WO2018156554A1 - 1-HYDROXY-1,3-DIHYDROBENZO[c][1,2]OXABOROLES AND THEIR USE AS HERBICIDES - Google Patents

1-HYDROXY-1,3-DIHYDROBENZO[c][1,2]OXABOROLES AND THEIR USE AS HERBICIDES Download PDF

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WO2018156554A1
WO2018156554A1 PCT/US2018/018913 US2018018913W WO2018156554A1 WO 2018156554 A1 WO2018156554 A1 WO 2018156554A1 US 2018018913 W US2018018913 W US 2018018913W WO 2018156554 A1 WO2018156554 A1 WO 2018156554A1
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alkyl
alkynyl
alkenyl
alkoxy
unsubstituted
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PCT/US2018/018913
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French (fr)
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Karla BRAVO-ALTAMIRANO
Olena CASTELLO
Joseph M. Gruber
Lowell MARKLEY
Dilpreet S. RIAR
Joshua Roth
Maurice C. Yap
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Dow Agrosciences Llc
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    • AHUMAN NECESSITIES
    • A01AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
    • A01NPRESERVATION 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
    • A01N55/00Biocides, pest repellants or attractants, or plant growth regulators, containing organic compounds containing elements other than carbon, hydrogen, halogen, oxygen, nitrogen and sulfur
    • A01N55/08Biocides, pest repellants or attractants, or plant growth regulators, containing organic compounds containing elements other than carbon, hydrogen, halogen, oxygen, nitrogen and sulfur containing boron
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07FACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
    • C07F5/00Compounds containing elements of Groups 3 or 13 of the Periodic Table
    • C07F5/02Boron compounds
    • C07F5/025Boronic and borinic acid compounds

Definitions

  • R represents H or an agriculturally acceptable salt or ester
  • Ri represents cyano; C1-C12 alkyl in which the alkyl is unsubstituted or substituted with OH, NH2, C1-C2 alkylamino, di-(Ci-C2 alkyl)amino, C1-C2 alkoxy, C1-C2 haloalkoxy, C1-C2 alkylthio or C1-C2 haloalkylthio; Ci-Cs haloalkyl; C3-C8 cycloalkyl; C2-C8 alkenyl; C2- C 8 haloalkenyl; C 2 -C 8 alkynyl; C 2 -C 8 haloalkynyl; -C(0)OR 6 ; -C(0)NR 7 R 8 ; C 8 -Ci 4 arylalkyl; C8-C14 arylalkenyl; Cs-Ci 4 arylalkynyl
  • R2, R3, R4 and R5 independently represent H; cyano; halo; nitro; N3 ⁇ 4; Ci-C 6 alkylamino; di-(Ci-C6 alkyl)amino; C1-C12 alkyl; Ci-C 8 alkoxy; Ci-C 8 haloalkyl; Ci-C 8 haloalkoxy; C3-C8 cycloalkyl; C2-C8 alkenyl; C2-C8 haloalkenyl; C2-C8 alkynyl; C2-C8 haloalkynyl; -C(0)OR6; -C(0)NR 7 Rs; aryl or aryloxy in which the aryl or aryloxy is unsubstituted or substituted with one or more R9; or where R3 and R 4 are taken together as -OCH2O-, -OCH2CH2O-, -OCH2CH2- or -OCF2O-, provided that R 2 , R 3
  • R 6 , R 7 and Rs independently represent H; C1-C12 alkyl; C3-C8 alkenyl; or C3-C8 alkynyl; in which the alkyl, alkenyl or alkynyl is unsubstituted or substituted with one or more OH, Ci-C 4 alkoxy, Ci-C 4 alkylthio, or phenyl groups, provided that R 6 , R 7 and Rs are sterically compatible; and
  • R9 represents halo, C1-C12 alkyl, Ci-Cs alkoxy, Ci-Cs haloalkyl, or Ci-Cs haloalkoxy; with the proviso that R3 is not -XYC(0)ORio, wherein
  • X represents O, NRn, S, SO, or SO2 where Rn is H, Ci-C6-alkyl, C3-C6-alkenyl, or
  • Y represents Ci-C6-alkyl, C3-C6-alkenyl, or C3-C 6 -alkynyl, in which the alkyl, alkenyl or alkynyl is unsubstituted or substituted with one or more halogen, Ci-C6-alkyl, Ci-C 6 - haloalkyl, Ci-C6-alkoxy, Ci-C6-haloalkoxy, C(0)0(Ci-C6-alkyl) or phenyl which is unsubstituted or substituted by halogen, Ci-C6-alkyl, Ci-C6-haloalkyl; and
  • Rio represents H, Ci-C6-alkyl, C3-C6-alkenyl, C3-C6- alkynyl, (Ci-C6-alkoxy)-Ci-C6- alkyl, (Ci-C6-alkoxy)-C3-C6-alkenyl, (C1-C6- alkoxy)-C3-C6-alkynyl, phenyl, phenyl-Ci-C6- alkyl, where the aliphatic and phenyl parts of the aforementioned radicals are unsubstituted, partly or completely halogenated.
  • herbicidal composition comprising a compound of Formula
  • R represents H or an agriculturally acceptable salt or ester
  • Ri represents cyano; C1-C12 alkyl in which the alkyl is unsubstituted or substituted with OH, NH2, C1-C2 alkylamino, di-(Ci-C2 alkyl)amino, C1-C2 alkoxy, C1-C2 haloalkoxy, C1-C2 alkylthio or C1-C2 haloalkylthio; Ci-Cs haloalkyl; C3-C8 cycloalkyl; C2-C8 alkenyl; C2- C 8 haloalkenyl; C 2 -C 8 alkynyl; C 2 -C 8 haloalkynyl; -C(0)OR 6 ; -C(0)NR 7 R 8 ; C 8 -Ci 4 arylalkyl; C 8 -Ci 4 arylalkenyl; C 8 -Ci 4 arylalkynyl; or aryl in which the aryl
  • R2, R3, R 4 and R5 independently represent H; cyano; halo; nitro; NH2; ⁇ -Ce alkylamino; di-(Ci-C6 alkyl)amino; C1-C12 alkyl; Ci-C 8 alkoxy; Ci-C 8 haloalkyl; Ci-C 8 haloalkoxy; C3-C 8 cycloalkyl; C2-C 8 alkenyl; C2-C 8 haloalkenyl; C2-C 8 alkynyl; C2-C 8 haloalkynyl; -C(0)OR6; -C(0)NR 7 R 8 ; aryl or aryloxy in which the aryl or aryloxy is unsubstituted or substituted with one or more R9; or where R3 and R 4 are taken together as -OCH2O-, -OCH2CH2O-, -OCH2CH2- or -OCF2O-, provided that R 2 ,
  • R 6 , R 7 and R 8 independently represent H; C1-C12 alkyl; C3-C 8 alkenyl; or C3-C 8 alkynyl; in which the alkyl, alkenyl or alkynyl is unsubstituted or substituted with one or more OH, Ci-C 4 alkoxy, Ci-C 4 alkylthio, or phenyl groups, provided that R 6 , R 7 and R 8 are sterically compatible;
  • R9 represents halo, C1-C12 alkyl, Ci-C 8 alkoxy, Ci-C 8 haloalkyl, or Ci-C 8 haloalkoxy; with the proviso that R3 is not -XYC(0)ORio, wherein
  • X represents O, NRn, S, SO, or SO2 where Rn is H, Ci-C6-alkyl, C3-C6-alkenyl, or C 3 -C6-alkynyl;
  • Y represents Ci-C6-alkyl, C3-C6-alkenyl, or C3-C 6 -alkynyl, in which the alkyl, alkenyl or alkynyl is unsubstituted or substituted with one or more halogen, Ci-C6-alkyl, Ci-C 6 - haloalkyl, Ci-C6-alkoxy, Ci-C6-haloalkoxy, C(0)0(Ci-C6-alkyl) or phenyl which is unsubstituted or substituted by halogen, Ci-C6-alkyl, Ci-C6-haloalkyl; and Rio represents H, Ci-C6-alkyl, C3-C6-alkenyl, C3-C6- alkynyl, (Ci-C6-alkoxy)-Ci-C6- alkyl, (Ci-C6-alkoxy)-C3-C6-alkenyl, (Ci
  • Also provided are methods of controlling undesirable vegetation comprising
  • herbicide As used herein, herbicide, herbicide composition, and herbicidal active ingredient mean a compound that controls undesirable vegetation when applied in an appropriate amount.
  • control of or controlling undesirable vegetation means killing or preventing the vegetation, or causing some other adversely modifying effect to the vegetation e.g., deviations from natural growth or development, regulation, desiccation, retardation, and the like.
  • a herbicidally effective or vegetation controlling amount is an amount of herbicidal active ingredient the application of which controls the relevant undesirable vegetation.
  • applying a herbicide, herbicidal composition, or herbicidal active ingredient means delivering it directly to the targeted vegetation or to the locus thereof or to the area where control of undesired vegetation is desired.
  • Methods of application include, but are not limited to, pre-emergently contacting soil or water, or post-emergently contacting the undesirable vegetation or area adjacent to the undesirable vegetation.
  • plants and vegetation include, but are not limited to, dormant seeds, germinant seeds, emerging seedlings, plants emerging from vegetative propagules, immature vegetation, and established vegetation.
  • agriculturally acceptable salts and esters for R refer to salts and esters of compounds of Formula (I) that exhibit herbicidal activity, or that are or can be converted in plants, water, or soil to the referenced herbicide.
  • exemplary agriculturally acceptable esters are those that are or can be hydrolyzed, oxidized, metabolized, or otherwise converted, e.g., in plants, water, or soil, to the corresponding 1-hydroxy-oxaborole or boronic acid which, depending upon the pH, may be in the dissociated or undissociated form.
  • Suitable agriculturally acceptable salts include those derived from alkali or alkaline earth metals and those derived from ammonia and amines.
  • Preferred cations include sodium, potassium, magnesium, and aminium cations of the formula:
  • Salts of the compounds of Formula (I) can be prepared by treatment of compounds of Formula (I) with a metal hydroxide, such as sodium hydroxide, with an amine, such as ammonia, trimethylamine, diethanolamine, 2-methyl- thiopropylamine, bisallylamine, 2-butoxyethylamine, morpholine, cyclododecylamine, or benzylamine, or with a tetraalkylammonium hydroxide, such as tetramethylammonium hydroxide or choline hydroxide.
  • Amine salts of compounds of Formula (I) are useful forms or derivatives of compounds of Formula (I) because they are water-soluble and lend them- selves to the preparation of desirable aqueous based herbicidal compositions.
  • Suitable agriculturally acceptable esters include straight chain or branched chain alkyl groups.
  • Typical C1-C12 alkyl groups include, but are not limited to, methyl, ethyl, propyl, 1- methylethyl, butyl, 1,1-dimethylethyl, 1-methylpropyl, pentyl, hexyl, heptyl, 1-methyl-hexyl, octyl, 2-ethylhexyl, nonyl, decyl and dodecyl. Methyl and ethyl are often preferred.
  • alkyl refers to saturated, straight-chained or branched hydrocarbon moieties. Unless otherwise specified, C1-C12 alkyl groups are intended (e.g., Ci-C 6 alkyl). Examples include, but are not limited to, methyl, ethyl, propyl, 1 -methyl-ethyl, butyl, 1- methyl-propyl, 2-methyl-propyl, 1,1 -dimethyl-ethyl, pentyl, 1 -methyl-butyl, 2-methyl-butyl, 3-methyl-butyl, 2,2-dimethyl-propyl, 1-ethyl-propyl, hexyl, 1,1-dimethyl-propyl, 1,2- dimethyl-propyl, 1-methyl-pentyl, 2-methyl-pentyl, 3-methyl-pentyl, 4-methyl-pentyl, 1,1- dimethyl-butyl, 1,2-dimethyl-butyl, 1,3-di
  • haloalkyl refers to straight-chained or branched alkyl groups, where in these groups the hydrogen atoms may partially or entirely be substituted with one or more halogen atom(s).
  • Ci-Cs groups are intended (e.g., Ci-C 6 haloalkyl). Examples include, but are not limited to, chloromethyl, bromomethyl, dichloromethyl, trichloromethyl, fluoromethyl, difluoromethyl, trifluoromethyl,
  • chlorofluoromethyl dichlorofluoromethyl, chlorodifluoromethyl, 1-chloroethyl, 1- bromoethyl, 1-fluoroethyl, 2-fluoroethyl, 2,2-difluoroethyl, 2,2,2-trifluoroethyl, 2-chloro-2- fluoroethyl, 2-chloro-2,2-difluoroethyl, 2,2-dichloro-2-fluoroethyl, 2,2,2-trichloroethyl, pentafluoroethyl, and l,l,l-trifluoroprop-2-yl.
  • cycloalkyl refers to saturated, cyclic hydrocarbon moieties. Unless otherwise specified, C3-C8 cycloalkyl groups are intended. Examples include cyclopropyl, 2,2-dimethyl-cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl and cyclooctyl.
  • alkenyl refers to unsaturated, straight-chained, or branched hydrocarbon moieties containing one or more double bond(s). Unless otherwise specified, C2-C8 alkenyl groups are intended (e.g., C3-C6 alkenyl). Alkenyl groups may contain more than one unsaturated bond.
  • Examples include, but are not limited to, ethenyl, 1-propenyl, 2- propenyl, 1-methylethenyl, 1-butenyl, 2-butenyl, 3-butenyl, 1 -methyl- 1-propenyl, 2-methyl- 1-propenyl, l-methyl-2-propenyl, 2-methyl-2-propenyl, 1-pentenyl, 2-pentenyl, 3-pentenyl, 4-pentenyl, 1-methyl-l-butenyl, 2-methyl- 1-butenyl, 3-methyl- 1-butenyl, l-methyl-2- butenyl, 2-methyl-2-butenyl, 3-methyl-2-butenyl, l-methyl-3-butenyl, 2-methyl-3 -butenyl, 3- methyl-3-butenyl, l,l-dimethyl-2-propenyl, 1 ,2-dimethyl- 1-propenyl, 1 ,2-dimethyl-2- propenyl, 1 -eth
  • haloalkenyl refers to straight-chained or branched alkenyl groups, where in these groups the hydrogen atoms may partially or entirely be substituted with one or more halogen atom(s). Unless otherwise specified, C2-C8 groups are intended.
  • Examples include, but are not limited to 1-chloroethenyl, 1-chloro- 1 -propenyl, 2-chloro-l -propenyl, 1- chloro-2-propenyl, 2-chloro-2-propenyl, 1-chloro- 1-butenyl, 2-chloro-l -butenyl, 3-chloro-l- butenyl, l-chloro-2-butenyl, 2-chloro-2-butenyl, 3-chloro-2-butenyl, l-chloro-3-butenyl, 2- chloro-3-butenyl, 3-chloro-3-butenyl, 1-fluoroethenyl, 1-fluoro-l -propenyl, 2-fluoro-l- propenyl, l-fluoro-2-propenyl, 2-fluoro-2-propenyl, 1-fluoro-l-butenyl, 2-fluoro-butenyl, 3-fluor
  • alkynyl represents straight-chained or branched hydrocarbon moieties containing one or more triple bond(s). Unless otherwise specified, C2-C8 alkynyl groups are intended (e.g., C3-C6 alkynyl). Alkynyl groups may contain more than one unsaturated bond.
  • Examples include, but are not limited to, C2-Cs-alkynyl, such as ethynyl, 1-propynyl, 2-propynyl (or propargyl), 1-butynyl, 2-butynyl, 3-butynyl, l-methyl-2-propynyl, 1-pentynyl, 2-pentynyl, 3-pentynyl, 4-pentynyl, 3-methyl- 1-butynyl, l-methyl-2-butynyl, l-methyl-3-butynyl, 2-methyl-3-butynyl, l,l-dimethyl-2-propynyl, l-ethyl-2-propynyl, 1-hexynyl, 2-hexynyl, 3-hexynyl, 4-hexynyl, 5-hexynyl, 3-methyl- 1-pentynyl, 4-methyl-l- pentynyl,
  • haloalkynyl refers to straight-chained or branched alkynyl groups, where in these groups the hydrogen atoms may partially or entirely be substituted with one or more halogen atom(s). Unless otherwise specified, C2-C8 groups are intended.
  • Examples include, but are not limited to, l-chloro-2-butynyl, l-chloro-3-butynyl, 2-chloro-3-butynyl, l,l-dichloro-2-propynyl, l-chloro-2-propynyl, 3 -chloro- 1-pentynyl, 4-chloro- 1-pentynyl, 1- chloro-2-pentynyl, 4-chloro-2-pentynyl, l-chloro-3-pentynyl, 2-chloro-3-pentynyl, 1-chloro- 4-pentynyl, 2-chloro-4-pentynyl, 3-chloro-4-pentynyl, l,l-dichloro-2-butynyl, 1,1-dichloro- 3-butynyl, l,2-dichloro-3-butynyl, 2,2-dichloro
  • alkoxy refers to a group of the formula R-0-, where R is alkyl as defined above (e.g., Ci-C 6 alkoxy). Unless otherwise specified, alkoxy groups wherein R is a Ci-C 8 alkyl group are intended.
