Patent Application
20250107525
The disclosure relates generally to the field of weed management. More specifically, to novel keto-diester compounds and compositions containing such compounds for the control of undesired vegetation.
The selective control of unwanted vegetation, such as weeds, is a major industry. The aim of using herbicides is to improve agricultural productivity by killing unwanted herbs and weeds. Vegetation can be controlled using herbicides that are pre-emergent or post-emergent. Pre-emergent herbicides, by definition, are herbicides that are applied prior to the emergence of weeds above the ground. Post-emergent herbicides are used to kill weeds after they have emerged above the ground
The use of some synthetic herbicides has led to both human and environmental toxicological issues. These problems have led to stringent regulations on the use of herbicides, which led to increases in the demand for bio-based herbicides. At present, bialaphos, phosphinothricin, and pelargonic acid are among the few commercially-available bio-based herbicides.
Furthermore, to date, weeds have evolved resistance to most herbicides, including those with 21 of the 31 known herbicide sites of action. Development of new bio-based herbicides is a key part of combating herbicide resistance.
Thus, new bio-based herbicides that are safe for humans, animals, and the environment are urgently needed.
Provided herein are novel keto-diester compounds, methods of making such compounds, biocontrol compositions comprising such compounds, and methods of using such compounds and compositions as herbicides.
In an embodiment, the disclosure relates to a keto-diester of formula (VIII)
or an herbicidally-effective salt thereof;
wherein n is independently 0, 1, 2, 3, 4, or 5; R1 and R2 are independently H or an alkyl group; R3 is independently:
where m is independently 0, 1, 2, 3, 4, 5; R4 and R5 are independently H, alkyl, aryl, heteroaryl, alkyl aryl, alkyl heteroaryl; X and Y are independently H, alkyl, NO2, SO2Me, CF3, halide, NH, OH, SH or a derivative thereof; and Z is independently CH or N.
In some embodiments of the disclosure, the composition optionally comprises a carrier and/or a surfactant. In some embodiments of the disclosure, the composition further comprises at least one additional biologically-active compound. In some embodiments of the disclosure, the at least one additional biologically-active compound in the composition is a fungicide, an insecticide, a nematocide, a bactericide, a pharmaceutical, or an acaricide.
In an embodiment, the disclosure relates to a method for preparing a novel keto-diester or an herbicidally effective salt thereof, where the method comprises condensation of a protected diester of formula (II)
with at least one alkyl or aryl acid in the presence of an activating agent and a base in a single pot reaction to prepare novel keto-diesters. In formula II, n is independently 0, 1, 2, 3, 4, or 5, and R1 and R2 are independently H or an alkyl group. The readily available alkyl or aryl acids may be activated in situ with an activating agent prior to condensation in a one pot reaction to yield novel ketodiesters. The activating agent may be a diimide, an inorganic chloride, or sterically hindered aromatic acid anhydride. The base may be a basic resin such as AMBERLITE IRA-410, DOWEX 1-X8 or AMBERCHROM 1X4 chloride form.
In an embodiment, the disclosure relates to a method for controlling undesired vegetation, the method comprising contacting the vegetation or its environment with an effective amount of a keto-diester as taught herein, a derivative thereof, or a herbicidally-effective salt thereof.
The patent or application file contains at least one drawing executed in color. Copies of this patent or patent application publication with color drawing(s) will be provided by the office upon request and payment of the necessary fec.
The inventors have surprisingly discovered that novel keto-diester compounds derived from carboxylic acids and compositions comprising such compounds present with herbicidal activity. Disclosed herein are methods of preparing such compounds and compositions comprising such compounds. Also disclosed are methods for controlling undesired vegetation by contacting the undesired vegetation or its environment with an effective amount of such a compound or composition.
The present disclosure is based on the finding that keto-diester derivatives as defined herein, exhibit surprisingly good herbicidal activity. Thus, according to the present disclosure there is provided a compound of formula (VIII) or an agronomically acceptable salt or zwitterionic species thereof for use as a herbicide.
The disclosure relates to novel keto-diesters of formula (VIII):
or an herbicidally-effective salt thereof; where n is independently 0, 1, 2, 3, 4, or 5; R1 and R2 are independently H or an alkyl group; R3 is independently
where m is independently 0, 1, 2, 3, 4, 5; R4 and R5 are independently H, alkyl, aryl, heteroaryl, alkyl aryl, alkyl heteroaryl; X and Y are independently H, alkyl, NO2, SO2Me, CF3, halide, NH, OH, SH or a derivative thereof; and Z is independently CH or N.
As used herein, the term, “alkyl” means a straight-chain, branched open-chain, or branched cyclic-chain saturated hydrocarbon group which is optionally mono-or polysubstituted, and in the latter case is referred to as “substituted alkyl”. Substituents may be halogen atoms, alkoxy, haloalkoxy, cyano, alkylthio, haloalkylthio, amino or nitro groups. In some embodiments the substituents are methoxy, methyl, fluoroalkyl, cyano, nitro, fluorine, chlorine, bromine, or iodine. The prefix “bis” also includes identical alkyl groups, e.g., dimethyl, diethyl, dipropyl, a combination of different alkyl groups, e.g., methyl (cthyl) or ethyl (methyl), or cyclic groups, e.g., —CH2 (CH2), CH2- wherein n=2, 3, or 4. The term aryl includes both substituted and unsubstituted phenyl, pyridyl, naphthyl, anthracenyl, imidazolyl, oxazolyl, thiazolyl.
The term “aliphatic” or “aliphatic group,” as used herein, denotes a hydrocarbon moiety that may be straight-chain (i.e., unbranched), branched, or cyclic (including fused, bridging, and spirofused polycyclic) and may be completely saturated or may contain one or more units of unsaturation, but which is not aromatic. Unless otherwise specified, aliphatic groups contain 1-20 carbon atoms. Aliphatic groups include, but are not limited to, linear or branched, alkyl, alkenyl, and alkynyl groups, and hybrids thereof such as (cycloalkyl) alkyl, (cycloalkenyl) alkyl or (cycloalkyl) alkenyl.
