci-C4)alkyl, and (Ci-C4)haloalkyl; R² is halogen, (Ci-C4)alkyl, -O-(Ci-C4)alkyl, or CF3; and n is 1 or 2; ii) a 4-(benzoylsulfamoyl)benzamide-based compound of the formula II or a salt thereof (e.g., as disclosed in WO 1999/16744 Al);

¹¹ , wherein R³ and R⁴ each independently is hydrogen, (Ci-Ce)alkyl, (C3-Ce)cycloalkyl, (C3-Ce)alkenyl, (C3-Ce)alkynyl; R⁵ is halogen, (Ci-C4)alkyl, (Ci-C4)haloalkyl, or -O-(Ci-C4)alkyl; and; mis 1 or 2; iii) a benzoylsulfamoylphenylurea of the formula III (e.g., as disclosed in EP 0365484 Bl):

, wherein R⁶ and R⁷ each independently is hydrogen, (Ci-Cs)alkyl, (C3-C8)cycloalkyl, (C3-Ce)alkenyl, or (C3-Ce)alkynyl; R⁸ is halogen,

(Ci-C4)alkyl, (Ci-C4)alkoxy, or CF3; and p is 1 or 2.

[0036] Examples of 4-(benzoylsulfamoyl)benzamide-based compounds of the formula II include: (i) R³ is cyclopropyl, R⁴ is hydrogen, R⁵ is 2-OCH3, and m is 1 (also referred to herein as “cyprosulfamide”); (ii) R³ is cyclopropyl, R⁴ is hydrogen, R⁵ is 5-Cl-2-OMe, and m is 2; (iii) R³ is ethyl, R⁴ is hydrogen, R⁵ is 2-OMe, and m is 1; (iv) R³ is isopropyl, R⁴ is hydrogen, R⁵ is 5-Cl-2-OMe, and m is 2; and (v) R³ is isopropyl, R⁴ is hydrogen, R⁵ is 2- OMe, and m is 1.

[0037] Examples of benzoylsulfamoylphenylureas of the formula III include l-[4-(N-2- methoxy benzoyl sulfamoyl) phenyl] -3 -methylurea, l-[4-(N-2-methoxy benzoyl sulfamoyl)phenyl] -3, 3 -dimethylurea, and l-[4-(N-4,5-dimethyl benzoyl sulfamoyl)phenyl]- 3 -methylurea.

[0038] In certain embodiments, the acylsulfonamide comprised within the mixture of the invention according to any one of the embodiments above is cyprosulfamide.

[0039] In certain embodiments, the mixture of the invention according to any one of the embodiments above is free of an additional safener, i.e., said mixture does not include an additional safener besides the acylsulfonamide.

[0040] In certain embodiments, the mixture of the invention according to any one of the embodiments above is free of an insecticide, i.e., said mixture does not include an insecticide.

[0041] In certain embodiments, the mixture of the invention according to any one of the embodiments above comprises florpyrauxifen-benzyl and cyprosulfamide.

[0042] In certain embodiments, the weight ratio between florpyrauxifen to said safener (fl orpyraxifen: safener) in the mixture of the invention according to any one of the embodiments above is from about 1 : 1 to about 1 : 15, e.g., from about 1 :2 to about 1: 12, from about 1:3 to about 1 : 10, from about 1 :4 to about 1 :8, respectively (calculated on an acid equivalent base of florpyrauxifen).

[0043] In another aspect, the present invention provides a composition comprising: (i) a mixture as defined herein; and (iii) agriculturally acceptable carrier.

[0044] The term “agriculturally acceptable carrier” as used herein refers to an inert substance which is known and accepted in the art for the formation of compositions for agricultural or horticultural use, and which facilitates the application of the active ingredients. The carrier may be in the form of a solid or a liquid.

[0045] Examples of solid carriers include, but are not limited to, mineral earths such as silica gels, silicates, talc, kaolin, sericite, attaclay, limestone, bentonite, lime, chalk, bole, mirabilite, loess, clay, dolomite, zeolite, diatomaceous earth, calcium carbonate, calcium sulfate, magnesium sulfate, magnesium oxide, sodium carbonate and bicarbonate, and sodium sulfate; ground synthetic materials; resins; waxes; fertilizers such as ammonium sulfate, ammonium phosphate, ammonium nitrate, ureas, and products of vegetable origin such as cereal meal, tree bark meal, wood meal, and nutshell meal; and cellulose powders.

