The present invention relates to herbicidal compounds, to processes for their preparation, to herbicidal compositions which comprise the herbicidal compounds, and to their use for controlling weeds, in particular in crops of useful plants, or for inhibiting plant growth.

Herbicidal 3-isoxazolidinones are known from US 4,405,357. Herbicidal isoxazolidine- 3, 5-diones are known from US 4,302,238. The present invention relates to novel 3- isoxazolidinone and isoxazolidine-3, 5-dione compounds. Thus, according to the present invention there is provided a compound of Formula (I): or an agronomically acceptable salt thereof, wherein:

A ¹ is CR ¹ R ² or C(O); A ² is selected from the group consisting of CR ⁷ R ⁸ , C(O), O, S(O) _P and N(R ¹¹ ); A ³ is selected from the group consisting of CR ⁹ R ¹⁰ , C(O), O, S(O) _P and N(R ¹¹ ); X ¹ is O or S; R ¹ is selected from the group consisting of hydrogen, halogen, HO-, Ci-Cealkoxy, Ci- Cealkoxy-Ci-Cealkoxy-, Ci-C3alkyl-C(O)O-, HOC(0)Ci-C6alkoxy-, Ci-C6alkoxy-C(0)-Ci- Cealkoxy-, Ci-C3alkyl-S(O) _p - and Ci-C3alkyl-S(0) _p Ci-C6alkoxy-; R ² is hydrogen; R ³ is Ci- Csalkyl; R ⁴ is Ci-Csalkyl; R ⁵ is selected from the group consisting of hydrogen, halogen, Ci- Cealkyl, Ci-Cehaloalkyl, Cs-Cecycloalkyl and Ci-Cealkoxy-; R ⁶ is selected from the group consisting of hydrogen, halogen, Ci-Cealkyl, Ci-Cehaloalkyl, Cs-Cecycloalkyl and Ci-Cealkoxy- ; provided that R ⁵ and R ⁶ are not both hydrogen; or R ⁵ and R ⁶ together are =0 or -(CH ₂ ) _n -; and R ⁷ is selected from the group consisting of hydrogen, halogen, Ci-Cealkyl, Ci-Cehaloalkyl, Cs-Cecycloalkyl and Ci-Cealkoxy-; R ⁸ is selected from the group consisting of hydrogen, halogen, Ci-Cealkyl, Ci-Cehaloalkyl, Cs-Cecycloalkyl and Ci-Cealkoxy-; or R ⁷ and R ⁸ together are -(CH ₂ ) _n -; and R ⁹ is selected from the group consisting of hydrogen, halogen, Ci-Cealkyl, Ci-Cehaloalkyl, Cs-Cecycloalkyl and Ci-Cealkoxy-; R ¹⁰ is selected from the group consisting of hydrogen, halogen, Ci-Cealkyl, Ci-Cehaloalkyl, Cs-Cecycloalkyl and Ci-Cealkoxy-; R ⁹ and R ¹⁰ together are -(CH ₂ ) _n -; R ¹¹ is hydrogen or Ci-Csalkyl; n is independently 2, 3, 4 ,5 or 6; and p is independently 0, 1 or 2. Ci -Cealkyl- includes, for example, methyl (Me, CH ₃ ), ethyl (Et, C2H5), n-propyl (n-Pr), isopropyl (Z-Pr), n-butyl (n-Bu), isobutyl (/-Bu), sec-butyl and tert-butyl (t-Bu). Ci-C ₃ alkyl includes methyl (Me, CH ₃ ), ethyl (Et, C2H5) and propyl (Pr e.g /so-propyl and n-propyl).

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

Ci-Cehaloalkyl- 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. Ci-C2haloalkyl 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.

Ci-Cealkoxy includes methoxy, ethoxy and iso-propoxy-.

Ci-Cehaloalkoxy- 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.

Ci-Cealkoxy-Ci-Cealkoxy- includes for example methoxymethoxy- and ethoxymethoxy-.

Ci-C ₃ alkyl-C(O)O- includes methyl-C(O)O- and ethyl-C(O)O-.

Ci-C6alkoxy-C(0)-Ci-C6alkoxy- includes methoxy-C(0)-methoxy- and ethoxy-C(O)- methoxy-.

Ci-C ₃ alkyl-S(0) _p Ci-C6alkoxy- includes methyl-S(0) _p methoxy- and ethyl- S(0) _p methoxy-.

C ₃ -C6cycloalkyl includes cyclopropyl, cyclopentyl and cyclohexyl.

Ci-C4alkyl-S- (alkylthio) includes, for example, methylthio, ethylthio, propylthio, isopropylthio, n-butylthio, isobutylthio, sec-butylthio or tert-butylthio, preferably methylthio or ethylthio.

Ci-C4alkyl-S(O)- (alkylsulfinyl) includes, for example, methylsulfinyl, ethylsulfinyl, propylsulfinyl, isopropylsulfinyl, n-butylsulfinyl, isobutylsulfinyl, sec-butylsulfinyl or tertbutylsulfinyl, preferably methylsulfinyl or ethylsulfinyl.

Ci-C4alkyl-S(O)2- (alkylsulfonyl) includes, for example, methylsulfonyl, ethylsulfonyl, propylsulfonyl, isopropylsulfonyl, n-butylsulfonyl, isobutylsulfonyl, sec-butylsulfonyl or tertbutylsulfonyl, preferably methylsulfonyl or ethylsulfonyl.

In one embodiment of the present invention, there is provided a compound of Formula (I) wherein X ¹ is O.

In another embodiment of the present invention, there is provided a compound of Formula (I) wherein R ³ and R ⁴ are methyl. In another embodiment of the present invention, there is provided a compound of Formula (I) wherein A ¹ is CR ¹ R ² and R ¹ is hydrogen. Thus, in a preferred embodiment of the present invention there is provided a compound of Formula 1 a:

In another embodiment of the present invention, there is provided a compound of Formula (I) wherein A ¹ is CR ¹ R ² and R ¹ is Ci-Cealkoxy.

In another embodiment of the present invention, there is provided a compound of Formula (I) wherein A ¹ is C(O). Thus, in a preferred embodiment of the present invention there is provided a compound of Formula 1 b:

In one embodiment of the present invention, there is provided a compound of Formula (I), Formula (la) or Formula (lb) wherein A ² is selected from the group consisting of CH ₂ , C(O), O, S and NH, preferably O.

In another embodiment of the present invention, there is provided a compound of Formula (I), Formula (la) or Formula (lb) wherein A ³ is selected from the group consisting of CH2, C(O), O, S and NH, preferably O.

In another embodiment of the present invention, there is provided a compound of Formula (I), Formula (la) or Formula (lb) wherein (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 CH ₂ and A ³ is O; (vi) A ² is O and A ³ is CH ₂ ; (vii) A ² is CH ₂ and A ³ is CH ₂ ; (viii) A ² is O and A ³ is S; or (ix) A ² is S and A ³ are O.

In a preferred embodiment of the present invention, there is provided a compound of Formula (I), Formula (la) or Formula (lb) wherein A ² and A ³ are O.

In another embodiment of the present invention, there is provided a compound of Formula (I), Formula (la) or Formula (lb) wherein R ⁵ and R ⁶ are independently selected from the group consisting of hydrogen, halogen and Ci-Cealkyl. In a more preferred embodiment, R ⁵ and R ⁶ are independently selected from the group consisting of hydrogen, methyl and fluoro. In another embodiment, R ⁵ and R ⁶ are halogen, preferably fluoro.

Compounds of Formula (I) may contain asymmetric centres and may be present as a single enantiomer, pairs of enantiomers in any proportion or, where more than one asymmetric centre are present, contain diastereoisomers in all possible ratios. Typically, one of the enantiomers has enhanced biological activity compared to the other possibilities.

The present invention also provides agronomically acceptable salts of compounds of Formula (I). Salts that the compounds of Formula (I) may form with amines, including primary, secondary and tertiary amines (for example ammonia, dimethylamine and triethylamine), alkali metal and alkaline earth metal bases, transition metals or quaternary ammonium bases are preferred.

The compounds of Formula (I) according to the invention can be used as herbicides by themselves, but they are generally formulated into herbicidal compositions using formulation adjuvants, such as carriers, solvents and surface-active agents (SAA). Thus, the present invention further provides a herbicidal composition comprising a herbicidal compound according to any one of the previous claims and an agriculturally acceptable formulation adjuvant. The composition can be in the form of concentrates which are diluted prior to use, although ready-to-use compositions can also be made. The final dilution is usually made with water, but can be made instead of, or in addition to, water, with, for example, liquid fertilisers, micronutrients, biological organisms, oil or solvents.

The herbicidal compositions generally comprise from 0.1 to 99 % by weight, especially from 0.1 to 95 % by weight, compounds of Formula I and from 1 to 99.9 % by weight of a formulation adjuvant which preferably includes from 0 to 25 % by weight of a surface-active substance.

The compositions can be chosen from a number of formulation types. These include an emulsion concentrate (EC), a suspension concentrate (SC), a suspo-emulsion (SE), a capsule suspension (CS), a water dispersible granule (WG), an emulsifiable granule (EG), an emulsion, water in oil (EG), an emulsion, oil in water (EW), a micro-emulsion (ME), an oil dispersion (OD), an oil miscible flowable (OF), an oil miscible liquid (OL), a soluble concentrate (SL), an ultra-low volume suspension (SU), an ultra-low volume liquid (UL), a technical concentrate (TK), a dispersible concentrate (DC), a soluble powder (SP), a wettable powder (WP) and a soluble granule (SG). The formulation type chosen in any instance will depend upon the particular purpose envisaged and the physical, chemical and biological properties of the compound of Formula (I). Soluble powders (SP) may 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 sulphate) or one or more water-soluble organic solids (such as a polysaccharide) and, optionally, one or more wetting agents, one or more dispersing agents or a mixture of said agents to improve water dispersibility/solubility. The mixture is then ground to a fine powder. Similar compositions may also be granulated to form water soluble granules (SG).

Wettable powders (WP) may 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 dispersing agents and, optionally, one or more suspending agents to facilitate the dispersion in liquids. The mixture is then ground to a fine powder. Similar compositions may also be granulated to form water dispersible granules (WG).