  • Examples include, but are not limited to, methoxy, ethoxy, propoxy, 1-methyl-ethoxy, butoxy, 1 -methyl -propoxy, 2-methyl-propoxy, 1,1-dimethyl- ethoxy, pentoxy, 1-methyl-butyloxy, 2-methyl-butoxy, 3-methyl-butoxy, 2,2-dimethyl- propoxy, 1-ethyl-propoxy, hexoxy, 1,1-dimethyl-propoxy, 1,2-dimethyl-propoxy, 1-methyl- pentoxy, 2-methyl-pentoxy, 3-methyl-pentoxy, 4-methyl-pentoxy, 1,1-dimethyl-butoxy, 1,2- dimethyl-butoxy, 1,3-dimethyl-butoxy, 2,2-dimethyl-butoxy, 2,3-dimethyl-butoxy, 3,3- dimethyl-butoxy, 1-ethyl-butoxy, 2-ethylbutoxy, 1 , 1 ,2-trimethyl-propoxy, 1,2,2-trimethyl- propoxy, 1 -ethyl
  • haloalkoxy refers to a group of the formula R-0-, where R is haloalkyl as defined above. Unless otherwise specified, haloalkoxy groups wherein R is a Ci-C 8 alkyl group are intended (e.g., Ci-C 6 haloalkoxy). Examples include, but are not limited to, chloromethoxy, bromomethoxy, dichloromethoxy, trichloromethoxy,
  • dichlorofluoromethoxy chlorodifluoromethoxy, 1-chloroethoxy, 1-bromoethoxy, 1- fluoroethoxy, 2-fluoroethoxy, 2,2-difluoroethoxy, 2,2,2-trifluoroethoxy, 2-chloro-2- fluoroethoxy, 2-chloro-2,2-difluoroethoxy, 2,2-dichloro-2-fluoroethoxy, 2,2,2- trichloroethoxy, pentafluoroethoxy, and l,l,l-trifluoroprop-2-oxy.
  • alkylthio refers to a group of the formula R-S- where R is alkyl as defined above. Unless otherwise specified, alkylthio groups wherein R is a Ci-C 8 alkyl group are intended. Examples include, but are not limited to, methylthio, ethyl thio, propylthio, 1- methylethylthio, butylthio, 1-methyl-propylthio, 2-methylpropylthio, 1,1-dimethylethylthio, pentylthio, 1-methylbutylthio, 2-methylbutylthio, 3-methylbutylthio, 2,2-dimethylpropylthio, 1-ethylpropylthio, hexylthio, 1,1-dimethylpropylthio, 1,2-dimethylpropylthio, 1- methylpentylthio, 2-methylpentylthio, 3-methylpentylthio, 4-methylpentylthio, 1-
  • haloalkylthio refers to an alkylthio group as defined above wherein the carbon atoms are partially or entirely substituted with one or more halogen atoms. Unless otherwise specified, haloalkylthio groups wherein R is a Ci-C 8 alkyl group are intended. Examples include, but are not limited to, chloromethylthio, bromomethylthio,
  • chlorodifluoromethylthio 1-chloroethylthio, 1-bromoethylthio, 1 -fluoroethylthio, 2- fluoroethylthio, 2,2-difluoroethylthio, 2,2,2-trifluoroethylthio, 2-chloro-2-fluoroethylthio, 2- chloro-2-difluoroethylthio, 2,2-dichloro-2-fluoroethylthio, 2,2,2-trichloroethylthio, pentafluoroethylthio, and l,l,l-trifluoroprop-2-ylthio.
  • aryl refers to a phenyl, indanyl, or naphthyl group. In some embodiments, phenyl is preferred. Unless otherwise specified, the aryl groups may be unsubstituted or substituted with one or more substituents selected from, e.g.
  • halogen hydroxy, nitro, cyano, formyl, Ci-C 6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, Ci-C 6 alkoxy, Ci-C 6 haloalkyl, Ci-C 6 haloalkoxy, Ci-C 6 acyl, Ci-C 6 alkylthio, Ci-C 6 alkylsulfinyl, Ci-C 6 alkylsulfonyl, (Ci-Ce alkoxy)carbonyl, Ci-C 6 carbamoyl, hydroxycarbonyl, (Ci-Ce alkyl)carbonyl, aminocarbonyl, (Ci-C6 alkylamino)carbonyl, (di(Ci- C 6 alkyl)amino)carbonyl, provided that the substituents are sterically compatible and the rules of chemical bonding and strain energy are satisfied.
  • preferred substituents include, for example, halogen, C1-C
  • arylalkyl refers to an alkyl, alkenyl, or alkynyl group substituted with an aryl group as defined herein.
  • alkoxycarbonyl refers to a group of the formula wherein is alkyl.
  • alkylamino refers to an amino group substituted with one or two alkyl, alkenyl, or alkynyl groups, which may be the same or different, e.g., Ci-C 6 alkyl, C3-C6 alkenyl, or C3-C6 alkynyl.
  • alkylcarbamyl refers to a carbamyl group substituted on the nitrogen with an alkyl group.
  • alkylsulfonyl refers to -SO2R, wherein R is alkyl (e.g. , C1-C10 alkyl).
  • X can for example be S, SO, or SO2.
  • carbamoyl or aminocarbonyl refers to a group of the formula
  • haloalkylamino refers to an alkylamino group wherein the alkyl carbon atoms are partially or entirely substituted with one or more halogen atoms.
  • Me refers to a methyl group
  • halogen refers to fluorine, chlorine, bromine, or iodine (or fluoride, chloride, bromide, or iodide).
  • plants and vegetation include, but are not limited to, germinant seeds, emerging seedlings, plants emerging from vegetative propagules, immature vegetation, and established vegetation.
  • R is H.
  • Ri is cyano
  • Ri is C1-C4 alkyl. In one embodiment, Ri is Me.
  • Ri is C2-C4 alkynyl. In one embodiment, Ri is ethynyl.
  • Ri is a substituted phenyl. In one embodiment, Ri is 4- chlorophenyl. In another embodiment, Ri is 2,4-dichlorophenyl.
  • R 4 is cyano. In another embodiment, R 4 is trifluoromethyl. In another embodiment, R 4 is fluoro.
  • Ri is methyl and one of R2, R3, R 4 , R5 is not hydrogen
  • a nucleophile for example a Grignard reagent, such as methylmagnesium bromide or
  • step a of Scheme 2 a 2-bromobenzaldehyde of Formula 2.0 is transformed into the 2-formylphenylboronate of Formula 2.1 , wherein Z 2 is an acyclic boronate such as
  • B(0(Ri5)) 2 and R15 Ci-C 4 alkyl, by treatment with an alkylboron reagent, such as trimethylborate or triisopropylborate, in the presence of n-butyllithium (n-BuLi), in an ethereal solvent, such as THF, at low temperature, for example -78 °C under an inert atmosphere.
  • an alkylboron reagent such as trimethylborate or triisopropylborate
  • a nucleophile for example a Grignard reagent, such as methylmagnesium bromide or ethynylmagnesium bromide, or a lithium reagent, such as methyllithium or phenyllithium, in an ethereal solvent,
  • the compounds of Formula 2.2 can be generated in a two-step, one pot process wherein the aforementioned steps (a and b) are reversed (b, then a).
  • step b of Scheme 4 the 1-hydroxy- oxaborole 4.1 is then allowed to react with a strong mineral acid, such as 6 Normal (N) hydrochloric acid (HC1), in a polar protic solvent, such as ethyl alcohol, at an elevated temperature, for example reflux under an inert atmosphere to provide the compound of
  • a strong mineral acid such as 6 Normal (N) hydrochloric acid (HC1)
  • a polar protic solvent such as ethyl alcohol
  • the geminal dibromide is hydrolyzed in the presence of silver nitrate in an aqueous alcohol, such as ethyl alcohol in water at an elevated temperature, such as reflux, to provide 4-bromo-3- formylbenzonitrile(5.2), as in step b.
  • an aqueous alcohol such as ethyl alcohol in water at an elevated temperature, such as reflux
  • the hydroxyl group is alkylated with an alkylating reagent such as methyl chloromethyl ether (MOMC1), in the presence of a base, such N,N- diisopropylethylamine (DIPEA), in a halogenated hydrocarbon solvent, such as
  • step e the substituted methoxymethoxymethyl derivative is converted to the 1 hydroxy-l,3-dihydrobenzo-[c][l,2]oxaborole-5-carbonitrile 5.5, wherein R 4 is cyano, and Ri, R2, R3, and R5 are as originally defined, by treatment with triisopropylborate and n-BuLi at low temperature in an anhydrous ether solvent, such as THF.
  • an anhydrous ether solvent such as THF.
  • a mineral acid such as concentrated HC1
  • the compounds of Formulae 1.2, 2.2, 3.2, 4.1, 4.2, 5.5, 5.6, and 5.7, wherein R, Ri, R2, R3, R4 and R5 are as originally defined, obtained by any of these processes, can be recovered by conventional means and purified by standard procedures, such as by trituration, recrystallization or chromatography.
  • the compounds of Formula (I) where R is an agriculturally acceptable salt or ester can be prepared from compounds of Formulae 1.2, 2.2, 3.2, 4.1, 4.2, 5.5, 5.6, and 5.7 using standard methods well known in the art.
  • the compounds provided herein are employed in mixtures containing a herbicidally effective amount of the compound along with at least one agriculturally acceptable adjuvant or carrier.
  • exemplary adjuvants or carriers include those that are not phytotoxic or significantly phytotoxic to valuable crops, e.g. , at the
  • compositions for selective weed control in the presence of crops can be designed for application directly to weeds or their locus or can be concentrates or formulations that are diluted with additional carriers and adjuvants before application.
  • They can be solids, such as, for example, dusts, granules, water dispersible granules, or wettable powders, or liquids, such as, for example, emulsifiable concentrates, solutions, emulsions or suspensions. They can also be provided as a pre-mix or tank-mixed.
  • Suitable agricultural adjuvants and carriers that are useful in preparing the herbicidal mixtures of the disclosure are well known to those skilled in the art.
  • Some of these adjuvants include, but are not limited to, crop oil concentrate (mineral oil (85%) + emulsifiers (15%)); nonylphenol ethoxylate; benzylcocoalkyldimethyl quaternary ammonium salt; blend of petroleum hydrocarbon, alkyl esters, organic acid, and anionic surfactant; C9-C11
  • alky lpoly glycoside phosphated alcohol ethoxylate; natural primary alcohol (C12-C16) ethoxylate; di-s ⁇ ?obutylphenol EO-PO block copolymer; polysiloxane-methyl cap;
  • Liquid carriers that can be employed include water and organic solvents.
  • the organic solvents typically used include, but are not limited to, petroleum fractions or hydrocarbons such as mineral oil, aromatic solvents, paraffinic oils, and the like; vegetable oils such as soybean oil, rapeseed oil, olive oil, castor oil, sunflower seed oil, coconut oil, corn oil, cottonseed oil, linseed oil, palm oil, peanut oil, safflower oil, sesame oil, tung oil and the like; esters of the above vegetable oils; esters of monoalcohols or dihydric, trihydric, or other lower polyalcohols (4-6 hydroxy containing), such as 2-ethylhexyl stearate, n -butyl oleate, isopropyl myristate, propylene glycol dioleate, di-octyl succinate, di-butyl adipate, di-octyl phthalate and the like; esters of mono-, di-
  • organic solvents include toluene, xylene, petroleum naphtha, crop oil, acetone, methyl ethyl ketone, cyclohexanone, trichloroethylene, perchloroethylene, ethyl acetate, amyl acetate, butyl acetate, propylene glycol monomethyl ether and diethylene glycol monomethyl ether, methyl alcohol, ethyl alcohol, isopropyl alcohol, amyl alcohol, ethylene glycol, propylene glycol, glycerine, N-methyl-2-pyrrolidinone, NN-dimethyl alkylamides, dimethyl sulfoxide, liquid fertilizers, and the like.
  • water is the carrier for the dilution of concentrates.
  • Suitable solid carriers include talc, pyrophyllite clay, silica, attapulgus clay, kaolin clay, kieselguhr, chalk, diatomaceous earth, lime, calcium carbonate, bentonite clay, Fuller's earth, cottonseed hulls, wheat flour, soybean flour, pumice, wood flour, walnut shell flour, lignin, and the like.
  • one or more surface- active agents are utilized in the compositions of the present disclosure. Such surface-active agents are, in some
  • the surface-active agents can be anionic, cationic or nonionic in character and can be employed as emulsifying agents, wetting agents, suspending agents, or for other purposes.
  • Surfactants conventionally used in the art of formulation and which may also be used in the present formulations are described, inter alia, in
  • Typical surface-active agents include salts of alkyl sulfates, such as diethanolammonium lauryl sulfate; alkylarylsulfonate salts, such as calcium
  • dodecylbenzenesulfonate alkylphenol-alkylene oxide addition products, such as
  • nonylphenol-Ci8 ethoxylate alcohol-alkylene oxide addition products, such as tridecyl alcohol-Ci6 ethoxylate
  • soaps such as sodium stearate
  • alky lnaphthalene- sulfonate salts such as sodium dibutylnaphthalenesulfonate
  • dialkyl esters of sulfosuccinate salts such as sodium di(2-ethylhexyl) sulfosuccinate
  • sorbitol esters such as sorbitol oleate
  • quaternary amines such as lauryl trimethylammonium chloride
  • polyethylene glycol esters of fatty acids such as polyethylene glycol stearate
  • salts of mono- and dialkyl phosphate esters such as soybean oil, rapeseed/canola oil, olive oil, castor oil, sunflower seed oil, coconut
  • some of these materials can be used interchangeably as an agricultural adjuvant, as a liquid carrier or as a surface active agent.
  • compositions may also contain other compatible components, for example, other herbicides, plant growth regulants, fungicides, insecticides, and the like and can be formulated with liquid fertilizers or solid, particulate fertilizer carriers such as ammonium nitrate, urea and the like.
  • concentration of the active ingredients in the herbicidal compositions of this disclosure is generally from about 0.001 to about 98 percent by weight.
  • compositions designed to be employed as concentrates the active ingredient is generally present in a concentration from about 5 to about 98 weight percent, preferably about 10 to about 90 weight percent.
  • Such compositions are typically diluted with an inert carrier, such as water, before application.
  • the diluted compositions usually applied to weeds or the locus of weeds generally contain about 0.0001 to about 1 weight percent active ingredient and preferably contain about 0.001 to about 0.05 weight percent.
  • compositions can be applied to weeds or their locus by the use of conventional ground or aerial dusters, sprayers, and granule applicators, by addition to irrigation or flood water, and by other conventional means known to those skilled in the art.
  • the compounds and compositions described herein are applied as a post-emergence application, pre-emergence application, in-water application to flooded paddy rice or water bodies (e.g. , ponds, lakes and streams), or burn-down application.
  • the compounds and compositions provided herein are utilized to control weeds in crops, including but not limited to citrus, apple, rubber, oil, palm, forestry, direct-seeded, water-seeded and transplanted rice, wheat, barley, oats, rye, sorghum, corn/maize, pastures, grasslands, rangelands, fallowland, turf, tree and vine orchards, aquatics, or row-crops, as well as non-crop settings, e.g. , industrial vegetation management (IVM) or rights-of-way.
  • the compounds and compositions are used to control woody plants, broadleaf and grass weeds, or sedges.
  • the compounds and compositions provided herein are utilized to control undesirable vegetation in rice.
  • the undesirable vegetation is Brachiaria platyphylla (Groseb.) Nash (broadleaf signalgrass, BRAPP), Digitaria sanguinalis (L.) Scop, (large crabgrass, DIGSA), Echinochloa crus-galli (L.) P. Beauv. (barnyardgrass, ECHCG), Echinochloa colonum (L.) LINK (junglerice, ECHCO),
  • Echinochloa oryzoides (Ard.) Fritsch (early watergrass, ECHOR), Echinochloa oryzicola (Vasinger) Vasinger (late watergrass, ECHPH), Ischaemum rugosum Salisb. (saramollagrass, ISCRU), Leptochloa chinensis (L.) Nees (Chinese sprangletop, LEFCH), Leptochloa fascicularis (Lam.) Gray (bearded sprangletop, LEFFA), Leptochloa panicoides (Presl.) Hitchc.
  • AMMCO Eclipta alba
  • Hassk. American false daisy, ECLAL
  • Heteranthera limosa SW.
  • Willd./Vahl ducksalad
  • Heteranthera reniformis R. & P. roundleaf mudplantain, HETRE
  • Ipomoea hederacea L.
  • Jacq. ivyleaf morningglory, IPOHE
  • Lindernia dubia (L.) Pennell (low false pimpernel, LIDDU), Monochoria korsakowii Regel & Maack (monochoria, MOOKA), Monochoria vaginalis (Burm. F.) C. Presl ex Kuhth, (monochoria, MOOVA), Murdannia nudiflora (L.) Brenan (doveweed, MUDNU),
  • Polygonum pensylvanicum L. (Pennsylvania smartweed, POLPY), Polygonum persicaria L. (ladysthumb, POLPE), Polygonum hydropiperoides Michx. (mild smartweed, POLHP), Rotala indica (Willd.) Koehne (Indian toothcup, ROTIN), Sagittaria species, (arrowhead, SAGSS), Sesbania exaltata (Raf.) Cory/Rydb. Ex Hill (hemp sesbania, SEBEX), or Sphenoclea zeylanica Gaertn. (gooseweed, SPDZE).
