Isoxalidine derivatives as herbicidal compounds.

Abstract

The present invention relates to a compound represented by formula (I), TIFF2025525368000032.tif4768(in the formula, A 1 , A 2 , A 3 , X 1 , R 3 , R 4 , R 5 , R 6 is as defined herein, or an agriculturally acceptable salt of said compound. The present invention further relates to herbicidal compositions comprising compounds of formula (I) and to the use of compounds of formula (I), in particular for the control of weeds in crops of useful plants.

Description

[Technical Field]

[0001] The present invention relates to herbicidal compounds, processes for their preparation, herbicidal compositions containing the herbicidal compounds, and their use, in particular for controlling weeds or inhibiting plant growth in crops of useful plants. Summary of the Invention [Means for solving the problem]

[0002] Herbicidal 3-isoxazolidinones are known from U.S. Pat. No. 4,405,357. Herbicidal isoxazolidine-3,5-diones are known from U.S. Pat. No. 4,302,238. The present invention relates to novel 3-isoxazolidinone and isoxazolidine-3,5-dione compounds. Thus, according to the present invention, compounds of formula (I) [ka] (In the formula, A 1 is CR 1 R 2 or C(O);A 2 is CR 7 R 8 , C(O), O, S(O) p and N(R 11 A is selected from the group consisting of 3 is CR 9 R 10 , C(O), O, S(O) p and N(R 11 ) selected from the group consisting of; X 1 is O or S; R 1 is hydrogen, halogen, HO-, C1-C6 alkoxy, C1-C6 alkoxy-C1-C6 alkoxy-, C1-C3 alkyl-C(O)O-, HOC(O)C1-C6 alkoxy-, C1-C6 alkoxy-C(O)-C1-C6 alkoxy-, C1-C3 alkyl-S(O) p - and C1-C3 alkyl-S(O) p C1-C6 alkoxy-; R2 is hydrogen; R 3 is C1-C3 alkyl; R 4 is C1-C3 alkyl; R 5 is selected from the group consisting of hydrogen, halogen, C1-C6 alkyl, C1-C6 haloalkyl, C3-C6 cycloalkyl, and C1-C6 alkoxy-; R 6 is selected from the group consisting of hydrogen, halogen, C1-C6 alkyl, C1-C6 haloalkyl, C3-C6 cycloalkyl, and C1-C6 alkoxy-; 5 and R 6 are not both hydrogen; or R 5 and R 6 together, =O or -(CH2) n - and;R 7 is selected from the group consisting of hydrogen, halogen, C1-C6 alkyl, C1-C6 haloalkyl, C3-C6 cycloalkyl, and C1-C6 alkoxy-; R 8 is selected from the group consisting of hydrogen, halogen, C1-C6 alkyl, C1-C6 haloalkyl, C3-C6 cycloalkyl, and C1-C6 alkoxy-; or R 7 and R 8 together, -(CH2) n - and;R 9 is selected from the group consisting of hydrogen, halogen, C1-C6 alkyl, C1-C6 haloalkyl, C3-C6 cycloalkyl, and C1-C6 alkoxy-; R 10 is selected from the group consisting of hydrogen, halogen, C1-C6 alkyl, C1-C6 haloalkyl, C3-C6 cycloalkyl, and C1-C6 alkoxy-; R 9 and R 10 together, -(CH2) n - and;R 11 is hydrogen or C1-C3 alkyl; n is independently 2, 3, 4, 5, or 6; and p is independently 0, 1, or 2. or an agriculturally acceptable salt thereof. DETAILED DESCRIPTION OF THE INVENTION

[0003] C1-C6 alkyl- includes, for example, methyl (Me, CH3), ethyl (Et, C2H5), n-propyl (n-Pr), isopropyl (i-Pr), n-butyl (n-Bu), isobutyl (i-Bu), sec-butyl, and tert-butyl (t-Bu). C1-C3 alkyl includes methyl (Me, CH3), ethyl (Et, C2H5), and propyl (Pr, e.g., isopropyl and n-propyl).

[0004] Halogen (or halo) includes, for example, fluorine, chlorine, bromine or iodine. The same applies correspondingly to halogen in the context of other definitions such as haloalkyl.

[0005] C1-C6 haloalkyl- includes, for example, fluoromethyl, difluoromethyl, trifluoromethyl, chloromethyl, dichloromethyl, trichloromethyl, 2,2,2-trifluoroethyl, 2-fluoroethyl, 2-chloroethyl, pentafluoroethyl, 1,1-difluoro-2,2,2-trichloroethyl, 2,2,3,3-tetrafluoropropyl, 2,2,2-trichloroethyl, and heptafluoro-n-propyl. C1-C2 haloalkyl is, for example, fluoromethyl, difluoromethyl, trifluoromethyl, chloromethyl, dichloromethyl, trichloromethyl, 2,2,2-trifluoroethyl, 2-fluoroethyl, 2-chloroethyl, pentafluoroethyl, or 1,1-difluoro-2,2,2-trichloroethyl.

[0006] C1-C6 alkoxy includes methoxy, ethoxy and iso-propoxy-.

[0007] C1-C6 haloalkoxy- includes, for example, fluoromethoxy, difluoromethoxy, trifluoromethoxy, 2,2,2-trifluoroethoxy, 1,1,2,2-tetrafluoroethoxy, 2-fluoroethoxy, 2-chloroethoxy, 2,2-difluoroethoxy or 2,2,2-trichloroethoxy, preferably difluoromethoxy, 2-chloroethoxy or trifluoromethoxy.

[0008] C1-C6 alkoxy-C1-C6 alkoxy- includes, for example, methoxymethoxy- and ethoxymethoxy-.

[0009] C1-C3 alkyl-C(O)O- includes methyl-C(O)O- and ethyl-C(O)O-.

[0010] C1-C6 alkoxy-C(O)-C1-C6 alkoxy- includes methoxy-C(O)-methoxy- and ethoxy-C(O)-methoxy-.

[0011] C1-C3 alkyl-S(O) p C1-C6 alkoxy- is methyl-S(O) p Methoxy- and ethyl-S(O) p Methoxy-containing.

[0012] C3-C6 cycloalkyl includes cyclopropyl, cyclopentyl and cyclohexyl.

[0013] C1-C4 alkyl-S-(alkylthio) includes, for example, methylthio, ethylthio, propylthio, isopropylthio, n-butylthio, isobutylthio, sec-butylthio or tert-butylthio, preferably methylthio or ethylthio.

[0014] C1-C4 alkyl-S(O)-(alkylsulfinyl) includes, for example, methylsulfinyl, ethylsulfinyl, propylsulfinyl, isopropylsulfinyl, n-butylsulfinyl, isobutylsulfinyl, sec-butylsulfinyl or tert-butylsulfinyl, preferably methylsulfinyl or ethylsulfinyl.

[0015] C1-C4 alkyl-S(O)2-(alkylsulfonyl) includes, for example, methylsulfonyl, ethylsulfonyl, propylsulfonyl, isopropylsulfonyl, n-butylsulfonyl, isobutylsulfonyl, sec-butylsulfonyl or tert-butylsulfonyl, preferably methylsulfonyl or ethylsulfonyl.

[0016] In one embodiment of the present invention, a compound of formula (I) 1 provides (where O is O).

[0017] Another embodiment of the present invention provides a compound of formula (I), wherein R 3 and R 4 is methyl).

[0018] Another embodiment of the present invention provides a compound of formula (I), wherein A 1 is CR 1 R 2 and R 1 is hydrogen). Thus, in one preferred embodiment of the present invention, [ka] The present invention provides a compound of the formula:

[0019] Another embodiment of the present invention provides a compound of formula (I), wherein A 1 is CR 1 R 2 and R 1 is C1-C6 alkoxy).

[0020] Another embodiment of the present invention provides a compound of formula (I), wherein A 1 is C(O). Thus, in one preferred embodiment of the present invention, [ka] The present invention provides a compound of the formula:

[0021] In one embodiment of the present invention, a compound of formula (I), formula (Ia) or formula (Ib) 2 is selected from the group consisting of CH2, C(O), O, S and NH, preferably O).

[0022] In another embodiment of the present invention, a compound of formula (I), formula (Ia) or formula (Ib), 3 is selected from the group consisting of CH2, C(O), O, S and NH, preferably O).

[0023] In another embodiment of the present invention, a compound of formula (I), formula (Ia) or formula (Ib) 2 and A 3 is O; or (ii) A 2 is NH and A 3 is O; or (iii) A 2 is O and A 3 is NH; (iv) A 2 and A 3 is NH; (v) A 2 is CH2 and A 3 is O; (vi) A 2 is O and A 3 is CH2; (vii) A 2 is CH2 and A 3 is CH2; (viii) A 2 is O and A 3 is S; or (ix) A 2 is S and A 3 provides (where O is O).

[0024] In a preferred embodiment of the present invention, a compound of formula (I), formula (Ia) or formula (Ib) 2 and A 3 provides (where O is O).

[0025] In another embodiment of the present invention, a compound of formula (I), formula (Ia) or formula (Ib), wherein R 5 and R 6are independently selected from the group consisting of hydrogen, halogen, and C1-C6 alkyl. 5 and R 6 are independently selected from the group consisting of hydrogen, methyl, and fluoro. 5 and R 6 is halogen, preferably fluoro.

[0026] Compounds of formula (I) may contain asymmetric centers and may exist as single enantiomers, pairs of enantiomers in any ratio, or, if two or more asymmetric centers are present, may contain diastereoisomers in all possible ratios. Typically, one of the enantiomers has greater biological activity than the other possible ones.

[0027] The present invention also provides agriculturally acceptable salts of compounds of formula (I). Salts of compounds of formula (I) may be formed with amines, such as primary, secondary, and tertiary amines (e.g., ammonia, dimethylamine, and triethylamine), with alkali metal and alkaline earth metal bases, transition metal, or quaternary ammonium bases being preferred.

[0028] Although the compounds of formula (I) of the present invention can be used as herbicides themselves, they are generally formulated into herbicidal compositions using formulation adjuvants such as carriers, solvents, and surfactants (SAA). Therefore, the present invention further provides a herbicidal composition comprising a herbicidal compound according to any one of the preceding claims and an agriculturally acceptable formulation adjuvant. The composition may be in the form of a concentrate that is diluted before use, but ready-to-use compositions can also be prepared. Final dilution is usually with water, but it can also be carried out with, for example, liquid fertilizers, trace elements, biological organisms, oils, or solvents instead of or in addition to water.

[0029] The herbicidal composition usually contains 0.1 to 99% by weight, in particular 0.1 to 95% by weight, of a compound of formula I and 1 to 99.9% by weight of a formulation adjuvant, which preferably contains 0 to 25% by weight of a surfactant.

