Herbicidal compounds

Abstract

The present invention relates to compounds having formula (I), (I) or an agronomically acceptable salt of said compound, wherein A1, A2, A3, X1, R2, R3, R4, R5, R6, R7 and R8 are as defined herein. The invention further relates to herbicidal compositions comprising compounds of formula (I) and to the use of compounds of formula (I) for controlling weeds, in particular in crops of useful plants. # imgabs0 #

Description

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

[0002] The herbicide 3-isoxazolidinone is known from US 4,405,357. The herbicide isoxazolidine-3,5-dione is known from US 4,302,238. The present invention relates to novel 3-isoxazolidinone and isoxazolidine-3,5-dione compounds. Therefore, according to the present invention, there is provided a compound of formula (I):

[0003]

[0004] or an agronomically acceptable salt thereof, wherein:

[0005] A 1 Yes CR 1 R 2 or C(O);A 2 Selected from the group consisting of: CR 9 R 10 、C(O)、O、S(O) p and N(R 13 );A 3 Selected from the group consisting of: CR 11 R 12 、C(O)、O、S(O) p and N(R 13 );X 1 O or S; R 1 Selected from the group consisting of 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-; R 2 is hydrogen; R 3 is a C1-C3 alkyl group; R 4 is a C1-C3 alkyl group; R 5 is selected from the group consisting of hydrogen, halogen, C1-C6 alkyl, C1-C6 haloalkyl, C3-C6 cycloalkyl and C1-C6 alkoxy-; and R 6 is selected from the group consisting of hydrogen, halogen, C1-C6 alkyl, C1-C6 haloalkyl, C3-C6 cycloalkyl and C1-C6 alkoxy-; or R 5 and R 6Together they are =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 they are =O or -(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-; or R 9 and R 10 Together is -(CH2) n -; and R 11 is selected from the group consisting of hydrogen, halogen, C1-C6 alkyl, C1-C6 haloalkyl, C3-C6 cycloalkyl and C1-C6 alkoxy-; R 12 is selected from the group consisting of hydrogen, halogen, C1-C6 alkyl, C1-C6 haloalkyl, C3-C6 cycloalkyl and C1-C6 alkoxy-; or R 11 and R 12 Together is -(CH2) n -; R 13 is hydrogen or C1-C3 alkyl; n is independently 2, 3, 4, 5 or 6; and p is independently 0, 1 or 2.

[0006] 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).

[0007] Halogen (or halo) includes, for example, fluorine, chlorine, bromine or iodine. The above applies correspondingly to halogen in other defined contexts, such as haloalkyl.

[0008] 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.

[0009] The C1-C6 alkoxy group includes methoxy, ethoxy and isopropoxy-.

[0010] 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.

[0011] The C1-C6 alkoxy-C1-C6 alkoxy- includes, for example, methoxymethoxy- and ethoxymethoxy-.

[0012] C1-C3 alkyl-C(O)O- includes methyl-C(O)O- and ethyl-C(O)O-.

[0013] C1-C6 alkoxy-C(O)-C1-C6 alkoxy- includes methoxy-C(O)-methoxy- and ethoxy-C(O)-methoxy-.

[0014] C1-C3 alkyl-S(O) p C1-C6 alkoxy - including methyl - S(O) p Methoxy- and Ethyl-S(O) p Methoxy-.

[0015] The C3-C6 cycloalkyl group includes cyclopropyl, cyclopentyl and cyclohexyl.

[0016] The C1-C4 alkyl-S-(alkylthio) includes, for example, methylthio, ethylthio, propylthio, isopropylthio, n-butylthio, isobutylthio, sec-butylthio or tert-butylthio, preferably methylthio or ethylthio.

[0017] The 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.

[0018] The 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.

[0019] In one embodiment of the present invention, there is provided a compound having formula (I), wherein X 1 It's O.

[0020] In another embodiment of the present invention, there is provided a compound having formula (I), wherein R 3 and R 4 It's methyl.

[0021] In another embodiment of the present invention, there is provided a compound having formula (I), wherein A 1 Yes CR 1 R 2 And R 1 Therefore, in a preferred embodiment of the present invention, there is provided a compound having formula 1a:

[0022]

[0023] In another embodiment of the present invention, there is provided a compound having formula (I), wherein A 1 Yes CR 1 R 2 And R 1 It is a C1-C6 alkoxy group.

[0024] In another embodiment of the present invention, there is provided a compound having formula (I), wherein A 1 Therefore, in a preferred embodiment of the present invention, there is provided a

[0025] Compound of formula 1b:

[0026]

[0027] In one embodiment of the present invention, a compound having formula (I), formula (Ia) or formula (Ib) is provided, wherein A 2 Selected from the group consisting of CH2, C(O), O, S and NH, preferably O.

[0028] In another embodiment of the present invention, there is provided a compound having formula (I), formula (Ia) or formula (Ib), wherein A 3 Selected from the group consisting of CH2, C(O), O, S and NH, preferably O.

[0029] In another embodiment of the present invention, there is provided a compound having formula (I), formula (Ia) or formula (Ib), wherein (i) A 2 and A 3 is 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 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 It's O.

[0030] In a preferred embodiment of the present invention, there is provided a compound having formula (I), formula (Ia) or formula (Ib), wherein A 2 and A 3 It's O.

[0031] In another embodiment of the present invention, there is provided a compound having formula (I), formula (Ia) or formula (Ib), wherein R 5 , R 6 , R 7 and R 8 is independently selected from the group consisting of hydrogen, C1-C6 alkyl and C1-C6 alkyl. 5 , R 6 , R 7 and R 8 is independently selected from the group consisting of hydrogen, methyl and fluoro. 5 and R 6 is halogen, preferably fluorine, and R 7 and R 8 It's hydrogen.

[0032] Compounds of formula (I) may contain asymmetric centers and may exist as single enantiomers, in pairs of enantiomers in any ratio, or, in the case of more than one asymmetric center, in all possible ratios of diastereomers. Typically, one of the enantiomers has an enhanced biological activity compared to the other possibilities.

[0033] The present invention also provides agronomically acceptable salts of compounds of formula (I). Preferably, the compounds of formula (I) can form salts with amines, including primary, secondary and tertiary amines (e.g., ammonia, dimethylamine and triethylamine), alkali metal bases and alkaline earth metal bases, transition metal bases or quaternary ammonium bases.

[0034] The compounds of formula (I) according to the invention can be used as herbicides themselves, but they are usually formulated into herbicidal compositions using formulation adjuvants such as carriers, solvents and surfactants (SAAs). 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, which is diluted before use, although ready-to-use compositions may also be prepared. The final dilution is usually carried out with water, but may be carried out using, for example, liquid fertilizers, micronutrients, biological organisms, oils or solvents instead of or in addition to water.

[0035] The herbicidal compositions generally comprise from 0.1 to 99% by weight, in particular from 0.1 to 95% by weight, of a compound of formula I and from 1 to 99.9% by weight of formulation adjuvants, which preferably include from 0 to 25% by weight of surface-active substances.

[0036] The composition can be selected from a number of formulation types. These include emulsion 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 emulsions (EW), microemulsions (ME), oil dispersants (OD), oil suspensions (OF), oil-soluble liquids (OL), soluble concentrates (SL), ultra-low volume suspensions (SU), ultra-low volume liquids (UL), parent drugs (TK), dispersible concentrates (DC), soluble powders (SP), wettable powders (WP) and soluble granules (SG). In any case, the formulation type selected will depend on the specific purpose envisioned and the physical, chemical and biological properties of the compound of formula (I).

[0037] 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 one or more wetting agents, one or more dispersants or a mixture of said agents to improve water dispersibility / water solubility. The mixture is then ground into a fine powder. Similar compositions can also be granulated to form water-soluble granules (SG).

[0038] 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 and preferably, one or more dispersants, and optionally, one or more suspending agents to facilitate dispersion in a liquid. The mixture is then ground into a fine powder. Similar compositions can also be granulated to form water dispersible granules (WG).

