Herbicidal compound

Abstract

The present invention relates to a compound of formula (I) JPEG2025522305000034.jpg4772(wherein A 1 、A 2 、A 3 、X 1 、R 2 、R 3 、R 4 、R 5 、R 6 、R 7 and R 8 are as defined herein) or an agriculturally acceptable salt of said compound. The present invention further relates to a herbicidal composition comprising a compound of formula (I) and to the use of a compound of formula (I) for controlling weeds in crops of particularly useful plants.

Description

Technical Field

[0001] The present invention relates to a herbicidal compound, a process for its preparation, a herbicidal composition containing this herbicidal compound, and its use for controlling weeds in crops of particularly useful plants or for inhibiting the growth of plants.

Summary of the Invention

Means for Solving the Problems

[0002] Herbicidal 3-isoxazolidinones are known from US Patent No. 4,405,357. Herbicidal isoxazolidine-3,5-diones are known from US Patent No. 4,302,238. The present invention relates to novel 3-isoxazolidinone and isoxazolidine-3,5-dione compounds. Accordingly, according to the present invention, a compound of formula (I):

Chemical Formula

Mode for Carrying Out 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, such as 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 and 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 isopropoxy-.

[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 including methoxy-.

[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, X 1 is O, and a compound of formula (I) is provided.

[0017] In another embodiment of the present invention, R 3 and R 4 are methyl, and a compound of formula (I) is provided.

[0018] In another embodiment of the present invention, A 1 is CR 1 R 2 and R 1 is hydrogen, and a compound of formula (I) is provided. Therefore, in a preferred embodiment of the present invention, a compound of formula 1a:

Chemical formula

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

[0020] In another embodiment of the present invention, A 1 Compounds of formula (I) in which is C(O) are provided. Thus, in a preferred embodiment of the present invention, a compound of formula 1b:

Chemical formula

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

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

[0023] In another embodiment of the present invention, (i) A 2 and A 3 are O; (ii) A 2 is NH, and A 3 is O; (iii) A 2 is O, and A 3 is NH; (iv) A 2 and A 3 are 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 is O, and compounds of formula (I), formula (Ia), or formula (Ib) are provided.

[0024] In a preferred embodiment of the present invention, A 2 and A 3 There are provided compounds of formula (I), formula (Ia) or formula (Ib) which are O.

[0025] In another embodiment of the present invention, R 5 , R 6 , R 7 and R 8 There are provided compounds of formula (I), formula (Ia) or formula (Ib) which are independently selected from the group consisting of hydrogen, C1-C6 alkyl and C1-C6 alkyl. In a more preferred embodiment, R 5 , R 6 , R 7 and R 8 are independently selected from the group consisting of hydrogen, methyl and fluoro. In another embodiment, R 5 and R 6 are halogen, preferably fluoro, and R 7 and R 8 are hydrogen.

[0026] The compounds of formula (I) may contain an asymmetric center, may exist as a single enantiomer, as a pair of enantiomers in any ratio, or, when two or more asymmetric centers are present, may contain all possible ratios of diastereoisomers. Typically, one of the enantiomers has high biological activity compared to other possibilities.

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

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

[0029] The herbicide composition usually contains 0.1 to 99% by weight, particularly 0.1 to 95% by weight, of the compound of formula I and 1 to 99.9% by weight of a formulation aid, and the formulation aid preferably contains 0 to 25% by weight of a surface-active substance.

[0030] The composition can be selected from several types of formulations. These include emulsifiable concentrates (EC), suspension concentrates (SC), suspoemulsions (SE), capsule suspensions (CS), water-dispersible granules (WG), emulsifiable granules (EG), oil-in-water emulsions (EO), water-in-oil (EW) emulsions, microemulsions (ME), oily suspensions (OD), oil-miscible flowables (OF), oil-miscible liquids (OL), soluble concentrates (SL), ultra-low volume suspensions (SU), ultra-low volume liquids (UL), industrial concentrates (TK), dispersible concentrates (DC), soluble powders (SP), wettable powders (WP), and soluble granules (SG). The type of formulation selected in any case will depend on the specific intended purpose 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), and optionally with one or more wetting agents, one or more dispersing agents or a mixture of said agents to improve the water dispersibility / solubility. The mixture is then milled 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 diluents 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 milled 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) and one or more powdered solid diluents or carriers, or by absorbing a compound of formula (I) (or a solution thereof in a suitable vehicle) into a porous granular material (such as pumice, attapulgite clay, fuller's earth, kieselguhr, diatomaceous earth or ground corn cob) from pre-formed blank granules, or by adsorbing a compound of formula (I) (or a solution thereof in a suitable vehicle) onto a hard core material (such as sand, silicate, carbonate, sulfate or phosphate minerals) and drying if necessary. Agents commonly used to assist absorption or adsorption include solvents (such as aliphatic and aromatic petroleum solvents, alcohols, ethers, ketones and esters) and fixing agents (such as polyvinyl acetate, polyvinyl alcohol, dextrin, carbohydrates and vegetable oils). One or more other additives can also be included in the granules (such as emulsifiers, wetting agents or dispersing agents).

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

[0035] The emulsifiable concentrate (EC) or the oil-in-water emulsion (EW) can be prepared by dissolving the 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 EC 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 (such as dimethylamides of C8-C 10 fatty acid dimethylamides) and chlorinated hydrocarbons. The EC product can result in an emulsion that naturally emulsifies upon addition of water and has sufficient stability for spray application with a suitable implement.

[0036] The preparation of EW involves obtaining the compound of formula (I) as a liquid (which can typically be melted at a moderate temperature below 70 °C if it is not liquid at room temperature) 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 EW include vegetable oils, chlorinated hydrocarbons (such as chlorobenzene), aromatic solvents (such as alkylbenzenes or alkylnaphthalenes), and other suitable organic solvents with low solubility in water.

[0037] Microemulsions (MEs) can be prepared by mixing a blend of one or more solvents and one or more SAAs with water to yield a thermodynamically stable isotropic liquid formulation spontaneously. The compounds of formula (I) are initially present in water or in the solvent / SAA blend. Suitable solvents for use in ME include those described above herein for use in EC or EW. MEs can be of the water-in-oil or oil-in-water type (which type is present can be determined by conductivity measurements) and can be suitable for the mixing of water-soluble and oil-soluble pesticidal agents in the same formulation. MEs are suitable as such or for dilution with water to form conventional water-in-oil emulsions.

[0038] Suspension concentrates (SCs) can contain an aqueous or non-aqueous suspension of fine insoluble solid particles of the compounds of formula (I). SCs can be prepared by subjecting the solid compounds of formula (I) in a suitable medium, optionally together with one or more dispersants, to a ball mill or bead mill to produce a fine particle suspension of the compounds. 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, the compounds of formula (I) can be subjected to a dry mill and added to water containing the agents described above hereinbefore to yield the desired final product.

[0039] Aerosol formulations contain the compounds of formula (I) and a suitable propellant (e.g., n-butane). The compounds of formula (I) can also be dissolved or dispersed in a suitable medium (e.g., water, or a hydratable liquid such as n-propanol) to yield a composition for use with a non-pressurized hand-operated spray pump.

[0040] The capsule suspension (CS) can be prepared in the same manner as the preparation of the EW formulation, but an aqueous dispersion of oil droplets is obtained, each of the oil droplets being encapsulated by a polymeric shell and prepared with an additional polymerization stage such that it contains the compound of formula (I) and optionally a carrier or diluent therefor. The polymeric shell can be produced by an interfacial polycondensation reaction or a coacervation method. This composition can provide a controlled release of the compound of formula (I), and they can be used for seed treatment. The compound of formula (I) can also be incorporated into a biodegradable polymer matrix to provide a controlled and sustained 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 the surface; the rain resistance on the treated surface; or the uptake or mobility. Such additives include surfactants (SAA), oil-based spray additives such as certain mineral oils or natural vegetable oils (such as soybean and rapeseed oils), modified vegetable oils such as methylated rapeseed oil (MRSO), and blends of these with other bio-enhancing adjuvants (formulation components that can assist or modify the action of the compound of formula (I)).

[0042] The wetting agent, dispersing agent, and emulsifying agent may be cationic, anionic, amphoteric, or nonionic SAA.

[0043] Suitable cationic SAA include quaternary ammonium compounds (such as 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 sulfonic acid, and a mixture 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 (reaction of one or more aliphatic alcohols with phosphoric acid (mainly mono-esters) or phosphorus pentoxide (mainly di-esters), e.g., the product of the reaction of lauryl alcohol with pyrophosphoric acid; furthermore, these products may be ethoxylated), sulfosuccinates, paraffin or olefin sulfonates, taurates, lignosulfonates, and phosphates / sulfates of tristyrylphenol.