[0030] The compositions can be selected from several formulation types, including emulsifiable concentrates (EC), suspension concentrates (SC), suspoemulsions (SE), capsule suspensions (CS), water-dispersible granules (WG), emulsifiable granules (EG), water-in-oil emulsions (EO), oil-in-water (EW) emulsions, microemulsions (ME), oil-based suspensions (OD), oil-miscible flowables (OF), oil-miscible liquids (OL), soluble concentrates (SL), ultra-low volume suspensions (SU), ultra-low volume liquids (UL), technical concentrates (TK), dispersible concentrates (DC), soluble powders (SP), wettable powders (WP), and soluble granules (SG). The type of formulation selected in any given case will depend on the specific purpose envisaged and the physical, chemical, and biological properties of the compound of formula (I).

[0031] Soluble powders (SP) can be prepared by mixing a compound of formula (I) with one or more water-soluble inorganic salts (such as sodium bicarbonate, sodium carbonate, or magnesium sulfate) or one or more water-soluble organic solids (such as polysaccharides), optionally with one or more wetting agents, one or more dispersing agents, or a mixture of the aforementioned agents to improve water dispersibility / solubility. The mixture is then ground into a fine powder. Similar compositions can also be granulated into water-soluble granules (SG).

[0032] Wettable powders (WP) can be prepared by mixing a compound of formula (I) with one or more solid excipients or carriers, one or more wetting agents, preferably one or more dispersing agents, and optionally one or more suspending agents to promote dispersion in a liquid. The mixture is then ground into a fine powder. Similar compositions can also be granulated into water-dispersible granules (WG).

[0033] Granules (GR) can be formed by granulating a mixture of a compound of formula (I) with one or more powdered solid excipients or carriers, or by absorbing a compound of formula (I) (or a solution thereof in a suitable agent) from preformed blank granules into a porous granular material (such as pumice, attapulgite clay, Fuller's earth, Kieselguhr, diatomaceous earth, or crushed corncob), or by adsorbing a compound of formula (I) (or a solution thereof in a suitable agent) onto a hard core material (such as sand, silica, carbonate, sulfate, or phosphate minerals), followed by optional drying. Agents commonly used to aid absorption or adsorption include solvents (such as aliphatic and aromatic petroleum-based solvents, alcohols, ethers, ketones, and esters) and binders (such as polyvinyl acetate, polyvinyl alcohol, dextrin, sugars, and vegetable oils). One or more other additives may also be included in the granules (e.g., emulsifiers, wetting agents, or dispersing agents).

[0034] Dispersible concentrates (DC) can be prepared by dissolving a compound of formula (I) in water or an organic solvent such as a ketone, alcohol, or glycol ether. These solutions may contain surfactants (e.g., to improve dilution with water or to prevent crystallization in the spray tank).

[0035] Emulsifiable concentrates (EC) or oil-in-water emulsions (EW) can be prepared by dissolving a compound of formula (I) in an organic solvent (optionally containing one or more wetting agents, one or more emulsifiers, or a mixture of said agents). Suitable organic solvents for use in ECs include aromatic hydrocarbons (such as alkylbenzenes or alkylnaphthalenes exemplified by SOLVESSO 100, SOLVESSO 150, and SOLVESSO 200 (SOLVESSO is a registered trademark)), ketones (such as cyclohexanone or methylcyclohexanone), and alcohols (such as benzyl alcohol, furfuryl alcohol, or butanol), N-alkylpyrrolidones (such as N-methylpyrrolidone or N-octylpyrrolidone), dimethylamides of fatty acids (C8-C9), and the like. 10EC products may emulsify spontaneously when water is added, resulting in emulsions that are stable enough to allow spray application with appropriate equipment.

[0036] The preparation of EWs involves obtaining a compound of formula (I) as a liquid (if not liquid at room temperature, it can be melted at a moderate temperature, typically below 70°C) or as a solution (by dissolving in a suitable solvent), and then emulsifying the resulting liquid or solution in water containing one or more SAAs under high shear to obtain an emulsion. Suitable solvents for use in EWs include vegetable oils, chlorinated hydrocarbons (such as chlorobenzene), aromatic solvents (such as alkylbenzenes or alkylnaphthalenes), and other suitable organic solvents with poor solubility in water.

[0037] Microemulsions (MEs) can be prepared by mixing a blend of one or more solvents and one or more SAA with water to spontaneously produce a thermodynamically stable, isotropic liquid formulation. The compound of formula (I) is initially present in water or the solvent / SAA blend. Suitable solvents for use in MEs include those described hereinabove for use in EC or EW. MEs can be oil-in-water or water-in-oil systems (which system is present can be determined by conductivity measurements) and can be suitable for mixing water-soluble and oil-soluble pesticides in the same formulation. MEs can remain as microemulsions or be suitable for dilution with water to form conventional oil-in-water emulsions.

[0038] Suspension concentrates (SCs) may comprise aqueous or non-aqueous suspensions of fine, insoluble solid particles of a compound of formula (I). SCs may be prepared by ball milling or bead milling a solid compound of formula (I) in a suitable medium, optionally with one or more dispersing agents, to produce a fine particle suspension of the compound. One or more wetting agents may be included in the composition, and a suspending agent may be included to reduce the rate at which the particles settle. Alternatively, a compound of formula (I) may be dry-milled and added to water containing the agents described hereinabove to produce the desired final product.

[0039] Aerosol formulations include a compound of formula (I) and a suitable propellant (e.g., n-butane). The compound of formula (I) may also be dissolved or dispersed in a suitable vehicle (e.g., water or a miscible liquid such as n-propanol) to provide a composition for use in a non-pressurized, manually operated spray pump.

[0040] Capsule suspensions (CS) can be prepared similarly to the preparation of EW formulations, but with an additional polymerization stage to obtain an aqueous dispersion of oil droplets, each of which is encapsulated by a polymeric shell and contains the compound of formula (I) and, optionally, a carrier or excipient therefor. The polymeric shell can be produced by an interfacial polycondensation reaction or a coacervation method. This composition can provide controlled release of the compound of formula (I), and they can be used for seed treatment. The compound of formula (I) can also be formulated in a biodegradable polymer matrix to provide controlled, slow release of the compound.

[0041] The composition may contain one or more additives to improve the biological performance of the composition, for example, by improving the wettability, retention, or dispersibility of the compound of formula (I) on a surface, its resistance to rain on the treated surface, or its uptake or mobility. Such additives include surface active agents (SAA), oil-based spray additives such as certain mineral oils or natural vegetable oils (such as soybean and rapeseed oil), modified vegetable oils such as methylated rapeseed oil (MRSO), and blends of these with other bio-enhancing adjuvants (formulation ingredients that can assist or modify the action of the compound of formula (I)).

[0042] Wetting agents, dispersing agents, and emulsifying agents may be cationic, anionic, amphoteric, or nonionic SAAs.

[0043] Suitable cationic SAAs include quaternary ammonium compounds (eg, cetyltrimethylammonium bromide), imidazolines, and amine salts.

[0044] Suitable anionic SAAs include alkali metal salts of fatty acids, salts of aliphatic monoesters of sulfuric acid (e.g., sodium lauryl sulfate), salts of sulfonated aromatic compounds (e.g., sodium dodecylbenzenesulfonate, calcium dodecylbenzenesulfonate, butylnaphthalene sulfonate, and mixtures of sodium di-isopropyl-sulfonate and sodium tri-isopropyl-naphthalenesulfonate), ether sulfates, alcohol ether sulfates (e.g., sodium laureth-3-sulfate), ether carboxylates (e.g., sodium laureth-3-carboxylate), phosphate esters (products of the reaction of one or more aliphatic alcohols with phosphoric acid (predominantly mono-esters) or phosphorus pentoxide (predominantly di-esters), e.g., the reaction of lauryl alcohol with tetraphosphoric acid; further, these products may be ethoxylated), sulfosuccinates, paraffin or olefin sulfonates, taurates, lignosulfonates, and phosphate / sulfate salts of tristyrylphenol.

[0045] Suitable amphoteric SAAs include betaines, propionates and glycinates.

[0046] Suitable nonionic SAAs include condensation products of alkylene oxides (such as ethylene oxide, propylene oxide, butylene oxide or mixtures thereof) with fatty alcohols (such as oleyl alcohol or cetyl alcohol) or alkylphenols (such as octylphenol, nonylphenol or octylcresol); partial esters derived from long chain fatty acids or hexitol anhydrides; condensation products of the above partial esters with ethylene oxide; block polymers (including ethylene oxide and propylene oxide); alkanolamides; simple esters (e.g., fatty acid polyethylene glycol esters); amine oxides (e.g., lauryl dimethylamine oxide); lecithin and sorbitan and their esters, alkyl polyglycosides and tristyrylphenols.

[0047] Suitable suspending agents include hydrophilic colloids (such as polysaccharides, polyvinylpyrrolidone, or sodium carboxymethylcellulose) and swelling clays (such as bentonite or attapulgite).

[0048] The compounds of the present invention can also be used in mixtures with one or more additional herbicides and / or plant growth regulators, such as acetochlor, acifluorfen (including acifluorfen sodium), aclonifen, ametryn, amicarbazone, aminopyralid, aminotriazole, atrazine, beflubutamid-M, benquitrione, bensulfuron (including bensulfuron-methyl), bentazone, bicyclopyrone, vilanaphos, bipyrazone, bispyribac-sodium, bixlozone, bromacil, bromoxynil, butachlor, butafenacil, carfentra, and the like. chlorantrazole (including carfentrazone-ethyl), cloransulam (including cloransulam-methyl), chlorimuron (including chlorimuron-ethyl), chlorotoluron, chlorsulfuron, cinmethylin, clasiphos, clethodim, clodinafop (including clodinafop-propargyl), clomazone, clopyralid, cyclopyranyl, cyclopyrimorate, cyclosulfamuron, cyhalofop (including cyhalofop-butyl), 2,4-D (including its choline salt and 2-ethylhexyl ester), 2,4-DB, dextromethorphan, cyclopentasiloxane ... Sumedipham, Dicamba (including its aluminum, aminopropyl, bis-aminopropylmethyl, choline, dichloroprop, diglycolamine, dimethylamine, dimethylammonium, potassium, and sodium salts), Diclosulam, Diflufenican, Diflufenzopyr, Dimethachlor, Dimethenamid-P, Dioxopyritrion, Diquat Dibromide, Diuron, Epirifenacil, Ethalfluralin, Ethofumesate, Fenoxaprop (including Fenoxaprop-P-ethyl), Fenoxasulfone, Fenoxaprop-P-ethyl 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 both ammonium salts), glyphosate (including its diammonium, isopropylammonium, and potassium salts), halaxifen (including haloxyfop-methyl), haloxyfop (including haloxyfop-methyl), hexazinone, hydantocidin, imazamox (including R-imazamox), imazapic, imazapyr, imazethapyr, indaziflam, iodosulfuron (including iodosulfuron-methyl-sodium), iofensulfuron (iofensulfuron-methyl-sodium), mesosulfuron (including mesosulfuron-sodium), ioxynil, isoproturon, isoxaflutole, lancotrione, MCPA, MCPB, mecoprop-P, mesosulfuron (including mesosulfuron-methyl), mesotrione, metamitron, metazachlor, methiozoline, metolachlor, metosulam, metribuzin, metsulfuron, napropamide, nicosulfuron, norflurazon, oxadiazon, oxasulfuron, oxyfluorfen, paraquat dichloride, pendimethalin, penoxsulam, phenmedipham, picloram, pinoxaden, prethion Lachlor, primisulfuron-methyl, prometryn, 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-metallo Chlor, sulfentrazone, sulfosulfuron, tebuthiuron, tefuryltrione, tembotrione, terbuthylazine, terbutryn, tetlfpyrrolimeth, thiencarbazone, thifensulfuron, thiafenacil, tolpyralate, topramezone, tralkoxydim, triafamone, triallate, triasulfuron, tribenuron (including tribenuron-methyl), triclopyr, trifloxysulfuron (including trifloxysulfuron-sodium), trifludimoxazine, 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- 4-amino-3-chloro-5-fluoro-6-(7-fluoro-1H-indol-6-yl)pyridine-2-carboxylic acid (and its agriculturally acceptable esters, such as 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. fluoro-6-(7-fluoro-1H-indol-6-yl)pyridine-2-carboxylate), 3-ethyl-sulfanyl-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) methyl)pyrimidin-1-yl]-2-pyridyl]oxy]acetate, 6-chloro-4-(2,7-dimethyl-1-naphthyl)-5-hydroxy-2-methyl-pyridazin-3-one, tetrahydro-furan-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-fluorophenyl) 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, 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,Examples include methyl 2-[(E)-[2-chloro-4-fluoro-5-[3-methyl-2,6-dioxo-4-(trifluoromethyl)pyrimidin-1-yl]phenyl]methyleneamino]oxypropanoate and methyl (2R)-2-[(E)-[2-chloro-4-fluoro-5-[3-methyl-2,6-dioxo-4-(trifluoromethyl)pyrimidin-1-yl]phenyl]methyleneamino]oxypropanoate.