The term “alkyl” as used herein is a branched or unbranched saturated hydrocarbon group of 1 to 24 carbon atoms, such as methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, s-butyl, t-butyl, n-pentyl, isopentyl, s-pentyl, neopentyl, hexyl, heptyl, octyl, nonyl, decyl, dodecyl, tetradecyl, hexadecyl, cicosyl, tetracosyl, and the like. The alkyl group can be cyclic or acyclic. The alkyl group can be branched or unbranched. The alkyl group can also be substituted or unsubstituted. For example, the alkyl group can be substituted with one or more groups including, but not limited to, alkyl, cycloalkyl, alkoxy, amino, ether, halide, hydroxy, nitro, silyl, sulfo-oxo, or thiol, as described herein. A “lower alkyl” group is an alkyl group containing from one to six (e.g., from one to four) carbon atoms. The term alkyl group can also be a C1 alkyl, C1-C2 alkyl, C1-C3 alkyl, C1-C4 alkyl, C1-C5 alkyl, C1-C6 alkyl, C1-C7 alkyl, C1-C8 alkyl, C1-C9 alkyl, C1-C10 alkyl, and the like up to and including a C1-C24 alkyl.
Throughout the specification “alkyl” is generally used to refer to both unsubstituted alkyl groups and substituted alkyl groups; however, substituted alkyl groups are also specifically referred to herein by identifying the specific substituent(s) on the alkyl group. For example, the term “halogenated alkyl” or “haloalkyl” specifically refers to an alkyl group that is substituted with one or more halide, e.g., fluorine, chlorine, bromine, or iodine. Alternatively, the term “monohaloalkyl” specifically refers to an alkyl group that is substituted with a single halide, e.g. fluorine, chlorine, bromine, or iodine. The term “polyhaloalkyl” specifically refers to an alkyl group that is independently substituted with two or more halides, i.e. each halide substituent need not be the same halide as another halide substituent, nor do the multiple instances of a halide substituent need to be on the same carbon. The term “alkoxyalkyl” specifically refers to an alkyl group that is substituted with one or more alkoxy groups, as described below. The term “aminoalkyl” specifically refers to an alkyl group that is substituted with one or more amino groups. The term “hydroxyalkyl” specifically refers to an alkyl group that is substituted with one or more hydroxy groups. When “alkyl” is used in one instance and a specific term such as “hydroxyalkyl” is used in another, it is not meant to imply that the term “alkyl” does not also refer to specific terms such as “hydroxyalkyl” and the like.
This practice is also used for other groups described herein. That is, while a term such as “cycloalkyl” refers to both unsubstituted and substituted cycloalkyl moieties, the substituted moieties can, in addition, be specifically identified herein; for example, a particular substituted cycloalkyl can be referred to as, e.g., an “alkylcycloalkyl.” Similarly, a substituted alkoxy can be specifically referred to as, e.g., a “halogenated alkoxy,” a particular substituted alkenyl can be, e.g., an “alkenylalcohol,” and the like. Again, the practice of using a general term, such as “cycloalkyl,” and a specific term, such as “alkylcycloalkyl,” is not meant to imply that the general term does not also include the specific term.
The term “cycloalkyl” as used herein is a non-aromatic carbon-based ring composed of at least three carbon atoms. Examples of cycloalkyl groups include, but are not limited to, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, norbornyl, and the like. The term “heterocycloalkyl” is a type of cycloalkyl group as defined above, and is included within the meaning of the term “cycloalkyl,” where at least one of the carbon atoms of the ring is replaced with a heteroatom such as, but not limited to, nitrogen, oxygen, sulfur, or phosphorus. The cycloalkyl group and heterocycloalkyl group can be substituted or unsubstituted. The cycloalkyl group and heterocycloalkyl group can be substituted with one or more groups including, but not limited to, alkyl, cycloalkyl, alkoxy, amino, ether, halide, hydroxy, nitro, silyl, sulfo-oxo, or thiol as described herein.
The term “aromatic group” as used herein refers to a ring structure having cyclic clouds of delocalized π electrons above and below the plane of the molecule, where the π clouds contain (4n+2) π electrons. A further discussion of aromaticity is found in Morrison and Boyd, Organic Chemistry, (5th Ed., 1987), Chapter 13, entitled “Aromaticity,” pages 477-497, incorporated herein by reference. The term “aromatic group” is inclusive of both aryl and heteroaryl groups.
The term “aryl” as used herein is a group that contains any carbon-based aromatic group including, but not limited to, benzene, naphthalene, phenyl, biphenyl, anthracene, and the like. The aryl group can be substituted or unsubstituted. The aryl group can be substituted with one or more groups including, but not limited to, alkyl, cycloalkyl, alkoxy, alkenyl, cycloalkenyl, alkynyl, cycloalkynyl, aryl, heteroaryl, aldehyde, —NH2, carboxylic acid, ester, ether, halide, hydroxy, ketone, azide, nitro, silyl, sulfo-oxo, or thiol as described herein. The term “biaryl” is a specific type of aryl group and is included in the definition of “aryl.” In addition, the aryl group can be a single ring structure or comprise multiple ring structures that are either fused ring structures or attached via one or more bridging groups such as a carbon-carbon bond. For example, biaryl to two aryl groups that are bound together via a fused ring structure, as in naphthalene, or are attached via one or more carbon-carbon bonds, as in biphenyl.
The term “heteroaryl” as used herein refers to an aromatic group that has at least one heteroatom incorporated within the ring of the aromatic group. Examples of heteroatoms include, but are not limited to, nitrogen, oxygen, sulfur, and phosphorus, where N-oxides, sulfur oxides, and dioxides are permissible heteroatom substitutions. The heteroaryl group can be substituted or unsubstituted. The heteroaryl group can be substituted with one or more groups including, but not limited to, alkyl, cycloalkyl, alkoxy, amino, ether, halide, hydroxy, nitro, silyl, sulfo-oxo, or thiol as described herein. Heteroaryl groups can be monocyclic, or alternatively fused ring systems. Heteroaryl groups include, but are not limited to, furyl, imidazolyl, pyrimidinyl, tetrazolyl, thienyl, pyridinyl, pyrrolyl, N-methylpyrrolyl, quinolinyl, isoquinolinyl, pyrazolyl, triazolyl, thiazolyl, oxazolyl, isoxazolyl, oxadiazolyl, thiadiazolyl, isothiazolyl, pyridazinyl, pyrazinyl, benzofuranyl, benzodioxolyl, benzothiophenyl, indolyl, indazolyl, benzimidazolyl, imidazopyridinyl, pyrazolopyridinyl, and pyrazolopyrimidinyl. Further not limiting examples of heteroaryl groups include, but are not limited to, pyridinyl, pyridazinyl, pyrimidinyl, pyrazinyl, thiophenyl, pyrazolyl, imidazolyl, benzo [d]oxazolyl, benzo [d]thiazolyl, quinolinyl, quinazolinyl, indazolyl, imidazo [1,2-b]pyridazinyl, imidazo [1,2-a]pyrazinyl, benzo [c][1,2,5]thiadiazolyl, benzo [c] [1,2,5]oxadiazolyl, and pyrido [2,3-b]pyrazinyl.