Granules (GR) may be formed either by granulating a mixture of a compound of Formula (I) and one or more powdered solid diluents or carriers, or from pre-formed blank granules by absorbing a compound of Formula (I) (or a solution thereof, in a suitable agent) in a porous granular material (such as pumice, attapulgite clays, fuller's earth, kieselguhr, diatomaceous earths or ground corn cobs) or by adsorbing a compound of Formula (I) (or a solution thereof, in a suitable agent) on to a hard core material (such as sands, silicates, mineral carbonates, sulphates or phosphates) and drying if necessary. Agents which are commonly used to aid absorption or adsorption include solvents (such as aliphatic and aromatic petroleum solvents, alcohols, ethers, ketones and esters) and sticking agents (such as polyvinyl acetates, polyvinyl alcohols, dextrins, sugars and vegetable oils). One or more other additives may also be included in granules (for example an emulsifying agent, wetting agent or dispersing agent).

Dispersible Concentrates (DC) may 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 surface-active agent (for example to improve water dilution or prevent crystallisation in a spray tank).

Emulsifiable concentrates (EC) or oil-in-water emulsions (EW) may be prepared by dissolving a compound of Formula (I) in an organic solvent (optionally containing one or more wetting agents, one or more emulsifying agents 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 Trade Mark), 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), dimethyl amides of fatty acids (such as Cs-C fatty acid dimethylamide) and chlorinated hydrocarbons. An EC product may spontaneously emulsify on addition to water, to produce an emulsion with sufficient stability to allow spray application through appropriate equipment.

Preparation of an EW involves obtaining a compound of Formula (I) either as a liquid (if it is not a liquid at room temperature, it may be melted at a reasonable temperature, typically below 70°C) or in solution (by dissolving it in an appropriate solvent) and then emulsifying the resultant 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 chlorobenzenes), aromatic solvents (such as alkylbenzenes or alkylnaphthalenes) and other appropriate organic solvents which have a low solubility in water.

Microemulsions (ME) may be prepared by mixing water with a blend of one or more solvents with one or more SAAs, to produce spontaneously a thermodynamically stable isotropic liquid formulation. A compound of Formula (I) is present initially in either the water or the solvent/SAA blend. Suitable solvents for use in MEs include those hereinbefore described for use in in ECs or in EWs. An ME may be either an oil-in-water or a water-in-oil system (which system is present may be determined by conductivity measurements) and may be suitable for mixing water-soluble and oil-soluble pesticides in the same formulation. An ME is suitable for dilution into water, either remaining as a microemulsion or forming a conventional oil-in-water emulsion.

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

Aerosol formulations comprise a compound of Formula (I) and a suitable propellant (for example n-butane). A compound of Formula (I) may also be dissolved or dispersed in a suitable medium (for example water or a water miscible liquid, such as n-propanol) to provide compositions for use in non-pressurised, hand-actuated spray pumps.

Capsule suspensions (CS) may be prepared in a manner similar to the preparation of EW formulations but with an additional polymerisation stage such that an aqueous dispersion of oil droplets is obtained, in which each oil droplet is encapsulated by a polymeric shell and contains a compound of Formula (I) and, optionally, a carrier or diluent therefor. The polymeric shell may be produced by either an interfacial polycondensation reaction or by a coacervation procedure. The compositions may provide for controlled release of the compound of Formula (I) and they may be used for seed treatment. A compound of Formula (I) may also be formulated in a biodegradable polymeric matrix to provide a slow, controlled release of the compound.

The composition may include one or more additives to improve the biological performance of the composition, for example by improving wetting, retention or distribution on surfaces; resistance to rain on treated surfaces; or uptake or mobility of a compound of Formula (I). Such additives include surface active agents (SAAs), spray additives based on oils, for example certain mineral oils or natural plant oils (such as soy bean and rape seed oil), modified plant oils such as methylated rape seed oil (MRSO), and blends of these with other bio-enhancing adjuvants (ingredients which may aid or modify the action of a compound of Formula (I).

Wetting agents, dispersing agents and emulsifying agents may be SAAs of the cationic, anionic, amphoteric or non-ionic type.

Suitable SAAs of the cationic type include quaternary ammonium compounds (for example cetyltrimethyl ammonium bromide), imidazolines and amine salts.

Suitable anionic SAAs include alkali metals salts of fatty acids, salts of aliphatic monoesters of sulphuric acid (for example sodium lauryl sulphate), salts of sulphonated aromatic compounds (for example sodium dodecylbenzenesulphonate, calcium dodecylbenzenesulphonate, butylnaphthalene sulphonate and mixtures of sodium di- /sopropyl- and tri-/sopropyl-naphthalene sulphonates), ether sulphates, alcohol ether sulphates (for example sodium laureth-3-sulphate), ether carboxylates (for example sodium laureth-3-carboxylate), phosphate esters (products from the reaction between one or more fatty alcohols and phosphoric acid (predominately mono-esters) or phosphorus pentoxide (predominately di-esters), for example the reaction between lauryl alcohol and tetraphosphoric acid; additionally these products may be ethoxylated), sulphosuccinamates, paraffin or olefine sulphonates, taurates, lignosulphonates and phosphates / sulphates of tristyrylphenols.

Suitable SAAs of the amphoteric type include betaines, propionates and glycinates.

Suitable SAAs of the non-ionic 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 said partial esters with ethylene oxide; block polymers (comprising ethylene oxide and propylene oxide); alkanolamides; simple esters (for example fatty acid polyethylene glycol esters); amine oxides (for example lauryl dimethyl amine oxide); lecithins and sorbitans and esters thereof, alkyl polyglycosides and tristyrylphenols.

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

The compounds of present invention can also be used in mixture with one or more additional herbicides and/or plant growth regulators. Examples of such additional herbicides or plant growth regulators include acetochlor, acifluorfen (including acifluorfen-sodium), aclonifen, ametryn, amicarbazone, aminopyralid, aminotriazole, atrazine, beflubutamid-M, benquitrione, bensulfuron (including bensulfuron-methyl), bentazone, bicyclopyrone, bilanafos, bipyrazone, bispyribac-sodium, bixlozone, bromacil, bromoxynil, butachlor, butafenacil, carfentrazone (including carfentrazone-ethyl), cloransulam (including cloransulam-methyl), chlorimuron (including chlorimuron-ethyl), chlorotoluron, chlorsulfuron, cinmethylin, clacyfos, clethodim, clodinafop (including clodinafop-propargyl), clomazone, clopyralid, cyclopyranil, cyclopyrimorate, cyclosulfamuron, cyhalofop (including cyhalofop- butyl), 2,4-D (including the choline salt and 2-ethylhexyl ester thereof), 2,4-DB, desmedipham, dicamba (including the aluminium, aminopropyl, bis-aminopropylmethyl, choline, dichloroprop, diglycolamine, dimethylamine, dimethylammonium, potassium and sodium salts thereof) diclosulam, diflufenican, diflufenzopyr, dimethachlor, dimethenamid-P, dioxopyritrione, diquat dibromide, diuron, epyrifenacil, ethalf lu ralin, ethofumesate, fenoxaprop (including fenoxaprop- P-ethyl), fenoxasulfone, fenpyrazone, fenquinotrione, fentrazamide, flazasulfuron, florasulam, florpyrauxifen (including florpyrauxifen-benzyl), fluazifop (including fluazifop-P-butyl), flucarbazone (including flucarbazone-sodium), flufenacet, flumetsulam, flumioxazin, fluometuron, fomesafen, flupyrsulfuron (including flupyrsulfuron-methyl-sodium), fluroxypyr (including fluroxypyr-meptyl), fomesafen, foramsulfuron, glufosinate (including L-glufosinate and the ammonium salts of both), glyphosate (including the diammonium, isopropylammonium and potassium salts thereof), halauxifen (including halauxifen-methyl), haloxyfop (including haloxyfop-methyl), hexazinone, hydantocidin, imazamox (including R- imazamox), imazapic, imazapyr, imazethapyr, indaziflam, iodosulfuron (including iodosulfuron-methyl-sodium), iofensulfuron (including iofensulfuron-sodium), ioxynil, isoproturon, isoxaflutole, lancotrione, MCPA, MCPB, mecoprop-P, mesosulfuron (including mesosulfuron-methyl), mesotrione, metamitron, metazachlor, methiozolin, metolachlor, metosulam, metribuzin, metsulfuron, napropamide, nicosulfuron, norflurazon, oxadiazon, oxasulfuron, oxyfluorfen, paraquat dichloride, pendimethalin, penoxsulam, phenmedipham, picloram, pinoxaden, pretilachlor, primisulfuron-methyl, prometryne, propanil, propaquizafop, propyrisulfuron, propyzamide, prosulfocarb, prosulfuron, pyraclonil, pyraflufen (including pyraflufen-ethyl), pyrasulfotole, pyridate, pyriftalid, pyrimisulfan, pyroxasulfone, pyroxsulam, quinclorac, quinmerac, quizalofop (including quizalofop-P-ethyl and quizalofop-P-tefuryl), rimisoxafen, rimsulfuron, saflufenacil, sethoxydim, simazine, S-metalochlor, sulfentrazone, sulfosulfuron, tebuthiuron, tefuryltrione, tembotrione, terbuthylazine, terbutryn, tetflupyrolimet, thiencarbazone, thifensulfuron, tiafenacil, tolpyralate, topramezone, tralkoxydim, triafamone, triallate, triasulfuron, tribenuron (including tribenuron-methyl), triclopyr, trifloxysulfuron (including trifloxysulfuron-sodium), trifludimoxazin, trifluralin, triflusulfuron, tripyrasulfone, 3-(2- chloro-4-fluoro-5-(3-methyl-2,6-dioxo-4-trifluoromethyl-3,6- dihydropyrimidin-1 (2H)-yl)phenyl)-

5-methyl-4,5-dihydroisoxazole-5-carboxylic acid ethyl ester, 4-hydroxy-1 -methoxy-5-methyl-3-