  • the compounds and compositions provided herein are utilized to control undesirable vegetation in cereals.
  • the undesirable vegetation is Alopecurus myosuroides Huds. (blackgrass, ALOMY), Apera spica-venti (L.) Beauv. (windgrass, APESV), Avenafatua L. (wild oat, AVEFA), Bromus tectorum L.
  • the compounds and compositions provided herein are utilized to control undesirable vegetation in range and pasture.
  • the undesirable vegetation is Ambrosia artemisiijolia L. (common ragweed, AMBEL), Cassia obtusifolia (sickle pod, CASOB), Centaurea maculosa auct. non Lam. (spotted knapweed, CENMA), Cirsium arvense (L.) Scop. (Canada thistle, CIRAR), Convolvulus arvensis L. (field bindweed, CONAR), Euphorbia esula L.
  • Wiggers (dandelion, TAROF), Trifolium repens L. (white clover, TRFRE), or Urtica dioica L. (common nettle, URTDI).
  • the compounds and compositions provided herein are utilized to control undesirable vegetation found in row crops.
  • the undesirable vegetation is Alopecurus myosuroides Huds. (blackgrass, ALOMY), Avenajatua L. (wild oat, AVEFA), Brachiaria platyphylla (Groseb.) Nash (broadleaf signalgrass, BRAPP), Digitaria sanguinalis (L.) Scop, (large crabgrass, DIGSA), Echinochloa crus-galli (L.) P. Beauv. (barnyardgrass, ECHCG), Echinochloa colonum (L.) Link (junglerice, ECHCO), Lolium multiflorum Lam.
  • application rates of about 1 to about 4,000 grams/hectare (g/ha) are employed in post-emergence operations. In some embodiments, rates of about 1 to about 4,000 g/ha are employed in pre-emergence operations.
  • the compounds, compositions, and methods provided herein are used in conjunction with one or more other herbicides to control a wider variety of undesirable vegetation
  • the presently claimed compounds can be formulated with the other herbicide or herbicides, tank-mixed with the other herbicide or herbicides or applied sequentially with the other herbicide or herbicides.
  • aminocyclopyrachlor aminopyralid, amiprofos -methyl, amitrole, ammonium sulfamate, anilofos, anisuron, asulam, atraton, atrazine, azafenidin, azimsulfuron, aziprotryne, barban, BCPC, beflubutamid, benazolin, bencarbazone, benfluralin, benfuresate, bensulfuron-methyl, bensulide, benthiocarb, bentazon-sodium, benzadox, benzfendizone, benzipram,
  • dimethachlor dimethametryn, dimethenamid, dimethenamid-P, dimexano, dimidazon, dinitramine, dinofenate, dinoprop, dinosam, dinoseb, dinoterb, diphenamid, dipropetryn, diquat, disul, dithiopyr, diuron, DMPA, DNOC, DSMA, EBEP, eglinazine, endothal, epronaz, EPTC, erbon, esprocarb, ethalfluralin, ethbenzamide, ethametsulfuron, ethidimuron, ethiolate, ethobenzamid, etobenzamid, ethofumesate, ethoxyfen, ethoxysulfuron, etinofen, etnipromid, etobenzanid, EXD, fenasulam, f
  • the compounds and compositions of the present disclosure can generally be employed in combination with known herbicide safeners, such as benoxacor, benthiocarb, brassinolide, cloquintocet (e.g. , mexyl), cyometrinil, daimuron, dichlormid, dicyclonon, dimepiperate, disulfoton, fenchlorazole-ethyl, fenclorim, flurazole, fluxofenim, furilazole, harpin proteins, isoxadifen-ethyl, mefenpyr-diethyl, MG 191, MON 4660, naphthalic anhydride (NA), oxabetrinil, R29148 and N-phenylsulfonylbenzoic acid amides, to enhance their selectivity.
  • known herbicide safeners such as benoxacor, benthiocarb, brassinolide, cloquintocet (e.g. , mex
  • exemplary resistant or tolerant weeds include, but are not limited to, biotypes resistant or tolerant to ALS inhibitors, photosystem II inhibitors, ACCase inhibitors, synthetic auxins, photosystem I inhibitors, 5-enolpyruvylshikimate-3- phosphate (EPSP) synthase inhibitors, microtubule assembly inhibitors, lipid synthesis inhibitors, PPO inhibitors, carotenoid biosynthesis inhibitors, very long chain fatty acid
  • VLCFA phytoene desaturase
  • PDS phytoene desaturase
  • HPPD HPPD inhibitor
  • mitosis inhibitors cellulose biosynthesis inhibitors
  • herbicides with multiple modes-of-action such as quinclorac
  • unclassified herbicides such as arylaminopropionic acids, difenzoquat, endothall, and organoarsenicals.
  • exemplary resistant or tolerant weeds include, but are not limited to, biotypes with resistance or tolerance to multiple herbicides, multiple chemical classes, and multiple herbicide modes-of-action.
  • the aqueous solution was made acidic and extracted with EtiO. None of the desired oxaborole product was identified by gas chromatography-mass spectrometry (GC-MS) in the second EtiO wash. The title compound was present in first Et20 wash, which was concentrated.
  • GC-MS gas chromatography-mass spectrometry
  • the reaction mixture was poured into 3 ⁇ 40 (30 mL), cooled in an ice bath, made basic (pH 12) with 2 N NaOH, made acidic (pH 4) with 2 N HC1 and extracted with EtOAc (2 x 25 mL).
  • the combined organic extracts were washed with brine (30 mL), dried over MgSC , concentrated under reduced pressure, and dried in vacuo at ambient temperature for 14 h. Recrystallization from EtOAc/hexanes afforded the title compound as a white solid (17 mg, 19%).
  • the mother liquor was concentrated under reduced pressure and dried in vacuo at room temperature for 14 h to leave a waxy pink solid which contained additional less pure material (40 mg, 45%).
  • Herbicidal evaluations were made visually on a scale of 0 to 100 where 0 represents no activity and 100 represents complete plant death. The data are displayed as indicated in Table A.
  • Post- Emergent Test I Seeds of test species were obtained from commercial suppliers and planted into a 13 centimeter (cm) diameter-round pot containing soil-less media mix (Metro-Mix 360 ® , Sun Gro Horticulture). Postemergence treatments were planted 8-12 days (d) prior to application and cultured in a greenhouse equipped with supplemental light sources to provide a 16 hour (h) photoperiod at 24-29 °C. All pots were surface irrigated.
  • a weighed amount, determined by the highest rate to be tested, of each compound was dissolved in 1.3 milliliters (mL) acetone-dimethyl sulfoxide (DMSO; 97:3, volume per volume (v/v)) and diluted with 4.1 mL water-isopropanol-crop oil concentrate (78:20:2, v/v/v) containing 0.02% Triton X-155 to obtain concentrated stock solutions.
  • DMSO acetone-dimethyl sulfoxide
  • v/v volume per volume
  • Formulated compounds were applied using a DeVilbiss ® compressed air sprayer at 2-
  • pots 4 pounds per square inch (psi). Following treatment, pots were returned to the greenhouse for the duration of the experiment. All pots were subirrigated as needed to provide optimum growing conditions. All pots were fertilized one time per week by subirrigating with Peters Peat-Lite Special ® fertilizer (20-10-20).
  • Phytotoxicity ratings were obtained 10 days after postemergence applications. All evaluations were made visually on a scale of 0 to 100 where 0 represents no activity and 100 represents complete plant death, and the data are presented as indicated in Table A. Visual assessments of plant injury were made based on growth reduction, discoloration, leaf deformity and necrosis.
  • APESV windgrass ( Apera spica-venti (L.) Beauv.)
  • ECHCG bamyardgrass (Echinochloa crus-galli)
  • HELAN sunflower (Helianthus annuus)
  • PANDI fall panicum (Panicum dichotomiflorum (L.) Michx.)
  • PHAMI littleseed canarygrass (Phalaris minor Retz.)
  • SETFA giant foxtail (Setaria faberi)

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Abstract

Provided herein are 1-hydroxy-1,3-dihydrobenzo[c][1,2]oxaboroles and their derivatives, and compositions and methods of use thereof as herbicides.

Description

l-HYDROXY-l,3-DIHYDROBENZO[c][l,2]OXABOROLES
AND THEIR USE AS HERBICIDES
BACKGROUND The occurrence of undesirable vegetation, i.e. , weeds, is a constant problem facing farmers in crops, pasture, and other settings. Weeds compete with crops and negatively impact crop yield. The use of chemical herbicides is an important tool in controlling undesirable vegetation.
There remains a need for new chemical herbicides that offer a broader spectrum of weed control, selectivity, minimal crop damage, storage stability, ease of handling, higher activity against weeds, and/or a means to address herbicide-tolerance that develops with respect to herbicides currently in use.
A number of compounds containing an oxaborole ring have been described in the literature; see, for example, U.S. Patents 5,880,188; 7,582,621; 7,767,657; 8,039,450; and 8,168,614; and, for example, U.S. Patent Application Publications 2012/0295875 and 2013/0131017. These oxaboroles have found use as industrial biocides, particularly as fungicides for the protection of plastic materials, as fungicides for skin, nails, hair, claws or hoofs, as anti-inflammatories for human diseases, as ectoparasiticides for the control of fleas and ticks and as anti-protozoal agents for the control of animal and human diseases. It has been found that certain such oxaboroles are also useful for the control of undesirable vegetation.
SUMMARY
Provided herein are compounds of Formula (I):
Figure imgf000002_0001
wherein
R represents H or an agriculturally acceptable salt or ester; Ri represents cyano; C1-C12 alkyl in which the alkyl is unsubstituted or substituted with OH, NH2, C1-C2 alkylamino, di-(Ci-C2 alkyl)amino, C1-C2 alkoxy, C1-C2 haloalkoxy, C1-C2 alkylthio or C1-C2 haloalkylthio; Ci-Cs haloalkyl; C3-C8 cycloalkyl; C2-C8 alkenyl; C2- C8 haloalkenyl; C2-C8 alkynyl; C2-C8 haloalkynyl; -C(0)OR6; -C(0)NR7R8; C8-Ci4 arylalkyl; C8-C14 arylalkenyl; Cs-Ci4 arylalkynyl; or aryl in which the aryl is unsubstituted or substituted with one or more R9;
R2, R3, R4 and R5 independently represent H; cyano; halo; nitro; N¾; Ci-C6 alkylamino; di-(Ci-C6 alkyl)amino; C1-C12 alkyl; Ci-C8 alkoxy; Ci-C8 haloalkyl; Ci-C8 haloalkoxy; C3-C8 cycloalkyl; C2-C8 alkenyl; C2-C8 haloalkenyl; C2-C8 alkynyl; C2-C8 haloalkynyl; -C(0)OR6; -C(0)NR7Rs; aryl or aryloxy in which the aryl or aryloxy is unsubstituted or substituted with one or more R9; or where R3 and R4 are taken together as -OCH2O-, -OCH2CH2O-, -OCH2CH2- or -OCF2O-, provided that R2, R3, R4 and R5 are sterically compatible and that at least one of R2, R3, R4 and R5 is other than H;
R6, R7 and Rs independently represent H; C1-C12 alkyl; C3-C8 alkenyl; or C3-C8 alkynyl; in which the alkyl, alkenyl or alkynyl is unsubstituted or substituted with one or more OH, Ci-C4 alkoxy, Ci-C4 alkylthio, or phenyl groups, provided that R6, R7 and Rs are sterically compatible; and
R9 represents halo, C1-C12 alkyl, Ci-Cs alkoxy, Ci-Cs haloalkyl, or Ci-Cs haloalkoxy; with the proviso that R3 is not -XYC(0)ORio, wherein
X represents O, NRn, S, SO, or SO2 where Rn is H, Ci-C6-alkyl, C3-C6-alkenyl, or
C3-C6-alkynyl;
Y represents Ci-C6-alkyl, C3-C6-alkenyl, or C3-C6-alkynyl, in which the alkyl, alkenyl or alkynyl is unsubstituted or substituted with one or more halogen, Ci-C6-alkyl, Ci-C6- haloalkyl, Ci-C6-alkoxy, Ci-C6-haloalkoxy, C(0)0(Ci-C6-alkyl) or phenyl which is unsubstituted or substituted by halogen, Ci-C6-alkyl, Ci-C6-haloalkyl; and
Rio represents H, Ci-C6-alkyl, C3-C6-alkenyl, C3-C6- alkynyl, (Ci-C6-alkoxy)-Ci-C6- alkyl, (Ci-C6-alkoxy)-C3-C6-alkenyl, (C1-C6- alkoxy)-C3-C6-alkynyl, phenyl, phenyl-Ci-C6- alkyl, where the aliphatic and phenyl parts of the aforementioned radicals are unsubstituted, partly or completely halogenated.
Also provided herein are herbicidal composition comprising a compound of Formula
(I):
Figure imgf000004_0001
wherein
R represents H or an agriculturally acceptable salt or ester;
Ri represents cyano; C1-C12 alkyl in which the alkyl is unsubstituted or substituted with OH, NH2, C1-C2 alkylamino, di-(Ci-C2 alkyl)amino, C1-C2 alkoxy, C1-C2 haloalkoxy, C1-C2 alkylthio or C1-C2 haloalkylthio; Ci-Cs haloalkyl; C3-C8 cycloalkyl; C2-C8 alkenyl; C2- C8 haloalkenyl; C2-C8 alkynyl; C2-C8 haloalkynyl; -C(0)OR6; -C(0)NR7R8; C8-Ci4 arylalkyl; C8-Ci4 arylalkenyl; C8-Ci4 arylalkynyl; or aryl in which the aryl is unsubstituted or substituted with one or more R9;
R2, R3, R4 and R5 independently represent H; cyano; halo; nitro; NH2; Ο-Ce alkylamino; di-(Ci-C6 alkyl)amino; C1-C12 alkyl; Ci-C8 alkoxy; Ci-C8 haloalkyl; Ci-C8 haloalkoxy; C3-C8 cycloalkyl; C2-C8 alkenyl; C2-C8 haloalkenyl; C2-C8 alkynyl; C2-C8 haloalkynyl; -C(0)OR6; -C(0)NR7R8; aryl or aryloxy in which the aryl or aryloxy is unsubstituted or substituted with one or more R9; or where R3 and R4 are taken together as -OCH2O-, -OCH2CH2O-, -OCH2CH2- or -OCF2O-, provided that R2, R3, R4 and R5 are sterically compatible and that at least one of R2, R3, R4 and R5 is other than H;
R6, R7 and R8 independently represent H; C1-C12 alkyl; C3-C8 alkenyl; or C3-C8 alkynyl; in which the alkyl, alkenyl or alkynyl is unsubstituted or substituted with one or more OH, Ci-C4 alkoxy, Ci-C4 alkylthio, or phenyl groups, provided that R6, R7 and R8 are sterically compatible;
R9 represents halo, C1-C12 alkyl, Ci-C8 alkoxy, Ci-C8 haloalkyl, or Ci-C8 haloalkoxy; with the proviso that R3 is not -XYC(0)ORio, wherein
X represents O, NRn, S, SO, or SO2 where Rn is H, Ci-C6-alkyl, C3-C6-alkenyl, or C3-C6-alkynyl;
Y represents Ci-C6-alkyl, C3-C6-alkenyl, or C3-C6-alkynyl, in which the alkyl, alkenyl or alkynyl is unsubstituted or substituted with one or more halogen, Ci-C6-alkyl, Ci-C6- haloalkyl, Ci-C6-alkoxy, Ci-C6-haloalkoxy, C(0)0(Ci-C6-alkyl) or phenyl which is unsubstituted or substituted by halogen, Ci-C6-alkyl, Ci-C6-haloalkyl; and Rio represents H, Ci-C6-alkyl, C3-C6-alkenyl, C3-C6- alkynyl, (Ci-C6-alkoxy)-Ci-C6- alkyl, (Ci-C6-alkoxy)-C3-C6-alkenyl, (Ci-C6- alkoxy)-C3-C6-alkynyl, phenyl, phenyl-Ci-C6- alkyl, where the aliphatic and phenyl parts of the aforementioned radicals are unsubstituted, partly or completely halogenated; and
an agriculturally acceptable adjuvant or carrier.
Also provided are methods of controlling undesirable vegetation comprising
(a) contacting the undesirable vegetation or area adjacent to the undesirable vegetation, or (b) pre-emergently contacting soil or water, with a herbicidally effective amount of at least one compound of Formula (I) or an agriculturally acceptable derivative (e.g. , agriculturally acceptable salts, solvates, hydrates, esters, amides or other derivatives) thereof.
DETAILED DESCRIPTION
As used herein, herbicide, herbicide composition, and herbicidal active ingredient mean a compound that controls undesirable vegetation when applied in an appropriate amount.
