Patent Application
20250127170
The present invention relates to herbicidally active triazine derivatives, as well as to processes and intermediates used for the preparation of such derivatives. The invention further extends to herbicidal compositions comprising such derivatives, as well as to the use of such compounds and compositions for controlling undesirable plant growth, in particular the use for controlling weeds, in crops of useful plants.
WO2021/259224, WO202/239607, U.S. Pat. No. 5,726,126, EP0584655, WO2004/009561, and WO0050409 all describe herbicidal derivatives.
The present invention is based on the finding that triazine derivatives of formula (I) as defined herein, exhibit surprisingly good herbicidal activity. Thus, according to the present invention there is provided a compound of formula (I) or an agronomically acceptable salt thereof:
R4 is selected from hydrogen, halogen, cyano, nitro, aminocarbonyl, aminothiocarbonyl, C1-C4alkyl, C1-C4haloalkyl, C1-C4alkoxy, C1-C4haloalkoxy and C1-C4alkylsulfonyl;
According to a second aspect of the invention, there is provided an agrochemical composition comprising a herbicidally effective amount of a compound of formula (I) and an agrochemically-acceptable diluent or carrier. Such an agricultural composition may further comprise at least one additional active ingredient.
According to a third aspect of the invention, there is provided a method of controlling or preventing undesirable plant growth, wherein a herbicidally effective amount of a compound of formula (I), or a composition comprising this compound as active ingredient, is applied to the plants, to parts thereof or the locus thereof.
According to a fourth aspect of the invention, there is provided the use of a compound of formula (I) as a herbicide.
According to a fifth aspect of the invention, there is provided a process for the preparation of compounds of formula (I).
As used herein, the term “halogen” or “halo” refers to fluorine (fluoro), chlorine (chloro), bromine (bromo) or iodine (iodo), preferably fluorine, chlorine or bromine.
As used herein, cyano means a —CN group.
As used herein, hydroxy means an —OH group.
As used herein, nitro means an —NO2 group.
As used herein, amino means an —NH2 group.
As used herein, the term “C1-C10alkyl” refers to a straight or branched hydrocarbon chain radical consisting solely of carbon and hydrogen atoms, containing no unsaturation, having from one to ten carbon atoms, and which is attached to the rest of the molecule by a single bond. C1-C6alkyl, C1-C4alkyl and C1-C2alkyl are to be construed accordingly. Examples of C1-C10alkyl include, but are not limited to, methyl (Me), ethyl (Et), n-propyl, 1-methylethyl (iso-propyl), n-butyl, and 1-dimethylethyl (t-butyl).
As used herein, the term “C1-C4alkoxy” refers to a radical of the formula —ORa where Ra is a C1-C4alkyl radical as generally defined above. C1-C3alkoxy is to be construed accordingly. Examples of C1-C4alkoxy include, but are not limited to, methoxy, ethoxy, propoxy, iso-propoxy and t-butoxy.
As used herein, the term “C1-C10haloalkyl” refers to a C1-C10alkyl radical as generally defined above substituted by one or more of the same or different halogen atoms. C1-C6haloalkyl and C1-C4haloalkyl iare to be construed accordingly. Examples of C1-C10haloalkyl include, but are not limited to chloromethyl, fluoromethyl, fluoroethyl, difluoromethyl, trifluoromethyl and 2,2,2-trifluoroethyl.
As used herein, the term “C2-C6alkenyl” refers to a straight or branched hydrocarbon chain radical group consisting solely of carbon and hydrogen atoms, containing at least one double bond that can be of either the (E)- or (Z)-configuration, having from two to six carbon atoms, which is attached to the rest of the molecule by a single bond. C3-C6alkenyl and C2-C4alkenyl are to be construed accordingly. Examples of C2-C6alkenyl include, but are not limited to, prop-1-enyl, allyl (prop-2-enyl) and but-1-enyl.
As used herein, the term “C2-C6haloalkenyl” refers to a C2-C6alkenyl radical as generally defined above substituted by one or more of the same or different halogen atoms. C3-C6alkenyl is to be construed accordingly. Examples of C2-C6haloalkenyl include, but are not limited to chloroethylene, fluoroethylene, 1,1-difluoroethylene, 1,1-dichloroethylene and 1,1,2-trichloroethylene.
As used herein, the term “C2-C6alkynyl” refers to a straight or branched hydrocarbon chain radical group consisting solely of carbon and hydrogen atoms, containing at least one triple bond, having from two to six carbon atoms, and which is attached to the rest of the molecule by a single bond. C3-C6alkynyl and C2-C4alkynyl are to be construed accordingly. Examples of C2-C6alkynyl include, but are not limited to, prop-1-ynyl, propargyl (prop-2-ynyl) and but-1-ynyl.
As used herein, the term “C1-C4haloalkoxy” refers to a C1-C4alkoxy group as defined above substituted by one or more of the same or different halogen atoms. C1-C3haloalkoxy is to be construed accordingly. Examples of C1-C4haloalkoxy include, but are not limited to, fluoromethoxy, difluoromethoxy, fluoroethoxy, trifluoromethoxy and trifluoroethoxy.
As used herein, the term “C1-C4haloalkoxyC1-C6alkyl” refers to a radical of the formula Rb—O—Ra— where Rb is a C1-C4haloalkyl radical as generally defined above, and Ra is a C1-C6alkylene radical as generally defined above.
As used herein, the term “C1-C4alkoxyC1-C6alkyl” refers to a radical of the formula Rb—O—Ra— where Rb is a C1-C4alkyl radical as generally defined above, and Ra is a C1-C6alkylene radical as generally defined above.
As used herein, the term “C1-C4alkylthio” refers to a radical of the formula —SRa, where Ra is a C1-C4alkyl radical as generally defined above.
As used herein, the term “C1-C4alkylsulfonyl” refers to a radical of the formula —S(O)2Ra, where Ra is a C1-C4alkyl radical as generally defined above. The terms “C1-C3alkylsulfonyl” and “C1-C2alkylsulfonyl”, are to be construed accordingly. Examples of C1-C6alkylsolfanyl include, but are not limited to methylsulfonyl.
As used herein, the term “C1-C6alkylcarbonyl” refers to a radical of the formula —C(O)Ra where Ra is a C1-C6alkyl radical as generally defined above. C1-C4alkylcarbonyl is to be construed accordingly.
As used herein, the term “C1-C6alkoxycarbonyl” refers to a radical of the formula —C(O)ORa where Ra is a C1-C6alkyl radical as generally defined above. C1-C4alkoxycarbonyl is to be construed accordingly.
As used herein, the term “aminocarbonyl” refers to a radical of the formula —C(O)NH2.
As used herein, the term “aminothiocarbonyl” refers to a radical of the formula —C(S)NH2.
As used herein, the term “C6-C10aryl” refers to a 6- to 10-membered aromatic ring system consisting solely of carbon and hydrogen atoms which may be mono-, bi- or tricyclic. Examples of such ring systems include phenyl, naphthalenyl, or indenyl.
As used herein, the term “C6-C10arylC1-C3alkyl” refers to an aryl moiety as generally defined above, which is attached to the rest of the molecule by a C1-C3alkylene linker as defined above.
As used herein, except where explicitly stated otherwise, the term “heteroaryl” refers to a 5- or 6-membered monocyclic aromatic ring which comprises 1, 2, 3 or 4 heteroatoms individually selected from nitrogen, oxygen and sulfur. The heteroaryl radical may be bonded to the rest of the molecule via a carbon atom or heteroatom. Examples of heteroaryl include, furyl, pyrrolyl, imidazolyl, thienyl, pyrazolyl, thiazolyl, isothiazolyl, oxazolyl, isoxazolyl, triazolyl, tetrazolyl, pyrazinyl, pyridazinyl, pyrimidyl or pyridyl.
As used herein, except where explicitly stated otherwise, the term “heteroarylC1-C3alkyl” refers to a heteroaryl ring as generally defined above attached to the rest of the molecule through a C1-C3alkylene linker as defined above.
