GB2594931A - Improvements in or relating to organic compounds - Google Patents

Improvements in or relating to organic compounds Download PDF

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Publication number
GB2594931A
GB2594931A GB2006686.6A GB202006686A GB2594931A GB 2594931 A GB2594931 A GB 2594931A GB 202006686 A GB202006686 A GB 202006686A GB 2594931 A GB2594931 A GB 2594931A
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United Kingdom
Prior art keywords
formula
compound
mmol
chloro
nmr
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GB2006686.6A
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GB202006686D0 (en
Inventor
Steven Wailes Jeffrey
Briggs Emma
Andrew Tate Joseph
Mary Ingram Katharine
Alan Morris James
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Syngenta Crop Protection AG Switzerland
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Syngenta Crop Protection AG Switzerland
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Priority to GB2006686.6A priority Critical patent/GB2594931A/en
Publication of GB202006686D0 publication Critical patent/GB202006686D0/en
Publication of GB2594931A publication Critical patent/GB2594931A/en
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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D213/00—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
    • C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
    • C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
    • C07D213/60—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
    • C07D213/72—Nitrogen atoms
    • C07D213/76—Nitrogen atoms to which a second hetero atom is attached
    • A—HUMAN NECESSITIES
    • A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
    • A01P—BIOCIDAL, PEST REPELLANT, PEST ATTRACTANT OR PLANT GROWTH REGULATORY ACTIVITY OF CHEMICAL COMPOUNDS OR PREPARATIONS
    • A01P13/00—Herbicides; Algicides
    • A—HUMAN NECESSITIES
    • A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
    • A01N—PRESERVATION OF BODIES OF HUMANS OR ANIMALS OR PLANTS OR PARTS THEREOF; BIOCIDES, e.g. AS DISINFECTANTS, AS PESTICIDES OR AS HERBICIDES; PEST REPELLANTS OR ATTRACTANTS; PLANT GROWTH REGULATORS
    • A01N43/00—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds
    • A01N43/34—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having rings with one nitrogen atom as the only ring hetero atom
    • A01N43/40—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having rings with one nitrogen atom as the only ring hetero atom six-membered rings
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D213/00—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
    • C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
    • C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
    • C07D213/60—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
    • C07D213/62—Oxygen or sulfur atoms
    • C07D213/63—One oxygen atom
    • C07D213/64—One oxygen atom attached in position 2 or 6
    • C07D213/643—2-Phenoxypyridines; Derivatives thereof
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D213/00—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
    • C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
    • C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
    • C07D213/60—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
    • C07D213/78—Carbon atoms having three bonds to hetero atoms, with at the most one bond to halogen, e.g. ester or nitrile radicals
    • C07D213/84—Nitriles
    • C07D213/85—Nitriles in position 3

Abstract

A compound of formula (I) or an agronomically acceptable salt thereof wherein X is O or S(O)p; Y is selected from C(HR4), O C(O) and S(O)p; each R1 is independently selected from halogen, -CN, nitro, C1-C4alkyl, C2-C4alkenyl, C2-C4alkynyl, C1-C4haloalkyl, C1-C4alkoxy-, C1-C4haloalkoxy- and -S(O)pC1-C4alkyl; each R2 is independently selected from halogen, -CN, NO2, C1-C4alkyl, C1-C4haloalkyl, C3-C6cycloalkyl C2-C4alkenyl, C2-C4alkynyl, -S(O)pC1-C4alkyl, C1-C4alkoxy, -C(O)C1-C4alkyl, -C(O)OC1-C4alkyl and C1-C4haloalkoxy; R3 is selected from C1-C6alkyl, C1-C6haloalkyl, C1-C6alkoxy- and C1-C6haloalkoxy-, with the proviso that when Y is O or S(O)p then R3 is not C1-C6alkoxy- or C1-C6haloalkoxy-; R4 is selected from hydrogen, halogen, -CN and -OH; m = 0, 1 or 2; n = 0, 1 or 2; and p = 0, 1 or 2. A method of controlling weeds at a locus comprising application to the locus of a weed a controlling amount of a composition comprising a compound of formula (I). Use of compound of formula (I) as a herbicide.

Description

IMPROVEMENTS IN OR RELATING TO ORGANIC COMPOUNDS
The present invention relates to novel herbicidal compounds, to processes for their preparation, to herbicidal compositions which comprise the novel compounds, and to their use for controlling weeds, in particular in crops of useful plants, or for inhibiting plant growth.
Herbicidal substituted phenoxypyrimidines are disclosed in, for example, W094/17059, W02015/089003, W02015/108779 and W02016/196606. The present invention relates to novel herbicidal phenoxypyridine compounds which show improved properties compared to the known pyrimidine compounds -especially improved crop selectivity.
Thus, according to the present invention there is provided compound of Formula (0: (I) or an agronomically acceptable salt thereof, wherein X is 0 or S(0)p; Y is selected from the group consisting of C(HR4), 0, C(0) and S(0)p; each R1 is independently selected from the group consisting of halogen, -CN, nitro, Ci-atalkyl, Cratalkenyl, Cratalkynyl, Crathaloalkyl, Ci-Caalkoxy-, Ci-athaloalkoxy-and -S(0)pa-C4alkyl; each IR2 is independently selected from the group consisting of halogen, -ON, NO2, Cratalkyl, Crathaloalkyl, C3-C6cycloalkyl Cratalkenyl, Cratalkynyl, -S(0)pCrC4alkyl, Cratalkoxy, -C(0)CrC4alkyl, -C(0)0C1-C4alkyl and CiathaloalkoxY; R3 is selected from the group consisting of Ci-C6alkyl, Ci-C6haloalkyl, CiCealkoxy-and Ci-C6haloalkoxy-with the proviso that when Y is 0 or S(0)r then R3 is not Ci-C6alkoxy-or Ci-C6haloalkoxY-i R4 is selected from the group consisting of hydrogen, halogen, -CN and -OH; m = 0, 1 or 2; n = 0, 1 or 2; and p = 0, 1 or 2.
Ci-atalkyl-and Ci-C6alkyl-includes, for example, methyl (Me, CH3), ethyl (Et, C2H5), n-propyl (n-Pr), isopropyl (i-Pr), n-butyl (n-Bu), isobutyl (i-Bu), sec-butyl and tert-butyl (t-Bu). Ci-C2alkyl is methyl (Me, CH3) or ethyl (Et, C2H5).
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-C6haloalkyl-and Crathaloalkyl-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, heptafluoro-n-propyl and perfluoro-n-hexyl. C1-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.
C1-C6alkoxy includes methoxy and ethoxy.
Ci-C6haloalkoxy-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-atalkyl-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(0)2-(alkylsulfonyl) includes, for example, methylsulfonyl, ethylsulfonyl, propylsulfonyl, isopropylsulfonyl, n-butylsulfonyl, isobutylsulfonyl, sec-butylsulfonyl or tert-butylsulfonyl, preferably methylsulfonyl or ethylsulfonyl.
In one embodiment of the present invention there is provided a compound of Formula (I) wherein X is 0.
In one embodiment of the present invention there is provided a compound of Formula (I), wherein Y is selected from the group consisting of CH2, 0(0) and S(0)pIn a more preferred embodiment Y is CH2 or 0(0), more preferably 0(0).
In one embodiment of the present invention there is provided a compound according to any one of the previous claims, wherein R3 is Ci-Cehaloalkyl. In a more preferred embodiment R3 is 4,4,4-trifluorobut-1-y1 or 3,3,3-trifluoroprop-1-y1 In one embodiment of the present invention there is provided a compound Formula (I) wherein n is 1 or 2 and each R1 is independently selected from the group consisting of halogen, -ON, nitro, Ci-C2alkyl, Ci-C2haloalkyl, Ci-C2alkoxy and aC2haloalkoxy-. In a preferred embodiment of the present invention there is provided a compound of Formula (I) wherein n is 1 and R1 is halogen (especially fluoro, chloro or bromo) or CN. In an especially preferred embodiment of the present invention there is provided a compound of Formula (I) wherein n is 1 and R1 is selected from the group consisting of chloro, bromo and ON, more preferably 3-chloro, 3-bromo or 3-ON, most preferably 3-chloro.
In one embodiment of the present invention there is provided a compound of Formula (I), wherein m = 0. In another embodiment of the present invention there is provided a compound of Formula (I) wherein m is 1 or 2. In a preferred embodiment of the present invention there is provided a compound of Formula (I) wherein m is 1 or 2 and each R2 is independently selected from the group consisting of halogen (especially fluoro, chloro or bromo), nitro, -CN and Crathaloalkyl (especially trifluoromethyl). In a further embodiment of the present invention there is provided a compound of Formula (I) wherein m is 1 or 2 and each R2 is independently selected from the group consisting of fluoro, chloro, bromo, nitro, -CN and trifluoromethyl. In a particularly preferred embodiment there is provided a compound of Formula (I), wherein m is 2 and each 52 is independently chloro or cyano.