[0039] Granules (GR) may be formed by granulating a mixture of a compound of formula (I) and one or more powdered solid diluents or carriers, or by absorbing the compound of formula (I) (or a solution thereof in a suitable agent) into a porous granular material such as pumice, attapulgite clay, Fuller's earth, kieselguhr, diatomaceous earths or corn cob meal, or from preformed blank particles by adsorbing the compound of formula (I) (or a solution thereof in a suitable agent) onto a hard core material such as sand, silicates, mineral carbonates, sulfates or phosphates and, if necessary, drying. Agents commonly used to aid absorption or adsorption include solvents (such as aliphatic and aromatic petroleum solvents, alcohols, ethers, ketones and esters) and adhesives (such as polyvinyl acetate, polyvinyl alcohol, dextrins, sugars and vegetable oils). One or more other additives may also be included in the granules (e.g., emulsifiers, wetting agents or dispersants).

[0040] 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 a surfactant (for example to improve water dilution or to prevent crystallization in a spray tank).

[0041] 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 (such as C8-C 10 EC products can spontaneously emulsify when added to water, producing an emulsion with sufficient stability to allow spray application by appropriate equipment.

[0042] The preparation of EWs involves obtaining a compound of formula (I) as a liquid (if it is not liquid at room temperature, it can be melted at a suitable temperature, typically below 70° C.) or in solution (by dissolving it in a suitable solvent), and then emulsifying the resulting liquid or solution into water containing one or more SAAs under high shear to produce 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 having low solubility in water.

[0043] Microemulsions (ME) can be prepared by mixing water with a blend of one or more solvents and one or more SAAs to spontaneously produce a thermodynamically stable, isotropic liquid formulation. The compound of formula (I) is initially present in water or in a solvent / SAA blend. Suitable solvents for use in MEs include those described above for use in ECs or EWs. MEs can be oil-in-water systems or water-in-oil systems (which system is present can be determined by conductivity measurements) and can be suitable for mixing water-soluble pesticides and oil-soluble pesticides in the same formulation. MEs are suitable for dilution into water, remaining as microemulsions or forming conventional oil-in-water emulsions.

[0044] Suspension concentrates (SC) may include aqueous or non-aqueous suspensions of finely dispersed insoluble solid particles of a compound of formula (I). SC may be prepared by ball milling or bead milling a solid compound of formula (I) with one or more dispersants in a suitable medium 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 of particle settling. Alternatively, a compound of formula (I) may be dry-milled and added to water containing the reagents described above to produce a desired final product.

[0045] Aerosol formulations comprise 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 medium (e.g. water or a water-miscible liquid such as n-propanol) to provide a composition for use in a non-pressurized hand-operated spray pump.

[0046] Capsule suspensions (CS) can be prepared in a similar manner to the preparation of EW formulations, but with an additional polymerization stage, so that an aqueous dispersion of oil droplets is obtained, wherein each oil droplet is wrapped by a polymer shell and contains a compound with formula (I) and optionally a carrier or diluent for the oil droplet. The polymer shell can be produced by an interfacial polycondensation reaction or by a coacervation procedure. These compositions can provide controlled release of compounds with formula (I) and they can be used for seed treatment. Compounds with formula (I) can also be formulated in a biodegradable polymer matrix to provide slow, controlled release of the compound.

[0047] The composition may include one or more additives to improve the biological performance of the composition, for example by improving wettability, retention or distribution on a surface; rain resistance on a treated surface; or absorption or flow of a compound of formula (I). Such additives include surfactants (SAAs), 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 bioenhancement adjuvants (ingredients that can assist or modify the action of a compound of formula (I)).

[0048] The wetting agent, dispersant and emulsifier may be a cationic type, anionic type, amphoteric type or nonionic type SAA.

[0049] Suitable cationic-type SAAs include quaternary ammonium compounds (eg, cetyltrimethylammonium bromide), imidazolines, and amine salts.

[0050] 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, butylnaphthalenesulfonate, and mixtures of sodium di-isopropyl-naphthalenesulfonate and sodium tri-isopropyl-naphthalenesulfonate), ether sulfates, alcohol ether sulfates (e.g., sodium laureth-3-sulfate), ether carboxylates (e.g., sodium laureth-3-carboxylate), phosphates (products from the reaction of one or more fatty alcohols with phosphoric acid (mainly monoesters) or with phosphorus pentoxide (mainly diesters), for example, the reaction of lauryl alcohol with tetraphosphoric acid; these products may additionally be ethoxylated), sulfosuccinamates, paraffin or olefin sulfonates, taurates, lignosulfonates, and phosphates / sulfates of tristyrylphenol.

[0051] Suitable amphoteric types of SAA include betaine, propionate and glycinate.

[0052] Suitable SAAs of the nonionic type 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 with 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 (comprising ethylene oxide and propylene oxide); alkanolamides; monoesters (such as fatty acid polyethylene glycol esters); amine oxides (such as lauryl dimethyl amine oxide); lecithin and sorbitan and their esters, alkyl polyglycosides and tristyrylphenol.

[0053] Suitable suspending agents include hydrophilic colloids (such as polysaccharides, polyvinyl pyrrolidone or sodium carboxymethyl cellulose) and swelling clays (such as bentonite or attapulgite).