As used herein, except where explicitly stated otherwise, the term “heterocyclyl” or “heterocyclic” refers to a stable 4- to 6-membered non-aromatic monocyclic ring radical which comprises 1, 2, or 3 heteroatoms individually selected from nitrogen, oxygen and sulfur. The heterocyclyl radical may be bonded to the rest of the molecule via a carbon atom or heteroatom. Examples of heterocyclyl include, but are not limited to, pyrrolinyl, pyrrolidyl, tetrahydrofuryl, tetrahydrothienyl, tetrahydrothiopyranyl, piperidyl, piperazinyl, tetrahydropyranyl, dihydroisoxazolyl, dioxolanyl, morpholinyl or δ-lactamyl.
As used herein, except where explicitly stated otherwise, the term “heterocyclylC1-C3alkyl” refers to a heterocyclyl ring as generally defined above attached to the rest of the molecule through a C1-C3alkylene linker as defined above.
The presence of one or more possible asymmetric carbon atoms in a compound of formula (I) means that the compounds may occur in chiral isomeric forms, i.e., enantiomeric or diastereomeric forms. Also atropisomers may occur as a result of restricted rotation about a single bond. Formula (I) is intended to include all those possible isomeric forms and mixtures thereof. The present invention includes all those possible isomeric forms and mixtures thereof for a compound of formula (I). Likewise, formula (I) is intended to include all possible tautomers (including lactam-lactim tautomerism and keto-enol tautomerism) where present. The present invention includes all possible tautomeric forms for a compound of formula (I). 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 invention includes all these possible isomeric forms and mixtures thereof for a compound of formula (I).
The compounds of formula (I) will typically be provided in the form of an agronomically acceptable salt, a zwitterion or an agronomically acceptable salt of a zwitterion. This invention covers all such agronomically acceptable salts, zwitterions and mixtures thereof in all proportions.
Suitable agronomically acceptable salts of the present invention 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, triethylsulfonium, triethylsulfoxonium, trimethylsulfonium, trimethylsulfoxonium, tripropylsulfonium and tripropylsulfoxonium.
The following list provides definitions, including preferred definitions, for substituents X1, X2, X3, Y, B, D, n, R1, R2, R3, R4, R5, R6, R7, R8, R9, R10, R11, R12, R13, R14, and R15 with reference to the compounds of formula (I) according to the invention. For any one of these substituents, any of the definitions given below may be combined with any definition of any other substituent given below or elsewhere in this document.
Preferably X1 is sulfur.
Preferably X2 is oxygen.
Preferably X3 is oxygen.
Preferably Y is C—H.
Preferably B is selected from O, NH and NMe, more preferably O. When R8 is OR9 then B is preferably selected from S, NH and NMe, most preferably NH and NMe.
Preferably n is an integer from 1 to 2, more preferably 2.
Preferably R1 is selected from hydrogen and C1-C4alkyl, more preferably C1-C2alkyl, most preferably methyl.
Preferably R2 is selected from hydrogen, C1-C4alkyl, and C3-C4alkynyl, more preferably C1-C2alkyl, most preferably methyl.
Preferably R3 is selected from hydrogen, chloro, and fluoro, more preferably hydrogen and fluoro. In one embodiment, R3 is fluoro.
Preferably R4 is selected from hydrogen, chloro, bromo, cyano and aminothiocarbonyl, more preferably chloro, bromo and cyano, most preferably chloro.
Preferably each R6 and R7 is independently selected from hydrogen, halogen, C1-C4alkyl and C1-C4alkoxycarbonyl, more preferably hydrogen, halogen and C1-C2alkyl, most preferably hydrogen, chloro, and methyl.
Preferably R8 is OR9. When B is O, preferably R8 is selected from SR9 and NR10R11, most preferably NR10R11.
Preferably R9 is selected from hydrogen, C1-C4alkyl, C1-C4haloalkyl, C1-C2alkoxyC1-C2alkyl, phenylC1-C2alkyl and phenylC1-C2alkyl substituted by 1 to 2 groups, which may be the same or different, represented by R13, more preferably hydrogen, C1-C4alkyl, C1-C2alkoxyC1-C2alkyl and phenylC1-C2alkyl, most preferably hydrogen, C1-C4alkyl and phenylC1-C2alkyl.
Preferably R10 is selected from the group consisting of hydrogen and SO2R14, more preferably SO2R14.
Preferably R11 is hydrogen.
Preferably R12 is selected from hydrogen, C1-C2alkyl and C1-C2alkylcarbonyl, more preferably hydrogen and methyl.
Preferably R13 is selected from halogen, C1-C4alkyl, C1-C4haloalkyl, C1-C4alkoxy, C1-C4haloalkoxy, cyano and C1-C4alkylsulfonyl.
Preferably R14 is selected from C1-C4alkyl and C1-C4alkyl(C1-C4alkyl)amino, more preferably methyl and isopropyl(methyl)amino.
Preferably each R15 is independently selected from hydrogen, halogen and C1-C2alkyl, more preferably hydrogen and methyl, most preferably hydrogen.
A preferred subset of compounds is one in which X1 is sulfur;
A more preferred subset of compounds is one in which X1 is sulfur;
A further preferred group of compounds is one in which X1 is sulfur;
In another preferred set of embodiments, X1 is sulfur;
In a particularly preferred set of embodiments, the compound of formula (I) is selected from:
In another particularly preferred set of embodiments, the compound of formula (I) is selected from:
Table 1 discloses 1134 specific compounds of formula (I), designated compounds 1-1 to 1-1134 respectively, wherein X1 is sulfur, X2 and X3 are oxygen, R1 and R2 are methyl, R4 is chloro, Y is C—H, and R3, B, D, and R8 are as defined in Table A above.
Table 2 discloses 1134 compounds of formula (I), designated compounds 2-1 to 2-1134 respectively, and wherein X1 and X2 are sulfur, X3 is oxygen, R1 and R2 are methyl, R4 is chloro, and Y is C—H, and the values of B, D, R3 and R8 are as defined in Table A.
Table 3 discloses 1134 compounds of formula (I), designated compounds 3-1 to 3-1134 respectively, wherein X1 is sulfur, X2 and X3 are oxygen, R1 and R2 are methyl, R4 is chloro, and Y is N, and the values of B, D, R3 and R8 are as given in Table A.
Table 4 discloses 1134 compounds of formula (I), designated compounds 4-1 to 4-1134 respectively, wherein X1 and X2 are sulfur, X3 is oxygen, R1 and R2 are methyl, R4 is chloro, and Y is N, and the values of B, D, R3 and R8 are as given in Table A.
Table 5 discloses 1134 compounds of formula (I), designated compounds 5-1 to 5-1134 respectively, wherein X1 is sulfur, X2 and X3 are oxygen, R1 and R2 are methyl, R4 is CN, and Y is N, and the values of B, D, R3 and R8 are as given in Table A.
Table 6 discloses 1134 compounds of formula (I), designated compounds 6-1 to 6-1134 respectively, wherein X1 and X2 are sulfur, X3 is oxygen, R1 and R2 are methyl, R4 is CN, and Y is C—H, and the values of B, D, R3 and R8 are as given in Table A.
Table 7 discloses 1134 compounds of formula (I), designated compounds 7-1 to 7-1134 respectively, wherein X1 is sulfur, X2 and X3 are oxygen, R1 and R2 are methyl, R4 is bromo, and Y is N, and the values of B, D, R3 and R8 are as given in Table A.
Table 8 discloses 1134 compounds of formula (I), designated compounds 8-1 to 8-1134 respectively, wherein X1 and X2 are sulfur, X3 is oxygen, R1 and R2 are methyl, R4 is bromo, and Y is C—H, and the values of B, D, R3 and R8 are as given in Table A.