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

[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 partial esters with ethylene oxide; block polymers (including ethylene oxide and propylene oxide); alkanolamides; simple esters (such as fatty acid polyethylene glycol esters); amine oxides (such as lauryldimethylamine oxide); lecithin and sorbitan and their esters, alkyl polyglycosides, and tristyrylphenol.

[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. Examples of such additional herbicides or plant growth regulators include acetochlor, acifluorfen (including acifluorfen-sodium), acronifen, ametryn, amicarbazone, aminopyralid, aminotriazole, atrazine, beflubutamid-M, bentriazone, bensulfuron (including bensulfuron-methyl), bentazone, bicyclopyrone, bilanafos, bipyrazone, bispyribac-sodium, bicyclopyrazone, bromacil, bromoxynil, butachlor, butaphenacil, carfentrazone (including carfentrazone-ethyl), chloransulam (including chloransulam-methyl), chlorimuron (including chlorimuron-ethyl), chlorotoluron, chlorosulfuron, cinmethylin, clofentezine, clethodim, clodinafop (including clodinafop-propargyl), chlormazone, clopyralid, cyclopyranil, cyclopyrimorate, cyclosulfamuron, cyhalofop (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, dichloroprop, diglycolamine, dimethylamine, dimethylammonium, potassium and sodium salts), dichlorsulam, diflufenican, diflufenzoppil, dimethachlor, dimethenamid-P, dioxopyrimethenone, diquat dibromide, diuron, epirifluorfen, ethalfluralin, ethofumesate, fenoxaprop (including fenoxaprop-P-ethyl), fenoxasulfuron, fenpyrazone, fenquinotrione, fentrazamide, flazasulfuron, florasulam, flupyradifurone (including flupyradifurone-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), halauxifen (including halauxifen - methyl), haloxyfop (including haloxyfop - methyl), hexazinone, hydantocidin, imazamox (including R - imazamox), imazapic, imazapyr, imazethapyr, indaziflam, iodosulfuron (including iodosulfuron - methyl - sodium), iofensulfuron (including iofensulfuron - sodium), ioxynil, isoproturon, isoxaflutole, rankotriol, MCPA, MCPB, mecoprop - P, mesosulfuron (including mesosulfuron - methyl), mesotrione, metazachlor, metazoxolon, metazachlor, methiozolin, metolachlor, metosulam, metribuzin, methosulfuron, napropamide,nicosulfuron, norflurazon, oxadiazon, oxasulfuron, oxyfluorfen, paraquat dichloride, pendimethalin, penoxsulam, phenmedipham, picloram, pinoxaden, pretilachlor, primisulfuron - methyl, prometryn, propanil, propaquizafop, propyrisulfuron, propyzamide, prosulfocarb, prosulfuron, pyraclonil, pyraflufen (including pyraflufen - ethyl), pyrazosulfuron - ethyl, pyridate, pyriftalid, pyrimisulfan, pyroxasulfone, pyroxysulam, cinchonazine, cinchonine, quizalofop (including quizalofop - P - ethyl and quizalofop - P - tefuryl), rimsulfuron, sulfentrazone, sulfosulfuron, tebuthiuron, tefuryltrione, tembotrione, terbuthylazine, terbutryn, tetflupyrolimet, thienecarbazone, thifensulfuron, thiafenox, topramezone, tralkoxydim, triafamone, triallate, triasulfuron, tribenuron (including tribenuron - methyl), triclopyr, trifloxysulfuron (including trifloxysulfuron - sodium), triflumizole, trifluralin, triflusulfuron, tripyrasulfone,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-methylimidazolidin-2-one, 4-amino-3-chloro-5-fluoro-6-(7-fluoro-1H-indol-6-yl)pyridine-2-carboxylic acid (including its agriculturally acceptable esters, for example, methyl 4-amino-3-chloro-5-fluoro-6-(7-fluoro-1H-indol-6-yl)pyridine-2-carboxylate, prop-2-ynyl 4-amino-3-chloro-5-fluoro-6-(7-fluoro-1H-indol-6-yl)pyridine-2-carboxylate and cyanomethyl 4-amino-3-chloro-5-fluoro-6-(7-fluoro-1H-indol-6-yl)pyridine-2-carboxylate), 3-ethylsulfanyl-N-(1,3,4-oxadiazol-2-yl)-5-(trifluoromethyl)-[1,2,4]triazolo[4,3-a]pyridine-8-carboxamide, 3-(isopropylsulfanylmethyl)-N-(5-methyl-1,3,4-oxadiazol-2-yl)-5-(trifluoromethyl)-[1,2,4]triazolo[4,3-a]pyridine-8-carboxamide,3-(Isopropylsulfonyl-methyl)-N-(5-methyl-1,3,4-oxadiazol-2-yl)-5-(trifluoromethyl)-[1,2,4]triazolo[4,3-a]-pyridine-8-carboxamide, 3-(ethylsulfonylmethyl)-N-(5-methyl-1,3,4-oxadiazol-2-yl)-5-(trifluoromethyl)-[1,2,4]triazolo[4,3-a]pyridine-8-carboxamide, ethyl 2-[[3-[[3-chloro-5-fluoro-6-[3-methyl-2,6-dioxo-4-(trifluoromethyl)pyrimidin-1-yl]-2-pyridyl]oxy]acetate, 6-chloro-4-(2,7-dimethyl-1-naphthyl)-5-hydroxy-2-methyl-pyridazin-3-one, 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-fluoro-3-methoxyphenyl)-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. 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 mixing partner of the compound of formula (I) may also be in the form of an ester or a salt, for example, as described in The Pesticide Manual, Sixteenth Edition, British Crop Protection Council, 2012.

[0050] The compound of formula (I) can also be used in a mixture with other pesticides such as fungicides, nematicides or insecticides, examples of which are shown 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 can be advantageously used in the above formulations (in which case, the "active ingredient" relates to each mixture of the compound of formula (I) and the mixing partner).

[0053] The compounds or mixtures of the present invention can also be used in combination with one or more herbicide phytotoxicity reducing agents. Examples of such phytotoxicity reducing agents include benoxacor, cloquintocet (including cloquintocet - mexyl), cyprosulfamide, dichlormid, fenchlorazole (including fenchlorazole - ethyl), fenclorim, flurioxypyr, furilazole, isoxadifen (including isoxadifen - ethyl), mefenpyr (including mefenpyr - diethyl), metcamifene, and oxabetrinil.

[0054] Particularly preferred is a mixture of the compound of formula (I) with cyprosulfamide, isoxadifen - ethyl, cloquintocet - mexyl and / or metcamifene.

[0055] The phytotoxicity reducing agent of the compound of formula (I) can also be in the form of an ester or a salt, for example, as described in The Pesticide Manual, 16 th Edition (BCPC), 2012. The 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 the compound of formula (I) to the phytotoxicity reducing agent is from 100:1 to 1:10, particularly from 20:1 to 1:1.

[0057] The present invention further provides a method for controlling weeds at a location, which comprises applying to said location a composition containing an amount of a compound of formula (I) effective for controlling weeds. Further, the present invention may further provide a method for selectively controlling weeds at a location containing crop plants and weeds, which comprises applying to said location a composition of the present invention in an amount effective for controlling weeds. "Control" means killing, reducing or delaying growth, or preventing or reducing germination. It is noted that the compounds of the present invention exhibit far improved selectivity as compared to known structurally similar compounds. Generally, the plants to be controlled are undesirable plants (weeds). "Location" means an area where plants are growing or are to grow. Application may be made to the location before and / or after emergence of the crop plants. A plurality of crop plants may be essentially resistant to the herbicidal effect of the compound of formula (I). Preferred crop plants include maize, wheat, barley, soybean and rice.

[0058] The application rate of the compound of formula I may vary within wide limits and depends on the nature of the soil, the method of application (pre-emergence or post-emergence; seed dressing; application to furrows; application to non-cultivated land, etc.), the crop plants, the weeds to be controlled, the prevailing climatic conditions, and other factors depending on the method of application, the time of application, and the target crop. The compounds of formula I of the present invention are usually applied in an amount of 10 - 2500 g / ha, particularly 25 - 1000 g / ha, and more particularly 25 - 250 g / ha.

[0059] Application is generally effected by spraying the composition with a large-area sprayer mounted on a tractor, but other methods such as dusting (in the case of powders), dripping or irrigation are also possible.