[0046] Examples of liquid carriers include, but are not limited to, water; aromatic hydrocarbons such as alkylbenzenes and alkylnaphthalenes; alcohols such as cyclohexanol, and decanol; ethylene glycol; polypropylene glycol; dipropropylene glycol; N,N- dimethylformamide; dimethylsulfoxide; dimethylacetamide; N-alkylpyrrolidones such as N-methyl-2-pyrrolidone; paraffins; various oils such as olive, castor, linseed, tung, sesame, corn, peanut, cotton-seed, soybean, rape-seed, or coconut oil; fatty acid esters; and ketones such as cyclohexanone, 2-heptanone, isophorone, and 4-hydroxy-4-methyl-2-pentanone.

[0047] In certain embodiments, the composition of the invention further comprises at least one, e.g., one, two, three, or more, excipient(s) such as a surfactant.

[0048] The term “agriculturally acceptable excipient” as used herein refers to an inert substance which is known and accepted in the art for the formation of compositions for agricultural or horticultural use, and that itself is not an active ingredient but is added to the formulation to improve one or more of its properties, such as stability, flowability, density, and the like. Examples of such excipients include, but are not limited to, pH modifiers (e.g., acids or bases), thickening agents (thickeners), sticking agents, surfactants, anti-oxidation agents, and anti-foaming agents.

[0049] The term “surfactant” as used herein refers to any agriculturally acceptable material which imparts or improves emulsifiability, spreading, wetting, dispersibility, or other surface-modifying properties of a herbicidal formulation, and optionally stability of said formulation, e.g., by inhibiting crystal growth or avoiding particle agglomeration. Nonlimiting examples of surfactants include (i) nonionic surfactants such as fatty alcohol surfactants (e.g., cetyl alcohol), monoglyceride surfactants (e.g., glycerol monolaurate), polysorbate surfactants (e.g., Tween-20, Tween-40, Tween-60, Tween-65, Tween-80, and Tween-85), tristyrylphenol ethoxylate surfactants (e.g., Soprophor® TS/54), ethoxylated alkylphenol surfactants (e.g., a nonylphenol ethoxylate such as Tergitol NP-9™), ethoxylated arylphenol surfactants, ethoxylated castor oil surfactants (e.g., Alkamuls® OR/36, Stepantex® CO-40, and Stepantex® CO-36), ethylene oxide- and propylene oxideblock copolymers, and polyvinyl alcohol-vinyl acetate copolymers; (ii) anionic surfactants such as fatty acid sulfonates (e.g., lauryl sulfonate); (iii) cationic surfactants such as quaternary ammonium surfactants (e.g., cetylpyridinium chloride and dimethyldioctadecylammonium chloride); and (iv) ampholytic surfactants such as cocamidopropyl betaine and (3-[(3-Cholamidopropyl) dimethylammonio]-l- propanesulfonate).

[0050] In certain embodiments, the weight ratio between florpyrauxifen to said safener (florpyrauxifemsafener) comprise within the composition of the invention according to any one of the embodiments above is from about 1 : 1 to about 1 : 15, e.g., from about 1 :2 to about 1 : 12, from about 1 :3 to about 1 : 10, from about 1 :4 to about 1:8, respectively (calculated on an acid equivalent base of florpyrauxifen).

[0051] According to the invention, the florpyrauxifen comprised within the composition of the invention may be in its acid free form rather than a salt form, in its salt form, in its ester form, each as defined herein, or any combination thereof.

[0052] In certain embodiments, the florpyrauxifen comprised within the composition of the invention according to any one of the embodiments above is in its benzyl ester form.

[0053] In certain embodiments, the safener comprised within the composition of the invention according to any one of the embodiments above is cyprosulfamide.

[0054] In certain embodiments, the florpyrauxifen comprised within the composition of the invention according to any one of the embodiments above is in its benzyl ester form; and the safener comprised within the composition of the invention according to any one of the embodiments above is cyprosulfamide.

[0055] In a further aspect, the present invention relates to a method of controlling weed, also referred to herein as undesired vegetation, comprising applying to a locus an effective amount of a mixture comprising: (i) florpyrauxifen or a salt, an ester, or a combination thereof as an herbicide; and (ii) an acylsulfonamide as a safener. The florpyrauxifen and acylsulfonamide utilized according to the method of the invention each is as defined in any one of the embodiments above.