The terms “heterocycle” or “heterocyclyl,” as used herein can be used interchangeably and refer to single and multi-cyclic aromatic or non-aromatic ring systems in which at least one of the ring members is other than carbon. Thus, the term is inclusive of, but not limited to, “heterocycloalkyl,” “heteroaryl,” “bicyclic heterocycle,” and “polycyclic heterocycle.” Heterocycle includes pyridine, pyrimidine, furan, thiophene, pyrrole, isoxazole, isothiazole, pyrazole, oxazole, thiazole, imidazole, oxazole, including, 1,2,3-oxadiazole, 1,2,5-oxadiazole and 1,3,4-oxadiazole, thiadiazole, including, 1,2,3-thiadiazole, 1,2,5-thiadiazole, and 1,3,4-thiadiazole, triazole, including, 1,2,3-triazole, 1,3,4-triazole, tetrazole, including 1,2,3,4-tetrazole and 1,2,4,5-tetrazole, pyridazine, pyrazine, triazine, including 1,2,4-triazine and 1,3,5-triazine, tetrazine, including 1,2,4,5-tetrazine, pyrrolidine, piperidine, piperazine, morpholine, azetidine, tetrahydropyran, tetrahydrofuran, dioxane, and the like. The term heterocyclyl group can also be a C2 heterocyclyl, C2-C3 heterocyclyl, C2-C4 heterocyclyl, C2-C5 heterocyclyl, C2-C6 heterocyclyl, C2-C7 heterocyclyl, C2-C8 heterocyclyl, C2-C9 heterocyclyl, C2-C10 heterocyclyl, C2-C11 heterocyclyl, and the like up to and including a C2-C18 heterocyclyl. For example, a C2 heterocyclyl comprises a group which has two carbon atoms and at least one heteroatom, including, but not limited to, aziridinyl, diazetidinyl, dihydrodiazetyl, oxiranyl, thiiranyl, and the like. Alternatively, for example, a C5 heterocyclyl comprises a group which has five carbon atoms and at least one heteroatom, including, but not limited to, piperidinyl, tetrahydropyranyl, tetrahydrothiopyranyl, diazepanyl, pyridinyl, and the like. It is understood that a heterocyclyl group may be bound either through a heteroatom in the ring, where chemically possible, or one of carbons comprising the heterocyclyl ring.
New herbicide classes are needed to increase the amount of bio-based herbicides available, and to overcome the rapid evolution of target-site and non-target-site-based herbicide resistance in weeds. The compounds described herein may be used for both weed management and herbicide resistance management.
It may be beneficial to apply a keto-diester of the disclosure alone or in combination with other herbicides, or in a mixture with other crop protection agents, for example together with agents for controlling arthropod pests, phytopathogenic fungi, or bacteria. Also of interest is the miscibility a keto-diester of the disclosure with mineral salt solutions, which are employed for treating nutritional and trace element deficiencies. Other additives such as non-phytotoxic oils and oil concentrates may also be added.
As used herein, the term “effective amount” denotes an amount of a keto-diester of the disclosure, which is sufficient for controlling undesired vegetation. Such an amount can vary in a broad range and is dependent on various factors, such as the undesired vegetation species or biotype to be controlled, the developmental stage of the target weed, the climatic conditions, and the specific keto-diester of the disclosure used.
The keto-diesters of the disclosure may be converted into customary types of compositions such as solutions, emulsions, suspensions, dusts, powders, pastes, granules, pressings, capsules, or mixtures thereof. Examples for composition types are suspensions, emulsifiable concentrates, emulsions, capsules, pastes, pastilles, wettable powders, wettable dusts, pressings, granules, insecticidal articles, or gel formulations. These and further formulation types are defined in the “Catalogue of pesticide formulation types and international coding system”, Technical Monograph No. 2, 6.sup.th Ed. May 2008, CropLife International.
A composition of the disclosure may comprise a keto-diester of the disclosure and optionally a carrier. Examples of suitable carriers are solvents, liquid carriers, solid carriers, fillers, surfactants, dispersants, emulsifiers, wetting agents, adjuvants, solubilizers, penetration enhancers, protective colloids, adhesion agents, thickeners, humectants, repellents, attractants, feeding stimulants, compatibilizers, bactericides, anti-freezing agents, anti-foaming agents, colorants, tackifiers, and binders.
A solvent may be water or an organic solvent. An organic solvent may be a mineral oil fraction, a vegetable oil, an oil of animal origin, an aliphatic hydrocarbon, a cyclic hydrocarbon, an aromatic hydrocarbon, an alcohol, dimethyl sulfoxide (DMSO), a ketone, a glycol, an ester, a fatty acid, a phosphonate, an amine, an amide, or a mixture thereof. A hydrocarbon may be toluene, paraffin, tetrahydronaphthalene, or alkylated naphthalenes. An alcohol may be at least one of ethanol, propanol, butanol, benzylalcohol, or cyclohexanol. A ketone may be at least one of acetone, pentanone, or cyclohexanone. An ester may be at least one of lactate, carbonate, fatty acid ester, or gamma-butyrolactone.
A composition disclosed herein may be used with at least one solid carrier or filler such as a mineral earths, fertilizer, product of vegetable origin, and mixtures thereof A mineral carth may be, for example, silicate, silica gel, talc, kaolin, limestone, lime, chalk, clay, dolomite, diatomaceous earth, bentonite, calcium sulfate, magnesium sulfate, or magnesium oxide. A fertilizer may be, for example, ammonium sulfate, ammonium phosphate, ammonium nitrate, or urea. A product of vegetable origin may be starch, cellulose, cereal meal, tree bark meal, wood meal, or nutshell meal.
Suitable surfactants for use in a composition disclosed herein may be, for example, at least one surface-active compound, block polymer, polyelectrolyte, or mixtures thereof. A surface-active compound may be, for example, an anionic, cationic, nonionic, or amphoteric surfactant. Examples of surfactants are listed in Mccutcheon's, Vol. 1: Emulsifiers & Detergents, Mccutcheon's Directories, Glen Rock, USA, 2020 (International Ed. or North American Ed.). Such surfactants can be used at least as emulsifier, dispersant, solubilizer, wetter, penetration enhancer, protective colloid, or adjuvant.