[0054] The compounds of the present invention can also be used in admixture 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), bensulfuron, ametryn, amitriptyline, aminopyralid, cypermethrin, atrazine, flubutyric acid-M, quinclorac, benquitrione, benzylsulfuron-methyl (including benzylsulfuron-methyl), bentazon, bicyclic pyrone, bialaphos, bispyribac-sodium, bixlozone, herbicide, bromoxynil, butachlor, flubutyric acid-butyl, mesotrione (including mesotrione-ethyl), chlorsulfuron (including chlorsulfuron-methyl), chlorsulfuron (including chlorsulfuron-ethyl), chlorotoluron, chlorsulfuron, cyproconazole, chlorpyrifos-butyl ... cyfos), clethodim, clodinafop-butyl (including clodinafop-butyl), clomazone, clopyralid, cyclopyranil, cyclopyrimorate, cyprosulfuron, cyhalofop-butyl (including cyhalofop-butyl-butyl), 2,4-D (including its choline salt and 2-ethylhexyl ester), 2,4-DB, betaine, dicamba (including its aluminum, aminopropyl, bis-aminopropylmethyl, choline, dichloropropane, diglycolamine, dimethylamine, dimethylammonium, potassium and sodium salts), bisclorac, fluazifop-butyl, fluazifop-butyl, dimethoate, dimethoate-s-propyl, dioxopyritrione, diquat dibromide, diquat , epyrifenacil, ethoxyfluralin, oxadiazine (including oxadiazine-ethyl), fenoxasulfone, benzazin, fenquinotrione, tetrazoline, fluazifop-butyl, bispyribac, florpyrauxifen (including florpyrauxifen-benzyl), fluazifop-butyl (including fluazifop-butyl-butyl), fluazifop-butyl (including fluazifop-sodium), flufenacet, fluazifop-butyl ... fluroxypyr-meptyl), fluazifop-butyl, foramsulfuron, glufosinate (including L-glufosinate and ammonium salts of both), glyphosate (including its hydrazine, isopropyl ammonium and potassium salts), halauxifen (including halauxifen-methyl), fluazifop-methyl (including fluazifop-methyl), hexazinone, hydantocidin, imazamox (including R-imazamox), imazapyr, imazapyr, imazamox, indazine fluazifop-butyl, iodosulfuron (including iodosulfuron-methyl-sodium), iofensulfuron (including iodofensulfuron-sodium), ioboxynil, isoproturon,Isotrione, lancotrione, MCPA, MCPB, mecoprop-P, mesosulfuron (including mesosulfuron-methyl), mesotrione, metamitron, metazachlor, methizolin, isopropyl metolachlor, sulfamethoxazole, metribuzin, metsulfuron-methyl, propamide, nicosulfuron, norfadine, oxadiazine, oxasulfuron, oxyfluorfen, paraquat dichloride, pendimethalin, penoxsulam, bendisulfuron, picloram, pinoxaden, pretilachlor, primisulfuron-methyl, promethazine, propanil, oxadiazine, propyrisulfuron, propyrisulfuron, promethazine, procarb, prosulfuron, dimethoate pyraflufen (including pyraflufen-ethyl), pyraflufen, pyraflufen, pyrimisulfan, pyroxasulfone, pyraflufen, quinclorac, quinclorac, quizalofop-P (including quizalofop-P-ethyl and quizalofop-P-tefuryl), rimisoxafen, sulfasulfuron, pyraflufen ... hiencarbazone), thifensulfuron-methyl, tiafenacil, tolpyralate, benpyrazone, trimethoprim-butyl, triafamone, wild wheat chlorpyrifos, bensulfuron-methyl, bensulfuron-methyl (including bensulfuron-methyl), triclopyr, trifloxysulfuron (including trifloxysulfuron-sodium), trifludimoxazin, trifluralin, trifloxysulfuron, triazosulfuron, 3-(2-chloro-4-fluoro-5-(3-methyl-2,6-dioxo-4-trifluoromethyl-3,6-dihydropyrimidin-1(2H)-yl)phenyl)-5-methyl-4,5-dihydroisoxazole-5-carboxylic acid ethyl ester, 4- Hydroxy-1-methoxy-5-methyl-3-[4-(trifluoromethyl)-2-pyridyl]imidazolidin-2-one, 4-hydroxy-1,5-dimethyl-3-[4-(trifluoromethyl)-2-pyridyl]imidazolidin-2-one, 5-ethoxy-4-hydroxy-1-methyl-3-[4-(trifluoromethyl)-2-pyridyl]imidazolidin-2-one, 4-hydroxy-1-methyl-3-[4-(trifluoromethyl)-2-pyridyl]imidazolidin-2-one, 4-hydroxy-1,5-dimethyl-3-[1-methyl-5-(trifluoromethyl)pyrazol-3-yl]imidazolidin-2-one, (4R)1-(5-tert-butylisoxazol-3-yl)-4-ethoxy-5-hydroxy-3-methyl-imidazolidin-2-one,4-amino-3-chloro-5-fluoro-6-(7-fluoro-1H-indol-6-yl)pyridine-2-carboxylic acid (including agrochemically acceptable esters thereof, for example, 4-amino-3-chloro-5-fluoro-6-(7-fluoro-1H-indol-6-yl)pyridine-2-carboxylic acid methyl ester, 4-amino-3-chloro-5-fluoro-6-(7-fluoro-1H-indol-6-yl)pyridine-2-carboxylic acid prop-2-ynyl ester and 4-amino-3-chloro-5-fluoro-6-(7-fluoro-1H-indol-6-yl)pyridine-2-carboxylic acid cyanomethyl ester), 3-ethyl-sulfanyl-N-(1,3,4-oxadiazol-2-yl)-5-(trifluoromethyl)-[1,2,4]triazolo[4,3-a]pyridine-8-carboxylic acid methyl)-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, 2-[[3-[[3-chloro-5-fluoro-6-[3-methyl -2,6-dioxo-4-(trifluoromethyl)pyrimidin-1-yl]-2-pyridyl]oxy]ethyl acetate, 6-chloro-4-(2,7-dimethyl-1-naphthyl)-5-hydroxy-2-methyl-pyridazin-3-one, (2R)-2-[(4-amino-3,5-dichloro-6-fluoro-2-pyridyl)oxy]propionic acid tetrahydrofuran-2-ylmethyl ester, (2R)-2-[(4-amino-3,5-dichloro-6-fluoro-2-pyridyl)oxy]propionic acid, 2-[(4-amino-3,5-dichloro-6-fluoro-2-pyridyl)oxy]propionic acid tetrahydrofuran-2-ylmethyl ester, 2-[(4-amino-3,5-dichloro-6-fluoro-2-pyridyl)oxy]propionic acid, 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, 6-amino-5-chloro-2-(4-chloro-2-fluoro-3-methoxy-phenyl)pyrimidine-4-carboxylic acid (2-fluorophenyl)methyl ester, 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, 2-[(E)-[2-chloro-4-fluoro-5-[3-methyl-2,6-dioxo-4-(trifluoromethyl)pyrimidin-1-yl]phenyl]methyleneamino]oxypropionic acid methyl ester, and (2R)-2-[(E)-[2-chloro-4-fluoro-5-[3-methyl-2,6-dioxo-4-(trifluoromethyl)pyrimidin-1-yl]phenyl]methyleneamino]oxypropionic acid methyl ester.

[0055] Mixtures of compounds of formula (I) may also be in the form of esters or salts, as mentioned, for example, in The Pesticide Manual, Sixteenth Edition, British Crop Protection Council, 2012.

[0056] The compounds of formula (I) can also be used in mixtures with other agrochemicals such as fungicides, nematicides or insecticides, examples of which are given in The Pesticide Manual.

[0057] The mixing ratio of the compound of formula (I) to the mixing partner is preferably from 1:100 to 1000:1.

[0058] These mixtures can advantageously be used in the abovementioned formulations ("active ingredient" in this case relates to the corresponding mixture of the compound of formula (I) with the mixing partner).

[0059] The compounds or mixtures of the present invention can also be used in combination with one or more herbicide safeners. Examples of such safeners include fenthiocarb, cloquintocet (including cloquintocet-mexyl), cyclopropylsulfonamide, dichloropropene, fenthiocarb (including fenthiocarb-ethyl), fenthiocarb, fluazifop, fenthiocarb, isoxadiazole (including isoxadiazole-ethyl), mefenpyr (including pyrazoles oxalic acid-diethyl), metcamifen and oxalonitrile.

[0060] Particularly preferred are mixtures of compounds of formula (I) with cyprosulfamide, isoxadifen, clofometrexate and / or metcamifen.

[0061] The safeners of compounds of formula (I) may also be in the form of esters or salts, as mentioned, for example, in The Pesticide Manual, 16th edition (BCPC), 2012. References to clofonethiol also apply to its lithium, sodium, potassium, calcium, magnesium, aluminum, iron, ammonium, quaternary ammonium, sulfonium or phosphonium salts (as disclosed in WO 02 / 34048).

[0062] 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.

[0063] The present invention further provides a method for controlling weeds in a place, the method comprising applying a composition comprising a compound of formula (I) to the place in a controlled amount of weeds. In addition, the present invention may further provide a method for selectively controlling weeds at a place including crop plants and weeds, wherein the method comprises applying a composition according to the present invention in a controlled amount of weeds to the place. 'Control' means killing, reducing or delaying growth or preventing or reducing germination. It should be noted that the compounds of the present invention show greatly improved selectivity compared to known structurally similar compounds. Plants to be controlled are usually unwanted plants (weeds). 'Place' means the area where the plant is growing or will grow. Application can be applied to the place before and / or after emergence of crop plants. Some crop plants can inherently tolerate the herbicidal effect of compounds with formula (I). Preferred crop plants include corn, wheat, barley, soybeans and rice.

[0064] The application rate of the compound of formula I can 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 the seed furrow; no-till application, etc.), the crop plant, one or more weeds to be controlled, the prevailing climatic conditions and other factors governed by the method of application, the time of application and the target crop. The compound of formula I according to the invention is usually applied at a rate of from 10 to 2500 g / ha, in particular from 25 to 1000 g / ha, more particularly from 25 to 250 g / ha.

[0065] Application is usually carried out by spraying the composition, typically by means of a tractor-mounted sprayer for large areas, but other methods such as dusting (for powders), dripping or drenching may also be used.

[0066] Crop plants are to be understood as also including those crop plants which have been rendered tolerant to other herbicides or classes of herbicides (e.g. ALS-inhibitors, GS-inhibitors, EPSPS-inhibitors, PPO-inhibitors, HPPD-inhibitors, inhibitor-PDS, inhibitor-SDPS and ACCase-inhibitors) by conventional methods of breeding or by genetic engineering. Examples of crops which have been rendered tolerant to imidazolinones (e.g. imazamox) by conventional methods of breeding are Summer rapeseed (canola). Examples of crops that have been rendered tolerant to herbicides by genetic engineering methods include, for example, maize varieties resistant to glyphosate and glufosinate, which are now and It is commercially available under the trademark ANTIQUID®.

