Weed control method

Abstract

A compound of formula I or an agronomically acceptable salt of said compound, wherein: R1, R2, R3, R4 and R5 are independently selected from the group consisting of hydrogen, halogen, amino, cyano, nitro, hydroxyl, C1-5 alkyl, C3-6 cycloalkyl, C1-2 haloalkyl, cyanomethyl, C1-2 alkoxyC1-2 alkyl, C1-4 alkoxy, C1-2 haloalkoxy, C2-3 alkenyl, C2-3 alkynyl, halophenyl, C1-2 alkoxycarbonyl, C1-2 alkylsulfanyl, C1-2 alkylsulfinyl, and C1-2 alkylsulfonyl; or R1 and R2 together with the carbon atoms to which they are attached form a 5-or 6-membered ring which may be optionally substituted with one or more groups selected from the group consisting of halogen, cyano, hydroxyl, C1-5 alkyl, C1-2 haloalkyl and C1-4 alkoxy, and wherein the 6-membered ring contains zero, one or two nitrogen atoms, and wherein the 5-membered ring contains one or two heteroatoms independently selected from the group consisting of nitrogen and oxygen; r6 is selected from the group consisting of hydrogen, C1-6 alkyl, and aryl C1-2 alkyl. # imgabs0 #

Description

[0001] The present invention relates to the use of certain compounds as herbicides, herbicidal compositions comprising these compounds, and their use for controlling weeds, in particular in crops of useful plants, or for inhibiting plant growth.

[0002] The present invention is based on the finding that certain fluoromethylphenylacetic acids of formula (I) as defined herein exhibit unexpectedly good herbicidal activity. Accordingly, the present invention provides a compound of formula (I) or an agrochemically acceptable salt thereof,

[0003]

[0004] wherein:

[0005] R 1 、R 2 、R 3 、R 4 and R 5 are independently selected from the group consisting of hydrogen, halogen, amino, cyano, nitro, hydroxy, C 1-5 alkyl, C 3-6 cycloalkyl, C 1-2 haloalkyl, cyanomethyl, C 1-2 alkoxyC 1-2 alkyl, C 1-4 alkoxy, C 1-2 haloalkoxy, C 2-3 alkenyl, C 2-3 alkynyl, halophenyl, C 1-2 alkoxycarbonyl, C 1-2 alkylthio, C 1-2 alkylsulfinyl and C 1-2 alkylsulfonyl; or

[0006] R 1 and R 2 together with the carbon atom to which they are attached form a 5- or 6-membered ring which may optionally be substituted by one or more groups selected from halogen, cyano, hydroxy, C 1-5 alkyl, C 1-2 haloalkyl and C 1-4 alkoxy, and wherein the 6-membered ring contains zero, one or two nitrogen atoms, and wherein the 5-membered ring contains one or two heteroatoms independently selected from the group consisting of nitrogen and oxygen;

[0007] R 6 is selected from the group consisting of hydrogen, C 1-6 alkyl and arylC 1-2 alkyl.

[0008] According to a second aspect of the present invention, there is provided the use of a compound of formula I as a herbicide.

[0009] According to a third aspect of the present 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.

[0010] According to a fourth aspect of the present invention, there is provided a method of controlling or preventing the growth of unwanted plants, wherein a herbicidally effective amount of a compound of formula (I) or a composition comprising such a compound as an active ingredient is applied to the plants, parts thereof or the locus thereof.

[0011] As used herein, the term "halogen" or "halo" means fluorine, chlorine, bromine or iodine, preferably fluorine, chlorine or bromine.

[0012] As used herein, cyano means a -CN group.

[0013] As used herein, hydroxy or hydroxyl means an -OH group.

[0014] As used herein, nitro means -NO 2 group.

[0015] As used herein, amino means -NH 2 group.

[0016] As used herein, the term "C 1 -C 5 alkyl" means a straight-chain or branched-chain hydrocarbon chain group consisting only of carbon and hydrogen atoms, which hydrocarbon chain group contains no unsaturation, has from one to five carbon atoms, and is attached to the remainder of the molecule by a single bond. C 1 -C 3 alkyl and C 1 -C 2 alkyl shall be interpreted accordingly. C 1 -C 5 alkyl examples include but are not limited to methyl (Me), ethyl (Et), n-propyl, 1-methylethyl (isopropyl), n-butyl and 1-dimethylethyl (tert-butyl).

[0017] As used herein, the term "C 3-8 cycloalkyl" means a saturated and stable monocyclic group containing from 3 to 8 carbon atoms. C 3-6 cycloalkyl shall be interpreted accordingly. C 3-8Examples of cycloalkyl groups include, but are not limited to, cyclopropyl, cyclobutyl, cyclopentyl, and cyclohexyl.

[0018] As used herein, the term "C 1 -C 4 alkoxy" refers to a group having the formula -OR a wherein R a is C 1 -C 4 alkyl as generally defined above. C 1 -C 2 alkoxy shall be construed accordingly. Examples of C 1-4 alkoxy include, but are not limited to, methoxy, ethoxy, propoxy, isopropoxy, and tert-butoxy.

[0019] As used herein, the term "C 1-4 alkoxy C 1-4 alkyl" refers to a group having the formula Rb-O-Ra-, wherein Rb is C 1-4 alkyl as generally defined above, and Ra is C 1-4 alkylene as generally defined above.

[0020] As used herein, the term "C 1 -C 2 haloalkyl" refers to C 1 -C 2 alkyl as generally defined above that is substituted with one or more identical or different halogen atoms. C 2 haloalkyl shall be construed accordingly. Examples of C 1 -C 2 haloalkyl include, but are not limited to, chloromethyl, fluoromethyl, fluoroethyl, difluoromethyl, trifluoromethyl, and 2,2,2-trifluoroethyl.

[0021] As used herein, the term "C 2 -C 3 alkenyl" refers to a straight-chain or branched hydrocarbon chain group consisting only of carbon and hydrogen atoms, the hydrocarbon chain group containing at least one double bond that can have an (E)- or (Z)-configuration, having from two to three carbon atoms, and attached to the remainder of the molecule by a single bond. C 2- C 3 Examples of alkenyl include, but are not limited to, vinyl, prop-1-enyl, and allyl (prop-2-enyl).

[0022] As used herein, the term "C 2 -C 3 alkynyl" refers to a straight-chain or branched hydrocarbon chain group consisting only of carbon and hydrogen atoms, the hydrocarbon chain group containing at least one triple bond, having from two to three carbon atoms, and attached to the remainder of the molecule by a single bond. C 2-C 3 Examples of alkynyl groups include, but are not limited to, ethynyl, prop-1-ynyl, and propargyl (prop-2-ynyl).

[0023] As used herein, the term "C 1 -C 2 haloalkoxy" refers to a C 1 -C 2 alkoxy group as defined above substituted with one or more identical or different halogen atoms. Examples of C 1 -C 2 haloalkoxy groups include, but are not limited to, fluoromethoxy, difluoromethoxy, fluoroethoxy, trifluoromethoxy, and trifluoroethoxy.

[0024] As used herein, the term "C 1-2 alkylthio" refers to a group having the formula -SR a wherein R a is a C 1-2 alkyl group as generally defined above.

[0025] As used herein, the term "C 1-2 alkylsulfinyl" refers to a group having the formula -S(O)R a wherein R a is a C 1-2 alkyl group as generally defined above.

[0026] As used herein, the term "C 1-2 alkylsulfonyl" refers to a group having the formula -S(O) 2 R a wherein R a is a C 1-2 alkyl group as generally defined above.

[0027] As used herein, the term "C 1-2 alkoxycarbonyl" refers to a group having the formula RaOC(O)-, wherein Ra is a C 1-2 alkyl group as generally defined above.

[0028] As used herein, the term "C 1-3 alkoxycarbonyl C 1-3 alkyl" refers to a group having the formula -R b C(O)OR a wherein R a is a C 1-3 alkyl group as generally defined above and R b is a C 1-3 alkylene group as generally defined above.

[0029] As used herein, the term "aryl C 1-2 alkyl" refers to a group formed by a C1-2 The alkylene group is attached to the aryl ring as defined above of the remainder of the molecule.

[0030] As used herein, the term "cyano C" 1-6 "alkyl" means a C as generally defined above substituted with one or more cyano groups 1-6 "alkyl". Cyano C 1-4 "alkyl" should be interpreted accordingly. Cyano C 1-6 "alkyl" examples include but are not limited to cyanomethyl.

[0031] The presence of one or more possible asymmetric carbon atoms in the compounds of formula (I) means that these compounds can exist in chiral isomeric forms, i.e., enantiomeric or diastereomeric forms. As a result of restricted rotation about a single bond, atropisomers may also exist. Formula (I) is intended to include all those possible isomeric forms and mixtures thereof. Unless otherwise stated, the present invention includes all those possible isomeric forms and mixtures thereof of the compounds of formula (I). Similarly, formula (I) is intended to include all possible tautomers (including lactam-lactim tautomerism and keto-enol tautomerism) (when present). The present invention includes all possible tautomeric forms of the compounds of formula (I). Similarly, in the presence of a disubstituted olefin, these can exist in the E or Z form or as a mixture of the two in any ratio. The present invention includes all these possible isomeric forms and mixtures thereof of the compounds of formula (I).

[0032] The compounds of formula (I) will typically be provided in the form of an agriculturally acceptable salt, zwitterion or salt of an agriculturally acceptable zwitterion. The present invention encompasses all such agriculturally acceptable salts, zwitterions and mixtures thereof in all proportions.

[0033] Suitable agriculturally acceptable salts of the present invention may have the following cations, including but not limited to metals, conjugate acids of amines, and organic cations. Examples of suitable metals include aluminum, calcium, cesium, copper, lithium, magnesium, manganese, potassium, sodium, iron, and zinc. Examples of suitable amines include allylamine, ammonia, amylamine, arginine, phenethylbenzylamine, benzathine penicillin, butenyl-2-amine, butylamine, butylethanolamine, cyclohexylamine, decylamine, dipentylamine, dibutylamine, diethanolamine, diethylamine, diethylenetriamine, diheptylamine, dihexylamine, diisopentylamine, diisopropylamine, dimethylamine, dioctylamine, dipropanolamine, dipropargylamine, dipropylamine, dodecylamine, ethanolamine, ethylamine, ethylbutylamine, ethylenediamine, ethylheptylamine, ethyloctylamine, ethylpropanolamine, heptadecylamine, heptylamine, hexadecylamine, hexenyl-2-amine, hexylamine, hexylheptylamine, hexyl octylamine, histidine, indoline, isopentylamine, 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, methylpyridine, piperazine, piperidine, propanolamine, propylamine, propylenediamine, pyridine, pyrrolidine, sec-butylamine, stearamide, 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, tributyloxysulfonium, triethylsulfonium, triethyloxysulfonium, trimethylsulfonium, trimethyloxysulfonium, tripropylsulfonium, and tripropyloxysulfonium.