Suitable anionic surfactants may be alkali, alkaline earth, ammonium salts of sulfonates, sulfates, phosphates, carboxylates, and mixtures thereof. Examples of sulfonates are alkylarylsulfonates, diphenylsulfonates, alpha-olefin sulfonates, lignine sulfonates, sulfonates of fatty acids and oils, sulfonates of ethoxylated alkylphenols, sulfonates of alkoxylated arylphenols, sulfonates of condensed naphthalenes, sulfonates of dodecyl-and tridecylbenzenes, sulfonates of naphthalenes and alkylnaphthalenes, sulfosuccinates or sulfosuccinamates. Examples of sulfates are sulfates of fatty acids and oils, of ethoxylated alkylphenols, of alcohols, of ethoxylated alcohols, or of fatty acid esters. Examples of phosphates are phosphate esters. Examples of carboxylates are alkyl carboxylates, and carboxylated alcohol or alkylphenol ethoxylates.
Suitable nonionic surfactants may be alkoxylates, N-substituted fatty acid amides, amine oxides, esters, sugar-based surfactants, polymeric surfactants, and mixtures thereof. Examples of alkoxylates are compounds such as alcohols, alkylphenols, amines, amides, arylphenols, fatty acids or fatty acid esters which have been alkoxylated with 1 to 50 equivalents. Ethylene oxide and/or propylene oxide may be employed for the alkoxylation, preferably ethylene oxide. Examples of N-substituted fatty acid amides are fatty acid glucamides or fatty acid alkanolamides. Examples of esters are fatty acid esters, glycerol esters or monoglycerides. Examples of sugar-based surfactants are sorbitans, ethoxylated sorbitans, sucrose and glucose esters or alkylpolyglucosides. Examples of polymeric surfactants are home-or copolymers of vinylpyrrolidone, vinylalcohols, or vinylacetate.
Suitable cationic surfactants may be quaternary surfactants, for example quaternary ammonium compounds with one or two hydrophobic groups, or salts of long-chain primary amines. Suitable amphoteric surfactants are alkylbetains and imidazolines. Suitable block polymers are block polymers of the A-B or A-B-A type comprising blocks of polyethylene oxide and polypropylene oxide, or of the A-B-C type comprising alkanol, polyethylene oxide and polypropylene oxide. Suitable polyelectrolytes are polyacids or polybases. Examples of polyacids are alkali salts of polyacrylic acid or polyacid comb polymers. Examples of polybases are polyvinylamines or polyethylencamines.
Suitable adjuvants may be compounds which have a neglectable or even no pesticidal activity themselves and which improve the biological performance of the keto-diesters of formula (III) on the target. Examples are surfactants and mineral or vegetable oils. Suitable thickeners are polysaccharides (such as xanthan gum, carboxymethylcellulose), inorganic clays (organically modified or unmodified), polycarboxylates, and silicates. Suitable bactericides are bronopol and isothiazolinone derivatives such as alkylisothiazolinones and benzisothiazolinones. Suitable anti-freezing agents are ethylene glycol, propylene glycol, urea and glycerin. Suitable anti-foaming agents are silicones, long chain alcohols, and salts of fatty acids.
Suitable colorants (such as red, blue, or green) are pigments of low water solubility and water-soluble dyes. Examples are inorganic colorants (such as iron oxide, titan oxide, iron hexacyanoferrate) and organic colorants (such as alizarin-, azo-and phthalocyanine colorants). Suitable tackifiers or binders are polyvinylpyrrolidons, polyvinylacetates, polyvinyl alcohols, polyacrylates, biological or synthetic waxes, and cellulose ethers.
In an embodiment, the disclosure relates to a method for preparing novel keto-diesters or herbicidally-effective salts thereof. The method comprises condensation of a protected diester of formula (II)
with at least one alkyl or aryl acid in the presence of an activating agent and a base in a single pot reaction to prepare novel keto-diesters. In formula II, n is independently 0, 1, 2, 3, 4, or 5; and R1 and R2 are independently H or an alkyl group. The readily available alkyl, aryl, heteroaryl, alkyl aryl, or alkyl heteroaryl acids may be activated in situ with an activating agent prior to condensation in a one pot reaction to yield novel ketodiesters. The activating agent may be a diimide, an inorganic chloride, or sterically hindered aromatic acid anhydride. The base may be a basic resin such as AMBERLITE IRA-410, DOWEX 1-X8, or AMBERCHROM 1X4 chloride form.
AMBERLITE IRA-410 chloride form is a strongly basic anion exchange resin. AMBERLITE is a registered trademark of DDP Specialty Electronic Materials; as a material for use in removing or replacing metallic or non-metallic ions or acid-forming Constituents from Fluids. DOWEX 1-X8 chloride form is a strongly basic anion exchanger. DOWEX is a trademark of The Dow Chemical Company for ionic and cationic synthetic resins. AMBERCHROM 1X4 chloride form is a fine mesh anion exchange resin. AMBERCHROM is a registered trademark of DDP Specialty Electronic Materials; as chromatographic resins and columns for use in separation, filtration, and purification of liquids and solids.
The at least one substituted alkyl, aryl acid may be 4-methylsulfonyl-2-nitrobenzoic acid, 2-chloro-4-(methylsulfonyl) benzoic acid, isovaleric acid, or phenyl propanoic acid. The base may be dimethylamino pyridine, pyridine, N-methyl morpholine.
The method for preparing the compounds taught herein may comprise adding at room temperature N, N′-dicyclohexylcarbodiimide (DCC) to a solution of a carboxylic acid in anhydrous dimethyl formamide (DMF). After cooling to 0° C., adding the protected diester, followed by N, N′-dimethylamino pyridine (DMAP). The reaction mixture may then be heated to 100° C. and stirred at the same temperature for about 30 to 45 hours. The method further comprises washing and drying the product, followed by purification. The simple synthesis of these compounds may provide a cost advantage over many currently-used commercial products that could be passed on to the farmer.
Following the disclosure, and as seen in the schematic diagram of
or reacting a compound of formula (IV) with a compound of formula (II) to obtain a compound of formula (V)
or reacting a compound of formula (VI) with a compound of formula (II) to obtain a compound of formula (VII)
where is n is independently 0, 1, 2, 3, 4, or 5; R1 and R2 are independently H or an alkyl group; X and Y are independently H, alkyl, NO2, SO2Me, CF3, halide, NH, OH, SH or a derivative thereof; and Z is CH or N.