[4-(trifluoromethyl)-2-pyridyl]imidazolidin-2-one, 4-hydroxy-1 ,5-dimethyl-3-[4-(trifluoromethyl)- 2-pyridyl]-imidazolidine-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-imidazo lidin-2-one, 4-amino-3-chloro-5- fluoro-6-(7-fluoro-1 H-indol-6-yl)pyridine-2-carboxylic acid

(including agrochemically acceptable esters thereof, for example, methyl 4-amino-3-chloro-5- fluoro-6-(7-fluoro-1 H-indol-6-yl)pyridine-2-carboxylate, prop-2-ynyl 4-amino-3-chloro-5-fluoro-

6-(7-fluoro-1 H-indol-6-yl)pyridine-2-carboxylate and cyanomethyl 4-amino-3-chloro-5-fluoro-

6-(7-fluoro-1 H-indol-6-yl)pyridine-2-carboxylate), 3-ethyl-sulfanyl-N-(1 ,3,4-oxadiazol-2-yl)-5- (trifluoromethyl)-[1 ,2,4]triazolo[4,3-a]pyridine-8-carboxamide, 3-(isopropylsulfanylmethyl)-N- (5-methyl-1 ,3,4-oxadiazol-2-yl)-5-(trifluoromethyl)-[1 ,2,4]triazolo[4,3-a]pyridine-8- carboxamide, 3-(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-(tri fluoromethyl)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-f luoro-2-pyridyl)oxy]-propanoate, (2R)-2-[(4-amino-3,5-dichloro-6-fluoro-2-pyridyl)oxy]propano ic acid, tetrahydrofuran-2- ylmethyl2-[(4-amino-3,5-dichloro-6-fluoro-2-pyridyl)oxy]prop anoate, 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)methyl6-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-p yrazol-3-yl]N,N- diethylcarbamate, methyl 2-[(E)-[2-chloro-4-fluoro-5-[3-methyl-2,6-dioxo-4- (trifluoromethyl)pyrimidin-l -yl]phenyl] methyleneamino]oxypropanoate and methyl (2R)-2- [(E)-[2-chloro-4-fluoro-5-[3-methyl-2,6-dioxo-4-(trifluorome thyl)pyrimidin-1 - yl]phenyl]methyleneamino] oxypropanoate.

The mixing partners of the compound of Formula (I) may also be in the form of esters or salts, as mentioned e.g. in The Pesticide Manual, Sixteenth Edition, British Crop Protection Council, 2012.

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

The mixing ratio of the compound of Formula (I) to the mixing partner is preferably from 1 : 100 to 1000:1.

The mixtures can advantageously be used in the above-mentioned formulations (in which case "active ingredient" relates to the respective mixture of compound of Formula (I) with the mixing partner).

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 benoxacor, cloquintocet (including cloquintocet-mexyl), cyprosulfamide, dichlormid, fenchlorazole (including fenchlorazole-ethyl), fenclorim, fluxofenim, furilazole, isoxadifen (including isoxadifen-ethyl), mefenpyr (including mefenpyr-diethyl), metcamifen and oxabetrinil.

Particularly preferred are mixtures of a compound of Formula (I) with cyprosulfamide, isoxadifen-ethyl, cloquintocet-mexyl and/or metcamifen.

The safeners of the compound of Formula (I) may also be in the form of esters or salts, as mentioned e.g. in The Pesticide Manual, 16 ^th Edition (BCPC), 2012. The reference to cloquintocet-mexyl also applies to a lithium, sodium, potassium, calcium, magnesium, aluminium, iron, ammonium, quaternary ammonium, sulfonium or phosphonium salt thereof as disclosed in WO 02/34048.

Preferably the mixing ratio of compound of Formula (I) to safener is from 100:1 to 1 :10, especially from 20:1 to 1 :1 .

The present invention still further provides a method of controlling weeds at a locus said method comprising applying to the locus a weed controlling amount of a composition comprising a compound of Formula (I). Moreover, the present invention may further provide a method of selectively controlling weeds at a locus comprising crop plants and weeds, wherein the method comprises application to the locus of a weed controlling amount of a composition according to the present invention. ‘Controlling’ means killing, reducing or retarding growth or preventing or reducing germination. It is noted that the compounds of the present invention show a much-improved selectivity compared to know, structurally similar compounds. Generally the plants to be controlled are unwanted plants (weeds). ‘Locus’ means the area in which the plants are growing or will grow. The application may be applied to the locus preemergence and/or postemergence of the crop plant. Some crop plants may be inherently tolerant to herbicidal effects of compounds of Formula (I). Preferred crop plants include maize, wheat, barley soybean and rice.

The rates of application of compounds of Formula I may vary within wide limits and depend on the nature of the soil, the method of application (pre- or post-emergence; seed dressing; application to the seed furrow; no tillage application etc.), the crop plant, the weed(s) to be controlled, the prevailing climatic conditions, and other factors governed by the method of application, the time of application and the target crop. The compounds of Formula I according to the invention are generally applied at a rate of from 10 to 2500 g/ha, especially from 25 to 1000 g/ha, more especially from 25 to 250 g/ha.

The application is generally made by spraying the composition, typically by tractor mounted sprayer for large areas, but other methods such as dusting (for powders), drip or drench can also be used.

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-, GS-, EPSPS-, PPO- , HPPD-, -PDS , -SDPS and ACCase-inhibitors) by conventional methods of breeding or by genetic engineering. An example of a crop that has been rendered tolerant to imidazolinones, e.g. imazamox, by conventional methods of breeding is Clearfield® summer rape (canola). Examples of crops that have been rendered tolerant to herbicides by genetic engineering methods include e.g. glyphosate- and glufosinate-resistant maize varieties commercially available under the trade names RoundupReady® and LibertyLink®.

Crop plants are also to be understood as being those which have been rendered resistant to harmful insects by genetic engineering methods, for example Bt maize (resistant to European corn borer), Bt cotton (resistant to cotton boll weevil) and also Bt potatoes (resistant to Colorado beetle). Examples of Bt maize are the Bt 176 maize hybrids of NK® (Syngenta Seeds). The Bt toxin is a protein that is formed naturally by Bacillus thuringiensis soil bacteria. Examples of toxins, or transgenic plants able to synthesise such toxins, are described in EP-A-451 878, EP-A-374 753, WO 93/07278, WO 95/34656, WO 03/052073 and EP-A-427 529. Examples of transgenic plants comprising one or more genes that code for an insecticidal resistance and express one or more toxins are KnockOut® (maize), Yield Gard® (maize), NuCOTIN33B® (cotton), Bollgard® (cotton), NewLeaf® (potatoes), NatureGard® and Protexcta®. Plant crops or seed material thereof can be both resistant to herbicides and, at the same time, resistant to insect feeding (“stacked” transgenic events). For example, seed can have the ability to express an insecticidal Cry3 protein while at the same time being tolerant to glyphosate. Crop plants are also to be understood to include those which are obtained by conventional methods of breeding or genetic engineering and contain so-called output traits (e.g. improved storage stability, higher nutritional value and improved flavour).

The compositions can be used to control unwanted plants (collectively, ‘weeds’). The weeds to be controlled may be both monocotyledonous species, for example Agrostis, Alopecurus, Avena, Brachiaria, Bromus, Cenchrus, Cyperus, Digitaria, Echinochloa, Eleusine, Lolium, Monochoria, Rottboellia, Sagittaria, Scirpus, Setaria and Sorghum, and dicotyledonous species, for example Abutilon, Amaranthus, Ambrosia, Chenopodium, Chrysanthemum, Conyza, Galium, Ipomoea, Nasturtium, Sida, Sinapis, Solanum, Stellaria, Veronica, Viola and Xanthium.

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

Processes for preparation of compounds, e.g. a compound of formula (I) (which optionally can be an agrochemically acceptable salt thereof), are now described, and form further aspects of the present invention.

SCHEME 1

In embodiments where A ¹ is -C(R ¹ )(R ² )- and X ¹ is O, compounds of formula (1 ) may be prepared from compounds of formula (2), where LG represents a suitable leaving group (such as Br or Cl), and compounds of formula (3). Compounds of formula (2) are treated with isoxazolidinones of formula (3) and a carbonate base, for example potassium carbonate, in a suitable solvent, for example dimethylformamide.

SCHEME 2

Compounds of formula (2) may be prepared from benzyl alcohols of formula (4). For example, where LG is Cl, benzyl alcohols of formula (4) are treated with a chlorinating agent, for example thionyl chloride.

SCHEME 3

Compounds of formula (4) may be prepared from compounds of formula (5), where Z is H or

O-alkyl.

(5) Z is H or O-alkyl

For example, where Z is H, compounds of formula (5) are treated with a reducing agent, for example sodium borohydride, in a suitable solvent, for example a toluene/isopropanol mixture.

SCHEME 4

The synthesis routes used to access compounds of formula (5) will vary depending on the nature of Z, A ² , A ³ , R ⁵ and R ⁶ . For example, where Z is H, compounds of formula (5) may be prepared from compounds of formula (6).

Formylating agent

Solvent

Compounds of formula (6) are reacted under suitable formylation conditions, for example, by treatment with titanium tetrachloride and dichloro(methoxy)methane in a suitable solvent, for example dichloromethane.

SCHEME 5

In another example, where A ² is S, A ³ is O, R ⁵ and R ⁶ are F, and Z is H, a compound of formula (5) may be prepared from 2-chloro-5-hydroxy-4-iodo-benzaldehyde (7). R ⁵ and R ⁶ are F, and Z is H

2-Chloro-5-hydroxy-4-iodo-benzaldehyde (7) is treated with [(bpy)CuSCF ₃ ] and a suitable base, for example potassium fluoride, in a suitable solvent, for example acetonitrile. SCHEME 6

In an alternative approach, compounds of formula (4) may be prepared from benzyl alcohols of formula (8).

Chlorinating agent

Solvent

Compounds of formula (8) are treated with a chlorinating agent, for example 1 ,3,5-trichloro- 1 , 3, 5-triazinane-2, 4, 6-trione, in a suitable solvent, for example acetonitrile.