Compounds of the invention may be prepared by techniques known to the person skilled in the art of organic chemistry. General methods for the production of compounds of formula (I) are described below. Unless otherwise stated in the text, the substituents X1, X2, X3, Y, B, D, R1, R2, R3, R4, R5, R6, R7, R8, R9, R10, R11, R12, R13, R14 and R15 are as defined hereinbefore. The starting materials used for the preparation of the compounds of the invention may be purchased from usual commercial suppliers or may be prepared by known methods. The starting materials as well as the intermediates may be purified before use in the next step by state of the art methodologies such as chromatography, crystallization, distillation and filtration.
Compounds of formula (I) may be prepared from compounds of formula (A) and compounds of formula (B) as shown in reaction scheme 1.
For example, a mixture of a compound of formula (A) and a compound of formula (B) may be treated with a base, such as triethylamine, and a carbonyl transfer reagent, such as phosgene or carbonyl diimidazole, in a suitable solvent such as toluene. Ureas or thioureas of formula (A) are available or may be prepared by methods well known in the literature. Compounds of formula (B) may be prepared from anilines of formula (C) as shown in reaction scheme 2.
For example, a compound of formula (C) may be treated with a carbonyl or thiocarbonyl transfer reagent, such as diphosgene, triphosgene or thiophosgene, in a suitable solvent, such as toluene. Anilines of formula (C) may be prepared from nitro compounds of formula (D) as shown in reaction scheme 3.
For example, a compound of formula (D) can be treated with a reducing agent, such as iron and ammonium chloride, in a suitable solvent, such as a mixture of water and ethanol. Nitro compounds of formula (D) may be prepared from acids of formula (E) and alcohols or amines of formula (F) as shown in reaction scheme 4.
For example, an acid of formula (E) may be treated with an activating agent such as oxalyl chloride in a suitable solvent, such as dichloromethane and dimethylformamide, and the resulting intermediate then treated with an alcohol or amine of formula (F) in the presence of a base, such as triethylamine, in a suitable solvent such as dichloromethane. Alcohols and amines of formula (F) are available or may be prepared by methods well known in the literature. Acids of formula (E) are available or may be prepared by methods well known in the literature.
Alternatively compounds of formula (I) may be prepared from alcohols or amines of formula (F) and acids of formula (G) as shown in reaction scheme 5.
For example, an acid of formula (G) may be treated with an activating agent such as oxalyl chloride in a suitable solvent, such as dichloromethane and dimethylformamide, and the resulting intermediate then treated with an alcohol or amine of formula (F) in the presence of a base, such as triethylamine, in a suitable solvent such as dichloromethane. Acids of formula (G) may be prepared from esters of formula (H) as shown in reaction scheme 6.
For example, an ester of formula (H) may be treated with sodium hydroxide in a suitable solvent, such as a mixture of water and ethanol. Esters of formula (H) can be prepared from compounds of formula (J) and compounds of formula (A) as shown in reaction scheme 7.
For example, a mixture of a compound of formula (A) and a compound of formula (J) may be treated with a base, such as triethylamine, and a carbonyl transfer reagent, such as phosgene or carbonyl diimidazole, in a suitable solvent such as toluene. Compounds of formula (J) may be prepared from anilines of formula (K) as shown in reaction scheme 8.
For example, a compound of formula (K) may be treated with a carbonyl or thiocarbonyl transfer reagent, such as diphosgene, triphosgene or thiophosgene, in a suitable solvent, such as toluene. Anilines of formula (K) are available or may be prepared from nitro compounds of formula (L) as shown in reaction scheme 9.
For example, a compound of formula (L) can be treated with a reducing agent, such as iron and ammonium chloride, in a suitable solvent, such as a mixture of water and ethanol. Nitro compounds of formula (L) are available or may be prepared by methods well known in the literature.
Compounds of formula (I-A), which are compounds of formula (I) in which R8 is an OH group, may be prepared from compounds of formula (I-B), which are compounds of formula (I) in which R8 is OR9, as shown in reaction scheme 10.
For example, a compound of formula (I-B) may be treated with hydrochloric acid in a suitable solvent, such as dioxane. Compounds of formula (I-C), which are compounds of formula (I) in which R8 is NR10R11, may be prepared from compounds of formula (I-A) as shown in reaction scheme 11.
For example, a compound of formual (I-A) may be treated with a halogenating reagent, such as oxalyl chloride, in a suitable solvent, such as dichloromethane, to form an acyl halide which may be treated with a reagent HNR10R11 in the presence of a base, such as triethylamine, in a suitable solvent, such as dichloromethane.
One skilled in the art will realise that it is often possible to alter the order in which the transformations described above are conducted, or to combine them in alternative ways to prepare a wide range of compounds of formula (I). Multiple steps may also be combined in a single reaction. All such variations are contemplated within the scope of the invention.
The skilled person will also be aware that some reagents will be incompatible with certain values or combinations of the substituents X1, X2, X3, Y, B, D, R1, R2, R3, R4, R5, R6, R7, R8, R9, R10, R11, R12, R13, R14 and R15 as defined herein, and any additional steps, such as protection and/or deprotection steps, which are necessary to achieve the desired transformation will be clear to the skilled person.
The compounds according to the invention can be used as herbicidal agents in unmodified form, but they are generally formulated into compositions in various ways using formulation adjuvants, such as carriers, solvents and surface-active substances. The formulations can be in various physical forms, e.g. in the form of dusting powders, gels, wettable powders, water-dispersible granules, water-dispersible tablets, effervescent pellets, emulsifiable concentrates, microemulsifiable concentrates, oil-in-water emulsions, oil-flowables, aqueous dispersions, oily dispersions, suspo-emulsions, capsule suspensions, emulsifiable granules, soluble liquids, water-soluble concentrates (with water or a water-miscible organic solvent as carrier), impregnated polymer films or in other forms known e.g. from the Manual on Development and Use of FAO and WHO Specifications for Pesticides, United Nations, First Edition, Second Revision (2010). For water-soluble compounds, soluble liquids, water-soluble concentrates or water soluble granules are preferred. Such formulations can either be used directly or diluted prior to use. The dilutions can be made, for example, with water, liquid fertilisers, micronutrients, biological organisms, oil or solvents.
The formulations can be prepared e.g. by mixing the active ingredient with the formulation adjuvants in order to obtain compositions in the form of finely divided solids, granules, solutions, dispersions or emulsions. The active ingredients can also be formulated with other adjuvants, such as finely divided solids, mineral oils, oils of vegetable or animal origin, modified oils of vegetable or animal origin, organic solvents, water, surface-active substances or combinations thereof.
The active ingredients can also be contained in very fine microcapsules. Microcapsules contain the active ingredients in a porous carrier. This enables the active ingredients to be released into the environment in controlled amounts (e.g. slow-release). Microcapsules usually have a diameter of from 0.1 to 500 microns. They contain active ingredients in an amount of about from 25 to 95% by weight of the capsule weight. The active ingredients can be in the form of a monolithic solid, in the form of fine particles in solid or liquid dispersion or in the form of a suitable solution. The encapsulating membranes can comprise, for example, natural or synthetic rubbers, cellulose, styrene/butadiene copolymers, polyacrylonitrile, polyacrylate, polyesters, polyamides, polyureas, polyurethane or chemically modified polymers and starch xanthates or other polymers that are known to the person skilled in the art. Alternatively, very fine microcapsules can be formed in which the active ingredient is contained in the form of finely divided particles in a solid matrix of base substance, but the microcapsules are not themselves encapsulated.