“HPPD (4-hydroxyphenyl-pyruvate dioxygenase) inhibitors” are substances that inhibit the biosynthesis of 4-hydroxyphenyl-pyruvate dioxygenase. Examples of HPPD inhibitors include benzobicyclon, benzofenap, bicyclopyrone (4-hydroxy-3-[[2- [(2-methoxyethoxy) methyl]-6-(trifluoromethyl)-3-pyridinyl]carbonyl]bicyclo [3.2.1]oct-3-en-2-one), fenquinotrione (2-[[8-chloro-3,4-dihydro-4-(4-methoxyphenyl)-3-oxo-2-quinoxalinyl]carbonyl]-1,3-cyclohexanedione), isoxachlortole, isoxaflutole, mesotrione, pyrasulfotole, pyrazolynate, pyrazoxyfen, sulcotrione, tefuryltrione, tembotrione, topramezone, 5-chloro-3- [(2-hydroxy-6-oxo-1-cyclohexen-1-yl) carbonyl]-1-(4-methoxyphenyl)-2 (1 H) quinoxalinone, 4-(2,6-diethyl-4-methylphenyl)-5-hydroxy-2,6-dimethyl-3 (2H)-pyridazinone, 4-(4-fluorophenyl)-6-[ (2-hydroxy-6-oxo-1-cyclohexen-1-yl) carbonyl]-2-methyl-1,2,4-triazine-3,5 (2H,4H)-dione, 5-[(2-hydroxy-6-oxo-lcyclohexen-1-yl) carbonyl]-2-(3-methoxyphenyl)-3-(3-methoxypropyl)-4 (3H)-pyrimidinone, 2-methyl-N-(4-methyl-1,2,5-oxadiazol-3-yl)-3-(methylsulfinyl)-4-(trifluoromethyl) benzamide and 2-methyl-3-(methylsulfonyl)-N-(1-methyl-1 H-tetrazol-5-yl)-4 (trifluoromethyl) benzamide.
U.S. Pat. No. 5,550,165 teaches pharmaceutical compositions capable of inhibiting the enzyme 4-hydroxyphenylpyruvate dioxygenase (HPPD) in mammals, and the preparation of pharmaceutical compositions for treating disorders and diseases in which intervention in the metabolic sequences catalyzed at least in part by HPPD is desirable. It is anticipated that at least some of the compounds presented in the current disclosure will also possess such properties. The compounds taught herein may also be useful as insecticides on blood-feeding insects (e.g., ticks, mosquitos, and bed bugs), as HPPD inhibitors have recently been found to be effective on these insects after a blood meal because the insects' HPPD is needed to detoxify high tyrosine levels from blood.
Application of a keto-diester of formula (VIII) or an herbicidally-effective salt thereof; where n is 0, 1, 2, 3, 4, or 5; R1 and R2 are independently H or an alkyl group; R3 is independently
where m is independently 0, 1, 2, 3, 4,5; R4 and R5 are independently H, alkyl, aryl, heteroaryl, alkyl aryl, alkyl heteroaryl; X and Y are independently H, alkyl, NO2, SO2Me, CF3, halide, NH, OH, SH or a derivative thereof; and Z is independently CH or N, or a derivative thereof according to the disclosure, or compositions comprising them, may be performed from a pre-dosage device, a knapsack sprayer, a spray tank, a spray plane, or an irrigation system. The composition may comprise water, buffer, and/or further adjuvants or carriers to the desired application concentration and the ready-to-use spray liquor or the composition according to the disclosure is thus obtained. Usually, 20 to 2000 liters, preferably 50 to 400 liters, of the ready-to-use spray liquid are applied per hectare of agricultural useful area.
The phytotoxic activity of compounds belonging to formula (III), (V), or (VII) classes were evaluated in a primary bioassay. The synthetic triketone herbicides mesotrione and sulcotrione were used as positive controls. The seeds of monocot bentgrass (Agrostis stolonifera) and dicot Arabidopsis (Arabidopsis thaliana) were exposed for 7 days to 1000 μM solution of each chemical. For example, within the III series, the compound III-2 significantly reduced growth of Agrostis seedlings: most of them developed symptoms of chlorosis, some pale green and with developed, shorter leaves compared to negative controls containing H2O or 10% acetone. The seedlings growing with compounds III-3 and III-1 did not develop chlorosis although growth of some of them was reduced. Arabidopsis seedling growth was significantly affected by all of the tested compounds. As seen in
The most active of these compounds (III-2) is more active than the commercial herbicides bentazon, clomazone, glyphosate, glufosinate, asulam, chloropropham, and S-ethyl dipropyl thiocarbamate (EPTC) in the same bioassay see Michel, A., et al. (2004, “Dose-response relationships between herbicides with different modes of action and growth of Lemna paucicostata—an improved ecotoxicological method,” Environ. Toxicol. Chem. 23 (4): 1074-1079).
The keto-diesters of formula (VIII) are suitable as herbicides. They may be used as herbicides individually, as a mixture, or as an appropriate composition.
Keto-diesters of formula (VIII) or compositions comprising them may be applied to plants mainly by spraying the leaves. Here, the application can be carried out using, for example, water as carrier and customary spraying techniques using spray liquor amounts of from about 50 to 1000 L/ha (for example from 300 to 400 L/ha). The keto-diesters of formula (VIII), or compositions comprising them may also be applied by the low-volume or the ultra-low-volume method, or in the form of microgranules.
A keto-diester of formula (VIII) or a composition comprising such may be applied before, during, and/or after emergence of the undesired vegetation. Similarly, a keto-diester of formula (VIII) or a composition comprising such may be applied before or during sowing.
The presence of one or more possible asymmetric carbon atoms in a compound of formula (VIII) means that the compound may occur in chiral isomeric form, i.e., enantiomeric or diastereomeric form. Atropisomers may also occur as a result of restricted rotation about a single bond. formula (VIII) is intended to include all those possible isomeric forms and mixtures thereof. The present disclosure includes all those possible isomeric forms and mixtures thereof for a keto-diester of formula (VIII). Likewise, keto-diesters of formula (VIII) are intended to include all possible tautomers (including lactam-lactim tautomerism and keto-enol tautomerism) where present. The present disclosure includes all possible tautomeric forms for a compound of formula (VIII). Similarly, where there are di-substituted alkenes, these may be present in E or Z form or as mixtures of both in any proportion. The present disclosure includes all these possible isomeric forms and mixtures thereof for a compound of formula (VIII).
A compound of formula (VIII) will typically be provided in the form of an agronomically acceptable salt, a zwitterion, or an agronomically acceptable salt of a zwitterion. This disclosure covers all such agronomically acceptable salts, zwitterions, and mixtures thereof in all proportions.
All compounds of formula (VIII) can be present as equilibrium of tautomers. For example, ketones with an α-hydrogen can exist in an equilibrium of the keto form and the enol form.
Unless stated to the contrary, the disclosure includes all such possible tautomers.