[0034] In a preferred embodiment, the agrochemically acceptable salts are selected from the group consisting of: sodium salts, potassium salts, aluminum salts, dimethylamine (DMA) salts, diethanolamine (DGA) salts, and choline salts. In a particularly preferred embodiment, the agrochemically acceptable salt is a choline salt.

[0035] The following list provides definitions for the substituents R 1 、R 2 、R 3 、R 4 、R 5 and R 6 of the compounds of formula (I) according to the present invention, including preferred definitions. For any one of these substituents, any definition given below may be combined with any definition of any other substituent given below or elsewhere in this document.

[0036] Preferably, R1 is selected from the group consisting of: hydrogen, halogen, amino, cyano, nitro, hydroxy, C 1-4 alkyl, C 3-4 cycloalkyl, C 1-2 haloalkyl, C 1-4 alkoxy, C 1-2 haloalkoxy, C 2-3 alkenyl, C 2-3 alkynyl, halophenyl and C 1-2 alkylthio, more preferably hydrogen, fluorine, chlorine, bromine, amino, cyano, C 1-4 alkyl, cyclopropyl, halomethyl, C 1-3 alkoxy, C 1 haloalkoxy, vinyl, ethynyl and methylthio, most preferably chlorine, bromine, cyano, methyl, ethyl, cyclopropyl, difluoromethyl, trifluoromethyl, methoxy, ethoxy, vinyl and ethynyl.

[0037] Preferably, R 2 is selected from the group consisting of: hydrogen, halogen, amino, cyano, nitro, hydroxy, C 1-4 alkyl, C 3-4 cycloalkyl, C 1-2 haloalkyl, C 1-4 alkoxy, C 1-2 haloalkoxy, C 2-3 alkenyl, C 2-3 alkynyl, halophenyl and C 1-2 alkylthio, more preferably hydrogen, fluorine, chlorine, bromine, cyano, C 1-4 alkyl, cyclopropyl, halomethyl, C 1-3 alkoxy, C 1 haloalkoxy, vinyl, ethynyl, fluorophenyl and methylthio, most preferably hydrogen, chlorine, bromine, cyano, methyl, cyclopropyl, difluoromethyl, trifluoromethyl, methoxy, vinyl and ethynyl.

[0038] Preferably, R 1 and R 2 are both halogen, advantageously, R 1 and R 2 are selected from chlorine and / or bromine. When R 1 and R 2 are selected from chlorine and / or bromine, R 3 to R 5 are preferably each hydrogen, and when R 1 and R 2 are each chlorine, the enantiomers are in the form of the (R) or (S) enantiomers.

[0039] Preferably, R 1 and R 2Together with the carbon atoms to which they are attached, form a 5-membered ring containing one or two heteroatoms independently selected from the group consisting of nitrogen and oxygen. More preferably, the 5-membered ring contains two oxygen atoms. Preferably, the 5-membered ring is partially saturated, and most preferably, the 5-membered ring is saturated. Preferably, the 5-membered ring is substituted by one or two substituents independently selected from the group consisting of fluorine, chlorine, and methyl, and more preferably, the 5-membered ring is substituted by two fluorines.

[0040] Preferably, R 1 and R 2 Together with the carbon atoms to which they are attached, form a 6-membered ring containing zero, one, or two nitrogen atoms. More preferably, the 6-membered ring contains zero or one nitrogen, provided that any nitrogen in the 6-membered ring is adjacent to the benzene ring in structure (I). Preferably, the 6-membered ring is aromatic.

[0041] Preferably, the 6-membered ring is substituted by zero or one substituent. If substituted, the substituent is preferably chlorine. Advantageously, the 6-membered ring contains one nitrogen and has one chlorine substituent, and R 3 to R 5 are each hydrogen.

[0042] Preferably, R 3 is selected from the group consisting of: hydrogen, halogen, amino, cyano, hydroxy, C 1 -C 5 alkyl, C 1-2 haloalkyl, C 1 -C 4 alkoxy, C 2 -C 3 alkenyl, C 2 -C 3 alkynyl, C 1 -C 2 haloalkoxy, and halophenyl, more preferably hydrogen, halogen, amino, trifluoromethoxy, trifluoromethyl, methyl, tert-butyl, and methoxy, and most preferably hydrogen, fluorine, and chlorine.

[0043] Preferably, R 4 is selected from the group consisting of: hydrogen, amino, fluorine, chlorine, and methoxy, and more preferably hydrogen.

[0044] Preferably, R 5 is selected from the group consisting of: hydrogen, fluorine, chlorine, amino, nitro, and methoxy, and more preferably hydrogen, chlorine, and methoxy.

[0045] Preferably, R 6 is selected from the group consisting of: hydrogen, C 1 -C 3 alkyl, and benzyl, and more preferably hydrogen.

[0046] Preferably, when R 3When R is trifluoromethyl, 1 R 2 R 4 and R 5 are each hydrogen.

[0047] Preferably, when R 1 is methyl, R 2 is cyano or methoxy, and R 3 to R 5 are each hydrogen.

[0048] Preferably, there is provided the use of a compound of formula I as a herbicide, wherein R 1 and R 2 are substituted as described above, and R 3 to R 5 are each hydrogen. Preferably, R 1 is methyl and R 2 is halogen, preferably chlorine.

[0049] Table of Examples

[0050] Table 1 below discloses 819 specific compounds of formula (I), designated as Compound Nos. 1-1 to 1-819 respectively, wherein R 6 is hydrogen.

[0051] Table 1

[0052]

[0053]

[0054]

[0055]

[0056]

[0057]

[0058]

[0059]

[0060]

[0061]

[0062]

[0063]

[0064]

[0065]

[0066]

[0067]

[0068]

[0069]

[0070]

[0071]

[0072]

[0073]

[0074]

[0075]

[0076]

[0077]

[0078]

[0079]

[0080]

[0081]

[0082]

[0083] The 819 compounds having the formula (I) are respectively designated as Compound Nos. 2-1 to 2-819, wherein R 6 is methyl and the value of R 1 -R 5 is as given in Table 1 for Compounds 1-1 to 1-819.

[0084] The 819 compounds having the formula (I) are respectively designated as Compound Nos. 3-1 to 3-819, wherein R 6 is ethyl and the value of R 1 -R 5 is as given in Table 1 for Compounds 1-1 to 1-819.

[0085] 819 compounds having the formula (I) were respectively designated as compound numbers 4-1 to 4-819, where R 6 is benzyl and R 1 -R 5 values are given in Table 1 for compounds 1-1 to 1-819.

[0086] 819 compounds having the formula (I) were respectively designated as compound numbers 5-1 to 5-819, where R 6 is lithium and R 1 -R 5 values are given in Table 1 for compounds 1-1 to 1-819.

[0087] 819 compounds having the formula (I) were respectively designated as compound numbers 6-1 to 6-819, where R 6 is sodium and R 1 -R 5 values are given in Table 1 for compounds 1-1 to 1-819.

[0088] 819 compounds having the formula (I) were respectively designated as compound numbers 7-1 to 7-819, where R 6 is ammonium and R 1 -R 5 values are given in Table 1 for compounds 1-1 to 1-819.

[0089] 819 compounds having the formula (I) were respectively designated as compound numbers 8-1 to 8-819, where R 6 is diisopropylammonium and R 1 -R 5 values are given in Table 1 for compounds 1-1 to 1-819.

[0090] 819 compounds having the formula (I) were respectively designated as compound numbers 9-1 to 9-819, where R 6 is N,N,N-trimethylethanolammonium and R 1 -R 5 values are given in Table 1 for compounds 1-1 to 1-819.

[0091] Compounds having the formula (I) can be prepared from esters having the formula (A), as shown in Reaction Scheme 1.

[0092] Reaction Scheme 1

[0093]

[0094] For example, a compound of formula (A) wherein R6 represents methyl or ethyl can be treated with a base (such as lithium hydroxide) in a suitable solvent (such as a mixture of methanol and water).

[0095] The compound of formula (A) can be prepared from a compound of formula (B) as shown in Reaction Scheme 2.

[0096] Reaction Scheme 2

[0097]

[0098] For example, a mixture of a compound of formula (B) wherein R6 represents methyl or ethyl in a suitable solvent (such as tetrahydrofuran) can be treated with a base (such as lithium diisopropylamide), followed by a methylation reagent (such as methyl iodide).

[0099] The compound of formula (B) can be prepared from an aryl halide of formula (C) as shown in Reaction Scheme 3.

[0100] Reaction Scheme 3

[0101]

[0102] For example, a mixture of a compound of formula (C) wherein X represents iodine or bromine and a compound of formula (D) wherein R6 represents methyl or ethyl can be treated in a suitable solvent (such as N,N - dimethylacetamide) with a catalyst (such as nickel(II) iodide), a ligand (such as 5,5'-dimethyl-2,2'-bipyridine), a metal (such as zinc), and a metal substance (such as magnesium dichloride).

[0103] The aryl halide of formula (C) is commercially available or can be prepared by methods well known in the literature.

[0104] The compound of formula (D) is commercially available or can be prepared by methods well known in the literature.

[0105] The compound of formula (A) can also be prepared from a compound of formula (E) as shown in Reaction Scheme 4.

[0106] Reaction Scheme 4

[0107]

[0108] For example, a compound of formula (E) wherein R6 represents methyl or ethyl can be treated in a suitable solvent (such as tetrahydrofuran) with a base (such as sodium bis(trimethylsilyl)amide), followed by a fluorination reagent (such as N - fluorobenzenesulfonimide).

[0109] The compound having formula (E) can also be prepared from an ester having formula (F) as shown in Reaction Scheme 5.

[0110] Reaction Scheme 5

[0111]

[0112] For example, the compound having formula (E) where R6 represents methyl or ethyl can be treated in a suitable solvent such as tetrahydrofuran with a base such as lithium diisopropylamide and subsequently with a methylation reagent such as methyl iodide.

