WO2023227737A9

WO2023227737A9 - Herbicidal compounds

Info

Publication number: WO2023227737A9
Application number: PCT/EP2023/064100
Authority: WO
Inventors: Paul Matthew BURTON; Neil Brian Carter; Rosemary Anna Croft; Suzanna DALE; Alan Joseph Hennessy; Nicholas Phillip Mulholland; Joseph Andrew TATE; Jeffrey Steven Wailes; Elizabeth Catherine FRYE
Original assignee: Syngenta Crop Protection Ag
Priority date: 2022-05-27
Filing date: 2023-05-25
Publication date: 2024-03-07
Also published as: GB202207819D0; WO2023227737A1

Abstract

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

Description

HERBICIDAL COMPOUNDS

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:

A¹ is CR¹R² or C(O); A² is selected from the group consisting of CR⁹R¹⁰, C(O), O, S(O)_P and N(R¹³); A³ is selected from the group consisting of CR¹¹R¹², C(O), O, S(O)_P and N(R¹³⁾; X¹ is O or S; R¹ is selected from the group consisting of hydrogen, halogen, HO-, Ci-Cealkoxy, Ci-Cealkoxy-CrCealkoxy-, Ci-C3alkyl-C(O)O-, HOC(O)Ci- Cealkoxy-, Ci-C6alkoxy-C(0)-Ci-C6alkoxy-, Ci-C3alkyl-S(O)_p- and Ci-C3alkyl-S(O)_pCi- Cealkoxy-; R² is hydrogen; R³ is Ci-Csalkyl; R⁴ is Ci-Csalkyl; R⁵ is selected from the group consisting of hydrogen, halogen, Ci-Cealkyl, Ci-Cehaloalkyl, Cs-Cecycloalkyl and Ci-Cealkoxy-; and R⁶ is selected from the group consisting of hydrogen, halogen, Cr Cealkyl, Ci-Cehaloalkyl, Cs-Cecycloalkyl and Ci-Cealkoxy-; or R⁵ and R⁶ together are =0 or -(CH₂)_n-; and R⁷ is selected from the group consisting of hydrogen, halogen, Cr Cealkyl, Ci-Cehaloalkyl, Cs-Cecycloalkyl and Ci-Cealkoxy-; R⁸ is selected from the group consisting of hydrogen, halogen, Ci-Cealkyl, Ci-Cehaloalkyl, Cs-Cecycloalkyl and Ci-Cealkoxy-; or R⁷ and R⁸ together are =0 or -(CH₂)_n-; and R⁹ is selected from the group consisting of hydrogen, halogen, Ci-Cealkyl, Ci-Cehaloalkyl, Cs-Cecycloalkyl and Ci-Cealkoxy-; R¹⁰ is selected from the group consisting of is selected from the group consisting of hydrogen, halogen, Ci-Cealkyl, Ci-Cehaloalkyl, Cs-Cecycloalkyl and Cr Cealkoxy-; or R⁹ and R¹⁰ together are -(CH₂)_n-; and R¹¹ is selected from the group consisting of hydrogen, halogen, Ci-Cealkyl, Ci-Cehaloalkyl, Cs-Cecycloalkyl and Cr Cealkoxy-; R¹² is selected from the group consisting of hydrogen, halogen, Ci-Cealkyl, Ci-Cehaloalkyl, Cs-Cecycloalkyl and Ci-Cealkoxy-; or R¹¹ and R¹² together are -(CH₂)_n- ; R¹³ 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, CH₃), ethyl (Et, C2H5), n-propyl (n-Pr), isopropyl (/-Pr), n-butyl (n-Bu), isobutyl (/-Bu), sec-butyl and tert-butyl (t-Bu). Ci-C₃alkyl includes methyl (Me, CH₃), 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-C₃alkyl-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(0)-methoxy-.

Ci-C₃alkyl-S(0)_pCi-C6alkoxy- includes methyl-S(0)_pmethoxy- and ethyl- S(0)_pmethoxy-.

C₃-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(0)- (alkylsulfinyl) includes, for example, methylsulfinyl, ethylsulfinyl, propylsulfinyl, isopropylsulfinyl, n-butylsulfinyl, isobutylsulfinyl, secbutylsulfinyl or tert-butylsulfinyl, preferably methylsulfinyl or ethylsulfinyl.

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

In one embodiment of the present invention, there is provided a compound of Formula (I) wherein X¹ is O.

In another embodiment of the present invention, there is provided a compound of Formula (I) wherein R³ and R⁴ are methyl.

In another embodiment of the present invention, there is provided a compound of Formula (I) wherein A¹ is CR¹R² and R¹ 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 A¹ is CR¹R² and R¹ is Ci-Cealkoxy.

In another embodiment of the present invention, there is provided a compound of Formula (I) wherein A¹ 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 A² 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 A³ 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) A² and A³ are O; (ii) A² is NH and A³ is O; (iii) A² is O and A³ is NH; (iv) A² and A³ are NH; (v) A² is CH₂ and A³ is O; (vi) A² is O and A³ is CH₂; (vii) A² is CH₂ and A³ is CH₂; (viii) A² is O and A³ is S; or (ix) A² is S and A³ are O.

In a preferred embodiment of the present invention, there is provided a compound of Formula (I), Formula (la) or Formula (lb) wherein A² and A³ are O.

In another embodiment of the present invention, there is provided a compound of Formula (I), Formula (la) or Formula (lb) wherein R⁵, R⁶, R⁷ and R⁸ are independently selected from the group consisting of hydrogen, Ci-Cealkyl and Ci- Cealkyl. In a more preferred embodiment, R⁵, R⁶, R⁷ and R⁸ are independently selected from the group consisting of hydrogen, methyl and fluoro. In another embodiment, R⁵ and R⁶ are halogen, preferably fluoro and R⁷ and R⁸ are hydrogen.

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 surfaceactive 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, ethalfluralin, 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-imidazolidin-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-(trifluoromethyl)pyrimidin-1-yl]-2-pyridyl]oxy]acetate,6- chloro-4-(2,7-dimethyl-1 -naphthyl)-5-hydroxy-2-methyl-pyridazin-3-one, tetrahydro- furan-2-ylmethyl(2R)-2-[(4-amino-3,5-dichloro-6-fluoro-2-pyridyl)oxy]-propanoate, (2R)-2-[(4-amino-3,5-dichloro-6-fluoro-2-pyridyl)oxy]propanoic acid, tetrahydrofuran- 2-ylmethyl2-[(4-amino-3,5-dichloro-6-fluoro-2-pyridyl)oxy]propanoate, 2-[(4-amino- 3,5-dichloro-6-fluoro-2-pyridyl)oxy]propanoic acid, 2-fluoro-N-(5-methyl-1 ,3,4- oxadiazol-2-yl)-3-[(R)-propylsulfinyl]-4-(trifluoromethyl)benzamide, 2-fluoro-N-(5- methyl-1 ,3,4-oxadiazol-2-yl)-3-propylsulfinyl-4-(trifluoromethyl)benzamide, (2- fluorophenyl)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-pyrazol-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-(trifluoromethyl)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 pre- emergence 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 postemergence; 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 Liberty Link® .