The formulation adjuvants that are suitable for the preparation of the compositions according to the invention are known per se. As liquid carriers there may be used: water, toluene, xylene, petroleum ether, vegetable oils, acetone, methyl ethyl ketone, cyclohexanone, acid anhydrides, acetonitrile, acetophenone, amyl acetate, 2-butanone, butylene carbonate, chlorobenzene, cyclohexane, cyclohexanol, alkyl esters of acetic acid, diacetone alcohol, 1,2-dichloropropane, diethanolamine, p-diethylbenzene, diethylene glycol, diethylene glycol abietate, diethylene glycol butyl ether, diethylene glycol ethyl ether, diethylene glycol methyl ether, N,N-dimethylformamide, dimethyl sulfoxide, 1,4-dioxane, dipropylene glycol, dipropylene glycol methyl ether, dipropylene glycol dibenzoate, diproxitol, alkylpyrrolidone, ethyl acetate, 2-ethylhexanol, ethylene carbonate, 1,1,1-trichloroethane, 2-heptanone, alpha-pinene, d-limonene, ethyl lactate, ethylene glycol, ethylene glycol butyl ether, ethylene glycol methyl ether, gamma-butyrolactone, glycerol, glycerol acetate, glycerol diacetate, glycerol triacetate, hexadecane, hexylene glycol, isoamyl acetate, isobornyl acetate, isooctane, isophorone, isopropylbenzene, isopropyl myristate, lactic acid, laurylamine, mesityl oxide, methoxypropanol, methyl isoamyl ketone, methyl isobutyl ketone, methyl laurate, methyl octanoate, methyl oleate, methylene chloride, m-xylene, n-hexane, n-octylamine, octadecanoic acid, octylamine acetate, oleic acid, oleylamine, o-xylene, phenol, polyethylene glycol, propionic acid, propyl lactate, propylene carbonate, propylene glycol, propylene glycol methyl ether, p-xylene, toluene, triethyl phosphate, triethylene glycol, xylenesulfonic acid, paraffin, mineral oil, trichloroethylene, perchloroethylene, ethyl acetate, amyl acetate, butyl acetate, propylene glycol methyl ether, diethylene glycol methyl ether, methanol, ethanol, isopropanol, and alcohols of higher molecular weight, such as amyl alcohol, tetrahydrofurfuryl alcohol, hexanol, octanol, ethylene glycol, propylene glycol, glycerol, N-methyl-2-pyrrolidone and the like.
Suitable solid carriers are, for example, talc, titanium dioxide, pyrophyllite clay, silica, attapulgite clay, kieselguhr, limestone, calcium carbonate, bentonite, calcium montmorillonite, cottonseed husks, wheat flour, soybean flour, pumice, wood flour, ground walnut shells, lignin and similar substances.
A large number of surface-active substances can advantageously be used in both solid and liquid formulations, especially in those formulations which can be diluted with a carrier prior to use. Surface-active substances may be anionic, cationic, non-ionic or polymeric and they can be used as emulsifiers, wetting agents or suspending agents or for other purposes. Typical surface-active substances include, for example, salts of alkyl sulfates, such as diethanolammonium lauryl sulfate; salts of alkylarylsulfonates, such as calcium dodecylbenzenesulfonate; alkylphenol/alkylene oxide addition products, such as nonylphenol ethoxylate; alcohol/alkylene oxide addition products, such as tridecylalcohol ethoxylate; soaps, such as sodium stearate; salts of alkylnaphthalenesulfonates, such as sodium dibutylnaphthalenesulfonate; dialkyl esters of sulfosuccinate salts, such as sodium di(2-ethylhexyl)sulfosuccinate; sorbitol esters, such as sorbitol oleate; quaternary amines, such as lauryltrimethylammonium chloride, polyethylene glycol esters of fatty acids, such as polyethylene glycol stearate; block copolymers of ethylene oxide and propylene oxide; and salts of mono- and di-alkylphosphate esters; and also further substances described e.g. in Mccutcheon's Detergents and Emulsifiers Annual, MC Publishing Corp., Ridgewood New Jersey (1981).
Further adjuvants that can be used in pesticidal formulations include crystallisation inhibitors, viscosity modifiers, suspending agents, dyes, anti-oxidants, foaming agents, light absorbers, mixing auxiliaries, antifoams, complexing agents, neutralising or pH-modifying substances and buffers, corrosion inhibitors, fragrances, wetting agents, take-up enhancers, micronutrients, plasticisers, glidants, lubricants, dispersants, thickeners, antifreezes, microbicides, and liquid and solid fertilisers.
The compositions according to the invention can include an additive comprising an oil of vegetable or animal origin, a mineral oil, alkyl esters of such oils or mixtures of such oils and oil derivatives. The amount of oil additive in the composition according to the invention is generally from 0.01 to 10%, based on the mixture to be applied. For example, the oil additive can be added to a spray tank in the desired concentration after a spray mixture has been prepared. Preferred oil additives comprise mineral oils or an oil of vegetable origin, for example rapeseed oil, olive oil or sunflower oil, emulsified vegetable oil, alkyl esters of oils of vegetable origin, for example the methyl derivatives, or an oil of animal origin, such as fish oil or beef tallow. Preferred oil additives comprise alkyl esters of C8-C22 fatty acids, especially the methyl derivatives of C12-C18 fatty acids, for example the methyl esters of lauric acid, palmitic acid and oleic acid (methyl laurate, methyl palmitate and methyl oleate, respectively). Many oil derivatives are known from the Compendium of Herbicide Adjuvants, 10th Edition, Southern Illinois University, 2010.
The herbicidal compositions generally comprise from 0.1 to 99% by weight, especially from 0.1 to 95% by weight, compounds of formula (I) and from 1 to 99.9% by weight of a formulation adjuvant which preferably includes from 0 to 25% by weight of a surface-active substance. The inventive compositions generally comprise from 0.1 to 99% by weight, especially from 0.1 to 95% by weight, of compounds of the present invention and from 1 to 99.9% by weight of a formulation adjuvant which preferably includes from 0 to 25% by weight of a surface-active substance. Whereas commercial products may preferably be formulated as concentrates, the end user will normally employ dilute formulations.
The rates of application vary within wide limits and depend on the nature of the soil, the method of application, the crop plant, the pest to be controlled, the prevailing climatic conditions, and other factors governed by the method of application, the time of application and the target crop. As a general guideline compounds may be applied at a rate of from 1 to 2000 l/ha, especially from 10 to 1000 l/ha.
Preferred formulations can have the following compositions (weight %):
The composition of the present may further comprise at least one additional pesticide. For example, the compounds according to the invention can also be used in combination with other herbicides or plant growth regulators. In a preferred embodiment the additional pesticide is a herbicide and/or herbicide safener.