[0060] Crop plants should be understood to include crop plants that have been given tolerance to another herbicide or herbicide classification (e.g., ALS-, GS-, EPSPS-, PPO-, HPPD-, PDS-, -SDPS and ACCase-inhibitors) by conventional breeding methods or genetic engineering. Examples of crops given tolerance to imidazolinones such as imazamox by conventional breeding methods are Clearfield® summer rape (canola). Examples of crops given tolerance to herbicides by recombinant DNA methods include, for example, glyphosate- and glufosinate-tolerant maize varieties marketed under the trade names RoundupReady® and LibertyLink®.

[0061] Crop plants should also be understood as those that have been given resistance to harmful insects by genetic engineering methods, such as Bt corn (resistant to the European corn borer), Bt cotton (resistant to the pink bollworm), 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 genetically modified 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®. Both the plant crop and its seed material can be resistant to herbicides and, at the same time, resistant to feeding by insects (so-called "stacked" genetically modified organisms). For example, the seeds can be glyphosate-resistant and at the same time capable of expressing an insecticidal Cry3 protein.

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

[0063] The composition can be used to control unwanted plants (collectively referred to as "weeds"). The weeds to be controlled can be, for example, monocotyledonous plant species such as Agrostis, Alopecurus, Avena, Brachiaria, Bromus, Cenchrus, Cyperus, Digitaria, Echinochloa, Eleusine, Lolium, Monochoria, Rottboellia, Sagittaria, Scirpus, Setaria, and Sorghum, and also dicotyledonous plant species such as Abutilon, Amaranthus, Ambrosia, Chenopodium, Chrysanthemum, Conyza, Galium, Ipomoea, Nasturtium, Sida, Sinapis, Solanum, Stellaria, Veronica, Viola, and Xanthium, etc.

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

[0065] Process for the preparation of a compound of formula (I) A process for the preparation of a compound, for example a compound of formula (I) which may optionally be its agrochemically acceptable salt, is described herein and forms a further aspect of the invention.

[0066] Scheme 1 A 1 is -C(R 1 )(R 2 )-, and, X 1In an embodiment where O is O, the compound of formula (1) can be prepared from the compound of formula (2) (wherein LG represents a suitable leaving group such as Br or Cl) and the compound of formula (3).

Chemical formula

[0067] The compound of formula (2) is treated with the compound of formula (3) and a carbonate base such as potassium carbonate in a suitable solvent such as acetone.

[0068] Scheme 2 The compound of formula (2) can be prepared from the benzyl alcohol of formula (4).

Chemical formula

[0069] For example, when LG is Br, the benzyl alcohol of formula (4) is treated with triphenylphosphine and carbon tetrabromide or phosphorus tribromide in a suitable solvent such as acetonitrile or dichloromethane.

[0070] Scheme 3 The compound of formula (4) can be prepared from the benzyl alcohol of formula (5).

Chemical formula

[0071] The compound of formula (5) is treated with a chlorinating reagent such as N-chlorosuccinimide in a suitable solvent such as acetonitrile.

[0072] Scheme 4 The benzyl alcohol of formula (5) can be prepared from the aldehyde of formula (6).

Chemical formula

[0073] The compound of formula (6) is treated with a reducing agent, such as sodium borohydride, in a suitable solvent such as water.

[0074] Scheme 5 The compound of formula (6) may be commercially available. Alternatively, these can be prepared synthetically. The synthetic route will vary depending on the nature of A 2 、A 3 、R 5 、R 6 、R 7 and R 8 For example, when A 2 and A 3 are O, the compound of formula (6) can be prepared from 3,4-dihydroxybenzaldehyde (7).

Chemical formula

[0075] 3,4-Dihydroxybenzaldehyde (7) is treated with a dibromide of formula (8) and a carbonate base, such as potassium carbonate, in a suitable solvent such as acetonitrile.

[0076] Scheme 6 In an alternative approach, the compound of formula (4) can be prepared from the compound of formula (9).

Chemical formula

[0077] The compound of formula (9) is treated with a reducing agent, such as sodium borohydride, in a suitable solvent such as water.

[0078] Scheme 7 The synthetic route used to obtain the compound of formula (9) will vary depending on the nature of A 2 、A 3 、R 5 、R 6 、R 7 and R 8 For example, when A2 and A 3 When O, the compound of formula (9) can be prepared from 2-chloro-4,5-dihydroxybenzaldehyde (10).

Chemical formula

[0079] 2-Chloro-4,5-dihydroxybenzaldehyde (10) is treated with the dibromide of formula (8) and a carbonate base, such as potassium carbonate, in a suitable solvent such as acetonitrile.

[0080] Scheme 8 Alternatively, the compound of formula (9) can be prepared from the aldehyde of formula (6).

Chemical formula

[0081] The compound of formula (6) is treated with a chlorinating reagent such as N-chlorosuccinimide in a suitable solvent such as 1,2-dichloroethane and, optionally, in the presence of a suitable combination of catalyst / ligand / additive. Suitable combinations of catalyst / ligand can include palladium(II) acetate and 2-aminobenzoic acid. Suitable additives can include trifluoroacetic acid and silver trifluoroacetate.

[0082] Scheme 9 In a further alternative approach, the compound of formula (1) (wherein A 1 is -C(R 1 )(R 2 ), X 1 is O, and also, A 2 and A 3 is O) can be prepared from the compound of formula (11).

Chemical formula

[0083] The synthetic processes and reaction conditions used to obtain the compound of formula (1) from the compound of formula (11) will vary depending on the nature of R 5 , R 6 , R 7 and R 8 .

[0084] Scheme 10 For example, when R 5 and R 6 are hydrogen, and R 7 and R 8 are methyl, the compound of formula (1) can be prepared from the compound of formula (12).

Chemical formula

[0085] The compound of formula (12) is treated with an acid, such as formic acid, undiluted or in a suitable solvent such as N-methyl-2-pyrrolidone.

[0086] Scheme 11 The compound of formula (12) can be prepared from the compound of formula (13).

Chemical formula

[0087] The compound of formula (13) is treated with 3-chloro-2-methyl-1-propene (14) and a suitable base, such as potassium carbonate, in a suitable solvent such as acetonitrile.

[0088] Scheme 12 The compound of formula (13) can be prepared from 5-chloro-6-(chloromethyl)-1,3-benzodioxol-2-one (15).

Chemical formula

[0089] 5-Chloro-6-(chloromethyl)-1,3-benzodioxol-2-one (15) is treated with a compound of formula (3) and a suitable base, such as potassium carbonate, in a suitable solvent such as dimethylformamide.

[0090] Scheme 13 5-Chloro-6-(chloromethyl)-1,3-benzodioxol-2-one (15) can be prepared from commercially available (6-chloro-1,3-benzodioxol-5-yl)methanol (16).

Chemical formula

[0091] (6-Chloro-1,3-benzodioxol-5-yl)methanol (16) is treated with phosphorus pentachloride in a suitable solvent such as chlorobenzene.

[0092] Scheme 14 A 1 is -C(=O)-, and, X 1 is O, the compound of formula (1) can be prepared from the compound of formula (17).

Chemical formula

[0093] The compound of formula (17) is treated with 2,2-dimethylmalonyl chloride and a suitable base, such as pyridine, in a suitable solvent such as dichloromethane.

[0094] Scheme 15 The compound of formula (17) can be prepared from the compound of formula (2) (wherein LG represents a suitable leaving group such as Br or Cl).

Chemical formula

[0095] For example, when LG is Br, the compound of formula (2) is treated in a suitable solvent such as acetone with N,O-diboc hydroxylamine, a suitable base such as potassium carbonate, and optionally, a suitable catalyst such as tetrabutylammonium iodide to give the compound of formula (18). The compound of formula (18) is treated with a suitable acid such as hydrochloric acid in a suitable solvent such as dioxane.

[0096] Scheme 16 Some compounds of formula (3) may be commercially available. For example, the compound of formula (3) wherein R 3 and R 4 are methyl and R 1 and R 2 are hydrogen is commercially available (CAS number 81778-07-6). Alternatively, the compound of formula (3) can be prepared synthetically. For example, when R 1 is 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 is hydrogen, the compound of formula (3) can be prepared from 3,3-dichloro-2,2-dimethylpropanoic acid (19).

Chemical Structure

[0097] 3,3-Dichloro-2,2-dimethylpropanoic acid (19) is treated with a suitable chlorinating reagent such as thionyl chloride and the catalyst dimethylformamide to afford 3,3-dichloro-2,2-dimethylpropanoyl chloride (20). 3,3-Dichloro-2,2-dimethylpropanoyl chloride (20) is treated with a suitable hydroxylamine source such as hydroxylamine (50% in H2O) to afford 3,3-dichloro-2,2-dimethyl-propanehydroxamic acid (21). 3,3-Dichloro-2,2-dimethyl-propanehydroxamic acid (21) is treated with an alcohol and a suitable base such as 1,8-diazabicyclo(5.4.0)undec-7-ene to afford the compound of formula (3).