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 OF FORMULA (I)

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 A¹ is -C(R¹)(R²)- and X¹ 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 compounds of formula (3) and a carbonate base, for example potassium carbonate, in a suitable solvent, for example acetone.

SCHEME 2

Compounds of formula (2) may be prepared from benzyl alcohols of formula (4).

For example, where LG is Br, benzyl alcohols of formula (4) are treated with triphenylphosphine and carbon tetrabromide or phosphorous tribromide in a suitable solvent, for example acetonitrile or dichloromethane.

SCHEME S

Compounds of formula (4) may be prepared from benzyl alcohols of formula (5).

Compounds of formula (5) are treated with a chlorinating agent, for example N- chlorosuccinimide, in a suitable solvent, for example acetonitrile.

SCHEME 4

Benzyl alcohols of formula (5) may be prepared from aldehydes of formula (6).

Compounds of formula (6) are treated with a reducing agent, for example sodium borohydride, in a suitable solvent, for example water.

SCHEME S

Compounds of formula (6) may be commercially available. Alternatively, they may be prepared synthetically. The synthetic route will vary depending on the nature of A², A³, R⁵, R⁶, R⁷ and R⁸. For example, where A² and A³ are O, compounds of formula (6) may be prepared from 3,4-dihydroxybenzaldehyde (7).

3,4-Dihydroxybenzaldehyde (7) is treated with dibromides of formula (8) and a carbonate base, for example potassium carbonate, in a suitable solvent, for example acetonitrile.

SCHEME 6

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

Compounds of formula (9) are treated with a reducing agent, for example sodium borohydride, in a suitable solvent, for example water.

SCHEME ?

The synthesis routes used to access compounds of formula (9) will vary depending on the nature of A², A³, R⁵, R⁶, R⁷ and R⁸. For example, where A² and A³ are O, compounds of formula (9) may be prepared from 2-chloro-4,5-dihydroxybenzaldehyde (10).

2-Chloro-4,5-dihydroxybenzaldehyde (10) is treated with dibromides of formula (8) and a carbonate base, for example potassium carbonate, in a suitable solvent, for example acetonitrile.

SCHEME S

Alternatively, compounds of formula (9) may be prepared from aldehydes of formula (6).

Compounds of formula (6) are treated with a chlorinating agent, for example N- chlorosuccinimide, in a suitable solvent, for example 1 ,2-dichloroethane, and optionally in the presence of a suitable catalyst/ligand/additive combination. Suitable catalyst/ligand combinations may include palladium^ I) acetate and 2-aminobenzoic acid. Suitable additives may include trifluoroacetic acid and silver trifluoroacetate.

SCHEME 9

In a further alternative approach, compounds of formula (1 ) where A¹ is -C(R¹)(R²)-, X¹ is O, and A² and A³ are O may be prepared from compounds of formula (1 1 ).

(1) where A¹ is -C(R¹)(R²)-, X¹ is O, and A² and A³ are O

The synthetic steps and reaction conditions used to access compounds of formula (1) from compounds of formula (11 ) will vary depending on the nature of R⁵, R⁶, R⁷ and R⁸.

SCHEME 10

For example, where R⁵ and R⁶ are hydrogen and R⁷ and R⁸ are methyl, compounds of formula (1 ) may be prepared from compounds of formula (12).

Compounds of formula (12) are treated with an acid, for example formic acid, either neat, or in a suitable solvent, for example /V-methyl-2-pyrrolidone.

SCHEME 11

Compounds of formula (12) may be prepared from compounds of formula (13).

Compounds of formula (13) are treated with 3-chloro-2-methyl-1 -propene (14) and a suitable base, for example potassium carbonate, in a suitable solvent, for example acetonitrile.

SCHEME 12

Compounds of formula (13) may be prepared from 5-chloro-6-(chloromethyl)-1 ,3- benzodioxol-2-one (15).

5-Chloro-6-(chloromethyl)-1 ,3-benzodioxol-2-one (15) is treated with compounds of formula (3) and a suitable base, for example potassium carbonate, in a suitable solvent, for example dimethylformamide.

SCHEME 13

5-Chloro-6-(chloromethyl)-1 ,3-benzodioxol-2-one (15) may be prepared from (6- Chloro-1 ,3-benzodioxol-5-yl)methanol (16) which is commercially available.

(6-Chloro-1 ,3-benzodioxol-5-yl)methanol (16) is treated with phosphorus pentachloride in a suitable solvent, for example chlorobenzene.

SCHEME 14

Where A¹ is -C(=O)- and X¹ is O, compounds of formula (1) may be prepared from compounds of formula (17).

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 15

Compounds of formula (17) may be prepared from compounds of formula (2), where LG represents a suitable leaving group (such as Br or Cl).

For example, where LG is is Br, compounds of formula (2) are treated with N,0-diboc hydroxylamine, a suitable base, for example potassium carbonate, and optionally, a suitable catalyst, for example tetrabutylammonium iodide, in a suitable solvent, for example acetone, to give compounds of formula (18). Compounds of formula (18) are treated with a suitable acid, for example hydrochloric acid, in a suitable solvent, for example dioxane.

SCHEME 16

Some compounds of formula (3) may be commercially available. For example, the compound of formula (3) where R³ and R⁴ are methyl and R¹ and R² are hydrogen is commercially available (CAS no 81778-07-6). Alternatively, compounds of formula (3) may be prepared synthetically. For example, where R¹ is Ci-Cealkoxy, Ci-Cealkoxy-Cr Cealkoxy-, HOC(0)Ci-C6alkoxy-, Ci-C6alkoxy-C(0)-Ci-C6alkoxy- or Ci-Csalkyl- S(0)_pCi-C6alkoxy- and R² is hydrogen, compounds of formula (3) may be prepared from 3,3-dichloro-2,2-dimethylpropanoic acid (19).