The compounds of present invention can also be used in mixture with one or more additional herbicides and/or plant growth regulators. Examples of such additional herbicides or plant growth regulators include acetochlor, acifluorfen (including acifluorfen-sodium), aclonifen, ametryn, amicarbazone, aminopyralid, aminotriazole, atrazine, beflubutamid-M, benquitrione, bensulfuron (including bensulfuron-methyl), bentazone, bicyclopyrone, bilanafos, bipyrazone, bispyribac-sodium, bixlozone, bromacil, bromoxynil, butachlor, butafenacil, carfentrazone (including carfentrazone-ethyl), cloransulam (including cloransulam-methyl), chlorimuron (including chlorimuron-ethyl), chlorotoluron, chlorsulfuron, cinmethylin, clacyfos, clethodim, clodinafop (including clodinafop-propargyl), clomazone, clopyralid, cyclopyranil, cyclopyrimorate, cyclosulfamuron, cyhalofop (including cyhalofop-butyl), 2,4-D (including the choline salt and 2-ethylhexyl ester thereof), 2,4-DB, desmedipham, dicamba (including the aluminium, aminopropyl, bis-aminopropylmethyl, choline, dichloroprop, diglycolamine, dimethylamine, dimethylammonium, potassium and sodium salts thereof) diclosulam, diflufenican, diflufenzopyr, dimethachlor, dimethenamid-P, dioxopyritrione, diquat dibromide, diuron, epyrifenacil, ethalfluralin, ethofumesate, fenoxaprop (including fenoxaprop-P-ethyl), fenoxasulfone, fenpyrazone, fenquinotrione, fentrazamide, flazasulfuron, florasulam, florpyrauxifen (including florpyrauxifen-benzyl), fluazifop (including fluazifop-P-butyl), flucarbazone (including flucarbazone-sodium), flufenacet, flumetsulam, flumioxazin, fluometuron, fomesafen flupyrsulfuron (including flupyrsulfuron-methyl-sodium), fluroxypyr (including fluroxypyr-meptyl), fomesafen, foramsulfuron, glufosinate (including L-glufosinate and the ammonium salts of both), glyphosate (including the diammonium, isopropylammonium and potassium salts thereof), halauxifen (including halauxifen-methyl), haloxyfop (including haloxyfop-methyl), hexazinone, hydantocidin, imazamox (including R-imazamox), imazapic, imazapyr, imazethapyr, indaziflam, iodosulfuron (including iodosulfuron-methyl-sodium), iofensulfuron (including iofensulfuron-sodium), ioxynil, isoproturon, isoxaflutole, lancotrione, MCPA, MCPB, mecoprop-P, mesosulfuron (including mesosulfuron-methyl), mesotrione, metamitron, metazachlor, methiozolin, metolachlor, metosulam, metribuzin, metsulfuron, napropamide, nicosulfuron, norflurazon, oxadiazon, oxasulfuron, oxyfluorfen, paraquat dichloride, pendimethalin, penoxsulam, phenmedipham, picloram, pinoxaden, pretilachlor, primisulfuron-methyl, prometryne, propanil, propaquizafop, propyrisulfuron, propyzamide, prosulfocarb, prosulfuron, pyraclonil, pyraflufen (including pyraflufen-ethyl), pyrasulfotole, pyridate, pyriftalid, pyrimisulfan, pyroxasulfone, pyroxsulam, quinclorac, quinmerac, quizalofop (including quizalofop-P-ethyl and quizalofop-P-tefuryl), rimisoxafen, rimsulfuron, saflufenacil, sethoxydim, simazine, S-metalochlor, sulfentrazone, sulfosulfuron, tebuthiuron, tefuryltrione, tembotrione, terbuthylazine, terbutryn, tetflupyrolimet, thiencarbazone, thifensulfuron, tiafenacil, tolpyralate, topramezone, tralkoxydim, triafamone, triallate, triasulfuron, tribenuron (including tribenuron-methyl), triclopyr, trifloxysulfuron (including trifloxysulfuron-sodium), trifludimoxazin, trifluralin, triflusulfuron, tripyrasulfone, 3-(2-chloro-4-fluoro-5-(3-methyl-2,6-dioxo-4-trifluoromethyl-3,6-dihydropyrimidin-1(2H)-yl)phenyl)-5-methyl-4,5-dihydroisoxazole-5-carboxylic acid ethyl ester, 4-hydroxy-1-methoxy-5-methyl-3-[4-(trifluoromethyl)-2-pyridyl]imidazolidin-2-one, 4-hydroxy-1,5-dimethyl-3-[4-(trifluoromethyl)-2-pyridyl]imidazolidin-2-one, 5-ethoxy-4-hydroxy-1-methyl-3-[4-(trifluoromethyl)-2-pyridyl]imidazolidin-2-one, 4-hydroxy-1-methyl-3-[4-(trifluoromethyl)-2-pyridyl]imidazolidin-2-one, 4-hydroxy-1,5-dimethyl-3-[1-methyl-5-(trifluoromethyl) pyrazol-3-yl]imidazolidin-2-one, (4R)1-(5-tert-butylisoxazol-3-yl)-4-ethoxy-5-hydroxy-3-methyl-imidazolidin-2-one, 4-amino-3-chloro-5-fluoro-6-(7-fluoro-1H-indol-6-yl) pyridine-2-carboxylic acid (including agrochemically acceptable esters thereof, for example, methyl 4-amino-3-chloro-5-fluoro-6-(7-fluoro-1H-indol-6-yl)pyridine-2-carboxylate, prop-2-ynyl 4-amino-3-chloro-5-fluoro-6-(7-fluoro-1H-indol-6-yl)pyridine-2-carboxylate and cyanomethyl 4-amino-3-chloro-5-fluoro-6-(7-fluoro-1H-indol-6-yl)pyridine-2-carboxylate), 3-ethylsulfanyl-N-(1,3,4-oxadiazol-2-yl)-5-(trifluoromethyl)-[1,2,4]triazolo[4,3-a]pyridine-8-carboxamide, 3-(isopropylsulfanylmethyl)-N-(5-methyl-1,3,4-oxadiazol-2-yl)-5-(trifluoromethyl)-[1,2,4]triazolo[4,3-a]pyridine-8-carboxamide, 3-(isopropylsulfonylmethyl)-N-(5-methyl-1,3,4-oxadiazol-2-yl)-5-(trifluoromethyl)-[1,2,4]triazolo[4,3-a]pyridine-8-carboxamide, 3-(ethylsulfonylmethyl)-N-(5-methyl-1,3,4-oxadiazol-2-yl)-5-(trifluoromethyl)-[1,2,4]triazolo[4,3-a]pyridine-8-carboxamide, ethyl-2-[[3-[[3-chloro-5-fluoro-6-[3-methyl-2,6-dioxo-4-(trifluoromethyl)pyrimidin-1-yl]-2-pyridyl]oxy]acetate, 6-chloro-4-(2,7-dimethyl-1-naphthyl)-5-hydroxy-2-methyl-pyridazin-3-one, tetrahydrofuran-2-ylmethyl (2R)-2-[(4-amino-3,5-dichloro-6-fluoro-2-pyridyl)oxy]propanoate, (2R)-2-[(4-amino-3,5-dichloro-6-fluoro-2-pyridyl)oxy]propanoic acid, tetrahydrofuran-2-ylmethyl 2-[(4-amino-3,5-dichloro-6-fluoro-2-pyridyl)oxy]propanoate, 2-[(4-amino-3,5-dichloro-6-fluoro-2-pyridyl)oxy]propanoic acid, 2-fluoro-N-(5-methyl-1,3,4-oxadiazol-2-yl)-3-[(R)-propylsulfinyl]-4-(trifluoromethyl)benzamide, 2-fluoro-N-(5-methyl-1,3,4-oxadiazol-2-yl)-3-propylsulfinyl-4-(trifluoromethyl)benzamide, (2-fluorophenyl)methyl 6-amino-5-chloro-2-(4-chloro-2-fluoro-3-methoxy-phenyl) pyrimidine-4-carboxylate, 6-amino-5-chloro-2-(4-chloro-2-fluoro-3-methoxy-phenyl) pyrimidine-4-carboxylic acid, 3-(3-chlorophenyl)-6-(5-hydroxy-1,3-dimethyl-pyrazole-4-carbonyl)-1,5-dimethyl-quinazoline-2,4-dione and [4-[3-(3-chlorophenyl)-1,5-dimethyl-2,4-dioxo-quinazoline-6-carbonyl]-2,5-dimethyl-pyrazol-3-yl] N,N-diethylcarbamate.
The mixing partners of the compound of formula (I) may also be in the form of esters or salts, as mentioned e.g. in The Pesticide Manual, Fourteenth Edition, British Crop Protection Council, 2006.
The compound of formula (I) can also be used in mixtures with other agrochemicals such as fungicides, nematicides or insecticides, examples of which are given in The Pesticide Manual.
The mixing ratio of the compound of formula (I) to the mixing partner is preferably from 1:100 to 1000:1.
The mixtures can advantageously be used in the above-mentioned formulations (in which case “active ingredient” relates to the respective mixture of compound of formula (I) with the mixing partner).
Compounds of formula (I) of the present invention may also be combined with herbicide safeners. Preferred combinations benoxacor, cloquintocet (including cloquintocet-mexyl), cyprosulfamide, dichlormid, fenchlorazole (including fenchlorazole-ethyl), fenclorim, fluxofenim, furilazole, isoxadifen (including isoxadifen-ethyl), mefenpyr (including mefenpyr-diethyl), metcamifen and oxabetrinil.
Particularly preferred are mixtures of a compound of formula (I) with cyprosulfamide, isoxadifen (including isoxadifen-ethyl), cloquintocet (including cloquintocet-mexyl) and/or N-(2-methoxybenzoyl)-4-[(methyl-aminocarbonyl)amino]benzenesulfonamide.