[0098] Scheme 17 The compound of formula (1) wherein X 1 is S can be prepared from the compound of formula (1) wherein X 1 is O.

Chemical formula

[0099] The compound of formula (1) wherein X 1 is O is treated with a suitable vulcanizing agent such as phosphorus pentasulfide in a suitable solvent such as toluene.

[0100] The following non-limiting examples provide specific synthetic methods for representative compounds of the present invention as referred to in Table 1 below.

Examples

[0101] Preparation Examples Example 1: Preparation of Compound 1.001 Step 1: Preparation of 2,2-difluoro-3H-1,4-benzodioxine-6-carbaldehyde Potassium carbonate (8.79 g, 86.9 mmol) was added to 3,4-dihydroxybenzaldehyde (3.00 g, 21.7 mmol) at RT in acetonitrile (45 mL). Then 1,2-dibromo-1,1-difluoro-ethane (17.0 g, 7.65 mL, 76.0 mmol) was added and the reaction was stirred at 90 °C for 18 h. Thereafter, a further portion of 1,2-dibromo-1,1-difluoro-ethane (17.0 g, 7.65 mL, 76.0 mmol) was added and the reaction was stirred for a further 24 h. The reaction was quenched with water and the product was extracted with ethyl acetate (3 times). The organic portions were combined, dried over MgSO4, filtered and concentrated under reduced pressure. The crude material was purified by flash column chromatography (0 - 20% ethyl acetate in cyclohexane). The product-containing fractions were combined and concentrated to give a 1:1 mixture of 2,2-difluoro-3H-1,4-benzodioxine-6-carbaldehyde (0.889 g, 4.44 mmol, 20%) and 3,3-difluoro-2H-1,4-benzodioxine-6-carbaldehyde (0.889 g, 4.44 mmol, 20%) as a pale orange oil. 1H NMR (400 MHz, CDCl3) δ ppm 9.11 (s, 1H, regioisomer 1 or 2), 9.10 (s, 1H, regioisomer 1 or 2), 7.61 - 7.56 (m, 4H, regioisomers 1 and 2), 7.20 - 7.15 (m, 2H, regioisomers 1 and 2), 4.36 - 4.30 (m, 4H, regioisomers 1 and 2).

[0102] Step 2: Preparation of (2,2-difluoro-3H-1,4-benzodioxin-6-yl)methanol Sodium borohydride (0.386 g, 10.2 mmol) in water (13.3 mL) was added portionwise at 0 °C to a vigorously stirred suspension of a 1:1 mixture of 3,3-difluoro-2H-1,4-benzodioxine-6-carbaldehyde (0.889 g, 4.44 mmol) and 2,2-difluoro-3H-1,4-benzodioxine-6-carbaldehyde (0.889 g, 4.44 mmol). The reaction was stirred for 5 h. The reaction was quenched with saturated aqueous NH4Cl and the product was extracted with ethyl acetate (2×). The organic portions were combined, dried over MgSO4, filtered and concentrated in vacuo to give a 1:1 mixture of (3,3-difluoro-2H-1,4-benzodioxin-6-yl)methanol (0.786 g, 3.89 mmol, 44%) and (2,2-difluoro-3H-1,4-benzodioxin-6-yl)methanol (0.786 g, 3.89 mmol, 44%) as a colorless oil. 1H NMR (400 MHz, CDCl3) δ ppm 7.06 - 6.97 (m, 6H, regioisomers 1 and 2), 4.63 (s, 4H, regioisomers 1 and 2), 4.26 - 4.22 (m, 4H, regioisomers 1 and 2).

[0103] Step 3: Preparation of (6-chloro-3,3-difluoro-2H-1,4-benzodioxin-7-yl)methanol (3,3-Difluoro-2H-1,4-benzodioxin-6-yl)methanol (0.786 g, 3.89 mmol) and a 1:1 mixture of (2,2-difluoro-3H-1,4-benzodioxin-6-yl)methanol (0.786 g, 3.89 mmol) and N-chlorosuccinimide (1.09 g, 8.16 mmol) were stirred in acetonitrile (25.9 mL) at 70 °C for 1 hour. The reaction mixture was concentrated onto isolute® and purified by flash column chromatography (0 - 30% ethyl acetate in cyclohexane). The product-containing fractions were combined and concentrated to give 6-chloro-3,3-difluoro-2H-1,4-benzodioxin-7-yl)methanol (0.588 g, 2.49 mmol, 32%) as a yellow oil. 1H NMR (400 MHz, CDCl3) δ ppm 7.28 (s, 1H), 7.07 (s, 1H), 4.71 (d, 2H), 4.24 (t, 2H), 1.91 (t, 1H).

[0104] Step 4: Preparation of 7-(bromomethyl)-6-chloro-3,3-difluoro-2H-1,4-benzodioxin To a solution of (6-chloro-3,3-difluoro-2H-1,4-benzodioxin-7-yl)methanol (0.392 g, 1.66 mmol) in dichloromethane (3.31 mL) was added carbon tetrabromide (0.659 g, 1.99 mmol). The solution was cooled to 0 °C and triphenylphosphine (0.652 g, 2.49 mmol) was added. The reaction mixture was warmed to RT and then stirred for 3 hours. The reaction mixture was absorbed onto isolute® and purified by flash column chromatography (0 - 20% ethyl acetate in cyclohexane). The product-containing fractions were concentrated to give 7-(bromomethyl)-6-chloro-3,3-difluoro-2H-1,4-benzodioxin (0.407 g, 1.36 mmol, 82%) as a white solid. 1H NMR (400 MHz, CDCl3) δ ppm 6.11 (s, 1H), 6.09 (s, 1H), 4.51 (s, 2H), 4.25 (t, 2H).

[0105] Procedure 5: Preparation of 2-[(6-chloro-3,3-difluoro-2H-1,4-benzodioxin-7-yl)methyl]-4,4-dimethyl-isoxazolidin-3-one To a solution of 7-(bromomethyl)-6-chloro-3,3-difluoro-2H-1,4-benzodioxin (0.300 g, 1.00 mmol) in acetone (9.0 mL) were added potassium carbonate (0.211 g, 1.50 mmol) and 4,4-dimethylisoxazolidin-3-one (0.152 g, 1.25 mmol). The reaction was stirred at RT overnight. The reaction mixture was diluted with acetone (10 mL), filtered through celite®, and then the mixture was pre-absorbed onto -isolute® and purified by flash column chromatography (0 - 30% ethyl acetate in cyclohexane). The product-containing fractions were concentrated to give 2-[(6-chloro-3,3-difluoro-2H-1,4-benzodioxin-7-yl)methyl]-4,4-dimethyl-isoxazolidin-3-one (0.302 g, 0.905 mmol, 90%) as a white solid. 1H NMR (400 MHz, CDCl3) δ ppm 7.08 (s, 1H), 7.01 (s, 1H), 4.75 (s, 2H), 4.24 (t, 2H), 4.03 (s, 2H), 1.27 (s, 6H).

[0106] Example 2: Preparation of Compound 1.002 Procedure 1: Preparation of 2-methyl-2,3-dihydro-1,4-benzodioxine-6-carbaldehyde and 3-methyl-2,3-dihydro-1,4-benzodioxine-6-carbaldehyde Potassium carbonate (29.3 g, 290 mmol) was added to a solution of 3,4-dihydroxybenzaldehyde (10.0 g, 72.4 mmol) in acetonitrile (145 mL) at RT. 1,2-Dibromopropane (73.1 g, 37.7 mL, 362 mmol) was added and the reaction was stirred at 90 °C overnight. The reaction was quenched with water and extracted with ethyl acetate (3 times). The organic portions were combined, dried over MgSO4, filtered, and concentrated under reduced pressure. The crude material was purified by flash column chromatography (0 - 20% ethyl acetate in cyclohexane). The product-containing fractions were combined and concentrated to give a 1:1 mixture of 2-methyl-2,3-dihydro-1,4-benzodioxine-6-carbaldehyde (1.84 g, 10.4 mmol, 14%) and 3-methyl-2,3-dihydro-1,4-benzodioxine-6-carbaldehyde (1.84 g, 10.4 mmol, 14%). 1H NMR (400 MHz, CDCl3) δ ppm 9.82 (s, 2H, regioisomers 1 and 2), 7.42 - 7.38 (m, 4H, regioisomers 1 and 2), 7.00 - 6.96 (m, 2H, regioisomers 1 and 2), 4.38 - 4.26 (m, 4H, regioisomers 1 and 2), 3.94 - 3.82 (m, 2H, regioisomers 1 and 2), 1.41 - 1.38 (m, 6H, regioisomers 1 and 2).