[0067] Crop plants are also to be understood as those which have been rendered resistant to harmful insects by genetic engineering methods, for example Bt maize (resistant to the European corn borer), Bt cotton (resistant to the boll weevil) and also Bt potato (resistant to the Colorado beetle). Examples of Bt maize are Bt 176 corn hybrid (Syngenta Seeds). Bt toxins are proteins naturally produced by the soil bacterium Bacillus thuringiensis. Examples of toxins or transgenic plants capable of synthesizing such toxins are described in EP-A-451 878, EP-A-374 753, WO 93 / 07278, WO 95 / 34656, WO 03 / 052073 and EP-A-427 529. Examples of transgenic plants comprising one or more genes encoding insecticide resistance and expressing one or more toxins are (Corn), Yield (corn), (cotton), (cotton), (potato), as well as Plant crops or their seed material can both be resistant to herbicides and at the same time resistant to insect feeding ("stacked" transgenic events). For example, a seed can have the ability to express an insecticidal Cry3 protein while at the same time being tolerant to glyphosate.

[0068] Crop plants are also to be understood as including those which are obtained by conventional methods of breeding or genetic engineering and contain so-called output traits (for example improved storage stability, higher nutritional value and improved flavor).

[0069] These compositions can be used to control unwanted vegetation (collectively referred to as 'weeds'). The weeds to be controlled may be monocotyledonous species, for example Agrostis, Alopecurus, Avena, Brachiaria, Bromus, Cenchrus, Cyperus, Digitaria, Echinochloa, Eleusine, Lolium, Monochoria, Rottboellia, Sagittaria, Scirpus, Setaria ) and Sorghum, and may also be dicotyledonous species such as Abutilon, Amaranthus, Ambrosia, Chenopodium, Chrysanthemum, Conyza, Galium, Ipomoea, Nasturtium, Sida, Sinapis, Solanum, Stellaria, Veronica, Viola and Xanthium.

[0070] In a further aspect of the invention there is provided the use of a compound of formula (I) as defined herein as a herbicide.

[0071] Process for preparing compounds having formula (I)

[0072] Processes for preparing compounds such as compounds of formula (I) (which optionally may be agrochemically acceptable salts thereof) are now described and form a further aspect of the invention.

[0073] Solution 1

[0074] In which A 1 Yes-C(R 1 )(R 2 )-and X 1 In embodiments where is O, compounds of formula (1) can be prepared from compounds of formula (2) wherein LG represents a suitable leaving group such as Br or Cl and compounds of formula (3).

[0075]

[0076] A compound of formula (2) is treated with a compound of formula (3) and a carbonate base (eg potassium carbonate) in a suitable solvent (eg acetone).

[0077] Solution 2

[0078] Compounds of formula (2) can be prepared from benzyl alcohols of formula (4).

[0079]

[0080] For example, where LG is Br, a benzyl alcohol of formula (4) is treated with triphenylphosphine and carbon tetrabromide or phosphorus tribromide in a suitable solvent such as acetonitrile or dichloromethane.

[0081] Solution 3

[0082] Compounds of formula (4) can be prepared from benzyl alcohols of formula (5).

[0083]

[0084] A compound of formula (5) is treated with a chlorinating agent such as N-chlorosuccinimide in a suitable solvent such as acetonitrile.

[0085] Solution 4

[0086] Benzyl alcohols having formula (5) can be prepared from aldehydes having formula (6).

[0087]

[0088] A compound of formula (6) is treated with a reducing agent such as sodium borohydride in a suitable solvent such as water.

[0089] Solution 5

[0090] Compounds of formula (6) may be commercially available. Alternatively, they may be prepared synthetically. The synthetic route will depend on A 2 , A 3 , R 5 , R 6 , R 7 and R 8 For example, in A 2 and A 3 In the case of O, the compound of formula (6) can be prepared from 3,4-dihydroxybenzaldehyde (7).

[0091]

[0092] 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.

[0093] Solution 6

[0094] In an alternative approach, compounds of formula (4) may be prepared from compounds of formula (9).

[0095]

[0096] A compound of formula (9) is treated with a reducing agent such as sodium borohydride in a suitable solvent such as water.

[0097] Solution 7

[0098] The synthetic route used to obtain the compound of formula (9) will depend on A 2 , A 3 , R 5 , R 6 , R 7 and R 8 For example, in A 2 and A 3 In the case of O, the compound of formula (9) can be prepared from 2-chloro-4,5-dihydroxybenzaldehyde (10).

[0099]

[0100] 2-Chloro-4,5-dihydroxybenzaldehyde (10) is treated with a dibromide of formula (8) and a carbonate base such as potassium carbonate in a suitable solvent such as acetonitrile.

[0101] Solution 8

[0102] Alternatively, compounds of formula (9) can be prepared from aldehydes of formula (6).

[0103]

[0104] The compound of formula (6) is treated with a chlorinating agent (e.g., N-chlorosuccinimide) in a suitable solvent (e.g., 1,2-ethylene dichloride) and optionally in the presence of a suitable catalyst / ligand / additive combination. Suitable catalyst / ligand combinations may include palladium acetate (II) and 2-aminobenzoic acid. Suitable additives may include trifluoroacetic acid and silver trifluoroacetate.

[0105] Solution 9

[0106] In another alternative method, a compound of formula (1) (wherein A 1 Yes-C(R1 )(R 2 )-,X 1 is O, and A 2 and A 3 (O) can be prepared from a compound having formula (11).

[0107]

[0108] The synthetic steps and reaction conditions used to obtain compounds of formula (1) from compounds of formula (11) will depend on R 5 , R 6 , R 7 and R 8 varies with the nature of the

[0109] Solution 10

[0110] For example, in R 5 and R 6 is hydrogen, and R 7 and R 8 In the case of a methyl group, the compound of formula (1) can be prepared from the compound of formula (12).

[0111]

[0112] A compound of formula (12) is treated with an acid such as formic acid, either neat or in a suitable solvent such as N-methyl-2-pyrrolidone.

[0113] Solution 11

[0114] Compounds of formula (12) can be prepared from compounds of formula (13).

[0115]

[0116] A 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.

[0117] Solution 12

[0118] Compounds having formula (13) can be prepared from 5-chloro-6-(chloromethyl)-1,3-benzodioxol-2-one (15).

[0119]

[0120] 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.

[0121] Solution 13

[0122] 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).

[0123]

[0124] (6-Chloro-1,3-benzodioxol-5-yl)methanol (16) is treated with phosphorus pentachloride in a suitable solvent such as chlorobenzene.

[0125] Solution 14

[0126] In A 1 is -C(=O)-, and X 1 When is O, the compound of formula (1) can be prepared from the compound of formula (17).

[0127]

[0128] A 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.

[0129] Solution 15

[0130] Compounds of formula (17) can be prepared from compounds of formula (2), wherein LG represents a suitable leaving group (such as Br or Cl).

[0131]

[0132] For example, where LG is Br, a compound of formula (2) is treated with N,O-di-tert-butyloxycarbonylhydroxylamine, a suitable base (e.g. potassium carbonate) and optionally a suitable catalyst (e.g. tetrabutylammonium iodide) in a suitable solvent (e.g. acetone) to give a compound of formula (18). A compound of formula (18) is treated with a suitable acid (e.g. hydrochloric acid) in a suitable solvent (e.g. dioxane).

[0133] Scheme 16

[0134] Some compounds of formula (3) may be commercially available. For example, compounds of formula (3) (wherein R 3 and R 4 is a methyl group, and R 1 and R 2is hydrogen) is commercially available (CAS No. 81778-07-6). Alternatively, compounds of formula (3) can be prepared synthetically. For example, in 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 In the case of hydrogen, the compound of formula (3) can be prepared from 3,3-dichloro-2,2-dimethylpropanoic acid (19).