[0113] The compound having formula (F) is commercially available or can be prepared by methods well known in the literature.

[0114] The compound having formula (B) can also be prepared from a compound having formula (G) as shown in Reaction Scheme 6.

[0115] Reaction Scheme 6

[0116]

[0117] For example, the compound having formula (G) where R6 represents methyl or ethyl can be treated in a suitable solvent such as dichloromethane with a fluorination reagent such as diethylaminosulfur trifluoride.

[0118] The compound having formula (G) is commercially available or can be prepared by methods well known in the literature.

[0119] The compound having formula (A) can also be prepared from a compound having formula (H) as shown in Reaction Scheme 7.

[0120] Reaction Scheme 7

[0121]

[0122] For example, the compound having formula (H) where R6 represents methyl or ethyl can be treated in a suitable solvent such as dichloromethane with a fluorination reagent such as diethylaminosulfur trifluoride.

[0123] The compound having formula (H) can be prepared from a compound having formula (J) as shown in Reaction Scheme 8.

[0124] Reaction Scheme 8

[0125]

[0126] For example, the compound having formula (J) where R6 represents methyl or ethyl can be treated in a suitable solvent such as tetrahydrofuran with a methylation reagent such as methylmagnesium bromide.

[0127] Compounds having formula (J) are commercially available or can be prepared by methods well-known in the literature.

[0128] The compounds according to the invention can be used as herbicides in unmodified form, but they are generally formulated into compositions with the aid of formulation auxiliaries (such as carriers, solvents and surface-active substances) in a variety of ways. These formulations can be in different physical forms, for example, in the form of: dusts, gels, wettable powders, water-dispersible granules, water-dispersible tablets, effervescent compressed tablets, emulsifiable concentrates, microemulsifiable concentrates, oil-in-water emulsions, flowable oils, aqueous dispersions, oily dispersions, suspoemulsions, capsule suspensions, emulsifiable granules, soluble liquids, water-soluble concentrates (with water or water-miscible organic solvents as carriers), impregnated polymer films or in other known forms, for example known from the Manual on Development and Use of FAO and WHO Specifications for Pesticides, United Nations, 1st Edition, Second Revision (2010). For water-soluble compounds, soluble liquids, water-soluble concentrates or water-soluble granules are preferred. Such formulations can be used directly or can be diluted before use. Dilution can be carried out with, for example, water, liquid fertilizers, micronutrients, biological organisms, oils or solvents.

[0129] These formulations can be prepared, for example, by mixing the active ingredient with formulation auxiliaries in order to obtain a composition in the form of a finely divided solid, granules, solution, dispersion or emulsion. These active ingredients can also be formulated together with other auxiliaries (such as finely divided solids, mineral oils, oils of plant or animal origin, modified oils of plant or animal origin, organic solvents, water, surface-active substances or combinations thereof).

[0130] These active ingredients can also be incorporated into very fine microcapsules. The microcapsules contain the active ingredient in a porous carrier. This enables the active ingredient to be released in a controlled amount (e.g., slowly) into the environment. The microcapsules generally have a diameter of from 0.1 to 500 micrometers. The amount of active ingredient they contain is about 25% to 95% by weight of the weight of the capsule. These active ingredients can be in the form of a monolithic solid, in the form of fine particles in a solid or liquid dispersion, or in the form of a suitable solution. The encapsulating film can comprise, for example, natural or synthetic rubber, cellulose, styrene / butadiene copolymer, polyacrylonitrile, polyacrylate, polyester, polyamide, polyurea, polyurethane or chemically modified polymers, as well as starch xanthate, or other polymers known to those skilled in the art. Alternatively, very fine microcapsules can be formed in which the active ingredient is contained in a solid matrix of a base substance in the form of fine dispersed particles, but these microcapsules are not themselves encapsulated.

[0131] Formulation adjuvants suitable for preparing the compositions according to the invention are known per se. As liquid carriers, the following can be used: water, toluene, xylene, petroleum ether, vegetable oil, acetone, methyl ethyl ketone, cyclohexanone, acid anhydride, acetonitrile, acetophenone, amyl acetate, 2-butanone, butylene carbonate, chlorobenzene, cyclohexane, cyclohexanol, alkyl acetate, diacetone alcohol, 1,2-dichloropropane, diethanolamine, p-diethylbenzene, diethylene glycol, diethylene glycol rosin acid ester, 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, alkyl pyrrolidone, ethyl acetate, 2-ethylhexanol, ethylene carbonate, 1,1,1-trichloroethane, 2-heptanone, α-pinene, d-limonene, ethyl lactate, ethylene glycol, ethylene glycol butyl ether, ethylene glycol methyl ether, γ-butyrolactone, glycerol, glycerol acetate, glycerol diacetate, glycerol triacetate, hexadecane, hexylene glycol, isoamyl acetate, isobornyl acetate, isooctane, isophorone, cumene, isopropyl myristate, lactic acid, laurylamine, isopropylideneacetone, methoxypropanol, methyl isoamyl ketone, methyl isobutyl ketone, methyl laurate, methyl octanoate, methyl oleate, dichloromethane, m-xylene, n-hexane, n-octylamine, stearic 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, xylene sulfonic acid, paraffin wax, mineral oil, trichloroethylene, perchloroethylene, ethyl acetate, amyl acetate, butyl acetate, propylene glycol methyl ether, diethylene glycol methyl ether, methanol, ethanol, isopropyl alcohol and higher molecular weight alcohols such as pentanol, tetrahydrofurfuryl alcohol, hexanol, octanol, ethylene glycol, propylene glycol, glycerol, N-methyl-2-pyrrolidone, etc.

[0132] Suitable solid carriers are, for example, talc, titanium dioxide, pyrophyllite clay, silica, attapulgite clay, diatomaceous earth, limestone, calcium carbonate, bentonite, calcium montmorillonite, cottonseed hulls, wheat flour, soybean flour, pumice, wood flour, ground walnut shells, lignin and similar substances.

[0133] Many surface-active substances can be advantageously used in both solid and liquid formulations, especially those which can be diluted by the carrier before use. The surface-active substances can 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 sulphates, such as diethanolammonium lauryl sulphate; salts of alkylarylsulphonates, such as calcium dodecylbenzenesulphonate; alkylphenol / alkylene oxide adducts, such as ethoxylated nonylphenol; alcohol / alkylene oxide adducts, such as ethoxylated tridecanol; soaps, such as sodium stearate; salts of alkylnaphthalenesulphonates, such as sodium dibutylnaphthalenesulphonate; salts of dialkyl esters of sulphosuccinic acid, such as sodium bis(2-ethylhexyl) sulphosuccinate; sorbitan esters, such as sorbitan oleate; quaternary amines, such as dodecyltrimethylammonium chloride; polyethylene glycol esters of fatty acids, such as polyethylene glycol stearate; block copolymers of ethylene oxide and propylene oxide; and salts of monoalkyl and dialkyl phosphates; and also other substances, for example as described in: McCutcheon's Detergents and Emulsifiers Annual, MC Publishing Corp., Ridgewood, New Jersey (1981).

[0134] Further auxiliaries which can be used in the pesticidal formulations include crystal growth inhibitors, viscosity regulators, suspending agents, dyes, antioxidants, foaming agents, light absorbers, mixing aids, defoamers, complexing agents, substances for neutralizing or altering the pH and buffers, corrosion inhibitors, fragrances, wetting agents, absorption enhancers, micronutrients, plasticizers, glidants, lubricants, dispersants, thickeners, antifreeze agents, microbicides, and liquid and solid fertilizers.

[0135] The composition according to the invention may comprise an additive, which additive comprises an oil of vegetable or animal origin, a mineral oil, an alkyl ester of such an oil or a mixture of such an oil and an oil derivative. The amount of the 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 may be added to the spray tank at the desired concentration after the spray mixture has been prepared. Preferred oil additives include mineral oils or oils of vegetable origin, such as rapeseed oil, olive oil or sunflower oil; emulsified vegetable oils; alkyl esters of oils of vegetable origin, such as methyl derivatives; or oils of animal origin, such as fish oil or tallow. Preferred oil additives include C 8 -C 22 alkyl esters of fatty acids, especially C 12 -C 18 methyl derivatives of fatty acids, such as methyl esters of lauric acid, palmitic acid and oleic acid (methyl laurate, methyl palmitate and methyl oleate, respectively). Many oil derivatives are known from Compendium of Herbicide Adjuvants, 10th Edition, Southern Illinois University, 2010.

[0136] The herbicidal composition generally comprises from 0.1% to 99% by weight, especially from 0.1% to 95% by weight, of a compound of formula (I) and from 1% to 99.9% by weight of a formulation adjuvant, which formulation adjuvant preferably comprises from 0 to 25% by weight of a surface-active substance. The composition of the invention generally comprises from 0.1% to 99% by weight, especially from 0.1% to 95% by weight, of the compound of the invention and from 1% to 99.9% by weight of a formulation adjuvant, which formulation adjuvant preferably comprises from 0 to 25% by weight of a surface-active substance. While commercial products may preferably be formulated as concentrates, the end user will generally employ dilute formulations.

[0137] The application rates vary within wide limits and depend on the nature of the soil, the method of application, the crop plant, the pests to be controlled, the prevailing climatic conditions, and other factors governed by the method of application, the time of application and the target crop. Generally speaking, the compound may be applied at a rate of 1 to 2000 l / ha, especially 10 to 1000 l / ha.

[0138] Preferred formulations may have the following composition (% by weight):

[0139] Emulsifiable Concentrate :

[0140] Active ingredient: 1% to 95%, preferably 60% to 90%

[0141] Surfactant: 1% to 30%, preferably 5% to 20%

[0142] Liquid carrier: 1% to 80%, preferably 1% to 35%

[0143] Dust :

[0144] Active ingredient: 0.1% to 10%, preferably 0.1% to 5%

[0145] Solid carrier: 99.9% to 90%, preferably 99.9% to 99%

[0146] Suspension Concentrate:

[0147] Active ingredient: 5% to 75%, preferably 10% to 50%

[0148] Water: 94% to 24%, preferably 88% to 30%

[0149] Surfactant: 1% to 40%, preferably 2% to 30%

[0150] Wettable Powder :

[0151] Active ingredient: 0.5% to 90%, preferably 1% to 80%

[0152] Surfactant: 0.5% to 20%, preferably 1% to 15%

[0153] Solid carrier: 5% to 95%, preferably 15% to 90%

[0154] Granule:

[0155] Active ingredient: 0.1% to 30%, preferably 0.1% to 15%

[0156] Solid carrier: 99.5% to 70%, preferably 97% to 85%

[0157] The composition of the present invention may further comprise at least one additional pesticidal agent. For example, the compounds according to the present invention may also be used in combination with other herbicides or plant growth regulators. In a preferred embodiment, the additional pesticidal agent is a herbicide and / or a herbicide safener.