3,3-Dichloro-2,2-dimethylpropanoic acid (19) is treated with a suitable chlorinating agent, for example thionyl chloride and catalytic dimethylformamide to give 3,3- dichloro-2,2-dimethylpropanoyl chloride (20). 3,3-Dichloro-2,2-dimethylpropanoyl chloride (20) is treated with a suitable source of hydroxylamine, for example hydroxylamine (50% in H₂O) to give 3,3-dichloro-2,2-dimethyl-propanehydroxamic acid (21 ). 3,3-Dichloro-2,2-dimethyl-propanehydroxamic acid (21 ) is treated with an alcohol and a suitable base, for example 1 ,8-diazabicyclo(5.4.0)undec-7-ene, to give compounds of formula (3).

SCHEME 17

Compounds of formula (1 ) where X¹ is S may be prepared from compounds of formula (1 ) where X¹ is O.

Compounds of formula (1 ) where X¹ is O are treated with a suitable thionation agent, for example phosphorus pentasulfide, in a suitable solvent, for example toluene. 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 1 : Preparation of Compound 1.001

Step 1 : Preparation of 2,2-difluoro-3H-1 ,4-benzodioxine-6-carbaldehyde

Potassium carbonate (8.79 g, 86.9 mmol) was added to 3,4-dihydroxybenzaldehyde (3.00 g, 21 .7 mmol) in acetonitrile (45 mL) at RT. Then 1 ,2-dibromo-1 ,1 -difluoro-ethane (17.0 g, 7.65 mL, 76.0 mmol) was added and the reaction stirred at 90 °C for 18 h. After this time a further portion of 1 ,2-dibromo-1 ,1 -difluoro-ethane (17.0 g, 7.65 mL, 76.0 mmol) was added and the reaction stirred for a further 24 h. The reaction was quenched with water and the product was 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 (0-20% ethyl acetate in cyclohexane). Product containing fractions were combined and concentrated to afford a 1 :1 mixture of 2,2-difluoro-3H-1 ,4-benzodioxine-6-carbaldehyde (0.889 g, 4.44 mmol, 20%) and 3,3-difluoro-2H-1 ,4-benzodioxine-6-carbaldehyde (0.889 g, 4.44 mmol, 20%) as a pale orange oil. 1 H NMR (400 MHz, CDCI3) 8 ppm 9.1 1 (s, 1 H, regioisomer 1 or 2), 9.10 (s, 1 H, regioisomer 1 or 2), 7.61 -7.56 (m, 4 H, regioisomer 1 and 2), 7.20-7.15 (m, 2 H, regioisomer 1 and 2), 4.36-4.30 (m, 4 H, regioisomer 1 and 2).

Step 2: Preparation of (2,2-difluoro-3H-1 ,4-benzodioxin-6-yl)methanol

Sodium borohydride (0.386 g, 10.2 mmol) was added portionwise to a vigorously stirred suspension of a 1 :1 mixture of 3,3-difluoro-2H-1 ,4-benzodioxine-6- carbaldehyde (0.889 g, 4.44 mmol) and 2,2-difluoro-3H-1 ,4-benzodioxine-6- carbaldehyde (0.889 g, 4.44 mmol) in water (13.3 mL) at 0 °C. The reaction was stirred for 5 h. The reaction was quenched with sat. aq. NH₄CI and the product was extracted using ethyl acetate (x2). The organic portions were combined, dried over MgSC , filtered and concentrated in vacuo to afford a 1 :1 mixture of (3,3-difluoro-2H-1 ,4- benzodioxin-6-yl)methanol (0.786 g, 3.89 mmol, 44%) and (2,2-difluoro-3H-1 ,4- benzodioxin-6-yl)methanol (0.786 g, 3.89 mmol, 44%) as a colourless oil. 1 H NMR (400 MHz, CDCI3) 5 ppm 7.06-6.97 (m, 6 H, regioisomer 1 and 2), 4.63 (s, 4 H, regioisomer 1 and 2), 4.26-4.22 (m, 4 H, regioisomer 1 and 2).

Step 3: Preparation of (6-chloro-3,3-difluoro-2H-1 ,4-benzodioxin-7-yl)methanol

A 1 :1 mixture of (3,3-difluoro-2H-1 ,4-benzodioxin-6-yl)methanol (0.786 g, 3.89 mmol) and (2,2-difluoro-3H-1 ,4-benzodioxin-6-yl)methanol (0.786 g, 3.89 mmol) and N- chlorosuccinimide (1 .09 g, 8.16 mmol) in acetonitrile (25.9 mL) was stirred at 70 °C for 1 h. The reaction mixture was concentrated onto isolute® and purified by flash column chromatography (0-30% ethyl acetate in cyclohexane). Product containing fractions were combined and concentrated to afford 6-chloro-3,3-difluoro-2H-1 ,4-benzodioxin- 7-yl)methanol (0.588 g, 2.49 mmol, 32%) as a yellow oil. 1 H NMR (400 MHz, CDCh) 8 ppm 7.28 (s, 1 H), 7.07 (s, 1 H), 4.71 (d, 2 H), 4.24 (t, 2 H), 1.91 (t, 1 H).

Step 4: Preparation of 7-(bromomethyl)-6-chloro-3,3-difluoro-2H-1 ,4-benzodioxine

To a solution of (6-chloro-3,3-difluoro-2H-1 ,4-benzodioxin-7-yl)methanol (0.392 g, 1 .66 mmol) in dichloromethane (3.31 mL) was added carbon tetrabromide (0.659 g, 1.99 mmol). The solution was cooled to 0 °C and triphenylphosphine (0.652 g, 2.49 mmol) was added. The reaction mixture was allowed to warm to RT and was then stirred for 3 h. The reaction mixture was absorbed onto isolute® and purified via flash column chromatography (0-20% ethyl acetate in cyclohexane). Product containing fractions were concentrated to afford 7-(bromomethyl)-6-chloro-3,3-difluoro-2H-1 ,4- benzodioxine (0.407 g, 1 .36 mmol, 82%) as a white solid. 1 H NMR (400 MHz, CDCI3) 8 ppm 6.1 1 (s, 1 H), 6.09 (s, 1 H), 4.51 (s, 2 H), 4.25 (t, 2 H).