[0135]

[0136] 3,3-Dichloro-2,2-dimethylpropanoic acid (19) is treated with a suitable chlorinating agent such as thionyl chloride and catalyst dimethylformamide to give 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 give 3,3-dichloro-2,2-dimethyl-propane hydroxamic acid (21). 3,3-Dichloro-2,2-dimethyl-propane hydroxamic acid (21) is treated with an alcohol and a suitable base such as 1,8-diazabicyclo(5.4.0)undec-7-ene to give a compound having formula (3).

[0137] Solution 17

[0138] A compound having the formula (1) (wherein X 1 is S) can be made from a compound having formula (1) (wherein X 1 O) preparation.

[0139]

[0140] A compound having the formula (1) (wherein X 1 (O) is treated with a suitable sulfiding agent (eg phosphorus pentasulfide) in a suitable solvent (eg toluene).

[0141] The following non-limiting examples provide specific synthetic methods for representative compounds of the present invention (as mentioned in Table 1 below).

[0142] Preparation Example

[0143] Example 1: Preparation of Compound 1.001

[0144] Step 1: Preparation of 2,2-difluoro-3H-1,4-benzodioxane-6-carbaldehyde

[0145] At room temperature, potassium carbonate (8.79g, 86.9mmol) was added to 3,4-dihydroxybenzaldehyde (3.00g, 21.7mmol) in acetonitrile (45mL). Then 1,2-dibromo-1,1-difluoro-ethane (17.0g, 7.65mL, 76.0mmol) was added, and the reaction was stirred at 90 ° C for 18h. After this, another portion of 1,2-dibromo-1,1-difluoro-ethane (17.0g, 7.65mL, 76.0mmol) was added, and the reaction was stirred for another 24h. The reaction was quenched with water and the product was extracted with ethyl acetate (x3). The organic parts were merged, dried over MgSO4, filtered and concentrated in vacuo. 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-benzodioxane-6-carbaldehyde (0.889 g, 4.44 mmol, 20%) and 3,3-difluoro-2H-1,4-benzodioxane-6-carbaldehyde (0.889 g, 4.44 mmol, 20%) as a light 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).

[0146] Step 2: Preparation of (2,2-difluoro-3H-1,4-benzodioxane-6-yl)methanol

[0147] Sodium borohydride (0.386 g, 10.2 mmol) was added to the suspension of 1:1 mixture of 3,3-difluoro-2H-1,4-benzodioxane-6-carboxaldehyde (0.889 g, 4.44 mmol) and 2,2-difluoro-3H-1,4-benzodioxane-6-carboxaldehyde (0.889 g, 4.44 mol) in water (13.3 mL) at 0 ° C. The reaction was stirred for 5 h. The reaction was quenched with saturated NH4Cl aqueous solution and the product was extracted with ethyl acetate (x2). 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-benzodioxan-6-yl)methanol (0.786 g, 3.89 mmol, 44%) and (2,2-difluoro-3H-1,4-benzodioxan-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).

[0148] Step 3: Preparation of (6-chloro-3,3-difluoro-2H-1,4-benzodioxane-7-yl)methanol

[0149] A 1:1 mixture of (3,3-difluoro-2H-1,4-benzodioxan-6-yl)methanol (0.786 g, 3.89 mmol) and (2,2-difluoro-3H-1,4-benzodioxan-6-yl)methanol (0.786 g, 3.89 mmol) and N-chlorosuccinimide (1.09 g, 8.16 mmol) in acetonitrile (25.9 mL) was stirred at 70 °C for 1 h. The reaction mixture was concentrated to On, and purified by flash column chromatography (0-30% ethyl acetate in cyclohexane). The fractions containing the product were combined and concentrated to give 6-chloro-3,3-difluoro-2H-1,4-benzodioxane-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).

[0150] Step 4: Preparation of 7-(bromomethyl)-6-chloro-3,3-difluoro-2H-1,4-benzodioxane

[0151] To a solution of (6-chloro-3,3-difluoro-2H-1,4-benzodioxane-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 allowed to warm to room temperature and then stirred for 3 h. The reaction mixture was absorbed into On, and purified by flash column chromatography (0-20% ethyl acetate in cyclohexane). The fractions containing the product were concentrated to give 7-(bromomethyl)-6-chloro-3,3-difluoro-2H-1,4-benzodioxane (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).

[0152] Step 5: Preparation of 2-[(6-chloro-3,3-difluoro-2H-1,4-benzodioxan-7-yl)methyl]-4,4-dimethyl-isoxazolidin-3-one

[0153] To a solution of 7-(bromomethyl)-6-chloro-3,3-difluoro-2H-1,4-benzodioxane (0.300 g, 1.00 mmol) in acetone (9.0 mL) was 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 room temperature overnight. The reaction mixture was diluted with acetone (10 mL) and filtered through Filter and then pre-absorb the mixture into On, and purified by flash column chromatography (0-30% ethyl acetate in cyclohexane). The fractions containing the product were concentrated to give 2-[(6-chloro-3,3-difluoro-2H-1,4-benzodioxane-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).

[0154] Example 2: Preparation of Compound 1.002

[0155] Step 1: Preparation of 2-methyl-2,3-dihydro-1,4-benzodioxane-6-carbaldehyde and 3-methyl-2,3-dihydro-1,4-benzodioxane-6-carbaldehyde

[0156] At room temperature, potassium carbonate (29.3g, 290mmol) was added to a solution of 3,4-dihydroxybenzaldehyde (10.0g, 72.4mmol) in acetonitrile (145mL). 1,2-dibromopropane (73.1g, 37.7mL, 362mmol) was added, and the reaction was stirred overnight at 90°C. The reaction was quenched with water and extracted with ethyl acetate (x3). The organic parts were merged, dried over MgSO4, filtered and concentrated in vacuo. The crude material was purified by flash column chromatography (0-20% ethyl acetate in cyclohexane). Product containing fractions were combined and concentrated to give a 1:1 mixture of 2-methyl-2,3-dihydro-1,4-benzodioxane-6-carbaldehyde (1.84 g, 10.4 mmol, 14%) and 3-methyl-2,3-dihydro-1,4-benzodioxane-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).

[0157] Step 2: Preparation of (3-methyl-2,3-dihydro-1,4-benzodioxan-6-yl)methanol and (2-methyl-2,3-dihydro-1,4-benzodioxan-6-yl)methanol

[0158] Sodium borohydride (0.886 g, 23.4 mmol) was added in batches to a suspension of a 1:1 mixture of 3-methyl-2,3-dihydro-1,4-benzodioxane-6-carboxaldehyde (1.81 g, 10.2 mmol) and 2-methyl-2,3-dihydro-1,4-benzodioxane-6-carboxaldehyde (1.81 g, 10.2 mmol) in water (30.5 mL) at 0 ° C. The reaction was stirred for 3 h. The reaction was quenched with saturated NH4Cl aqueous solution and extracted with ethyl acetate (x2). The organic portions were combined, dried over MgSO4, filtered and concentrated in vacuo to give a 1:1 mixture of (3-methyl-2,3-dihydro-1,4-benzodioxan-6-yl)methanol (1.82 g, 10.1 mmol, 50%) and (2-methyl-2,3-dihydro-1,4-benzodioxan-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, regioisomers 1 and 2), 6.85-6.84 (m, 4H, regioisomers 1 and 2), 4.57 (s, 4H, regioisomers 1 and 2), 4.27-4.20 (m, 4H, regioisomers 1 and 2), 3.88-3.78 (m, 2H, regioisomers 1 and 2), 1.37-1.35 (m, 6H, regioisomers 1 and 2).