[0158] The compounds of the present invention can also be used in mixtures 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), acibenzolar, ametryn, amicarbazone, aminopyralid, aminotriazole, atrazine, butafenacil-M, benquitrione, bensulfuron-methyl (including bensulfuron-methyl), bentazone, bicyclopyrone, bilanafos, bispyribac-sodium, bixlozone, bromacil, bromoxynil, butachlor, butafenacil, carfentrazone-ethyl (including carfentrazone-ethyl), chlorimuron-ethyl (including chlorimuron-ethyl), chlorotoluron, chlorsulfuron, cinmethylin, clacyfos, clethodim, clodinafop-propargyl (including clodinafop-propargyl), clomazone, clopyralid, cyclopyranil, cyclopyrimorate, cyclosulfamuron, cyhalofop-butyl (including cyhalofop-butyl), 2,4-D (including its choline salt and 2-ethylhexyl ester), 2,4-DB, desmedipham, dicamba (including its aluminum, aminopropyl, bis-aminopropylmethyl, choline, dichloropropyl, diethylene glycolamine, dimethylamine, dimethylammonium, potassium salt and sodium salt), diclosulam, diflufenican, flucarbazone, dimethenamid, dimethenamid-P, dioxopyritrione, diquat dibromide, diuron, epyrifenacil, ethalfluralin, ethofumesate, fenoxaprop-P-ethyl (including fenoxaprop-P-ethyl), fenoxasulfone, flufenpyr-ethyl, flumioxazin, flumipropyn, flupropacil, fluroxypyr (including fluroxypyr-meptyl), fluthiacet-methyl, foramsulfuron, glufosinate (including L-glufosinate and the ammonium salts of both), glyphosate (including its diamine, isopropylammonium and potassium salts), halauxifen-methyl (including halauxifen-methyl), haloxyfop-methyl (including haloxyfop-methyl), hexazinone, hydantocidin, imazamox (including R-imazamox), imazapic, imazapyr, imazethapyr, indaziflam, iodosulfuron-methyl-sodium (including iodosulfuron-methyl-sodium), iofensulfuron (including iofensulfuron-sodium), ioxynil, isoproturon,isoxaflutole, lancotrione, MCPA, MCPB, mecoprop-P, mesosulfuron-methyl (including mesosulfuron-methyl), mesotrione, bentazone, pretilachlor, methiozolin, S-metolachlor, penoxsulam, metamitron, oxadiazon, oxyfluorfen, paraquat dichloride, pendimethalin, penoxsulam, benzthiazuron, picloram, pinoxaden, pretilachlor, flupyrsulfuron-methyl, prometryn, propanil, clomazone, propyrisulfuron, propyzamide, pyributicarb, flazasulfuron, diclazylpyr, pyraflufen (including pyraflufen-ethyl), sulfentrazone, pyridafol, pyribambenz-propyl, pyrimisulfan, pyroxasulfone, flazasulfuron, quinclorac, cloransulam-methyl, quizalofop (including quizalofop-P-ethyl and quizalofop-P-tefuryl), rimisoxafen, sulfosulfuron, pyriminobac-methyl, clethodim, simazine, S-metolachlor, mesotrione, sulfosulfuron, buthiuron, tefuryltrione, mesotrione, terbuthylazine, terbutryn, tetflupyrolimet, thiencarbazone, thifensulfuron-methyl, tiafenacil, tolpyralate, pyrazolynate, tralkoxydim, triafamone, tri-allate, ethoxysulfuron, tribenuron-methyl (including tribenuron-methyl), picloram, tritosulfuron (including tritosulfuron-sodium), trifludimoxazin, trifluralin, flazasulfuron, triazofenamide, ethyl 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-carboxylate, 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 its agrochemically acceptable esters, e.g., 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)pyridin-2-ylformate), 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-pyridinyl]oxy]acetate and 6-chloro-4-(2,7-dimethyl-1-naphthyl)-5-hydroxy-2-methyl-pyridazin-3-one.

[0159] The mixed formulations of the compounds of formula (I) can also be in the form of esters or salts, as mentioned, for example, in: The Pesticide Manual, Fourteenth Edition, British Crop Protection Council, 2006.

[0160] The compounds 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.

[0161] The mixing ratio of the compounds of formula (I) with the mixed formulations is preferably from 1:100 to 1000:1.

[0162] These mixtures can be advantageously used in the above-mentioned formulations (in which case the "active ingredient" refers to the corresponding mixture of the compounds of formula (I) with the mixed formulations).

[0163] The compounds of formula (I) according to the invention can also be combined with herbicide safeners. Examples of such safeners include benoxacor, cloquintocet (including mefenpyr-diethyl), cyprosulfamide, dichlormid, oxabetrinil (including oxabetrinil-ethyl), mefenpyr, flurazole, isoxadifen, isoxadifen-ethyl, pyrazoxyfen (including pyrazoxyfen-diethyl), metcamifen and dichlobenil.

[0164] Particularly preferred are mixtures of the compounds of formula (I) with cyprosulfamide, isoxadifen-ethyl, cloquintocet (including mefenpyr-diethyl) and / or N-(2-methoxybenzoyl)-4-[(methylaminocarbonyl)amino]benzenesulfonamide.

[0165] These safeners of the compounds of formula (I) can also be in the form of esters or salts, as mentioned, for example, in the "Pesticide Manual" (14th edition (BCPC), 2006). The reference to mefenpyr-diethyl also applies to its lithium, sodium, potassium, calcium, magnesium, aluminium, iron, ammonium, quaternary ammonium, sulfonium or phosphonium salts (as disclosed in WO 02 / 34048), and the reference to oxabetrinil-ethyl also applies to oxabetrinil etc.

[0166] Preferably, the mixing ratio of the compounds of formula (I) with the safener is from 100:1 to 1:10, in particular from 20:1 to 1:1.

[0167] These mixtures can advantageously be used in the abovementioned formulations (in which case the "active ingredient" relates to the corresponding mixture of the compounds of formula (I) with the safener).

[0168] The compounds of formula (I) according to the invention are useful as herbicides. Accordingly, the invention further includes a method for controlling unwanted plants, which method comprises applying to the plants or the locus containing them an effective amount of a compound of the invention or a herbicidal composition containing said compound. 'Controlling' means killing, reducing or delaying 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.

[0169] The application rate of the compounds of formula (I) can vary within wide limits and depends on the nature of the soil, the method of application (pre-emergence; post-emergence; application to the seed furrow; no-till application etc.), the crop plants, one or more weeds to be controlled, the main climatic conditions and other factors which are 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 10 to 2000 g / ha, in particular 50 to 1000 g / ha. A preferred range is 10 - 200 g / ha.

[0170] Application is typically carried out by spraying the composition, typically by means of a tractor-mounted sprayer for large areas, but other methods such as dusting (for powders), dripping or flooding can also be used.

[0171] Useful plants for which the compositions according to the invention can be used include crops such as cereals, e.g. barley and wheat, cotton, rapeseed, rape, sunflower, maize, rice, soybeans, sugar beet, sugar cane and turf.

[0172] Crop plants can also include trees, such as fruit trees, palm trees, coconut trees or other nuts. Also included are vines (such as grapes), bush fruit trees, fruit plants and vegetables.

[0173] Crops should be understood to also include those crops which have been given tolerance to herbicides or multiple classes of herbicides (e.g. ALS-inhibitors, GS-inhibitors, EPSPS-inhibitors, PPO-inhibitors, ACC enzyme-inhibitors and HPPD-inhibitors) by conventional breeding methods or by genetic engineering. Examples of crops which have been given tolerance to imidazolinones (e.g., imazamox) by conventional breeding methods are summer rape (canola). Examples of crops which have been given tolerance to herbicides by genetic engineering methods include, for example, maize varieties with glyphosate and glufosinate resistance, which are commercially available under the trade names and are commercially available.

[0174] Crops should also be understood to include those crops which have been given resistance to harmful insects by genetic engineering methods, such as Bt maize (resistant to the European corn borer), Bt cotton (resistant to the boll weevil) and also Bt potato (resistant to the Colorado beetle). An example of Bt maize is the Bt 176 maize hybrid (Syngenta Seeds) of. The Bt toxin is a protein naturally formed by the soil bacterium Bacillus thuringiensis. Examples of toxins or transgenic plants capable of synthesizing 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 containing one or more genes encoding insecticidal resistance and expressing one or more toxins are (maize), Yield (maize), (cotton), (cotton), (Potato), and Plant crops or their seed materials can be herbicide - resistant and at the same time insect - feeding resistant (“stacked” transgenic events). For example, the seeds can have the ability to express the insecticidal Cry3 protein while being tolerant to glyphosate.

[0175] Crops should also be understood to include those crops obtained by conventional breeding methods or genetic engineering and containing so - called output traits (such as improved storage stability, higher nutritional value, and improved flavor).

[0176] Other useful plants include, for example, turf grasses on golf courses, lawns, parks, and roadsides or commercially grown for turf, as well as ornamental plants (such as flowers or shrubs).

[0177] Compounds and compositions of the present invention having formula (I) can typically be used to control a 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.

[0178] The compounds having formula (I) can also be used for pre-harvest drying of crops, such as but not limited to potatoes, soybeans, sunflowers, and cotton. Pre-harvest drying is used to dry the crop leaves without causing significant damage to the crop itself to facilitate harvesting.

[0179] The compounds / compositions of the present invention are particularly useful for non-selective burn-down applications and can therefore also be used to control volunteer or escape crop plants.

[0180] The different aspects and embodiments of the present invention will now be illustrated in more detail by way of examples. It should be understood that modifications can be made to the details without departing from the scope of the present invention. The following examples are for illustration purposes and not intended to limit the present invention.