The safeners of the compound of formula (I) may also be in the form of esters or salts, as mentioned e.g. in The Pesticide Manual, 14th Edition (BCPC), 2006. The reference to cloquintocet-mexyl also applies to a lithium, sodium, potassium, calcium, magnesium, aluminium, iron, ammonium, quaternary ammonium, sulfonium or phosphonium salt thereof as disclosed in WO 02/34048, and the reference to fenchlorazole-ethyl also applies to fenchlorazole, etc.
Preferably the mixing ratio of compound of formula (I) to safener is from 100:1 to 1:10, especially from 20:1 to 1:1. The mixtures can advantageously be used in the above-mentioned formulations (in which case “active ingredient” relates to the respective mixture of compound of formula (I) with the safener).
The compounds of formula (I) of this invention are useful as herbicides. The present invention therefore further comprises a method for controlling unwanted plants comprising applying to the said plants or a locus comprising them, an effective amount of a compound of the invention or a herbicidal composition containing said compound. ‘Controlling’ means killing, reducing or retarding growth or preventing or reducing germination. Generally the plants to be controlled are unwanted plants (weeds). ‘Locus’ means the area in which the plants are growing or will grow.
The rates of application of compounds of formula (I) may vary within wide limits and depend on the nature of the soil, the method of application (pre-emergence; post-emergence; application to the seed furrow; no tillage application etc.), the crop plant, the weed(s) to be controlled, the prevailing climatic conditions, and other factors governed by the method of application, the time of application and the target crop. The compounds of formula (I) according to the invention are generally applied at a rate of from 10 to 2000 g/ha, especially from 50 to 1000 g/ha. A preferred range is 10-200 g/ha.
The application is generally made by spraying the composition, typically by tractor mounted sprayer for large areas, but other methods such as dusting (for powders), drip or drench can also be used.
Useful plants in which the composition according to the invention can be used include crops such as cereals, for example barley and wheat, cotton, oilseed rape, sunflower, maize, rice, soybeans, sugar beet, sugar cane and turf.
Crop plants can also include trees, such as fruit trees, palm trees, coconut trees or other nuts. Also included are vines such as grapes, fruit bushes, fruit plants and vegetables.
Crops are to be understood as also including those crops which have been rendered tolerant to herbicides or classes of herbicides (e.g. ALS-, GS-, EPSPS-, PPO-, ACCase- and HPPD-inhibitors) by conventional methods of breeding or by genetic engineering. An example of a crop that has been rendered tolerant to imidazolinones, e.g. imazamox, by conventional methods of breeding is Clearfield® summer rape (canola). Examples of crops that have been rendered tolerant to herbicides by genetic engineering methods include e.g. glyphosate-and glufosinate-resistant maize varieties commercially available under the trade names RoundupReady® and LibertyLink®.
Crops are also to be understood as being those which have been rendered resistant to harmful insects by genetic engineering methods, for example Bt maize (resistant to European corn borer), Bt cotton (resistant to cotton boll weevil) and also Bt potatoes (resistant to Colorado beetle). Examples of Bt maize are the Bt 176 maize hybrids of NK® (Syngenta Seeds). The Bt toxin is a protein that is formed naturally by Bacillus thuringiensis soil bacteria. Examples of toxins, or transgenic plants able to synthesise such toxins, are described in EP-A-451 878, EP-A-374 753, WO 93/07278, WO 95/34656, WO 03/052073 and EP-A-427 529. Examples of transgenic plants comprising one or more genes that code for an insecticidal resistance and express one or more toxins are KnockOut® (maize), Yield Gard® (maize), NuCOTIN33B® (cotton), Bollgard® (cotton), NewLeaf® (potatoes), NatureGard® and Protexcta®. Plant crops or seed material thereof can be both resistant to herbicides and, at the same time, resistant to insect feeding (“stacked” transgenic events). For example, seed can have the ability to express an insecticidal Cry3 protein while at the same time being tolerant to glyphosate.
Crops are also to be understood to include those which are obtained by conventional methods of breeding or genetic engineering and contain so-called output traits (e.g. improved storage stability, higher nutritional value and improved flavour).
Other useful plants include turf grass for example in golf-courses, lawns, parks and roadsides, or grown commercially for sod, and ornamental plants such as flowers or bushes.
Compounds of formula (I) and compositions of the invention can typically be used to control a wide variety of monocotyledonous and dicotyledonous weed species. Examples of monocotyledonous species that can typically be controlled include Alopecurus myosuroides, Avena fatua, Brachiaria plantaginea, Bromus tectorum, Cyperus esculentus, Digitaria sanguinalis, Echinochloa crus-galli, Lolium perenne, Lolium multiflorum, Panicum miliaceum, Poa annua, Setaria viridis, Setaria faberi and Sorghum bicolor. Examples of dicotyledonous species that can be controlled include Abutilon theophrasti, Amaranthus retroflexus, Bidens pilosa, Chenopodium album, Euphorbia heterophylla, Galium aparine, Ipomoea hederacea, Kochia scoparia, Polygonum convolvulus, Sida spinosa, Sinapis arvensis, Solanum nigrum, Stellaria media, Veronica persica and Xanthium strumarium.
Unwanted plants are to be understood as also including those weeds that have been rendered tolerant to herbicides or classes of herbicides (e.g. ALS-, GS-, EPSPS-, PPO-, ACCase- and HPPD-inhibitors) by evolution, by conventional methods of breeding or by genetic engineering. Examples include Amaranthus palmeri that has evolved resistance to glyphosate and/or acetolactate synthase (ALS) inhibiting herbicides.
The compounds of the present invention can be used in methods of controlling unwanted plants or weeds which are resistant to protoporphyrinogen oxidase (PPO) inhibitors. For example, Amaranthus palmeri and Amaranthus tuberculatus populations have evolved as PPO-resistant weeds e.g. due to amino acid substitutions in PPX2L such as those occurring at amino acids R128 (also referred to as R98) and G399, or a codon (glycine) deletion in PPX2L at codon 210 (Δ210), the codon numbering being based on NCBI reference DQ386114. The compounds of the present invention can be used in methods of controlling Amaranthus palmeri and/or Amaranthus tuberculatus with mutations or deletions at the previously mentioned codons or equivalents, and it would be obvious to try the compounds to control unwanted plants or weeds with other mutations conferring tolerance or resistance to PPO inhibitors that may arise.
The compounds of formula (I) are also useful for pre-harvest desiccation in crops, for example, but not limited to, potatoes, soybean, sunflowers and cotton. Pre-harvest desiccation is used to desiccate crop foliage without significant damage to the crop itself to aid harvesting.
Compounds/compositions of the invention are particularly useful in non-selective burn-down applications, and as such may also be used to control volunteer or escape crop plants.
Various aspects and embodiments of the present invention will now be illustrated in more detail by way of example. It will be appreciated that modification of detail may be made without departing from the scope of the invention.
The Examples which follow serve to illustrate, but do not limit, the invention.
Oxalyl chloride (0.65 ml, 7.4 mmol) was added dropwise to a stirred solution of 2-chloro-5-nitro-benzoic acid (1.0 g, 4.9 mmol) in dichloromethane (20 ml) at ambient temperature. The resulting solution was stirred at room temperature for 5 mins, then dimethylformamide (5 drops) was added and the resulting solution stirred for a further 60 mins. The solvent was evaporated under reduced pressure and the residue dissolved in dichloromethane (20 ml). To this solution was added a solution of triethylamine (0.76 ml, 5.4 mmol) and ethyl (3S)-3-hydroxybutanoate (0.72 ml, 5.4 mmol) in dichloromethane (5 ml) and the resulting mixture stirred at ambient temperature for 4 hours, then evaporated under reduced pressure and the residue purified by chromatography to provide [(1S)-3-ethoxy-1-methyl-3-oxo-propyl] 2-chloro-5-nitro-benzoate (1.2 g).