SCHEME 7

Compounds of formula (8) may be commercially available. Alternatively, they may be prepared synthetically. The synthetic route will vary depending on the nature of A ² , A ³ , R ⁵ and R ⁶ . In one approach, compounds of formula (8) may be prepared from compounds of formula (9).

For example, where Z is H, compounds of formula (9) are treated with a reducing agent, for example sodium borohydride, in a suitable solvent, for example methanol. SCHEME 8

Compounds of formula (9) may be commercially available. Alternatively, they may be prepared synthetically. The synthetic route will vary depending on the nature of Z, A ² , A ³ , R ⁵ and R ⁶ . For example, where A ² and A ³ are O and Z is H, compounds of formula (9) may be prepared from 3,4-dihydroxybenzaldehyde (10).

(9) where A ² and A ³ are O and Z is H

In one approach, 3,4-dihydroxybenzaldehyde (10) is treated with dibromides of formula (1 1 ) and a suitable base, for example potassium carbonate, in a suitable solvent, for example acetonitrile.

SCHEME 9

In a further alternative approach, compounds of formula (1 ) where A ² and A ³ = O, may be prepared from 2-chloro-6-chloropiperonyl alcohol (12) according to the following scheme.

2-Chloro-6-chloropiperonyl alcohol (12) is treated with a suitable oxidative chlorinating agent, for example phosphorous pentachloride, in a suitable solvent, for example chlorobenzene. 5- Chloro-6-(chloromethyl)-1 ,3-benzodioxol-2-one (13) is treated with isoxazolidinones of formula (3) and a carbonate base, for example potassium carbonate, in a suitable solvent, for example dimethylformamide. Compounds of formula (14) are treated with ketones of formula (15) and an acid catalyst, for example para-toluenesulfonic acid, in a suitable solvent, for example toluene.

SCHEME 10

In a variant of Scheme 9, compounds of formula (1 ) where A ² and A ³ = O, may be prepared from compounds of formula (14) and compounds of formula (11 ).

Compounds of formula (14) are treated with dibromides of formula (11 ) and a suitable base, for example potassium carbonate, in a suitable solvent, for example dimethylformamide.

SCHEME 11

Where A ¹ is -C(=O)-, compounds of formula (1 ) may be prepared from compounds of formula (5) where Z is H according to the following scheme.

Compounds of formula (5) are treated with a hydroxylamine source, for example hydroxylamine hydrochloride, and suitable base, for example sodium acetate, in a suitable solvent, for example ethanol, to give compounds of formula (16). Compounds of formula (16) are treated with a suitable reducing agent, for example, sodium cyanoborohydride and a suitable acid, for example, 4 M hydrochloric acid in dioxane, in a suitable solvent, for example, methanol. Compounds of formula (17) are treated with 2,2-dimethylmalonyl chloride and a suitable base, for example pyridine, in a suitable solvent, for example dichloromethane.

SCHEME 12

Compounds of formula (3) may be commercially available. For example, the compound of formula (3) where R ³ and R ⁴ are methyl and R ¹ and R ² are hydrogen is commercially available (CAS no 81778-07-6). Alternatively, compounds of formula (3) may be prepared synthetically. For example, where R ¹ is Ci-Cealkoxy, Ci-Cealkoxy-Ci-Cealkoxy-, HOC(0)Ci-C6alkoxy-, Ci- C6alkoxy-C(0)-Ci-C6alkoxy- or Ci-C3alkyl-S(0) _p Ci-C6alkoxy- and R ² is hydrogen, compounds of formula (3) may be prepared from 3,3-dichloro-2,2-dimethylpropanoic acid (18).

3,3-Dichloro-2,2-dimethylpropanoic acid (18) is treated with a suitable chlorinating agent, for example thionyl chloride, to give 3,3-dichloro-2,2-dimethylpropanoyl chloride (19). 3,3- Dichloro-2,2-dimethylpropanoyl chloride (19) is treated with a suitable source of hydroxylamine, for example hydroxylamine (50% in H2O), to give 3,3-dichloro-2,2-dimethyl- propanehydroxamic acid (20). 3,3-Dichloro-2,2-dimethyl-propanehydroxamic acid (20) is treated with an alcohol and a suitable base, for example 1 ,8-diazabicyclo(5.4.0)undec-7-ene, to give compounds of formula (3).

SCHEME 13

Compounds of formula (21 ) may be prepared from compounds of formula (22).

(22) (21 )

Compounds of formula (22) are treated with a suitable Lewis acid source, for example boron trifluoride diethyl etherate in a suitable solvent, for example toluene.

SCHEME 14

Compounds of formula (23) may be prepared from compounds of formula (24).

Compounds of formula (24) are treated with a suitable base, for example potassium carbonate, in a suitable solvent, for example acetone.

SCHEME 15

Compounds of formula (24) may be prepared from compounds of formula (17).

Compounds of formula (17) are treated with 3,3-dichloro-2,2-dimethylpropanoyl chloride (19) and a suitable base, for example pyridine, in a suitable solvent, for example dichloromethane, and optionally in the presence of a suitable additive, for example chloro(trimethyl)silane.

The following non-limiting examples provide specific synthesis methods for representative compounds of the present invention, as referred to in Table 1 below. PREPARATION EXAMPLES

EXAMPLE P1 : Preparation of Compound 1.001

Step 1 : Preparation of 6-chloro-2,2-dimethyl-1 ,3-benzodioxole-5-carbaldehyde

To a solution of 5-chloro-2,2-dimethyl-1 ,3-benzodioxole (5.00 g, 26.5 mmol) in dichloromethane (50.0 mL) at -5 °C was added dichloro(methoxy)methane (3.74 g, 2.94 mL, 31.8 mmol) followed by titanium tetrachloride (5.59 g, 3.24 mL, 29.2 mmol). The reaction mixture was stirred for 1 .5 h at 0 °C. Ice water was added and the product was extracted with dichloromethane. The organic portion was filtered through a layer of celite®, passed through a phase separator then concentrated in vacuo. The crude material was purified by flash column chromatography (0-40% ethyl acetate in isohexane). Product containing fractions were combined and concentrated to afford 6-chloro-2,2-dimethyl-1 ,3-benzodioxole-5- carbaldehyde (1.6 g, 7.5 mmol, 28%) as a white solid. 1 H NMR (400 MHz, CDCI3) 8 ppm 10.29 (s, 1 H), 6.80 (s, 1 H), 6.78 (s, 1 H), 1.72 (s, 6 H).

Step 2: Preparation of (6-chloro-2,2-dimethyl-1 ,3-benzodioxol-5-yl)methanol

Sodium borohydride (0.856 g, 22.6 mmol) was added portion wise over 15 min to a vigorously stirred solution of 6-chloro-2,2-dimethyl-1 ,3-benzodioxole-5-carbaldehyde (1 .60 g, 7.55 mmol) in toluene (5.0 mL) and isopropanol (2.0 mL) at RT under a nitrogen atmosphere. The reaction was stirred for 2 h. To the reaction was added ethyl acetate and brine. The phases were separated and the aqueous portion extracted with a further portion of ethyl acetate. The organic portions were combined, dried over MgSCU, filtered and concentrated in vacuo to afford (6-chloro-2,2-dimethyl-1 ,3-benzodioxol-5-yl)methanol (1 .45 g, 6.76 mmol, 44%) as a white solid. 1 H NMR (400 MHz, chloroform) 8 ppm 6.84 (s, 1 H), 6.75 (s, 1 H), 4.67 (d, 2 H), 1.83 (t, 1 H), 1.68 (s, 6 H).

Step 3: Preparation of 5-chloro-6-(chloromethyl)-2,2-dimethyl-1 ,3-benzodioxole

(6-Chloro-2,2-dimethyl-1 ,3-benzodioxol-5-yl)methanol (1.45 g, 6.76 mmol) and thionyl chloride (4.9 mL) were stirred at 60 °C for 1 h. The reaction mixture was concentrated in vacuo, azeotroping with toluene, to afford 5-chloro-6-(chloromethyl)-2,2-dimethyl-1 ,3-benzodioxole (0.90 g, 3.9 mmol, 57%) as a white solid. 1 H NMR (400 MHz, chloroform) 8 ppm 6.80 (s, 1 H), 6.76 (s, 1 H), 4.62 (s, 2 H), 1 .68 (s, 6 H).

Step 4: Preparation of 2-[(6-chloro-2,2-dimethyl-1 ,3-benzodioxol-5-yl)methyl]-4,4- dimethyl-isoxazolidin-3-one To a solution of 5-chloro-6-(chloromethyl)-2,2-dimethyl-1 ,3-benzodioxole (260 mg, 1.12 mmol) in dimethylformamide (2.5 mL) was added potassium carbonate (310 mg, 2.21 mmol) and 4,4- dimethylisoxazolidin-3-one (130 mg, 1.13 mmol). The reaction was stirred at RT overnight. The reaction was quenched with water (50 mL) and the resulting precipitate filtered and washed with water. The crude material was purified by flash column chromatography (0-20% ethyl acetate in cyclohexane). Product containing fractions were combined and concentrated to afford 2-[(6-chloro-2,2-dimethyl-1 ,3-benzodioxol-5-yl)methyl]-4,4-dimethyl-isoxazolidin-3- one (229 mg, 0.73 mmol, 66%) as a colourless oil which solidified on standing. 1 H NMR (400 MHz, CDCI ₃ ) 8 ppm 6.74 (s, 1 H), 6.71 (s, 1 H), 4.72 (s, 2 H), 4.01 (s, 2 H), 1.68 (s, 6 H), 1.27 (s, 6 H).

EXAMPLE P2: Preparation of Compound 1.002

Step 1 : Preparation of 6-chloro-2,2-dimethyl-1 ,3-benzodioxole-5-carbaldehyde oxime Sodium acetate (0.745 g, 8.98 mmol) and hydroxylamine hydrochloride (0.624 g, 8.97 mmol) were added to a solution of 6-chloro-2,2-dimethyl-1 ,3-benzodioxole-5-carbaldehyde (1.59 g, 7.48 mmol) in ethanol (16 mL) and the reaction mixture was stirred at reflux for 1 h. The reaction mixture was allowed to cool to RT and then concentrated in vacuo. The residue was diluted with water and dichloromethane. The layers were separated and the organic portion passed through a hydrophobic frit then concentrated in vacuo to afford 6-chloro-2,2-dimethyl- 1 ,3-benzodioxole-5-carbaldehyde oxime (1.66 g, 7.29 mmol, 98%) as a white solid. 1 H NMR (400 MHz, CDCI3) 8 ppm 8.48 (s, 1 H), 7.19 (s, 1 H), 6.73 (s, 1 H), 1.68 (s, 6 H).