[0181] Example

[0182] Synthesis Example

[0183] Example 1 Preparation of 2-Fluoro-2-(3-methoxy-2-methyl-phenyl)propanoic acid (Compound 1-250) Step 1 Synthesis of Ethyl 2-Fluoro-2-(3-methoxy-2-methyl-phenyl)acetate

[0184]

[0185] To a round-bottom flask was added 1-Iodo-3-methoxy-2-methyl-benzene (901 mg, 3.63 mmol), 5,5'-Dimethyl-2,2'-bipyridine (0.363 mmol, 67 mg), Magnesium dichloride (519 mg, 5.45 mmol), Zinc (713 mg, 10.9 mmol), Nickel(II) iodide (114 mg, 0.363 mmol). The flask was evacuated and backfilled with nitrogen (×3), then N,N-Dimethylacetamide (4 mL / mmol) was added. Then Ethyl 2-chloro-2-fluoroacetate (1.28 g, 9.08 mmol) was added dropwise. The reaction was heated to 80 °C for 3 hours. The reaction was cooled and the sample was filtered through a plug of silica and washed with EtOAc (3 × 15 mL). Then the combined organic washes were washed with water (3 × 25 mL). The organic layer was concentrated under reduced pressure. The crude product was loaded onto silica by dry loading and purified by flash column chromatography (0-20% EtOAc / cyclohexane) to afford Ethyl 2-Fluoro-2-(3-methoxy-2-methyl-phenyl)acetate (521 mg, 2.30 mmol, 63%) as a yellow liquid.

[0186] 1 H NMR (400 MHz, chloroform) δ = 7.18 - 7.23 (1H, m), 7.01 (1H, d), 6.88 (1H, d), 5.91 - 6.06 (1H, m), 4.16 - 4.32 (2H, m), 3.83 (3H, s), 2.29 (3H, d), 1.23 - 1.28 (3H, m) ppm

[0187] Step 2 Synthesis of Ethyl 2-Fluoro-2-(3-methoxy-2-methyl-phenyl)propanoate (Compound 3-250)

[0188]

[0189] At -78 °C in N 2 To a solution of ethyl 2-fluoro-2-(3-methoxy-2-methyl-phenyl)acetate (473 mg, 2.09 mmol) in anhydrous tetrahydrofuran (15 mL) was added dropwise lithium diisopropylamide (2.0 mol / L, 4.18 mmol). The resulting reaction mixture was stirred at the same temperature for 20 min and then methyl iodide (4.18 mmol, 0.593 g) in tetrahydrofuran (1 mL) was added. The reaction was stirred at -78 °C for 10 min and then gradually warmed to room temperature and stirred overnight. The reaction mixture was quenched with saturated NH 4 Cl aqueous solution and extracted with EtOAc (3 × 20 mL). The combined organic phases were passed through a phase separation column and concentrated under reduced pressure. The crude residue was loaded onto silica gel by dry loading and purified by chromatography (0 to 10% cyclohexane:EtOAc) to give ethyl 2-fluoro-2-(3-methoxy-2-methyl-phenyl)propionate (Compound 3-250) as a pale yellow liquid (288 mg, 1.20 mmol, 57%).

[0190] 1 H NMR (400 MHz, chloroform) δ = 7.16 - 7.22 (1H, m), 7.06 (1H, d), 6.88 (1H, d), 4.16 - 4.31 (2H, m), 3.82 (3H, s), 2.20 (3H, d), 1.97 (3H, d), 1.24 (3H, t) ppm

[0191] Step 3 Synthesis of 2-fluoro-2-(3-methoxy-2-methyl-phenyl)propanoic acid (Compound 1-250)

[0192]

[0193] To a stirred solution of ethyl 2-fluoro-2-(3-methoxy-2-methyl-phenyl)propionate (217 mg, 0.904 mmol) in 2-MeTHF:MeOH:H2O (1:1:1, 3 mL) at room temperature was added sodium hydroxide (72 mg, 1.80 mmol). The reaction mixture was stirred overnight and then diluted with 2M HCl aqueous solution and extracted with ethyl acetate (3 × 15 mL). The combined organic extracts were passed through a phase separation column and concentrated under reduced pressure to give 2-fluoro-2-(3-methoxy-2-methyl-phenyl)propanoic acid (Compound 1-250) as pale yellow crystals (173 mg, 0.814 mmol, 90%).

[0194] 1¹H NMR (400 MHz, chloroform) δ = 7.18 - 7.24 (m, 1H), 7.07 (d, 1H), 6.91 (d, 1H), 3.83 (s, 3H), 2.25 (s, 3H), 2.04 (d, 3H) ppm

[0195] Example 2 Preparation of 2-(2-Chloro-4-fluorophenyl)-2-fluoropropanoic acid (Compound 1-133)

[0196] Step 1 Synthesis of methyl 2-(2-chloro-4-fluorophenyl)propionate

[0197]

[0198] Methyl 2-(2-chloro-4-fluorophenyl)acetate (1.05 g, 5.08 mmol) was added to a round-bottom flask. The flask was evacuated and backfilled with nitrogen three times, and then tetrahydrofuran (24 mL) was added. The colorless solution was cooled to -78 °C. Lithium diisopropylamide (2.0 mol / L, 2.7 mL, 5.4 mmol) was added dropwise, and the reaction was stirred at -78 °C for 30 minutes. Methyl iodide (0.34 mL, 5.4 mmol) was added to the reaction mixture, and the reaction mixture was warmed to room temperature and stirred for 3 hours. The reaction mixture was diluted with water (30 mL) and extracted with ethyl acetate (4 × 15 mL). The combined organic layers were concentrated in vacuo onto a solid support for column chromatography (0 - 10% ethyl acetate in cyclohexane) to afford methyl 2-(2-chloro-4-fluorophenyl)propionate (0.817 g, 3.58 mmol, 70%).

[0199] 1 ¹H NMR (400 MHz, chloroform) δ = 7.30 (dd, 1H), 7.13 (dd, 1H), 6.98 (dt, 1H), 4.17 (q, 1H), 3.69 (s, 3H), 1.49 (d, 3H) ppm

[0200] Step 2 Synthesis of methyl 2-(2-chloro-4-fluorophenyl)-2-fluoropropionate (Compound 2-133)

[0201]

[0202] Methyl 2-(2-chloro-4-fluorophenyl)propionate (0.817 g, 3.58 mmol) was added to a three-necked round-bottom flask. The flask was evacuated and backfilled with nitrogen three times, and then tetrahydrofuran (15 mL) was added. The solution was cooled to -78 °C, and sodium bis(trimethylsilyl)amide (1.0 mol / L in THF, 3.9 mL, 3.9 mmol) was added dropwise to the stirred solution. The reaction was stirred at -78 °C for 30 minutes, and then N-fluorobenzenesulfonimide (1.24 g, 3.95 mmol) in tetrahydrofuran (6 mL) was added. The reaction mixture was stirred for 30 minutes and then allowed to warm to room temperature. The reaction was stirred for 3 hours and then quenched with water. The reaction mixture was extracted with ethyl acetate (3 × 10 mL). The combined organic layers were concentrated in vacuo and purified by flash column chromatography (0-10% ethyl acetate in cyclohexane) to give methyl 2-(2-chloro-4-fluorophenyl)-2-fluoropropionate (Compound 2-133) (0.647 g, 2.07 mmol, 58%).

[0203] 1 H NMR (400 MHz, chloroform) δ = 7.59 (dd, 1H), 7.16 - 7.13 (m, 1H), 7.09 - 7.03 (m, 1H), 3.80 (s, 3H), 1.96 (d, 3H) ppm

[0204] Also prepared by this general method were:

[0205] Methyl 2-(2-bromo-3-chlorophenyl)-2-fluoropropionate (Compound 2-192)

[0206] 1 H NMR (400 MHz, chloroform) δ = 7.54 - 7.49 (m, 2H), 7.35 (t, 1H), 3.79 (s, 3H), 2.04 - 1.95 (m, 3H)

[0207] Methyl 2-(3-cyano-2-methylphenyl)-2-fluoropropionate (Compound 2-249)

[0208] 1 H NMR (400 MHz, chloroform) δ ppm 7.62 - 7.69 (m, 2H), 7.35 (t, 1H), 3.80 (s, 3H), 2.56 (d, 3H), 2.00 (d, 3H)

[0209] Methyl 2-(3-bromo-2-chlorophenyl)-2-fluoropropionate (Compound 2-139)

[0210] 11H NMR (400 MHz, DMSO-d6) δ = 7.92 - 7.87 (m, 1H), 7.76 - 7.71 (m, 1H), 7.45 - 7.34 (m, 1H), 3.74 (s, 3H), 1.94 (d, 3H)

[0211] Ethyl 2-(3-chloro-2-fluorophenyl)-2-fluoropropionate (Compound 3-085)

[0212] 1 1H NMR (400 MHz, chloroform) δ = 7.49 - 7.38 (m, 2H), 7.16 (dd, 1H), 4.35 - 4.21 (m, 2H), 1.96 (dd, 3H), 1.28 (t, 3H)

[0213] Methyl 2-(3-chloro-2-ethylphenyl)-2-fluoropropionate (Compound 2-289)

[0214] 1 1H NMR (400 MHz, DMSO-d6) δ = 7.52 (t, 2H), 7.33 (dt, 1H), 3.71 (s, 3H), 2.85 - 2.60 (m, 2H), 1.97 (d, 3H), 1.05 (t, 3H)

[0215] Step 3 Synthesis of 2-(2-chloro-4-fluorophenyl)-2-fluoropropanoic acid (Compound 1-133)

[0216]

[0217] To a round-bottom flask, 2-(2-chloro-4-fluorophenyl)-2-fluoromethyl propionate (647 mg, 2.07 mmol), 2-methyltetrahydrofuran (2 mL), water (2 mL), methanol (2 mL) and sodium hydroxide (167 mg, 4.18 mmol) were added. The mixture was stirred overnight at room temperature. The reaction mixture was added dropwise to 2 M HCl to obtain a turbid white precipitate. The mixture was extracted with ethyl acetate (3 × 10 mL), and the combined organic layers were concentrated in vacuo. The crude product was purified by reverse-phase column chromatography (40% - 55% acetonitrile in water, containing 0.1% formic acid) to give 2-(2-chloro-4-fluorophenyl)-2-fluoropropanoic acid (Compound 1-133) (421 mg, 1.81 mmol, 88%).