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

To a solution of 7-(bromomethyl)-6-chloro-3,3-difluoro-2H-1 ,4-benzodioxine (0.300 g, 1 .00 mmol) in acetone (9.0 mL) was added potassium carbonate (0.21 1 g, 1 .50 mmol) and 4,4-dimethylisoxazolidin-3-one (0.152 g, 1.25 mmol). The reaction was stirred at RT overnight. The reaction mixture was diluted with acetone (10 mL) and filtered through celite® then the mixture was pre-absorbed onto isolute® and purified via flash column chromatography (0-30% ethyl acetate in cyclohexane). Product containing fractions were concentrated to afford 2-[(6-chloro-3,3-difluoro-2H-1 ,4-benzodioxin-7- yl)methyl]-4,4-dimethyl-isoxazolidin-3-one (0.302 g, 0.905 mmol, 90%) as a white solid. 1 H NMR (400 MHz, CDCI₃) 5 ppm 7.08 (s, 1 H), 7.01 (s, 1 H), 4.75 (s, 2 H), 4.24 (t, 2 H), 4.03 (s, 2 H), 1.27 (s, 6 H).

Example 2: Preparation of Compound 1.002

Step 1 : Preparation of 2-methyl-2,3-dihydro-1 ,4-benzodioxine-6-carbaldehyde and 3- methyl-2,3-dihydro-1 ,4-benzodioxine-6-carbaldehyde

Potassium carbonate (29.3 g, 290 mmol) was added to a solution of 3,4- dihydroxybenzaldehyde (10.0 g, 72.4 mmol) in acetonitrile (145 mL) at RT. 1 ,2- Dibromopropane (73.1 g, 37.7 mL, 362 mmol) was added and the reaction stirred at 90 °C overnight. The reaction was quenched with water 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 (0-20% ethyl acetate in cyclohexane). Product containing fractions were combined and concentrated to afford a 1 :1 mixture of 2-methyl-2,3-dihydro-1 ,4- benzodioxine-6-carbaldehyde (1.84 g, 10.4 mmol, 14%) and 3-methyl-2,3-dihydro-1 ,4- benzodioxine-6-carbaldehyde (1.84 g, 10.4 mmol, 14%). 1 H NMR (400 MHz, CDCI3) 5 ppm 9.82 (s, 2 H, regioisomer 1 and 2), 7.42-7.38 (m, 4 H, regioisomer 1 and 2), 7.00- 6.96 (m, 2 H, regioisomer 1 and 2), 4.38-4.26 (m, 4 H, regioisomer 1 and 2), 3.94-3.82 (m, 2 H, regioisomer 1 and 2), 1.41 -1.38 (m, 6 H, regioisomer 1 and 2).

Step 2: Preparation of (3-methyl-2,3-dihydro-1 ,4-benzodioxin-6-yl)methanol and (2- methyl-2,3-dihydro-1 ,4-benzodioxin-6-yl)methanol

Sodium borohydride (0.886 g, 23.4 mmol) was added portionwise to a vigorously stirred suspension of a 1 :1 mixture of 3-methyl-2,3-dihydro-1 ,4-benzodioxine-6- carbaldehyde (1.81 g, 10.2 mmol) and 2-methyl-2,3-dihydro-1 ,4-benzodioxine-6- carbaldehyde (1 .81 g, 10.2 mmol) in water (30.5 mL) at 0 °C. The reaction was stirred for 3 h. The reaction was quenched with sat. aq. NH₄CI and extracted with ethyl acetate (x2). The organic portions were combined, dried over MgSC , filtered and concentrated in vacuo to afford a 1 :1 mixture of (3-methyl-2,3-dihydro-1 ,4-benzodioxin-6- yl)methanol (1.82 g, 10.1 mmol, 50%) and (2-methyl-2,3-dihydro-1 ,4-benzodioxin-6- yl)methanol (1.82 g, 10.1 mmol, 50%) as a colourless oil. 1 H NMR (400 MHz, CDCh) 8 ppm 6.92-6.88 (m, 2 H, regioisomer 1 and 2), 6.85-6.84 (m, 4 H, regioisomer 1 and 2), 4.57 (s, 4 H, regioisomer 1 and 2), 4.27-4.20 (m, 4 H, regioisomer 1 and 2), 3.88- 3.78 (m, 2 H, regioisomer 1 and 2), 1 .37-1 .35 (m, 6 H, regioisomer 1 and 2).

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

A 1 :1 mixture of 2-methyl-2,3-dihydro-1 ,4-benzodioxin-6-yl)methanol (0.567 g, 3.15 mmol) and (3-methyl-2,3-dihydro-1 ,4-benzodioxin-6-yl)methanol (0.567 g, 3.15 mmol) and /V-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 onto isolute® and purified by flash column chromatography (0-40% ethyl acetate in cyclohexane). Product containing fractions were combined and concentrated to afford a mixture of regioisomeric products. This mixture was purified by reverse phase preparative HPLC purification (1 -5% acetonitrile in water). Product containing fractions were combined and concentrated to afford (6-chloro-2-methyl-2,3-dihydro-1 ,4-benzodioxin-7- yl)methanol (0.241 g, 1.12 mmol, 18%) as a white solid and (6-chloro-3-methyl-2,3- dihydro-1 ,4-benzodioxin-7-yl)methanol (0.154 g, 0.717 mmol, 1 1%) as a white solid. 1 H NMR (400 MHz, CDCI₃) 8 ppm 6.96 (s, 1 H), 6.90 (s, 1 H), 4.65 (s, 2 H), 4.27-4.18 (m, 2 H), 3.78-3.83 (m, 1 H), 1 .36 (d, 3 H) and 1 H NMR (400 MHz, CDCI₃) 8 ppm 6.96 (s, 1 H), 6.88 (s, 1 H), 4.64 (s, 2 H), 4.27-4.18 (m, 2 H), 3.78-3.83 (m, 1 H), 1.35 (d, 3 H).