As used herein, control of or controlling undesirable vegetation means killing or preventing the vegetation, or causing some other adversely modifying effect to the vegetation e.g., deviations from natural growth or development, regulation, desiccation, retardation, and the like.
As used herein, a herbicidally effective or vegetation controlling amount is an amount of herbicidal active ingredient the application of which controls the relevant undesirable vegetation.
As used herein, applying a herbicide, herbicidal composition, or herbicidal active ingredient means delivering it directly to the targeted vegetation or to the locus thereof or to the area where control of undesired vegetation is desired. Methods of application include, but are not limited to, pre-emergently contacting soil or water, or post-emergently contacting the undesirable vegetation or area adjacent to the undesirable vegetation.
As used herein, plants and vegetation include, but are not limited to, dormant seeds, germinant seeds, emerging seedlings, plants emerging from vegetative propagules, immature vegetation, and established vegetation.
As used herein, agriculturally acceptable salts and esters for R refer to salts and esters of compounds of Formula (I) that exhibit herbicidal activity, or that are or can be converted in plants, water, or soil to the referenced herbicide. Exemplary agriculturally acceptable esters are those that are or can be hydrolyzed, oxidized, metabolized, or otherwise converted, e.g., in plants, water, or soil, to the corresponding 1-hydroxy-oxaborole or boronic acid which, depending upon the pH, may be in the dissociated or undissociated form.
Suitable agriculturally acceptable salts include those derived from alkali or alkaline earth metals and those derived from ammonia and amines. Preferred cations include sodium, potassium, magnesium, and aminium cations of the formula:
RioRiiRi2Ri3N+
wherein Rio, Rii, R12 and R13 each, independently represents hydrogen or C1-C12 alkyl, C3-C12 alkenyl, or C3-C12 alkynyl, each of which is optionally substituted by one or more substituents such as hydroxy, C1-C4 alkoxy, C1-C4 alkylthio, or phenyl groups, provided that Rio, R11 , R12 and R13 are sterically compatible. Additionally, any two Rio, R11, R12 and R13 together may represent an aliphatic difunctional moiety containing one to twelve carbon atoms and up to two oxygen or sulfur atoms. Salts of the compounds of Formula (I) can be prepared by treatment of compounds of Formula (I) with a metal hydroxide, such as sodium hydroxide, with an amine, such as ammonia, trimethylamine, diethanolamine, 2-methyl- thiopropylamine, bisallylamine, 2-butoxyethylamine, morpholine, cyclododecylamine, or benzylamine, or with a tetraalkylammonium hydroxide, such as tetramethylammonium hydroxide or choline hydroxide. Amine salts of compounds of Formula (I) are useful forms or derivatives of compounds of Formula (I) because they are water-soluble and lend them- selves to the preparation of desirable aqueous based herbicidal compositions.
Suitable agriculturally acceptable esters include straight chain or branched chain alkyl groups. Typical C1-C12 alkyl groups include, but are not limited to, methyl, ethyl, propyl, 1- methylethyl, butyl, 1,1-dimethylethyl, 1-methylpropyl, pentyl, hexyl, heptyl, 1-methyl-hexyl, octyl, 2-ethylhexyl, nonyl, decyl and dodecyl. Methyl and ethyl are often preferred.
As used herein, "alkyl" refers to saturated, straight-chained or branched hydrocarbon moieties. Unless otherwise specified, C1-C12 alkyl groups are intended (e.g., Ci-C6 alkyl). Examples include, but are not limited to, methyl, ethyl, propyl, 1 -methyl-ethyl, butyl, 1- methyl-propyl, 2-methyl-propyl, 1,1 -dimethyl-ethyl, pentyl, 1 -methyl-butyl, 2-methyl-butyl, 3-methyl-butyl, 2,2-dimethyl-propyl, 1-ethyl-propyl, hexyl, 1,1-dimethyl-propyl, 1,2- dimethyl-propyl, 1-methyl-pentyl, 2-methyl-pentyl, 3-methyl-pentyl, 4-methyl-pentyl, 1,1- dimethyl-butyl, 1,2-dimethyl-butyl, 1,3-dimethyl-butyl, 2,2-dimethyl-butyl, 2,3-dimethyl- butyl, 3,3-dimethyl-butyl, 1 -ethyl-butyl, 2-ethyl-butyl, 1,1,2-trimethyl-propyl, 1,2,2- trimethyl -propyl, 1 -ethyl- 1-methyl-propyl, and l-ethyl-2-methyl-propyl. As used herein, "haloalkyl" refers to straight-chained or branched alkyl groups, where in these groups the hydrogen atoms may partially or entirely be substituted with one or more halogen atom(s). Unless otherwise specified, Ci-Cs groups are intended (e.g., Ci-C6 haloalkyl). Examples include, but are not limited to, chloromethyl, bromomethyl, dichloromethyl, trichloromethyl, fluoromethyl, difluoromethyl, trifluoromethyl,
chlorofluoromethyl, dichlorofluoromethyl, chlorodifluoromethyl, 1-chloroethyl, 1- bromoethyl, 1-fluoroethyl, 2-fluoroethyl, 2,2-difluoroethyl, 2,2,2-trifluoroethyl, 2-chloro-2- fluoroethyl, 2-chloro-2,2-difluoroethyl, 2,2-dichloro-2-fluoroethyl, 2,2,2-trichloroethyl, pentafluoroethyl, and l,l,l-trifluoroprop-2-yl.
As used herein, "cycloalkyl" refers to saturated, cyclic hydrocarbon moieties. Unless otherwise specified, C3-C8 cycloalkyl groups are intended. Examples include cyclopropyl, 2,2-dimethyl-cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl and cyclooctyl.
As used herein, "alkenyl" refers to unsaturated, straight-chained, or branched hydrocarbon moieties containing one or more double bond(s). Unless otherwise specified, C2-C8 alkenyl groups are intended (e.g., C3-C6 alkenyl). Alkenyl groups may contain more than one unsaturated bond. Examples include, but are not limited to, ethenyl, 1-propenyl, 2- propenyl, 1-methylethenyl, 1-butenyl, 2-butenyl, 3-butenyl, 1 -methyl- 1-propenyl, 2-methyl- 1-propenyl, l-methyl-2-propenyl, 2-methyl-2-propenyl, 1-pentenyl, 2-pentenyl, 3-pentenyl, 4-pentenyl, 1-methyl-l-butenyl, 2-methyl- 1-butenyl, 3-methyl- 1-butenyl, l-methyl-2- butenyl, 2-methyl-2-butenyl, 3-methyl-2-butenyl, l-methyl-3-butenyl, 2-methyl-3 -butenyl, 3- methyl-3-butenyl, l,l-dimethyl-2-propenyl, 1 ,2-dimethyl- 1-propenyl, 1 ,2-dimethyl-2- propenyl, 1 -ethyl- 1-propenyl, l-ethyl-2-propenyl, 1-hexenyl, 2-hexenyl, 3-hexenyl, 4- hexenyl, 5-hexenyl, 1 -methyl- 1-pentenyl, 2-methyl- 1-pentenyl, 3-methyl- 1-pentenyl, 4- methyl- 1-pentenyl, l-methyl-2-pentenyl, 2-methyl-2-pentenyl, 3-methyl-2-pentenyl, 4- methyl-2-pentenyl, l-methyl-3-pentenyl, 2-methyl-3-pentenyl, 3-methyl-3-pentenyl, 4- methyl-3-pentenyl, l-methyl-4-pentenyl, 2-methyl-4-pentenyl, 3-methyl-4-pentenyl, 4- methyl-4-pentenyl, l,l-dimethyl-2-butenyl, l,l-dimethyl-3-butenyl, 1 ,2-dimethyl- 1-butenyl, l,2-dimethyl-2-butenyl, l,2-dimethyl-3-butenyl, 1,3-dimethyl-l-butenyl, l,3-dimethyl-2- butenyl, l,3-dimethyl-3-butenyl, 2,2-dimethyl-3-butenyl, 2, 3-dimethyl- 1-butenyl, 2,3- dimethyl-2-butenyl, 2,3-dimethyl-3-butenyl, 3,3-dimethyl-l-butenyl, 3,3-dimethyl-2-butenyl,
1 - ethyl- 1-butenyl, l-ethyl-2-butenyl, l-ethyl-3 -butenyl, 2-ethyl-l-butenyl, 2-ethyl-2-butenyl,
2- ethyl-3-butenyl, l,l,2-trimethyl-2-propenyl, 1 -ethyl- l-methyl-2-propenyl, l-ethyl-2- methyl- 1-propenyl, and l-ethyl-2-methyl-2-propenyl. As used herein, "haloalkenyl" refers to straight-chained or branched alkenyl groups, where in these groups the hydrogen atoms may partially or entirely be substituted with one or more halogen atom(s). Unless otherwise specified, C2-C8 groups are intended. Examples include, but are not limited to 1-chloroethenyl, 1-chloro- 1 -propenyl, 2-chloro-l -propenyl, 1- chloro-2-propenyl, 2-chloro-2-propenyl, 1-chloro- 1-butenyl, 2-chloro-l -butenyl, 3-chloro-l- butenyl, l-chloro-2-butenyl, 2-chloro-2-butenyl, 3-chloro-2-butenyl, l-chloro-3-butenyl, 2- chloro-3-butenyl, 3-chloro-3-butenyl, 1-fluoroethenyl, 1-fluoro-l -propenyl, 2-fluoro-l- propenyl, l-fluoro-2-propenyl, 2-fluoro-2-propenyl, 1-fluoro-l-butenyl, 2-fluoro-l-butenyl, 3-fluoro- 1-butenyl, l-fluoro-2-butenyl, 2-fluoro-2-butenyl, 3-fluoro-2-butenyl, l-fluoro-3- butenyl, 2-fluoro-3-butenyl, and 3-fluoro-3-butenyl.
As used herein, "alkynyl" represents straight-chained or branched hydrocarbon moieties containing one or more triple bond(s). Unless otherwise specified, C2-C8 alkynyl groups are intended (e.g., C3-C6 alkynyl). Alkynyl groups may contain more than one unsaturated bond. Examples include, but are not limited to, C2-Cs-alkynyl, such as ethynyl, 1-propynyl, 2-propynyl (or propargyl), 1-butynyl, 2-butynyl, 3-butynyl, l-methyl-2-propynyl, 1-pentynyl, 2-pentynyl, 3-pentynyl, 4-pentynyl, 3-methyl- 1-butynyl, l-methyl-2-butynyl, l-methyl-3-butynyl, 2-methyl-3-butynyl, l,l-dimethyl-2-propynyl, l-ethyl-2-propynyl, 1-hexynyl, 2-hexynyl, 3-hexynyl, 4-hexynyl, 5-hexynyl, 3-methyl- 1-pentynyl, 4-methyl-l- pentynyl, l-methyl-2-pentynyl, 4-methyl-2-pentynyl, l-methyl-3 -pentynyl, 2-methyl-3- pentynyl, l-methyl-4-pentynyl, 2-methyl-4-pentynyl, 3-methyl-4-pentynyl, l,l-dimethyl-2- butynyl, l,l-dimethyl-3-butynyl, l,2-dimethyl-3-butynyl, 2,2-dimethyl-3-butynyl,
3,3-dimethyl-l-butynyl, l-ethyl-2-butynyl, l-ethyl-3-butynyl, 2-ethyl-3-butynyl, and
1- ethyl- l-methyl-2-propynyl.
As used herein, "haloalkynyl" refers to straight-chained or branched alkynyl groups, where in these groups the hydrogen atoms may partially or entirely be substituted with one or more halogen atom(s). Unless otherwise specified, C2-C8 groups are intended. Examples include, but are not limited to, l-chloro-2-butynyl, l-chloro-3-butynyl, 2-chloro-3-butynyl, l,l-dichloro-2-propynyl, l-chloro-2-propynyl, 3 -chloro- 1-pentynyl, 4-chloro- 1-pentynyl, 1- chloro-2-pentynyl, 4-chloro-2-pentynyl, l-chloro-3-pentynyl, 2-chloro-3-pentynyl, 1-chloro- 4-pentynyl, 2-chloro-4-pentynyl, 3-chloro-4-pentynyl, l,l-dichloro-2-butynyl, 1,1-dichloro- 3-butynyl, l,2-dichloro-3-butynyl, 2,2-dichloro-3-butynyl, 3, 3-dichloro- 1-butynyl, 1-fluoro-
2- butynyl, l-fluoro-3-butynyl, 2-fluoro-3-butynyl, and l,l-difluoro-2-propynyl, l-fluoro-2- propynyl, 3-fluoro- 1-pentynyl, 4-fluoro- 1-pentynyl, l-fluoro-2-pentynyl, 4-fluoro-2- pentynyl, l-fluoro-3-pentynyl, 2-fluoro-3-pentynyl, l-fluoro-4-pentynyl, 2-fluoro-4-pentynyl, 3-fluoro-4-pentynyl, l,l-difluoro-2-butynyl, l,l-difluoro-3-butynyl, l,2-difluoro-3-butynyl, 2,2-difluoro-3-butynyl, and 3,3-difluoro-l-butynyl.
As used herein, "alkoxy" refers to a group of the formula R-0-, where R is alkyl as defined above (e.g., Ci-C6 alkoxy). Unless otherwise specified, alkoxy groups wherein R is a Ci-C8 alkyl group are intended. Examples include, but are not limited to, methoxy, ethoxy, propoxy, 1-methyl-ethoxy, butoxy, 1 -methyl -propoxy, 2-methyl-propoxy, 1,1-dimethyl- ethoxy, pentoxy, 1-methyl-butyloxy, 2-methyl-butoxy, 3-methyl-butoxy, 2,2-dimethyl- propoxy, 1-ethyl-propoxy, hexoxy, 1,1-dimethyl-propoxy, 1,2-dimethyl-propoxy, 1-methyl- pentoxy, 2-methyl-pentoxy, 3-methyl-pentoxy, 4-methyl-pentoxy, 1,1-dimethyl-butoxy, 1,2- dimethyl-butoxy, 1,3-dimethyl-butoxy, 2,2-dimethyl-butoxy, 2,3-dimethyl-butoxy, 3,3- dimethyl-butoxy, 1-ethyl-butoxy, 2-ethylbutoxy, 1 , 1 ,2-trimethyl-propoxy, 1,2,2-trimethyl- propoxy, 1 -ethyl- 1-methyl-propoxy, and l-ethyl-2-methyl-propoxy.
As used herein, "haloalkoxy" refers to a group of the formula R-0-, where R is haloalkyl as defined above. Unless otherwise specified, haloalkoxy groups wherein R is a Ci-C8 alkyl group are intended (e.g., Ci-C6 haloalkoxy). Examples include, but are not limited to, chloromethoxy, bromomethoxy, dichloromethoxy, trichloromethoxy,
fluoromethoxy, difluoromethoxy, trifluoromethoxy, chlorofluoromethoxy,
dichlorofluoromethoxy, chlorodifluoromethoxy, 1-chloroethoxy, 1-bromoethoxy, 1- fluoroethoxy, 2-fluoroethoxy, 2,2-difluoroethoxy, 2,2,2-trifluoroethoxy, 2-chloro-2- fluoroethoxy, 2-chloro-2,2-difluoroethoxy, 2,2-dichloro-2-fluoroethoxy, 2,2,2- trichloroethoxy, pentafluoroethoxy, and l,l,l-trifluoroprop-2-oxy.
As used herein, "alkylthio" refers to a group of the formula R-S- where R is alkyl as defined above. Unless otherwise specified, alkylthio groups wherein R is a Ci-C8 alkyl group are intended. Examples include, but are not limited to, methylthio, ethyl thio, propylthio, 1- methylethylthio, butylthio, 1-methyl-propylthio, 2-methylpropylthio, 1,1-dimethylethylthio, pentylthio, 1-methylbutylthio, 2-methylbutylthio, 3-methylbutylthio, 2,2-dimethylpropylthio, 1-ethylpropylthio, hexylthio, 1,1-dimethylpropylthio, 1,2-dimethylpropylthio, 1- methylpentylthio, 2-methylpentylthio, 3-methylpentylthio, 4-methylpentylthio, 1,1- dimethylbutylthio, 1,2-dimethylbutylthio, 1,3-dimethylbutylthio, 2,2-dimethylbutylthio, 2,3- dimethylbutylthio, 3,3-dimethylbutylthio, 1-ethylbutylthio, 2-ethylbutylthio, 1,1,2- trimethylpropylthio, 1,2,2-trimethylpropylthio, 1 -ethyl- 1-methylpropylthio, and l-ethyl-2- methylpropylthio .
As used herein, "haloalkylthio" refers to an alkylthio group as defined above wherein the carbon atoms are partially or entirely substituted with one or more halogen atoms. Unless otherwise specified, haloalkylthio groups wherein R is a Ci-C8 alkyl group are intended. Examples include, but are not limited to, chloromethylthio, bromomethylthio,
dichloromethylthio, trichloromethylthio, fluoromethylthio, difluoromethylthio,
trifluoromethylthio , chlorofluoromethylthio , dichlorofluoromethylthio ,
chlorodifluoromethylthio, 1-chloroethylthio, 1-bromoethylthio, 1 -fluoroethylthio, 2- fluoroethylthio, 2,2-difluoroethylthio, 2,2,2-trifluoroethylthio, 2-chloro-2-fluoroethylthio, 2- chloro-2-difluoroethylthio, 2,2-dichloro-2-fluoroethylthio, 2,2,2-trichloroethylthio, pentafluoroethylthio, and l,l,l-trifluoroprop-2-ylthio.