[0049] The compound of formula (I) may also be in the form of an ester or salt, as described, for example, in The Pesticide Manual, Sixteenth Edition, British Crop Protection Council, 2012.

[0050] The compounds of formula (I) may also be used in mixtures with other pesticides such as fungicides, nematicides or insecticides, examples of which are given in The Pesticide Manual.

[0051] The mixing ratio of the compound of formula (I) to the mixing partner is preferably 1:100 to 1000:1.

[0052] This mixture may be advantageously used in the formulations described above (in which case "active ingredient" relates to the respective mixture of compound of formula (I) and mixing partner).

[0053] The compounds or mixtures of the present invention may also be used in combination with one or more herbicidal safeners, examples of which include 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.

[0054] Particularly preferred are mixtures of compounds of formula (I) with cyprosulfamide, isoxadifen-ethyl, cloquintocet-mexyl and / or metcamifen.

[0055] The safeners of the compounds of formula (I) can also be used as described, for example, in The Pesticide Manual, 16 th Edition (BCPC), 2012. Reference to cloquintocet-mexyl also applies to its lithium, sodium, potassium, calcium, magnesium, aluminum, iron, ammonium, quaternary ammonium, sulfonium or phosphonium salts, as disclosed in WO 02 / 34048.

[0056] Preferably, the mixing ratio of compound of formula (I) to safener is from 100:1 to 1:10, in particular from 20:1 to 1:1.

[0057] The present invention also provides a method for controlling weeds in a locus, comprising applying to the locus a weed-controlling amount of a composition containing a compound of formula (I). The present invention may further provide a method for selectively controlling weeds in a locus containing crop plants and weeds, comprising applying to the locus a weed-controlling amount of a composition of the present invention. "Control" means killing, reducing or delaying growth, or preventing or reducing germination. It is noted that the compounds of the present invention exhibit significantly improved selectivity compared to known structurally similar compounds. Generally, the plants to be controlled are undesirable plants (weeds). "Locus" refers to the area where plants are growing or will grow. Application may be to the locus before and / or after emergence of the crop plants. Several crop plants may be inherently resistant to the herbicidal effect of the compound of formula (I). Preferred crop plants include corn, wheat, barley, soybean, and rice.

[0058] The application rates of the compounds of formula I may vary within wide limits and depend on the nature of the soil, the method of application (pre- or post-emergence; seed dressing; application in the seed furrow; application on non-arable land, etc.), the crop plants, the weeds to be controlled, the prevailing climatic conditions, and other factors governed by the application method, application time, and target crop. The compounds of formula I of the invention are usually applied in amounts of 10 to 2500 g / ha, in particular 25 to 1000 g / ha, and even more particularly 25 to 250 g / ha.

[0059] Application is generally accomplished by spraying the composition, typically with a tractor-mounted large area sprayer, although other methods such as dusting (if powder), dripping or drench can also be used.

[0060] It should be understood that crop plants also include those that have been rendered tolerant to other herbicides or classes of herbicides (e.g., ALS-, GS-, EPSPS-, PPO-, HPPD-, -PDS, -SDPS, and ACCase-inhibitors) by conventional breeding methods or genetic engineering. An example of a crop that has been rendered tolerant to imidazolinones, such as imazamox, by conventional breeding methods is Clearfield® summer rape (canola). Examples of crops that have been rendered tolerant to herbicides by genetic engineering methods include glyphosate- and glufosinate-resistant corn varieties commercially available, for example, under the trade names RoundupReady® and LibertyLink®.

[0061] Crop plants should also be understood as those that have been rendered resistant to harmful insects by genetic engineering, such as Bt corn (resistant to the European corn borer), Bt cotton (resistant to the Mexican boll weevil), and Bt potato (resistant to the Colorado potato beetle). An example of Bt corn is the Bt176 corn hybrid from NK® (Syngenta Seeds). Bt toxins are natural proteins formed by the soil bacterium Bacillus thuringiensis. Examples of toxins or genetically modified plants capable of synthesizing such toxins are described in EP 451 878, EP 374 753, WO 93 / 07278, WO 95 / 34656, WO 03 / 052073, and EP 427 529. Examples of transgenic plants containing one or more genes encoding insecticide resistance and expressing one or more toxins are KnockOut® (corn), Yield Gard® (corn), NuCOTIN33B® (cotton), Bollgard® (cotton), NewLeaf® (potato), NatureGard®, and Protexcta®. Plant crops or their seed material can both be tolerant to herbicides and simultaneously resistant to insect feeding ("stacked" transgenics). For example, seeds can be tolerant to glyphosate and simultaneously capable of expressing the insecticidal Cry3 protein.

[0062] Crop plants should also be understood to include those obtained by conventional breeding methods or by genetic engineering and which contain so-called output traits (such as improved storage stability, higher nutritional value and improved flavor).

[0063] The compositions can be used to control undesirable plants (collectively "weeds"), such as Agrostis, Alopecurus, Avena, Brachiaria, Bromus, Cenchrus, Cyperus, Digitaria, Echinochloa, Eleusine, Lolium, Monochoria, Rottboellia, Sagittaria, Scirpus, Setaria, and Sorghum. orghum, as well as dicotyledonous species such as Abutilon, Amaranthus, Ambrosia, Chenopodium, Chrysanthemum, Conyza, Galium, Ipomoea, Nasturtium, Sida, Sinapis, Solanum, Stellaria, Veronica, Viola, and Xanthium.

[0064] In a further aspect of the present invention there is provided the use of a compound of formula (I) as defined herein as a herbicide.

[0065] Processes for the preparation of compounds, for example compounds of formula (I), optionally in the form of pesticidally acceptable salts thereof, are now described and form further aspects of the invention.

[0066] Scheme 1 A 1 -C(R 1 )(R 2 )- and X 1In embodiments where LG is O, a compound of formula (1) can be prepared from a compound of formula (2) (wherein LG represents a suitable leaving group (e.g., Br or Cl)) and a compound of formula (3). The compound of formula (2) is treated with an isoxazolidinone of formula (3) and a carbonate base, such as potassium carbonate, in a suitable solvent, such as dimethylformamide. [ka]

[0067] Scheme 2 Compounds of formula (2) can be prepared from benzyl alcohols of formula (4). [ka] For example, when LG is Cl, the benzyl alcohol of formula (4) is treated with a chlorinating agent such as thionyl chloride.

[0068] Scheme 3 Compounds of formula (4) can be prepared from compounds of formula (5) where Z is H or O-alkyl. [ka] For example, when Z is H, a compound of formula (5) is treated with a reducing agent, such as sodium borohydride, in a suitable solvent, such as a toluene / isopropanol mixture.

[0069] Scheme 4 The synthetic route used to access compounds of formula (5) is 2 , A 3 , R 5 and R 6 For example, when Z is H, a compound of formula (5) can be prepared from a compound of formula (6). [ka] A compound of formula (6) is reacted under suitable formylation conditions, for example by treatment with titanium tetrachloride and dichloro(methoxy)methane in a suitable solvent, for example dichloromethane.

[0070] Scheme 5 In another example, A 2 is S and A 3 is O and R 5 and R 6 When is F and Z is H, compounds of formula (5) can be prepared from 2-chloro-5-hydroxy-4-iodo-benzaldehyde (7). [ka] 2-Chloro-5-hydroxy-4-iodo-benzaldehyde (7) is treated with [(bpy)CuSCF3] and a suitable base, such as potassium fluoride, in a suitable solvent, such as acetonitrile.

[0071] Scheme 6 In an alternative approach, compounds of formula (4) can be prepared from benzyl alcohols of formula (8). [ka] A compound of formula (8) is treated with a chlorinating agent, such as 1,3,5-trichloro-1,3,5-triazinane-2,4,6-trione, in a suitable solvent, such as acetonitrile.

[0072] Scheme 7 Compounds of formula (8) may be commercially available. Alternatively, they may be prepared synthetically. The synthetic route is 2 , A 3 , R 5 and R 6 In one approach, compounds of formula (8) can be prepared from compounds of formula (9). [ka] For example, when Z is H, a compound of formula (9) is treated with a reducing agent, such as sodium borohydride, in a suitable solvent, such as methanol.

[0073] Scheme 8 Compounds of formula (9) may be commercially available. Alternatively, they may be prepared synthetically. The synthetic route is 2 , A 3 , R 5 and R 6 It varies depending on the properties of. For example, A 2 and A 3 When is O and Z is H, compounds of formula (9) can be prepared from 3,4-dihydroxybenzaldehyde (10). [ka] In one approach, 3,4-dihydroxybenzaldehyde (10) is treated with a dibromide of formula (11) and a suitable base, such as potassium carbonate, in a suitable solvent, such as acetonitrile.