Step 4: Preparation of 7-(bromomethyl)-6-chloro-2-methyl-2,3-dihydro-1 ,4- benzodioxine

To a solution of (6-chloro-2-methyl-2,3-dihydro-1 ,4-benzodioxin-7-yl)methanol (0.198 g, 0.922 mmol) in dichloromethane (1.84 mL) was added carbon tetrabromide (0.367 g, 1.1 1 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 RT and was then stirred for 3 h. The reaction mixture was absorbed onto isolute® and purified via flash column chromatography (0-15% ethyl acetate in cyclohexane). Product containing fractions were concentrated to afford 7-(bromomethyl)-6-chloro-2-methyl-2,3-dihydro- 1 ,4-benzodioxine (0.214 g, 0.771 mmol, 84%) as a white solid. 1 H NMR (400 MHz, CDCh) 8 ppm 6.93 (s, 1 H), 6.91 (s, 1 H), 4.52 (s, 2 H), 4.25-4.20 (m, 2 H), 3.85-3.79 (m, 1 H), 1.35 (d, 3 H). Step 5: Preparation of 2-[(6-chloro-2-methyl-2,3-dihydro-1 ,4-benzodioxin-7-yl)methyl]- 4,4-dimethyl-isoxazolidin-3-one

To a solution of 7-(bromomethyl)-6-chloro-2-methyl-2,3-dihydro-1 ,4-benzodioxine (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 (0.1 11 g, 0.917 mmol). The reaction was stirred at RT overnight. The reaction mixture was diluted with ethyl acetate (10 mL), filtered through celite®, pre-absorbed onto isolute® and purified via flash column chromatography (0-30% ethyl acetate in cyclohexane). Product containing fractions were concentrated to afford 2-[(6-chloro-2-methyl-2,3-dihydro-1 ,4-benzodioxin-7- yl)methyl]-4,4-dimethyl-isoxazolidin-3-one (0.199 g, 0.638 mmol, 84%) as a white solid. 1 H NMR (400 MHz, CDCI₃) 8 ppm 6.90 (s, 1 H), 6.84 (s, 1 H), 4.72 (s, 2 H), 4.25- 4.22 (m, 2 H), 4.01 (s, 2 H), 3.84-3.77 (m, 1 H), 1 .36 (d, 3 H), 1 .26 (s, 6 H).

Example 3: Preparation of Compound 1.006

Preparation of 5-ethoxy-4,4-dimethyl-isoxazolidin-3-one

Step 1 : Preparation of 3,3-dichloro-2,2-dimethyl-propanoyl chloride

3,3-Dichloro-2,2-dimethyl-propanoic acid (88.0 g, 514 mmol) was added to a stirred solution of thionyl chloride (148 mL) at RT. The mixture was heated to 70 °C 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 2: 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 min at RT. The reaction mixture was extracted with dichloromethane, passed through a hydrophobic frit 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, CDCI3) 8 ppm 6.40 (br s, 1 H), 6.12 (s, 1 H), 1.40 (s, 6 H). Step 3: Preparation of 5-ethoxy-4,4-dimethyl-isoxazolidin-3-one

A solution of 3,3-dichloro-2,2-dimethyl-propanehydroxamic acid (0.500 g, 2.69 mmol) and 1 ,8-Diazabicyclo(5.4.0)undec-7-ene (0.919 g, 0.90 mL, 5.91 mmol) in ethanol (5 mL) was heated at 120 °C for 45 min by microwave irradiation. The mixture was concentrated in vacuo and the residue diluted with dichloromethane. 2 M HCI was added and the product extracted with dichloromethane (x5). The organic portions were combined, dried over MgSC , filtered and concentrated in vacuo to afford 5-ethoxy- 4,4-dimethyl-isoxazolidin-3-one (0.269 g, 1 .69 mmol, 63%) as a colourless oil. 1 H NMR (400 MHz, CDCI₃) 8 ppm 8.20 (br s, 1 H), 4.99 (s, 1 H), 3.90-3.80 (m, 1 H), 3.60-3.50 (m, 1 H), 1 .32 (s, 3 H), 1 .18 (s, 3 H), 1 .28-1 .19 (m, 3 H).

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

Step 1 : Preparation of 6-(chloromethyl)-2,2,3,3-tetrafluoro-1 ,4-benzodioxine

(2,2,3,3-Tetrafluoro-1 ,4-benzodioxin-6-yl)methanol (0.394 g, 1.65 mmol) was dissolved in thionyl chloride (5.0 mL) under a nitrogen atmosphere and stirred at RT overnight. The reaction mixture was then concentrated in vacuo to give 6- (chloromethyl)-2,2,3,3-tetrafluoro-1 ,4-benzodioxine (0.371 g, 1.45 mmol, 87%) as a yellow oil. 1 H NMR (400 MHz, CDCI₃) 8 ppm 7.22-7.15 (m, 2 H), 7.14-7.09 (m, 1 H), 4.52 (s, 2 H).

Step 2: Preparation of 5-chloro-7-(chloromethyl)-2,2,3,3-tetrafluoro-1 ,4-benzodioxine

Trichloroisocyanuric acid (0.840 g, 3.61 mmol) was added to a solution of 6- (chloromethyl)-2, 2, 3, 3-tetrafluoro-1 ,4-benzodioxine (0.371 g, 1.45 mmol) in 1 -butyl-3- methyl-imidazol-3-ium hexafluorophosphate (10 mL) and the reaction stirred at 140 °C until complete as monitored by GCMS. The reaction mixture was absorbed onto silica gel and purified via flash column chromatography (100% isohexane). Product containing fractions were concentrated to afford 6-chloro-7-(chloromethyl)-2, 2,3,3- tetrafluoro-1 ,4-benzodioxine (0.247 g, 0.849 mmol, 59%). 1 H NMR (400 MHz, CDCI3) 8 ppm 7.31 (s, 1 H), 7.23 (s, 1 H), 4.62 (s, 2 H). Step 3: Preparation of 2-[(6-chloro-2,2,3,3-tetrafluoro-1 ,4-benzodioxin-7-yl)methyl]-5- ethoxy-4,4-dimethyl-isoxazolidin-3-one

To 6-chloro-7-(chloromethyl)-2,2,3,3-tetrafluoro-1 ,4-benzodioxine (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-/V-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 celite® then purified by reverse phase preparative HPLC purification. Product containing fractions were combined and concentrated to afford 2-[(6-chloro-2, 2,3,3- tetrafluoro-1 ,4-benzodioxin-7-yl)methyl]-5-ethoxy-4,4-dimethyl-isoxazolidin-3-one (16 mg, 0.038 mmol, 14%). 1 H NMR (400 MHz, CDCI₃) 8 ppm 7.22 (s, 1 H), 7.19 (s, 1 H), 4.92-4.89 (m, 2 H), 4.70-4.68 (m, 1 H), 3.75-3.68 (m, 1 H), 3.52-3.47 (m, 1 H), 1.29- 1.16 (m, 9 H).