[0107] Step 2: Preparation of (3-methyl-2,3-dihydro-1,4-benzodioxin-6-yl)methanol and (2-methyl-2,3-dihydro-1,4-benzodioxin-6-yl)methanol Sodium borohydride (0.886 g, 23.4 mmol) was added portionwise at 0 °C to a vigorously stirred suspension of a 1:1 mixture of 3-methyl-2,3-dihydro-1,4-benzodioxine-6-carbaldehyde (1.81 g, 10.2 mmol) and 2-methyl-2,3-dihydro-1,4-benzodioxine-6-carbaldehyde (1.81 g, 10.2 mmol) in water (30.5 mL). The reaction was stirred for 3 h. The reaction was quenched with saturated aqueous NH4Cl and extracted with ethyl acetate (2×). The organic portions were combined, dried over MgSO4, filtered, and concentrated in vacuo to afford a 1:1 mixture of (3-methyl-2,3-dihydro-1,4-benzodioxin-6-yl)methanol (1.82 g, 10.1 mmol, 50%) and (2-methyl-2,3-dihydro-1,4-benzodioxin-6-yl)methanol (1.82 g, 10.1 mmol, 50%) as a colorless oil. 1H NMR (400 MHz, CDCl3) δ ppm 6.92 - 6.88 (m, 2H, isomers 1 and 2), 6.85 - 6.84 (m, 4H, isomers 1 and 2), 4.57 (s, 4H, isomers 1 and 2), 4.27 - 4.20 (m, 4H, isomers 1 and 2), 3.88 - 3.78 (m, 2H, isomers 1 and 2), 1.37 - 1.35 (m, 6H, isomers 1 and 2).

[0108] Step 3: Preparation of (6-chloro-2-methyl-2,3-dihydro-1,4-benzodioxin-7-yl)methanol and (6-chloro-3-methyl-2,3-dihydro-1,4-benzodioxin-7-yl)methanol (2-Methyl-2,3-dihydro-1,4-benzodioxin-6-yl)methanol (0.567 g, 3.15 mmol) and (3-methyl-2,3-dihydro-1,4-benzodioxin-6-yl)methanol (0.567 g, 3.15 mmol), a 1:1 mixture, and N-chlorosuccinimide (0.882 g, 6.61 mmol) were stirred in acetonitrile (21.0 mL) at 70 °C for 1 hour. The reaction mixture was concentrated on isolute (registered trademark) and purified by flash column chromatography (0 - 40% ethyl acetate in cyclohexane). The product-containing fractions were combined and concentrated to obtain a mixture of positional isomer products. This mixture was purified by reverse-phase preparative HPLC (1 - 5% acetonitrile in water). The product-containing fractions were combined and concentrated to give (6-chloro-2-methyl-2,3-dihydro-1,4-benzodioxin-7-yl)methanol (0.241 g, 1.12 mmol, 18%) as a white solid and (6-chloro-3-methyl-2,3-dihydro-1,4-benzodioxin-7-yl)methanol (0.154 g, 0.717 mmol, 11%) as a white solid. 1H NMR (400 MHz, CDCl3) δ ppm 6.96 (s, 1H), 6.90 (s, 1H), 4.65 (s, 2H), 4.27 - 4.18 (m, 2H), 3.78 - 3.83 (m, 1H), 1.36 (d, 3H) and 1H NMR (400 MHz, CDCl3) δ ppm 6.96 (s, 1H), 6.88 (s, 1H), 4.64 (s, 2H), 4.27 - 4.18 (m, 2H), 3.78 - 3.83 (m, 1H), 1.35 (d, 3H).

[0109] Step 4: Preparation of 7-(bromomethyl)-6-chloro-2-methyl-2,3-dihydro-1,4-benzodioxin A solution of (6-chloro-2-methyl-2,3-dihydro-1,4-benzodioxin-7-yl)methanol (0.198 g, 0.922 mmol) in dichloromethane (1.84 mL) was added carbon tetrabromide (0.367 g, 1.11 mmol). The solution was cooled to 0 °C and triphenylphosphine (0.363 g, 1.38 mmol) was added. The reaction mixture was warmed to RT and then stirred for 3 h. The reaction mixture was absorbed onto isolute® and purified by flash column chromatography (0 - 15% ethyl acetate in cyclohexane). The product-containing fractions were concentrated to give 7-(bromomethyl)-6-chloro-2-methyl-2,3-dihydro-1,4-benzodioxin (0.214 g, 0.771 mmol, 84%) as a white solid. 1H NMR (400 MHz, CDCl3) δ ppm 6.93 (s, 1H), 6.91 (s, 1H), 4.52 (s, 2H), 4.25 - 4.20 (m, 2H), 3.85 - 3.79 (m, 1H), 1.35 (d, 3H).

[0110] Step 5: Preparation of 2-[(6-chloro-2-methyl-2,3-dihydro-1,4-benzodioxin-7-yl)methyl]-4,4-dimethyl-isoxazolidin-3-one A solution of 7-(bromomethyl)-6-chloro-2-methyl-2,3-dihydro-1,4-benzodioxin (0.212 g, 0.764 mmol) in acetone (6.4 mL) was added with potassium carbonate (0.161 g, 1.15 mmol) and 4,4-dimethylisoxazolidin-3-one (0.111 g, 0.917 mmol). The reaction was stirred overnight at RT. The reaction mixture was diluted with ethyl acetate (10 mL), filtered through celite®, pre-absorbed on isolute®, and purified by flash column chromatography (0 - 30% ethyl acetate in cyclohexane). The product-containing fractions were concentrated to give 2-[(6-chloro-2-methyl-2,3-dihydro-1,4-benzodioxin-7-yl)methyl]-4,4-dimethyl-isoxazolidin-3-one (0.199 g, 0.638 mmol, 84%) as a white solid. 1H NMR (400 MHz, CDCl3) δ ppm 6.90 (s, 1H), 6.84 (s, 1H), 4.72 (s, 2H), 4.25 - 4.22 (m, 2H), 4.01 (s, 2H), 3.84 - 3.77 (m, 1H), 1.36 (d, 3H), 1.26 (s, 6H).

[0111] Example 3: Preparation of Compound 1.006 Preparation of 5-ethoxy-4,4-dimethyl-isoxazolidin-3-one Step 1: 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 RT. The mixture was heated to 70 °C over 5 h. The excess thionyl chloride was removed by crude distillation (75 °C). The residue was then purified by distillation (40 °C at 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).

[0112] Step 2: Preparation of 3,3-dichloro-2,2-dimethyl-propanehydroxamic acid To hydroxylamine (50% by mass) in water (8.09 g, 7.5 mL, 122 mmol), 3,3-dichloro-2,2-dimethyl-propanoyl chloride (3.00 g, 15.8 mmol) was added dropwise. The reaction mixture was stirred at RT for 10 minutes. The reaction mixture was extracted with dichloromethane, passed through a hydrophobic frit, and concentrated under reduced pressure 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).

[0113] Step 3: Preparation of 5-ethoxy-4,4-dimethyl-isoxazolidin-3-one A solution of 3,3-dichloro-2,2-dimethyl-propanehydroxamic acid (0.500 g, 2.69 mmol) and 1,8-diazabicyclo(5.4.0)undec-7-ene (0.919 g, 0.90 mL, 5.91 mmol) in ethanol (5 mL) was heated by microwave irradiation at 120 °C for 45 minutes. The mixture was concentrated under reduced pressure and the residue was diluted with dichloromethane. 2M HCl was added and the product was extracted with dichloromethane (5 times). The organic portions were combined, dried over MgSO4, filtered, and concentrated under reduced pressure to give 5-ethoxy-4,4-dimethyl-isoxazolidin-3-one (0.269 g, 1.69 mmol, 63%) as a colorless oil. 1H NMR (400 MHz, CDCl3) δ ppm 8.20 (br s, 1H), 4.99 (s, 1H), 3.90 - 3.80 (m, 1H), 3.60 - 3.50 (m, 1H), 1.32 (s, 3H), 1.18 (s, 3H), 1.28 - 1.19 (m, 3H).

[0114] Preparation of 2-[(6-chloro-2,2,3,3-tetrafluoro-1,4-benzodioxin-7-yl)methyl]-5-ethoxy-4,4-dimethyl-isoxazolidin-3-one Step 1: Preparation of 6-(chloromethyl)-2,2,3,3-tetrafluoro-1,4-benzodioxin (2,2,3,3-Tetrafluoro-1,4-benzodioxin-6-yl)methanol (0.394 g, 1.65 mmol) was dissolved in thionyl chloride (5.0 mL) under a nitrogen atmosphere and stirred overnight at RT. The reaction mixture was then concentrated under reduced pressure to give 6-(chloromethyl)-2,2,3,3-tetrafluoro-1,4-benzodioxin (0.371 g, 1.45 mmol, 87%) as a yellow oil. 1H NMR (400 MHz, CDCl3) δ ppm 7.22 - 7.15 (m, 2H), 7.14 - 7.09 (m, 1H), 4.52 (s, 2H).