[0074] Scheme 9 In a further alternative approach, a compound of formula (1) 2 and A 3 ═O) can be prepared from 2-chloro-6-chloropiperonyl alcohol (12) by the following scheme: [ka] 2-Chloro-6-chloropiperonyl alcohol (12) is treated with a suitable oxidative chlorinating agent, such as phosphorus pentachloride, in a suitable solvent, such as chlorobenzene. 5-Chloro-6-(chloromethyl)-1,3-benzodioxol-2-one (13) is treated with an isoxazolidinone of formula (3) and a carbonate base, such as potassium carbonate, in a suitable solvent, such as dimethylformamide. Compounds of formula (14) are treated with a ketone of formula (15) and an acid catalyst, such as para-toluenesulfonic acid, in a suitable solvent, such as toluene.

[0075] Scheme 10 In a variation of Scheme 9, a compound of formula (1) 2 and A 3 =O) can be prepared from a compound of formula (14) and a compound of formula (11). [ka] A compound of formula (14) is treated with a dibromide of formula (11) and a suitable base, such as potassium carbonate, in a suitable solvent, such as dimethylformamide.

[0076] Scheme 11 A 1 When is -C(=O)-, compounds of formula (1) may be prepared from compounds of formula (5) (where Z is H) by the following scheme: [ka] Compounds of formula (5) are treated with a hydroxylamine source, such as hydroxylamine hydrochloride, and a suitable base, such as sodium acetate, in a suitable solvent, such as ethanol, to give compounds of formula (16). Compounds of formula (16) are treated with a suitable reducing agent, such as sodium cyanoborohydride, and a suitable acid, such as 4M hydrochloric acid in dioxane, in a suitable solvent, such as methanol. Compounds of formula (17) are treated with 2,2-dimethylmalonyl chloride and a suitable base, such as pyridine, in a suitable solvent, such as dichloromethane.

[0077] Scheme 12 Compounds of formula (3) may be commercially available. For example, compounds of formula (3) (wherein R 3 and R 4 is methyl and R 1 and R 2 where R is hydrogen) is commercially available (CAS number 81778-07-6). Alternatively, compounds of formula (3) can be prepared synthetically. For example, 1is C1-C6 alkoxy, C1-C6 alkoxy-C1-C6 alkoxy-, HOC(O)C1-C6 alkoxy-, C1-C6 alkoxy-C(O)-C1-C6 alkoxy- or C1-C3 alkyl-S(O) p C1-C6 alkoxy-, and R 2 When is hydrogen, compounds of formula (3) can be prepared from 3,3-dichloro-2,2-dimethylpropanoic acid (18). [ka] Treatment of 3,3-dichloro-2,2-dimethylpropanoic acid 18 with a suitable chlorinating agent, such as thionyl chloride, gives 3,3-dichloro-2,2-dimethylpropanoyl chloride 19. Treatment of 3,3-dichloro-2,2-dimethylpropanoyl chloride 19 with a suitable source of hydroxylamine, such as hydroxylamine (50% in HO), gives 3,3-dichloro-2,2-dimethylpropanehydroxamic acid 20. Treatment of 3,3-dichloro-2,2-dimethylpropanehydroxamic acid 20 with an alcohol and a suitable base, such as 1,8-diazabicyclo(5.4.0)undec-7-ene, gives the compound of formula 3.

[0078] Scheme 13 Compounds of formula (21) can be prepared from compounds of formula (22). [ka] A compound of formula (22) is treated with a suitable Lewis acid source, for example, boron trifluoride diethyl etherate, in a suitable solvent, for example, toluene.

[0079] Scheme 14 Compounds of formula (23) can be prepared from compounds of formula (24). [ka] A compound of formula (24) is treated with a suitable base, such as potassium carbonate, in a suitable solvent, such as acetone.

[0080] Scheme 15 Compounds of formula (24) can be prepared from compounds of formula (17). [ka] A compound of formula (17) is treated with 3,3-dichloro-2,2-dimethylpropanoyl chloride (19) and a suitable base, such as pyridine, in a suitable solvent, such as dichloromethane, optionally in the presence of a suitable additive, such as chloro(trimethyl)silane.

[0081] The following non-limiting examples provide specific synthetic methods for representative compounds of the invention referenced in Table 1 below.

[0082] Preparation Examples Example P1: Preparation of Compound 1.001 Step 1: Preparation of 6-chloro-2,2-dimethyl-1,3-benzodioxole-5-carbaldehyde To a solution of 5-chloro-2,2-dimethyl-1,3-benzodioxole (5.00 g, 26.5 mmol) in dichloromethane (50.0 mL) was added dichloro(methoxy)methane (3.74 g, 2.94 mL, 31.8 mmol) followed by titanium tetrachloride (5.59 g, 3.24 mL, 29.2 mmol) at -5 °C. The reaction mixture was stirred at 0 °C for 1.5 hours. Ice-cold water was added, and the product was extracted with dichloromethane. The organic portion was filtered through a layer of Celite®, passed through a phase separator, and then concentrated in vacuo. The crude material was purified by flash column chromatography (0 to 40% ethyl acetate in isohexane). The product-containing fractions were combined and concentrated to give 6-chloro-2,2-dimethyl-1,3-benzodioxole-5-carbaldehyde (1.6 g, 7.5 mmol, 28%) as a white solid. 1H NMR(400MHz,CDCl3)δ ppm 10.29(s,1H),6.80(s,1H),6.78(s,1H),1.72(s,6H).

[0083] Step 2: Preparation of (6-chloro-2,2-dimethyl-1,3-benzodioxol-5-yl)methanol Sodium borohydride (0.856 g, 22.6 mmol) was added portionwise over 15 minutes to a vigorously stirred solution of 6-chloro-2,2-dimethyl-1,3-benzodioxole-5-carbaldehyde (1.60 g, 7.55 mmol) in toluene (5.0 mL) and isopropanol (2.0 mL) at room temperature under a nitrogen atmosphere. The reaction was stirred for 2 hours. Ethyl acetate and brine were added to the reaction. The phases were separated, and the aqueous portion was extracted with an additional portion of ethyl acetate. The organic portions were combined, dried over MgSO4, filtered, and concentrated in vacuo to give (6-chloro-2,2-dimethyl-1,3-benzodioxol-5-yl)methanol (1.45 g, 6.76 mmol, 44%) as a white solid. 1H NMR (400 MHz, chloroform) δ ppm 6.84 (s, 1H), 6.75 (s, 1H), 4.67 (d, 2H), 1.83 (t, 1H), 1.68 (s, 6H).

[0084] Step 3: Preparation of 5-chloro-6-(chloromethyl)-2,2-dimethyl-1,3-benzodioxole (6-Chloro-2,2-dimethyl-1,3-benzodioxol-5-yl)methanol (1.45 g, 6.76 mmol) and thionyl chloride (4.9 mL) were stirred at 60° C. for 1 hour. The reaction mixture was concentrated in vacuo and azeotroped with toluene to give 5-chloro-6-(chloromethyl)-2,2-dimethyl-1,3-benzodioxole (0.90 g, 3.9 mmol, 57%) as a white solid. 1H NMR (400 MHz, chloroform) δ ppm 6.80 (s, 1H), 6.76 (s, 1H), 4.62 (s, 2H), 1.68 (s, 6H).

[0085] Step 4: Preparation of 2-[(6-chloro-2,2-dimethyl-1,3-benzodioxol-5-yl)methyl]-4,4-dimethyl-isoxazolidin-3-one To a solution of 5-chloro-6-(chloromethyl)-2,2-dimethyl-1,3-benzodioxole (260 mg, 1.12 mmol) in dimethylformamide (2.5 mL) was added potassium carbonate (310 mg, 2.21 mmol) and 4,4-dimethylisoxazolidin-3-one (130 mg, 1.13 mmol). The reaction was stirred at room temperature overnight. The reaction was quenched with water (50 mL), and the resulting precipitate was filtered and washed with water. The crude material was purified by flash column chromatography (0–20% ethyl acetate in cyclohexane). Product-containing fractions were combined and concentrated to give 2-[(6-chloro-2,2-dimethyl-1,3-benzodioxol-5-yl)methyl]-4,4-dimethyl-isoxazolidin-3-one (229 mg, 0.73 mmol, 66%) as a colorless oil that solidified upon standing. 1H NMR(400MHz,CDCl3)δ ppm 6.74(s,1H),6.71(s,1H),4.72(s,2H),4.01(s,2H),1.68(s,6H),1.27(s,6H).

[0086] Example P2: Preparation of Compound 1.002 Step 1: Preparation of 6-chloro-2,2-dimethyl-1,3-benzodioxole-5-carbaldehyde oxime Sodium acetate (0.745 g, 8.98 mmol) and hydroxylamine hydrochloride (0.624 g, 8.97 mmol) were added to a solution of 6-chloro-2,2-dimethyl-1,3-benzodioxole-5-carbaldehyde (1.59 g, 7.48 mmol) in ethanol (16 mL), and the reaction mixture was stirred at reflux for 1 hour. The reaction mixture was cooled to room temperature and then concentrated in vacuo. The residue was diluted with water and dichloromethane. The layers were separated, and the organic portion was passed through a hydrophobic frit and then concentrated in vacuo to give 6-chloro-2,2-dimethyl-1,3-benzodioxole-5-carbaldehyde oxime (1.66 g, 7.29 mmol, 98%) as a white solid. 1H NMR(400MHz,CDCl3)δ ppm 8.48(s,1H),7.19(s,1H),6.73(s,1H),1.68(s,6H).

[0087] Step 2: Preparation of N-[(6-chloro-2,2-dimethyl-1,3-benzodioxol-5-yl)methyl]hydroxylamine A solution of sodium cyanoborohydride (1.37 g, 21.7 mmol) in methanol (5.0 mL) and 4 M hydrochloric acid in dioxane (5.6 mL) were added dropwise simultaneously over 30 min to a stirred solution of 6-chloro-2,2-dimethyl-1,3-benzodioxole-5-carbaldehyde oxime (1.65 g, 7.25 mmol) and a trace of methyl orange in methanol (20 mL) at room temperature. During the addition, care was taken to maintain the reaction mixture at 19-27 °C and a pH below 3. Upon completion of the addition, the reaction mixture was stirred at room temperature for 30 min, during which time the reaction mixture was kept acidic by the addition of small amounts of 4 M hydrochloric acid in dioxane. The reaction mixture was cooled to 0 °C, and the pH was adjusted to 9.4 by the dropwise addition of concentrated sodium hydroxide. The reaction mixture was concentrated in vacuo, followed by the addition of ethyl acetate (25 mL) and water (50 mL), and the layers were separated. The organic portion was dried over MgSO, filtered, and concentrated in vacuo to give N-[(6-chloro-2,2-dimethyl-1,3-benzodioxol-5-yl)methyl]hydroxylamine (1.66 g, 7.23 mmol, 100%) as a pale yellow solid. H NMR (400 MHz, CDCl) δ ppm 6.78 (s, 1H), 6.74 (s, 1H), 4.04 (s, 2H), 1.67 (s, 6H).