Example 4: Preparation of Compound 1.009

Step 1 : Preparation of /V-[(6-chloro-2,3-dihydro-1 ,4-benzodioxin-7- yl)methyl]hydroxylamine

/V,0-Bis(tert-butoxycarbonyl)hydroxylamine (0.620 g, 2.58 mmol), potassium carbonate (0.755 g, 5.41 mmol), 6-chloro-7-(chloromethyl)-2,3-dihydro-1 ,4- benzodioxine (0.504 g, 2.30 mmol) and tetrabutylammonium iodide (93 mg, 0.25 mmol) were dissolved in acetone (25 mL) and heated to 60 °C for 5 h. The reaction mixture was filtered and concentrated in vacuo. The residue was treated with 4 M HCI in dioxane (10 mL) and stirred for 2 h. The reaction mixture was concentrated in vacuo and then water and dichloromethane were added. Concentrated NaOH was added dropwise to basify the solution to pH 9. The layers were separated, and the aqueous layer extracted with another potion of dichloromethane. The organic portions were combined, dried over MgSC , filtered and concentrated in vacuo to afford /V-[(6-chloro- 2,3-dihydro-1 ,4-benzodioxin-7-yl)methyl]hydroxylamine (0.424 g, 1.97 mmol, 85%) as a white solid. 1 H NMR (400 MHz, CDCI3) 8 ppm 6.93-6.90 (m, 2 H), 4.23 (s, 4 H), 4.05 (s, 2 H).

Step 2: Preparation of 2-[(6-chloro-2,3-dihydro-1 ,4-benzodioxin-7-yl)methyl]-4,4- dimethyl-isoxazolidine-3, 5-dione 2,2-Dimethylpropanedioyl dichloride (0.337 g, 0.265 mL, 1.99 mmol) in dichloromethane (12.5 mL) was added dropwise over 15 min to a solution of A/-[(6- chloro-2,3-dihydro-1 ,4-benzodioxin-7-yl)methyl]hydroxylamine (0.424 g, 1.97 mmol) and pyridine (0.553 g, 0.565 mL, 6.92 mmol) in dichloromethane (12.5 mL) at 0 °C. The reaction mixture was stirred for 1 h and then left to stand overnight at RT. The reaction mixture was acidified with 2 M HCI, partitioned by passage through a hydrophobic frit, and concentrated in vacuo. The reaction mixture was absorbed onto silica gel and purified via flash column chromatography (0-100% ethyl acetate in isohexane). Product containing fractions were concentrated to afford 2-[(6-chloro-2,3- dihydro- 1 ,4-benzodioxin-7-yl)methyl]-4,4-dimethyl-isoxazolidine-3, 5-dione (0.570 g, 1 .83 mmol, 93%) as an orange solid. 1 H NMR (400 MHz, CDCh) 8 ppm 6.92 (s, 1 H), 6.85 (s, 1 H), 4.94 (s, 2 H), 4.25 (s, 4 H), 1 .45 (s, 6 H).

Example 5: Preparation of Compound 1.004

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

(6-Chloro-1 ,3-benzodioxol-5-yl)methanol (2.80 g, 15.0 mmol) in chlorobenzene (10 mL) was added dropwise over 10 min to a solution of phosphorus pentachloride (60.0 mmol, 13.2 g) in chlorobenzene (18 mL). The reaction was stirred at 135 °C for 4 h then quenched with water and extracted with DCM. The organic portion was dried over MgSCU, filtered and concentrated onto celite®. Purification via flash column chromatography (0-30% ethyl acetate in cyclohexane) afforded 5-chloro-6- (chloromethyl)-l ,3-benzodioxol-2-one (3.12 g, 14.2 mmol, 95%). 1 H NMR (400 MHz, CDCh) 6 ppm 7.43 (s, 1 H), 7.36 (s, 1 H), 4.71 (s, 2 H).

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

5-chloro-6-(chloromethyl)-1 ,3-benzodioxol-2-one (3.10 g, 14.2 mmol), 4,4- dimethylisoxazolidin-3-one (1.71 g, 14.9 mmol) and potassium carbonate (5.99 g, 42.5 mmol) were combined in DMF (31 mL) under a nitrogen atmosphere. The reaction was stirred at RT for 3 h then quenched with 2 M HCI and extracted with ethyl acetate (x2). The combined organic portions were washed with brine, dried over MgSCU, filtered and concentrated onto celite®. Purification via flash column chromatography (10-100% ethyl acetate in cyclohexane) afforded 2-[(2-chloro-4,5-dihydroxy-phenyl)methyl]-4,4- dimethyl-isoxazolidin-3-one (2.75 g, 10.1 mmol, 72%). 1 H NMR (400 MHz, d6-DMSO) 6 ppm 9.49 (br s, 2 H), 6.76 (s, 1 H), 6.75 (s, 1 H), 4.55 (s, 2 H), 4.00 (s, 2 H), 1 .12 (s, 6 H).

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

Potassium carbonate (1.9 g, 14.0 mmol) was added to a solution of 2-[(2-chloro-4,5- dihydroxy-phenyl)methyl]-4,4-dimethyl-isoxazolidin-3-one (2.5 g, 9.20 mmol) in acetonitrile (30 mL). The mixture was stirred for 1 h and then 3-chloro-2-methyl-prop-

1 -ene (0.925 g, 1 mL, 10.0 mmol) was added dropwise. The reaction mixture was heated to reflux overnight then quenched with 2 M HCI and extracted ethyl acetate (x4). The combined organic portions were washed with brine, dried over MgSC , filtered and concentrated. The crude material was purified by flash column chromatography (0-15% ethyl acetate in isohexane) to afford 2-[[2-chloro-5-hydroxy- 4-(2-methylallyloxy)phenyl]methyl]-4,4-dimethyl-isoxazolidin-3-one (0.607 g, 1 .86 mmol, 20%). 1 H NMR (400 MHz, CDCI₃) 6 ppm 6.92 (s, 1 H), 6.85 (s, 1 H), 5.62 (s, 1 H), 5.08 (s, 1 H), 5.04 (s, 1 H), 4.73 (s, 2 H), 4.48 (s, 2 H), 4.01 (s, 2 H), 1.83 (s, 3H), 1.26 (s, 6H).

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

2-[[2-Chloro-5-hydroxy-4-(2-methylallyloxy)phenyl]methyl]-4,4-dimethyl-isoxazolidin-

3-one (40 mg, 0.123 mmol) and formic acid (10 mL, 252 mmol) were combined and heated to reflux for 30 min. The reaction mixture was concentrated then diluted in DCM and washed with sat. aq. NaHCOs. The aqueous layer was extracted with DCM (x2). The combined organic portions were washed with water, dried over MgSC , filtered and concentrated. The crude material was purified by reverse phase preparative HPLC to afford 2-[(6-chloro-2,2-dimethyl-3H-1 ,4-benzodioxin-7-yl)methyl]-4,4-dimethyl- isoxazolidin-3-one (19 mg, 0.058 mmol, 48%). 1 H NMR (400 MHz, CDCI3) 6 ppm 6.91 (s, 1 H), 6.81 (s, 1 H), 4.72 (s, 2 H), 4.02 (s, 2 H), 3.86 (s, 2 H), 1.33 (s, 6 H), 1.26 (s, 6 H).