[0056] The term "locus" as used herein refers not only to areas where the weed may already be developed, but also to areas where weeds have yet to emerge, and to areas under cultivation. Locus includes the crop and propagation material of the crop (all the generative parts of the crop such as seeds and vegetative plant material such as cuttings and tubers, which can be used for the multiplication of the plant). Examples of propagation material of the crop include seeds, tubers, spores, corms, bulbs, rhizomes, sprouts basal shoots, stolons, buds and other parts of plants, including seedlings and young plants, which could be transplanted after germination or after emergence from soil. Locus also includes the area surrounding the crop and the growing media of the crop, such as soil and crop field.

[0057] In certain embodiments, the locus is a field of crop. The term “crop” (or “plant”) as used herein refers to whole plants, plant organs (e.g., leaves, stems, twigs, roots, trunks, limbs, shoots, fruits, etc.), plant cells, or plant seeds. Particular such embodiments are those wherein said crop is com (maize).

[0058] The weeds that can be controlled by the method of the present invention include grass weeds and broadleaved weeds, or monocotiledoneous weeds and dicotiledoneous weeds.

[0059] In certain embodiments, the florpyrauxifen utilized according to the method of the invention according to any one of the embodiments above is in its ester form such as benzyl ester form; and the safener utilized according to the method of the of the invention according to any one of the embodiments above is cyprosulfamide.

[0060] In certain embodiments, the florpyrauxifen or a salt, an ester, or a combination thereof and acylsulfonamide, utilized according to the method of the invention according to any one of the embodiments defined above, are applied from a sole composition, e.g., in the form of a “ready mix” (“ready-for-use”) composition, which is optionally diluted with water before use.

[0061] In certain embodiments, the florpyrauxifen or a salt, an ester, or a combination thereof and acylsulfonamide, utilized according to the method of the invention according to any one of the embodiments defined above, are applied from two separate compositions (i.e., one of said compositions comprises said florpyrauxifen, and the second composition comprises said acylsulfonamide), either: (i) concurrently (simultaneously), e.g., in the form of a “tank mix”, or (ii) sequentially in any order, e.g., after diluting each one said compositions with water.

[0062] The composition(s) applied according to the method of the invention according to any one of the embodiments defined above, each independently may be of any type known in the art, e.g., in the form of a liquid formulation such as a soluble liquid, suspension concentrate, emulsifiable concentrate, oil dispersion, suspoemulsion, concentrated aqueous emulsion, or a dry formulation such as a granule, a wettable powder, a soluble powder, a water-dispersible granule, or a dry flowable. [0063] In certain embodiments, florpyrauxifen or a salt, an ester, or a combination thereof utilized according to the method disclosed herein according to any one of the embodiments above is applied at a rate in the range of from about 0.05 to about 80 g/ha, e.g., in the range of from about 1 to 60 g/ha, from about 1 to 35 g/ha , from about 1 to 33 g/ha, from about 2 to about 50 g/ha, from about 5 to about 40 g/ha, or from about 7 to about 30 g/ha, or from about 7 to 12 g/ha, or from about 4 to 9 g/ha, or from about 11 to 16 g/ha (calculated on an acid equivalent base of florpyrauxifen).

[0064] In certain embodiments, the acylsulfonamide utilized according to the method disclosed herein according to any one of the embodiments above is applied at a rate in the range of from about 0.5 to about 100 g/ha, e.g., in the range of from about 1 to 80 g/ha, from about 1 to 60 g/ha, from about 5 to about 70 g/ha, from about 10 to about 60 g/ha, or from about 20 to about 50 g/ha, or from about 20 to 45 g/ha, or from about 30 to 45 g/ha, or from about 40 to 55 g/ha.

[0065] In certain embodiments, florpyrauxifen or a salt, an ester, or a combination thereof utilized according to the method disclosed herein according to any one of the embodiments above is applied at a rate in the range of from about 0.5 to about 80 g/ha, e.g., in the range of from about 1 to 60 g/ha, from about 2 to about 50 g/ha, from about 5 to about 40 g/ha, or from about 7 to about 30 g/ha (calculated on an acid equivalent base of florpyrauxifen); and the acylsulfonamide utilized according to the method disclosed herein according to any one of the embodiments above is applied at a rate in the range of from about 0.5 to about 100 g/ha, e.g., in the range of from about 1 to 80 g/ha, from about 5 to about 70 g/ha, from about 10 to about 60 g/ha, or from about 20 to about 50 g/ha.