As used herein, "aryl," as well as derivative terms such as "aryloxy," refers to a phenyl, indanyl, or naphthyl group. In some embodiments, phenyl is preferred. Unless otherwise specified, the aryl groups may be unsubstituted or substituted with one or more substituents selected from, e.g. , halogen, hydroxy, nitro, cyano, formyl, Ci-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, Ci-C6 alkoxy, Ci-C6 haloalkyl, Ci-C6 haloalkoxy, Ci-C6 acyl, Ci-C6 alkylthio, Ci-C6 alkylsulfinyl, Ci-C6 alkylsulfonyl, (Ci-Ce alkoxy)carbonyl, Ci-C6 carbamoyl, hydroxycarbonyl, (Ci-Ce alkyl)carbonyl, aminocarbonyl, (Ci-C6 alkylamino)carbonyl, (di(Ci- C6 alkyl)amino)carbonyl, provided that the substituents are sterically compatible and the rules of chemical bonding and strain energy are satisfied. In some embodiments, preferred substituents include, for example, halogen, C1-C2 alkyl, and C1-C2 haloalkyl.
As used herein, "arylalkyl", "arylalkenyl", and "arylalkynyl" refer to an alkyl, alkenyl, or alkynyl group substituted with an aryl group as defined herein.
Figure imgf000010_0001
As used herein, "alkoxycarbonyl" refers to a group of the formula wherein is alkyl.
As used herein, "alkylamino", "dialkylamino", "alkenylamino", "dialkenylamino", "alkynylamino", "dialkynylamino", refers to an amino group substituted with one or two alkyl, alkenyl, or alkynyl groups, which may be the same or different, e.g., Ci-C6 alkyl, C3-C6 alkenyl, or C3-C6 alkynyl.
As used herein, "alkylcarbamyl" refers to a carbamyl group substituted on the nitrogen with an alkyl group.
As used herein, "alkylsulfonyl" refers to -SO2R, wherein R is alkyl (e.g. , C1-C10 alkyl). X can for example be S, SO, or SO2. As used herein, "carbamyl" (also referred to as carbamoyl or aminocarbonyl) refers to a group of the formula
Figure imgf000011_0001
As used herein, "haloalkylamino" refers to an alkylamino group wherein the alkyl carbon atoms are partially or entirely substituted with one or more halogen atoms.
As used herein, "Me" refers to a methyl group.
As used herein, the term "halogen," including derivative terms such as "halo," refers to fluorine, chlorine, bromine, or iodine (or fluoride, chloride, bromide, or iodide).
As used herein, plants and vegetation include, but are not limited to, germinant seeds, emerging seedlings, plants emerging from vegetative propagules, immature vegetation, and established vegetation.
COMPOUNDS
Provided herein are compounds of Formula (I) as defined herein (e.g. , in the
Summary above) and agriculturally acceptable derivatives thereof.
In some embodiments, R is H.
In some embodiments, Ri is cyano.
In some embodiments, Ri is C1-C4 alkyl. In one embodiment, Ri is Me.
In some embodiments, Ri is C2-C4 alkynyl. In one embodiment, Ri is ethynyl.
In some embodiments, Ri is a substituted phenyl. In one embodiment, Ri is 4- chlorophenyl. In another embodiment, Ri is 2,4-dichlorophenyl.
In some embodiments, R4 is cyano. In another embodiment, R4 is trifluoromethyl. In another embodiment, R4 is fluoro.
In one embodiment, Ri is methyl and one of R2, R3, R4, R5 is not hydrogen
METHODS OF PREPARING THE COMPOUNDS
Exemplary procedures to synthesize the compounds of Formula (I) are provided below. The general syntheses of some l-hydroxy-3-substituted- l,3-dihydrobenzo[c][l,2]- oxaboroles 1.2 and 2.2 wherein Ri, R2, R3, R4 and R5 are as defined originally, are shown in Schemes 1 and 2.
In step a of Scheme 1, a 2-bromobenzaldehyde of Formula 1.0 is transformed into the 2-formylphenylboronate of Formula 1.1, wherein Zi is a cyclic boronate such as B(-OC(Ri4)2C(Ri4)20-) or B(-OCH2C(Ri4)2CH20-) and RM = Me, by reaction with a boron reagent, such as bis(pinacolato)diboron or 5,5,5 '5 ' -tetramethyl-2,2'-bi(l ,3,2-dioxaborinane), in the presence of a base, such as potassium acetate, and a catalyst, such as [Ι , - bis(diphenylphosphino)ferrocene]dichloropalladium(II) (Pd(dppf)Cl2), in a polar, aprotic solvent, such as 1 ,4-dioxane, at an elevated temperature, for example 70 °C, from 2 to 16 hours, under an inert atmosphere. The boronate of Formula 1.1 , wherein Zi = B(- OC(Ri4)2C(Ri4)20-) or B(-OCH2C(Ri4)2CH20-) and RM = Me, is then converted to the compound of Formula 1.2, wherein Ri, R2, R3, R* and R5 are as defined originally, via reaction with a nucleophile, for example a Grignard reagent, such as methylmagnesium bromide or ethynylmagnesium bromide, or a lithium reagent, such as methyllithium or phenyllithium, in an ethereal solvent, such as diethyl ether (Et20) or tetrahydrofuran (THF), at low temperature, for example -78 °C under an inert atmosphere, as in step b in Scheme 1.
Scheme 1
Figure imgf000012_0001
1.0 1.1 1.2
In step a of Scheme 2, a 2-bromobenzaldehyde of Formula 2.0 is transformed into the 2-formylphenylboronate of Formula 2.1 , wherein Z2 is an acyclic boronate such as
B(0(Ri5))2 and R15 = Ci-C4 alkyl, by treatment with an alkylboron reagent, such as trimethylborate or triisopropylborate, in the presence of n-butyllithium (n-BuLi), in an ethereal solvent, such as THF, at low temperature, for example -78 °C under an inert atmosphere. The boronate of Formula 2.1, wherein Z2 = B(0(Ris))2 and R15 = Ci-C4 alkyl, is then converted to the compound of Formula 2.2, wherein Ri , R2, R3, R4 and R5 are as defined originally, via reaction with a nucleophile, for example a Grignard reagent, such as methylmagnesium bromide or ethynylmagnesium bromide, or a lithium reagent, such as methyllithium or phenyllithium, in an ethereal solvent, such as Et20 or THF, at low temperature, for example -78 °C under an inert atmosphere, as in step b in Scheme 2.
Alternatively, the compounds of Formula 2.2 can be generated in a two-step, one pot process wherein the aforementioned steps (a and b) are reversed (b, then a). Scheme 2
Figure imgf000013_0001
2.0 2.2
b, then a
Alternatively, when R4 = F and Ri, R2, R3, and R5 are as defined originally, the 2- formylphenylboronic acid of Formula 3.0 is transformed into the corresponding pinacol borate 3.1, via reaction with 2,3-dimethylbutane-2,3-diol hexahydrate in a hydrocarbon solvent under Dean-Stark conditions at an elevated temperature, such as reflux, as in step a of Scheme 3. In step b of Scheme 3, the 2-formylphenylpinacol borate 3.1 is then allowed to react with a nucleophile, for example a Grignard reagent, such as methylmagnesium bromide or ethynylmagnesium bromide, or a lithium reagent, such as methyllithium or phenyllithium, in an ethereal solvent, such as Et20 or THF, at low temperature, for example -78 °C under an inert atmosphere to provide the compound of Formula 3.2, wherein R4 = F and Ri, R2, R3, and R5
Figure imgf000013_0002
3.0 3.1 3.2
Alternatively, the 2-formylphenylboronic acid of Formula 4.0 is transformed into the corresponding l-hydroxy-3-cyano-l,3-dihydrobenzo[c][l,2]-oxaboroles 4.1, wherein when Ri = CN, R4 = F, and R2, R3, and R5 are as defined originally, via reaction with an aqueous solution of sodium cyanide in an ethereal solvent, such as THF, at a temperature such as ambient temperature, as in step a of Scheme 4. In step b of Scheme 4, the 1-hydroxy- oxaborole 4.1 is then allowed to react with a strong mineral acid, such as 6 Normal (N) hydrochloric acid (HC1), in a polar protic solvent, such as ethyl alcohol, at an elevated temperature, for example reflux under an inert atmosphere to provide the compound of
Formula 4.2, wherein Ri = CO2CH2CH3, R4 = F, and R2, R3, and R5 are as defined originally. Scheme 4
Figure imgf000014_0001
4.0 4.1 4.2
The general synthesis for some l-hydroxy-3-substituted- l,3-dihydrobenzo[c][l,2]- oxaborole-5-carbonitriles 4.5, 4.6 and 4.7, wherein R4 = cyano and R, Ri, R2, R3, and R5 are as defined previously, is shown in Scheme 5. In step a, 3-methyl-4-bromobenzonitrile (5.0), wherein R4 = cyano and R2, R3, and R5 are as defined previously, is brominated with N- bromosuccinimide in the presence of azobisisobutyronitrile (ΑΙΒΝ) in an inert organic solvent to provide 4-bromo-3-(dibromomethyl)benzonitrile (5.1). Then the geminal dibromide is hydrolyzed in the presence of silver nitrate in an aqueous alcohol, such as ethyl alcohol in water at an elevated temperature, such as reflux, to provide 4-bromo-3- formylbenzonitrile(5.2), as in step b. In step c, the aldehyde is treated with a Grignard reagent to provide a substituted hydroxymethyl compound 5.3, wherein R4 = cyano and Ri, R2, R3, and R5 are as originally defined. The hydroxyl group is alkylated with an alkylating reagent such as methyl chloromethyl ether (MOMC1), in the presence of a base, such N,N- diisopropylethylamine (DIPEA), in a halogenated hydrocarbon solvent, such as
dichloromethane (CH2CI2), to provide a substituted methoxymethoxymethyl compound 5.4, as in step d. In step e, the substituted methoxymethoxymethyl derivative is converted to the 1 hydroxy-l,3-dihydrobenzo-[c][l,2]oxaborole-5-carbonitrile 5.5, wherein R4 is cyano, and Ri, R2, R3, and R5 are as originally defined, by treatment with triisopropylborate and n-BuLi at low temperature in an anhydrous ether solvent, such as THF. The nitrile (R4 = cyano) can then be hydrolyzed to the corresponding acid 5.6, wherein R4 = C(0)OR6 and R6 = H, by treatment with a mineral acid, such as concentrated HC1, at an elevated temperature, such as reflux, as in step /. In step g, the acid is treated with thionyl chloride in a hydrocarbon solvent, such as 1 ,2-dichloroethane, at an elevated temperature, such as reflux, and then allowed to react with an amine source, such as ammonium hydroxide, in a polar aprotic solvent, such as THF, at a temperature from 0 to 25 °C to provide the amide 5.7, wherein R4 = C(0)NR7Rs, R7 and Rs = H, and Ri, R2, R3, and R5 are as originally defined. Scheme 5
Figure imgf000015_0001
5.6 5.7
The compounds of Formulae 1.2, 2.2, 3.2, 4.1, 4.2, 5.5, 5.6, and 5.7, wherein R, Ri, R2, R3, R4 and R5 are as originally defined, obtained by any of these processes, can be recovered by conventional means and purified by standard procedures, such as by trituration, recrystallization or chromatography. The compounds of Formula (I) where R is an agriculturally acceptable salt or ester can be prepared from compounds of Formulae 1.2, 2.2, 3.2, 4.1, 4.2, 5.5, 5.6, and 5.7 using standard methods well known in the art.
COMPOSITIONS AND METHODS In some embodiments, the compounds provided herein are employed in mixtures containing a herbicidally effective amount of the compound along with at least one agriculturally acceptable adjuvant or carrier. Exemplary adjuvants or carriers include those that are not phytotoxic or significantly phytotoxic to valuable crops, e.g. , at the
concentrations employed in applying the compositions for selective weed control in the presence of crops, and/or do not react or significantly react chemically with the compounds provided herein or other composition ingredients. Such mixtures can be designed for application directly to weeds or their locus or can be concentrates or formulations that are diluted with additional carriers and adjuvants before application. They can be solids, such as, for example, dusts, granules, water dispersible granules, or wettable powders, or liquids, such as, for example, emulsifiable concentrates, solutions, emulsions or suspensions. They can also be provided as a pre-mix or tank-mixed.
Suitable agricultural adjuvants and carriers that are useful in preparing the herbicidal mixtures of the disclosure are well known to those skilled in the art. Some of these adjuvants include, but are not limited to, crop oil concentrate (mineral oil (85%) + emulsifiers (15%)); nonylphenol ethoxylate; benzylcocoalkyldimethyl quaternary ammonium salt; blend of petroleum hydrocarbon, alkyl esters, organic acid, and anionic surfactant; C9-C11
alky lpoly glycoside; phosphated alcohol ethoxylate; natural primary alcohol (C12-C16) ethoxylate; di-s<?obutylphenol EO-PO block copolymer; polysiloxane-methyl cap;
nonylphenol ethoxylate + urea ammonium nitrrate; emulsified methylated seed oil; tridecyl alcohol (synthetic) ethoxylate (8EO); tallow amine ethoxylate (15 EO); PEG(400) dioleate- 99.
Liquid carriers that can be employed include water and organic solvents. The organic solvents typically used include, but are not limited to, petroleum fractions or hydrocarbons such as mineral oil, aromatic solvents, paraffinic oils, and the like; vegetable oils such as soybean oil, rapeseed oil, olive oil, castor oil, sunflower seed oil, coconut oil, corn oil, cottonseed oil, linseed oil, palm oil, peanut oil, safflower oil, sesame oil, tung oil and the like; esters of the above vegetable oils; esters of monoalcohols or dihydric, trihydric, or other lower polyalcohols (4-6 hydroxy containing), such as 2-ethylhexyl stearate, n -butyl oleate, isopropyl myristate, propylene glycol dioleate, di-octyl succinate, di-butyl adipate, di-octyl phthalate and the like; esters of mono-, di- and poly-carboxylic acids and the like. Specific organic solvents include toluene, xylene, petroleum naphtha, crop oil, acetone, methyl ethyl ketone, cyclohexanone, trichloroethylene, perchloroethylene, ethyl acetate, amyl acetate, butyl acetate, propylene glycol monomethyl ether and diethylene glycol monomethyl ether, methyl alcohol, ethyl alcohol, isopropyl alcohol, amyl alcohol, ethylene glycol, propylene glycol, glycerine, N-methyl-2-pyrrolidinone, NN-dimethyl alkylamides, dimethyl sulfoxide, liquid fertilizers, and the like. In some embodiments, water is the carrier for the dilution of concentrates.
Suitable solid carriers include talc, pyrophyllite clay, silica, attapulgus clay, kaolin clay, kieselguhr, chalk, diatomaceous earth, lime, calcium carbonate, bentonite clay, Fuller's earth, cottonseed hulls, wheat flour, soybean flour, pumice, wood flour, walnut shell flour, lignin, and the like. In some embodiments, one or more surface- active agents are utilized in the compositions of the present disclosure. Such surface-active agents are, in some
embodiments, employed in both solid and liquid compositions, e.g. , those designed to be diluted with carrier before application. The surface-active agents can be anionic, cationic or nonionic in character and can be employed as emulsifying agents, wetting agents, suspending agents, or for other purposes. Surfactants conventionally used in the art of formulation and which may also be used in the present formulations are described, inter alia, in
McCutcheon 's Detergents and Emulsifiers Annual, MC Publishing Corp., Ridgewood, New Jersey, 1998, and in Encyclopedia of Surfactants , Vol. I-III, Chemical Publishing Co., New York, 1980-81. Typical surface-active agents include salts of alkyl sulfates, such as diethanolammonium lauryl sulfate; alkylarylsulfonate salts, such as calcium
dodecylbenzenesulfonate; alkylphenol-alkylene oxide addition products, such as
nonylphenol-Ci8 ethoxylate; alcohol-alkylene oxide addition products, such as tridecyl alcohol-Ci6 ethoxylate; soaps, such as sodium stearate; alky lnaphthalene- sulfonate salts, such as sodium dibutylnaphthalenesulfonate; dialkyl esters of sulfosuccinate salts, such as sodium di(2-ethylhexyl) sulfosuccinate; sorbitol esters, such as sorbitol oleate; quaternary amines, such as lauryl trimethylammonium chloride; polyethylene glycol esters of fatty acids, such as polyethylene glycol stearate; block copolymers of ethylene oxide and propylene oxide; salts of mono- and dialkyl phosphate esters; vegetable or seed oils such as soybean oil, rapeseed/canola oil, olive oil, castor oil, sunflower seed oil, coconut oil, corn oil, cottonseed oil, linseed oil, palm oil, peanut oil, safflower oil, sesame oil, tung oil and the like; and esters of the above vegetable oils, e.g. , methyl esters.