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 suspoemulsion (SE), a capsule suspension (CS), a water dispersible granule (WG), an emulsifiable granule (EG), an emulsion, water in oil (EO), an emulsion, oil in water (EW), a micro-emulsion (ME), an oil dispersion (OD), an oil miscible flowable (OF), an oil miscible liquid (014, 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 preformed 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 (EVV) 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 C8-C10 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 (0. 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 W. 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-isopropyl-and tri-isopropyl-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 20 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 °leyl 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, bensulfuron (including bensulfuron-methyl), bentazone, bicyclopyrone, bilanafos, bispyribac-sodium, bixIozone, bromacil, bromoxynil, butachlor, butafenacil, carfentrazone (including carfentrazone- ethyl), cloransulam (including cloransulam-methyl), chlorimuron (including chlorimuron-ethyl), chlorotoluron, chlorsulfuron, cinmethylin, clacyfos, clethodim, clodinafop (including clodinafop- propargy1), clomazone, clopyralid, cyclopyranil, cyclopyrimorate, cyclosulfamuron, cyhalofop (including cyhalofop-butyl), 2,4-0 (including the choline salt and 2- 0 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, diquat dibromide, diuron, epyrifenacil, ethalfluralin, ethofumesate, fenoxaprop (including fenoxaprop-P-ethyl), fenoxasulfone, fenquinotrione, fentrazamide, flazasulfuron, florasulam, florpyrauxifen (including florpyrauxifen-benzyl), fluazifop (including fluazifop-P-butyl), flucarbazone (including flucarbazone-sodium), flufenacet, flumetsulam, flumioxazin, fluometuron, flupyrsulfuron (including flupyrsulfuron-methyl-sodium), fluroxypyr (including fluroxypyr-meptyl), fomesafen, foramsulfuron, glufosinate (including the ammonium salt thereof), glyphosate (including the diammonium, isopropylammonium and potassium salts thereof), halauxifen (including halauxifen-methyl), haloxyfop (including haloxyfop-methyl), hexazinone, hydantocidin, 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 pyraflufenethyl), pyrasulfotole, pyridate, pyriftalid, pyrimisulfan, pyroxasulfone, pyroxsulam, quinclorac, quinmerac, quizalofop (including quizalofop-P-ethyl and quizalofop-P-tefuryl), 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, 3-(2-chloro-4-fluoro-5-(3-methy1-2,6-dioxo-4-trifluoromethyl5 3,6-dihydropyrimidin-1(2H)-yl)pheny1)-5-methyl-4, 5-dihydroisoxazole-5-carboxylic acid ethyl ester, 4-hydroxy-1-methoxy-5-methy1-344-(trifluoromethyl)-2- pyridyl]imidazolidin-2-one, 4-hydroxy-1,5-dimethy1-344-(trifluoromethyl)-2- pyridyl]imidazolidin-2-one, 5-ethoxy-4-hydroxy-1-methyl-344-(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- (trifluoromethyppyrazol-3-yl]imidazolidin-2-one, (4R)1-(5-tert-butylisoxazol-3-y1)-4- ethoxy-5-hydroxy-3-methyl-imidazolidin-2-one, 312-(3,4-dimethoxypheny1)-6-methy1- 3-oxo-pyridazine-4-carbonyllbicyclo[3.2.1]octane-2,4-dione, 2-[2-(3,4- dimethoxypheny1)-6-methy1-3-oxo-pyridazine-4-carbonyl] -5-methyl-cyclohexane-1,3-dione, 212-(3,4-dimethoxypheny1)-6-methy1-3-oxo-pyridazine 4 carbonyl]cyclohexane-1,3-dione, 2-[2-(3,4-dimethoxypheny1)-6-methy1-3-oxo- pyridazine-4-carbony1]-5,5-dimethyl-cyclohexane-1,3-dione, 6-[2-(3,4- dimethoxypheny1)-6-methy1-3-oxo-pyridazine-4-carbonyl]-2,2,4, 4-tetramethyl-cyclohexane-1,3,5-trione, 2-[2-(3,4-dimethoxypheny1)-6-methyl-3-oxo-pyridazine 4 carbony1]-5-ethyl-cyclohexane-1,3-dione, 2-[2-(3,4-dimethoxypheny1)-6-methy1-3-oxo- pyridazine 4 carbony1]-4,4,6,6-tetramethyl-cyclohexane-1,3-dione, 2-[6-cyclopropy1-2-(3,4-d i m ethoxypheny1)-3-oxo-pyridazi ne-4-carbony1]-5-m ethyl-cycl ohexane-1,3-d ione, 3-[6-cyclopropy1-2-(3,4-dimethoxypheny1)-3-oxo-pyridazine-4- carbonyl]bicyclo[3.2.1]octane-2,4-dione, 2-[6-cyclopropy1-2-(3,4-dimethoxypheny1)-3-25 oxo-pyridazine-4-carbony1]-5,5-dimethyl-cyclohexane-1,3-dione, 616-cyclopropy1-2-(3,4-d i m ethoxypheny1)-3-oxo-pyridazi ne-4-carbony1]-2,2,4,4-tetram ethyl- cyclohexane-1,3,5-trione, 246-cyclopropy1-2-(3,4-dimethoxypheny1)-3-oxo-pyridazine- 4-carbonyl]cyclohexane-1,3-dione, 4-[2-(3,4-d imethoxypheny1)-6-methy1-3-oxo- pyridazine-4-carbony1]-2,2,6,6-tetramethyl-tetrahydropyran-3,5-dione, 4-[630 cyclopropy1-2-(3,4-dimethoxypheny1)-3-oxo-pyridazine-4-carbonyl]-2,2,6,6- tetramethyl-tetrahydropyran-3,5-dione, 4-amino-3-chloro-5-fluoro-6-(7-fluoro-1H-indo1-6-yl)pyridine-2-carboxylic acid (including agrochemically acceptable esters thereof, for example, methyl 4-amino-3-chloro-5-fluoro-6-(7-fluoro-1H-indo1-6- yl)pyridine-2-carboxylate), 3-ethylsulfanyl-N-(1,3,4-oxadiazol-2-y1)-5-(trifluoromethyl)- [1,2,4]triazolo[4,3-a]pyridine-8-carboxamide, 3-(isopropylsulfanylmethyl)-N-(5-methyl- 1,3,4-oxadiazol-2-y1)-5-(trifluoromethy1)11,2,4]triazolo[4,3-a] pyridine-8-carboxamide, 3-(isopropylsulfonylmethyl)-N-(5-methyl-1,3,4-oxadiazol-2-y1)-5- (trifluoromethyl)-I1 [1,2,4]triazolo[4,3-a]pyridine-8-carboxamide, 3-(ethylsulfonylmethyl)-N-(5-methy1- 1,3,4-oxadiazol-2-y0-5-(trifluoromethy1)11,2,4]triazolo[4,3-a] pyridine-8-carboxamide, ethyl 24[34[3-chloro-5-fluoro-643-methy1-2,6-dioxo-4- (trifluoromethyppyrimidin-1-y1]-2-pyridyl]oxy]acetate, 6-chloro-4-(2,7-dimethy1-1-naphthyl)-5-hydroxy-2-methyl-pyridazin-3-one, 112-chloro-6-(5-chloropyrimidin-2-yhoxy-pheny11-4,4, 4-trifluoro-butan-1-one and 5-[2-chloro-6-(5-chloropyrimidin-2-yhoxy-pheny1]-3- (difluoromethyhisoxazole.
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 (1) 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 (1) 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 (1) may also be in the form of esters or salts, as mentioned e.g. in The Pesticide Manual, 16th 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 application to the locus of a weed controlling amount of a composition comprising a compound of Formula (1). 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 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-, FPO-, HPPD-, -PDS 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 NKO (Syngenta Seeds). The Bt toxin is a protein that is formed naturally by Bacillus thuringiensis soil bacteria. Examples of toxins, or transgenic
H
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 KnockOutO (maize), Yield Gard® (maize), NuCOTIN33B0 (cotton), Bollgard0 (cotton), NewLeaf0 (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 Abut//on, Amaranthus, Ambrosia, Chenopodium, Chrysanthemum, Conyza, Gal/um, lpomoea, Nasturtium, Sida, Sinapis, Solanurn, Ste//aria, 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
XH
Formula A R2 LG (m)
N I
Formula B Formula I
N
A compound of Formula I may be prepared from a compound of Formula A by reaction with a compound of Formula B (where LG1 represents a suitable leaving group such as F, Cl, Br or SO2Me) in a suitable solvent, optionally with a suitable base. Suitable solvents may include DMF or CH3CN. Suitable bases may include K2CO3.
PG x
XH R(n
Formula C R3 Formula A A compound of Formula A may be prepared from a compound of Formula C (where PG represents a suitable protecting group, such as Me, Ac or THP) using a suitable reagent and in a suitable solvent. For example when X = 0 and PG = Me, suitable reagents may include BBr3 or LiOtBu/dodecanethiol and suitable solvents may include DCM, DCE or THF. R3 0 PG x R3LG2
Formula E R(n Formula D Formula Ca A compound of Formula Ca (a compound of Formula C where Y = 0) may be prepared from a compound of Formula D by an alkylation reaction with a compound of Formula E (where LG2 represents a suitable leaving group such as Cl, Br, I, OTf, OMs or OTs) in the presence of a suitable base and in a suitable solvent. Suitable bases may include K2CO3, suitable solvents may include DMF.
PG x
Formula F Formula Cb A compound of Formula Cb (a compound of Formula C where Y = CH2) may be prepared from a compound of Formula F by a reduction reaction using a suitable reagent and in a suitable solvent. Suitable reduction conditions may include triethylsilane/trifluoroacetic acid. Suitable solvents may include DCM.
Formula F
PG R3M
X
Formula H R(n) Formula G A compound of Formula F may be prepared from a compound G by reaction with a compound of Formula H (where M represents a suitable organometallic group such a Li, Mg-Hal or Zn-Hal) in a suitable solvent. Suitable solvents may include THF. HO 0
PG R3H
X Formula R R3
PG R(1
Formula J Formula Cc A compound of Formula Cc (a compound of Formula C where Y = C(0) and R3 = alkoxy or haloalkoxy) may be prepared from a compound of Formula J via an esterification reaction with a compound of Formula R (where R= alkoxy or haloalkoxy), optionally in the presence of a suitable activating agent and in a suitable solvent. Suitable activating agents for the esterificafion reaction may include sulfuric acid and suitable solvents may include toluene.
R3LG2 PG Formula E x R(n) Formula K Formula Cd A compound of Formula Cd (a compound of Formula C where Y = S) may be prepared from a compound of Formula K via an alkylation reaction with a compound of Formula E optionally in the presence of a suitable base and in a suitable solvent. Suitable bases may include K2CO3. Suitable solvents may include DMF.
R(n) PG R3SH PG Formula Q x p. Formula P Formula Cd In an alternative approach, a compound of Formula Cd (a compound of Formula C where Y = S) may be prepared from a compound of Formula P (where Z1 represents a suitable halogen, such as I or Br) by reaction with a compound of Formula Q in the presence of a suitable catalyst and a suitable base and in a suitable solvent. Suitable catalysts may include Xantphos Pd G3. Suitable bases may include Hunig's base.
Suitable solvents may include 1,4-dioxane. Compounds of Formula P and of Formula Q are commercially available or may be prepared by methods known in the literature.
PG R3LG2 x Formula E Formula 0 Formula Ce A compound of Formula Ce (a compound of Formula C where Y = CHCN) may be prepared from a compound of Formula 0 via an alkylation reaction with a compound of Formula E in the presence of a suitable base and in a suitable solvent. Suitable bases may include NaOH and suitable solvents may include DMSO.
R(n Oxidation Formula L Formula le V7 A compound of Formula le (a compound of Formula I where Y = C(0) and IR' = alkyl or haloalkyl) may be prepared from a compound of Formula L via an oxidation reaction by a suitable oxidising agent in a suitable solvent. Suitable oxidising agents may include Dess-Martin periodinane. Suitable solvents may include DCM.
A compound of Formula L may be prepared from a compound of Formula M via reaction with a compound of Formula H (where M represents a suitable organometallic group such a Li, Mg-Hal or Zn-Hal) in a suitable solvent. Suitable solvents may include TH F. R3M Formula H Formula L Formula M Formula N LG-y-s..R2(m) Formula B
XH R(n R(n
Formula M A compound of Formula M may be prepared from a compound of Formula N via reaction with a compound of Formula B where LG1 represents a suitable leaving group such as F, Cl, Br or SO2Me) in a suitable solvent, optionally with a suitable base. Suitable solvents may include DMF or CH3CN. Suitable bases may include K2CO3.
The following non-limiting examples provide specific synthesis methods for representative compounds of the present invention, as referred to in Table 1 below.
Example 1: Synthesis of 3-[(5-chloro-3-fluoro-2-pyridyl)oxy]-2-(3,3,3-trifluoropropoxy) benzonitrile (A3) Step 1: Synthesis of 3-methoxy-2-(3,3,3-trifluoropropoxy)benzonitrile OH 0 To a stirred solution of 2-hydroxy-3-methoxy-benzonitrile (500mg, 3.35 mmol) and K2CO3 (927mg, 6.70 mmol) in DMF (10 mL) was added 3-bromo-1,1,1-trifluoropropane (712mg, 4.02 mmol). The reaction was heated at 80°C for 2 hours, allowed to cool to RT, diluted with water and extracted with Et20 (x3). The combined organic extracts were washed with brine, dried over Mg304 and evaporated to dryness under reduced pressure. The crude product was purified by flash chromatography on silica gel using a gradient of 5-50% Et0Ac/isohexane as eluent to give the desired product (142mg, 17.2%) as a white solid.