[0088] Step 3: Preparation of 2-[(6-chloro-2,2-dimethyl-1,3-benzodioxol-5-yl)methyl]-4,4-dimethyl-isoxazolidine-3,5-dione 2,2-Dimethylpropanedioyl dichloride (1.22 g, 0.96 mL, 7.23 mmol) in dichloromethane (10 mL) was added dropwise over 15 min to a solution of N-[(6-chloro-2,2-dimethyl-1,3-benzodioxol-5-yl)methyl]hydroxylamine (1.66 g, 7.23 mmol) and pyridine (1.16 g, 1.18 mL, 14.5 mmol) in dichloromethane (10 mL) at 0 °C. The reaction mixture was stirred at room temperature for 2 h and allowed to stand overnight. The reaction mixture was acidified with 2 M hydrochloric acid, passed through a phase separator, and the organic portion was concentrated in vacuo. The crude material was absorbed onto silica gel and purified by flash column chromatography (0–10% ethyl acetate in isohexane). The product-containing fractions were concentrated to give 2-[(6-chloro-2,2-dimethyl-1,3-benzodioxol-5-yl)methyl]-4,4-dimethyl-isoxazolidine-3,5-dione (1.94 g, 5.94 mmol, 82%) as a white solid. 1H NMR (400 MHz, CDCl3) δ ppm 6.78 (s, 1H), 6.71 (s, 1H), 4.96 (s, 2H), 1.68 (s, 6H), 1.44 (s, 6H).

[0089] Example P3: Preparation of Compound 1.005 Step 1: Preparation of 5-chloro-6-(chloromethyl)-1,3-benzodioxol-2-one A solution of chloropiperonyl alcohol (10.0 g, 53.6 mmol) in chlorobenzene (50 mL) was added slowly over 10 minutes to a solution of phosphorus pentachloride (45.6 g, 214 mmol) in chlorobenzene (50 mL). The reaction was heated to reflux for 5 hours and then cooled to room temperature. The reaction mixture was added dropwise to water with stirring and then extracted with dichloromethane (×2). The organic portions were combined, passed through a phase separator, and concentrated in vacuo. The crude material was purified by flash column chromatography (0–50% ethyl acetate in isohexane). Product-containing fractions were combined and concentrated to give 5-chloro-6-(chloromethyl)-1,3-benzodioxol-2-one (10.8 g, 49.4 mmol, 92%) as a brown oil. 1H NMR(400MHz,CDCl3)δ ppm 7.42(s,1H),7.35(s,1H),4.70(s,2H).

[0090] Step 2: Preparation of 2-[(2-chloro-4,5-dihydroxy-phenyl)methyl]-4,4-dimethyl-isoxazolidin-3-one To a solution of 5-chloro-6-(chloromethyl)-1,3-benzodioxol-2-one (10.8 g, 49.4 mmol) in dimethylformamide (111 mL) was added potassium carbonate (20.7 g, 150 mmol) and 4,4-dimethylisoxazolidin-3-one (5.69 g, 49.4 mmol). The reaction was stirred at room temperature for 65 hours. The reaction was acidified to pH 2 with 2 M hydrochloric acid and extracted with diethyl ether (×4). The organic portions were combined, dried over MgSO4, filtered, and concentrated in vacuo. The crude material was purified by flash column chromatography (20–100% ethyl acetate in isohexane). The product-containing fractions were combined and concentrated to give 2-[(2-chloro-4,5-dihydroxyphenyl)methyl]-4,4-dimethyl-isoxazolidin-3-one (9.95 g, 36.6 mmol, 74%) as an off-white solid. 1H NMR (400 MHz, d6-DMSO) δ ppm 9.43 (br.s, 1H), 9.31 (br.s, 1H), 6.76 (s, 1H), 6.74 (s, 1H), 4.55 (s, 2H), 4.00 (s, 2H), 1.12 (s, 6H).

[0091] Step 3: Preparation of 2-[(6-chloro-2,2-diethyl-1,3-benzodioxol-5-yl)methyl]-4,4-dimethyl-isoxazolidin-3-one Pentan-3-one (1.2 g, 1.5 mL, 14 mmol) was added dropwise to a solution of 2-[(2-chloro-4,5-dihydroxyphenyl)methyl]-4,4-dimethyl-isoxazolidin-3-one (150 mg, 0.552 mmol) and p-toluenesulfonic acid (27.0 mg, 0.149 mmol) in toluene (3 mL) in a sealed microwave vial. The solution was heated at 160 °C by microwave irradiation for 2 h. The reaction mixture was concentrated onto Celite® and purified by flash column chromatography (0–10% ethyl acetate in isohexane). Product-containing fractions were combined and concentrated to give 2-[(6-chloro-2,2-diethyl-1,3-benzodioxol-5-yl)methyl]-4,4-dimethyl-isoxazolidin-3-one (9.0 mg, 0.03 mmol, 5%) as a brown gum. 1H NMR(400MHz,CDCl3)δ ppm 6.73(s,1H),6.69(s,1H),4.72(s,2H),4.02(s,2H),1.91(q,4H),1.26(s,6H),0.96(t,6H).

[0092] Example P4: Preparation of compound 1.014 Step 1: Preparation of (6-chloro-2,2-difluoro-1,3-benzodioxol-5-yl)methanol A solution of (2,2-difluoro-1,3-benzodioxol-5-yl)methanol (7.66 g, 40.7 mmol) and 1,3,5-trichloro-1,3,5-triazinane-2,4,6-trione (13.2 g, 57.0 mmol) in acetonitrile (100 mL) was stirred overnight at room temperature. The reaction mixture was concentrated onto silica gel and purified by flash column chromatography (0 to 50% ethyl acetate in isohexane). The product-containing fractions were combined and concentrated to give (6-chloro-2,2-difluoro-1,3-benzodioxol-5-yl)methanol (2.30 g, 10.3 mmol, 25%) as a white solid. H NMR (400 MHz, CDCl) δ ppm 7.29 (s, 1H), 7.10 (s, 1H), 4.74 (s, 2H), 1.98 (s, 1H).

[0093] Step 2: Preparation of 5-(bromomethyl)-6-chloro-2,2-difluoro-1,3-benzodioxole To a solution of (6-chloro-2,2-difluoro-1,3-benzodioxol-5-yl)methanol (1.50 g, 6.76 mmol) in dichloromethane (13.0 mL) was added carbon tetrabromide (2.69 g, 8.11 mmol), and the solution was cooled to 0 °C in an ice bath. Triphenylphosphine (2.66 g, 10.1 mmol) was added, and the reaction was then warmed to room temperature and stirred for 3 h. The reaction mixture was concentrated onto Isolute® and purified by flash column chromatography (0–15% ethyl acetate in cyclohexane). The product-containing fractions were concentrated to give 5-(bromomethyl)-6-chloro-2,2-difluoro-1,3-benzodioxole (1.94 g, 6.76 mmol, 100%) as a colorless gum. 1H NMR(400MHz,CDCl3)δ ppm 7.18(s,1H),7.13(s,1H),4.57(s,2H).

[0094] Step 3: Preparation of 3,3-dichloro-2,2-dimethyl-propanoyl chloride 3,3-Dichloro-2,2-dimethyl-propanoic acid (88.0 g, 514 mmol) was added to a stirred solution of thionyl chloride (148 mL) at room temperature. The mixture was heated to 70 °C for 5 h. Excess thionyl chloride was removed by crude distillation (75 °C). The residue was then purified by distillation (40 °C, 5 mbar) to give 3,3-dichloro-2,2-dimethyl-propanoyl chloride (87.0 g, 459 mmol, 89%) as a colorless oil. 1H NMR (400 MHz, CDCl3) δ ppm 6.17 (s, 1H), 1.50 (s, 6H).

[0095] Step 4: Preparation of 3,3-dichloro-2,2-dimethyl-propanehydroxamic acid To hydroxylamine (50% by weight) in water (8.09 g, 7.5 mL, 122 mmol) was added 3,3-dichloro-2,2-dimethyl-propanoyl chloride (3.00 g, 15.8 mmol) dropwise. The reaction mixture was stirred at room temperature for 10 minutes. The reaction mixture was extracted with dichloromethane, passed through a phase separator, and concentrated in vacuo to give 3,3-dichloro-2,2-dimethyl-propanehydroxamic acid (1.94 g, 10.4 mmol, 66%) as a white solid. 1H NMR (400 MHz, CDCl3) δ ppm 6.40 (br.s, 1H), 6.12 (s, 1H), 1.40 (s, 6H).

[0096] Step 5: Preparation of 4,4-dimethyl-5-(2-trimethylsilylethoxy)isoxazolidin-3-one A solution of 1,8-diazabicyclo(5.4.0)undec-7-ene (0.835 g, 0.82 mL, 5.38 mmol) and 3,3-dichloro-2,2-dimethyl-propanehydroxamic acid (0.500 g, 2.69 mmol) in 2-trimethylsilylethanol (5.0 mL) was heated at 75 °C overnight. The reaction mixture was diluted with EtOAc and washed with 2 M hydrochloric acid (×2) and brine. The organic portion was concentrated to give 4,4-dimethyl-5-(2-trimethylsilylethoxy)isoxazolidin-3-one (0.308 g, 1.33 mmol, 50%) as a pale orange gum. This material was used crude in the next reaction without further purification.

[0097] Step 6: Preparation of 2-[(6-chloro-2,2-difluoro-1,3-benzodioxol-5-yl)methyl]-4,4-dimethyl-5-(2-trimethylsilylethoxy)isoxazolidin-3-one To a solution of 5-(bromomethyl)-6-chloro-2,2-difluoro-1,3-benzodioxole (0.300 g, 1.05 mmol) in acetone (9.0 mL) was added potassium carbonate (0.295 g, 2.10 mmol) and 4,4-dimethyl-5-(2-trimethylsilylethoxy)isoxazolidin-3-one (0.292 g, 1.26 mmol). The reaction was stirred at room temperature overnight. The reaction mixture was diluted with ethyl acetate, filtered through Celite®, concentrated onto Isolute®, and purified by flash column chromatography (0-40% ethyl acetate in cyclohexane). Concentration of the product-containing fractions gave 2-[(6-chloro-2,2-difluoro-1,3-benzodioxol-5-yl)methyl]-4,4-dimethyl-5-(2-trimethylsilylethoxy)isoxazolidin-3-one (0.157 g, 0.360 mmol, 34%) as a colorless gum. H NMR (400 MHz, CDCl) δ ppm 7.18 (s, 1H), 7.13 (s, 1H), 4.95 (d, 1H), 4.92 (s, 1H), 4.71 (d, 1H), 3.75 (ddd, 1H), 3.50 (ddd, 1H), 1.32 (s, 3H), 1.23 (s, 3H), 0.95-0.87 (m, 2H), 0.00 (s, 9H).