Example 6: Preparation of Compound 1.005

Step 1 : Preparation of 2-[[2-chloro-4-hydroxy-5-(2-methylallyloxy)phenyl]methyl]-4,4- dimethyl-isoxazolidin-3-one Potassium carbonate (1.9 g, 14.0 mmol) was added to a solution of 2-[(2-chloro-4,5- dihydroxy-phenyl)methyl]-4,4-dimethyl-isoxazolidin-3-one (2.5 g, 9.20 mmol) in acetonitrile (30 mL). The mixture was stirred for 1 h and then 3-chloro-2-methyl-prop-

1 -ene (0.925 g, 1 mL, 10.0 mmol) was added dropwise. The reaction mixture was heated to reflux overnight then quenched with 2 M HCI and extracted ethyl acetate (x4). The combined organic portions were washed with brine, dried over MgSC , filtered and concentrated. The crude material was purified by flash column chromatography (0-15% ethyl acetate in isohexane) to afford 2-[[2-chloro-4-hydroxy- 5-(2-methylallyloxy)phenyl]methyl]-4,4-dimethyl-isoxazolidin-3-one (0.363 g, 1.1 1 mmol, 12%). 1 H NMR (400 MHz, CDCI₃) 6 ppm 6.96 (s, 1 H), 6.84 (s, 1 H), 5.69 (s, 1 H), 5.06 (s, 1 H), 5.02 (s, 1 H), 4.74 (s, 2 H), 4.47 (s, 2 H), 3.98 (s, 2 H), 1 .82 (s, 3 H), 1.24 (s, 6 H).

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

2-[[2-chloro-4-hydroxy-5-(2-methylallyloxy)phenyl]methyl]-4,4-dimethyl-isoxazolidin-3- one (40 mg, 0.123 mmol) and formic acid (10 mL, 252 mmol) were combined and heated to reflux for 30 min. The reaction mixture was concentrated then diluted in DCM and washed with sat. aq. NaHCOs. The aqueous layer was extracted with DCM (x2). The combined organic portions were washed with water, dried over MgSC , filtered and concentrated. The crude material was purified by reverse phase preparative HPLC to afford 2-[(6-chloro-3,3-dimethyl-2H-1 ,4-benzodioxin-7-yl)methyl]-4,4-dimethyl- isoxazolidin-3-one (12 mg, 0.037 mmol, 30%). 1 H NMR (400 MHz, CDCI3) 6 ppm 6.86 (s, 1 H), 6.85 (s, 1 H), 4.73 (s, 2 H), 4.02 (s, 2 H), 3.86 (s, 2 H), 1.33 (s, 6 H), 1.27 (s, 6 H).

Example 7: Preparation of Compound 1.029

Step 1 : Preparation of 7-chlorochromane-6-carbaldehyde

1 ,2-Dichloroethane (74 mL) and 2,2,2-trifluoroacetic acid (8.52 g, 5.76 mL, 74.0 mmol) were added to a mixture of chromane-6-carbaldehyde (1.20 g, 7.40 mmol), N- chlorosuccinimide (1.48 g, 11.1 mmol), palladium^ I) acetate (0.175 g, 0.740 mmol), 2- aminobenzoic acid (0.311 g, 2.22 mmol), and silver trifluoroacetate (0.167 g, 0.740 mmol). The reaction mixture was heated to 60 °C for 18 h then partitioned between sat. aq. NaHCOs and DCM. The aqueous layer was extracted with DCM (x2) and the combined organic portions were passed through a hydrophobic filter paper and then concentrated. The crude material was purified by reverse phase flash column chromatography to afford 7-chlorochromane-6-carbaldehyde (0.442 g, 2.25 mmol, 30%). 1 H NMR (400 MHz, CDCI₃) 6 ppm 10.29 (s, 1 H), 7.66 (t, 1 H), 6.84 (s, 1 H), 4.29-4.22 (m, 2 H), 2.79 (t, 2 H), 2.06-1.97 (m, 2 H).

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

Diisobutylaluminium hydride (6.55 mL of a 1 M solution in toluene, 6.55 mmol) was added dropwise to a solution of 7-chlorochromane-6-carbaldehyde (0.515 g, 2.62 mmol) in 2-methyltetrahydrofuran (5.95 mL) at 0 °C under a nitrogen atmosphere. The reaction mixture was stirred at RT for 3 h then quenched by the dropwise addition of ethyl acetate at 0 °C. Sat. aq. potassium sodium tartrate was added and the mixture stirred vigorously for 1 h. The mixture was then extracted with ethyl acetate (2x). The combined organic portions were passed through a hydrophobic frit and concentrated to afford (7-chlorochroman-6-yl)methanol (0.361 g, 1.82 mmol, 69%). 1 H NMR (400 MHz, CDCI₃) 3 ppm 7.10 (s, 1 H), 6.83 (s, 1 H), 4.66 (d, 2 H), 4.20-4.14 (m, 2 H), 2.75 (t, 2 H), 2.03-1 .95 (m, 2 H), 1 .86 (br t, 1 H).

Step 3: Preparation of 7-chloro-6-(chloromethyl)chromane

(7-Chlorochroman-6-yl)methanol (0.31 1 g, 1.57 mmol) and thionyl chloride (7.44 mL, 102 mmol) were combined and stirred overnight at RT under a nitrogen atmosphere. The reaction mixture was added dropwise to water and extracted with ethyl acetate (x3). The combined organic portions were passed through a hydrophobic filter paper and then concentrated to afford 7-chloro-6-(chloromethyl)chromane (0.265 g, 1.22 mmol, 78%). 1 H NMR (400 MHz, CDCI3) 5 ppm 7.10 (s, 1 H), 6.84 (s, 1 H), 4.64 (s, 2 H), 4.20-4.15 (m, 2 H), 2.75 (t, 2 H), 2.03-1 .93 (m, 2 H).