[0115] Step 2: Preparation of 5-chloro-7-(chloromethyl)-2,2,3,3-tetrafluoro-1,4-benzodioxin Trichlorocyanuric acid (0.840 g, 3.61 mmol) was added to a solution of 6-(chloromethyl)-2,2,3,3-tetrafluoro-1,4-benzodioxin (0.371 g, 1.45 mmol) in 1-butyl-3-methyl-imidazol-3-ium hexafluorophosphate (10 mL), and the reaction was stirred at 140 °C until completion as monitored by GCMS. The reaction mixture was absorbed onto silica gel and purified by flash column chromatography (100% isohexane). The product-containing fractions were concentrated to give 6-chloro-7-(chloromethyl)-2,2,3,3-tetrafluoro-1,4-benzodioxin (0.247 g, 0.849 mmol, 59%). 1H NMR (400 MHz, CDCl3) δ ppm 7.31 (s, 1H), 7.23 (s, 1H), 4.62 (s, 2H).

[0116] Step 3: Preparation of 2-[(6-chloro-2,2,3,3-tetrafluoro-1,4-benzodioxin-7-yl)methyl]-5-ethoxy-4,4-dimethyl-isoxazolidin-3-one To 6-chloro-7-(chloromethyl)-2,2,3,3-tetrafluoro-1,4-benzodioxin (80 mg, 0.27 mmol) and potassium carbonate (48 mg, 0.34 mmol) was added a solution of 5-ethoxy-4,4-dimethyl-isoxazolidin-3-one (54 mg, 0.34 mmol) and tetra-N-butylammonium iodide (12.5 mg, 0.034 mmol) in acetonitrile (0.8 mL). The reaction mixture was stirred overnight. The reaction mixture was diluted with ethyl acetate (10 mL), filtered through celite®, and then purified by reverse-phase preparative HPLC. The product-containing fractions were combined and concentrated to give 2-[(6-chloro-2,2,3,3-tetrafluoro-1,4-benzodioxin-7-yl)methyl]-5-ethoxy-4,4-dimethyl-isoxazolidin-3-one (16 mg, 0.038 mmol, 14%). 1H NMR (400 MHz, CDCl3) δ ppm 7.22 (s, 1H), 7.19 (s, 1H), 4.92 - 4.89 (m, 2H), 4.70 - 4.68 (m, 1H), 3.75 - 3.68 (m, 1H), 3.52 - 3.47 (m, 1H), 1.29 - 1.16 (m, 9H).

[0117] Example 4: Preparation of Compound 1.009 Step 1: Preparation of N-[(6-chloro-2,3-dihydro-1,4-benzodioxin-7-yl)methyl]hydroxylamine N,O-Bis(tert-butoxycarbonyl)hydroxylamine (0.620 g, 2.58 mmol), potassium carbonate (0.755 g, 5.41 mmol), 6-chloro-7-(chloromethyl)-2,3-dihydro-1,4-benzodioxine (0.504 g, 2.30 mmol) and tetrabutylammonium iodide (93 mg, 0.25 mmol) were dissolved in acetone (25 mL) and heated at 60 °C for 5 h. The reaction mixture was filtered and concentrated under reduced pressure. The residue was treated with 4 M HCl in dioxane (10 mL) and stirred for 2 h. The reaction mixture was concentrated under reduced pressure, then water and dichloromethane were added. Concentrated NaOH was added dropwise to basify the solution to pH 9. The layers were separated and the aqueous layer was extracted with a further portion of dichloromethane. The organic portions were combined, dried over MgSO4, filtered and concentrated under reduced pressure to give N-[(6-chloro-2,3-dihydro-1,4-benzodioxin-7-yl)methyl]hydroxylamine (0.424 g, 1.97 mmol, 85%) as a white solid. 1H NMR (400 MHz, CDCl3) δ ppm 6.93 - 6.90 (m, 2H), 4.23 (s, 4H), 4.05 (s, 2H).

[0118] Step 2: Preparation of 2-[(6-chloro-2,3-dihydro-1,4-benzodioxin-7-yl)methyl]-4,4-dimethyl-isoxazolidine-3,5-dione 2,2-Dimethylpropanedioyl dichloride (0.337 g, 0.265 mL, 1.99 mmol) in dichloromethane (12.5 mL) was added dropwise to a solution of N-[(6-chloro-2,3-dihydro-1,4-benzodioxin-7-yl)methyl]hydroxylamine (0.424 g, 1.97 mmol) and pyridine (0.553 g, 0.565 mL, 6.92 mmol) in dichloromethane (12.5 mL) at 0 °C over 15 minutes. The reaction mixture was stirred for 1 hour and then left to stand overnight at RT. The reaction mixture was acidified with 2 M HCl, partitioned through a hydrophobic frit, and concentrated under reduced pressure. The reaction mixture was absorbed onto silica gel and purified by flash column chromatography (0 - 100% ethyl acetate in isohexane). The product-containing fractions were concentrated to give 2-[(6-chloro-2,3-dihydro-1,4-benzodioxin-7-yl)methyl]-4,4-dimethyl-isoxazolidine-3,5-dione (0.570 g, 1.83 mmol, 93%) as an orange solid. 1H NMR (400 MHz, CDCl3) δ ppm 6.92 (s, 1H), 6.85 (s, 1H), 4.94 (s, 2H), 4.25 (s, 4H), 1.45 (s, 6H).

[0119] Example 5: Preparation of Compound 1.004 Step 1: Preparation of 5-chloro-6-(chloromethyl)-1,3-benzodioxol-2-one (6-Chloro-1,3-benzodioxol-5-yl)methanol (2.80 g, 15.0 mmol) in chlorobenzene (10 mL) was added dropwise to a solution of phosphorus pentachloride (60.0 mmol, 13.2 g) in chlorobenzene (18 mL) over 10 minutes. The reaction was stirred at 135 °C for 4 hours, then quenched with water and extracted with DCM. The organic portion was dried over MgSO4, filtered, and concentrated over celite®. Purification by flash column chromatography (0 - 30% ethyl acetate in cyclohexane) gave 5-chloro-6-(chloromethyl)-1,3-benzodioxol-2-one (3.12 g, 14.2 mmol, 95%). 1H NMR (400 MHz, CDCl3) δ ppm 7.43 (s, 1H), 7.36 (s, 1H), 4.71 (s, 2H).

[0120] Step 2: Preparation of 2-[(2-chloro-4,5-dihydroxy-phenyl)methyl]-4,4-dimethyl-isoxazolidin-3-one 5-Chloro-6-(chloromethyl)-1,3-benzodioxol-2-one (3.10 g, 14.2 mmol), 4,4-dimethylisoxazolidin-3-one (1.71 g, 14.9 mmol), and potassium carbonate (5.99 g, 42.5 mmol) were combined in DMF (31 mL) under a nitrogen atmosphere. The reaction was stirred at RT for 3 hours, then quenched with 2 M HCl and extracted with ethyl acetate (twice). The combined organic portions were washed with brine, dried over MgSO4, filtered, and concentrated over celite®. Purification by flash column chromatography (10 - 100% ethyl acetate in cyclohexane) gave 2-[(2-chloro-4,5-dihydroxy-phenyl)methyl]-4,4-dimethyl-isoxazolidin-3-one (2.75 g, 10.1 mmol, 72%). 1H NMR (400 MHz, d6-DMSO) δ ppm 9.49 (br s, 2H), 6.76 (s, 1H), 6.75 (s, 1H), 4.55 (s, 2H), 4.00 (s, 2H), 1.12 (s, 6H).

[0121] Step 3: Preparation of 2-[[2-chloro-5-hydroxy-4-(2-methylallyloxy)phenyl]methyl]-4,4-dimethyl-isoxazolidin-3-one Potassium carbonate (1.9 g, 14.0 mmol) was added to a solution of 2-[(2-chloro-4,5-dihydroxy-phenyl)methyl]-4,4-dimethyl-isoxazolidin-3-one (2.5 g, 9.20 mmol) in acetonitrile (30 mL). The mixture was stirred for 1 hour and then 3-chloro-2-methyl-prop-1-ene (0.925 g, 1 mL, 10.0 mmol) was added dropwise. The reaction mixture was heated to reflux overnight and then quenched with 2 M HCl and extracted with ethyl acetate (4 times). The combined organic portions were washed with brine, dried over MgSO4, filtered and concentrated. The crude material was purified by flash column chromatography (0 - 15% ethyl acetate in isohexane) to give 2-[[2-chloro-5-hydroxy-4-(2-methylallyloxy)phenyl]methyl]-4,4-dimethyl-isoxazolidin-3-one (0.607 g, 1.86 mmol, 20%). 1H NMR (400 MHz, CDCl3) δ ppm 6.92 (s, 1H), 6.85 (s, 1H), 5.62 (s, 1H), 5.08 (s, 1H), 5.04 (s, 1H), 4.73 (s, 2H), 4.48 (s, 2H), 4.01 (s, 2H), 1.83 (s, 3H), 1.26 (s, 6H).