1H NMR (400MHz, CDCI3) 6 7.19-7.11 (m, 3H), 4.39 (t, 2H), 3.89 (s, 3H), 2.77-2.63 (m, 2H) Step 2: Synthesis of 3-hydroxy-2-(3,3,3-trifluoropropoxy)benzonitrile
OH
To a stirred solution of 3-methoxy-2-(3,3,3-trifluoropropoxy)benzonitrile (499mg, 2.04 mmol) in DCM (20 mL) was added dropwise BBr3 (5.09 mL of a 1M solution in DCM, 5.09 mmol). The reaction was heated at reflux for 60 hours, allowed to cool to RT, quenched with water and extracted with DCM (x3). The combined organic extracts were washed with brine, dried over MgSat and evaporated to dryness under reduced pressure. The crude product was purified by flash chromatography on silica gel using a gradient of 5-100% Et0Actisohexane as eluent to give the desired product (380mg, 81%) as an orange solid.
1H NMR (400 MHz, CDCI3) ö 7.19 (dd, 1H), 7.17-7.04 (m, 2H), 5.82 (s, 1H), 4.51 (t, 2H), 2.79-2.63 (m, 2H).
Step 3: Synthesis of 34(5-chloro-3-fluoro-2-pyridyl)oxy]-2-(3,3,3-trifluoropropoxy)benzonitrile (A3) /SF
OH
To a stirred solution of 3-hydroxy-2-(3,3,3-trifluoropropoxy)benzonitrile (63mg, 0.27 mmol) and K2003 (75 mg, 0.54 mmol) in DMF (2 mL) was added 5-chloro-2,3-difluoropyridine (49 mg, 0.32 mmol). The reaction was heated at 80°C overnight, then allowed to cool to RT, diluted with water and extracted with Et0Ac (x3). The combined organic extracts were washed with brine, dried over MgSO4 and evaporated to dryness under reduced pressure. The crude product was purified by flash chromatography on silica gel using a gradient of 5-50% Et0Ac in isohexane as eluent to give the desired product (52 mg, 53%) as a colourless oil.
1H NMR (400 MHz, CDCI3) ö 7.83 (s, 1H), 7.57 (dd, 1H), 7.51 (dd, 1H), 7.43 (dd, 1H), 7.29-7.22 (m, 1H), 4.39 (t, 2H), 2.62-2.49 (m, 2H).
Example 2: Synthesis of 2-(4,4,4-trifluorobutoxy)-3-[(3-fluoro-5-chloro-2-pyridypoxy]benzonitrile (A8) Step 1: Synthesis of 2-(4,4,4-trifluorobutoxy)-3-methoxybenzonitrile To a stirred solution of 2-hydroxy-3-methoxybenzonitrile (2.00 g, 13.4 mmol) in Ndimethylformamide (20 mL) was added K2CO3 (3.71 g, 26.8 mmol) followed by 4,4,4-trifluoro-1-bromobutane (3.07 g, 16.1 mmol). The reaction was stirred at 80°C overnight, after which the reaction mixture was cooled to RT, diluted with Et0Ac and acidified with 2M HCI. The phases were separated then the aqueous was re-extracted with Et0Ac and the combined organics washed with brine, dried over MgSO4 and evaporated to dryness under reduced pressure. The crude residue was purified by flash chromatography on silica gel using a gradient of 5-100% Et0Ac in isohexane as eluent to give the desired product as a yellow oil (3.28 g, 94%).
1H NMR (400MHz, CDCI3) .5 7.18-7.08 (m, 3H), 4.21 (t, 2H), 3.88 (s, 3H), 2.53-2.39 (m, 2H), 2.10-2.00 (m, 2H) Step B: Synthesis of 2-(4,4,4-trifluorobutoxy)-3-hydroxybenzonitrile
F F F F
OH
A stirred solution of 2-(4,4,4-trifluorobutoxy)-3-methoxybenzonitrile (3.28 g, 12.7 mmol) in DCM (250 mL) was cooled to 0°C and had boron tribromide (1 M in DCM, 31.6 mL, 31.6 mmol) added dropwise under a nitrogen atmosphere. The reaction was stirred at 0°C for 1 hour and at room temperature overnight. The reaction was then heated to reflux for 3 days after which the reaction mixture was cooled to RT, quenched with water and diluted with DCM. The phases were separated then the aqueous was re-extracted with DCM and the combined organics washed with brine, dried over MgSO4 and evaporated to dryness under reduced pressure. The crude residue was purified by flash chromatography on silica gel using a gradient of 5- 100% Et0Ac in isohexane as eluent to give the desired product as a yellow solid (2.11 g, 68%).
1H NMR (400MHz, CDCI3) 6 7.19 (dd, 1H), 7.13 (dd, 1H), 7.08 (t, 1H), 5.69 (s, 1H), 4.31 (t, 2H), 2.50-2.34 (m, 2H), 2.18-2.09 (m, 2H) Step 3: Synthesis of 2-(4,4,4-trifluorobutoxy)-3-[(3-fluoro-5-chloro-2-pyridyfloxy]benzonitrile (A8)
F F
OH
To a stirred solution of 2-hydroxy-3-methoxybenzonitrile (0.200 g, 0.816 mmol) in N- dimethylformamide (5 mL) was added K2003 (0.225 g, 1.63 mmol) followed by 2,3-difluoro-5-chloropyridine (0.146 g, 0.979 mmol). The reaction was stirred at 80°C overnight, after which the reaction mixture was cooled to RI and diluted with Et0Ac and water. The phases were separated then the aqueous was re-extracted with Et0Ac and the combined organics washed with brine, dried over MgSat and evaporated to dryness under reduced pressure. The crude residue was purified by flash chromatography on silica gel using a gradient of 5-50% Et0Ac in isohexane as eluent to give the desired product as a white solid (0.235 g, 77%).
1h1 NMR (400MHz, CDCI3) 6 7.86 (s, 1H), 7.56 (dd, 1H), 7.49 (d, 1H), 7.41 (d, 1H), 7.21 (t, 1H), 4.22 (t, 2H), 2.30-2.15 (m, 2H), 1.97-1.86 (m, 2H) Example 3: Synthesis of 242-[(5-chloro-3-fluoro-2-pyridyl)oxy]pheny1]-6,6, 6-trifluoro-hexanenitrile (A43) Step 1: Synthesis of 6,6,6-trifluoro-2-(2-methoxyphenyl)hexanenitrile To a solution of 2-(2-methoxyphenyl)acetonitrile (0.50 g, 3.4 mmol) in dimethylsulfoxide (5 mL) was added sodium hydroxide (50 mass% solution in H20) (0.75 mL, 14 mmol) followed by 4-bromo-1,1,1-trifluoro-butane (0.46 mL, 3.7 mmol) and the reaction mixture stirred at room temperature overnight. The reaction was diluted with water and extracted with Et0Ac. The organic phase was washed with water, dried over MgSO4 and evaporated to dryness under reduced pressure. The crude product was purified by flash chromatography on silica gel using a gradient of 0-50% Et0Ac/cyclohexane as eluent to give the desired product (0.91g, 94%).
1H NMR (400 MHz, CDCI3) ö 7.40 (dd, 1H), 7.36 -7.29 (m, 1H), 7.00 (dt, 1H), 6.93 - 6.88 (m, 1H), 4.24 -4.19 (m, 1H), 3.86 (s, 3H), 2.19-1.91 (m, 4H), 1.84-1.64 (m, 2H).
Step 2: Synthesis of 6,6,6-trifluoro-2-(2-hydroxyphenyl)hexanenitrile To a solution of 6,6,6-trifluoro-2-(2-methoxyphenyl)hexanenitrile (0.90 g, 3.1 mmol) in DCM (31 mL) at 0°C under an N2 atmosphere was added dropwise boron tribromide (1M solution in DCM) (7.9 mL, 7.9 mmol). The reaction was allowed to stir at RT for 18 hours, quenched with saturated aqueous NaHCO3 solution and the phases separated. The organic phase was evaporated to dryness under reduced pressure and the crude product purified by flash chromatography on silica gel using a gradient of 0-100% Et0Ac/cyclohexane as eluent to give the desired product (0.77g, 35%). 1H NMR (400 MHz, CDCI3) 6 7.39 (dd, 1H), 7.21 (dt, 1H), 6.99 (dt, 1H), 6.78 (dd, 1H), 5.27 (br s, 1H), 4.20 (t, 1H), 2.19 -2.04 (m, 2H), 2.04-1.93 (m, 2H), 1.93-1.68 (m, 2H).
Step 3: Synthesis of 242-[(5-chloro-3-fluoro-2-pyridyl)oxy]phenyl]-6,6, 6-trifluoro-hexanenitrile (A43) To a mixture of 6,6,6-trifluoro-2-(2-hydroxyphenyl)hexanenitrile (0.10 g, 0.41 mmol) and potassium carbonate (0.11 g, 0.82 mmol) in DMF (1.0 mL) was added 5-chloro2,3-difluoro-pyridine (0.074 g, 0.49 mmol). The reaction was heated at 120°C for 1h under microwave irradiation. The reaction was diluted with water and extracted with Et0Ac (x2). The combined organic extracts were dried over MgSO4 and evaporated to dryness under reduced pressure. The crude product was purified first by flash chromatography on silica gel using a gradient of 0-35% Et0Ac/cyclohexane as eluent and secondly by mass-directed preparative reverse phase HPLC to give the desired product (15.4 mg, 10%).
1H NMR (400 MHz, CDCI3) 6 7.91 (d, 1H), 7.57 (ddd, 2H), 7.44 -7.35 (m, 1H), 7.34 -7.28 (m, 1H), 7.12 (dd, 1H), 4.12 (dd,1 H), 2.16-1.94 (m, 4H), 1.84-1.62 (m, 2H).
Example 4: Synthesis of 243-bromo-2-(5,5,5-trifluoropentyl)phenoxy]-5-chloro- 3-fluoro-pyridine (A48) Step 1: Synthesis of 1-(2-bromo-6-methoxy-phenyl)-5,5,5-trifluoro-pentan-1-ol Br A reaction flask was charged with magnesium turnings (0.226 g, 9.30 mmol), a catalytic amount of iodine and Et20 (5.8 mL). The mixture was heated to reflux and 4-bromo-1,1,1-trifluoro-butane (0.685 mL, 5.58 mmol) was added over 30 minutes.
The mixture was allowed to cool to room temperature and transferred dropwise to a second reaction flask charged with a solution of 2-bromo-6-methoxy-benzaldehyde (1.00 g, 4.65 mmol) in THF (9.30 mL) at -78°C. The reaction mixture was allowed to warm to room temperature, quenched with 1M HCI and partitioned between ether and brine. The organic phase was dried over MgSO4 and evaporated to dryness under reduced pressure. The crude product was purified by flash chromatography on silica gel using a gradient of 0-20% Et0Ac/cyclohexane as eluent to give the desired product (1.40g, 74%).
1H NMR (400 MHz, CDCI3) ö 7.19 (dd, 1H), 7.09 (t, 1H), 6.88 (d, 1H), 5.12 (ddd, 1H), 3.90 (s, 3H), 3.72 (d, 1H), 2.22 -2.04 (m, 2H), 2.01 -1.75 (m, 3H), 1.75 -1.56 (m, 1H).
Step 2: Synthesis of 1-bromo-3-methoxy-2-(5,5,5-trifluoropentyl)benzene Br To a stirred solution of 1-(2-bromo-6-methoxy-phenyl)-5,5,5-trifluoro-pentan-1-ol (1.40 g, 4.28 mmol) in DCM (14.3 mL) was added triethylsilane (2.73 mL, 17.1 mmol).