[0066] In certain embodiments, the ratio between the application rate (g/ha) of florpyrauxifen or a salt, an ester, or a combination thereof and the application rate (g/ha) of the acylsulfonamide, utilized according to the method disclosed herein according to any one of the embodiments above, is from about 1 :50 to about 50: 1, e.g., from about 1 :30 to about 30: 1, from about 1 :20 to about 20: 1, or from about 1 : 10 to about 10: 1, respectively (calculated on an acid equivalent base of florpyrauxifen).

[0067] It should be noted that all numbers throughout this specification which refer to florpyrauxifen, e.g., ratios and application rate, are calculated on an acid equivalent base of florpyrauxifen. The term “acid equivalent” (a.e.) refers to the amount of the acid form of an active ingredient such as florpyrauxifen that is calculated from the amount of a salt or ester form of that active ingredient. For example, if the acid form of an active ingredient "Z” has a molecular weight of 100 Dalton, and the salt form of Z has a molecular weight of 130 Dalton, an application of 130 g ai/ha of the Z salt would be equal to applying 100 g ae/ha of the acid form of Z: 130 g ai/ha Z salt * (100 Da Z acid / 130 Da Z salt) = 100 g ae/ha Z acid. Specifically, 100 g of florpyrauxifen in the form of benzyl-ester thereof (439.24 g/mol) equals to 79 g of florpyrauxifen in the acid form thereof (349.11 g/mol).

[0068] Unless otherwise indicated, all numbers expressing, e.g., application rates or ratios between components, used in this specification, are to be understood as being modified in all instances by the term "about". Accordingly, unless indicated to the contrary, the numerical parameters set forth in this specification are approximations that may vary by up to plus or minus 10% depending upon the desired properties to be obtained by the present invention.

[0069] The invention will now be illustrated by the following non-limiting Examples.

CLAUSES

[0070] CLAUSE 1 : A mixture comprising: (i) florpyrauxifen or a salt, an ester, or a combination thereof as an herbicide; and (ii) an acylsulfonamide as a safener.

[0071] CLAUSE 2: The mixture of clause 1, further comprising an additional herbicide.

[0072] CLAUSE 3: The mixture of clause 2, wherein said additional herbicide is selected from the group consisting of a very long-chain fatty acid synthesis inhibitor such as dimethenamid; an acetolactate synthase inhibitor such as thiencarbazone; and a hydroxyphenyl pyruvate dioxygenase inhibitor such as topramezone, mesotrione and tembotrione.

[0073] CLAUSE 4: The mixture of clause 1, wherein said mixture comprises florpyrauxifen or a salt, an ester, or a combination thereof, as the only herbicide; and an acylsulfonamide as the only safener.

[0074] CLAUSE 5: The mixture of any one of clauses 1-4, wherein said florpyrauxifen is in the form of a free acid or an ester thereof.

[0075] CLAUSE 6: The herbicidal mixture of clause 5, wherein florpyrauxifen is in the form of benzyl ester thereof. [0076] CLAUSE 7: The mixture of any one of clauses 1-6, wherein said acylsulfonamide is cyprosulfamide.

[0077] CLAUSE 8: The mixture of any one of clauses 1-7, wherein said mixture does not include an additional safener.

[0078] CLAUSE 9: The mixture of any one of clauses 1-8, wherein said mixture does not contain an insecticide.

[0079] CLAUSE 10: The mixture of any one of clauses 1-9, wherein the weight ratio between florpyrauxifen to said safener is from about 1 : 1 to about 1 : 15, respectively (calculated on an acid equivalent base of florpyrauxifen).

[0080] CLAUSE 11 : A composition comprising: (i) a mixture as defined in any one of clauses 1-10; and (iii) agriculturally acceptable carrier.

[0081] CLAUSE 12: The composition of clause 11, further comprising at least one agriculturally acceptable excipient such as a surfactant.

[0082] CLAUSE 13: The composition of clause 11 or 12, wherein the weight ratio between florpyrauxifen to said safener is from about 1 : 1 to about 1 : 15, respectively (calculated on an acid equivalent base of florpyrauxifen).