[0218] 1 1H NMR (400 MHz, chloroform) δ = 7.58 (dd, 1H), 7.18 (dd, 1H), 7.14 - 6.99 (m, 1H), 2.04 (d, 3H) ppm

[0219] Also prepared by this general method are:

[0220] 2-(2-Bromo-3-chloro-phenyl)-2-fluoro-propanoic acid (Compound 1-192)

[0221] 1 H NMR (400 MHz, chloroform) δ = 7.55 - 7.50 (m, 2H), 7.41 - 7.30 (m, 1H), 2.04 (d, 3H) ppm

[0222] 2-(3-Cyano-2-methyl-phenyl)-2-fluoro-propanoic acid (Compound 1-249)

[0223] 1 H NMR (400 MHz, chloroform) δ = 7.68 (dd, 2H), 7.36 (t, 1H), 2.64 (d, 3H), 2.02 - 2.10 (m, 3H) ppm

[0224] 2-(3-Bromo-2-chloro-phenyl)-2-fluoro-propanoic acid (Compound 1-139)

[0225] 1 H NMR (400 MHz, chloroform) δ ppm 7.70 (dd, 1H), 7.58 (dd, 1H), 7.23 (t, 1H), 2.01 (d, 3H)

[0226] 2-(3-Chloro-2-ethyl-phenyl)-2-fluoro-propanoic acid (Compound 1-289)

[0227] 1 H NMR (400 MHz, DMSO-d6) δ ppm 13.73 (br s, 1H), 7.52 - 7.46 (m, 2H), 7.33 - 7.26 (m, 1H), 2.87 - 2.72 (m, 2H), 2.00 - 1.87 (m, 3H), 1.10 (t, 3H)

[0228] Example 3 Preparation of 2-(2,3-dichlorophenyl)-2-fluoro-propanoic acid (Compound 1-138)

[0229] Step 1 Synthesis of methyl 2-(2,3-dichlorophenyl)-2-fluoro-acetate

[0230]

[0231] At 0 °C under nitrogen, diethylaminosulfur trifluoride (1.86 g, 11.5 mmol) was added dropwise to methyl 2-(2,3-dichlorophenyl)-2-hydroxyacetate (1.51 g, 5.76 mmol) in anhydrous dichloromethane (20 mL). The reaction was stirred overnight at room temperature. The reaction mixture was quenched with saturated NaHCO 3 solution and extracted with dichloromethane (3 × 30 mL). The combined organic extracts were passed through a phase separation column and concentrated under reduced pressure. The crude product was purified by flash column chromatography (0 - 70% EtOAc / cyclohexane) to afford methyl 2-(2,3-dichlorophenyl)-2-fluoroacetate (1.34 g, 5.64 mmol, 84%) as a yellow liquid.

[0232] 1 H NMR (400 MHz, chloroform) δ ppm 7.53 (dt, 1H), 7.43 (dd, 1H), 7.24 - 7.34 (m, 1H), 6.24 (d, 1H), 3.80 (s, 3H)

[0233] Step 2 Synthesis of methyl 2-(2,3-dichlorophenyl)-2-fluoropropionate (Compound 2-138)

[0234]

[0235] At -78 °C under a nitrogen atmosphere, lithium diisopropylamide (2 mol / L, 13.1 mmol) in hexane was added dropwise to a stirred solution of methyl 2-(2,3-dichlorophenyl)-2-fluoroacetate (1.24 g, 5.24 mmol) in THF (10 mL). The resulting reaction mixture was stirred at the same temperature for 10 min. Then methyl iodide (1.52 g, 10.5 mmol) in THF (1 mL) was added, and the reaction was stirred at -78 °C for 10 min. The reaction was warmed to room temperature and stirred for 2.5 h. The reaction mixture was quenched with aqueous NH 4 Cl, extracted with EtOAc (3 × 20 mL), separated through a phase separation column and concentrated under reduced pressure. The crude residue was purified by flash column chromatography (0 to 60% cyclohexane:EtOAc) to afford methyl 2-(2,3-dichlorophenyl)-2-fluoropropionate (Compound 2-138) (992 mg, 3.95 mmol, 75%) as a bright yellow liquid.

[0236] 1 H NMR (400 MHz, chloroform) δ ppm 7.54 (dd, 1H), 7.50 (dd, 1H), 7.27 - 7.33 (m, 1H), 3.79 (s, 3H), 1.91 - 2.01 (m, 3H)

[0237] Also prepared by this general method are:

[0238] Methyl 2-(3-chlorophenyl)-2-fluoro-propionate (Compound 2-018)

[0239] 1 H NMR (400 MHz, chloroform) δ ppm 7.28 - 7.54 (m, 4H), 3.78 (s, 3H), 1.92 (d, 3H)

[0240] Methyl 2-(3-chloro-2-methoxyphenyl)-2-fluoro-propionate (Compound 2-682)

[0241] 1 H NMR (400 MHz, chloroform) δ ppm 7.39 - 7.45 (m, 2H), 7.11 (td, 1H), 3.88 (s, 3H), 3.79 (s, 3H), 1.88 - 1.97 (m, 3H)

[0242] Methyl 2-(3-chloro-2-methylphenyl)-2-fluoro-propionate (Compound 2-239)

[0243] 1 H NMR (400 MHz, chloroform) δ ppm 7.38 (dd, 2H), 7.12 - 7.21 (m, 1H), 3.77 (s, 3H), 2.36 (d, 3H), 1.98 (d, 3H)

[0244] Methyl 2-(2-chlorophenyl)-2-fluoro-propionate (Compound 2-126)

[0245] 1 H NMR (400 MHz, chloroform) δ ppm 7.54 - 7.67 (m, 1H), 7.27 - 7.43 (m, 3H), 3.79 (s, 3H), 1.97 (d, 3H)

[0246] Ethyl 2-(2-bromophenyl)-2-fluoro-propionate (Compound 3-181)

[0247] 1 H NMR (400 MHz, chloroform) δ ppm 7.55 - 7.62 (m, 2H), 7.39 (t, 1H), 7.29 (t, 1H), 4.26 (q, 2H), 1.98 (d, 3H), 1.25 (t, 3H)

[0248] Methyl 2-(2,4-dichlorophenyl)-2-fluoro-propionate (Compound 2-134)

[0249] 11H NMR (400 MHz, chloroform) δ ppm 7.54 (d, 1H), 7.38 - 7.43 (m, 1H), 7.33 (dd, 1H), 3.79 (s, 3H), 1.95 (d, 3H)

[0250] Ethyl 2-(3-chloro-2-trifluoromethylphenyl)-2-fluoro-propionate (Compound 3-432)

[0251] 1 1H NMR (400 MHz, chloroform) δ ppm 7.84 (d, 1H), 7.77 - 7.73 (m, 1H), 7.52 - 7.45 (m, 1H), 4.36 - 4.20 (m, 2H), 1.99 (d, 3H), 1.26 (t, 3H)

[0252] Step 3 Synthesis of 2-(2,3-dichlorophenyl)-2-fluoro-propanoic acid (Compound 1-138)

[0253]

[0254] To a stirred solution of methyl 2-(2,3-dichlorophenyl)-2-fluoro-propionate (414 mg, 1.65 mmol) in 2-MeTHF:MeOH:H2O (1:1:1, 6 mL) was added sodium hydroxide (132 mg, 3.29 mmol). The reaction mixture was stirred at room temperature for 3 h. The reaction mixture was added to 2 M aqueous HCl and extracted with ethyl acetate (3 × 15 mL). The combined organic extracts were passed through a phase separation column and concentrated under reduced pressure to give 2-(2,3-dichlorophenyl)-2-fluoro-propanoic acid (Compound 1-138) as pale pink crystals (364 mg, 1.53 mmol, 93%).

[0255] 1 1H NMR (400 MHz, chloroform) δ ppm 7.51 - 7.56 (m, 2H), 7.28 - 7.34 (m, 1H), 2.02 (d, 3H)

[0256] The individual enantiomers of Compound 1-138 were prepared by chiral chromatography (as described above 1 1H NMR).

[0257] Also prepared by this general method were:

[0258] 2-(3-chloro-2-methoxyphenyl)-2-fluoro-propanoic acid (Compound 1-682)

[0259] 11H NMR (400 MHz, DMSO-d6) δ ppm 7.55 (ddt, 2H), 7.22 (td, 1H), 3.78 (s, 3H), 1.80 - 1.88 (m, 3H)

[0260] 2-(3-Chloro-2-methyl-phenyl)-2-fluoro-propanoic acid (Compound 1-239)

[0261] 1 1H NMR (400 MHz, chloroform) δ ppm 7.43 (d, 1H), 7.38 (d, 1H), 7.15 - 7.22 (m, 1H), 2.43 (d, 3H), 1.99 - 2.11 (m, 3H)

[0262] 2-Fluoro-2-(quinolin-8-yl)-propanoic acid (Compound 1-800)

[0263] 1 1H NMR (400 MHz, chloroform) δ 8.95 (s, 1H), 8.45 (dd, 1H), 8.17 (dd, 1H), 7.94 (d, 1H), 7.74 (d, 1H), 7.65 - 7.60 (m, 1H), 2.15 (d, 3H) ppm

[0264] 2-(2-Chlorophenyl)-2-fluoro-propanoic acid (Compound 1-126)

[0265] 1 1H NMR (400 MHz, chloroform) δ ppm 7.56 - 7.74 (m, 1H), 7.30 - 7.46 (m, 3H), 6.48 (br s, 1H), 2.02 (d, 3H)

[0266] 2-(3-Chlorophenyl)-2-fluoro-propanoic acid (Compound 1-018)

[0267] 1 1H NMR (400 MHz, chloroform) δ ppm 7.53 (s, 1H), 7.29 - 7.43 (m, 3H), 1.94 (d, 3H)

[0268] 2-(2-Bromophenyl)-2-fluoro-propanoic acid (Compound 1-181)

[0269] 1 1H NMR (400 MHz, chloroform) δ ppm 7.58 - 7.62 (m, 2H), 7.39 (t, 1H), 7.29 - 7.21 (m, 1H), 5.0 (br s, 1H), 2.03 (d, 3H)

[0270] 2-(3-chloro-2-fluorophenyl)-2-fluoro-propanoic acid (Compound 1-085)