After stirring for 15 minutes, trifluoroacetic acid (1.97 mL, 25.7 mmol) was added and the reaction was heated to 40°C overnight. The reaction was allowed to cool to ST and evaporated to dryness under reduced pressure. The crude product was purified by flash chromatography on silica gel using a gradient of 0-10% Et0Ac/cyclohexane as eluent to give the desired product (1.30 g, 98%) 1H NMR (400 MHz, CDCI3) O 7.14 (dd, 1H), 7.05 -6.99 (m, 1H), 6.81 -6.76 (m, 1H), 3.83 -3.79 (m, 3H), 2.81 (t, 2H), 2.19 -2.05 (m, 2H), 1.68-1.53 (m, 4H).
Step 3: Synthesis of 3-bromo-2-(5,5,5-trifluoropentyl)phenol To a solution of 1-bromo-3-methoxy-2-(5,5,5-trifluoropentyl)benzene (0.35 g, 1.1 mmol) in DCM (11 mL) at 0°C under an N2 atmosphere was added dropwise boron tribromide (1M solution in DCM) (2.8 mL, 2.8 mmol). The reaction was allowed to warm to RT and stirred overnight. The reaction was diluted with DCM and quenched with saturated aqueous NaHCO3 solution. The phases were separated, and the organic phase evaporated to dryness under reduced pressure to give the desired product (0.29 g, 87%).
1H NMR (400 MHz, CDCI3) 6 7.14 (dd, 1H), 6.92 (t, 1H), 6.73 -6.66 (m, 1H), 4.79 (s, 1H), 2.82 (t, 2H), 2.20 -2.07 (m, 2H), 1.71 -1.59 (m, 4H).
Step 4: Synthesis of 243-bromo-2-(5,5,5-trifluoropentyl)phenoxy]-5-chloro-3-fluoro-pyridine (A48) To a mixture of 3-bromo-2-(5,5,5-trifluoropentyl)phenol (0.33 g, 1.1 mmol) and potassium carbonate (0.31 g, 2.2 mmol) in DMF (3.3 mL) was added 5-chloro-2,3-difluoro-pyridine (0.20 g, 1.3 mmol). The reaction mixture was heated at 80°C for 1 h, 13 allowed to cool to RT, quenched with water and extracted with Et0Ac (x2). The combined organic extracts were dried over MgSat and evaporated to dryness under reduced pressure. The crude product was purified by flash chromatography on silica gel using a gradient of 0-15% Et0Ac/cyclohexane as eluent to give the desired product (0.30g, 63%).
1H NMR (400 MHz, CDCI3) 6 7.88 (d, 1H), 7.55 (dd, 1H), 7.46 (dd, 1H), 7.14 -7.08 (m, 1H), 7.01 (dd, 1H), 2.84 -2.71 (m, 2H), 2.14 -2.00 (m, 2H), 1.68-1.54 (m, 4H).
Example 5: Synthesis of 3-[(5-chloro-3-fluoro-2-pyridypoxy]-2-(5,5,5-trifluoropentyl)benzonitrile (A49) Step 1: Synthesis of 3-methoxy-2-(535,5-trifluoropentyl)benzonitrile A solution of 1-bromo-3-methoxy-2-(5,5,5-trifluoropentyl)benzene (0.20 g, 0.64 mmol), Pd(OAc)2 (0.015 g, 0.064 mmol), X-Phos (0.063 g, 0.13 mmol), KOAc (0.064 g, 0.64 mmol) and potassium ferrocyanide trihydrate (0.14 g, 0.32 mmol) in water (1.0 mL) and 1,4-dioxane (1.0 mL) was degassed and heated at reflux for 4 hours. The reaction mixture was diluted with brine and extracted with Et0Ac. The organic extract was dried over MgSO4 and evaporated to dryness. The crude product was purified by flash chromatography on silica gel using a gradient of 0-20% Et0Ac/cyclohexane as eluent to give the desired product (0.16g, 97%).
1H NMR (400 MHz, CDCI3) 6 7.30 -7.23 (m, 2H), 7.23 -7.18 (m, 1H), 7.06 (dd, 1H), 3.86 (s, 3H), 2.91 -2.84 (m, 2H), 2.19 -2.07 (m, 2H), 1.73-1.58 (m, 4H).
Step 2: Synthesis of 3-hydroxy-2-(5,5,5-trifluoropentyl)benzonitrile To a solution of 3-methoxy-2-(5,5,5-trifluoropentyl)benzonitrile (0.16 g, 0.62 mmol) in DCM (6.2 mL) at 0°C under N2 atmosphere was added dropwise boron tribromide (1M solution in DCM) (1.6 mL, 1.6 mmol). The reaction was allowed to warm to RT and stirred overnight. The reaction was diluted with further DCM and quenched by addition of saturated aqueous NaHCO3 solution. The phases were separated and the organic phase was evaporated to dryness under reduced pressure. The crude product was purified by flash chromatography on silica gel using a gradient of 0-35% Et0Ac/cyclohexane as eluent to give the desired product (0.099 g, 65%) 1H NMR (400 MHz, CDCI3) 6 7.25 -7.12 (m, 2H), 6.99 (dd, 1H), 5.47 (s, 1H), 2.92 -2.85 (m, 2H), 2.20 -2.06 (m, 2H), 1.77-1.62 (m, 4H).
Step 3: Synthesis of 3-[(5-chloro-3-fluoro-2-pyridyl)oxy]-2-(5,5,5-trifluoropentyl)benzonitrile (A49) To a mixture of 3-hydroxy-2-(5,5,5-trifluoropentyl)benzonitrile (99 mg, 0.41 mmol) and potassium carbonate (0.113 g, 0.81 mmol) in dimethylformamide (1 mL) was added 5-chloro-2,3-difluoro-pyridine (0.073 g, 0.49 mmol) and the reaction mixture heated at 80°C for 4h. The reaction was diluted with H20 and extracted with Et0Ac (x2). The combined organic extracts were dried over MgSO4 and evaporated to dryness under reduced pressure. The crude product was purified by flash chromatography on silica gel using a gradient of 0-15% Et0Ac/cyclohexane as eluent to give the desired product (0.072g, 47%).
1H NMR (400 MHz, CDCI3) b 7.87 (d, 1H), 7.63-7.48 (m, 2H), 7.43 -7.29 (m, 2H), 2.89 -2.82 (m, 2H), 2.17 -2.02 (m, 2H), 1.77-1.66 (m, 2H), 1.66-1.57 (m, 2H) Example 6: Synthesis of 1-[2-[(5-chloro-3-fluoro-2-pyridypoxy]-6-fluoro-phenyl]-4,4, 4-trifluoro-butan-1-one (A50) Step 1: Synthesis of 2-[(5-chloro-34luoro-2-pyridyl)oxy]-6-fluoro-benzaldehyde
OH
To a mixture of 2-fluoro-6-hydroxy-benzaldehyde (0.25 g, 1.8 mmol) and potassium carbonate (0.49 g, 3.6 mmol) in DMF (2.5 mL) was added 5-chloro-2,3-difluoropyridine (0.32 g, 2.1 mmol). The reaction mixture was heated at 120°C for lh under microwave irradiation. The reaction was diluted with water and extracted with Et0Ac (x2). The combined organic extracts were dried over MgSO4 and evaporated to dryness under reduced pressure. The crude product was purified by flash chromatography on silica gel using a gradient of 0-30% Et0Ac/cyclohexane as eluent to give the desired product (0.20 g, 42%).
1H NMR (400 MHz, CDCI3) 6 10.29 (s, 1H), 7.79 (d, 1H), 7.63 (d, 1H), 7.56 (dd, 1H), 7.12 (ddd, 1H), 7.04 (d, 1H).
Step 2: Synthesis of 142-[(5-chloro-3-fluoro-2-pyridyfloxy]-6-fluoro-pheny1]-4,4, 4-trifluoro-butan-1-ol A reaction flask was charged with magnesium turnings (0.036 g, 1.5 mmol), a catalytic amount of iodine and Et20 (1 mL). The mixture was heated to reflux and 1,1,1-trifluoro-3-iodo-propane (0.10 mL, 0.89 mmol) was added over 30 minutes. The mixture was allowed to cool to room temperature and transferred to a second reaction flask charged with 2-[(5-chloro-3-fluoro-2-pyridyl)oxy]-6-fluoro-benzaldehyde (0.20 g, 0.74 mmol) and THF (1.5 mL) at -78°C. The reaction mixture was allowed to warm to room temperature, quenched with 1M HCI and partitioned between ether and brine. The organic phase was dried over MgSat and evaporated to dryness under reduced pressure. The crude product was purified by flash chromatography on silica gel using a gradient of 0-20% Et0Ac/cyclohexane as eluent to give the desired product (0.18g, 66%).
1H NMR (400 MHz, CDCI3) 67.88 (d, 1H), 7.57 (dd, 1H), 7.30 (dt, 1H), 7.05 -6.95 (m, 1H), 6.88 (d, 1H), 5.05 -4.98 (m, 1H), 2.65 (dd, 1H), 2.40 -2.21 (m, 2H), 2.18 -2.00 (m, 2H).
Step 3: Synthesis of 142-[(5-chloro-3-fluoro-2-pyridypoxy]-6-fluoro-phenyn- 4,4,4-trifluoro-butan-1-one (A50)
CI
To a solution of 1-[2-[(5-chloro-3-fluoro-2-pyridyfioxy]-6-fluoro-phenyl]-4,4, 4-trifluorobutan-1-ol (0.16 g, 0.44 mmol) in DCM (2.2 mL) was added Dess-Martin periodinane (0.29 g, 0.65 mmol) and stirred at RT for 5h. The reaction was diluted with further DCM and washed with saturated aqueous NaHCO3 solution and brine. The organic phase was dried over MgSO4 and evaporated to dryness under reduced pressure.
The crude product was purified by flash chromatography on silica gel using a gradient of 0-20% Et0Ac/cyclohexane as eluent to give the desired product (0.135g, 85%).
1H NMR (400 MHz, CDCI3) ö 7.85 (d, 1H), 7.57-7.44 (m, 2H), 7.10 -7.00 (m, 2H), 3.17 -3.11 (m, 2H), 2.51 -2.39 (m, 2H).
Example 7: Synthesis of 3,3,3-trifluoropropyl 2-chloro-6-[(5-chloro-3-fluoro-2-pyridyfloxy]benzoate (A55).
Step 1: Synthesis of 3,3,3-trifluoropropyl 2-chloro-6-hydroxy-benzoate
CI OH
To a mixture of 2-chloro-6-hydroxy-benzoic acid 0.50 g, 2.9 mmol), 3,3,3-trifluoropropan-1-ol (0.51 mL, 5.8 mmol) and conc. sulfuric acid (0.30 mL) in toluene (5.0 mL) were added powdered 4A molecular sieves were added. The reaction was heated at reflux for 3hrs and allowed to cool to RT overnight. The reaction mixture was poured into water and extracted with Et0Ac (x3). The combined organic extracts were washed with brine, dried over MgSO4 and evaporated to dryness to give the crude desired product (0.60g) as a white solid.
Step 2: Synthesis of 3,3,3-trifluoropropyl 2-chloro-6-[(5-chloro-3-fluoro-2-pyridyl)oxy]benzoate (A55).