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

7-Chloro-6-(chloromethyl)chromane (0.265 g, 1.22 mmol), 4,4-dimethylisoxazolidin-3- one (0.183 g, 1.59 mmol), potassium carbonate (0.337 g, 2.44 mmol) and acetone (7.32 mL) were combined and stirred at RT for 2 days. The reaction mixture was diluted with water and extracted with ethyl acetate (x3). The organic portions were combined, passed through a hydrophobic filter paper and concentrated. The crude material was purified by reverse phase flash column chromatography to afford 2-[(7-chlorochroman- 6-yl)methyl]-4,4-dimethyl-isoxazolidin-3-one (80 mg, 0.270 mmol, 22%). 1 H NMR (400 MHz, CDCI₃) 3 ppm 6.99 (s, 1 H), 6.82 (s, 1 H), 4.73 (s, 2 H), 4.20-4.14 (m, 2 H), 4.00 (s, 2 H), 2.73 (t, 2 H), 2.02-1.94 (m, 2 H), 1.25 (s, 6 H).

Example 8: Preparation of Compound 1.038

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

Trimethyl(trimethylsilyloxy)silane (0.180 g, 0.237 mL, 1.11 mmol) and phosphorus pentasulfide (82 mg, 0.370 mmol) were added to a solution of 2-[(6-chloro-3,3-difluoro- 2H-1 ,4-benzodioxin-7-yl)methyl]-4,4-dimethyl-isoxazolidin-3-one (0.130 g, 0.370 mmol) in toluene (4 mL) under an atmosphere of argon. The reaction mixture was heated to 1 10 °C for 1 h and then concentrated. The crude material was purified by flash column chromatography (0-60% ethyl acetate in hexane) to afford 2-[(6-chloro- 3,3-difluoro-2H-1 ,4-benzodioxin-7-yl)methyl]-4,4-dimethyl-isoxazolidine-3-thione (75 mg, 0.204 mmol, 55%). 1 H NMR (400 MHz, d6-DMSO) 6 ppm 7.46 (s, 1 H), 7.14 (s, 1 H), 5.19 (s, 2 H), 4.64 (t, 2 H), 4.18 (s, 2 H), 1 .21 (s, 6 H).

Further examples of compounds of Formula (I) were made in an analagous manner to the Examples described above, and are shown with charactertising data in Tale 1 below.

Table 1. Compounds of the present invention

BIOLOGICAL EXAMPLES

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 (post-emergence) 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 (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 250 g/ha. 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 postemergence, 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%); NT indicates not tested.

TABLE B1. Post-emergence Test

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

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

[c] A 55 : 45 ratio mixture of 1.018 : 1.021 was tested

TABLE B2. Pre-emergence Test

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

[b] A 55 : 45 ratio mixture of 1.017 : 1.020 was tested [c] A 55 : 45 ratio mixture of 1.018 : 1.021 was tested 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 (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 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%); NT indicates not tested.

TABLE B3. Post-emergence Test

TABLE B4. Pre-emergence Test

Claims

1. A compound of Formula (I),

wherein

A¹ is CR¹R² or C(O);

A² is selected from the group consisting of CR⁹R¹⁰, C(O), O, S(O)_P and N(R¹³);

A³ is selected from the group consisting of CR¹¹R¹², C(O), O, S(O)_P and N(R¹³⁾;

X¹ is O or S;

R¹ is selected from the group consisting of hydrogen, halogen, HO-, Cr Cealkoxy, Ci-Cealkoxy-Ci-Cealkoxy-, Ci-C3alkyl-C(O)O-, HOC(0)Ci-C6alkoxy-, Ci-C6alkoxy-C(0)-Ci-C6alkoxy-, Ci-C3alkyl-S(O)_p- and Ci-C3alkyl-S(O)_pCi- Cealkoxy-;

R² is hydrogen,

R³ is Ci-C₃alkyl;

R⁴ is Ci-C₃alkyl;

R⁵ is selected from the group consisting of hydrogen, halogen, Ci-Cealkyl, Ci- Cehaloalkyl, Cs-Cecycloalkyl and Ci-Cealkoxy-; and

R⁶ is selected from the group consisting of hydrogen, halogen, Ci-Cealkyl, Cr Cehaloalkyl, Cs-Cecycloalkyl and Ci-Cealkoxy-; or R⁵ and R⁶ together are =0 or -(CH₂)_n-; and

R⁷ is selected from the group consisting of hydrogen, halogen, Ci-Cealkyl, Cr Cehaloalkyl, Cs-Cecycloalkyl and Ci-Cealkoxy-;

R⁸ is selected from the group consisting of hydrogen, halogen, Ci-Cealkyl, Cr Cehaloalkyl, Cs-Cecycloalkyl and Ci-Cealkoxy-; or

R⁷ and R⁸ together are =0 or -(CH₂)_n-; and

R⁹ is selected from the group consisting of hydrogen, halogen, Ci-Cealkyl, Cr Cehaloalkyl, Cs-Cecycloalkyl and Ci-Cealkoxy-;

R¹⁰ is selected from the group consisting of is selected from the group consisting of hydrogen, halogen, Ci-Cealkyl, Ci-Cehaloalkyl, Cs-Cecycloalkyl and Ci-Cealkoxy-; or

R⁹ and R¹⁰ together are -(CH₂)_n-; and

R¹¹ is selected from the group consisting of hydrogen, halogen, Ci-Cealkyl, Cr Cehaloalkyl, Cs-Cecycloalkyl and Ci-Cealkoxy-;

R¹² is selected from the group consisting of hydrogen, halogen, Ci-Cealkyl, Cr Cehaloalkyl, Cs-Cecycloalkyl and Ci-Cealkoxy-; or

R¹¹ and R¹² together are -(CH₂)_n-;

R¹³ is hydrogen or Ci -Csalkyl ; n is independently 2, 3,4 ,5 or 6; and p is independently 0, 1 or 2.

2. The compound of Formula (I) wherein X¹ is O.

3. The compound of Formula (I) according to claim 1 or claim 2, wherein R³ and R⁴ are methyl.

4. The compound of Formula (I) accordingly to any one of the previous claims, wherein A¹ is CR¹R² and R¹ is hydrogen.

5. The compound of Formula (I) accordingly to any one of claims 1 to 3, wherein A¹ is CR¹R² and R¹ is Ci-Cealkoxy.

6. The compound of Formula (I) accordingly to any one of claims 1 to 3, wherein A¹ is C(O).

7. The compound according to any one of the previous claims, wherein A² is O.

8. The compound according to any one of the previous claims wherein A² and A³ are O.

9. The compound according to any of the previous claims, wherein R⁵, R⁶, R⁷ and R⁸ are 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 previous 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 1 1 , wherein the additional pesticide is a herbicide or herbicide safener.

13. A method of controlling weeds at a locus 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.