[0159] Step 3: Preparation of (6-chloro-2-methyl-2,3-dihydro-1,4-benzodioxan-7-yl)methanol and (6-chloro-3-methyl-2,3-dihydro-1,4-benzodioxan-7-yl)methanol

[0160] A 1:1 mixture of (2-methyl-2,3-dihydro-1,4-benzodioxan-6-yl)methanol (0.567 g, 3.15 mmol) and (3-methyl-2,3-dihydro-1,4-benzodioxan-6-yl)methanol (0.567 g, 3.15 mmol) and N-chlorosuccinimide (0.882 g, 6.61 mmol) in acetonitrile (21.0 mL) was stirred at 70 °C for 1 h. The reaction mixture was concentrated to On, and purified by flash column chromatography (0-40% ethyl acetate in cyclohexane). The fractions containing the product are combined and concentrated to obtain a mixture of regional isomeric products. The mixture is purified by reverse phase preparative HPLC purification (1-5% acetonitrile in water). The fractions containing the product are combined and concentrated to obtain (6-chloro-2-methyl-2,3-dihydro-1,4-benzodioxane-7-yl) methanol (0.241g, 1.12mmol, 18%) as a white solid and (6-chloro-3-methyl-2,3-dihydro-1,4-benzodioxane-7-yl) methanol (0.154g, 0.717mmol, 11%) as a white solid. 1H NMR (400MHz, CDCl3) δppm 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 (400MHz, CDCl3) δppm 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).

[0161] Step 4: Preparation of 7-(bromomethyl)-6-chloro-2-methyl-2,3-dihydro-1,4-benzodioxane

[0162] To a solution of (6-chloro-2-methyl-2,3-dihydro-1,4-benzodioxane-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 allowed to warm to room temperature and then stirred for 3 h. The reaction mixture was absorbed into On, and purified by flash column chromatography (0-15% ethyl acetate in cyclohexane). The fractions containing the product were concentrated to give 7-(bromomethyl)-6-chloro-2-methyl-2,3-dihydro-1,4-benzodioxane (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).

[0163] Step 5: Preparation of 2-[(6-chloro-2-methyl-2,3-dihydro-1,4-benzodioxan-7-yl)methyl]-4,4-dimethyl-isoxazolidin-3-one

[0164] To a solution of 7-(bromomethyl)-6-chloro-2-methyl-2,3-dihydro-1,4-benzodioxane (0.212 g, 0.764 mmol) in acetone (6.4 mL) was added potassium carbonate (0.161 g, 1.15 mmol) and 4,4-dimethylisoxazolidin-3-one (0.111 g, 0.917 mmol). The reaction was stirred at room temperature overnight. The reaction mixture was diluted with ethyl acetate (10 mL) and filtered through Filter, pre-absorb The product was concentrated to give 2-[(6-chloro-2-methyl-2,3-dihydro-1,4-benzodioxane-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).

[0165] Example 3: Preparation of Compound 1.006

[0166] Preparation of 5-ethoxy-4,4-dimethyl-isoxazolidin-3-one

[0167] Step 1: Preparation of 3,3-dichloro-2,2-dimethyl-propionyl chloride

[0168] 3,3-dichloro-2,2-dimethyl-propionic 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 at 5 mbar) to obtain 3,3-dichloro-2,2-dimethyl-propionyl 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).

[0169] Step 2: Preparation of 3,3-dichloro-2,2-dimethyl-propane hydroxamic acid

[0170] 3,3-dichloro-2,2-dimethyl-propanoyl chloride (3.00 g, 15.8 mmol) was added dropwise to an aqueous solution (8.09 g, 7.5 mL, 122 mmol) of hydroxylamine (50% by mass). The reaction mixture was stirred at room temperature for 10 min. The reaction mixture was extracted with dichloromethane, passed through a hydrophobic glass frit and concentrated in vacuo to obtain 3,3-dichloro-2,2-dimethyl-propane hydroxamic 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).

[0171] Step 3: Preparation of 5-ethoxy-4,4-dimethyl-isoxazolidin-3-one

[0172] A solution of 3,3-dichloro-2,2-dimethyl-propane hydroxamic 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 at 120 ° C for 45 min by microwave irradiation. The mixture was concentrated in vacuo and the residue was diluted with dichloromethane. 2M HCl was added and the product was extracted with dichloromethane (x5). The organic parts were combined, dried over MgSO4, filtered and concentrated in vacuo to obtain 5-ethoxy-4,4-dimethyl-isoxazolidin-3-one (0.269 g, 1.69 mmol, 63%) as a colorless oil. 1H NMR (400MHz, CDCl3) δppm8.20(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).

[0173] Preparation of 2-[(6-chloro-2,2,3,3-tetrafluoro-1,4-benzodioxane-7-yl)methyl]-5-ethoxy-4,4-dimethyl-isoxazolidin-3-one

[0174] Step 1: Preparation of 6-(chloromethyl)-2,2,3,3-tetrafluoro-1,4-benzodioxane

[0175] Under nitrogen atmosphere, (2,2,3,3-tetrafluoro-1,4-benzodioxane-6-yl)methanol (0.394 g, 1.65 mmol) was dissolved in thionyl chloride (5.0 mL) and stirred at room temperature overnight. The reaction mixture was then concentrated in vacuo to give 6-(chloromethyl)-2,2,3,3-tetrafluoro-1,4-benzodioxane (0.371 g, 1.45 mmol, 87%) as a yellow oil. 1HNMR (400 MHz, CDCl3) δ ppm 7.22-7.15 (m, 2H), 7.14-7.09 (m, 1H), 4.52 (s, 2H).

[0176] Step 2: Preparation of 5-chloro-7-(chloromethyl)-2,2,3,3-tetrafluoro-1,4-benzodioxane

[0177] Trichloroisocyanuric acid (0.840 g, 3.61 mmol) was added to a solution of 6-(chloromethyl)-2,2,3,3-tetrafluoro-1,4-benzodioxane (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 fractions containing the product were concentrated to give 6-chloro-7-(chloromethyl)-2,2,3,3-tetrafluoro-1,4-benzodioxane (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).

[0178] Step 3: Preparation of 2-[(6-chloro-2,2,3,3-tetrafluoro-1,4-benzodioxan-7-yl)methyl]-5-ethoxy-4,4-dimethyl-isoxazolidin-3-one

[0179] To 6-chloro-7-(chloromethyl)-2,2,3,3-tetrafluoro-1,4-benzodioxane (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) and filtered through Filtered and then purified by reverse phase preparative HPLC purification. The fractions containing the product were combined and concentrated to give 2-[(6-chloro-2,2,3,3-tetrafluoro-1,4-benzodioxane-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).

[0180] Example 4: Preparation of Compound 1.009

[0181] Step 1: Preparation of N-[(6-chloro-2,3-dihydro-1,4-benzodioxan-7-yl)methyl]hydroxylamine

[0182] N, O-bis (tert-butoxycarbonyl) hydroxylamine (0.620g, 2.58mmol), potassium carbonate (0.755g, 5.41mmol), 6-chloro-7-(chloromethyl)-2,3-dihydro-1,4-benzodioxane (0.504g, 2.30mmol) and tetrabutylammonium iodide (93mg, 0.25mmol) were dissolved in acetone (25mL) and heated to 60°C for 5h. The reaction mixture was filtered and concentrated in vacuo. The residue was treated with 4M HCl (10mL) in dioxane and stirred for 2h. The reaction mixture was concentrated in vacuo, and then water and dichloromethane were added. Concentrated NaOH was added dropwise to alkalize the solution to pH 9. The layers were separated and the aqueous layer was extracted with another portion of dichloromethane. The organic portions were combined, dried over MgSO4, filtered and concentrated in vacuo to give N-[(6-chloro-2,3-dihydro-1,4-benzodioxan-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).

[0183] Step 2: Preparation of 2-[(6-chloro-2,3-dihydro-1,4-benzodioxan-7-yl)methyl]-4,4-dimethyl-isoxazolidine-3,5-dione

[0184] 2,2-Dimethylmalonyl 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-benzodioxane-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 min. The reaction mixture was stirred for 1 h and then allowed to stand overnight at room temperature. The reaction mixture was acidified with 2M HCl, partitioned by passing it through a hydrophobic frit, and concentrated in vacuo. 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-benzodioxan-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).

[0185] Example 5: Preparation of Compound 1.004

[0186] Step 1: Preparation of 5-chloro-6-(chloromethyl)-1,3-benzodioxol-2-one

[0187] (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 min. The reaction was stirred at 135 °C for 4 h, then quenched with water and extracted with DCM. The organic portion was dried over MgSO4, filtered and concentrated to 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).