To a mixture of 3,3,3-trifluoropropyl 2-chloro-6-hydroxy-benzoate (0.159, 0.56 mmol) and potassium carbonate (0.239, 1.7 mmol) in DMF (1.5 mL). The reaction mixture was heated at 80°C for 3h then allowed to cool to RT. The reaction was diluted with water and extracted with Et0Ac (x2). The combined organic extracts were dried over MgSO4 and evaporated to dryness under reduced pressure. The crude product was purified by flash chromatography on silica gel using a gradient of 0-30% Et0Ac/cyclohexane as eluent to give the desired product (0.065g, 29%).
1H NMR (400 MHz, CDC13) 5 7.89 (d, 1H), 7.53 (dd, 1H), 7.46 -7.38 (m, 1H), 7.36 - 7.30 (m, 1H), 7.17 (dd, 1H), 4.48 (t, 2H), 2.51 (tq, 2H).
Example 8: Synthesis of 3-[(5-chloro-3-fluoro-2-pyridypoxy]-2-(3,3,3-trifluoropropylsulfanyl) benzonitrile (A63). 1 5
Step 1: Synthesis of 2-iodo-3-methoxy-benzonitrile
CI
A solution of 3-methoxybenzonitrile (0.34 M in THF) containing 1.0 eq of ZnCl2 and (2,2,6,6-tetramethy1-1-piperidy0lithium (0.52 M in THF) were mixed in a 5mL reaction loop at ST using a flow rate of 2mL/minute. The output solution was added to a solution of 12 (25 g in 120 mL of THF). Once 120 mL of material had been processed, the reaction was quenched by addition of saturated aqueous NH4CI solution and diluted with water. Saturated aqueous sodium thiosulfate solution was added and extracted with Et0Ac (x3). The combined organic extracts were washed with saturated aqueous sodium thiosulfate solution, water and brine, dried over MgSO4 and evaporated to dryness under reduced pressure. The crude product was purified by flash chromatography on silica gel using a gradient of 0-20% of Et0Ac/cyclohexane as eluent to give the desired product (7.71 g, 66% based on processed material) as a beige solid.
1H NMR (400 MHz, CDCI3) 67.41 (t, 1H), 7.24 (dd, 1H), 7.00 (dd, 1H), 3.93 (s, 3H) Step 2: Synthesis of 3-methoxy-2-(3,3,3-trifluoropropyisulfanyflbenzonitrile To a degassed solution of 2-iodo-3-methoxy-benzonitrile (0.50 g, 1.9 mmol) and Hunig's base (0.66 mL, 3.9 mmol) in 1,4-dioxane (9.7 mL) were added Xantphos Pd G3 (0.19 g, 0.19 mmol) and 3,3,3-trifluoropropane-1-thiol (0.28 g, 2.1 mmol). The reaction was heated to 130°C under microwave irradiation for 2h 30 min. The reaction was evaporated to dryness under reduced pressure and the crude product purified by flash chromatography on silica gel using a gradient of 0-100% Et0Ac/cyclohexane as gradient to give the desired product (0.44g, 70%).
1h1 NMR (400 MHz, CDCI3) 67.47-7.40 (m, 1H), 7.31 (dd, 1H), 7.14 (dd, 1H), 3.96 (s, 3H), 3.15-3.05 (m, 2H), 2.46 -2.25 (m, 2H).
Step 3: Synthesis of 3-hydroxy-2-(3,3,3-trifluoropropylsulfanyl)benzonitrile To a solution of 3-methoxy-2-(3,3,3-trifluoropropylsulfanyl)benzonitrile (0.44 g, 1.7 mmol) in DCM (17 mL) at 0°C under an N2 atmosphere was added dropwise boron tribromide (1M solution in DCM) (4.2 mL, 4.2 mmol). The reaction was stirred at room temperature overnight. The reaction was then quenched by the addition of saturated aqueous NaHCO3. The phases were separated and the organic phase was evaporated to dryness under reduced pressure. The crude product was purified by flash chromatography on silica gel using a gradient of 0-60% Et0Ac/cyclohexane as eluent to give the desired product (0.34g, 65%).
NMR (400 MHz, CDCI3) ö 7.47-7.40(m, 2H), 7.35 (d, 1H), 7.28 (d, 1H), 6.95 (br s, 1H), 3.08-3.01 (m, 2H), 2.48-2.38 (m, 2H).
Step 4: Synthesis of 3-[(5-chloro-3-fluoro-2-pyridyl)oxy]-2-(3,3,3-trifluoropropylsulfanyl) benzonitrile (A63).
To a mixture of 3-hydroxy-2-(3,3,3-trifluoropropylsulfanyl)benzonitrile (0.16 g, 0.65 mmol) and K2CO3 (0.18 g, 1.3 mmol) in DMF (1.6 mL) was added 5-chloro-2,3-difluoro-pyridine (0.12 g, 0.78 mmol). The reaction mixture was heated at 80°C for 4h, allowed to cool to RT, diluted with water and extracted with Et0Ac (x2). The combined organic extracts were dried over MgSat and evaporated to dryness under reduced pressure. The crude product was purified by flash chromatography on silica gel using a gradient of 0-30% Et0Acicyclohexane as eluent to give the desired product (0.14g, 57%).
1H NMR (400 MHz, CDCI3) 5 7.82 (d, 1H), 7.66 (dd, 1H), 7.61 -7.52 (m, 2H), 7.47 - 7.41 (m, 1H), 3.13 -3.06 (m, 2H), 2.40 -2.28 (m, 2H).
Example 9: Synthesis of 3-[(5-chloro-3-fluoro-2-pyridyl)oxy]-2-(3,3,3-trifluoropropylsulfinyl) benzonitrile (A64) Step 1: Synthesis of 3-[(5-chloro-3-fluoro-2-pyridyl)oxy]-2-(3,3,3-trifluoropropylsulfinyl) benzonitrile (A64) To a solution of 3-[(5-chloro-3-fluoro-2-pyridyl)oxy]-2-(3,3,3-trifluoropropylsulfanyl) benzonitrile (0.048 g, 0.13 mmol) in DCM (1.3 mL) at 0°C was added mCPBA (0.028g, 0.13 mmol). The reaction was stirred at 0°C for 10 minutes.
The reaction was diluted with DCM and washed with saturated aqueous sodium metabisulfite and saturated aqueous sodium bicarbonate. The organic phase was evaporated to dryness under reduced pressure. The crude product was purified by flash chromatography on silica gel using a gradient of 0-40% Et0Ac/cyclohexane as eluent to give the desired product (0.043g, 85%).
1H NMR (400 MHz, CDCI3) 67.87 (d, 1H), 7.79 (dd, 1H), 7.69 (t, 1H), 7.61 (dd, 1H), 7.49 (dd, 1H), 3.56 -3.45 (m, 1H), 3.39-3.31 (m, 1H), 2.88 -2.68 (m, 1H), 2.61-2.45 (m, 1H).
Example 10: Synthesis of 3-[(5-chloro-3-fluoro-2-pyridypoxy]-2-(3,3, 3-trifluoropropylsulfonypbenzonitrile (A65) Step 1: Synthesis of of 3-[(5-chloro-3-fluoro-2-pyridyfloxy]-2-(3,3,3-trifluoropropylsulfonyl) benzonitrile (A65) )<F
CI
To a solution of 3-[(5-chloro-3-fluoro-2-pyridyl)oxy]-2-(3,3,3-trifluoropropylsulfanyl) benzonitrile (0.057 g, 0.15 mmol) in DCM (1.5 mL) was added mCPBA (0.17 g, 0.76 mmol) at 0°C. The reaction was stirred at 0°C for 1 hour, then diluted with DCM and washed with saturated aqueous sodium metabisulfite and saturated aqueous sodium bicarbonate. The organic phase was evaporated to dryness under reduced pressure. The crude product was purified by flash chromatography on silica gel using a gradient of 0-35% Et0Ac/cyclohexane as eluent to give the desired product (0.049g, 79%).
1H NMR (400 MHz, CDCI3) 6 7.88 -7.83 (m, 3H), 7.70 -7.64 (m, 1H), 7.61 (dd, 1H), 3.78 -3.69 (m, 2H), 2.78 -2.64 (m, 2H).
Table 1 -Examples of herbicidal compounds of the present invention.
Compound Structure Data 1H NMR (400MHz, CDCI3 unless stated)
F
F F>
9.00 (s, 1H), 8.54 (dd, 1H), --.......o 7.55 (dd, 1H), 7.42 (dd, 1H), Al N 7.31-7.22 (m, 1H), 7.13 (d, 0 N, i^I'L}D 1H), 4.35 (t, 2H), 2.58-2.44 I (m, 2H) II c)
F
F
F 7.79 (d, tH) 7.51 (dd, 1H) 7.44 (dd, 1H) 7.36 -7.42 A2 o (m, tH) 7.23 -7.28 (m, c) N 11".. 1 H) 4.39 (t, 2H) 2.62-2.51 (m, 211) 0 I --.--.F
F
F
F
F
7.83 (s, 1H), 7.57 (dd, 1H), A3 0 7.51 (dd, 1H), 7.43 (dd, 1H), N, 7.29-7.22 (m, 1H), 4.39 (t, 2H), 2.62-2.49 (m, 2H) II.0 N.
_ I
F-11.r..1%^1/11.---%.1%Cl
F
F F>
8.40 (s, 1H), 7.99 (dd, 1H), 7.54 (dd, 1H), 7.40 (dd, 1H), A4 7.30-7.24 (m, 1H), 7.12 (d, 1H), 4.32 2H), 2.58-2.45 (t, Si N, I (m, 2H) ---- -%-.-1 ^.....,s,..7.....,..",...,.. %.1'^ N Compound Structure Data 1H NMR (400MHz, CDCI3 unless stated)
F
F
F
8.39 (s, 1H), 7.98 (dd, 1H), 0 7.52 (dd, 1H), 7.41 (dd, 1H), A5 N 7.26 (t, 1H), 7.12 (d, 1H), 0 N, 4.34 (t, 2H), 2.58-2.43 (m,
----
---
Si 2H)
F
F
F
F
F 8.05 (s, 1H), 7.71 (dd, 1H), 7.49 (d, 1H), 7.39 (d, 1H), A6 o 7.22 (t, 1H), 6.98 (d, 1H), N 0N 4.34 (t, 2H), 2.60-2.46 (m, \../...% 2H) -"--, 0....... I --S-"... ......a.-----CI
F
F F .."