Suitable agronomically acceptable salts useful in the present disclosure can be with cations that include but are not limited to, metals, conjugate acids of amines and organic cations. Examples of suitable metals include aluminium, calcium, cesium, copper, lithium, magnesium, manganese, potassium, sodium, iron and zinc. Examples of suitable amines include allylamine, ammonia, amylamine, arginine, benethamine, benzathine, butenyl-2-amine, butylamine, butylethanolamine, cyclohexylamine, decylamine, diamylamine, dibutylamine, diethanolamine, diethylamine, diethylenetriamine, diheptylamine, dihexylamine, diisoamylamine, diisopropylamine, dimethylamine, dioctylamine, dipropanolamine, dipropargylamine, dipropylamine, dodecylamine, ethanolamine, ethylamine, ethylbutylamine, ethylenediamine, ethylheptylamine, ethyloctylamine, ethylpropanolamine, heptadecylamine, heptylamine, hexadecylamine, hexenyl-2-amine, hexylamine, hexylheptylamine, hexyloctylamine, histidine, indoline, isoamylamine, isobutanolamine, isobutylamine, isopropanolamine, isopropylamine, lysine, meglumine, methoxyethylamine, methylamine, methylbutylamine, methylethylamine, methylhexylamine, methylisopropylamine, methylnonylamine, methyloctadecylamine, methylpentadecylamine, morpholine, N,N-diethylethanolamine, N-methylpiperazine, nonylamine, octadecylamine, octylamine, oleylamine, pentadecylamine, pentenyl-2-amine, phenoxyethylamine, picoline, piperazine, piperidine, propanolamine, propylamine, propylenediamine, pyridine, pyrrolidine, sec-butylamine, stearylamine, tallowamine, tetradecylamine, tributylamine, tridecylamine, trimethylamine, triheptylamine, trihexylamine, triisobutylamine, triisodecylamine, triisopropylamine, trimethylamine, tripentylamine, tripropylamine, tris (hydroxymethyl) aminomethane, and undecylamine. Examples of suitable organic cations include benzyltributylammonium, benzyltrimethylammonium, benzyltriphenylphosphonium, choline, tetrabutylammonium, tetrabutylphosphonium, tetraethylammonium, tetraethylphosphonium, tetramethylammonium, tetramethylphosphonium, tetrapropylammonium, tetrapropylphosphonium, tributylsulfonium, tributylsulfoxonium, tricthylsulfonium, tricthylsulfoxonium, trimethylsulfonium, trimethylsulfoxonium, tripropylsulfonium, and tripropylsulfoxonium.
Compounds disclosed herein can also be mixed with one or more other biologically active compounds or agents including herbicides, herbicide safeners, fungicides, insecticides, nematocides, bactericides, acaricides, growth regulators such as insect molting inhibitors and rooting stimulants, chemosterilants, semiochemicals, repellents, attractants, pheromones, feeding stimulants, plant nutrients, other biologically active compounds or entomopathogenic bacteria, virus or fungi to form a multi-component pesticide giving an even broader spectrum of agricultural protection. Mixtures of the compounds of the disclosure with other herbicides can broaden the spectrum of activity against additional weed species, and suppress the proliferation of any resistant biotypes. Thus, the present disclosure also pertains to a composition comprising a compound as described (in a herbicidally effective amount) and at least one additional biologically active compound or agent (in a biologically effective amount) and can further comprise at least one of a surfactant, a solid diluent or a liquid diluent. The other biologically active compounds or agents can be formulated in compositions comprising at least one of a surfactant, solid or liquid diluent. For mixtures comprising the keto-diesters taught herein, one or more other biologically active compounds or agents can be formulated together with a compound of as described to form a premix, or one or more other biologically active compounds or agents can be formulated separately from the compound as claimed, and the compositions combined together before application (e.g., in a spray tank) or alternatively applied in succession.
Unless otherwise explained, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this disclosure belongs. The singular terms “a”, “an”, and “the” include plural referents unless context clearly indicates otherwise. Similarly, the word “or” is intended to include “and” unless the context clearly indicate otherwise.
As used herein, the term “about” is defined as plus or minus ten percent of a recited value. For example, about 1.0 g means 0.9 g to 1.1 g.
As used herein, the terms “comprises,” “comprising,” “includes,” “including,” “has,” “having,” “contains”, “containing,” “characterized by” or any other variation thereof, are intended to cover a non-exclusive inclusion, subject to any limitation explicitly indicated. For example, a composition, mixture, process or method that comprises a list of elements is not necessarily limited to only those elements but may include other elements not expressly listed or inherent to such composition, mixture, process or method.
The transitional phrase “consisting of” excludes any element, step, or ingredient not specified. If in the claim, such would close the claim to the inclusion of materials other than those recited except for impurities ordinarily associated therewith. When the phrase “consisting of” appears in a clause of the body of a claim, rather than immediately following the preamble, it limits only the element set forth in that clause; other elements are not excluded from the claim as a whole.
The transitional phrase “consisting essentially of” is used to define a composition, process or method that includes materials, steps, features, components, or elements, in addition to those literally disclosed, provided that these additional materials, steps, features, components, or elements do not materially affect the basic and novel characteristic(s) of the claimed composition. The term “consisting essentially of” occupies a middle ground between “comprising” and “consisting of”.
As referred to herein, the term “seedling”, used either alone or in a combination of words means a young plant developing from the embryo of a seed.
Compounds described herein can exist as one or more stereoisomers. The various stereoisomers include enantiomers, diastereomers, atropisomers and geometric isomers. Stereoisomers are isomers of identical constitution but differing in the arrangement of their atoms in space and include enantiomers, diastereomers, cis-trans isomers (also known as geometric isomers) and atropisomers. Atropisomers result from restricted rotation about single bonds where the rotational barrier is high enough to permit isolation of the isomeric species. One skilled in the art will appreciate that one stereoisomer may be more active and/or may exhibit beneficial effects stereoisomer(s). Additionally, the skilled artisan knows how when enriched relative to the other stereoisomer(s) or when separated from the other to separate, enrich, and/or to selectively prepare said stereoisomers. The compounds described herein may be present as a mixture of stereoisomers, individual stereoisomers, as an optically active form, or as chiral salts of racemic stereoisomers.
Embodiments of the present disclosure are shown and described herein. It will be obvious to those skilled in the art that such embodiments are provided by way of example only. Numerous variations, changes, and substitutions will occur to those skilled in the art without departing from the invention. Various alternatives to the embodiments of the invention described herein may be employed in practicing the invention. It is intended that the included claims define the scope of the invention and that methods and structures within the scope of these claims and their equivalents are covered thereby. All publications, patents, and patent applications mentioned in this specification are herein incorporated by reference to the same extent as if each individual publication, patent, or patent application was specifically and individually indicated to be incorporated by reference.