[0271] 1 H NMR (400 MHz, chloroform) δ ppm 13.78 (br s, 1H), 7.68 (t, 1H), 7.63 - 7.53 (m, 1H), 7.36 - 7.28 (m, 1H), 1.91 (d, 3H)

[0272] 2-(2,4-dichlorophenyl)-2-fluoro-propanoic acid (Compound 1-134)

[0273] 1 H NMR (400 MHz, chloroform) δ ppm 13.7 (br s, 1H), 7.65 - 7.70 (m, 2H), 7.52 (ddd, 1H), 1.91 (d, 3H)

[0274] 2-(3-chloro-2-trifluoromethylphenyl)-2-fluoro-propanoic acid (Compound 1-432)

[0275] 1 H NMR (400 MHz, chloroform) δ ppm 7.87 - 7.80 (m, 1H), 7.80 - 7.73 (m, 1H), 7.48 (t, 1H), 2.04 (d, 3H)

[0276] Example 4 Preparation of 2-(4-bromophenyl)-2-fluoro-propanoic acid (Compound 1-004)

[0277] Step 1 Synthesis of ethyl 2-(4-bromophenyl)-2-hydroxy-propanoate

[0278]

[0279] At -78 °C under an argon atmosphere, methylmagnesium bromide (1 mol / L, 9.06 mL, 9.06 mmol) was added to a stirred solution of ethyl 2-(4-bromophenyl)-2-oxo-acetate (2.00 g, 7.55 mmol) in tetrahydrofuran (38 mL), and the reaction was stirred at this temperature for 20 min. The reaction was warmed to room temperature, and the reaction was quenched with saturated NH 4 Cl solution. Ethyl acetate was added, the layers were separated and the aqueous phase was extracted twice with ethyl acetate. The combined organic layers were washed with brine, dried over Na 2 SO 4Dry, filter and concentrate under reduced pressure. Purify the crude product by normal phase chromatography (0 - 40% EtOAc / cyclohexane) to afford the desired compound ethyl 2-(4-bromophenyl)-2-hydroxypropionate as a colorless oil (1.75 g, 6.40 mmol, 85%).

[0280] 1 H NMR (400 MHz, chloroform) δ ppm 7.45 - 7.52 (m, 4H), 4.20 - 4.31 (m, 2H), 1.77 (s, 3H), 1.28 (t, 3H)

[0281] Step 2 Synthesis of ethyl 2-(4-bromophenyl)-2-fluoropropionate (Compound 3-004)

[0282]

[0283] At 0 °C under an argon atmosphere, add diethylaminosulfur trifluoride (1.30 g, 7.68 mmol) to a solution of ethyl 2-(4-bromophenyl)-2-hydroxypropionate (1.75 g, 6.40 mmol) in anhydrous dichloromethane (13 mL). Stir the resulting mixture at 0 °C for 20 minutes. Carefully add saturated NaHCO 3 aqueous solution (15 mL). Separate the organic phase, wash with water (20 mL), dry over Na 2 SO 4 and concentrate in vacuo. Purify the crude product by normal phase chromatography (0 - 20% EtOAc / cyclohexane) to afford ethyl 2-(4-bromophenyl)-2-fluoropropionate (Compound 3-004) as a colorless oil (1.75 g, 6.03 mmol, 94%).

[0284] 1 H NMR (400 MHz, chloroform) δ ppm 7.54 (d, 2H), 7.41 (d, 2H), 4.24 (q, 2H), 1.92 (d, 3H), 1.27 (t, 3H)

[0285] Also prepared by this general method are:

[0286] Ethyl 2-fluoro-2-[4-(trifluoromethyl)phenyl]propionate (Compound 3-006)

[0287] 1 H NMR (400 MHz, chloroform) δ ppm 7.64 - 7.71 (m, 4H), 4.25 (q, 2H), 1.97 (d, 3H), 1.29 (t, 3H)

[0288] Ethyl 2-(4-chlorophenyl)-2-fluoro-propionate (Compound 3-003)

[0289] 1 H NMR (400 MHz, chloroform) δ ppm 7.48 (d, 2H), 7.38 (d, 2H), 4.24 (q, 2H), 1.93 (d, 3H), 1.29 (t, 3H)

[0290] Step 3 Synthesis of 2-(4-bromophenyl)-2-fluoro-propionic acid (Compound 1-004)

[0291]

[0292] To ethyl 2-(4-bromophenyl)-2-oxo-acetate (1.06 g, 3.85 mmol) in tetrahydrofuran (19 mL) and water (5 mL) was added lithium hydroxide (277 mg, 11.6 mmol). The reaction mixture was stirred overnight at room temperature. THF was removed under reduced pressure and the remaining water was then acidified to pH = 1 with 6M HCl and extracted twice with dichloromethane. The combined organic extracts were washed with brine, dried over Na 2 SO 4 dried, filtered and concentrated under reduced pressure to afford 2-(4-bromophenyl)-2-fluoro-propionic acid (Compound 1-004) as a white solid (878 mg, 3.55 mmol, 92 %).

[0293] 1 H NMR (400 MHz, DMSO-d6) δ ppm 13.63 (br s, 1H), 7.64 (d, 2H), 7.43 (d, 2H), 1.85 (d, 3H)

[0294] Also prepared by this general method were:

[0295] 2-Fluoro-2-[4-(trifluoromethyl)phenyl]propionic acid (Compound 1-006)

[0296] 1 H NMR (400 MHz, DMSO-d6) δ ppm 13.74 (br s, 1H), 7.82 (d, 2H), 7.73 (d, 2H), 1.90 (d, 3H)

[0297] 2-(4-Chlorophenyl)-2-fluoro-propionic acid (Compound 1-003)

[0298] 11H NMR (400 MHz, chloroform) δ ppm 10.1 (br s, 1H), 7.50 (d, 2H), 7.40 (d, 2H), 1.96 (d, 3H)

[0299] Example Preparation of 2-(3-chloro-2-cyclopropyl-phenyl)-2-fluoro-propionic acid (Compound 1-337)

[0300] Step 1 Synthesis of methyl 2-(3-chloro-2-cyclopropyl-phenyl)-2-fluoro-propionate (Compound 2-337)

[0301]

[0302] A mixture of methyl 2-(2-bromo-3-chloro-2-phenyl)-2-fluoro-propionate (Compound 2-192, prepared as described in Example 2; 370 mg, 0.81 mmol), cyclopropylzinc bromide (0.5 M in tetrahydrofuran; 2 ml, 2 mmol), [(2-dicyclohexylphosphino-2',6'-bis(N,N-dimethylamino)-1,1'-biphenyl)-2-(2'-amino-1,1'-biphenyl)]palladium(II) mesylate (33 mg, 0.04 mmol), tetrahydrofuran (6 ml) and aqueous potassium phosphate solution (1 M; 3.5 ml, 3.5 mmol) was stirred at ambient temperature for 27 h, then saturated aqueous ammonium chloride solution (15 ml) was added. The resulting mixture was extracted with ethyl acetate (3 × 10 ml), and the combined organic extracts were dried, filtered and evaporated under reduced pressure to leave an orange residue, which was purified by normal phase chromatography (eluting with 0-20% ethyl acetate in cyclohexane) to afford methyl 2-(3-chloro-2-cyclopropyl-phenyl)-2-fluoro-propionate (Compound 2-337), which was used without further purification.

[0303] Example 2 Synthesis of 2-(3-chloro-2-cyclopropyl-phenyl)-2-fluoro-propionic acid (Compound 1-337)

[0304]

[0305] A mixture of 2-(3-chloro-2-cyclopropyl-phenyl)-2-fluoro-propanoic acid (200 mg, 0.78 mmol), sodium hydroxide (68 mg, 1.7 mmol), 2-methyltetrahydrofuran (1 ml), methanol (1 ml) and water (1 ml) was stirred at ambient temperature for 4 hours and then slowly added to hydrochloric acid (2 M; 20 ml). The resulting mixture was extracted with ethyl acetate (3 × 10 ml) and the combined organic extracts were dried, filtered and evaporated under reduced pressure to leave a residue which was purified by column chromatography to afford 2-(3-chloro-2-cyclopropyl-phenyl)-2-fluoro-propanoic acid (Compound 1-337) (1.3 mg) as a yellow oil.

[0306] 1 H NMR (400 MHz, chloroform) δ ppm 7.41 (br d, 2H), 7.24 - 7.16 (m, 1H), 2.11 - 2.00 (m, 3H), 1.92 - 1.80 (m, 1H), 1.10 - 0.92 (m, 3H), 0.61 - 0.51 (m, 1H)

[0307] Example 6 Preparation of ethyl 2-(2-bromophenyl)-2-fluoroacetate

[0308] Step 1 Synthesis of 2-(2-bromophenyl)-2-fluoroacetic acid

[0309]

[0310] A solution of 2-bromophenyl-acetic acid (750 mg, 3.5 mmol), 1-chloromethyl-4-fluoro-1,4-diazabicyclo[2.2.2]octane bis(tetrafluoroborate) (1.65 g, 4.7 mmol) and N,N-dimethylaminopyridine (0.85 g, 7 mmol) in acetonitrile (17.5 ml) was stirred at ambient temperature for 3 hours and then the solvent was removed under reduced pressure. The residue was dissolved in water, acidified by adding 2N hydrochloric acid and the resulting mixture was extracted with ethyl acetate (×3). The combined organic extracts were washed with water and brine, dried over magnesium sulfate, filtered and the filtrate was evaporated under reduced pressure to afford a yellow oil which was purified by normal phase chromatography (0 - 50% ethyl acetate eluent in cyclohexane) to give 2-(2-bromophenyl)-2-fluoroacetic acid (450 mg) as a yellow oil.

[0311] 1 H NMR (400 MHz, chloroform) δ ppm 7.61 (d, 1H), 7.51 (d, 1H), 7.38 (t, 1H), 7.22 - 7.33 (m, 1H), 6.27 (d, 1H), 5.80 (br s, 1H)

[0312] Step 2 Synthesis of Ethyl 2-(2-bromophenyl)-2-fluoroacetate

[0313]

[0314] A solution of 2-(2-bromophenyl)-2-fluoroacetic acid (450 mg, 1.9 mmol) and hydrogen chloride (1.25 M in ethanol; 4.66 ml, 5.8 mmol) in ethanol (5 ml) was heated at 70 °C for 17 h, then cooled to ambient temperature and evaporated under reduced pressure to afford ethyl 2-(2-bromophenyl)-2-fluoroacetate (476 mg) as a yellow oil, which was used without further purification.