[0122] Step 4: Preparation of 2-[(6-chloro-2,2-dimethyl-3H-1,4-benzodioxin-7-yl)methyl]-4,4-dimethyl-isoxazolidin-3-one 2-[[2-Chloro-5-hydroxy-4-(2-methylallyloxy)phenyl]methyl]-4,4-dimethyl-isoxazolidin-3-one (40 mg, 0.123 mmol) and formic acid (10 mL, 252 mmol) were combined and heated to reflux for 30 minutes. The reaction mixture was concentrated, then diluted in DCM and washed with saturated aqueous NaHCO3. The aqueous layer was extracted with DCM (2 times). The combined organic portions were washed with water, dried over MgSO4, filtered and concentrated. The crude material was purified by reverse phase preparative HPLC to give 2-[(6-chloro-2,2-dimethyl-3H-1,4-benzodioxin-7-yl)methyl]-4,4-dimethyl-isoxazolidin-3-one (19 mg, 0.058 mmol, 48%). 1H NMR (400 MHz, CDCl3) δ ppm 6.91 (s, 1H), 6.81 (s, 1H), 4.72 (s, 2H), 4.02 (s, 2H), 3.86 (s, 2H), 1.33 (s, 6H), 1.26 (s, 6H).

[0123] Example 6: Preparation of Compound 1.005 Step 1: Preparation of 2-[[2-chloro-4-hydroxy-5-(2-methylallyloxy)phenyl]methyl]-4,4-dimethyl-isoxazolidin-3-one Potassium carbonate (1.9 g, 14.0 mmol) was added to a solution of 2-[(2-chloro-4,5-dihydroxy-phenyl)methyl]-4,4-dimethyl-isoxazolidin-3-one (2.5 g, 9.20 mmol) in acetonitrile (30 mL). The mixture was stirred for 1 hour, then 3-chloro-2-methyl-prop-1-ene (0.925 g, 1 mL, 10.0 mmol) was added dropwise. The reaction mixture was heated to reflux overnight, then quenched with 2 M HCl and extracted with ethyl acetate (4 times). The combined organic portions were washed with brine, dried over MgSO4, filtered, and concentrated. The crude material was purified by flash column chromatography (0 - 15% ethyl acetate in isohexane) to give 2-[[2-chloro-4-hydroxy-5-(2-methylallyloxy)phenyl]methyl]-4,4-dimethyl-isoxazolidin-3-one (0.363 g, 1.11 mmol, 12%). 1H NMR (400 MHz, CDCl3) δ ppm 6.96 (s, 1H), 6.84 (s, 1H), 5.69 (s, 1H), 5.06 (s, 1H), 5.02 (s, 1H), 4.74 (s, 2H), 4.47 (s, 2H), 3.98 (s, 2H), 1.82 (s, 3H), 1.24 (s, 6H).

[0124] Step 2: Preparation of 2-[(6-chloro-3,3-dimethyl-2H-1,4-benzodioxin-7-yl)methyl]-4,4-dimethyl-isoxazolidin-3-one 2-[[2-chloro-4-hydroxy-5-(2-methylallyloxy)phenyl]methyl]-4,4-dimethyl-isoxazolidin-3-one (40 mg, 0.123 mmol) and formic acid (10 mL, 252 mmol) were combined and heated to reflux for 30 minutes. The reaction mixture was concentrated, then diluted in DCM and washed with saturated aqueous NaHCO3. The aqueous layer was extracted with DCM (2 times). The combined organic portions were washed with water, dried over MgSO4, filtered and concentrated. The crude material was purified by reverse phase preparative HPLC to give 2-[(6-chloro-3,3-dimethyl-2H-1,4-benzodioxin-7-yl)methyl]-4,4-dimethyl-isoxazolidin-3-one (12 mg, 0.037 mmol, 30%). 1H NMR (400 MHz, CDCl3) δ ppm 6.86 (s, 1H), 6.85 (s, 1H), 4.73 (s, 2H), 4.02 (s, 2H), 3.86 (s, 2H), 1.33 (s, 6H), 1.27 (s, 6H).

[0125] Example 7: Preparation of Compound 1.029 Step 1: Preparation of 7-chlorochroman-6-carbaldehyde 1,2-Dichloroethane (74 mL) and trifluoroacetic acid (8.52 g, 5.76 mL, 74.0 mmol) were added to a mixture of chroman-6-carbaldehyde (1.20 g, 7.40 mmol), N-chlorosuccinimide (1.48 g, 11.1 mmol), palladium(II) acetate (0.175 g, 0.740 mmol), 2-aminobenzoic acid (0.311 g, 2.22 mmol), and silver trifluoroacetate (0.167 g, 0.740 mmol). The reaction mixture was heated to 60 °C over 18 h and then partitioned between saturated aqueous NaHCO3 and DCM. The aqueous layer was extracted with DCM (twice), the combined organic portions were passed through hydrophobic filter paper, and then concentrated. The crude material was purified by reverse-phase flash column chromatography to afford 7-chlorochroman-6-carbaldehyde (0.442 g, 2.25 mmol, 30%). 1H NMR (400 MHz, CDCl3) δ ppm 10.29 (s, 1H), 7.66 (t, 1H), 6.84 (s, 1H), 4.29 - 4.22 (m, 2H), 2.79 (t, 2H), 2.06 - 1.97 (m, 2H).

[0126] Step 2: Preparation of (7-chlorochroman-6-yl)methanol Diisobutylaluminum hydride (1 M solution in 6.55 mL of toluene, 6.55 mmol) was added dropwise to a solution of 7-chlorochroman-6-carbaldehyde (0.515 g, 2.62 mmol) in 2-methyltetrahydrofuran (5.95 mL) at 0 °C under a nitrogen atmosphere. The reaction mixture was stirred at RT for 3 h and then quenched by the dropwise addition of ethyl acetate at 0 °C. Saturated aqueous sodium potassium tartrate was added and the mixture was stirred vigorously for 1 h. The mixture was then extracted with ethyl acetate (twice). The combined organic portions were passed through a hydrophobic frit and concentrated to afford (7-chlorochroman-6-yl)methanol (0.361 g, 1.82 mmol, 69%). 1H NMR (400 MHz, CDCl3) δ ppm 7.10 (s, 1H), 6.83 (s, 1H), 4.66 (d, 2H), 4.20 - 4.14 (m, 2H), 2.75 (t, 2H), 2.03 - 1.95 (m, 2H), 1.86 (br t, 1H).

[0127] Step 3: Preparation of 7-chloro-6-(chloromethyl)chroman (7-Chlorochroman-6-yl)methanol (0.311 g, 1.57 mmol) and thionyl chloride (7.44 mL, 102 mmol) were combined and stirred overnight at RT under a nitrogen atmosphere. The reaction mixture was added dropwise to water and extracted with ethyl acetate (3 times). The combined organic portions were passed through hydrophobic filter paper and then concentrated to give 7-chloro-6-(chloromethyl)chroman (0.265 g, 1.22 mmol, 78%). 1H NMR (400 MHz, CDCl3) δ ppm 7.10 (s, 1H), 6.84 (s, 1H), 4.64 (s, 2H), 4.20 - 4.15 (m, 2H), 2.75 (t, 2H), 2.03 - 1.93 (m, 2H).

[0128] Step 4: Preparation of 2-[(7-chlorochroman-6-yl)methyl]-4,4-dimethyl-isoxazolidin-3-one 7-Chloro-6-(chloromethyl)chroman (0.265 g, 1.22 mmol), 4,4-dimethylisoxazolidin-3-one (0.183 g, 1.59 mmol), potassium carbonate (0.337 g, 2.44 mmol) and acetone (7.32 mL) were combined and stirred for 2 days at RT. The reaction mixture was diluted with water and extracted with ethyl acetate (3 times). The organic portions were combined, passed through hydrophobic filter paper and concentrated. The crude material was purified by reverse-phase flash column chromatography to give 2-[(7-chlorochroman-6-yl)methyl]-4,4-dimethyl-isoxazolidin-3-one (80 mg, 0.270 mmol, 22%). 1H NMR (400 MHz, CDCl3) δ ppm 6.99 (s, 1H), 6.82 (s, 1H), 4.73 (s, 2H), 4.20 - 4.14 (m, 2H), 4.00 (s, 2H), 2.73 (t, 2H), 2.02 - 1.94 (m, 2H), 1.25 (s, 6H).