Oftentimes, some of these materials, such as vegetable or seed oils and their esters, can be used interchangeably as an agricultural adjuvant, as a liquid carrier or as a surface active agent.
Other adjuvants commonly used in agricultural compositions include compatibilizing agents, antifoam agents, sequestering agents, neutralizing agents and buffers, corrosion inhibitors, dyes, odorants, spreading agents, penetration aids, sticking agents, dispersing agents, thickening agents, freezing point depressants, antimicrobial agents, and the like. The compositions may also contain other compatible components, for example, other herbicides, plant growth regulants, fungicides, insecticides, and the like and can be formulated with liquid fertilizers or solid, particulate fertilizer carriers such as ammonium nitrate, urea and the like. The concentration of the active ingredients in the herbicidal compositions of this disclosure is generally from about 0.001 to about 98 percent by weight. Concentrations from about 0.01 to about 90 percent by weight are often employed. In compositions designed to be employed as concentrates, the active ingredient is generally present in a concentration from about 5 to about 98 weight percent, preferably about 10 to about 90 weight percent. Such compositions are typically diluted with an inert carrier, such as water, before application. The diluted compositions usually applied to weeds or the locus of weeds generally contain about 0.0001 to about 1 weight percent active ingredient and preferably contain about 0.001 to about 0.05 weight percent.
The present compositions can be applied to weeds or their locus by the use of conventional ground or aerial dusters, sprayers, and granule applicators, by addition to irrigation or flood water, and by other conventional means known to those skilled in the art.
In some embodiments, the compounds and compositions described herein are applied as a post-emergence application, pre-emergence application, in-water application to flooded paddy rice or water bodies (e.g. , ponds, lakes and streams), or burn-down application.
In some embodiments, the compounds and compositions provided herein are utilized to control weeds in crops, including but not limited to citrus, apple, rubber, oil, palm, forestry, direct-seeded, water-seeded and transplanted rice, wheat, barley, oats, rye, sorghum, corn/maize, pastures, grasslands, rangelands, fallowland, turf, tree and vine orchards, aquatics, or row-crops, as well as non-crop settings, e.g. , industrial vegetation management (IVM) or rights-of-way. In some embodiments, the compounds and compositions are used to control woody plants, broadleaf and grass weeds, or sedges.
In some embodiments, the compounds and compositions provided herein are utilized to control undesirable vegetation in rice. In certain embodiments, the undesirable vegetation is Brachiaria platyphylla (Groseb.) Nash (broadleaf signalgrass, BRAPP), Digitaria sanguinalis (L.) Scop, (large crabgrass, DIGSA), Echinochloa crus-galli (L.) P. Beauv. (barnyardgrass, ECHCG), Echinochloa colonum (L.) LINK (junglerice, ECHCO),
Echinochloa oryzoides (Ard.) Fritsch (early watergrass, ECHOR), Echinochloa oryzicola (Vasinger) Vasinger (late watergrass, ECHPH), Ischaemum rugosum Salisb. (saramollagrass, ISCRU), Leptochloa chinensis (L.) Nees (Chinese sprangletop, LEFCH), Leptochloa fascicularis (Lam.) Gray (bearded sprangletop, LEFFA), Leptochloa panicoides (Presl.) Hitchc. (Amazon sprangletop, LEFPA), Panicum dichotomiflorum (L.) Michx. (fall panicum, PANDI), Paspalum dilatatum Poir. (dallisgrass, PASDI), Cyperus difformis L. (smallflower flatsedge, CYPDI), Cyperus esculentus L. (yellow nutsedge, CYPES), Cyperus iria L. (rice flatsedge, CYPIR), Cyperus rotundus L. (purple nutsedge, CYPRO), Eleocharis species (ELOSS), Fimbristylis miliacea (L.) Vahl (globe fringerush, FIMMI), Schoenoplectus juncoides Roxb. (Japanese bulrush, SCPJU), Schoenoplectus maritimus L. (sea clubrush, SCPMA), Schoenoplectus mucronatus L. (ricefield bulrush, SCPMU), Aeschynomene species, (jointvetch, AESSS), Alternanthera philoxeroides (Mart.) Griseb. (alligatorweed, ALRPH), Alisma plantago-aquatica L. (common waterplantain, ALSPA), Amaranthus species, (pigweeds and amaranths, AMASS), Ammannia coccinea Rottb. (redstem,
AMMCO), Eclipta alba (L.) Hassk. (American false daisy, ECLAL), Heteranthera limosa (SW.) Willd./Vahl (ducksalad, HETLI), Heteranthera reniformis R. & P. (roundleaf mudplantain, HETRE), Ipomoea hederacea (L.) Jacq. (ivyleaf morningglory, IPOHE),
Lindernia dubia (L.) Pennell (low false pimpernel, LIDDU), Monochoria korsakowii Regel & Maack (monochoria, MOOKA), Monochoria vaginalis (Burm. F.) C. Presl ex Kuhth, (monochoria, MOOVA), Murdannia nudiflora (L.) Brenan (doveweed, MUDNU),
Polygonum pensylvanicum L., (Pennsylvania smartweed, POLPY), Polygonum persicaria L. (ladysthumb, POLPE), Polygonum hydropiperoides Michx. (mild smartweed, POLHP), Rotala indica (Willd.) Koehne (Indian toothcup, ROTIN), Sagittaria species, (arrowhead, SAGSS), Sesbania exaltata (Raf.) Cory/Rydb. Ex Hill (hemp sesbania, SEBEX), or Sphenoclea zeylanica Gaertn. (gooseweed, SPDZE).
In some embodiments, the compounds and compositions provided herein are utilized to control undesirable vegetation in cereals. In certain embodiments, the undesirable vegetation is Alopecurus myosuroides Huds. (blackgrass, ALOMY), Apera spica-venti (L.) Beauv. (windgrass, APESV), Avenafatua L. (wild oat, AVEFA), Bromus tectorum L.
(downy brome, BROTE), Lolium multiflorum Lam. (Italian ryegrass, LOLMU), Phalaris minor Retz. (littleseed canary grass, PHAMI), Poa annua L. (annual bluegrass, POAAN), Setaria pumila (Poir.) Roemer & J.A. Schultes (yellow foxtail, SETLU), Setaria viridis (L.) Beauv. (green foxtail, SETVI), Cirsium arvense (L.) Scop. (Canada thistle, CIRAR), Galium aparine L. (catchweed bedstraw, GALAP), Kochia scoparia (L.) Schrad. (kochia, KCHSC), Lamium purpureum L. (purple deadnettle , LAMPU), Matricaria recutita L. (wild chamomile, MATCH), Matricaria matricarioides (Less.) Porter (pineappleweed, MATMT), Papaver rhoeas L. (common poppy, PAPRH), Polygonum convolvulus L. (wild buckwheat, POLCO), Salsola tragus L. (Russian thistle, SASKR), Stellaria media (L.) Vill. (common chickweed, STEME), Veronica persica Poir. (Persian speedwell, VERPE), Viola arvensis Murr. (field violet, VIOAR), or Viola tricolor L. (wild violet, VIOTR). In some embodiments, the compounds and compositions provided herein are utilized to control undesirable vegetation in range and pasture. In certain embodiments, the undesirable vegetation is Ambrosia artemisiijolia L. (common ragweed, AMBEL), Cassia obtusifolia (sickle pod, CASOB), Centaurea maculosa auct. non Lam. (spotted knapweed, CENMA), Cirsium arvense (L.) Scop. (Canada thistle, CIRAR), Convolvulus arvensis L. (field bindweed, CONAR), Euphorbia esula L. (leafy spurge, EPHES), Lactuca serriola L./Torn. (prickly lettuce, LACSE), Plantago lanceolata L. (buckhorn plantain, PLALA), Rumex obtusifolius L. (broadleaf dock, RUMOB), Sida spinosa L. (prickly sida, SIDSP), Sinapis arvensis L. (wild mustard, SINAR), Sonchus arvensis L. (perennial sowthistle, SONAR), Solidago species (goldenrod, SOOSS), Taraxacum officinale G.H. Weber ex
Wiggers (dandelion, TAROF), Trifolium repens L. (white clover, TRFRE), or Urtica dioica L. (common nettle, URTDI).
In some embodiments, the compounds and compositions provided herein are utilized to control undesirable vegetation found in row crops. In certain embodiments, the undesirable vegetation is Alopecurus myosuroides Huds. (blackgrass, ALOMY), Avenajatua L. (wild oat, AVEFA), Brachiaria platyphylla (Groseb.) Nash (broadleaf signalgrass, BRAPP), Digitaria sanguinalis (L.) Scop, (large crabgrass, DIGSA), Echinochloa crus-galli (L.) P. Beauv. (barnyardgrass, ECHCG), Echinochloa colonum (L.) Link (junglerice, ECHCO), Lolium multiflorum Lam. (Italian ryegrass, LOLMU), Panicum dichotomiflorum Michx. (fall panicum, PANDI), Panicum miliaceum L. (wild-proso millet, PANMI), Setaria faberi Herrm. (giant foxtail, SETFA), Setaria viridis (L.) Beauv. (green foxtail, SETVI), Sorghum halepense (L.) Pers. (Johnsongrass, SORHA), Sorghum bicolor (L.) Moench ssp. Arundinaceum (shattercane, SORVU), Cyperus esculentus L. (yellow nutsedge, CYPES), Cyperus rotundus L. (purple nutsedge, CYPRO), Abutilon theophrasti Medik. (velvetleaf, ABUTH), Amaranthus species (pigweeds and amaranths, AMASS), Ambrosia artemisiijolia L. (common ragweed, AMBEL), Ambrosia psilostachya DC. (western ragweed, AMBPS), Ambrosia trijida L. (giant ragweed, AMBTR), Asclepias syriaca L. (common milkweed, ASCSY), Chenopodium album L. (common lambsquarters, CHEAL), Cirsium arvense (L.) Scop. (Canada thistle, CIRAR), Commelina benghalensis L. (tropical spiderwort, COMBE), Datura stramonium L. (jimsonweed, DATST), Daucus carota L. (wild carrot, DAUCA), Euphorbia heterophylla L. (wild poinsettia, EPHHL), Erigeron bonariensis L. (hairy fleabane, ERIBO), Erigeron canadensis L. (Canadian fleabane, ERICA), Helianthus annuus L. (common sunflower, HELAN), Jacquemontia tamnijolia (L.) Griseb. (smallflower morningglory, IAQTA), Ipomoea hederacea (L.) Jacq. (ivyleaf morningglory, IPOHE), Ipomoea lacunosa L. (white morningglory, IPOLA), Lactuca serriola L./Torn. (prickly lettuce, LACSE), Portulaca oleracea L. (common purslane, POROL), Sida spinosa L.
(prickly sida, SIDSP), Sinapis arvensis L. (wild mustard, SINAR), Solanum ptychanthum Dunal (eastern black nightshade, SOLPT), or Xanthium strumarium L. (common cocklebur, XANST).
In some embodiments, application rates of about 1 to about 4,000 grams/hectare (g/ha) are employed in post-emergence operations. In some embodiments, rates of about 1 to about 4,000 g/ha are employed in pre-emergence operations.
In some embodiments, the compounds, compositions, and methods provided herein are used in conjunction with one or more other herbicides to control a wider variety of undesirable vegetation When used in conjunction with other herbicides, the presently claimed compounds can be formulated with the other herbicide or herbicides, tank-mixed with the other herbicide or herbicides or applied sequentially with the other herbicide or herbicides. Some of the herbicides that can be employed in conjunction with the compounds of the present disclosure include: 4-CPA, 4-CPB, 4-CPP, 2,4-D, 2,4-D choline salt, 2,4-D esters and amines, 2,4-DB, 3,4-DA, 3,4-DB, 2,4-DEB, 2,4-DEP, 3,4-DP, 2,3,6-TBA, 2,4,5-T, 2,4,5-TB, acetochlor, acifluorfen, aclonifen, acrolein, alachlor, allidochlor, alloxydim, allyl alcohol, alorac, ametridione, ametryn, amibuzin, amicarbazone, amidosulfuron,
aminocyclopyrachlor, aminopyralid, amiprofos -methyl, amitrole, ammonium sulfamate, anilofos, anisuron, asulam, atraton, atrazine, azafenidin, azimsulfuron, aziprotryne, barban, BCPC, beflubutamid, benazolin, bencarbazone, benfluralin, benfuresate, bensulfuron-methyl, bensulide, benthiocarb, bentazon-sodium, benzadox, benzfendizone, benzipram,
benzobicyclon, benzofenap, benzofluor, benzoylprop, benzthiazuron, bicyclopyrone, bifenox, bilanafos, bispyribac-sodium, borax, bromacil, bromobonil, bromobutide, bromofenoxim, bromoxynil, brompyrazon, butachlor, butafenacil, butamifos, butenachlor, buthidazole, buthiuron, butralin, butroxydim, buturon, butylate, cacodylic acid, cafenstrole, calcium chlorate, calcium cyanamide, cambendichlor, carbasulam, carbetamide,
carboxazole,chlorprocarb, carfentrazone-ethyl, CDEA, CEPC, chlomethoxyfen, chloramben, chloranocryl, chlorazifop, chlorazine, chlorbromuron, chlorbufam, chloreturon, chlorfenac, chlorfenprop, chlorflurazole, chlorflurenol, chloridazon, chlorimuron, chlornitrofen, chloropon, chlorotoluron, chloroxuron, chloroxynil, chlorpropham, chlorsulfuron, chlorthal, chlorthiamid, cinidon-ethyl, cinmethylin, cinosulfuron, cisanilide, clethodim, cliodinate, clodinafop-propargyl, clofop, clomazone, clomeprop, cloprop, cloproxydim, clopyralid, cloransulam-methyl, CMA, copper sulfate, CPMF, CPPC, credazine, cresol, cumyluron, cyanatryn, cyanazine, cycloate, cyclosulfamuron, cycloxydim, cycluron, cyhalofop-butyl, cyperquat, cyprazine, cyprazole, cypromid, daimuron, dalapon, dazomet, delachlor, desmedipham, desmetryn, di-allate, dicamba, dichlobenil, dichloralurea, dichlormate, dichlorprop, dichlorprop-P, diclofop, diclosulam, diethamquat, diethatyl, difenopenten, difenoxuron, difenzoquat, diflufenican, diflufenzopyr, dimefuron, dimepiperate,
dimethachlor, dimethametryn, dimethenamid, dimethenamid-P, dimexano, dimidazon, dinitramine, dinofenate, dinoprop, dinosam, dinoseb, dinoterb, diphenamid, dipropetryn, diquat, disul, dithiopyr, diuron, DMPA, DNOC, DSMA, EBEP, eglinazine, endothal, epronaz, EPTC, erbon, esprocarb, ethalfluralin, ethbenzamide, ethametsulfuron, ethidimuron, ethiolate, ethobenzamid, etobenzamid, ethofumesate, ethoxyfen, ethoxysulfuron, etinofen, etnipromid, etobenzanid, EXD, fenasulam, fenoprop, fenoxaprop, fenoxaprop-P-ethyl, fenoxaprop-P-ethyl + isoxadifen-ethyl, fenoxasulfone, fenteracol, fenthiaprop, fentrazamide, fenuron, ferrous sulfate, flamprop, flamprop-M, flazasulfuron, florasulam, fluazifop, fluazifop-P-butyl, fluazolate, flucarbazone, flucetosulfuron, fluchloralin, flufenacet, flufenican, flufenpyr-ethyl, flumetsulam, flumezin, flumiclorac-pentyl, flumioxazin, flumipropyn, fluometuron, fluorodifen, fluoroglycofen, fluoromidine, fluoronitrofen, fluothiuron, flupoxam, flupropacil, flupropanate, flupyrsulfuron, fluridone, flurochloridone, fluroxypyr, flurtamone, fluthiacet, fomesafen, foramsulfuron, fosamine, furyloxyfen, glufosinate, glufosinate-ammonium, glyphosate, halosafen, halosulfuron-methyl, haloxydine, haloxyfop-methyl, haloxyfop-P-methyl, halauxifen-methyl, hexachloroacetone, hexaflurate, hexazinone, imazamethabenz, imazamox, imazapic, imazapyr, imazaquin, imazethapyr, imazosulfuron, indanofan, indaziflam, iodobonil, iodomethane, iodosulfuron, iofensulfuron, ioxynil, ipazine, ipfencarbazone, iprymidam, isocarbamid, isocil, isomethiozin, isonoruron, isopolinate, isopropalin, isoproturon, isouron, isoxaben, isoxachlortole, isoxaflutole, isoxapyrifop, karbutilate, ketospiradox, lactofen, lenacil, linuron, MAA, MAMA, MCPA esters and amines, MCPA-thioethyl, MCPB, mecoprop, mecoprop-P, medinoterb, mefenacet, mefluidide, mesoprazine, mesosulfuron, mesotrione, metam, metamifop, metamitron, metazachlor, metazosulfuron, metflurazon, methabenzthiazuron, methalpropalin, methazole, methiobencarb, methiozolin, methiuron, methometon, methoprotryne, methyl bromide, methyl isothiocyanate, methyldymron, metobenzuron, metobromuron, metolachlor, metosulam, metoxuron, metribuzin, metsulfuron, molinate, monalide, monisouron, monochloroacetic acid, monolinuron, monuron, morfamquat, MSMA, naproanilide, napropamide, napropamide-M, naptalam, neburon, nicosulfuron, nipyraclofen, nitralin, nitrofen, nitrofluorfen, norflurazon, noruron, OCH, orbencarb, ori/20-dichlorobenzene, orthosulfamuron, oryzalin, oxadiargyl, oxadiazon, oxapyrazon, oxasulfuron, oxaziclomefone, oxyfluorfen, paraflufen-ethyl, parafluron, paraquat, pebulate, pelargonic acid, pendimethalin, penoxsulam, pentachlorophenol, pentanochlor, pentoxazone, perfluidone, pethoxamid, phenisopham, phenmedipham, phenmedipham-ethyl, phenobenzuron, phenylmercury acetate, picloram, picolinafen, pinoxaden, piperophos, potassium arsenite, potassium azide, potassium cyanate, pretilachlor, primisulfuron-methyl, procyazine, prodiamine, profluazol, profluralin, profoxydim, proglinazine, prohexadione-calcium, prometon, prometryn, propachlor, propanil, propaquizafop, propazine, propham, propisochlor, propoxycarbazone, propyrisulfuron, propyzamide, prosulfalin, prosulfocarb, prosulfuron, proxan, prynachlor, pydanon, pyraclonil, pyraflufen, pyrasulfotole, pyrazogyl, pyrazolynate, pyrazosulfuron-ethyl, pyrazoxyfen, pyribenzoxim, pyributicarb, pyriclor, pyridafol, pyridate, pyriftalid, pyriminobac, pyrimisulfan, pyrithiobac-methyl, pyroxasulfone, pyroxsulam, quinclorac, quinmerac, quinoclamine, quinonamid, quizalofop, quizalofop-P-ethyl, rhodethanil, rimsulfuron, saflufenacil, S-metolachlor, sebuthylazine, secbumeton, sethoxydim, siduron, simazine, simeton, simetryn, SMA, sodium arsenite, sodium azide, sodium chlorate, sulcotrione, sulfallate, sulfentrazone, sulfometuron, sulfosate, sulfosulfuron, sulfuric acid, sulglycapin, swep, TCA, tebutam, tebuthiuron, tefuryltrione, tembotrione, tepraloxydim, terbacil, terbucarb, terbuchlor, terbumeton, terbuthylazine, terbutryn, tetrafluron, thenylchlor, thiazafluron, thiazopyr, thidiazimin, thidiazuron, thiencarbazone-methyl, thifensulfuron, thiobencarb, tiocarbazil, tioclorim, topramezone, tralkoxydim, triafamone, tri-allate, triasulfuron, triaziflam, tribenuron, tricamba, triclopyr esters and amines, tridiphane, trietazine, trifloxysulfuron, trifluralin, triflusulfuron, trifop, trifopsime, trihydroxytriazine, trimeturon, tripropindan, tritac, tritosulfuron, vernolate and xylachlor.