[0315] 1 H NMR (400 MHz, chloroform) δ ppm 7.61 (d, 1H), 7.50 (d, 1H), 7.36 (t, 1H), 7.22 - 7.30 (m, 1H), 6.20 (d, 1H), 4.18 - 4.33 (m, 2H), 1.25 (t, 3H)

[0316] Example 7 Preparation of Methyl 2-(3-chloro-2-ethylphenyl)acetate

[0317] Step 1 Synthesis of 2-(3-chloro-2-ethylphenyl)acetic acid

[0318]

[0319] Diethylzinc (1 M in hexanes; 8.5 ml, 8.5 mmol) was added dropwise to a stirred mixture of 2-(2-bromo-3-chloro-2-phenyl)-acetic acid (1.06 g, 4.2 mmol), [(2-dicyclohexylphosphino-2',6'-bis(N,N-dimethylamino)-1,1'-biphenyl)-2-(2'-amino-1,1'-biphenyl)]palladium(II) methanesulfonate (92 mg, 0.1 mmol), 2-dicyclohexylphosphino-2',6'-bis(N,N-dimethylamino)-1,1'-biphenyl (95 mg, 0.21 mmol) and 2-methyltetrahydrofuran (21 ml) at 0 °C. The resulting mixture was warmed and stirred at ambient temperature for 4 h, then cooled to 0 °C and 2 N hydrochloric acid was added dropwise. 1 N hydrochloric acid (50 ml) was added and the resulting mixture was extracted with ethyl acetate (3 x 50 ml) and the combined organic extracts were dried, filtered and evaporated under reduced pressure to leave a residue which was purified by reverse phase chromatography (eluting with 40%-80% acetonitrile in water and formic acid (0.1%)) to afford 2-(3-chloro-2-ethyl-phenyl)-acetic acid (586 mg) as a white solid.

[0320] 1 H NMR (400 MHz, DMSO-d6) δ ppm 12.48 (s, 1H), 7.33 (dd, 1H), 7.23 - 7.12 (m, 2H), 3.67 (s, 2H), 2.71 (q, 2H), 1.08 (t, 3H)

[0321] Step 2 Synthesis of methyl 2-(3-chloro-2-ethyl-phenyl)-acetate

[0322]

[0323] Thionyl chloride (1.8 ml, 25 mmol) was added dropwise to a stirred solution of 2-(3-chloro-2-ethyl-phenyl)-acetic acid (0.79 g, 4.0 mmol) in methanol (10 ml). The resulting mixture was stirred at ambient temperature for 10 min, then concentrated under reduced pressure and purified by reverse phase chromatography (eluting with 50%-100% acetonitrile in water plus 0.1% formic acid) to afford methyl 2-(3-chloro-2-ethyl-phenyl)-acetate (635 mg) as a light coloured oil.

[0324] 1 H NMR (400 MHz, DMSO-d6) δ ppm 7.34 (dd, 1H), 7.22 - 7.15 (m, 2H), 3.78 (s, 2H), 3.62 (s, 3H), 2.70 (q, 2H), 1.06 (t, 3H)

[0325] Commercial Compound:

[0326] Prior to the priority date of the present application, many compounds of the present invention (such as 1-074 and 2-181) were available from commercial sources (such as Enamine).

[0327] Biological Examples

[0328] Pre-emergence Biological Efficacy

[0329] Weed and / or crop seeds were sown in standard soil in pots. After one day of cultivation under controlled conditions in a greenhouse (at 24°C / 19°C, day / night; 16 hours of light), the plants were sprayed with an aqueous spray solution obtained as follows: an industrial-grade active ingredient was formulated in a small amount of acetone and a special solvent and emulsifier mixture called IF50 (11.12% Emulsogen EL360 TM + 44.44% N-methylpyrrolidone + 44.44% Dowanol DPM ethylene glycol ether) to produce a 50 g / l solution, which was then diluted with 0.2% Genapol XO80 as a diluent to obtain the test compound at the desired final dose.

[0330] These test plants were then grown under controlled conditions in a greenhouse (at 24°C / 18°C, day / night; 15 hours of light; 50% humidity) and watered twice daily. After 13 days, the test was evaluated (100 = complete damage to the plants; 0 = no damage to the plants). The results are shown in Table 2 below.

[0331] Table 2

[0332]

[0333]

[0334] Post-emergence Biological Efficacy

[0335] Weed and / or crop seeds are sown in standard soil in pots. After 14 days of cultivation under controlled conditions in a greenhouse (24 °C / 19 °C, day / night; 16 h of light), the plants are sprayed with an aqueous spray solution obtained as follows: the technical-grade active ingredient is formulated in a small amount of acetone and a special solvent and emulsifier mixture called IF50 (11.12% Emulsogen EL360 TM + 44.44% N-methylpyrrolidone + 44.44% Dowanol DPM ethylene glycol ether) to produce a 50 g / l solution, which is then diluted with 0.2% Genapol XO80 as a diluent to obtain the test compound at the desired final dose.

[0336] These test plants are then grown under controlled conditions in a greenhouse (24 °C / 18 °C, day / night; 15 h of light; 50% humidity) and watered twice daily. After 13 days, the test is evaluated (100 = complete damage to the plants; 0 = no damage to the plants). The results are shown in Table 3 below.

[0337] Table 3

[0338]

[0339] The present invention is defined by the claims.

Claims

1. A compound of formula I or an agronomically acceptable salt of said compound: Wherein: R 1 、R 2 、R 3 、R 4 and R 5 are independently selected from the group consisting of: hydrogen, halogen, amino, cyano, nitro, hydroxy, C 1-5 alkyl, C 3-6 cycloalkyl, C 1-2 haloalkyl, cyanomethyl, C 1-2 alkoxyC 1-2 alkyl, C 1-4 alkoxy, C 1-2 haloalkoxy, C 2-3 alkenyl, C 2-3 alkynyl, halophenyl, C 1-2 alkoxycarbonyl, C 1-2 alkylthio, C 1-2 alkylsulfinyl and C 1-2 alkylsulfonyl; or R 1 and R 2 together with the carbon atom to which they are attached form a 5- or 6-membered ring, which 5- or 6-membered ring may optionally be substituted by one or more groups selected from halogen, cyano, hydroxy, C 1-5 alkyl, C 1-2 haloalkyl and C 1-4 alkoxy, and wherein the 6-membered ring contains zero, one or two nitrogen atoms, and wherein the 5-membered ring contains one or two heteroatoms independently selected from the group consisting of nitrogen and oxygen; R 6 selected from the group consisting of: hydrogen, C 1-6 alkyl and aryl C 1-2 alkyl.

2. The compound according to claim 1, Wherein, R 1 selected from the group consisting of: hydrogen, halogen, amino, cyano, nitro, hydroxy, C 1-4 alkyl, C 3-4 cycloalkyl, C 1-2 haloalkyl, C 1-4 alkoxy, C 1-2 haloalkoxy, C 2-3 alkenyl, C 2-3 alkynyl, halophenyl and C 1-2 alkylthio, more preferably hydrogen, fluorine, chlorine, bromine, amino, cyano, C 1-4 alkyl, cyclopropyl, halomethyl, C 1-3 alkoxy, C 1 haloalkoxy, vinyl, ethynyl and methylthio, most preferably chlorine, bromine, cyano, methyl, ethyl, cyclopropyl, difluoromethyl, trifluoromethyl, methoxy, ethoxy, vinyl and ethynyl.

3. The compound according to claim 1 or 2, Wherein, R 2 selected from the group consisting of: hydrogen, halogen, amino, cyano, nitro, hydroxy, C 1-4 alkyl, C 3-4 cycloalkyl, C 1-2 haloalkyl, C 1-4 alkoxy, C 1-2 haloalkoxy, C 2-3 alkenyl, C 2-3 alkynyl, halophenyl and C 1-2 alkylthio, more preferably hydrogen, fluorine, chlorine, bromine, cyano, C 1-4 alkyl, cyclopropyl, halomethyl, C 1-3 alkoxy, C 1 haloalkoxy, vinyl, ethynyl, fluorophenyl and methylthio, most preferably hydrogen, chlorine, bromine, cyano, methyl, cyclopropyl, difluoromethyl, trifluoromethyl, methoxy, vinyl and ethynyl.

4. The compound according to claim 1, Wherein, R 1 and R 2 together with the carbon atom to which they are attached form a 5-membered ring containing a heteroatom independently selected from the group consisting of nitrogen and oxygen, and preferably, the 5-membered ring contains two oxygen atoms.

5. The compound according to claim 4, Wherein, The 5-membered ring is partially or fully saturated.

6. The compound according to any one of the preceding claims, Wherein, R 3 selected from the group consisting of hydrogen, halogen, amino, cyano, hydroxy, C 1 -C 5 -alkyl, C 1-2 -haloalkyl, C 1 -C 4 -alkoxy, C 2 -C 3 -alkenyl, C 2 -C 3 -alkynyl, C 1 -C 2 -haloalkoxy and halophenyl, more preferably hydrogen, halogen, amino, trifluoromethoxy, trifluoromethyl, methyl, tert-butyl and methoxy, most preferably hydrogen, fluorine and chlorine.

7. The compound according to any one of the preceding claims, Wherein, R 4 selected from the group consisting of: hydrogen, amino, fluoro, chloro, methoxy; preferably hydrogen.

8. The compound according to any one of the preceding claims, Wherein, R 5 is selected from the group consisting of hydrogen, fluorine, chlorine, amino, nitro and methoxy; preferably selected from hydrogen, chlorine and methoxy.

9. The compound according to any one of the preceding claims, Wherein, R 6 is selected from the group consisting of: hydrogen, C 1 -C 3 -alkyl and benzyl; preferably hydrogen.

10. Use of the compound according to any one of claims 1 to 9 as a herbicide.

11. A herbicidal composition according to claim 10, further comprising at least one additional pesticidal agent.

12. The herbicidal composition according to claim 11, Wherein, The additional pesticidal agent is a herbicide or a herbicide safener.

13. A method for controlling weeds in a locus, the method comprising applying to the locus a compound of formula (I) according to any one of claims 1 to 9 or an agronomically acceptable salt of said compound in an amount effective to control weeds, or a herbicidal composition according to any one of claims 10 to 12.

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