[0098] Step 7: Preparation of 2-[6-chloro-2,2-difluoro-1,3-benzodioxol-5-yl)methyl]-5-hydroxy-4,4-dimethyl-isoxazolidin-3-one To a solution of 2-[(6-chloro-2,2-difluoro-1,3-benzodioxol-5-yl)methyl]-4,4-dimethyl-5-(2-trimethylsilylethoxy)isoxazolidin-3-one (0.157 g, 0.360 mmol) in toluene (3.6 mL) was added dropwise at 0 °C. The reaction mixture was stirred at room temperature under nitrogen for 48 hours. Additional boron trifluoride diethyl etherate (0.358 g, 0.32 mL, 2.52 mmol) was added, and the reaction mixture was stirred at room temperature under nitrogen for an additional 24 hours. The reaction was quenched with saturated aqueous NaHCO and extracted with ethyl acetate (x3). The organic portions were combined, dried over MgSO, filtered, and concentrated in vacuo. The crude material was purified by flash column chromatography (0–50% ethyl acetate in cyclohexane). The product-containing fractions were combined and concentrated to give 2-[(6-chloro-2,2-difluoro-1,3-benzodioxol-5-yl)methyl]-5-hydroxy-4,4-dimethyl-isoxazolidin-3-one (60.0 mg, 0.179 mmol, 50%) as a white solid. H NMR (400 MHz, CDCl) δ ppm: 7.16 (s, 1H), 7.12 (s, 1H), 5.30 (d, 1H), 4.92–4.88 (m, 1H), 4.79–4.75 (m, 1H), 3.20 (d, 1H), 1.30 (s, 3H), 1.26 (s, 3H).

[0099] Example P5: Preparation of compound 1.019 Step 1: Preparation of 1-(4-chloro-2-fluoro-phenyl)-2-methyl-propan-2-ol To a stirred solution of methyl 2-(4-chloro-2-fluoro-phenyl)acetate (10.0 g, 49.4 mmol) in anhydrous THF (250 mL) was added methylmagnesium chloride (3 M solution in THF, 49.4 mL, 148 mmol) dropwise over 20 minutes. The reaction mixture was stirred at room temperature overnight, then quenched with saturated aqueous NH4Cl and extracted with EtOAc (x2). The combined organic portions were washed with brine, dried over sodium sulfate, and concentrated. Purification by flash column chromatography gave 1-(4-chloro-2-fluoro-phenyl)-2-methyl-propan-2-ol (5.0 g, 24.7 mmol, 50%). 1H NMR(400MHz,CDCl3)δ ppm 7.20-7.16(m,1H),7.08-7.06(m,2H),2.77(s,2H),1.23(s,6H).

[0100] Step 2: Preparation of 6-chloro-2,2-dimethyl-3H-benzofuran To a stirred solution of 1-(4-chloro-2-fluoro-phenyl)-2-methyl-propan-2-ol (7.20 g, 35.5 mmol) in THF (80 mL) was added potassium tert-butoxide (1 M solution in THF, 88.8 mL, 88.8 mmol). The reaction was stirred at 65 °C for 18 h, then quenched with 1 M hydrochloric acid and extracted with EtOAc. The organic phase was dried over sodium sulfate and concentrated. Purification by flash column chromatography (ethyl acetate / hexanes) gave 6-chloro-2,2-dimethyl-3H-benzofuran (4.5 g, 24.6 mmol, 69%). 1H NMR (400 MHz, CDCl3) δ ppm 7.01 (d, 1H), 6.77 (d, 1H), 6.70 (s, 1H), 2.95 (s, 2H), 1.46 (s, 6H).

[0101] Step 3: Preparation of 6-chloro-2,2-dimethyl-3H-benzofuran-5-carbaldehyde Dimethylformamide (0.93 mL, 12.0 mmol) was added dropwise to phosphoryl chloride (2.73 g, 1.63 mL, 17.8 mmol) with stirring at 0° C. The mixture was stirred at 0° C. for 15 minutes, and then 6-chloro-2,2-dimethyl-3H-benzofuran (1.0 g, 5.48 mmol) was slowly added. The reaction was stirred at room temperature for 30 minutes and then at 80° C. overnight. The reaction mixture was cooled to 0° C. and quenched by adding cold water. The mixture was extracted with EtOAc (×2), and the combined organic portions were concentrated. Purification by flash column chromatography gave 6-chloro-2,2-dimethyl-3H-benzofuran-5-carbaldehyde (0.170 g, 0.81 mmol, 15%). 1H NMR (400MHz, CDCl3): δ ppm 10.29(s,1H),7.73(s,1H),6.74(s,1H),2.99(s,2H),1.49(s,6H).

[0102] Step 4: Preparation of (6-chloro-2,2-dimethyl-3H-benzofuran-5-yl)methanol Sodium borohydride (0.057 g, 1.44 mmol) was added portionwise over 15 minutes to a stirred solution of 6-chloro-2,2-dimethyl-3H-benzofuran-5-carbaldehyde (0.101 g, 0.48 mmol) in toluene (0.48 mL), isopropanol (0.096 mL), and water (0.096 mL) at room temperature under a nitrogen atmosphere. The reaction was stirred for 1 hour, then ethyl acetate and brine were added. The phases were separated, and the aqueous phase was extracted with an additional portion of ethyl acetate. The organic portions were combined, dried over MgSO4, filtered, and concentrated. Purification by flash column chromatography (0–10% ethyl acetate in cyclohexane) gave (6-chloro-2,2-dimethyl-3H-benzofuran-5-yl)methanol (0.045 g, 0.21 mmol, 44%). 1H NMR(400MHz,CDCl3)δ ppm 7.19(s,1H),6.74(s,1H),4.67(d,2H),2.97(s,2H),2.00(t,1H)1.46(s,6H).

[0103] Step 5: Preparation of 2-[(6-chloro-2,2-dimethyl-3H-benzofuran-5-yl)methyl]-4,4-dimethyl-isoxazolidin-3-one Thionyl chloride (0.25 g, 0.15 mL, 2.1 mmol) and (6-chloro-2,2-dimethyl-3H-benzofuran-5-yl)methanol (0.045 g, 0.21 mmol) were combined and stirred at 60° C. for 1 hour. The reaction mixture was concentrated and then repeatedly dissolved in toluene and concentrated (×3). The resulting residue was combined with 4,4-dimethylisoxazolidin-3-one (0.031 g, 0.27 mmol), dimethylformamide (0.26 mL), and potassium carbonate (0.062 g, 0.45 mmol), and the mixture was stirred at room temperature overnight. Water and methyl tert-butyl ether were added, and the phases were separated. The aqueous layer was extracted with additional portions of methyl tert-butyl ether (×2), and the combined organic portions were then washed with saturated aqueous NaHCO and brine (×2). The organic layer was dried over MgSO, filtered, and concentrated. Purification by flash column chromatography (0–25% ethyl acetate in cyclohexane) gave 2-[(6-chloro-2,2-dimethyl-3H-benzofuran-5-yl)methyl]-4,4-dimethyl-isoxazolidin-3-one (0.041 g, 0.13 mmol, 59%). 1H NMR (400 MHz, CDCl3) δ ppm 7.10 (s, 1H), 6.74 (s, 1H), 4.75 (s, 2H), 4.00 (s, 2H), 2.96 (s, 2H), 1.46 (s, 6H), 1.25 (s, 6H).

[0104] Example P6: Preparation of compound 1.028 Preparation of ethyl 5-chloro-6-[(4,4-dimethyl-3-oxo-isoxazolidin-2-yl)methyl]-1,3-benzodioxole-2-carboxylate To a solution of 2-[(2-chloro-4,5-dihydroxy-phenyl)methyl]-4,4-dimethyl-isoxazolidin-3-one (0.497 g, 1.83 mmol) in dimethylformamide (4.94 mL) was added potassium carbonate (0.532 g, 3.66 mmol) and ethyl dibromoacetate (0.90 g, 0.47 mL, 3.66 mmol). The reaction mixture was heated to 70 °C for 3 h, then diluted with water and extracted with EtOAc (×2). The combined organic portions were washed with water and concentrated. Purification by flash column chromatography (0–30% acetone in cyclohexane) gave ethyl 5-chloro-6-[(4,4-dimethyl-3-oxo-isoxazolidin-2-yl)methyl]-1,3-benzodioxole-2-carboxylate (0.296 g, 0.832 mmol, 46%). 1H NMR(400MHz,CDCl3)δ ppm 6.91(s,1H),6.88(s,1H),6.33(s,1H),4.80-4.69(m,2H),4.32(q,2H),4.02(s,2H),1.34(t,3H),1.26(s,6H).

[0105] Example P7: Preparation of compound 1.029 Step 1: Preparation of methyl 6-chloro-2-oxo-3H-1,3-benzoxazole-5-carboxylate To a solution of methyl 5-amino-2-chloro-4-hydroxybenzoate (2.105 g, 10.44 mmol) in acetonitrile (41.8 mL) were added 1,8-diazabicyclo[5.4.0]undec-7-ene (3.35 g, 3.284 mL, 20.88 mmol) and 1,1'-carbonyldiimidazole (1.89 g, 11.5 mmol). The reaction mixture was stirred at room temperature for 1 hour, then diluted with saturated aqueous NH4Cl and extracted with EtOAc (x2). The combined organic portions were concentrated onto isolute® and purified by reverse-phase flash column chromatography to give impure methyl 6-chloro-2-oxo-3H-1,3-benzoxazole-5-carboxylate (2.675 g), which was used in the subsequent step without further purification. 1H NMR(400MHz,d6-DMSO)δ ppm 7.62(s,1H),7.45(s,1H),3.85(s,3H).

[0106] Step 2: Preparation of 6-chloro-5-(hydroxymethyl)-3H-1,3-benzoxazol-2-one Diisobutylaluminum hydride (1 M solution in hexane, 27.1 mL, 27.1 mmol) was added dropwise to a solution of methyl 6-chloro-2-oxo-3H-1,3-benzoxazole-5-carboxylate (1.77 g, 7.76 mmol) in 2-methyltetrahydrofuran (22 mL) at 0° C. under a nitrogen atmosphere. The reaction mixture was stirred at 0° C. for 30 minutes and then at room temperature for 90 minutes. Additional diisobutylaluminum hydride (1 M solution in hexane, 7.76 mL, 7.76 mmol) was added at 0° C., and the reaction was stirred at room temperature for 18 hours. The final portion of diisobutylaluminum hydride (1 M solution in hexane, 7.76 mL, 7.76 mmol) was then added at 0° C., and the reaction was stirred at room temperature for 2 hours. The reaction mixture was quenched by the dropwise addition of EtOAc at 0° C. Saturated aqueous potassium sodium tartrate was added, and the mixture was stirred vigorously at room temperature for 1.5 hours, then extracted with EtOAc (×3). The combined organic portions were washed with brine, dried over MgSO4, and concentrated. Purification by reverse-phase flash column chromatography gave 6-chloro-5-(hydroxymethyl)-3H-1,3-benzoxazol-2-one (0.517 g, 2.59 mmol, 33%). 1H NMR (400 MHz, d6-DMSO) δ ppm 7.43 (s, 1H), 7.21 (s, 1H), 4.53 (s, 2H).