Compounds also prepared by this general method include:
Tin dichloride hydrate (2.57 g, 13.3 mmol) was added to a stirred solution of [(1S)-3-ethoxy-1-methyl-3-oxo-propyl] 2-chloro-5-nitro-benzoate (1.05 g, 2.8 mmol) in ethyl acetate (21 ml). The resulting mixture was heated at reflux for 1 hour, then cooled to room temperature and evaporated under reduced pressure. The residue was purified by chromatography to provide [(1S)-3-ethoxy-1-methyl-3-oxo-propyl] 5-amino-2-chloro-benzoate (0.8 g).
Compounds also prepared by this general method include:
Diphosgene (0.26 ml, 2.1 mmol) was added to a stirred solution of [(1S)-3-ethoxy-1-methyl-3-oxo-propyl] 5-amino-2-chloro-benzoate (500 mg, 1.75 mmol) in dry toluene (10 ml). The resulting mixture was heated at reflux for 2 hours, then allowed to cool and evaporated under reduced pressure. The residue was dissolved in toluene (50 ml) then evaporated under reduced pressure to provide [(1S)-3-ethoxy-1-methyl-3-oxo-propyl] 2-chloro-5-isocyanato-benzoate as a light brown liquid (500 mg).
Compounds also prepared by this general method include:
A solution of 1,3-dimethylthiourea (41 mg, 0.38 mmol) and triethylamine (0.058 ml, 0.42 mmol) in toluene (2 ml) was added to a stirred solution of [(1S)-3-ethoxy-1-methyl-3-oxo-propyl] 2-chloro-5-isocyanato-benzoate (100 mg, 0.32 mmol) in toluene (1 ml) at room temperature. The resulting mixture was heated to reflux and carbonyldiimidazole (80 mg, 0.48 mmol) added portionwise over 15 minutes. The mixture was heated at reflux for 3 hours, cooled and evaporated under reduced pressure to give a brown oil which was purified by chromatography to provide [(1S)-3-ethoxy-1-methyl-3-oxo-propyl] 2-chloro-5-(3,5-dimethyl-2,6-dioxo-4-thioxo-1,3,5-triazinan-1-yl) benzoate (Compound 1-360; S-enantiomer) (67 mg).
1H NMR (400 MHz, CDCl3) δ 7.75 (d,1H), 7.6 (d,1H), 7.3 (dd,1H), 5.5 (m,1H), 4.15 (q,2H), 3.8 (s,6H), 2.8 (dd, 1H), 2.6 (dd, 1H), 1.45 (d,3H), 1.2 (t,3H) ppm.
Compounds also prepared by this general method include:
Fuming nitric acid (2.8 ml, 43 mmol) was added slowly to a stirred solution of 2-chloro-4-fluoro-benzoic acid (5.0 g, 28.6 mmol) in concentrated sulphuric acid (20 ml) at 0° C. The resulting mixture was allowed to warm to ambient temperature over 20 minutes, then poured into iced water. The resulting mixture was filtered and the solid dried to provide 2-chloro-4-fluoro-5-nitro-benzoic acid (6.4 g). 1H NMR (400 MHz, CDCl3) δ 8.6 (d,1H), 7.05 (s,1H), 5.9 (br s, 1H) ppm.
Thionyl chloride (9.9 ml, 133 mmol) was added dropwise to a stirred solution of 2-chloro-4-fluoro-5-nitro-benzoic acid (20 g, 88 mmol) in ethanol (200 ml) at ambient temperature. The resulting mixture was heated at 60° C. for 18 hours, then allowed to cool and evaporated under reduce pressure to provide ethyl 2-chloro-4-fluoro-5-nitro-benzoate as a white solid (22.3 g). 1H NMR (400 MHz, CHCl3) δ 8.65 (d,1H), 7.45 (d,1H), 4.45 (q,2H), 1.45 (s,3H) ppm.
Tin dichloride hydrate (1.1 g, 5.8 mmol) was added to a stirred solution of ethyl 2-chloro-4-fluoro-5-nitro-benzoate (500 mg, 1.9 mmol) in ethyl acetate (30 ml). The resulting mixture was heated at reflux for 1 hour, then cooled to room temperature and evaporated under reduced pressure. The residue was purified by chromatography to provide ethyl 5-amino-2-chloro-4-fluoro-benzoate as an oil (275 mg). 1H NMR (400 MHz, CHCl3) δ 7.35 (d,1H), 7.1 (d,1H), 4.4 (q,2H), 1.4 (s,3H) ppm (amine protons not observed).
Diphosgene (0.29 ml, 2.4 mmol) was added to a stirred solution of ethyl 5-amino-2-chloro-4-fluoro-benzoate (450 mg, 1.96 mmol) in dry toluene (9 ml). The resulting mixture was heated at reflux for 2 hours, then allowed to cool and evaporated under reduced pressure. The residue was dissolved in toluene (50 ml) then evaporated under reduced pressure to provide ethyl 2-chloro-4-fluoro-5-isocyanato-benzoate as a light brown liquid (500 mg).
A solution of 1,3-dimethylthiourea (260 mg, 2.5 mmol) and triethylamine (0.37 ml, 2.7 mmol) in toluene (10 ml) was added to a stirred solution of ethyl 2-chloro-4-fluoro-5-isocyanato-benzoate (500 mg, 2 mmol) in toluene (5 ml) at room temperature. The resulting mixture was heated to reflux and carbonyldiimidazole (510 mg, 3.1 mmol) added portionwise over 15 minutes. The mixture was heated at reflux for 3 hours, cooled and evaporated under reduced pressure to give a brown oil which was purified by chromatography to provide 2-chloro-5-(3,5-dimethyl-2,6-dioxo-4-thioxo-1,3,5-triazinan-1-yl)-4-fluoro-benzoate as a gum (547 mg). 1H NMR (400 MHz, CDCl3) δ 7.95 (d,1H), 7.45 (d,1H), 4.4 (q,2H), 3.8 (s,6H), 1.45 (d,3H) ppm.
Concentrated sulphuric acid (0.8 ml, 15 mmol) was added to a stirred solution of 2-chloro-5-(3,5-dimethyl-2,6-dioxo-4-thioxo-1,3,5-triazinan-1-yl)-4-fluoro-benzoate (550 mg, 1.5 mmol) in glacial acetic acid (5.5 ml) at ambient temperature. The resulting mixture was heated at reflux for 17 hours, then cooled and evaporated under reduced pressure. Water was added to the residue and the mixture extracted with dichloromethane. The organic phase was dried over magnesium sulfate, filtered and evaporated under reduced pressure to provide 2-chloro-5-(3,5-dimethyl-2,6-dioxo-4-thioxo-1,3,5-triazinan-1-yl)-4-fluoro-benzoic acid as a glassy solid (440 mg). 1H NMR (400 MHz, CDCl3) δ 8.15 (d,1H), 7.45 (d,1H), 3.8 (s,6H) ppm (acid proton not observed).
Oxalyl chloride (0.38 ml, 4.3 mmol) and then dimethylformamide (6 mg, 0.09 mmol)) was added dropwise to a stirred solution of 2-chloro-5-(3,5-dimethyl-2,6-dioxo-4-thioxo-1,3,5-triazinan-1-yl)-4-fluoro-benzoic acid (300 mg, 0.87 mmol) in tetrahydrofuran (6 ml) at ambient temperature. The resulting solution was stirred at room temperature for 2 hours, then the solvent was evaporated under reduced pressure and the residue dissolved in acetonitrile (6 ml). To this stirred solution at 0° C. was added pyridine (0.7 ml, 8.7 mmol), followed by 1-(1-aminocyclopropyl)-2-methoxy-ethanone (134 mg, 1.0 mmol). The resulting mixture was stirred at 0° C. for 1 hour, then at ambient temperature for 30 minutes. Water and ethyl acetate were added, the phases separated and the organic phase was dried over magnesium sulfate, filtered and evaporated under reduced pressure to leave a residue which was purified by chromatography to provide ethyl 1-[[2-chloro-5-(3,5-dimethyl-2,6-dioxo-4-thioxo-1,3,5-triazinan-1-yl)-4-fluoro-benzoyl]amino]cyclopropanecarboxylate (Compound 1-240) (80 mg). 1H NMR (400 MHz, CDCl3) δ 7.7 (d,1H), 7.3 (d,1H), 6.85 (s,1H), 4.15 (q,2H), 3.75 (s,6H), 1.65 (m,2H), 1.25 (m,5H) ppm.