The compounds and compositions of the present disclosure can generally be employed in combination with known herbicide safeners, such as benoxacor, benthiocarb, brassinolide, cloquintocet (e.g. , mexyl), cyometrinil, daimuron, dichlormid, dicyclonon, dimepiperate, disulfoton, fenchlorazole-ethyl, fenclorim, flurazole, fluxofenim, furilazole, harpin proteins, isoxadifen-ethyl, mefenpyr-diethyl, MG 191, MON 4660, naphthalic anhydride (NA), oxabetrinil, R29148 and N-phenylsulfonylbenzoic acid amides, to enhance their selectivity.
The compounds, compositions, and methods described herein be used to control undesirable vegetation on glyphosate-tolerant-, glufosinate-tolerant-, dicamba-tolerant-, phenoxy auxin- tolerant-, pyridyloxy auxin- tolerant-, aryloxyphenoxypropionate-tolerant-, acetyl CoA carboxylase (ACCase) inhibitor- tolerant-, imidazolinone-tolerant-, acetolactate synthase (ALS) inhibitor- tolerant-, 4-hydroxyphenyl-pyruvate dioxygenase (HPPD) inhibitor -tolerant-, protoporphyrinogen oxidase (PPO) inhibitor -tolerant-, triazine-tolerant-, and bromoxynil-tolerant- crops (such as, but not limited to, soybean, cotton, canola/oilseed rape, rice, cereals, corn, turf, etc), for example, in conjunction with glyphosate, glufosinate, dicamba, phenoxy auxins, pyridyloxy auxins, aryloxyphenoxypropionates, ACCase inhibitors, imidazolinones, ALS inhibitors, HPPD inhibitors, PPO inhibitors, triazines, and bromoxynil. The compositions and methods may be used in controlling undesirable vegetation in crops possessing multiple or stacked traits conferring tolerance to multiple chemistries and/or inhibitors of multiple modes-of-action.
The compounds and compositions provided herein may also be employed to control herbicide resistant or tolerant weeds. Exemplary resistant or tolerant weeds include, but are not limited to, biotypes resistant or tolerant to ALS inhibitors, photosystem II inhibitors, ACCase inhibitors, synthetic auxins, photosystem I inhibitors, 5-enolpyruvylshikimate-3- phosphate (EPSP) synthase inhibitors, microtubule assembly inhibitors, lipid synthesis inhibitors, PPO inhibitors, carotenoid biosynthesis inhibitors, very long chain fatty acid
(VLCFA) inhibitors, phytoene desaturase (PDS) inhibitors, glutamine synthetase inhibitors, HPPD inhibitors, mitosis inhibitors, cellulose biosynthesis inhibitors, herbicides with multiple modes-of-action such as quinclorac, and unclassified herbicides such as arylaminopropionic acids, difenzoquat, endothall, and organoarsenicals. Exemplary resistant or tolerant weeds include, but are not limited to, biotypes with resistance or tolerance to multiple herbicides, multiple chemical classes, and multiple herbicide modes-of-action.
The described embodiments and following examples are for illustrative purposes and are not intended to limit the scope of the claims. Other modifications, uses, or combinations with respect to the compositions described herein will be apparent to a person of ordinary skill in the art without departing from the spirit and scope of the claimed subject matter.
EXAMPLES
SYNTHESIS OF PRECURSORS Example 1: Preparation of 4-bromo-3-(dibromomethyl)benzonitrile (Compound CI)
Figure imgf000025_0001
To a solution of 3-methyl-4-bromobenzonitrile (15 grams (g), 0.076 moles (mol)) in carbon tetrachloride were added azobisisobutyronitrile (AIBN; 3.1 g, 0.019 mol) and N- bromosuccinimide (NBS; 40.6 g, 0.23 mol) at room temperature. The resulting mixture was stirred at reflux at 80 °C for 24 hours (h) and then allowed to cool to room temperature. The reaction mass was diluted with ethyl acetate (EtOAc), and the solution was washed with water (H2O) and brine solution, dried over sodium sulfate (Na2S04) and concentrated to a brown oil. Purification by column chromatography (silica (S1O2); 230-400 mesh) provided the title compound as colorless solid (18 g, 69%): mp 82-85 °C; ¾ NMR (400 MHz, CDCb) δ 8.31 (d, / = 2.0 Hz, 1H), 7.66 (d, 7 = 8.3 Hz, 1H), 7.45 (dd, J = 8.3, 2.0 Hz, 1H), 7.29 - 7.24 (m, 1H), 7.00 (s, 1H); EIMS m/z 353.
Example 2: Preparation of of 4-bromo-3-formylbenzonitrile (Compound C2)
Figure imgf000025_0002
To a solution of 4-bromo-3-(dibromomethyl)benzonitrile (18 g, 0.051 mol) in ethanol (EtOH; 200 milliliters (mL)) at 60 °C was added dropwise a solution of silver nitrate (AgN03; 21.8 g, 0.128 mol) in H20 (100 mL). The temperature was increased to 75 °C, and the mixture was stirred at reflux for 6 h. After allowing to cool to room temperature, the reaction mass was filtered and subsequently washed with EtOAc. The organic layer was washed with H2O and brine, dried over Na2S04 and concentrated. The yellow-colored crude material was triturated with n-hexane to provide the title compound as a yellow solid (8.5 g, 85%): mp 138-141 °C; ¾ NMR (400 MHz, CDCh) δ 10.35 (d, / = 0.6 Hz, 1H), 8.18 (dd, / = 2.1, 0.5 Hz, 1H), 7.86 - 7.79 (m, 1H), 7.74 - 7.65 (m, 1H); EIMS m/z 210. Example 3: Preparation of 4-bromo-3-(hydroxymethyl)benzonitrile (Compound C3)
Figure imgf000026_0001
To a solution of 4-bromo-3-formylbenzonitrile (1 g, 0.0047 mol) in methanol (10 mL) was added sodium borohydride(NaBH4; 0.18 g, 0.0047 mol) in portions, and the resulting mixture was stirred at 0 °C for 30 minutes (min). The reaction was quenched with saturated ammonium chloride (NH4C1) solution, and the mixture was concentrated under vacuum to remove the methanol. The resulting mass was dissolved in EtOAc, and the organic layer was washed with ¾0 and brine, dried over Na2S04 and concentrated. Trituration of the colorless solid which was obtained with n-hexane provided the title compound as white solid (0.9 g, 90%): mp: 131-133° C; ¾ NMR (400 MHz, CDCb) δ 7.86 (dt, J = 1.8, 0.9 Hz, 1H), 7.67 (d, / = 8.1 Hz, 1H), 7.45 (ddt, / = 8.2, 2.0, 0.7 Hz, 1H), 4.79 (s, 2H).
Example 4: Preparation of 4-bromo-3-(l-hydroxyethyl)benzonitrile (Compound C4)
Figure imgf000026_0002
To a solution of 4-bromo-3-formylbenzonitrile (1 g, 0.0047 mol) in dry
tetrahydrofuran (THF) at 0 °C was added methylmagnesium chloride (3 molar (M) solution in diethyl ether (Et20); 0.38 g, 0.0051 mol). The reaction mixture was stirred at 0 °C for 2 h and was then quenched with saturated NH4C1 and extracted with EtOAc. The organic layer was washed with H2O and brine, dried over Na2S04 and concentrated. Purification by flash column chromatography (S1O2; gradient of 0-20% EtOAc in hexane) yielded the title compound as a white solid (0.72 g, 72%).
Compounds C5-C7 in Table 1 were made in accordance with the procedure disclosed in Example 4. Table 1: Structures and Analytical Data
- - (d,
(d,
Figure imgf000027_0001
Example 5: Preparation of 4-bromo-3-((methoxymethoxy)methyl)benzonitrile
(Compound C8)
Figure imgf000028_0001
To a solution of 4-bromo-3-(l -hydroxy ethyl)benzonitrile (0.95 g, 0.0045 mol) in dichloromethane (CH2CI2; 10 mL) at 0 °C were added NN-diisopropylethylamine (DIPEA; 2.0 g, 0.0157 mol) and methyl chloromethyl ether (MOMCl; 0.72 g, 0.009 mol) slowly. The resulting mixture was stirred at room temperature overnight. The reaction mass was quenched with H2O and extracted with CH2CI2. The organic layer was washed with H2O and brine, dried over Na2S04 and concentrated to provide the crude product. Purification by flash column chromatography (S1O2; gradient of 0-15 % EtOAc in hexane) gave the title compound as a colorless oil (1 g, 90%).
Compounds C9-C12 in Table 2 were made in accordance with the procedures disclosed in Example 5.
Table 2: Structures and Analytical Data
Figure imgf000029_0001
Example 6: Preparation of 2-(5,5-dimethyl-l,3,2-dioxaborinan-2-yl)-4,5- dimethoxybenzaldehyde (Compound C13)
Figure imgf000030_0001
To 2-bromo-4,5-dimethoxybenzaldehyde (2.0 g, 8.16 millimoles (mmol)), 5, 5,5', 5'- tetramethyl-2,2'-bi(l,3,2-dioxaborinane) (2.120 g, 9.39 mmol) and potassium acetate (2.403 g, 24.48 mmol), which had been degassed by vacuum and back-filled with nitrogen (3x), was added dioxane (20 mL). The reaction mixture was then evacuated and back-filled with nitrogen (3x). [l,l'-Bis(diphenylphosphino)ferrocene]dichloropalladium(II) (Pd(dppf)Cl2; 0.666 g, 0.816 mmol) was added, and the reaction mixture was evacuated and back-filled with nitrogen again. The orange/red reaction mixture was heated for 2 h at 70 °C and then stirred under nitrogen overnight. The reaction mixture was diluted with EtOAc and filtered through Celite™, and the filter cake was washed with additional EtOAc. The solvent was concentrated to yield a dark red oil. Purification by flash column chromatography (SiC ; gradient of 0-100% EtOAc in hexane) furnished the title compound as a deep purple oil (2.23 g, 98%).
Compounds C14-C15 in Table 3 were made in accordance with the procedures disclosed in Example 6. In the case of C14 and C15, the reaction mixtures were stirred at 70 °C overnight.
Table 3: Structures and Analytical Data
Figure imgf000030_0002
Figure imgf000031_0001
Example 7: Preparation of 3-ethynyl-5-fluorobenzo[c][l,2]oxaborol-l(3H)-ol
(Compound C16)
Figure imgf000031_0002
A suspension of (4-fluoro-2-formylphenyl)boronic acid (4 g, 23.82 mmol) and 2,3- dimethylbutane-2,3-diol hexahydrate (5.39 g, 23.82 mmol) in benzene (70 mL) were stirred at reflux under nitrogen for 14 h, and the water was removed via azeotrope with a Dean-Stark apparatus. The mixture was cooled, concentrated under reduced pressure, and taken up in hexane (120 mL). The solution was washed with ¾0 (4 x 120 mL) and brine (70 mL), dried over magnesium sulfate (MgS04), and concentrated under reduced pressure to leave a yellow liquid. White prisms of the title compound (1.48 g, 24.9%), which appeared upon standing at room temperature for 14 h, were collected by filtration. Three crops were collected (4.69 g, 75%): mp 66-67 °C; ¾ NMR (400 MHz, DMSO-ifc) δ 10.39 (d, / = 2.6 Hz, 1H), 7.83 (dd, / = 8.3, 5.9 Hz, 1H), 7.66 (dd, / = 9.5, 2.6 Hz, 1H), 7.55 (td, / = 8.5, 2.7 Hz, 1H), 1.34 (s, 12H); 19F NMR (376 MHz, DMSO-ifc) δ -108.72; 13C NMR (101 MHz, DMSO-ifc) δ 192.91, 164.87, 162.38, 143.29, 143.22, 137.71, 137.63, 120.27, 120.07, 114.07, 113.86, 84.20, 24.48.
Example 8: Preparation of l-(6-bromobenzo[rf][l,3]dioxol-5-yl)ethanol (Compound C17)
Figure imgf000032_0001
6-Bromobenzo[J][l,3]dioxole-5-carbaldehyde (1 g, 4.37 mmol) was dissolved in THF (20 mL), and the solution was cooled to -78 °C in a dry ice/acetone bath. Methylmagnesium bromide (3.0 M in Et20; 1.145 g, 9.61 mmol) was added in one portion, and the reaction mixture was allowed to stir for 45 min. Triisopropyl borate (0.821 g, 4.37 mmol) was added, and the reaction mixture was allowed to warm to room temperature while stirring overnight. The mixture was diluted with 2 normal (N) sodium hydroxide (NaOH) and Et20. The aqueous solution was made acidic and extracted with EtiO. None of the desired oxaborole product was identified by gas chromatography-mass spectrometry (GC-MS) in the second EtiO wash. The title compound was present in first Et20 wash, which was concentrated. Purification by flash column chromatography (SiC ; gradient of 0-100% EtOAc in hexane) furnished the title compound as a white solid (725 mg, 67%): mp 53-55 °C; Ή NMR (400 MHz, DMSO-ifc) δ 7.12 (s, 1H), 7.08 (s, 1H), 6.04 (dd, J = 15.5, 1.0 Hz, 2H), 5.35 (d, / = 4.2 Hz, 1H), 4.87 (qd, / = 6.3, 4.2 Hz, 1H), 1.24 (d, / = 6.3 Hz, 3H); EIMS m/z 244.
SYNTHESIS OF INVENTIVE COMPOUNDS
Example 9: Preparation of l-hydroxy-l,3-dihydrobenzo[c][l,2]oxaborole-5-carbonitrile (Compound C18)
Figure imgf000032_0002
To a solution of 4-bromo-3-((methoxymethoxy)methyl)benzonitrile (0.9 g, 0.0035 mol) in dry THF (10 mL) was added triisopropylborate (0.79 g, 0.0043 mol). The reaction mixture was cooled to -78 °C in a dry ice/acetone bath, and a cold solution of n-butyllithium (2.5 M in hexane; 1.7 mL, 0.0043 mol) was added slowly over a period of 30 min. The temperature of the reaction was allowed to reach room temperature gradually. After 30 min stirring at room temperature, the reaction mixture was quenched with 2 N hydrochloric acid (HC1) and extracted with EtOAc. The organic layer was washed with ¾0 and brine, dried over Na2S04 and concentrated to provide the crude product. Recrystallization from an EtOAc and hexane mixture gave the title compound as colorless solid (0.27 g, 50%).