Step 2: Preparation of AZ-[(6-chloro-2,2-dimethyl-1 ,3-benzodioxol-5- yl)methyl]hydroxylamine

Solutions of sodium cyanoborohydride (1.37 g, 21.7 mmol) in methanol (5.0 mL) and 4 M hydrochloric acid in dioxane (5.6 mL) were added dropwise simultaneously over 30 min to a stirred solution of 6-chloro-2,2-dimethyl-1 ,3-benzodioxole-5-carbaldehyde oxime (1 .65 g, 7.25 mmol) and a trace of methyl orange in methanol (20 mL) at RT. During the addition care was taken to keep the reaction mixture between 19 and 27 °C and the pH below 3. Upon completion of addition, the reaction mixture was stirred at RT for 30 min, during which time the reaction mixture was kept acidic by the addition of small amounts 4 M hydrochloric acid in dioxane. The reaction mixture was cooled to 0 °C and the pH adjusted to 9.4 through the dropwise addition of concentrated sodium hydroxide. The reaction mixture was concentrated in vacuo then ethyl acetate (25 mL) and water (50 mL) were added and the layers separated. The organic portion was dried over MgSC , filtered and concentrated in vacuo to afford A/-[(6- chloro-2,2-dimethyl-1 ,3-benzodioxol-5-yl)methyl]hydroxylamine (1.66 g, 7.23 mmol, 100%) as a pale yellow solid. 1 H NMR (400 MHz, CDCI3) 8 ppm 6.78 (s, 1 H), 6.74 (s, 1 H), 4.04 (s, 2 H), 1.67 (s, 6 H).

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

2,2-Dimethylpropanedioyl dichloride (1 .22 g, 0.96 mL, 7.23 mmol) in dichloromethane (10 mL) was added dropwise over 15 min to a solution of A/-[(6-chloro-2,2-dimethyl-1 ,3-benzodioxol- 5-yl)methyl]hydroxylamine (1.66 g, 7.23 mmol) and pyridine (1.16 g, 1.18 mL, 14.5 mmol) in dichloromethane (10 mL) at 0 °C. The reaction mixture was stirred at RT for 2 h and left to stand overnight. The reaction mixture was acidified with 2 M hydrochloric acid, passed through a phase separator and the organic portion was concentrated in vacuo. The crude material was absorbed onto silica gel and purified via flash column chromatography (0-10% ethyl acetate in isohexane). Product containing fractions were concentrated to afford 2-[(6-chloro-2,2- dimethyl-1 ,3-benzodioxol-5-yl)methyl]-4,4-dimethyl-isoxazolidine-3, 5-dione (1.94 g, 5.94 mmol, 82%) as a white solid. 1 H NMR (400 MHz, CDCI3) 8 ppm 6.78 (s, 1 H), 6.71 (s, 1 H), 4.96 (s, 2 H), 1 .68 (s, 6 H), 1 .44 (s, 6 H).

EXAMPLE P3: Preparation of Compound 1.005

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

A solution of chloropiperonyl alcohol (10.0 g, 53.6 mmol) in chlorobenzene (50 mL) was added slowly to a solution of phosphorous pentachloride (45.6 g, 214 mmol) in chlorobenzene (50 mL) over 10 min. The reaction was heated to reflux for 5 h then cooled to RT. The reaction mixture was added dropwise to water with stirring then extracted with dichloromethane (x2). The organic portions were combined, passed through a phase separator and concentrated in vacuo. The crude material was purified by flash column chromatography (0-50% ethyl acetate in isohexane). Product containing fractions were combined and concentrated to afford 5- chloro-6-(chloromethyl)-1 ,3-benzodioxol-2-one (10.8 g, 49.4 mmol, 92%) as a brown oil. 1 H NMR (400 MHz, CDCI3) 8 ppm 7.42 (s, 1 H), 7.35 (s, 1 H), 4.70 (s, 2 H).

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

To a solution of 5-chloro-6-(chloromethyl)-1 ,3-benzodioxol-2-one (10.8 g, 49.4 mmol) in dimethylformamide (1 11 mL) was added potassium carbonate (20.7 g, 150 mmol) and 4,4- dimethylisoxazolidin-3-one (5.69 g, 49.4 mmol). The reaction was stirred at RT for 65 h. The reaction was acidified to pH 2 with 2 M hydrochloric acid and extracted with diethyl ether (x4). The organic portions were combined, dried over MgSC , filtered and concentrated in vacuo. The crude material was purified by flash column chromatography (20-100% ethyl acetate in isohexane). Product containing fractions were combined and concentrated to afford 2-[(2- chloro-4,5-dihydroxy-phenyl)methyl]-4,4-dimethyl-isoxazolidi n-3-one (9.95 g, 36.6 mmol, 74%) as an off white solid. 1 H NMR (400 MHz, d6-DMSO) 5 ppm 9.43 (br. s, 1 H), 9.31 (br. s, 1 H), 6.76 (s, 1 H), 6.74 (s, 1 H), 4.55 (s, 2 H), 4.00 (s, 2 H), 1.12 (s, 6 H).

Step 3: Preparation of 2-[(6-chloro-2,2-diethyl-1 ,3-benzodioxol-5-yl)methyl]-4,4- dimethyl-isoxazolidin-3-one

Pentan-3-one (1.2 g, 1.5 mL, 14 mmol) was added dropwise to a solution of 2-[(2-chloro-4,5- dihydroxy-phenyl)methyl]-4,4-dimethyl-isoxazolidin-3-one (150 mg, 0.552 mmol) and p- toluene sulfonic acid (27.0 mg, 0.149 mmol) in toluene (3 mL) inside a sealed microwave vial. The solution was heated at 160 °C for 2 h by microwave irradiation. The reaction mixture was concentrated onto celite® and purified via flash column chromatography (0-10% ethyl acetate in isohexane). Product containing fractions were combined and concentrated to afford 2-[(6- chloro-2,2-diethyl-1 ,3-benzodioxol-5-yl)methyl]-4,4-dimethyl-isoxazolidin-3-one (9.0 mg, 0.03 mmol, 5%) as a brown gum. 1 H NMR (400 MHz, CDCI3) 8 ppm 6.73 (s, 1 H), 6.69 (s, 1 H), 4.72 (s, 2 H), 4.02 (s, 2 H), 1 .91 (q, 4 H), 1 .26 (s, 6 H), 0.96 (t, 6 H).

EXAMPLE P4: Preparation of Compound 1.014

Step 1 : Preparation of (6-chloro-2,2-difluoro-1 ,3-benzodioxol-5-yl)methanol

A solution of (2,2-difluoro-1 ,3-benzodioxol-5-yl)methanol (7.66 g, 40.7 mmol) and 1 ,3,5- trichloro-1 ,3, 5-triazinane-2, 4, 6-trione (13.2 g, 57.0 mmol) in acetonitrile (100 mL) was stirred at RT overnight. The reaction mixture was concentrated onto silica gel and purified by flash column chromatography (0-50% ethyl acetate in isohexane). Product containing fractions were combined and concentrated to afford (6-chloro-2,2-difluoro-1 ,3-benzodioxol-5- yl)methanol (2.30 g, 10.3 mmol, 25%) as a white solid. 1 H NMR (400 MHz, CDCI3) 8 ppm 7.29 (s, 1 H), 7.10 (s, 1 H), 4.74 (s, 2 H), 1.98 (s, 1 H).

Step 2: Preparation of 5-(bromomethyl)-6-chloro-2,2-difluoro-1 ,3-benzodioxole

To a solution of (6-chloro-2,2-difluoro-1 ,3-benzodioxol-5-yl)methanol (1.50 g, 6.76 mmol) in dichloromethane (13.0 mL) was added carbon tetrabromide (2.69 g, 8.1 1 mmol) and the solution was cooled to 0 °C in an ice bath. Triphenylphosphine (2.66 g, 10.1 mmol) was added and the reaction was then allowed to warm to RT and stir for 3 h. The reaction mixture was concentrated onto isolate® and purified via flash column chromatography (0-15% ethyl acetate in cyclohexane). Product containing fractions were concentrated to afford 5- (bromomethyl)-6-chloro-2,2-difluoro-1 ,3-benzodioxole (1.94 g, 6.76 mmol, 100%) as a colourless gum. 1 H NMR (400 MHz, CDCh) 8 ppm 7.18 (s, 1 H), 7.13 (s, 1 H), 4.57 (s, 2 H).

Step 3: Preparation of 3,3-dichloro-2,2-dimethyl-propanoyl chloride

3,3-Dichloro-2,2-dimethyl-propanoic acid (88.0 g, 514 mmol) was added to a stirred solution of thionyl chloride (148 mL) at RT. 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 afford 3,3-dichloro-2,2-dimethyl-propanoyl chloride (87.0 g, 459 mmol, 89%) as a colourless oil. 1 H NMR (400 MHz, CDCI3) 8 ppm 6.17 (s, 1 H), 1 .50 (s, 6 H).

Step 4: Preparation of 3,3-dichloro-2,2-dimethyl-propanehydroxamic acid

To hydroxylamine (50 mass%) in water (8.09 g, 7.5 mL, 122 mmol) was added 3,3-dichloro- 2,2-dimethyl-propanoyl chloride (3.00 g, 15.8 mmol) dropwise. The reaction mixture was stirred for 10 mins at RT. The reaction mixture was extracted with dichloromethane, passed through a phase separator and concentrated in vacuo to afford 3,3-dichloro-2,2-dimethyl- propanehydroxamic acid (1.94 g, 10.4 mmol, 66%) as a white solid. 1 H NMR (400 MHz, CDCh) 8 ppm 6.40 (br. s, 1 H), 6.12 (s, 1 H), 1.40 (s, 6 H).