Compounds also prepared by this general method include:
3-(Ethyliminomethyleneamino)-N,N-dimethyl-propan-1-amine hydrochloride (550 mg, 2.9 mmol) and 1-hydroxybenzotriazole (410 mg, 2.9 mmol) were added to a stirred solution of 2-chloro-5-(3,5-dimethyl-2,6-dioxo-4-thioxo-1,3,5-triazinan-1-yl)-4-fluoro-benzoic acid (prepared as described in example 2, step 6; 500 mg, 1.45 mmol) in dimethylformamide (15 ml) at ambient temperature. The resulting solution was stirred at room temperature for 15 minutes, then a solution of ethyl 3-amino-2-hydroxy-propanoate (385 mg, 2.9 mmol) and N,N-Diisopropylethylamine (380 mg, 2.9 mmol) in dimethylformamide (5 ml) was added. The resulting mixture was stirred at ambient temperature for 19 hours. Water and ethyl acetate were added, the phases separated and the organic phase was dried over sodium sulfate, filtered and evaporated under reduced pressure to leave a residue which was purified by chromatography to provide ethyl 3-[[2-chloro-5-(3,5-dimethyl-2,6-dioxo-4-thioxo-1,3,5-triazinan-1-yl)-4-fluoro-benzoyl]amino]-2-hydroxy-propanoate (Compound 1-1131) (323 mg). 1H NMR (400 MHz, CD3SOCD3) δ 8.7 (t,1H), 7.75 (d, 1H), 7.6 (d,1H), 5.65 (d,1H), 4.2 (q,1H), 4.05 (q,2H), 3.6 (s,6H), 3.45 (m,1H), 3.4 (m,1H), 1.2 (t,3H) ppm.
Oxalyl chloride (0.012 ml, 0.14 mmol) and then dimethylformamide (1 drop) were added to a stirred solution of 2-[2-chloro-5-(3,5-dimethyl-2,6-dioxo-4-thioxo-1,3,5-triazinan-1-yl)-4-fluoro-benzoyl]oxy-2-methyl-propanoic acid (prepared as described in Example 2; 30 mg, 0.07 mmol) in dichloromethane (0.9 ml) at ambient temperature. The resulting solution was stirred at room temperature for 1.5 hours, then ethylamine (2M in tetrahydrofuran; 0.1 ml, 0.2 mmol). The resulting mixture was stirred at ambient temperature for 30 minutes, then water was added. The resulting mixture was extracted with dichloromethane (2×1 ml) and the combined organic extracts were dried, filtered and evaporated under reduced pressure to leave a residue which was purified by chromatography to provide [2-(ethylamino)-1,1-dimethyl-2-oxo-ethyl] 2-chloro-5-(3,5-dimethyl-2,6-dioxo-4-thioxo-1,3,5-triazinan-1-yl)-4-fluoro-benzoate (Compound 1-168) as a beige solid (19 mg). 1H NMR (400 MHz, CD3OD) δ 8.1 (d,1H), 7.6 (d,1H), 3.75 (s,6H), 3.25 (q,2H), 1.7 (s,6H), 1.1 (t,3H) ppm (NH not observed).
The combination is thoroughly mixed with the adjuvants and the mixture is thoroughly ground in a suitable mill, affording wettable powders that can be diluted with water to give suspensions of the desired concentration.
Emulsions of any required dilution, which can be used in plant protection, can be obtained from this concentrate by dilution with water.
Ready-for-use dusts are obtained by mixing the combination with the carrier and grinding the mixture in a suitable mill.
The combination is mixed and ground with the adjuvants, and the mixture is moistened with water. The mixture is extruded and then dried in a stream of air.
The finely ground combination is uniformly applied, in a mixer, to the kaolin moistened with polyethylene glycol. Non-dusty coated granules are obtained in this manner.
The finely ground combination is intimately mixed with the adjuvants, giving a suspension concentrate from which suspensions of any desired dilution can be obtained by dilution with water.
28 parts of the combination are mixed with 2 parts of an aromatic solvent and 7 parts of toluene diisocyanate/polymethylene-polyphenylisocyanate-mixture (8:1). This mixture is emulsified in a mixture of 1.2 parts of polyvinylalcohol, 0.05 parts of a defoamer and 51.6 parts of water until the desired particle size is achieved. To this emulsion a mixture of 2.8 parts 1,6-diaminohexane in 5.3 parts of water is added. The mixture is agitated until the polymerization reaction is completed.
The obtained capsule suspension is stabilized by adding 0.25 parts of a thickener and 3 parts of a dispersing agent. The capsule suspension formulation contains 28% of the active ingredients. The medium capsule diameter is 8-15 microns.
The resulting formulation is applied to seeds as an aqueous suspension in an apparatus suitable for that purpose.
Seeds of weeds and/or crops were sown in standard soil in pots (Amaranthus palmeri (AMAPA), Lolium perenne (LOLPE), Euphorbia heterophylla (EPHHL), Ipomoea hederacea (IPOHE), Setaria faberi (SETFA), Echinochloa crus-galli (ECHCG)). After cultivation for one day under controlled conditions in a glasshouse (at 24/19° C., day/night; 16 hours light), the plants were sprayed with an aqueous spray solution derived from the formulation of the technical active ingredient in a small amount of acetone and a special solvent and emulsifier mixture referred to as IF50 (11.12% Emulsogen EL360™+44.44% N-methylpyrrolidone+44.44% Dowanol DPM glycol ether), to create a 50 g/l solution which was then diluted using 0.2% Genapol XO80 as diluent to give the desired final dose of test compound.
The test plants were then grown under controlled conditions in the glasshouse (at 24/18° C., day/night; 15 hours light; 50% humidity) and watered twice daily. After 13 days the test was evaluated (100=total damage to plant; 0=no damage to plant). The results are shown in Table 9 below.
Post-Emergence Biological Efficacy
Seeds of weeds and/or crops were sown in standard soil in pots (Amaranthus palmeri (AMAPA), Chenopodium album (CHEAL), Euphorbia heterophylla (EPHHL), Ipomoea hederacea (IPOHE), Eleusine indica (ELEIN), Lolium perenne (LOLPE), Digitaria sanguinalis (DIGSA), Setaria faberi (SETFA), Echinochloa crus-galli (ECHCG)). After cultivation for 14 days under controlled conditions in a glasshouse (at 24/19° C., day/night; 16 hours light), the plants were sprayed with an aqueous spray solution derived from the formulation of the technical active ingredient in a small amount of acetone and a special solvent and emulsifier mixture referred to as IF50 (11.12% Emulsogen EL360™+44.44% N-methylpyrrolidone+44.44% Dowanol DPM glycol ether), to create a 50 g/l solution which was then diluted using 0.2% Genapol XO80 as diluent to give the desired final dose of test compound. The test plants were then grown under controlled conditions in the glasshouse (at 24/18° C., day/night; 15 hours light; 50% humidity) and watered twice daily. After 13 days the test was evaluated (100=total damage to plant; 0=no damage to plant). The results are shown in Table 10 below.
| Number | Date | Country | Kind |
|---|---|---|---|
| 21216845.4 | Dec 2021 | EP | regional |
| 22151241.1 | Jan 2022 | EP | regional |
| Filing Document | Filing Date | Country | Kind |
|---|---|---|---|
| PCT/EP2022/086095 | 12/15/2022 | WO |