7.79 (s, 1H), 7.49 (d, 1H), 7.45-7.35 (m, 2H), 7.21 (t, A7 -.......o 1H), 4.22 (t, 2H), 2.31-2.18 N (M, 21-), 1.97-1.89 (m, 2H) 0 N 1111 I
F F
F
F F
7.86 (s, 1H), 7.56 (dd, 1H), 7.49 (d, 1H), 7.41 (d, 1H), A8 7.21 (t, 1H), 4.22 (t, 2H), 2.30-2.15 (m, 2H), 1.97-1.86 0 o.........i."..1 (al, 2H) N, _ 1 Data 1H NMR (400MHz, CDCI3 unless stated) Structure Compound o 9.00 (s, 1H), 8.54 (dd, 1H), 7.54 (d, 1H), 7.41 (d, 1H), 7.25 (t, 1H), 7.12 (d, 1H), 4.20 (t, 2H), 2.27-2.11 (m, 2H), 1.94-1.82 (m, 2H) A9 8.40 (s, 1H), 7.98 (dd, 1H), 7.51 (dd, 1H), 7.39 (dd, 1H), 7.22 (t, 1H), 7.10 (d, 1H), 4.20 (t, 2H), 2.23-2.09 (m, 2H), 1.92-1.81 (m, 2H) A10 8.42 (s, 1H), 7.99 (dd, 1H), 7.52 (d, 1H), 7.39 (d, 1H), 7.22 (t, 1H), 7.10(d) 1H), 4.19 (t, 2H), 2.24-2.10 (m, 2H), 1.93-1.82 (m, 2H) All Compound Structure Data 1H NMR (400MHz, CDCI3 unless stated) Al2 F F F Sp0 0 N, 8.06 (s, 1H), 7.70 (dd, 1H), 7.48 (d, 1H), 7.37 (d, 1H), 7.20 (t, 1H), 6.94 (d, 1H), 4.19 (t, 2H), 2.28-2.12 (m, N......., I 2H), 1.94-1.83 (m, 2H) s..---N '......--%-ci A13 0.../ 0 F '.....--k-""----.%%Cl I 7.80 (s, 1H), 7.48 (d, 1H), MO:--# I 7.21-7.15 (m, 2H), 6.99-6.95 (m, 2H), 3.85 (t, 2H), 1.61- 1.52 (m, 2H), 0.74 (t, 3H) A14 0 F F F F 1 Cl CI 8.04 (d, 1H), 7.78 (s, 1H), 7.62 (t, 1H), 7.51 (d, 1H), 7.37 (t, 1H), 7.29-7.20 (m, 1H), 4.36 (t, 211), 2.50-2.37 III 0 r--- ...."e I
N
A15 0 01 F F -..<.,..........r.............\,... 8.37 (s, 1H), 8.06 (d, 1H), 7.93 (d, 1H), 7.65 (t, 1H), 7.39 (t, 1H), 7.20 (d, 1H), 7.09 (d, 1H), 4.34 (t, 2H), r---- F 2.50-2.36 (nil, 2H) Compound Structure Data 1H NMR (400MHz, CDCI3 unless stated)
F F
F
re 8.07-7.98 (m, 2H), 7.68 (dd, no, 7.61 (t, 1H), 7.33 (t, 1H), A16 0 0 7.20 (d, 1H), 6.94 (d, 1H), 4.35 (t, 2H), 2.50-2.32 (m, 2H) SI Ns......,..c. Cl
F
F F
r---- 8.33 (s, 1H), 8.05 (d, 1H), 0 0 7.91 (d, 1H), 7.64 (t, 1H), A17 7.38 (t, 1H), 7.21 (d, 1H), 7.09 (d, 1H), 4.34 (t, 2H), 1. Yi 2.50-2.30 (m, 2H) N:ck........ Th<F
F
F
F
F F
r8.94 (s, 1H), 8.51 (dd, 1H), 0 0 8.09 (dd, 1H), 7.68 (t, 1H), A18 7.41 (t, 1H), 7.22 (d, 1H), o 7.11 (d, 1H), 4.37 (t, 2H), 2.52-2.37 (m, 2H) Compound Structure Data 1H NMR (400MHz, CDCI3 unless stated) A19 0 Oil F.0'. ck...........-....... F r8.03 (d, 1H), 7.71 (s, 1H), 7.62 (t, 1H), 7.40-7.31 (m, 2H), 7.22 (d, 1H), 4.36 (t, 2H), 2.51-2.38 (m, 2H) F F 1 F 0 I A20 Pei F F F.........:"."."..."..".. I 7.86 (d, 1H), 7.52 (dd, 1H), 7.33 -7.14 (m, 3H), 7.05 (d, 1H), 2.58 (t, 2H), 2.14-1.95 (m, 2H), 1.67 (quin, 2H), 1.61 F 01 -1.50 (m, 2H) A21 1. F N^,",,...z....".-.,.........\., ...."^ N 8.46 (d, 1H), 7.93 (dd, 1H), 7.32 -7.22 (m, 3H), 7.06 -6.99 (m, 2H), 2.53 (t, 2H), 2.09-1.97 (m, 2H), 1.70 -1.59 (m, 2H), 1.59 -1.49 (m, F F 2H) oY Compound Structure Data 1H NMR (400MHz, CDCI3 unless stated) F F 8.11 (d, 1H), 7.63 (dd, 1H),
F
7.29 -7.16 (m, 3H), 7.02 (dd, 1H), 6.85 (d, 1H), 2.60 -2.53 A22 (m, 2H), 2.09 -1.97 (m, 2H), 1.69-1.60 (m, 2H), 1.60 - 0 1.50 (in, 2H) 01 Nck...... ..., CI
F
F F
8.45 -8.41 (m, 1H), 7.90 (dd, 1H), 7.31 -7.20 (m, 3H), 7.08 A23 -7.02 (m, 1H), 6.99 (d, 1H), 2.56 (t, 2H), 2.09 -1.96 (m, 0 2E1), 1.69-1.59 (m, 2H), 1.59 01 -1.50 (m, 2H) N\<
F
F
F
F
F F
9.04 (d, 1H), 8.49 (dd, 1H), 7.33 -7.24 (m, 3H), 7.08 -A24 7.01 (m, 2H), 2.54 (t, 2H), 2.11-1.97 (m, 21-1), 1.69 - 0 1.61 (m, 2H), 1.61 -1.50 (m, 401 N-....-. I
I
Compound Structure Data 1H NMR (400MHz, CDCI3 unless stated) A25 II0 I F F I 7.81 (d, 1H), 7.37 -7.30 (m, 1H), 7.30 -7.22 (m, 2H), 7.22 -7.16 (m, 1H), 7.03 (dd, 1H), 2.60 (t, 2H), 2.11-1.99 (m, 2H), 1.72-1.61 (m, 2H), 1.61 F -1.52 (m, 2H)
F
N........-A26 14111 0 F N...."..k.......r.,..... F 7.81 (d, 1H), 7.34 (ddd, 1H), F F F 7.27 (t, 2H), 7.24 -7.17 (m, /... 1 1H), 7.04 (d, 1H), 2.67 (t, 2H), i 2.15 -1.99 (m, 2H), 1.93- 1.82 (m, 2H) A27 00 0 F ---4%-t.--.N+..° 9.02 (d, 1H), 8.50 (dd, 1H), 7.35 -7.25 (m, 3H), 7.10 -7.04 (m, 2H), 2.61 (t, 2H), 2.12 -1.99 (m, 2H), 1.90-F 1 1.81 (m, 2H)
F I
/.. I Compound Structure Data 1H NMR (400MHz, CDCI3 unless stated) A28 0 F F 8.42 (dd, 1H), 7.91 (dd, 1H), 7.33 -7.22 (m, 4H), 7.08 -7.00 (m, 2H), 2.62 (t, 2H), 2.11-1.99 (m, 2H), 1.90-F F 1.81 (m, 2H)
F F on N
A29 101 F CI 8.10 (d, 1H), 7.65 (dd, 1H), F 7.32 -7.24 (m, 3H), 7.24 -F 7.18 (m, 1H), 7.05 -7.01 (m, o 1H), 6.87 (d, 1H), 2.63 (t, 2H), N.--"Z----r%'---1 2.12-1.98 (m, 2H), 1.90- 1.81 (m, 2H) A30 01 F F.%**** N 0 F Nctzt.....",..._,..,,,,,.
A31 10 F 7.88 -7.84 (m, 1H), 7.53 (dd, 1H), 7.31 -7.17 (m, 4H), 7.09 -7.04 (m, 1H), 2.72 -2.62 (m, 2H), 2.14 -2.00 (m, 2H), 1.93 F -1) F -1.83 (m, 211 o Yi N -..._
F
Compound Structure Data 1H NMR (400MHz, CDCI3 unless stated)
F
F
F
7.87 (dd, 1H), 7.82 (d, 1H), 0 7.60 -7.54 (m, 1H), 7.39 A32 F (ddd, 1H), 7.33 (dt, 1H), 7.15 0 (dd, 1H), 3.24 -3.19 (m, 2H), 2.56 -2.43 (m, 2H) I.--%.'"----F
F
F
F
0 8.39 (dd, 1H), 7.97 (dd, 1H), 7.87 (dd, 1H), 7.64 -7.57 (m, A33 0 1H), 7.38 (dt, 1H), 7.18 (dd, 1H), 7.12 (d, 1H), 3.18 -3.12 01 (m, 2H), 2.52 -2.40 (m, 2H) N-,.3/4.,,,......... ThF
F
F
F
F
F 8.09 (d, 1H), 7.85 (dd, 1H), 7.71 (dd, 1H), 7.59 -7.53 (m, 0 1H), 7.32 (dt, 1H), 7.12 (dd, A34 1H), 6.99 (d, 1H), 7.03 -6.94 0 (m, 1H), 3.20 -3.14 (m, 2H), 01 r\C--7...--%%%-.-- CI 2.53 -2.41 (m, 2H)
F
F
F
7.90 -7.84 (m, 2H), 7.62 -A35 F 7.54 (m, 2H), 7.36 (dt, 1H), 7.19 (dd, 1H), 3.23 -3.16 (m, 0 2H), 2.56 -2.42 (m, 2H)
II
CI
Compound Structure Data 1H NMR (400MHz, CDCI3 unless stated) A36 0 1----- F 01 8.09 -8.03 (m, 1H), 7.78 (d, 11110 0 1H), 7.64 -7.58 (m, 1H), 7.51 0 (dd, 1H), 7.40 -7.33 (m, 1H), :---.. 7.23 (dd, 1H), 4.18 (q, 2H), 1.16 (t, 3H) A37 HO F F 01 F
F
N
A38 HO 5 F *-*%-#..------C1 I I 8.06 (d, 1H), 7.69 (dd, 1H), F 7.57 (dd, 1H), 7.37 -7.27 (m, F 2H), 7.01 (dd, 1H), 6.97 (d, 0;-.. 1H), 4.94 (td, 1H), 2.46 (d, 1H), 2.38 -1.91 (m, 4H) A39 HO 5 0 F cs......z.z.........-.........6F F 8.38 (dd, 1H), 7.95 (dd, 1H), F F 7.60 (dd, 1H), 7.41 -7.31 (m, F 211), 7.10 (d, 111), 7.05 (dd, 1H), 4.94 -4.89 (m, 1H), 2.39 -1.92 (m, .51-1) Compound Structure Data 1H NMR (400MHz, CDCI3 unless stated) A40 HO 411 F N 8.39 (d, 1H), 7.96 (dd, 1H), 7.60 (dd, 1H), 7.37 (dquin, F...%, N 2H), 7.14 -7.07 (m, 1H), 7.04 F (dd, 1H), 4.92 -4.85 (m, 1H), 2.29 -2.09 (in, 3H), 2.09- 0 1.92 (in, 2H) A41 F el 0 0....,..z".........."..-...... F I 7.85 (s, 1H), 7.53 (d, 1H), CI 7.42 (m, 1H), 7.07 (t, 1H), 7.00 (d, 1H), 2.51 (s, 3H) A42 HO illin F F I F 7.80 (d, 1H), 7.58 (dd, 1H), 0 F I 7.40 -7.27 (m, 3H), 7.03 (dd, F 1H), 5.04 -4.97 (iii, 1H), 2.40 I\1---- -1.94 (m, 5H) A43 ell F F F 1 7.91 (d, 1H), 7.57 (ddd, 2H), N-. F I 7.44 -7.35 (in, 1H), 7.34- 0 CI 7.28 (in, 1H), 7.12 (dd, 1H), /. 4.12 (dd, 1H), 2.16 -1.94 (in, N-..."......:".. 4H), 1.84 -1.62 (m, 2H) Compound Structure Data 1H NMR (400MHz, CDCI3 unless stated)
F F F
7.89 (d, 1H), 7.57 -7.52 (m, F 2H), 7.42 -7.35 (m, 1H), 7.35 A44 F -7.28 (m, 1H), 7.09 (td, 1H), 5.90 -5.62 (m, 1H), 2.33- 0 2.10 (m, 4H) ID N *"k.,,, ,...,-,.... I
CI
F
F
F 7.88 (d, 1H), 7.55 (dd, 1H) A45 F 7.30-7.17 (m, 2H), 6.99 (d, 1H), 2.82 (t, 2H), 2.17-2.05 CI 0 (m, 2H), 1.87-1.80 (m, 2H).