[0107] Step 3: Preparation of 5-(bromomethyl)-6-chloro-3H-1,3-benzoxazol-2-one Carbon tetrabromide (0.821 g, 0.34 mL, 2.48 mmol) and triphenylphosphine (0.812 g, 3.10 mmol) were added to a solution of 6-chloro-5-(hydroxymethyl)-3H-1,3-benzoxazol-2-one (0.412 mg, 2.06 mmol) in dichloromethane (6.88 mL). The reaction mixture was stirred at room temperature for 30 minutes and then concentrated. Purification by flash column chromatography (0 to 50% acetone in cyclohexane) gave 5-(bromomethyl)-6-chloro-3H-1,3-benzoxazol-2-one (0.428 g, 1.63 mmol, 79.0%). 1H NMR (400 MHz, d6-DMSO) δ ppm 7.54 (s, 1H), 7.36 (s, 1H), 4.78 (s, 2H).

[0108] Step 4: Preparation of 6-chloro-5-[(4,4-dimethyl-3-oxo-isoxazolidin-2-yl)methyl]-3H-1,3-benzoxazol-2-one Potassium carbonate (0.261 g, 1.79 mmol) was added to a solution of 4,4-dimethylisoxazolidin-3-one (0.939 g, 8.15 mmol) in acetone (6.4 mL) with stirring at room temperature. Then, a solution of 5-(bromomethyl)-6-chloro-3H-1,3-benzoxazol-2-one (0.428 g, 1.63 mmol) in acetone (6.4 mL) was added dropwise over 15 min. The reaction mixture was concentrated onto Isolute® and purified by flash column chromatography (0 to 70% acetone in cyclohexane), then purified again by reverse-phase flash column chromatography to give 6-chloro-5-[(4,4-dimethyl-3-oxo-isoxazolidin-2-yl)methyl]-3H-1,3-benzoxazol-2-one (0.269 g, 0.907 mmol, 56%). 1H NMR(400MHz,CDCl3)δ ppm 7.25(s,1H),7.12(s,1H),4.85(s,2H),4.05(s,2H),1.27(s,6H).

[0109] Example P8: Preparation of compound 1.031 Step 1: Preparation of 2-chloro-5-hydroxy-4-iodo-benzaldehyde To a stirred solution of 2-chloro-5-hydroxybenzaldehyde (4.00 g, 25.6 mmol) in DCM (100 mL) and MeOH (100 mL) was added NIS (6.34 g, 28.1 mmol), and the reaction mixture was stirred at room temperature for 2 h. The reaction mixture was diluted with water and extracted with DCM (×3). The combined organic layers were then washed with brine, dried over Na2SO4, and concentrated. Purification by flash column chromatography (0–100% EtOAc in hexanes) gave 2-chloro-5-hydroxy-4-iodobenzaldehyde (3.50 g, 12.4 mmol, 48%). 1H NMR (400 MHz, d6-DMSO) δ ppm 11.1 (s, 1H), 10.2 (s, 1H), 7.98 (s, 1H), 7.35 (s, 1H).

[0110] Step 2: Preparation of 5-chloro-2,2-difluoro-1,3-benzoxathiol-6-carbaldehyde Under a nitrogen atmosphere, potassium fluoride (0.069 g, 1.22 mmol) and [(bpy)CuSCF] (0.469 g, 1.44 mmol) were added to a solution of 2-chloro-5-hydroxy-4-iodo-benzaldehyde (0.333 g, 1.18 mmol) in acetonitrile (10 mL). The reaction mixture was heated at 100 °C by microwave irradiation for 1 h, then diluted with water and extracted with EtOAc (×3). The combined organic layers were washed with brine, dried over NaSO, and concentrated. Purification by flash column chromatography (0–100% EtOAc in hexanes) gave 5-chloro-2,2-difluoro-1,3-benzoxathiol-6-carbaldehyde (0.265 g, 1.12 mmol, 95%). 1H NMR(400MHz,d6-DMSO)δ ppm 10.23(s,1H),8.00(s,1H),7.69(s,1H).

[0111] Step 3: Preparation of (5-chloro-2,2-difluoro-1,3-benzoxathiol-6-yl)methanol Sodium borohydride (0.040 g, 1.05 mmol) was added to a solution of 5-chloro-2,2-difluoro-1,3-benzoxathiol-6-carbaldehyde (0.250 g, 1.05 mmol) in MeOH (15 mL) at 0 °C under a nitrogen atmosphere. The reaction mixture was stirred at room temperature for 2 h, then diluted with saturated aqueous NH4Cl and extracted with dichloromethane (×2). The combined organic layers were washed with brine, dried over Na2SO4, and concentrated to give (5-chloro-2,2-difluoro-1,3-benzoxathiol-6-yl)methanol (0.120 g, 0.50 mmol, 48%). 1H NMR (400 MHz, d6-DMSO) δ ppm 7.55 (s, 1H), 7.35 (s, 1H), 5.58 (t, 1H), 5.53 (d, 2H).

[0112] Step 4: Preparation of 6-(bromomethyl)-5-chloro-2,2-difluoro-1,3-benzoxathiol Phosphorus tribromide (2.88 g, 1 mL, 10.6 mmol) was added to a solution of (5-chloro-2,2-difluoro-1,3-benzoxathiol-6-yl)methanol (0.20 g, 0.84 mmol) and DCM (30 mL) at 0 °C under a nitrogen atmosphere. The reaction mixture was stirred at room temperature for 2 h, then diluted with water and extracted with dichloromethane (×2). The combined organic layers were washed with brine, dried over Na SO , and concentrated to give 6-(bromomethyl)-5-chloro-2,2-difluoro-1,3-benzoxathiol (0.150 g, 0.50 mmol, 60%). H NMR (400 MHz, d6-DMSO) δ ppm 7.85 (s, 1H), 7.65 (s, 1H), 4.72 (s, 2H).

[0113] Step 5: Preparation of 2-[(5-chloro-2,2-difluoro-1,3-benzoxathiol-6-yl)methyl]-4,4-dimethyl-isoxazolidin-3-one Potassium carbonate (0.172 g, 1.24 mmol) was added to a solution of 6-(bromomethyl)-5-chloro-2,2-difluoro-1,3-benzoxathiol (0.250 g, 0.82 mmol) and 4,4-dimethylisoxazolidin-3-one (0.115 g, 0.99 mmol) in tetrahydrofuran (20 mL). The reaction mixture was stirred at 60 °C for 3 hours, then diluted with water and extracted with dichloromethane. The organic portion was washed with brine, dried over Na SO , and concentrated. Purification by reverse-phase flash column chromatography gave 2-[(5-chloro-2,2-difluoro-1,3-benzoxathiol-6-yl)methyl]-4,4-dimethyl-isoxazolidin-3-one (0.060 g, 0.18 mmol, 21%). 1H-NMR(400MHz,d6-DMSO)δ ppm 7.83(s,1H),7.32(s,1H),4.71(s,2H),4.06(s,2H),1.13(s,6H).

[0114] Example P9: Preparation of compound 1.032 Step 1: Preparation of 6-chloro-2,2-difluoro-1,3-benzodioxole-5-carbaldehyde A solution of (2,2-difluoro-1,3-benzodioxol-5-yl)methanol (0.99 g, 5.3 mmol) and N-chlorosuccinimide (1.7 g, 13 mmol) in acetonitrile (5 mL) was stirred overnight at room temperature. The reaction mixture was concentrated onto silica gel and purified by flash column chromatography (0 to 50% EtOAc in isohexane) to give 6-chloro-2,2-difluoro-1,3-benzodioxole-5-carbaldehyde (0.380 g, 1.72 mmol, 33%). 1H NMR (400 MHz, CDCl3) δ ppm 10.31 (s, 1H), 7.62 (s, 1H), 7.19 (s, 1H).

[0115] Step 2: Preparation of 6-chloro-2,2-difluoro-1,3-benzodioxole-5-carbaldehyde oxime Pyridine (0.065 mL, 0.80 mmol) and hydroxylamine hydrochloride (0.057 g, 0.82 mmol) were added to a solution of 6-chloro-2,2-difluoro-1,3-benzodioxole-5-carbaldehyde (0.160 g, 0.73 mmol) in ethanol (5 mL), and the mixture was heated to reflux for 4 hours. The reaction mixture was concentrated, then diluted with dichloromethane and washed with 1 M hydrochloric acid, water, and brine. The organic portion was dried over MgSO and concentrated to give 6-chloro-2,2-difluoro-1,3-benzodioxole-5-carbaldehyde oxime (0.150 g, 0.64 mmol, 88%). H NMR (400 MHz, CDCl) δ ppm 8.50 (s, 1H), 7.58 (s, 1H), 7.10 (s, 1H).

[0116] Step 3: Preparation of N-[(6-chloro-2,2-difluoro-1,3-benzodioxol-5-yl)methyl]hydroxylamine A solution of sodium cyanoborohydride (0.801 g, 12.7 mmol) in methanol (7 mL) and 4 M hydrochloric acid in dioxane (3.19 mL, 12.7 mmol) were added dropwise over 15 min to a stirred solution of 6-chloro-2,2-difluoro-1,3-benzodioxole-5-carbaldehyde oxime (2.31 g, 9.81 mmol) and a trace of methyl orange in methanol (50 mL) at room temperature. During the addition, care was taken to maintain the reaction mixture at 19-27 °C and the pH below 3. The reaction mixture was stirred at room temperature for 2 h, during which time the reaction mixture was kept acidic by adding small amounts of 4 M hydrochloric acid in dioxane. The reaction mixture was concentrated, and the resulting residue was washed with diethyl ether. The residue was then diluted with dichloromethane and water, and the aqueous phase was adjusted to pH 9 by adding aqueous potassium carbonate. The layers were separated, and the aqueous phase was extracted with an additional portion of dichloromethane. The combined organic portions were washed with brine (×2), dried over MgSO4, and concentrated to give N-[(6-chloro-2,2-difluoro-1,3-benzodioxol-5-yl)methyl]hydroxylamine (2.30 g, 9.68 mmol, 99%). 1H NMR (400 MHz, CDCl3) δ ppm 7.16 (s, 1H), 7.12 (s, 1H), 4.12 (s, 2H).