Having now generally described this invention, the same will be better understood by reference to certain specific examples, which are included herein only to further illustrate the invention and are not intended to limit the scope of the invention as defined by the claims.
A general reaction scheme for the preparation of keto-diesters is shown below. The newly prepared keto-diesters have formula (III), where R1 and R2 are independently H or an alkyl group; X and Y are independently H, alkyl, NO2, SO2Me, CF3, halide, NH, OH, SH or a derivative thereof; and Z is CH or N.
Exemplary novel keto-diesters were prepared by adding at room temperature (2.0 equiv.) N, N′-dicyclohexylcarbodiimide (DCC) to a solution of aryl carboxylic acid (formula I, 2.0 equiv.) in anhydrous dimethyl formamide (DMF). After 15 minutes, the reaction mixture was cooled to 0° C. and the protected diester (formula II, 1.0 equiv.) was added, followed by N, N′-dimethylamino pyridine (DMAP) (2.0 equiv.) The reaction mixture was heated to 100° C. and stirred at the same temperature for about 30 to 45 hours. At the end of the reaction, the insoluble urea was filtered off and washed with dichloromethane. The combined washings were extracted with 1N HCl, and washed with water and brine. After the organic phase was dried over sodium sulfate, the solvent was removed, and the residue was purified by flash-column chromatography.
Exemplary keto-diesters prepared by this method were 5-(2-chloro-4-(methylsulfonyl) benzoyl)-2,2-dimethyl-1,3-dioxane-4,6-dione (formula III-1), 2,2-dimethyl-5-(2-nitro-4-(trifluoromethyl) benzoyl)-1,3-dioxane-4,6-dione (formula III-2), 2,2-dimethyl-5-(4-(methylsulfonyl)-2-nitrobenzoyl)-1,3-dioxane-4,6-dione (formula III-3), 2,2-dimethyl-5-(3-phenylpropanoyl)-1,3-dioxane-4,6-dione (formula III-4), 8-(3-phenylpropanoyl)-6,10-dioxaspiro [4.5] decane-7,9-dione (formula III-5), 5-(3-phenylpropanoyl)-2,2-dipropyl-1,3-dioxane-4,6-dione (formula III-6), 2,2-dimethyl-5-(3-methylbutanoyl)-1,3-dioxane-4,6-dione (formula VII-1) and 8-(3-methylbutanoyl)-6,10-dioxaspiro [4.5] decane-7,9-dione (formula VII-2).
III-1=5-(2-chloro-4-(methylsulfonyl) benzoyl)-2,2-dimethyl-1,3-dioxane-4,6-dione (R1=R2=Me, X=Cl, Y=SO2Me and Z=H): 1H NMR (400 MHZ, MeOD) δ 7.88 (d, J=1.7 Hz, 1H), 7.83 (dd, J=8.0, 1.7 Hz, 1H), 7.39 (d, J=8.0 Hz, 1H), 3.15 (s, 3H), 1.68 (s, 6H). HRMS (ESI) m/z calculated for C14H12CIO7S [M-H]− 358.9992, found 359.0036.14. A method for controlling undesired vegetation, the method comprising contacting the vegetation, or its environment with an effective amount of a composition of claim 2.
III-2=2,2-dimethyl-5-(2-nitro-4-(trifluoromethyl) benzoyl)-1,3-dioxane-4,6-dione (R1=R2=Me, X=NO2, Y=CF3 and Z=H): 1H NMR (400 MHZ, MeOD) δ 8.38 (s, 1H), 7.97 (d, J=7.4 Hz, 1H), 7.51 (d, J=7.8 Hz, 1H), 1.66 (s, 6H). HRMS (ESI) m/z calculated for C14H9F3NO7 [M-H]− 360.0331, found 360.0391.
III-3=2,2-dimethyl-5-(4-(methylsulfonyl)-2-nitrobenzoyl)-1,3-dioxane-4,6-dione (R1=R2=Me, X=NO2, Y=SO2Me and Z=H): 1NMR (400 MHZ, MeOD) δ 8.61 (d, J=1.7 Hz, 1H), 8.30-8.15 (m, 1H), 7.57 (d, J=8.0 Hz, 1H), 3.22 (s, 3H), 1.67 (s, 6H). HRMS (ESI) m/z calculated for C14H12NO9S [M-H]− 370.0233, found 370.0245.
III-4=2,2-dimethyl-5-(3-phenylpropanoyl)-1,3-dioxane-4,6-dione (R1=R2=Me, X, Y, Z=H): 1H NMR (400 MHZ, CDCl3) δ 7.30-7.17 (m, 5H), 3.46-3.28 (m, 2H), 3.01 (dd, J=8.9, 6.7 Hz, 2H), 1.65 (s, 6H). 13C NMR (101 MHz, CDCl3) δ 196.6, 170.6, 160.3, 139.8, 128.7, 128.6, 126.6, 105.0, 92.0, 37.3, 32.1, 26.9.
III-5=8-(3-phenylpropanoyl)-6, 10-dioxaspiro [4.5] decane-7,9-dione (n=1-cyclopentenyl, X, Y, Z=H): 1H NMR (500 MHZ, CDCl3) δ 15.19 (s, 1H), 7.40-7.10 (m, 5H), 3.49-3.33 (m, 2H), 3.02 (dd, J=8.8, 6.7 Hz, 2H), 2.20-2.00 (m, 4H), 2.00-1.69 (m, 4H). 13C NMR (126 MHz, CDCl3) δ 196.6, 171.3, 161.0, 139.8, 128.7, 128.6, 126.7, 114.3, 92.6, 37.9, 37.3, 32.1, 23.2.
III-6=5-(3-phenylpropanoyl)-2,2-dipropyl-1,3-dioxane-4,6-dione (R1=R2=n-propyl, X, Y, Z=H): 1H NMR (400 MHZ, CDCl3) δ 15.35 (s, 1H), 7.38-7.13 (m, 5H), 3.51-3.29 (m, 2H), 3.01 (dd, J=8.9, 6.6 Hz, 2H), 1.95-1.71 (m, 4H), 1.59-1.35 (m, 4H), 0.93 (t, J=7.4 Hz, 6H). 13C NMR (101 MHZ, CDCl3) δ 196.2, 170.7, 160.3, 139.9, 128.7, 128.6, 126.6, 108.4, 92.0, 39.8, 37.4, 32.0, 16.4, 13.9.