OP 1 I
I
F
F F
7.88 (d, 1H), 7.54 (dd, 1H), 7.30 -7.15 (m, 1H), 7.00 -A46 6.92 (m, 1H), 6.86 (d, 1H), F 2.68 -2.59 (m, 2H), 2.14 - 1.97 (m, 2H), 1.70 -1.51 (m, F 0 4H) SI N-----Z.-"...-- CI
F
F F
7.87 (d, 1H), 7.54 (dd, 1H), 7.31 -7.23 (m, 1H), 7.18 (t, A47 1H), 7.03 -6.95 (m, 1H), F 2.78-2.70 (m, 2H), 2.16-1.99 CI 0 (m, 2H), 1.69 -1.54 (m, 4H) Oa.."-- 1
I
Ck="--.---..-t1 Compound Structure Data 1H NMR (400MHz, CDCI3 unless stated)
F F
F
7.88 (d, 1H), 7.55 (dd, 1H), 7.46 (dd, 1H), 7.14 -7.08 (m, A48 1H), 7.01 (dd, 1H), 2.84 -2.71 F (m, 2H), 2.14 -2.00 (m, 2H), Br 0 1.68 -1.54 (m, 4H)
----
SI 1
I
%...-...-C1
F
F F
7.87 (d, 1H), 7.63 -7.48 (m, 2H), 7.43 -7.29 (m, 2H), 2.89 A49 -2.82 (m, 2H), 2.17 -2.02 (m, F 2H), 1.77-1.66 (m, 2H), 1.66
N
o -1.57 (m, 2H) 1401 Yi
N
F
F
F
0 7.85 (d, 1H), 7.57 -7.44 (m, A50 F 2H), 7.10 -7.00 (m, 2H), 3.17 -3.11 (m, 2H), 2.51 -2.39 (nn, F 0 2H)
I
N........... CI
F
F
F
7.90 (d, 1H), 7.54 (dd, 1H), A51 0 F 7.48 (dd, 1H), 7.32 (t, 1H), 7.17 (dd, 1H), 3.14 -3.08 (m, Br 0 2H), 2.60 -2.47 (m, 2H) Pe 1 I I Compound Structure Data 1H NMR (400MHz, CDCI3 unless stated) A52 CI 0 40 F 7.90 (d, 1H), 7.54 (dd, 1H), 7.42 -7.35 (m, 1H), 7.34 -7.28 (m, 1H), 7.13 (dd, 1H), 3.15 -3.07 (m, 2H), 2.59-F 2.46 (m, 2H)
F
F
I
A53 N 0 F 7.90 (d, 1H), 7.68 -7.58 (m, F 3H), 7.47 (dd, 1H), 3.23 -3.17 F (m, 2H), 2.63 -2.50 (m, 2H)
F
N-..'- I
I
A54 F o Or F F CI 7.85 (d, 1H), 7.57 -7.44 (m, F re F 2H), 7.10 -7.01 (m, 2H), 4.41 0 0...... (t, 2H), 2.54 -2.41 (m, 2H) NI%."----;"---.---'.
A55 o ISN F 7.89 (d, 1H), 7.53 (dd, 1H), CI F F 7.46 -7.38 (m, 1H), 7.36 -I-- F 7.30 (m, 1H), 7.17 (dd, 1H), o 4.48 (t, 2H), 2.51 (tq, 2H) Compound Structure Data 1H NMR (400MHz, CDCI3 unless stated) A56 0 in F F CI 7.89 (d, 1H), 7.53 (dd, 1H), 7.49 (dd, 1H), 7.34 (t, 1H), 7.21 (dd, 1H), 4.48 (t, 21-1), 2.58 -2.46 (m, 2H) Br 1----- F 0 F -.." N......--A57 F ---...." F 0 F.S..%....--..."Cl 7.82 (d, 1H), 7.50 (dd, 1H), 7.27 -7.18 (m, 2H), 7.06 -6.99 (m, 1H), 6.99 -6.93 (m, 1H), 3.95 (t, 2H), 1.94-1.77 F -...... ell 0 - I (m, 4H) N-7 A58 0 la F F 7.89 (d, 1H), 7.50 (dd, 1H), F 7.46 -7.43 (m, 1H), 7.30-N 7.26 (m, 2H), 7.19 (d, on 1H), 2.58 (q, 2H), 1.35 (s, 6H) A59 N -.-_ F F I 8.00 (d, 1H), 7.69 (dd, 1H), 7.56 (dd, 1H), 7.41 -7.35 (m, 1H), 7.35 -7.27 (m, 1H), 7.12 (dd, 1H), 4.12 (dd, 1H), 2.16-2.04 (m, 2H), 2.04 -1.93 (m, " F F 2H), 1.84 -1.64 (m, 2H) 0 I; Compound Structure Data 1H NMR (400MHz, CDCI3 unless stated) A60 N -, le F N I N.-..."-----F I 8.19 (d, 1H), 7.80 (dd, 1H), 7.55 (dd, 1H), 7.46 -7.40 (m, 1H), 7.40 -7.32 (m, 1H), 7.22 (dd, 1H), 4.02 (dd, 1H), 2.19 -1.97 (m, 4H), 1.87 -1.66 (m, -.....,:- F 2H) o A61 HO en F F F CI 7.87 (d, 1H), 7.57 (dd, 1H), 7.30 -7.23 (m, 2H), 7.00 (dd, CI 0 F 1H), 5.25 (dt, 1H), 2.87 (d, 1H), 2.41 -2.21 (m, 2H), 2.19 NI.-....- -1.99 (m, 2H) A62 HO 4 0 F - 7.88 (d, 1H), 7.57 (dd, 1H), 7.30 (dt, 1H), 7.05 -6.95 (m, 1H), 6.88 (d, 1H), 5.05 -4.98 (m, 1H), 2.65 (dd, 1H), 2.40 -2.21 (m, 2H), 2.18-2.00 (m, F F C1 2H)
F
A63 N..... 1401 F F CI 7.82 (d, 1H), 7.66 (dd, 1H), -...."-. S'''.. ....)<F 7.61 -7.52 (m, 2H), 7.47-F 7.41 (m, 1H), 3.13 -3.06 (m, 0 2H), 2.40 -2.28 ( m, 2H) i Compound Structure Data 1H NMR (400MHz, CDCI3 unless stated) A64 oS F F F 7.87 (d, 1H), 7.79 (dd, 1H), F 7.69 (t, 1H), 7.61 (dd, 1H), 7.49 (dd, 1H), 3.56 -3.45 (m, N._ 1H), 3.39-3.31 (m, 1H), 2.88- 2.68 (m, 1H), 2.61-2.45 (m, 1411 N 1H) *":"----.'CI
F
F
0 F 7.88 -7.83 (m, 3H), 7.70 -\\ 0=S F 7.64 (m, 1H), 7.61 (dd, 1H), A65 N 3.78 -3.69 (m, 2H), 2.78- 0 2.64 ( m, 2H)
N I
%:-*"'r%-C1
F
F
F 7.89 (d, 1H), 7.57 (dd, 1H), HO 7.48 (dd, 1H), 7.19 (t, 1H), A66 F 7.04 (dd, 1H), 5.25 (dt, 1H), Br 0 2.81 (d, 1H), 2.43-2.31 (m, SI1H), 2.30 -2.00 (m, 3H)
F
F
F
7.82 (d, 1H), 7.55 (dd, 1H), A67..,'" F 7.45 -7.34 (m, 2H), 7.14 (dd,
S
1H), 3.04 -2.93 (m, 2H), 2.34 CI 0 -2.21 (m, 2H) SI NI....S%-...--'--.%%-- 01 Compound Structure Data 1H NMR (400MHz, CDCI3 unless stated) A68 0'. 40 F CI 7.82 (d, 1H), 7.55 -7.46 (m, CI.....-- XF 2H), 7.38 (dd, 1H), 7.20 (dd, F 1H), 3.71 (ddd, 1H), 3.30 0 ---'. (ddd, 1H), 2.70 -2.56 (m, 2H)
N
A69 CI O_S 0 F I 7.81 (d, 1H), 7.65 -7.59 (m, *::.el F I 1H), 7.58 -7.49 (m, 2H), 7.28 F -7.24 (m, 1H), 3.69 -3.62 (m, 0 2H), 2.69 -2.56 (m, 2H) #...
A70 N 0=S SI F F I\L":--""r.%''.-I CI 8.19 (d, 1H), 8.03 (d, 1H), 7.94 -7.86 (m, 2H), 7.67 (dd, 1H), 3.66 -3.60 (m, 2H), 2.44 -2.32 (m, 2H), 2.25 -2.16 (nn, o F N I 2H) \\ I A71 --..". s ----- F F N 8.18 (d, 1H), 8.02 (d, 1H), 1401../.- F I 7.69 (dd, 1H), 7.55 (t, 1H), 7.46 (dd, 1H), 3.07 -3.00 (m, 2H), 2.34 -2.19 (m, 2H), 1.82 I -1.74 (m, 2H) o
N
Compound Structure Data 1H NMR (400MHz, CDCI3 unless stated)
F F
F
"'#. 7.76 (d, 1H), 7.62 (dd, 1H), A72...--' 7.50 (t, 1H), 7.43 -7.37 (m, S F 2H), 3.03 (t, 2H), 2.31 -2.18 N (m, 2H), 1.80 -1.73 (m, 2H) le 1
I
F
F F
0..---#.- 7.93 (d, 1H), 7.88 -7.80 (m, A73 \\ 2H), 7.72 (dd, 1H), 7.64 (dd" ".
N 0=8 F 1H), 3.58 (t, 2H), 2.43 -2.27 (m, 2H), 2.14 (quin, 2H) e 0 r
F
F F
77.- 7.91 (d, 1H), 7.70 (dd, 1H), 7.64 (dd, 1H), 7.51 (t, 1H), A74../ 7.43 (dd, 1H), 3.02 (t, 2H), S F 2.29 -2.18 (m, 2H), 1.83 - *-....... SIN 1.73 (m, 2H)
F
F F
-*"-# 7.82 (d, 1H), 7.64 (dd, 1H), 7.57 (dd, 1H), 7.51 (t, 1H), A75 S F 7.46 -7.39 (m, 1H), 3.02 (t, N 2H), 2.35 -2.18 (m, 2H), 1.84 0 -1.73 (m, 2H) leNI.....'.