[0129] Example 8: Preparation of Compound 1.038 Preparation of 2-[(6-chloro-3,3-difluoro-2H-1,4-benzodioxin-7-yl)methyl]-4,4-dimethyl-isoxazolidine-3-thione Trimethyl(trimethylsilyloxy)silane (0.180 g, 0.237 mL, 1.11 mmol) and phosphorus pentasulfide (82 mg, 0.370 mmol) were added to a solution of 2-[(6-chloro-3,3-difluoro-2H-1,4-benzodioxin-7-yl)methyl]-4,4-dimethyl-isoxazolidin-3-one (0.130 g, 0.370 mmol) in toluene (4 mL) under an argon atmosphere. The reaction mixture was heated to 110 °C over 1 hour and then concentrated. The crude material was purified by flash column chromatography (0 - 60% ethyl acetate in hexane) to give 2-[(6-chloro-3,3-difluoro-2H-1,4-benzodioxin-7-yl)methyl]-4,4-dimethyl-isoxazolidine-3-thione (75 mg, 0.204 mmol, 55%). 1H NMR (400 MHz, d6-DMSO) δ ppm 7.46 (s, 1H), 7.14 (s, 1H), 5.19 (s, 2H), 4.64 (t, 2H), 4.18 (s, 2H), 1.21 (s, 6H).

[0130] Further examples of the compounds of formula (I) can be formed in the same manner as in the above examples and are shown by the characteristic data in Table 1 below.

[0131]

Table 1-1

Table 1-2

Table 1-3

Table 1-4

Table 1-5

Table 1-6

Table 1-7

[0132] Biological Examples Seeds of various test species: redroot pigweed (Amaranthus retoflexus) (AMARE), giant foxtail (Setaria faberi) (SETFA), barnyard grass (Echinochloa crus-galli) (ECHCG), and ivy-leaved morning glory (Ipomoea hederacea) (IPOHE) are sown in standard soil in pots. After cultivation for 1 day (before germination) or 8 days (after germination) under controlled conditions in a greenhouse (24 / 16 °C, day / night; 14-hour light; 65% humidity), the plants are sprayed with an aqueous spray solution obtained from i) a formulation of the active ingredient in an acetone / water (50:50) solution containing 0.5% Tween 20 (polyoxyethylene sorbitan monolaurate, CAS RN 9005-64-5), or ii) dissolving the active ingredient in a small amount of acetone and a special solvent and emulsifier mixture (referred to as IF50 (11.12% Emulsogen EL360 (trademark) + 44.44% N-methylpyrrolidone + 44.44% Dowanol DPM glycol ether)), and then diluting to the required concentration using 0.2% Genapol XO80 (CAS No. 9043-30-5) in water as a diluent. The compound is applied at 250 g / ha. Then, the test plants are grown in the greenhouse under controlled conditions (24 / 16 °C, day / night; 14-hour light; 65% humidity) and watered twice a day. After 13 days, for before and after germination, the percentage of damage caused to the plants in the test is evaluated. The biological activity is shown in the following table on a 5-point scale (5 = 81 - 100%; 4 = 61 - 80%; 3 = 41 - 60%; 2 = 21 - 40%; 1 = 0 - 20%); NT indicates not tested.

[0133]

Table 2

[0134]

Table 3

[0135] A variety of test species: Seeds of Leptochloa chinesis (LEFCH), Echinochloa crus-galli (ECHCG), and Cyperus esculentus (CYPES) are sown in standard soil in pots. After cultivation for 1 day (before germination) or 13 days (after germination) under controlled conditions in a greenhouse (30 / 20 °C, day / night; 18 hours of light; 75% humidity), the technical active ingredient is dissolved in a small amount of acetone and a special solvent and emulsifier mixture (designated as IF50 (11.12% Emulsogen EL360 (trademark) + 44.44% N-methylpyrrolidone + 44.44% Dowanol DPM glycol ether)), and then diluted to the required concentration using 0.2% Genapol XO80 (CAS No. 9043-30-5) in water as a diluent. The resulting aqueous spray solution is sprayed onto the plants. The compound is applied at 500 g / ha. Then, the test plants are grown in the greenhouse under controlled conditions (30 / 20 °C, day / night; 18 hours of light; 75% humidity) and watered twice a day. After 13 days, the percentage of damage caused to the plants in the test is evaluated for before and after germination. The biological activity is shown in the following table on a 5-point scale (5 = 81 - 100%; 4 = 61 - 80%; 3 = 41 - 60%; 2 = 21 - 40%; 1 = 0 - 20%); NT indicates not tested.

[0136]

Table 4

[0137]

Table 5

Claims

1. A compound of formula (I) 【Chemical 1】 wherein A 1 is CR 1 R 2 or C(O); A 2 is selected from the group consisting of CR 9 R 10 , C(O), O, S(O) p and N(R 13 ); A 3 is selected from the group consisting of CR 11 R 12 , C(O), O, S(O) p and N(R 13) selected from the group consisting of; X 1 is O or S; R 1 is selected from the group consisting of hydrogen, halogen, HO−, C 1 to C 6 alkoxy, C 1 to C 6 alkoxy-C 1 to C 6 alkoxy-, C 1 to C 3 alkyl-C(O)O−, HOC(O)C 1 to C 6 alkoxy-, C 1 to C 6 alkoxy-C(O)-C 1 to C 6 alkoxy-, C 1 to C 3 alkyl-S(O) p - and C 1 to C 3 alkyl-S(O) p C 1 to C 6 alkoxy-; R 2 is hydrogen; R 3 is C 1 to C 3 alkyl; R 4 is C 1 to C 3 alkyl; R 5 is selected from the group consisting of hydrogen, halogen, C 1 -C 6 -alkyl, C 1 -C 6 -haloalkyl, C 3 -C 6 -cycloalkyl and C 1 -C 6 -alkoxy; and R 6 is selected from the group consisting of hydrogen, halogen, C 1 to C 6 alkyl, C 1 to C 6 haloalkyl, C 3 to C 6 cycloalkyl and C 1 to C 6 alkoxy -; or R 5 and R 6 together are =O or -(CH 2 ) n -; and R 7 is selected from the group consisting of hydrogen, halogen, C 1 to C 6 alkyl, C 1 to C 6 haloalkyl, C 3 to C 6 cycloalkyl and C 1 to C 6 alkoxy-; R 8 is selected from the group consisting of hydrogen, halogen, C 1 to C 6 alkyl, C 1 to C 6 haloalkyl, C 3 to C 6 cycloalkyl and C 1 to C 6 alkoxy; or R 7 and R 8 together are =O or -(CH 2 ) n -; and R 9 is selected from the group consisting of hydrogen, halogen, C 1 to C 6 alkyl, C 1 to C 6 haloalkyl, C 3 to C 6 cycloalkyl and C 1 to C 6 alkoxy-; R 10 is selected from the group consisting of hydrogen, halogen, C 1 -C 6 -alkyl, C 1 -C 6 -haloalkyl, C 3 -C 6 -cycloalkyl and C 1 -C 6 -alkoxy -; or is selected from the group consisting of R 9 and R 10 together are —(CH 2 ) n —; and R 11 is selected from the group consisting of hydrogen, halogen, C 1 to C 6 alkyl, C 1 to C 6 haloalkyl, C 3 to C 6 cycloalkyl and C 1 to C 6 alkoxy-; R 12 is selected from the group consisting of hydrogen, halogen, C 1 to C 6 alkyl, C 1 to C 6 haloalkyl, C 3 to C 6 cycloalkyl and C 1 to C 6 alkoxy; or R 11 and R 12 together are -(CH 2 ) n -; R 13 is hydrogen or C 1 ~C 3 alkyl; n is independently 2, 3, 4, 5 or 6; and p is independently 0, 1 or 2).

2. X 1 is O, a compound of formula (I).

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

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

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

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

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

8. A 2 and A 3 is O, the compound according to any one of claims 1 to 7.

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

10. A herbicidal composition comprising a compound of formula (I) according to any one of claims 1 to 9 and an agriculturally acceptable formulation adjuvant.

11. The 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 injury reducer.

13. A method of controlling weeds at a location, the method comprising applying to the location an amount of the composition according to any one of claims 10 to 12 effective to control the weeds.

14. Use of a compound of formula (I) according to any one of claims 1 to 9 as a herbicide.

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