Step 5: Preparation of 4,4-dimethyl-5-(2-trimethylsilylethoxy)isoxazolidin-3-one

A solution of 1 ,8-Diazabicyclo(5.4.0)undec-7-ene (0.835 g, 0.82 mL, 5.38 mmol) and 3,3- dichloro-2,2-dimethyl-propanehydroxamic acid (0.500 g, 2.69 mmol) in 2-trimethylsilylethanol (5.0 mL) was heated at 75 °C overnight. The reaction mixture was diluted with EtOAc and washed with 2 M hydrochloric acid (x2) and brine. The organic portion was concentrated to give 4,4-dimethyl-5-(2-trimethylsilylethoxy)isoxazolidin-3-one (0.308 g, 1 .33 mmol, 50%) as a pale orange gum. This material was used crude in the next reaction without further purification.

Step 6: Preparation of 2-[(6-chloro-2,2-difluoro-1 ,3-benzodioxol-5-yl)methyl]-4,4- dimethyl-5-(2-trimethylsilylethoxy)isoxazolidin-3-one

To a solution of 5-(bromomethyl)-6-chloro-2,2-difluoro-1 ,3-benzodioxole (0.300 g, 1 .05 mmol) in acetone (9.0 mL) was added potassium carbonate (0.295 g, 2.10 mmol) and 4,4-dimethyl- 5-(2-trimethylsilylethoxy)isoxazolidin-3-one (0.292 g, 1.26 mmol). The reaction was stirred at RT overnight. The reaction mixture was diluted with ethyl acetate, filtered through celite®, concentrated onto isolate® and purified via flash column chromatography (0-40% ethyl acetate in cyclohexane). Product containing fractions were concentrated to afford 2-[(6-chloro- 2,2-difluoro-1 ,3-benzodioxol-5-yl)methyl]-4,4-dimethyl-5-(2-trimethylsilyl ethoxy)isoxazolidin- 3-one (0.157 g, 0.360 mmol, 34%) as a colourless gum. 1 H NMR (400 MHz, CDCI3) 5 ppm 7.18 (s, 1 H), 7.13 (s, 1 H), 4.95 (d, 1 H), 4.92 (s, 1 H), 4.71 (d, 1 H), 3.75 (ddd, 1 H), 3.50 (ddd, 1 H), 1.32 (s, 3 H), 1.23 (s, 3 H), 0.95-0.87 (m, 2 H), 0.00 (s, 9 H).

Step 7: Preparation of 2-[6-chloro-2,2-difluoro-1 ,3-benzodioxol-5-yl)methyl]-5-hydroxy- 4,4-dimethyl-isoxazolidin-3-one

To a solution of 2-[(6-chloro-2,2-difluoro-1 ,3-benzodioxol-5-yl)methyl]-4,4-dimethyl-5-(2- trimethylsilylethoxy)isoxazolidin-3-one (0.157 g, 0.360 mmol) in toluene (3.6 mL) at 0 °C was added boron trifluoride diethyl etherate (0.358 g, 0.32 mL, 2.52 mmol) dropwise. The reaction mixture was stirred at RT under nitrogen for 48 h. Additional boron trifluoride diethyl etherate (0.358 g, 0.32 mL, 2.52 mmol) was added and the reaction mixture was stirred at RT under nitrogen for a further 24 h. The reaction was quenched with sat. aq. NaHCOs and extracted with ethyl acetate (x3). The organic portions were combined, dried over MgSC , filtered and concentrated in vacuo. The crude material was purified by flash column chromatography (0- 50% ethyl acetate in cyclohexane). Product containing fractions were combined and concentrated to afford 2-[(6-chloro-2,2-difluoro-1 ,3-benzodioxol-5-yl)methyl]-5-hydroxy-4,4- dimethyl-isoxazolidin-3-one (60.0 mg, 0.179 mmol, 50%) as a white solid. 1 H NMR (400 MHz, CDCI3) 5 ppm 7.16 (s, 1 H), 7.12 (s, 1 H), 5.30 (d, 1 H), 4.92-4.88 (m, 1 H), 4.79-4.75 (m, 1 H), 3.20 (d, 1 H), 1 .30 (s, 3 H), 1 .26 (s, 3 H).

EXAMPLE P5: Preparation of Compound 1.019

Step 1 : Preparation of 1-(4-chloro-2-fluoro-phenyl)-2-methyl-propan-2-ol

To a stirred solution of methyl 2-(4-chloro-2-fluoro-phenyl)acetate (10.0 g, 49.4 mmol) in anhydrous THF (250 ml) was added methyl magnesium chloride (3 M solution in THF, 49.4 mL, 148 mmol) dropwise over 20 min. The reaction mixture was stirred at RT overnight then quenched with sat. aq. NH ₄ CI and extracted with EtOAc (x2). The combined organic portions were washed with brine, dried over sodium sulfate and concentrated. Purification by flash column chromatography afforded 1 -(4-chloro-2-fluoro-phenyl)-2-methyl-propan-2-ol (5.0 g, 24.7 mmol, 50%). 1 H NMR (400 MHz, CDCI3) 5 ppm 7.20-7.16 (m, 1 H), 7.08-7.06 (m, 2 H), 2.77 (s, 2 H), 1.23 (s, 6 H).

Step 2: Preparation of 6-chloro-2,2-dimethyl-3H-benzofuran

To a stirred solution of 1 -(4-chloro-2-fluoro-phenyl)-2-methyl-propan-2-ol (7.20 g, 35.5 mmol) in THF (80 mL) was added potassium tert-butoxide (1 M solution in THF, 88.8 mL, 88.8 mmol). The reaction was stirred at 65 °C for 18 h then quenched with 1 M hydrochloric acid and extracted with EtOAc. The organic phase was dried over sodium sulfate and concentrated. Purification by flash column chromatography (ethyl acetate / hexane) afforded 6-chloro-2,2- dimethyl-3H-benzofuran (4.5 g, 24.6 mmol, 69%). 1 H NMR (400 MHz, CDCI3) 5 ppm 7.01 (d, 1 H), 6.77 (d, 1 H), 6.70 (s, 1 H), 2.95 (s, 2 H), 1 .46 (s, 6 H).

Step 3: Preparation of 6-chloro-2,2-dimethyl-3H-benzofuran-5-carbaldehyde

Dimethylformamide (0.93 mL, 12.0 mmol) was added dropwise to phosphoryl chloride (2.73 g, 1.63 mL, 17.8 mmol) with stirring at 0 °C. The mixture was stirred for 15 min at 0 °C then 6- chloro-2,2-dimethyl-3H-benzofuran (1.0 g, 5.48 mmol) was added slowly. The reaction was stirred at RT for 30 min, then at 80 °C overnight. The reaction mixture was cooled to 0 °C and quenched by the addition of cold water. The mixture was extracted with EtOAc (x2) and the combined organic portions were concentrated. Purification by flash column chromatography afforded 6-chloro-2,2-dimethyl-3H-benzofuran-5-carbaldehyde (0.170 g, 0.81 mmol, 15%). 1 H NMR (400 MHz, CDCI3): 5 ppm 10.29 (s, 1 H), 7.73 (s, 1 H), 6.74 (s, 1 H), 2.99 (s, 2 H), 1.49 (s, 6 H).

Step 4: Preparation of (6-chloro-2,2-dimethyl-3H-benzofuran-5-yl)methanol

Sodium borohydride (0.057 g, 1.44 mmol) was added portion wise over 15 min to a stirred solution of 6-chloro-2,2-dimethyl-3H-benzofuran-5-carbaldehyde (0.101 g, 0.48 mmol) in toluene (0.48 mL), isopropanol (0.096 mL) and water (0.096 mL) at RT under a nitrogen atmosphere. The reaction was stirred for 1 h then ethyl acetate and brine were added. The phases were separated and the aqueous phase was extracted with a further portion of ethyl acetate. The organic portions were combined, dried over MgSC , filtered and concentrated. Purification by flash column chromatography (0-10% ethyl acetate in cyclohexane) afforded (6-chloro-2,2-dimethyl-3H-benzofuran-5-yl)methanol (0.045 g, 0.21 mmol, 44%). 1 H NMR (400 MHz, CDCI3) 5 ppm 7.19 (s, 1 H), 6.74 (s, 1 H), 4.67 (d, 2 H), 2.97 (s, 2 H), 2.00 (t, 1 H) 1.46 (s, 6 H).

Step 5: Preparation of 2-[(6-chloro-2,2-dimethyl-3H-benzofuran-5-yl)methyl]-4,4- dimethyl-isoxazolidin-3-one

Thionyl chloride (0.25 g, 0.15 mL, 2.1 mmol) and (6-chloro-2,2-dimethyl-3H-benzofuran-5- yl)methanol (0.045 g, 0.21 mmol) were combined and stirred at 60 °C for 1 h. The reaction mixture was concentrated then repeatedly dissolved in toluene and concentrated (x3). The resulting residue was combined with 4,4-dimethylisoxazolidin-3-one (0.031 g, 0.27 mmol), dimethylformamide (0.26 mL) and potassium carbonate (0.062 g, 0.45 mmol) and the mixture was stirred at RT overnight. Water and methyl tert-butyl ether were added and the phases were separated. The aqueous layer was extracted with further portions of methyl tert-butyl ether (x2), then the combined organic portions were washed with a sat. aq. NaHCOs and brine (x2). The organic layer was dried over MgSCU, filtered and concentrated. Purification by flash column chromatography (0-25% ethyl acetate in cyclohexane) afforded 2-[(6-chloro-2,2- dimethyl-3H-benzofuran-5-yl)methyl]-4,4-dimethyl-isoxazolidi n-3-one (0.041 g, 0.13 mmol, 59%). 1 H NMR (400 MHz, CDCI3) 5 ppm 7.10 (s, 1 H), 6.74 (s, 1 H), 4.75 (s, 2 H), 4.00 (s, 2 H), 2.96 (s, 2 H), 1 .46 (s, 6 H), 1 .25 (s, 6 H).