CI
Compound Structure Data 1H NMR (400MHz, CDCI3 unless stated) A76 N--...... o F F CI 7.87 -7.81 (m, 3H), 7.67-7.57 (m, 2H), 3.58 (t, 2H), 2.42 -2.29 (m, 2H), 2.20 -2.10 (m, 2H) o,..11 F F -"-S.....1... NZ-A77 N 0 --II 01 -----... F N NC-Z---r-..%%-- F 8.12 (d, 1H), 7.93 -7.85 (m, 2H), 7.82 (dd, 1H), 7.68 (dd, 1H), 3.68 -3.60 (m, 2H), 2.44 -2.32 (m, 2H), 2.27 -2.14 (m, ---S F F I I 2H) 0 ----A78 N.., el..----- F I F 8.11 (d, 1H), 7.82 (dd, 1H), 7.68 (dd, 1H), 7.55 (t, 1H), 7.49 -7.45 (m, 1H), 3.06 (t, 2H), 2.30 -2.19 (m, 2H), 1.82 F F -1.75 (m, 2H)
--- N
S I
N-P--
A79 CI 0 140 F Nc----N 8.24 (d, 1H), 7.97 (d, 1H), F I 7.49 -7.41 (m, 1H), 7.40-F 7.34 (m, 1H), 7.20 (dd, 1H), I 3.16 (t, 2H), 2.56 (tq, 2H) Yi Compound Structure Data 1H NMR (400MHz, CDCI3 unless stated) A80 CI 0 1. o F NF 8.17 (d, 1H), 7.77 (dd, 1H), 7.50 -7.40 (in, 1H), 7.39-7.33 (m, 1H), 7.20 (dd, 1H), 3.16 (t, 2H), 2.65 -2.50 (m, F N 2H)
F I
I
A81 F F F 4111 kit'''. N F 8.16 (d, 1H), 7.83 (dd, 1H), 7.59 (dd, 1H), 7.42 -7.36 (in, 2H), 2.91 -2.81 (in, 2H), 2.17 -2.03 (m, 2H), 1.76-1.67 (m, N.6. I I 2H), 1.67 -1.60 (m, 2H) A82 F F SI I N*............"--....... N CI 8.23 (d, 1H), 8.03 (d, 1H), 7.60 (dd, 1H), 7.43 -7.34 (in, 2H), 2.87 -2.79 (in, 21-1), 2.16 -2.03 (m, 2H), 1.76-1.67 (in, N-..... I 2H), 1.67 -1.60 (m, 2H)
F
A83 CI 0 F F I 8.16 (d, 1H), 7.78-7.74 (m, 0 F 1H), 7.45 (t, 1H), 7.38 (d, 1H), I 7.23 (t, 1H), 4.52 (t, 2H), 0 2.61-2.50 (m, 2H) Compound Structure Data 1H NMR (400MHz, CDCI3 unless stated)
F F
F
8.17 (d, 1H), 7.77 (dd, 1H), 0 0 N 7.55 (d, 1H), 7.42 -7.35 (m, A84 I I 1H), 7.29 (d, 1H), 4.55 -4.49 (m, 2H), 2.64 -2.50 (m, 2H) Br NI--.',..--7%-%*F
F
F F
8.24 (d, 1H), 7.98 (d, 1H), 0 N 7.55 (dd, 1H), 7.38 (t, 1H), A85 0 I I 7.30 -7.25 (m, 1H), 4.52 (t, B 2H), 2.57 (tq, 2H) S or N..................;-..,,,ci
F
F F
/ 8.24 (d, 1H), 7.98 (d, 1H), N 7.48 -7.41 (m, 1H), 7.41-A86 o o I I 7.36 (m, 1H), 7.28 -7.21 (m, CI o 1H), 4.51 (t, 2H), 2.56 (tq, 2H) 1\1-%-:"...----'-'..
CI
F
F F
8.18 (d, 1H), 8.02 (d, 1H), N 7.80 -7.67 (m, 2H), 7.54 (dd, A87 N 0 I I 1H), 4.51 (t, 2H), 2.59 (tq, o 2H) " ci Compound Structure Data 1H NMR (400MHz, CDCI3 unless stated) A88 F F N"........"?...,..-."., 8.21 (d, 1H), 7.98 (d, 1H), I F ci 7.47 -7.40 (m, 1H), 7.10 (t, r<F 1H), 7.03 (d, 1H), 4.76 -4.73 N (M, 2H), 3.74 (q, 2H) o 0 oY A89 N s.--* ../ ........kF 7.82 (d, 1H), 7.63 (dd, 1H), 7.57 (dd, 1H), 7.49 (t, 1H), 7.43-7.40 (m, 1H), 2.96 (t, 2H), 2.11-2.02 (m, 2H), 1.70- 411 o F 1.56 (m, 4H)
F
F ----- 1 N"._
----- -CI
A90 N o II..,-o=s o ---.....-- 7.85-7.81 (m, 3H), 7.63-7.60 (m, 2H), 3.53-3.49 (m, 2H), 2.19-2.10 (m, 2H), 1.97-1.88 (M, 2H), 1.77-1.71 (m, 2H) 1101 F [.......5
F
N, _,..-.."-..". I
----- -CI
A91 N 140.....-- F N...".........".F I 8.11 (d, 1H), 7.81 (dd, 1H), o XF 7.67 (d, 1H), 7.54 (t, 1H), N 7.47-7.43 (m, 1H), 2.99 (t, I 2H), 2.10-2.03 (m, 2H), 1.66- 1.61 (m, 4H) Compound Structure Data 1H NMR (400MHz, CDCI3 unless stated) A92 N 0=8 F ii 8.11 (d, 1H), 7.91-7.80 (m, o II.,... L,F N c>........".....-",F 3H), 7.65 (dd, 1H), 3.60-3.55 100./ (m, 2H), 2.17-2.12 (m, 2H), N F 2.05-1.98 (m, 2H), 1.80-1.74 (m, 2H)
Biological Examples
Seeds of a variety of test species are sown in standard soil in pots Amaranthus retofiexus (AMARE), Abut/Ion theophrasti (ABUTH), Setaria faberi (SETFA), Echinochloa crus-gaN (ECHCG), lpomoea 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 the formulation of the technical active ingredient in acetone / water (50:50) solution containing 0.5% Tween 20 (polyoxyethelyene sorbitan monolaurate, CAS RN 900564-5). Compounds are applied at 500 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 Bi. Post-emergence Test Compound at AMARE ABUTH SETFA ECHCG!PONE (Rg/hae) A70 250 5 2 5 5 4 A71 250 5 4 5 5 4 A72 250 5 4 4 4 5 A73 250 5 2 3 4 2 A74 250 5 3 3 3 2 A75 250 5 4 5 5 4 A76 250 5 4 5 4 4 A77 250 5 5 5 5 4 A78 250 5 4 4 4 3 Compound Rate AMARE ABUTH SETFA ECHCG!PONE (g/ha) A79 250 5 5 5 5 3 A80 250 5 5 5 5 4 A81 250 5 5 5 5 4 A82 250 5 5 5 5 4 A83 250 5 5 5 5 4 A84 250 5 5 5 5 5 A85 250 5 5 5 5 4 A86 250 5 5 5 5 4 A87 250 5 4 4 4 4 A90 250 5 2 4 4 4 A91 250 5 4 4 4 4 A92 250 5 4 4 4 4 TABLE B2. Pre-emergence Test Compound Rate AMARE ABUTH SETFA ECHCG IPOHE (g/ha) A70 250 5 2 5 5 4 A71 250 4 4 5 3 2 A72 250 5 3 5 5 2 A73 250 5 3 4 4 3 A74 250 5 1 5 2 1 A75 250 5 1 5 4 2 A76 250 5 3 5 5 4 A77 250 5 5 5 5 5 A78 250 5 4 5 4 4 A79 250 5 3 5 5 2 A80 250 5 3 5 5 4 A81 250 5 3 5 5 3 A82 250 5 3 5 5 1 A83 250 5 3 5 5 3 A84 250 5 3 5 5 4 ABS 250 5 3 5 5 3 A86 250 5 3 5 5 3 A87 250 5 2 5 4 2 A90 250 5 2 5 5 4 A91 250 5 2 5 4 5 A92 250 5 4 5 4 5

Claims (15)

  1. Claims A compound of Formula (I): (I) or an agronomically acceptable salt thereof, wherein X is 0 or S(0)p; Y is selected from the group consisting of C(HR4), 0, C(0) and S(0)p; each R1 is independently selected from the group consisting of halogen, -CN, nitro, C1-aralkyl, C2-C4alkenyl, Cratalkynyl, C1-C4haloalkyl, C1atalkoxy-, CiC4haloalkoxy-and -S(0)pCi-C4alkyl; each R2 is independently selected from the group consisting of halogen, -CN, NO2, Cratalkyl, Crathaloalkyl, C3-C6cycloalkyl Cratalkenyl, Cratalkynyl, -S(0)pCi-C4alkyl, Cratalkoxy, -C(0)Ci-C4alkyl, -C(0)0C1-C4alkyl and CiC4haloalkoxY; R3 is selected from the group consisting of Ci-Cealkyl, Ci-Cshaloalkyl, Ci-Csalkoxy-and Ci-Cshaloalkoxy-with the proviso that when Y is 0 or S(0)p then IR2 is not Ci-Csalkoxy-or Ci-Cshaloalkoxy-; R4 is selected from the group consisting of hydrogen, halogen, -CN and -OH; m = 0, 1 or 2; n = 0, 1 or 2; and p = 0, 1 or 2.
  2. 2. A compound of Formula (I) according to claim 1, wherein Xis 0.
  3. 3. A compound of Formula (I) according to claim 1 or claim 2, wherein Y is selected from the group consisting of CH2, 0(0) and S(0)p.
  4. 4. A compound according to claim 3, wherein Y is 0(0).
  5. 5. A compound according to any one of the previous claims, wherein R3 is Ci-C6haloalkyl.
  6. A compound according to claim 5, wherein R3 is 4,4,4-trifluorobut-1-y1 or 3,3,3-trifluoroprop-1-yl.
  7. 7. A compound according to any one of the previous claims, wherein n is 1 and R1 is selected from the group consisting of chloro, bromo and -CN.
  8. 8. A compound according to claim 7, wherein R1 is 3-chloro.
  9. 9. A compound according to any one of the previous claims, wherein m is 1 or 2 and R2 is independently selected from the group consisting of chloro, fluoro, nitro, cyano and trifluoromethyl.
  10. 10. A compound according to claim 9, wherein m is 2 and each R2 is independently chloro or cyano.
  11. 11. A herbicidal composition comprising a compound according to any one of the previous claims and an agriculturally acceptable formulation adjuvant.
  12. 12. A herbicidal composition according to claim 11, further comprising at least one additional pesticide.
  13. 13. A herbicidal composition according to claim 12, wherein the additional pesticide is a herbicide or herbicide safener.
  14. 14. A method of controlling weeds at a locus comprising application to the locus of a weed controlling amount of a composition according to any one of claims 11 to 13.
  15. 15. Use of a compound of Formula (I) as defined in claim 1 as a herbicide.
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WO2023186691A1 (en) 2022-03-28 2023-10-05 Bayer Aktiengesellschaft Substituted 2-c-azines and salts thereof, and use thereof as herbicidal active substances
WO2023186690A1 (en) 2022-03-28 2023-10-05 Bayer Aktiengesellschaft Substituted 2-aminoazines and salts thereof, and use thereof as herbicidal active substances

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WO2023186691A1 (en) 2022-03-28 2023-10-05 Bayer Aktiengesellschaft Substituted 2-c-azines and salts thereof, and use thereof as herbicidal active substances
WO2023186690A1 (en) 2022-03-28 2023-10-05 Bayer Aktiengesellschaft Substituted 2-aminoazines and salts thereof, and use thereof as herbicidal active substances

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