[0117] Step 4: Preparation of 3,3-dichloro-N-[(6-chloro-2,2-difluoro-1,3-benzodioxol-5-yl)methyl]-N-hydroxy-2,2-dimethyl-propanamide Chloro(trimethyl)silane (0.46 g, 4.2 mmol) was added dropwise to a solution of N-[(6-chloro-2,2-difluoro-1,3-benzodioxol-5-yl)methyl]hydroxylamine (1.0 g, 4.2 mmol) and pyridine (1.2 mL, 15 mmol) in dichloromethane (20 mL) at −10° C. under a nitrogen atmosphere. The reaction was stirred at −10° C. for 30 minutes, and then a solution of 3,3-dichloro-2,2-dimethyl-propanoyl chloride (0.80 g, 4.2 mmol) in dichloromethane (20 mL) was added dropwise over 10 minutes at 0° C. The reaction mixture was stirred at room temperature for 18 hours, then diluted with dichloromethane, water, brine, and washed with a 1:1 mixture of brine and 2 M hydrochloric acid (×2). The organic portion was washed with a final portion of brine, then dried over MgSO and concentrated. Purification by flash column chromatography (0–10% EtOAc in isohexane) gave 3,3-dichloro-N-[(6-chloro-2,2-difluoro-1,3-benzodioxol-5-yl)methyl]-N-hydroxy-2,2-dimethyl-propanamide (1.21 g, 3.11 mmol, 74%). 1H NMR (400 MHz, CDCl3) δ ppm 7.15 (s, 2H), 6.66 (s, 1H), 6.49 (br s, 1H), 4.95 (s, 2H), 1.49 (s, 6H).

[0118] Step 5: Preparation of 5-chloro-2-[(6-chloro-2,2-difluoro-1,3-benzodioxol-5-yl)methyl]-4,4-dimethyl-isoxazolidin-3-one Potassium carbonate (0.862 g, 6.24 mmol) was added to a solution of 3,3-dichloro-N-[(6-chloro-2,2-difluoro-1,3-benzodioxol-5-yl)methyl]-N-hydroxy-2,2-dimethyl-propanamide (1.22 g, 3.12 mmol) in acetone (14 mL). The reaction mixture was stirred at room temperature for 3 hours, then diluted with dichloromethane and washed with water. The organic portion was concentrated to give 5-chloro-2-[(6-chloro-2,2-difluoro-1,3-benzodioxol-5-yl)methyl]-4,4-dimethyl-isoxazolidin-3-one (0.923 g, 2.61 mmol, 84%). 1H NMR(400MHz,CDCl3)δ ppm 7.19(s,1H),7.13(s,1H),6.07(s,1H),4.95(d,1H),4.81(d,1H),1.39(s,3H),1.38(s,3H).

[0119] Additional compounds of the invention, made in a manner similar to those described above in Examples P1-P9, are shown in Table 1 below.

[0120] [Table 1] JPEG2025525368000021.jpg246130 JPEG2025525368000022.jpg253131 JPEG2025525368000023.jpg248128 JPEG2025525368000024.jpg249131 JPEG2025525368000025.jpg145129

[0121] Biological Examples Exam B1 Seeds of the various test species: Amaranthus retoflexus (AMARE), Setaria faberi (SETFA), Echinochloa crus-galli (ECHCG), and Ipomoea hederacea (IPOHE) are sown in standard soil in pots. After 1 day of incubation (pre-germination) or 8 days of incubation (post-germination), the plants are sprayed under controlled conditions in a greenhouse (24 / 16°C, day / night; 14 hours of light; 65% humidity) with either i) a formulation of the technical active ingredient in an acetone / water (50:50) solution containing 0.5% Tween 20 (polyoxyethylene sorbitan monolaurate, CAS RN9005-64-5), or ii) an aqueous spray solution obtained by dissolving the technical active ingredient in a small amount of acetone and a special solvent and emulsifier mixture called IF50 (11.12% Emulsogen EL360™ + 44.44% N-methylpyrrolidone + 44.44% Dowanol DPM glycol ether), which is then diluted to the required concentration using 0.2% Genapol XO80 (CAS number 9043-30-5) in water as excipient). Unless otherwise stated, compounds are applied at 250 g / ha. Test plants are then grown in a greenhouse under controlled conditions (24 / 16°C, day / night; 14 h light; 65% humidity) and watered twice daily. After 13 days for pre- and post-emergence, the tests are evaluated for the percentage of damage caused to the plants. Biological activity is shown in the table below on a 5-point scale (5 = 81-100%; 4 = 61-80%; 3 = 41-60%; 2 = 21-40%; 1 = 0-20%).

[0122] [Table 2]

[0123] [Table 3]

[0124] Exam B2 Seeds of the different test species: Leptochloa chinesis (LEFCH), Echinochloa crus-galli (ECHCG) and Cyperus esculentus (CYPES) are sown in standard soil in pots. After 1 day of incubation (pre-germination) or 13 days of incubation (post-germination), the plants are sprayed with an aqueous spray solution obtained by dissolving the technical active ingredient in a small amount of acetone and a special solvent and emulsifier mixture called IF50 (11.12% Emulsogen EL360™ + 44.44% N-methylpyrrolidone + 44.44% Dowanol DPM glycol ether), which is then diluted to the required concentration using 0.2% Genapol XO80 (CAS number 9043-30-5) in water as an excipient, under controlled conditions in a greenhouse (30 / 20 ° C, day / night; 18 hours of light; 75% humidity). The compound is applied at 500 g / ha. The test plants are then grown in a greenhouse under controlled conditions in a greenhouse (30 / 20 ° C, day / night; 18 hours of light; 75% humidity) and watered twice a day. After 13 days for pre- and post-emergence, the tests are evaluated for the percentage of damage caused to the plants. The biological activity is shown in the table below on a 5-point scale (5 = 81-100%; 4 = 61-80%; 3 = 41-60%; 2 = 21-40%; 1 = 0-20%).

[0125] [Table 4]

[0126] [Table 5]

[0127] Test B3: Comparative test (pre-emergence) Seeds of the test species (Echinochloa crus-galli; ECHCG) were sown in standard soil in pots. After one day of incubation, the plants were sprayed under controlled conditions in a greenhouse (24 / 16°C, day / night; 14 hours of light; 65% humidity) with 0.6 ml of an aqueous spray solution resulting from a combination of the technical active ingredients in a combined solution containing 45 ml of 10.6% Emulsogen EL (registration number 61791-12-6), 42.2% N-methylpyrrolidone, 42.2% dipropylene glycol monomethyl ether (CAS RN34590-94-8) and 0.2% X-77 (CAS RN11097-66-8).

[0128] The test plants were then grown under controlled conditions in a greenhouse (24 / 16°C, day / night; 14 hours of light; 65% humidity) and watered twice daily. After 14 days, the test was evaluated (100 = complete damage to the plant; 0 = no damage to the plant).

[0129] [Table 6]

[0130] C1 is a known compound disclosed in U.S. Pat. No. 4,405,357. As can be seen, R 5 / R 6 The introduction of substituents results in unexpected improvements in observed weed control.

Claims

1. Formula (I) 【Chemical 1】 (In the formula, A 1 is CR 1 R 2 or C(O); A 2 is CR 7 R 8 , C(O), O, S(O) p and N(R 11 ) selected from the group consisting of; A 3 is CR 9 R 10 , C(O), O, S(O) p and N(R 11 ) selected from the group consisting of; X 1 is O or S; R 1 is hydrogen, halogen, HO-, C 1 ~C 6 Alkoxy, C 1 ~C 6 Alkoxy-C 1 ~C 6 Alkoxy-, C 1 ~C 3 Alkyl-C(O)O-, HOC(O)C 1 ~C 6 Alkoxy-, C 1 ~C 6 Alkoxy-C(O)-C 1 ~C 6 Alkoxy-, C 1 ~C 3 Alkyl-S(O) p - and C 1 ~C 3 Alkyl-S(O) p C 1 ~C 6 alkoxy-; R 2 is hydrogen; R 3 is C 1 ~C 3 is alkyl; R 4 is C 1 ~C 3 is alkyl; R 5 is hydrogen, halogen, C 1 ~C 6 Alkyl, C 1 ~C 6 Haloalkyl, C 3 ~C 6 Cycloalkyl and C 1 ~C 6 alkoxy-; R 6 is hydrogen, halogen, C 1 ~C 6 Alkyl, C 1 ~C 6 Haloalkyl, C 3 ~C 6 Cycloalkyl and C 1 ~C 6 alkoxy-; 5 and R 6 are not both hydrogen; or R 5 and R 6 together represent ═O or —(CH 2 ) n - and; R 7 is hydrogen, halogen, C 1 ~C 6 Alkyl, C 1 ~C 6 Haloalkyl, C 3 ~C 6 Cycloalkyl and C 1 ~C 6 alkoxy-; R 8 is hydrogen, halogen, C 1 ~C 6 Alkyl, C 1 ~C 6 Haloalkyl, C 3 ~C 6 Cycloalkyl and C 1 ~C 6 alkoxy-; Or R 7 and R 8 together, -(CH 2 ) n - and; R 9 is hydrogen, halogen, C 1 ~C 6 Alkyl, C 1 ~C 6 Haloalkyl, C 3 ~C 6 Cycloalkyl and C 1 ~C 6 alkoxy-; R 10 is hydrogen, halogen, C 1 ~C 6 Alkyl, C 1 ~C 6 Haloalkyl, C 3 ~C 6 Cycloalkyl and C 1 ~C 6 alkoxy- or selected from the group consisting of; Or R 9 and R 10 together, -(CH 2 ) n - and; R 11 is hydrogen or C 1 ~C 3 is alkyl; n is independently 2, 3, 4, 5, or 6; p is independently 0, 1 or 2. Compound.

2. X 1 is O.

3. R 3 and R 4 3. A compound of formula (I) according to claim 1 or claim 2, wherein is methyl.

4. A 1 But, CR 1 R 2 and R 1 A compound of formula (I) according to any one of claims 1 to 3, wherein is hydrogen.

5. A 1 But, CR 1 R 2 and R 1 But C 1 ~C 6 A compound of formula (I) according to any one of claims 1 to 3, which is alkoxy.

6. A 1 A compound of formula (I) according to any one of claims 1 to 3, wherein is C(O).

7. A 2 and A 3 The compound according to any one of claims 1 to 6, wherein is O.

8. R 5 and R 6 The compound of any one of claims 1 to 7, wherein is independently selected from the group consisting of hydrogen, methyl and fluoro.

9. R 5 and R 6 and are both methyl.

10. R 5 and R 6 The compound of any one of claims 1 to 8, wherein both are fluoro.

11. A herbicidal composition comprising a compound of formula (I) according to any one of claims 1 to 10 and agriculturally acceptable formulation adjuvants.

12. 12. The herbicidal composition of claim 11 further comprising at least one additional pesticide.

13. 13. The herbicidal composition of claim 12, wherein the additional pesticide is a herbicide or a herbicidal safener.

14. 14. A method of controlling weeds in a locus, the method comprising applying to the locus a weed-controlling amount of a composition according to any one of claims 11 to 13.

15. Use of a compound of formula (I) as defined in any one of claims 1 to 10 as a herbicide.

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