EXAMPLE P6: Preparation of Compound 1.028

Preparation of ethyl 5-chloro-6-[(4,4-dimethyl-3-oxo-isoxazolidin-2-yl)methyl]-1 ,3- benzodioxole-2-carboxylate

To a solution of 2-[(2-chloro-4,5-dihydroxy-phenyl)methyl]-4,4-dimethyl-isoxa zolidin-3-one (0.497 g, 1 .83 mmol) in dimethylformamide (4.94 mL) was added potassium carbonate (0.532 g, 3.66 mmol) and ethyl dibromoacetate (0.90 g, 0.47 mL 3.66 mmol). The reaction mixture was heated to 70°C for 3 h then diluted with water and extracted with EtOAc (x2). The combined organic portions were washed with water and concentrated. Purification by flash column chromatography (0-30% acetone in cyclohexane) afforded ethyl 5-chloro-6-[(4,4- dimethyl-3-oxo-isoxazolidin-2-yl)methyl]-1 ,3-benzodioxole-2-carboxylate (0.296 g, 0.832 mmol, 46%). 1 H NMR (400 MHz, CDCI3) 5 ppm 6.91 (s, 1 H), 6.88 (s, 1 H), 6.33 (s, 1 H), 4.80-4.69 (m, 2 H), 4.32 (q, 2 H), 4.02 (s, 2 H), 1 .34 (t, 3 H), 1 .26 (s, 6 H).

EXAMPLE P7: Preparation of Compound 1.029

Step 1 : Preparation of methyl 6-chloro-2-oxo-3H-1 ,3-benzoxazole-5-carboxylate

To a solution of methyl 5-amino-2-chloro-4-hydroxybenzoate (2.105 g, 10.44 mmol) in acetonitrile (41 .8 mL) was added 1 ,8-diazabicyclo[5.4.0]undec-7-ene (3.35 g, 3.284 mL, 20.88 mmol) and 1 ,T-carbonyldiimidazole (1.89 g, 11.5 mmol). The reaction mixture was stirred at RT for 1 h then diluted with sat. aq. NH4CI and extracted with EtOAc (x2). The combined organic portions were concentrated onto isolute® and purified by reverse phase flash column chromatography to afford impure methyl 6-chloro-2-oxo-3H-1 ,3-benzoxazole-5-carboxylate (2.675 g) which was used in the subsequent step without further purification. 1 H NMR (400 MHz, d6-DMSO) 5 ppm 7.62 (s, 1 H), 7.45 (s, 1 H), 3.85 (s, 3 H).

Step 2: Preparation of 6-chloro-5-(hydroxymethyl)-3H-1 ,3-benzoxazol-2-one

Diisobutylaluminium hydride (1 M solution in hexanes, 27.1 mL, 27.1 mmol) was added dropwise to a solution of methyl 6-chloro-2-oxo-3H-1 ,3-benzoxazole-5-carboxylate (1.77 g, 1

7.76 mmol) in 2-methyltetrahydrofuran (22 mL) at 0°C under an atmosphere of nitrogen. The reaction mixture was stirred at 0°C for 30 min then at RT for 90 min. Further diisobutylaluminium hydride (1 M solution in hexanes, 7.76 mL, 7.76 mmol) was added at 0°C and the reaction was stirred at RT for 18 h. A final portion of diisobutylaluminium hydride (1 M solution in hexanes, 7.76 mL, 7.76 mmol) was then added at 0°C and the reaction was stirred at RT for 2 h. The reaction mixture was quenched by the dropwise addition of EtOAc at 0°C. Sat. aq. potassium sodium tartrate was added and the mixture was stirred vigorously for 1 .5 h at RT then extracted with EtOAc (x3). The combined organic portions were washed with brine, dried over MgSO4 and concentrated. Purification by reverse phase flash column chromatography afforded 6-chloro-5-(hydroxymethyl)-3H-1 ,3-benzoxazol-2-one (0.517 g, 2.59 mmol, 33%). 1 H NMR (400 MHz, d6-DMSO) 5 ppm 7.43 (s, 1 H), 7.21 (s, 1 H), 4.53 (s, 2 H).

Step 3: Preparation of 5-(bromomethyl)-6-chloro-3H-1 ,3-benzoxazol-2-one

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

Step 4: Preparation of 6-chloro-5-[(4,4-dimethyl-3-oxo-isoxazolidin-2-yl)methyl]-3H -1 ,3- benzoxazol-2-one

Potassium carbonate (0.261 g, 1.79 mmol) was added to a solution of 4,4- dimethylisoxazolidin-3-one (0.939 g, 8.15 mmol) in acetone (6.4 mL) with stirring at RT. A solution of 5-(bromomethyl)-6-chloro-3H-1 ,3-benzoxazol-2-one (0.428 g, 1.63 mmol) in acetone (6.4 mL) was then added dropwise over 15 min. The reaction mixture was concentrated onto isolute® and purified by flash column chromatography (0-70% acetone in cyclohexane) and then purified again by reverse phase flash column chromatography to afford 6-chloro-5-[(4,4-dimethyl-3-oxo-isoxazolidin-2-yl)methyl]-3H -1 ,3-benzoxazol-2-one (0.269 g, 0.907 mmol, 56%). 1 H NMR (400 MHz, CDCI3) 5 ppm 7.25 (s, 1 H), 7.12 (s, 1 H), 4.85 (s, 2 H), 4.05 (s, 2 H), 1.27 (s, 6 H). EXAMPLE P8: Preparation of Compound 1.031

Step 1 : Preparation of 2-chloro-5-hydroxy-4-iodo-benzaldehyde

To a stirred solution of 2-chloro-5-hydroxy-benzaldehyde (4.00 g, 25.6 mmol) in DCM (100 mL) and MeOH (100 mL) was added NIS (6.34 g, 28.1 mmol) and the reaction mixture was stirred at RT for 2 h. The reaction mixture was diluted with water and extracted with DCM (x3) then the combined organic layers were washed with brine, dried over Na2SO4 and concentrated. Purification by flash column chromatography (0-100% EtOAc in hexane) afforded 2-chloro-5-hydroxy-4-iodo-benzaldehyde (3.50 g, 12.4 mmol, 48%). 1 H NMR (400 MHz, d6-DMSO) 5 ppm 11.1 (s, 1 H), 10.2 (s, 1 H), 7.98 (s, 1 H), 7.35 (s, 1 H).

Step 2: Preparation of 5-chloro-2,2-difluoro-1 ,3-benzoxathiole-6-carbaldehyde

Under an atmosphere of nitrogen, potassium fluoride (0.069 g, 1 .22 mmol) and [(bpy)CuSCF ₃ ] (0.469 g, 1.44 mmol) were added to a solution of 2-chloro-5-hydroxy-4-iodo-benzaldehyde (0.333 g, 1.18 mmol) in acetonitrile (10 mL). The reaction mixture was heated at 100 °C for 1 h by microwave irradiation then diluted with water and extracted with EtOAc (x3). The combined organic layers were washed with brine, dried over Na2SO4 and concentrated. Purification by flash column chromatography (0-100% EtOAc in hexane) afforded 5-chloro-

2.2-difluoro-1 ,3-benzoxathiole-6-carbaldehyde (0.265 g, 1.12 mmol, 95%). 1 H NMR (400 MHz, d6-DMSO) 5 ppm 10.23 (s, 1 H), 8.00 (s, 1 H), 7.69 (s, 1 H).

Step 3: Preparation of (5-chloro-2,2-difluoro-1 ,3-benzoxathiol-6-yl)methanol

Sodium borohydride (0.040 g, 1.05 mmol) was added to a solution of 5-chloro-2,2-difluoro-

1 .3-benzoxathiole-6-carbaldehyde (0.250 g, 1.05 mmol) in MeOH (15 mL) at 0 °C under an atmosphere of nitrogen. The reaction mixture was stirred at RT for 2 h then diluted with sat. aq. NH4CI and extracted with dichloromethane (x2). The combined organic layers were washed with brine, dried over Na2SO4 and concentrated to afford (5-chloro-2,2-difluoro-1 ,3- benzoxathiol-6-yl)methanol (0.120 g, 0.50 mmol, 48%). 1 H NMR (400 MHz, d6-DMSO) 5 ppm 7.55 (s, 1 H), 7.35 (s, 1 H), 5.58 (t, 1 H), 5.53 (d, 2 H).

Step 4: Preparation of 6-(bromomethyl)-5-chloro-2,2-difluoro-1 ,3-benzoxathiole

Phosphorus tribromide (2.88 g, 1 mL, 10.6 mmol) was added to a solution of (5-chloro-2,2- dif luoro-1 ,3-benzoxathiol-6-yl)methanol (0.20 g, 0.84 mmol) and DCM (30 mL) at 0 °C under an atmosphere of nitrogen. The reaction mixture and was stirred at RT for 2 h then diluted with water and extracted with dichloromethane (x2). The combined organic layers were washed with brine, dried over Na2SC>4 and concentrated to afford 6-(bromomethyl)-5-chloro- 2,2-difluoro-1 ,3-benzoxathiole (0.150 g, 0.50 mmol, 60%). 1 H NMR (400 MHz, d6-DMS0) 5 ppm 7.85 (s, 1 H), 7.65 (s, 1 H), 4.72 (s, 2 H).

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

Potassium carbonate (0.172 g, 1.24 mmol) was added to a solution of 6-(bromomethyl)-5- chloro-2,2-difluoro-1 ,3-benzoxathiole (0.250 g, 0.82 mmol) and 4,4-dimethylisoxazolidin-3- one (0.1 15 g, 0.99 mmol) in tetrahydrofuran (20 mL). The reaction mixture was stirred at 60 °C for 3 h then diluted with water and then extracted with dichloromethane. The organic portion was washed with brine, dried over Na2SO4 and concentrated. Purification by reverse phase flash column chromatography afforded 2-[(5-chloro-2,2-difluoro-1 ,3-benzoxathiol-6-yl)methyl]- 4,4-dimethyl-isoxazolidin-3-one (0.060 g, 0.18 mmol, 21 %). 1 H-NMR (400 MHz, d6-DMSO) 5 ppm 7.83 (s, 1 H), 7.32 (s, 1 H), 4.71 (s, 2 H), 4.06 (s, 2 H), 1.13 (s, 6 H).