[0188] Step 2: Preparation of 2-[(2-chloro-4,5-dihydroxy-phenyl)methyl]-4,4-dimethyl-isoxazolidin-3-one

[0189] Under nitrogen atmosphere, 5-chloro-6-(chloromethyl)-1,3-benzodioxole-2-one (3.10 g, 14.2 mmol), 4,4-dimethylisoxazolidine-3-one (1.71 g, 14.9 mmol) and potassium carbonate (5.99 g, 42.5 mmol) were combined in DMF (31 mL). The reaction was stirred at room temperature for 3 h, then quenched with 2M HCl and extracted with ethyl acetate (x2). The combined organic portion was washed with brine, dried over MgSO4, filtered and concentrated to 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).

[0190] Step 3: Preparation of 2-[[2-chloro-5-hydroxy-4-(2-methylallyloxy)phenyl]methyl]-4,4-dimethylisoxazolidin-3-one

[0191] Potassium carbonate (1.9g, 14.0mmol) is added to a solution of 2-[(2-chloro-4,5-dihydroxy-phenyl)methyl]-4,4-dimethyl-isoxazolidin-3-one (2.5g, 9.20mmol) in acetonitrile (30mL). The mixture is stirred for 1h, and then 3-chloro-2-methylprop-1-ene (0.925g, 1mL, 10.0mmol) is added dropwise. The reaction mixture is heated to reflux overnight, then quenched with 2MHCl and extracted with ethyl acetate (x4). The combined organic portion is washed with brine, dried over MgSO4, filtered and concentrated. The crude material is purified by flash column chromatography (0-15% ethyl acetate in isohexane) to obtain 2-[[2-chloro-5-hydroxy-4-(2-methylallyloxy)phenyl]methyl]-4,4-dimethyl-isoxazolidin-3-one (0.607g, 1.86mmol, 20%). 1H NMR (400MHz, CDCl3) δppm 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).

[0192] Step 4: Preparation of 2-[(6-chloro-2,2-dimethyl-3H-1,4-benzodioxan-7-yl)methyl]-4,4-dimethyl-isoxazolidin-3-one

[0193] 2-[[2-chloro-5-hydroxy-4-(2-methylallyloxy)phenyl]methyl]-4,4-dimethyl-isoxazolidine-3-one (40mg, 0.123mmol) and formic acid (10mL, 252mmol) are combined and heated to reflux for 30min.The reaction mixture is concentrated, then diluted in DCM and washed with saturated NaHCO3aqueous solution.The water layer is extracted with DCM (x2).The combined organic part is washed with water, dried over MgSO4, filtered and concentrated.The crude material is purified by reverse phase preparative HPLC to obtain 2-[(6-chloro-2,2-dimethyl-3H-1,4-benzodioxane-7-yl)methyl]-4,4-dimethyl-isoxazolidine-3-one (19mg, 0.058mmol, 48%). 1H NMR (400MHz, CDCl3) δppm 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).

[0194] Example 6: Preparation of Compound 1.005

[0195] Step 1: Preparation of 2-[[2-chloro-4-hydroxy-5-(2-methylallyloxy)phenyl]methyl]-4,4-dimethylisoxazolidin-3-one

[0196] Potassium carbonate (1.9g, 14.0mmol) is added to a solution of 2-[(2-chloro-4,5-dihydroxy-phenyl)methyl]-4,4-dimethyl-isoxazolidin-3-one (2.5g, 9.20mmol) in acetonitrile (30mL). The mixture is stirred for 1h, and then 3-chloro-2-methylprop-1-ene (0.925g, 1mL, 10.0mmol) is added dropwise. The reaction mixture is heated to reflux overnight, then quenched with 2MHCl and extracted with ethyl acetate (x4). The combined organic portion is washed with brine, dried over MgSO4, filtered and concentrated. The crude material is purified by flash column chromatography (0-15% ethyl acetate in isohexane) to obtain 2-[[2-chloro-4-hydroxy-5-(2-methylallyloxy)phenyl]methyl]-4,4-dimethyl-isoxazolidin-3-one (0.363g, 1.11mmol, 12%). 1H NMR (400MHz, CDCl3) δppm 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).

[0197] Step 2: Preparation of 2-[(6-chloro-3,3-dimethyl-2H-1,4-benzodioxan-7-yl)methyl]-4,4-dimethyl-isoxazolidin-3-one

[0198] 2-[[2-chloro-4-hydroxy-5-(2-methylallyloxy)phenyl]methyl]-4,4-dimethyl-isoxazolidine-3-one (40mg, 0.123mmol) and formic acid (10mL, 252mmol) are combined and heated to reflux for 30min. The reaction mixture is concentrated, then diluted in DCM and washed with saturated NaHCO3 aqueous solution. The water layer is extracted with DCM (x2). The combined organic portion is washed with water, dried over MgSO4, filtered and concentrated. The crude material is purified by reverse phase preparative HPLC to obtain 2-[(6-chloro-3,3-dimethyl-2H-1,4-benzodioxane-7-yl)methyl]-4,4-dimethyl-isoxazolidine-3-one (12mg, 0.037mmol, 30%). 1H NMR (400MHz, CDCl3) δppm 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).

[0199] Example 7: Preparation of Compound 1.029

[0200] Step 1: Preparation of 7-chlorochroman-6-carbaldehyde

[0201] 1,2-dichloroethane (74mL) and 2,2,2-trifluoroacetic acid (8.52g, 5.76mL, 74.0mmol) are added to a mixture of chroman-6-carboxaldehyde (1.20g, 7.40mmol), N-chlorosuccinimide (1.48g, 11.1mmol), palladium (II) acetate (0.175g, 0.740mmol), 2-aminobenzoic acid (0.311g, 2.22mmol) and silver trifluoroacetate (0.167g, 0.740mmol). The reaction mixture is heated to 60 ° C for 18h and then distributed between saturated NaHCO3 aqueous solution and DCM. The water layer is extracted with DCM (x2), and the combined organic part is passed through a hydrophobic filter paper and then concentrated. The crude material is purified by reverse phase flash column chromatography to obtain 7-chlorochroman-6-carboxaldehyde (0.442g, 2.25mmol, 30%). 1H NMR (400MHz, CDCl3) δppm 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).

[0202] Step 2: Preparation of (7-chlorochroman-6-yl)methanol

[0203] At 0 ℃, under nitrogen atmosphere, diisobutylaluminum hydride (6.55mL 1M toluene solution, 6.55mmol) is added dropwise to a solution of 7-chlorochroman-6-carboxaldehyde (0.515g, 2.62mmol) in 2-methyltetrahydrofuran (5.95mL). The reaction mixture is stirred at room temperature for 3h, then quenched by dropping ethyl acetate at 0 ℃. Saturated sodium potassium tartrate aqueous solution is added and the mixture is vigorously stirred for 1h. The mixture is then extracted with ethyl acetate (2x). The combined organic part is passed through a hydrophobic glass frit and concentrated to obtain (7-chlorochroman-6-yl) methanol (0.361g, 1.82mmol, 69%). 1H NMR (400MHz, CDCl3) δppm 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).

[0204] Step 3: Preparation of 7-chloro-6-(chloromethyl)chroman

[0205] (7-chlorochroman-6-yl)methanol (0.311 g, 1.57 mmol) and thionyl chloride (7.44 mL, 102 mmol) are combined and stirred overnight at room temperature under a nitrogen atmosphere. The reaction mixture is added dropwise to water and extracted with ethyl acetate (x3). The combined organic portion is then concentrated through a hydrophobic filter paper to obtain 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).

[0206] Step 4: Preparation of 2-[(7-chlorochroman-6-yl)methyl]-4,4-dimethyl-isoxazolidin-3-one

[0207] By 7- chloro-6- (chloromethyl) chroman (0.265g, 1.22mmol), 4,4- dimethyl-isoxazolidine-3-one (0.183g, 1.59mmol), potassium carbonate (0.337g, 2.44mmol) and acetone (7.32mL) merge, and at room temperature stir for 2 days.Reactant mixture is diluted with water and extracted with ethyl acetate (x3).Organic part is merged, by hydrophobic filter paper and concentrated.Crude material is purified by reverse phase flash column chromatography, to obtain 2- [(7- chloro-chroman-6-yl) methyl] -4,4- dimethyl-isoxazolidine-3-one (80mg, 0.270mmol, 22%). 1H NMR (400MHz, CDCl3) δppm 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).