[0083] CLAUSE 14: The composition of any one of clauses 11-13, wherein said florpyrauxifen in the form of a free acid or an ester thereof.

[0084] CLAUSE 15: The composition of clause 14, wherein florpyrauxifen is in the form of benzyl ester thereof.

[0085] CLAUSE 16: The composition of any one of clauses 11-15, wherein said acylsulfonamide is cyprosulfamide.

[0086] CLAUSE 17: A method of controlling weed comprising applying to a locus an effective amount of a mixture comprising: (i) florpyrauxifen or a salt, an ester, or a combination thereof as an herbicide; and (ii) an acylsulfonamide as a safener.

[0087] CLAUSE 18: The method of clause 17, wherein said locus is a field of crop. [0088] CLAUSE 19: The method of clause 18, wherein said crop is corn (maize).

[0089] CLAUSE 20: The method according to any one of clauses 17-19, wherein florpyrauxifen or a salt, an ester, or a combination thereof; and said acyl sulfonamide are applied from a sole composition.

[0090] CLAUSE 21 : The method according to any one of clauses 17-19, wherein florpyrauxifen or a salt, an ester, or a combination thereof; and said acyl sulfonamide are applied from two separate compositions, either concurrently or sequentially in any order.

[0091] CLAUSE 22: The method of clause 20 or 21, wherein each one of said compositions is a soluble liquid composition, suspension concentrate, emulsifiable concentrate, oil dispersion, suspoemulsion, or concentrated aqueous emulsion.

[0092] CLAUSE 23: The method of clause of any one of clauses 17-22, wherein: (i) said acylsulfonamide is applied at a rate in the range of from about 0.5 to about 100 g/ha, preferably in the range of from about 1 to 80 g/ha; and/or (ii) florpyrauxifen or a salt, an ester, or a combination thereof is applied at a rate in the range of from about 0.5 to about 80 g/ha, preferably in the range of from about 1 to 60 g/ha (calculated on an acid equivalent base of florpyrauxifen).

[0093] CLAUSE 24: The method of any one of clauses 17-23, wherein the ratio between the application rate (g/ha) of said acylsulfonamide and the application rate (g/ha) of florpyrauxifen or a salt, an ester, or a combination thereof is from about 1 :50 to about 50: 1, respectively (calculated on an acid equivalent base of florpyrauxifen).

[0094] CLAUSE 25: The method of any one of clauses 17-24, wherein said florpyrauxifen in the form of a free acid or an ester thereof.

[0095] CLAUSE 26: The method of clause 25, wherein florpyrauxifen is in the form of benzyl ester thereof.

[0096] CLAUSE 27: The method of any one of clauses 17-26, wherein said acyl sulfonamide is cyprosulfamide. EXAMPLES

Example 1. Assessment of the phytotoxicity of a mixture of florpyrauxifen-benzyl and a safener in corn (maize)

[0097] Objective. Assessing the phytotoxicity of florpyrauxifen-benzyl combined with safeners in corn.

[0098] Materials and methods. Two trials were conducted in a greenhouse using pots. The trials included control groups, florpyrauxifen-benzyl applied alone at two different dosage rates; and florpyrauxifen-benzyl applied at two dose rates combined with safeners, as depicted in Table 1. Among the safeners tested were isoxadifen-ethyl and cyprosulfamide.

Table 1 g ai/Ha = gram active ingredient per hectare

[0099] Trial 1 Seeds of com were planted in pots, and when the plants reached the 2-3 leaves stage, they were sprayed according to the protocol described in Table 1. Phytotoxicity assessments were conducted at two time points: 7 days after application (DAA) and 14 DAA (Figures 1 A and IB, respectively). The scoring system ranged from 0 to 3, with 0 indicating no phytotoxicity and 3 indicating major phytotoxicity.

[00100] Results. The phytotoxicity results are presented in Figures 1A and IB and show that florpyrauxifen-benzyl alone exhibited phytotoxicity to the corn plants (entries 2 and 3) and the safener isoxadifen-ethyl was not able to sufficiently reduce the phytotoxicity of the florpyrauxifen- benzyl at both rates tests (entries 6 and 7). In contrast, the combination of florpyrauxifen-benzyl with cyprosulfamide reduced significantly the phytotoxicity of the florpyrauxifen-benzyl at both rates and at 7 DAA and 14 DAA (entries 4 and 5). At 14 DAA isoxadifen even increased phytotoxicity.