EXAMPLE P9: Preparation of Compound 1.032

Step 1 : Preparation of 6-chloro-2,2-difluoro-1 ,3-benzodioxole-5-carbaldehyde

A solution of (2,2-difluoro-1 ,3-benzodioxol-5-yl)methanol (0.99 g, 5.3 mmol) and N- chlorosuccinimide (1.7 g, 13 mmol) in acetonitrile (5 mL) was stirred at RT overnight. The reaction mixture was concentrated onto silica gel and purified by flash column chromatography (0-50% EtOAc in isohexane) to afford 6-chloro-2,2-difluoro-1 ,3-benzodioxole-5-carbaldehyde (0.380 g, 1.72 mmol, 33%). 1 H NMR (400 MHz, CDCI3) 5 ppm 10.31 (s, 1 H), 7.62 (s, 1 H), 7.19 (s, 1 H).

Step 2: Preparation of 6-chloro-2,2-difluoro-1 ,3-benzodioxole-5-carbaldehyde oxime

Pyridine (0.065 mL, 0.80 mmol) and hydroxylamine hydrochloride (0.057 g, 0.82 mmol) were added to a solution of 6-chloro-2,2-difluoro-1 ,3-benzodioxole-5-carbaldehyde (0.160 g, 0.73 mmol) in ethanol (5 mL) and the mixture was heated to reflux for 4 h. The reaction mixture was concentrated then diluted in dichloromethane and washed with 1 M hydrochloric acid, water and brine. The organic portion was dried over MgSC and concentrated to afford 6- chloro-2,2-difluoro-1 ,3-benzodioxole-5-carbaldehyde oxime (0.150 g, 0.64 mmol, 88%). 1 H NMR (400 MHz, CDCI3) 5 ppm 8.50 (s, 1 H), 7.58 (s, 1 H), 7.10 (s, 1 H).

Step 3: Preparation of N-[(6-chloro-2,2-difluoro-1 ,3-benzodioxol-5- yl)methyl]hydroxylamine

Solutions of sodium cyanoborohydride (0.801 g, 12.7 mmol) in methanol (7 mL) and 4 M hydrochloric acid in dioxane (3.19 mL, 12.7 mmol) were added dropwise simultaneously over 15 min to a stirred solution of 6-chloro-2,2-difluoro-1 ,3-benzodioxole-5-carbaldehyde oxime (2.31 g, 9.81 mmol) and a trace of methyl orange in methanol (50 mL) at RT. During the addition care was taken to keep the reaction mixture between 19 and 27 °C and the pH below 3. The reaction mixture was stirred at room temp for 2 h, during which time the reaction mixture was kept acidic by the addition of small amounts 4 M hydrochloric acid in dioxane. The rection mixture was concentrated and the resulting residue was washed with diethyl ether. The residue was then diluted in dichloromethane and water and the aqueous phase was adjusted to pH 9 by the addition of aq. potassium carbonate. The layers were separated and the aqueous phase was extracted with a further portion of dichloromethane. The combined organic portions were washed with brine (x2), dried over MgSC and concentrated to afford N-[(6-chloro-2,2-difluoro-1 ,3-benzodioxol-5-yl)methyl]hydroxylamine (2.30 g, 9.68 mmol, 99%). 1 H NMR (400 MHz, CDCI3) 5 ppm 7.16 (s, 1 H), 7.12 (s, 1 H), 4.12 (s, 2 H).

Step 4: Preparation of 3,3-dichloro-N-[(6-chloro-2,2-difluoro-1 ,3-benzodioxol-5- yl)methyl]-N-hydroxy-2,2-dimethyl-propanamide

Chloro(trimethyl)silane (0.46 g, 4.2 mmol) was added dropwise to a solution of N-[(6-chloro- 2,2-difluoro-1 ,3-benzodioxol-5-yl)methyl]hydroxylamine (1.0 g, 4.2 mmol) and pyridine (1.2 mL, 15 mmol) in dichloromethane (20 mL) at -10 °C under an atmosphere of nitrogen. The reaction was stirred at -10 °C for 30 min then a solution of 3,3-dichloro-2,2-dimethyl-propanoyl chloride (0.80 g, 4.2 mmol) in dichloromethane (20 mL) was added dropwise over 10 min at 0 °C. The reaction mixture was stirred at RT for 18 h then diluted in dichloromethane and washed with water, brine and a 1 :1 mixture of brine and 2 M hydrochloric acid (x2). The organic portion was washed with a final portion of brine then dried over MgSC and concentrated. Purification by flash column chromatography (0-10% EtOAc in isohexane) afforded 3,3- dichloro-N-[(6-chloro-2,2-difluoro-1 ,3-benzodioxol-5-yl)methyl]-N-hydroxy-2,2-dimethyl- propanamide (1.21 g, 3.11 mmol, 74%). 1 H NMR (400 MHz, CDCI3) 5 ppm 7.15 (s, 2 H), 6.66 (s, 1 H), 6.49 (br s, 1 H), 4.95 (s, 2 H), 1 .49 (s, 6 H).

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

Potassium carbonate (0.862 g, 6.24 mmol) was added to a solution of 3,3-dichloro-N-[(6- chloro-2,2-difluoro-1 ,3-benzodioxol-5-yl)methyl]-N-hydroxy-2,2-dimethyl-propanami de (1 .22 g, 3.12 mmol) in acetone (14 mL). The reaction mixture was stirred for 3 h at RT then diluted in dichloromethane and washed with water. The organic portion was concentrated to afford 5- chloro-2-[(6-chloro-2,2-difluoro-1 ,3-benzodioxol-5-yl)methyl]-4,4-dimethyl-isoxazolidin-3-one (0.923 g, 2.61 mmol, 84%). 1 H NMR (400MHz, CDCI3) 5 ppm 7.19 (s, 1 H), 7.13 (s, 1 H), 6.07 (s, 1 H), 4.95 (d, 1 H), 4.81 (d, 1 H), 1 .39 (s, 3 H), 1 .38 (s, 3 H). Additional compounds of the invention, made in an analogous manner to those described above in Examples P1 to P9 are shown in Table 1 below. Table 1 Compounds of the present invention

BIOLOGICAL EXAMPLES TEST B1

Seeds of a variety of test species are sown in standard soil in pots Amaranthus retoflexus (AMARE), Setaria faberi (SETFA), Echinochloa crus-galli (ECHCG), Ipomoea hederacea (IPOHE). After cultivation for one day (pre-emergence) or after 8 days cultivation (postemergence) under controlled conditions in a glasshouse (at 24/16°C, day/night; 14 hours light; 65% humidity), the plants are sprayed with an aqueous spray solution derived from either i) the formulation of the technical active ingredient in acetone / water (50:50) solution containing 0.5% Tween 20 (polyoxyethelyene sorbitan monolaurate, CAS RN 9005-64-5) or ii) the dissolution of the technical active ingredient in a small amount of acetone and a special solvent and emulsifier mixture referred to as IF50 (11.12% Emulsogen EL360 TM + 44.44% N- methylpyrrolidone + 44.44% Dowanol DPM glycol ether, which was then diluted to required concentration using 0.2% Genapol XO80 (CAS No.9043-30-5) in water as the diluent. Compounds are applied at 250 g/ha unless otherwise stated. The test plants are then grown in a glasshouse under controlled conditions in a glasshouse (at 24/16°C, day/night; 14 hours light; 65% humidity) and watered twice daily. After 13 days for pre and post-emergence, the test is evaluated for the percentage damage caused to the plant. The biological activities are 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%).

TABLE B1. Post-emergence Test

‘Applied at 170g/ha

TABLE B2. Pre-emergence Test

‘Applied at 170g/ha

TEST B2 Seeds of a variety of test species are sown in standard soil in pots Leptochloa chinesis (LEFCH), Echinochloa crus-galli (ECHCG) and Cyperus esculentus (CYPES). After cultivation for one day (pre-emergence) or after 13 days cultivation (post-emergence) under controlled conditions in a glasshouse (at 30/20°C, day/night; 18 hours light; 75% humidity), the plants are sprayed with an aqueous spray solution derived from the dissolution of the technical active ingredient in a small amount of acetone and a special solvent and emulsifier mixture referred to as IF50 (1 1.12% Emulsogen EL360 TM + 44.44% N-methylpyrrolidone + 44.44% Dowanol DPM glycol ether, which was then diluted to required concentration using 0.2% Genapol XO80 (CAS No.9043-30-5) in water as the diluent. Compounds are applied at 500 g/ha. The test plants are then grown in a glasshouse under controlled conditions in a glasshouse (at 30/20°C, day/night; 18 hours light; 75% humidity) and watered twice daily. After 13 days for pre and post-emergence, the test is evaluated for the percentage damage caused to the plant. The biological activities are 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%).

TABLE B3. Post-emergence Test

TABLE B4. Pre-emergence Test

TEST B3: COMPARATIVE TEST (PRE-EMERGENCE)

Seeds of test species (Echinochloa crus-galli; ECHCG) were sown in standard soil in pots. After cultivation for one day under controlled conditions in a glasshouse (at 24/16°C, day/night;

14 hours light; 65 % humidity), the plants were sprayed with an aqueous spray solution derived from the formulation of the technical active ingredient in 0.6 ml acetone and 45 ml formulation solution containing 10.6% Emulsogen EL (Registry number 61791 -12-6), 42.2% N-methyl pyrrolidone, 42.2% dipropylene glycol monomethyl ether (CAS RN 34590-94-8) and 0.2 % X- 77 (CAS RN 1 1097-66-8).

The test plants were then grown in a glasshouse under controlled conditions (at 24/16°C, day/night; 14 hours light; 65 % humidity) and watered twice daily. After 14 days, the test was evaluated (100 = total damage to plant; 0 = no damage to plant). TABLE B5 Comparative pre-emergence data

C1 is a known compound disclosed in US 4,405,357. As can be seen, the introduction of the R ⁵ /R ⁶ substituent in the compounds of the present invention provides an unexpected improvement in the weed control observed.