VII-1=2,2-dimethyl-5-(3-methylbutanoyl)-1,3-dioxane-4,6-dione (R1=R2=R3=R4=Me): 1H NMR (400 MHZ, CDCl3) δ 15.31 (s, 1H), 2.99 (d, J=7.1 Hz, 2H), 2.21 (dp, J=13.6, 6.8 Hz, 1H), 1.74 (s, 6H), 1.03 (s, 3H), 1.01 (s, 3H). 13C NMR (101 MHZ, CDCl3) δ 197.7, 170.7, 160.4, 104.8, 92.0, 44.0, 27.5, 26.9, 22.7.
VII-2=8-(3-methylbutanoyl)-6,10-dioxaspiro [4.5] decane-7,9-dione (n=1-cyclopentenyl, R3=R4=Me): 1H NMR (500 MHZ, CDCl3) δ 15.20 (s, 1H), 2.98 (d, J=7.1 Hz, 2H), 2.23-2.13 (m, 5H), 1.85 (ddd, J=7.8, 5.7, 2.5 Hz, 4H), 1.02 (s, 3H), 1.01 (s, 3H). 13C NMR (126 MHZ, CDCl3) δ 197.7, 171.4, 161.2, 114.1, 92.6, 43.9, 38.0, 27.6, 23.3, 22.7.
The data presented here shows that keto-diesters of formula (III), or (VII) where R1 and R2 are independently H or an alkyl group; X and Y are independently H, alkyl, NO2, SO2Me, CF3, halide, NH, OH, SH or a derivative thereof; and Z is CH or N may be prepared in a one to two step reaction.
The effects of the keto-diesters of the invention in the growth of monocot and dicot seedlings were tested.
The phytotoxic activity of compounds belonging to formula III (III-1, III-2, and III-3) was evaluated in a primary bioassay. The synthetic triketone herbicides mesotrione and sulcotrione were used as positive controls. For comparative purposes, water as well as 10% acetone in water were used as negative controls. The seeds of monocot bentgrass (Agrostis stolonifera) and dicot Arabidopsis (Arabidopsis thaliana) were exposed for 7 days to 1000 μM solution of each chemical. The compound III-2 significantly impacted growth of the bentgrass seedlings: most of them were chlorotic, some pale green and with developed, shorter leaves compared to negative controls—containing H2O or 10% acetone. The seedlings growing with compounds III-3 and III-1 did not develop chlorosis, although growth of some of them was reduced. Arabidopsis seedling growth was significantly affected by all of the tested compounds. As seen in
Next, a detailed assessment of the phytotoxic activity of the potential herbicide candidates was done by calculating dose-response curve base on growth rate of duckweed (Lemna paucicostata) frond surface. Mesotrione and sulcotrione were used as positive controls and water and 1% acetone in water were used as negative controls. As seen in Table 1 below, III-2 was the most phytotoxic tested compound with an IC50 of 1.9 μM while the remaining two chemicals were less potent: III-1 with 192.9 μM and III-3 46 μM. When comparing with the data provided by Michel, A., et al. (2004, Supra), the most active of the newly prepared compounds (III-2) is more active than the commercial herbicides bentazon, clomazone, glyphosate, glufosinate, asulam, chloropropham, and EPTC in the same bioassay.
The phytotoxic activity of compounds belonging to formula (III), compounds (III-4), (III-5), and (III-6) was evaluated in a primary bioassay. The synthetic triketone herbicides mesotrione and sulcotrione were used as positive controls. For comparative purposes, water as well as 10% acetone in water were used as negative controls. The seeds of monocot bentgrass (Agrostis stolonifera) and dicot Arabidopsis (Arabidopsis thaliana) were exposed for 7 days to 1000 μM solution of each chemical. Novel compounds belonging to (formula V) significantly impacted germination and growth of the bentgrass seedlings: most of them were chlorotic and developed shorter leaves compared to negative controls—containing H2O or 10% acetone. As seen in
Next, a detailed assessment of the phytotoxic activity of the potential herbicide candidates was done by calculating dose-response curves base on growth rate of duckweed (Lemna paucicostata) frond surface. Mesotrione and sulcotrione were used as positive controls and water and 1% acetone in water were used as negative controls. As seen in Table 1 below, compounds III-4, III-6, and III-5 were the most phytotoxic tested compounds with an IC50 of 13.2 μM, 2.6 μM and 17.9 μM. Again, when comparing with the data provided by Michel, A., et al. (2004, Supra), the newly prepared compound with formula III-6 is more active than the commercial herbicides bentazon, clomazone, glyphosate, glufosinate, asulam, chloropropham, or EPTC in the same bioassay.
The phytotoxic activity of compounds belonging to formula (VII) (compounds (VII-1) and (VII-2)) was evaluated in a primary bioassay. The synthetic triketone herbicides mesotrione and sulcotrione were used as positive controls. For comparative purposes, water as well as 10% acetone in water were used as negative controls. The seeds of monocot bentgrass (Agrostis stolonifera) and dicot Arabidopsis (Arabidopsis thaliana) were exposed for 7 days to 1000 μM solution of each chemical. Novel compounds belonging to the formula (VII) significantly impacted bentgrass and Arabidopsis seed germination and growth of the seedlings: most of them were chlorotic and developed shorter leaves when compared to negative controls—containing H2O or 10% acetone. As seen in
Next, a detailed assessment of the phytotoxic activity of the potential herbicide candidates was done by calculating dose-response curve based on the growth rate of duckweed (Lemna paucicostata) frond surface. Mesotrione and sulcotrione were used as positive controls and water and 1% acetone in water were used as negative controls. As seen in Table 1 below, both the tested compounds of formula (VII) displayed significant phytotoxic activity with an IC50 of 1.14 μM for VII-1 and 3.3 μM for VII-2. Again, when comparing with the data provided by Michel, A., et al. (2004, Supra), most of the newly prepared compounds with formula VII are more active than the commercial herbicides bentazon, clomazone, glyphosate, glufosinate, asulam, chloropropham, or EPTC in the same bioassay.
The results in this example show that the keto-diesters of formula (III), (V), or (VII) where R1 and R2 are independently H or an alkyl group; X and Y are independently H, alkyl, NO2, SO2Me, CF3, halide, NH, OH, SH or a derivative thereof; and Z is CH or N, have herbicidal activity.
This application claims priority benefit from U.S. Provisional Application No. 63/514,591, filed Jul. 20, 2023. The contents of this patent application are hereby expressly incorporated by reference in their entirety.
| Number | Date | Country | |
|---|---|---|---|
| 63514591 | Jul 2023 | US |