[00101] Trial 2 Seeds of com were planted in pots, and when the plants reached the 4-5 leaves stage, they were sprayed according to the protocol described in Trial 1 for UTC water (entry 1), florpyrauxifen at 11.25 g/ha (entry 3), florpyrauxifen-benzyl (11.25 g/ha) + cyprosulfamide (45 g/ha) (entry 5) and florpyrauxifen-benzyl (11.25 g/ha) + isoxadifen- ethyl (50 g/ha) (entry 7). Phytotoxicity assessments were conducted at two time points: 7 DAA and 14 DAA (Figures 2A and 2B, respectively). The scoring system ranged from 0 to 3, with 0 indicating no phytotoxicity and 3 indicating major phytotoxicity. [00102] Results. The phytotoxicity results are presented in Figures 2A and 2B and show that isoxadifen-ethyl was not able to reduce the phytotoxicity of florpyrauxifien-baenzyl on corn (entry 7), whereas cyprosulfamide reduced significantly the phytotoxicity of florpyrauxifien-baenzyl (entry 5), at 7 DAA as well as at 14 DAA.

REFERENCES

Cataneo A.C., Ferreira L.C., Mischan MM., Velini E.D., Corniani N., Cerdeira A.L. Mefenpyr-diethyl action on fenoxaprop-p-ethyl detoxification in wheat varieties. Planta Daninha, 2013, 31, 387-393. Davies J., Caseley J.C. Herbicide safeners: a review. Pesticide Science, 1999, 55, 1043-1058.

Giannakopoulos G., Dittgen J., Schulte W ., Zoellner P., Helmke H., Lagojda A., Edwards R. Safening activity and metabolism of the safener cyprosulfamide in maize and wheat. Pest management science, 2020, 76, 3413-3422. Kraehmer H., Laber B., Rosinger C., Schulz A. Herbicides as weed control agents: state of the art: I. Weed control research and safener technology: the path to modern agriculture. Plant physiology, 2014, 166, 1119-1131.

Hatzios K.K., Burgos N. Metabolism-based herbicide resistance: regulation by safeners. Weed science, 2004, 52, 454-467.

Claims

1. A mixture comprising: (i) florpyrauxifen in the form of an ester thereof as an herbicide; and (ii) an acylsulfonamide as a safener.

2. The mixture of claim 1, further comprising an additional herbicide.

3. The mixture of claim 2, wherein said additional herbicide is selected from the group consisting of a very long-chain fatty acid synthesis inhibitor such as dimethenamid; an acetolactate synthase inhibitor such as thiencarbazone; and a hydroxyphenyl pyruvate dioxygenase inhibitor such as topramezone, mesotrione and tembotrione.

4. The mixture of claim 1, wherein said mixture comprises said florpyrauxifen in the form of an ester, as the only herbicide; and said acylsulfonamide as the only safener.

5. The herbicidal mixture of any one of claims 1-4, wherein said florpyrauxifen is in the form of benzyl ester thereof.

6. The mixture of any one of claims 1-5, wherein said acyl sulfonamide is cyprosulfamide.

7. The mixture of any one of claims 1-6, wherein said florpyrauxifen is in the form of benzyl ester thereof; and said acylsulfonamide is cyprosulfamide.

8. The mixture of any one of claims 1-7, wherein said mixture does not include an additional safener.

9. The mixture of any one of claims 1-8, wherein said mixture does not contain an insecticide.

10. A composition comprising: (i) a mixture as defined in any one of claims 1-9; and (iii) agriculturally acceptable carrier.

11. The composition of claim 10, wherein the weight ratio between florpyrauxifen to said safener is from about 1 : 1 to about 1 : 15, respectively (calculated on an acid equivalent base of florpyrauxifen).

12. A method of controlling weed comprising applying to a locus an effective amount of a mixture comprising: (i) florpyrauxifen in the form of an ester thereof as an herbicide; and (ii) an acylsulfonamide as a safener.

13. The method of claim 12, wherein said locus is a field of corn (maize) crop.

14. The method according to any one of claims 12 or 13, wherein said florpyrauxifen in the form of an ester; and said acylsulfonamide are applied from a sole composition.

15. The method according to any one of claims 12 or 13, wherein said florpyrauxifen in the form of an ester; and said acylsulfonamide are applied from two separate compositions, either concurrently or sequentially in any order.