[0208] Example 8: Preparation of Compound 1.038

[0209] Preparation of 2-[(6-chloro-3,3-difluoro-2H-1,4-benzodioxan-7-yl)methyl]-4,4-dimethyl-isoxazolidine-3-thione

[0210] Under argon atmosphere, trimethyl (trimethylsilyloxy) silane (0.180g, 0.237mL, 1.11mmol) and phosphorus pentasulfide (82mg, 0.370mmol) are added to a solution of 2-[(6-chloro-3,3-difluoro-2H-1,4-benzodioxane-7-yl)methyl]-4,4-dimethyl-isoxazolidine-3-one (0.130g, 0.370mmol) in toluene (4mL). The reaction mixture is heated to 110 ° C for 1h and then concentrated. The crude material is purified by flash column chromatography (0-60% ethyl acetate in hexane) to obtain 2-[(6-chloro-3,3-difluoro-2H-1,4-benzodioxane-7-yl)methyl]-4,4-dimethyl-isoxazolidine-3-thione (75mg, 0.204mmol, 55%). 1H NMR (400MHz, d6-DMSO) δppm 7.46 (s, 1H), 7.14 (s, 1H), 5.19 (s, 2H), 4.64 (t, 2H), 4.18 (s, 2H), 1.21 (s, 6H).

[0211] Additional examples of compounds of formula (I) were prepared in a manner analogous to the above examples and are shown with characterizing data in Table 1 below.

[0212] Table 1. Compounds of the present invention

[0213]

[0214]

[0215]

[0216]

[0217]

[0218]

[0219]

[0220]

[0221]

[0222]

[0223]

[0224] Biological Examples

[0225] Seeds of various test species (Amaranthus retoflexus (AMARE), Setariafaberi (SETFA), Echinochloa crus-galli (ECHCG), Ipomoea hederacea (IPOHE)) were sown in standard soil in pots. After one day of cultivation (pre-emergence) or after 8 days of cultivation (post-emergence) in a greenhouse under controlled conditions (24°C / 16°C, day / night; 14 h light; 65% humidity), the plants were sprayed with an aqueous spray solution obtained as follows: i) the technical active ingredient was formulated in an acetone / water (50:50) solution containing 0.5% Tween 20 (polyoxyethylene sorbitan monolaurate, CAS RN 9005-64-5), or ii) the technical active ingredient was dissolved in a small amount of acetone and a special solvent and emulsifier mixture called IF50 (11.12% Emulsogen EL360 TM + 44.44% N-methylpyrrolidone + 44.44% Dowanol DPM glycol ether) and then diluted to the desired concentration using 0.2% Genapol XO80 (CAS No. 9043-30-5) in water as a diluent. The compound was applied at 250 g / ha. The test plants were then grown in a greenhouse under controlled conditions (24°C / 16°C, day / night; 14 hours of light; 65% humidity) and watered twice a day. Before emergence and 13 days after emergence, the percentage of damage to the plants was evaluated. The biological activity is shown in the following table on a five-point scale (5 = 81%-100%; 4 = 61%-80%; 3 = 41%-60%; 2 = 21%-40%; 1 = 0-20%); NT indicates not tested.

[0226] Table B1. Post-emergence tests

[0227]

[0228]

[0229] [a] A 55:45 mixture of 1.016:1.019 was tested [b] A 55:45 mixture of 1.017:1.020 was tested [c] A 55:45 mixture of 1.018:1.021 was tested Table B2. Pre-emergence testing

[0230]

[0231] [a] A 55:45 ratio mixture of 1.016:1.019 was tested

[0232] [b] A 55:45 ratio mixture of 1.017:1.020 was tested

[0233] [c] Tested a 55:45 ratio mixture of 1.018:1.021

[0234] Seeds of the following various test species were sown in standard soil in pots: Leptochloachinesis (LEFCH), Echinochloa crus-galli (ECHCG) and Cyperusesculentus (CYPES). After one day of cultivation (pre-emergence) or 13 days of cultivation (post-emergence) in a greenhouse under controlled conditions (at 30°C / 20°C, day / night; 18 hours of light; 75% humidity), the plants were sprayed with an aqueous spray solution obtained as follows: the technical grade active ingredient was dissolved in a small amount of acetone and a special solvent and emulsifier mixture called IF50 (11.12% Emulsogen EL360 TM + 44.44% N-methylpyrrolidone + 44.44% Dowanol DPM glycol ether) and then diluted to the desired concentration using 0.2% Genapol XO80 (CAS No. 9043-30-5) in water as a diluent. The compound was applied at 500 g / ha. These test plants were then grown in a greenhouse under controlled conditions in a greenhouse (at 30°C / 20°C, day / night; 18 hours of light; 75% humidity) and watered twice a day. Before emergence and 13 days after emergence, the percentage of damage caused to the plants by the test was evaluated. The biological activity is shown in the following table on a five-point scale (5 = 81%-100%; 4 = 61%-80%; 3 = 41%-60%; 2 = 21%-40%; 1 = 0-20%); NT indicates not tested.

[0235] Table B3. Post-emergence testing

[0236]

[0237]

[0238] Table B4. Pre-emergence test

[0239]

Claims

1. A compound having formula (I), in A 1 Yes CR 1 R 2 or C(O); A 2 Selected from the group consisting of: CR 9 R 10 、C(O)、O、S(O) p and N(R 13 ); A 3 Selected from the group consisting of: CR 11 R 12 、C(O)、O、S(O) p and N(R 13 ); X 1 is O or S; R 1 Selected from the group consisting of 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-; R 2 is hydrogen, R 3 is a C1-C3 alkyl group; R 4 is a C1-C3 alkyl group; R 5 is selected from the group consisting of hydrogen, halogen, C1-C6 alkyl, C1-C6 haloalkyl, C3-C6 cycloalkyl and C1-C6 alkoxy-; and R 6 is selected from the group consisting of hydrogen, halogen, C1-C6 alkyl, C1-C6 haloalkyl, C3-C6 cycloalkyl and C1-C6 alkoxy-; or R 5 and R 6 Together they are =O or -(CH2) n -;and R 7 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 they are =O or -(CH2) n -;and R 9 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-; or R 9 and R 10 Together is -(CH2) n -;and R 11 Selected from the group consisting of hydrogen, halogen, C1-C6 alkyl, C1-C6 haloalkyl, C3-C6 cycloalkyl and C1-C6 alkoxy-; R 12 is selected from the group consisting of hydrogen, halogen, C1-C6 alkyl, C1-C6 haloalkyl, C3-C6 cycloalkyl and C1-C6 alkoxy-; or R 11 and R 12 Together is -(CH2) n -; R 13 is hydrogen or C1-C3 alkyl; n is independently 2, 3, 4, 5 or 6; and p is independently 0, 1 or 2.

2. The compound of formula (I) according to claim 1, wherein X 1 It's O.

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

4. A compound of formula (I) according to any one of the preceding claims, wherein A 1 Yes CR 1 R 2 , and R 1 It's hydrogen.

5. A compound of formula (I) according to any one of claims 1 to 3, wherein A 1 Yes CR 1 R 2 , and R 1 It is a C1-C6 alkoxy group.

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

7. A compound according to any one of the preceding claims, wherein A 2 This is O.

8. A compound according to any one of the preceding claims, wherein A 2 Japanese A 3 This is O.

9. A compound according to any one of the preceding claims, wherein R 5 , R 6 , R 7 and R 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 the preceding claims, and an agriculturally acceptable formulation adjuvant.

11. The herbicidal composition according to claim 10, further comprising at least one additional pesticide.

12. The herbicidal composition according to claim 11, wherein The additional pesticide is a herbicide or a herbicide safener.

13. A method of controlling weeds at a locus, the method comprising applying to the locus a weed controlling amount of a composition according to any one of claims 10 to 12.

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

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