Example 10: Preparation of l-hydroxy-l,3-dihydrobenzo[c][l,2]oxaborole-5-carboxylic acid (Compound C19)
Figure imgf000033_0001
A solution of l-hydroxy-l,3-dihydrobenzo[c][l,2]oxaborole-5-carbonitrile (0.2 g, 1.3 mmol) in concentrated HCl (20 mL) was stirred at reflux at 100 °C for 4 h. The mixture was cooled to room temperature, and the solid that was obtained was filtered and dried to provide the title compound as a colorless solid (0.19 g, 86%).
Example 11: Preparation of 3-(4-chlorophenyl)-l-hydroxy-l,3- dihydrobenzo[c][l,2]oxaborole-5-carboxamide (Compound F21)
Figure imgf000033_0002
This procedure is based upon one by Matsubara, H.; Seto, K; Tahara, T.; Takahashi,
S. Bull. Chem. Soc. Jpn. 1989, 62, 3896-3901. A suspension of 1 -hydroxy- 1,3- dihydrobenzo[c][l,2]oxaborole-5-carboxylic acid (0.07 g, 0.393 mmol) and thionyl chloride (2 mL, 27.4 mmol) in 1 ,2-dichloroethane (2 mL) was heated to gentle reflux under nitrogen for 14 h. The mixture was cooled to ambient temperature, concentrated under reduced pressure, suspended in 1 ,2-dichloroethane (5 mL), and again concentrated under reduced pressure. The residue was suspended in THF (2 mL), cooled in an ice bath and treated with aqueous ammonium hydroxide (NH4OH, 38%; 0.3 mL). The reaction mixture was allowed to warm to room temperature over 4 h, diluted with H2O (30 mL), and washed with EtOAc (30 mL). The aqueous layer was made acidic (pH 3) with 0.5 N HCl and extracted with EtOAc (2 x 20 mL). The combined organic extracts were washed with H2O (40 mL) and brine (20 mL), dried over MgSC , concentrated under reduced pressure and dried in vacuo at 43 °C for 5 h to leave a brown semi-solid. Purification by reversed phase chromatography (SiC ; gradient of acetonitrile in H2O) provided the desired product as a white solid (5 mg, 7%).
Example 12: Preparation of 5,6-dimethoxy-3-(prop-l-yn-l-yl)benzo[c][l,2]oxaborol- l(3H)-ol (Compound F2)
Figure imgf000034_0001
To a solution of 2-(5,5-dimethyl-l,3,2-dioxaborinan-2-yl)-4,5- dimethoxybenzaldehyde (0.200 g, 0.719 mmol) in THF (3 mL) cooled to -78 °C in a dry ice/acetone bath under nitrogen was added prop-l-yn-l-ylmagnesium bromide (0.5 M in THF; 2.88 mL, 1.438 mmol) dropwise so as to maintain the internal temperature below -65 °C. The reaction mixture was stirred under nitrogen at -78 °C for 30 min. The cooling bath was removed, and the mixture was stirred for 2 h under nitrogen while warming to room temperature. Then, 2 N NaOH (3 mL) was added via syringe, and the hazy reaction mixture was stirred for 2 h under nitrogen at room temperature. The mixture was diluted with Et20 and H2O. The aqueous layer was separated and washed with Et20 (2x). The aqueous layer was made acidic (pH 1-2) with concentrated HC1 and extracted with EtiO (2x). The combined ether extracts were dried over MgSOz)., filtered and concentrated in vacuo to yield a solid, which was triturated with hexanes and collected via vacuum filtration, washing the solid with more hexanes. The solid was air-dried to provide the title compound as a pale pink solid (120 mg, 72%).
Example 13: Preparation of 5,6-dimethoxy-3-phenylbenzo[c][l,2]oxaborol-l(3H)-ol (Compound F32)
Figure imgf000035_0001
To a solution of 2-(5,5-dimethyl-l,3,2-dioxaborinan-2-yl)-4,5- dimethoxybenzaldehyde (0.200 g, 0.719 mmol) in THF (3 mL) cooled to -78 °C in a dry ice/acetone bath under nitrogen was added phenyllithium (1.8 M in dibutyl ether; 0.60 mL, 1.079 mmol) dropwise so as to maintain the internal temperature below -65 °C. The reaction mixture was stirred under nitrogen at -78 °C for 30 min. The cooling bath was removed, and the mixture was stirred for 2 h under nitrogen while warming to room temperature. Then, 2 N NaOH (3 mL) was added via syringe, and the hazy reaction mixture was stirred for 2 h under nitrogen at room temperature. The mixture was diluted with Et20 and H2O. The aqueous layer was separated and washed with EtiO (2x). The aqueous layer was made acidic (pH 1-2) with concentrated HC1 and extracted with EtiO (2x). The combined ether extracts were dried over MgSOz)., filtered and concentrated in vacuo to yield a solid, which was triturated with hexanes and collected via vacuum filtration, washing the solid with more hexanes. The solid was air-dried to provide the title compound as a pale pink solid (82 mg, 42%).
Example 14: Preparation of l-hydroxy-3-phenyl-l,3-dihydrobenzo[c][l,2]oxaborole-5- carbonitrile (Compound F33)
Figure imgf000035_0002
To a solution of 4-(5,5-dimethyl-l,3,2-dioxaborinan-2-yl)-3-formylbenzonitrile
(0.202 g, 0.831 mmol) in THF (4 mL) cooled to -78 °C in a dry ice/acetone bath under nitrogen was added phenyllithium (1.8 M in dibutyl ether; 0.693 mL, 1.247 mmol) dropwise over 5 min. The reaction mixture was warmed to room temperature and stirred for 2 h. To the reaction flask was added 2 N NaOH (3 mL) via syringe, and the reaction mixture was stirred overnight under nitrogen. The mixture was diluted with EtiO, and the aqueous layer was washed with Et20. The aqueous layer was made acidic (pH 1) with concentrated HCl and extracted with EtiO (2x). The combined ether extracts were dried over MgSOz)., filtered and concentrated in vacuo to yield a pale yellow clear oil. The oil was treated with
EtiO/hexanes and EtOAc/hexanes to afford a pale yellow solid which was collected via decanting of the mother liquor. The title compound (48 mg, 23%) was isolated as a pale yellow solid after drying under house vacuum.
Example 15: Preparation of 5-chloro-4-fluoro-3-methylbenzo[c][l,2]oxaborol-l(3H)-ol (Compound F10)
Figure imgf000036_0001
To a solution of 6-bromo-3-chloro-2-fluorobenzaldehyde (1 g, 4.21 mmol) in THF (20 mL) cooled to -78 °C in a dry ice/acetone bath was added in one portion methyllithium (1.6 M in Et20; 0.204 g, 9.26 mmol). The cooling bath was immediately removed, and the reaction mixture was allowed to warm to 20 °C. After 10 min at 20 °C, the reaction mixture was cooled to -78 °C in a dry ice/acetone bath, and triisopropyl borate (0.792 g, 4.21 mmol) was added in one portion. The cold bath was removed, and stirring was continued for 12 h. A 2 N NaOH solution (50 mL) was added to the reaction mixture, and the mixture was allowed to stir for 2 h. The reaction mixture was diluted with Et20 (50 mL). The organic phase was discarded, and the aqueous phase was made acidic (pH 3) using concentrated HCl. The mixture was extracted with Et20 (50 mL), and the organic layer was dried over MgSC and filtered. Concentration of the organic solution yielded a yellow oil which was triturated with hexanes to yield the title compound as a tan solid (68 mg, 8%).
Example 16: Preparation of 3-methylbenzo[c][l,2]oxaborol-l(3H)-ol (Compound F16)
Figure imgf000036_0002
To a solution of (2-formylphenyl)boronic acid (1 g, 6.67 mmol) in THF (20 mL) cooled to -78 °C in a dry ice/acetone bath was added in one portion methylmagnesium bromide (0.954 g, 8.00 mmol). The cooling bath was removed, and after 12 h of stirring, the reaction was quenched with ¾0 (10 mL). The pH was lowered to 2 by the addition of concentrated HC1. The aqueous layer was extracted with EtOAc (2 x 50 mL), and the combined organic extracts were dried over Na2S04 and filtered. Purification by flash column chromatography (S1O2; gradient of 0-100% EtOAc in hexanes gradient) provided the title compound as a yellow oil (187 mg, 18%).
Example 17: Preparation of 3-ethynyl-5-fluorobenzo[c][l,2]oxaborol-l(3H)-ol
(Compound F28)
Figure imgf000037_0001
To a solution of 5-fluoro-2-(4,4,5,5-tetramethyl-l,3,2-dioxaborolan-2- yl)benzaldehyde (1.0 g, 4 mmol) in THF (10 mL) was added a solution of ethynylmagnesium bromide (0.5 M solution in THF; 10.4 mL, 5.2 mmol), in order to maintain a temperature below -65 °C. The reaction mixture was stirred at -78 °C for 1 h, was warmed to room temperature, cooled to -78 °C and treated with dilute NaOH (0.1 N; 12 mL). The temperature spiked briefly to -25 °C, and the mixture was cooled to -78 °C for 45 min. The cooling bath was removed, and the reaction mixture was warmed to ambient temperature for 1 h. The mixture was extracted with Et20 (150 mL), and the organic layer was washed with brine (80 mL), dried over MgS04 and concentrated under reduced pressure to leave a yellow gum. The aqueous layer was cooled in an ice bath, made acidic (pH 4) with 0.2 N HC1, and extracted with Et20 (3 x 150 mL). The organic layer was washed with brine (100 mL), dried over MgS04, concentrated under reduced pressure, and trituated with CH2Ch/hexanes to leave a white solid which was collected by filtration (190 mg isolated). The aqueous layer was then extracted with EtOAc (3 x 150 mL). The combined organic layers were washed with brine (100 mL), dried over MgS04, and concentrated under reduced pressure to leave a yellow gum which was purified using reverse phase chromatography (S1O2; gradient of acetonitrile in H2O). The major fraction was concentrated under reduced pressure, extracted with EtOAc, washed with brine, dried over MgS04, concentrated under reduced pressure and
recrystallized from EtOAc/hexanes to afford fluffy, yellowish needles (144 mg isolated). The mother liquor was left at 4 °C for 2 h to precipitate additional material as fluffy yellowish needles (72 mg isolated). The mother liquor was concentrated under reduced pressure and the residue was recrystallized from EtOAc/hexanes to afford a white solid (63 mg isolated). Total yield 469 mg (65%). Example 18: Preparation of 5-fluoro-l-hydroxy-l,3-dihydrobenzo[c][l,2]oxaborole-3- carbonitrile (Compound F13)
Figure imgf000038_0001
This procedure is based upon Xia, Y. et al. PCT Int. Appl. WO2009140309 A2, 2009. A solution of sodium cyanide (NaCN; 58.4 mg, 1.19 mmol) in ¾0 (1 mL) was added to a stirred solution of (4-fluoro-2-formylphenyl)boronic acid (Aldrich; 200 mg, 1.19 mmol) in THF (1.5 mL) at room temperature. The mixture was stirred for 64 h. 2 N HCl was added to bring the pH to 3, and the reaction mixture was stirred at ambient temperature for 30 min. The mixture was extracted with EtOAc (3 x 15 mL), and the combined organic extracts were washed with H2O (30 mL) and brine (10 mL), dried over MgSC and concentrated under reduced pressure. After multiple unsuccessful recrystallization attempts (from
EtOAc/hexanes and EtiO/hexanes), the concentrated residue was left at 4 °C for 14 h. The title compound was isolated as a yellow solid upon drying in vacuo at ambient temperature for 5 h (151 mg, 67%). Example 19: Preparation of ethyl 5-fluoro-l-hydroxy-l,3- dihydrobenzo[c][l,2]oxaborole-3-carboxylate (Compound F9)
Figure imgf000038_0002
This procedure is based upon Xia, Y. et al. PCT Int. Appl. WO2009140309 A2, 2009. A mixture of 5-fluoro-l-hydroxy-l,3-dihydrobenzo[c][l,2]oxaborole-3-carbonitrile (0.07 g, 0.396 mmol) and HCl (12 N; 0.5 mL) in H20 (7 μί) was added to ethanol (4 mL). The reaction mixture was heated to reflux under nitrogen, stirred for 3 h and cooled to ambient temperature. The mixture was treated with concentrated HC1 (12 N; 0.2 mL) and allowed to stir at room temperature under nitrogen for 14 h. The reaction mixture was poured into ¾0 (30 mL), cooled in an ice bath, made basic (pH 12) with 2 N NaOH, made acidic (pH 4) with 2 N HC1 and extracted with EtOAc (2 x 25 mL). The combined organic extracts were washed with brine (30 mL), dried over MgSC , concentrated under reduced pressure, and dried in vacuo at ambient temperature for 14 h. Recrystallization from EtOAc/hexanes afforded the title compound as a white solid (17 mg, 19%). The mother liquor was concentrated under reduced pressure and dried in vacuo at room temperature for 14 h to leave a waxy pink solid which contained additional less pure material (40 mg, 45%).
Example 20: Preparation of 3-methyl-[l,3]dioxolo[4',5':4,5]benzo[l,2-c][l,2]oxaborol- l(3H)-ol (Compound F31)
Figure imgf000039_0001
[0001] To a solution of l-(6-bromobenzo[J|[l,3]dioxol-5-yl)ethanol (500 mg, 2.040 mmol) in THF (10 mL) cooled to -78 °C in a dry ice/acetone bath was added in one portion n-butyllithium (2.5 M in hexanes; 327 mg, 5.10 mmol). The cooling bath was immediately removed, and the reaction mixture was allowed to warm to 20 °C. After 10 min at 20 °C, the reaction was cooled to -78 °C in a dry ice/acetone bath and triisopropyl borate (384 mg, 2.040 mmol) was added in one portion. The cold bath was removed, and stirring was continued for 12 h. A 2 N NaOH solution (50 mL) was added to the reaction mixture, and the mixture was allowed to stir for 2 h. The reaction mixture was diluted with Et20. The organic phase was discarded, and the aqueous phase was made acidic (pH 3) using concentrated HC1. The mixture was extracted with EtiO, and the organic layer was dried over MgSC and filtered. Concentration of the organic solution yielded a yellow oil which was triturated with hexanes to yield the title compound as a light brown solid (134 mg, 34%). Table 4: Compound Number, Structure, Appearance, and Preparation Method
Figure imgf000040_0001
Figure imgf000041_0001
-40-
Figure imgf000042_0001
Figure imgf000043_0001
-42-
Figure imgf000044_0001
-43-
Figure imgf000045_0001
Figure imgf000046_0001
Figure imgf000047_0001
Table 5. Analytical Data for Compounds in Table 4
Figure imgf000047_0002
Commp
pound IR (cm-1) MASS NMR Data
(°C)
No.
¾ NMR (400 MHz, DMSO-ifc) δ 9.78
ESIMS
159- (s, 1H), 7.96 - 7.81 (m, 3H), 5.94 (td, /
F6 - m/z 198
161 = 2.5, 1.6 Hz, 1H), 1.85 (d, / = 2.3 Hz,
([M+H]+)
3H)
¾ NMR (400 MHz, DMSO-ifc) δ 9.75
ESIMS
138- (s, 1H), 8.15 (dd, / = 1.7, 0.8 Hz, 1H),
F7 - m/z 234
140 7.87 (dd, J = 8.0, 1.6 Hz, 1H), 7.47 - ([M-H]-)
7.22 (m, 6H), 6.31 (s, 1H)
lH NMR (400 MHz, DMSO-ifc) δ 9.34 (s, 1H), 7.66 (d, 7 = 8.1 Hz, 1H), 7.49 -
ESIMS
126- 7.42 (m, 2H), 7.43 - 7.33 (m, 3H), 7.06
F8 - m/z 265
130 (dt, / = 2.3, 0.7 Hz, 1H), 7.00 (ddd, / =
([M+H]+)
8.1, 2.2, 0.6 Hz, 1H), 6.10 (d, / = 0.8 Hz, 1H), 3.83 (s, 3H)
¾ NMR (400 MHz, DMSO-ifc) δ 9.70 (s, 1H), 7.79 (m, 1H), 7.28 (m, 2H), 5.78 (s, 1H), 4.18 (m, 2H), 1.23 (t, / = 7.1 Hz, 3H);
IR (ATR) 1737, ESIMS
105- 13C NMR (101 MHz, DMSO-ifc) δ
F9 1436, 1220, 1088 m/z 223
107 169.1, 165.4, 163.0, 153.6, 153.5, 133.0, cm"1 ([M-H]")
132.9, 116.0, 115.8, 109.0, 108.8, 77.7, 77.6, 61.2, 13.9;
19F NMR (376 MHz, DMSO-ifc) δ -108.8
lH NMR (400 MHz, DMSO-ifc) δ 9.47 (s, 1H), 7.60 - 7.51 (m, 2H), 5.41 (q, / =
94- 6.6 Hz, 1H), 1.46 (dd, / = 6.6, 0.8 Hz,
F10 - - 98 3H)
19F NMR (376 MHz, DMSO-ifc) δ -124.74
IR (ATR) 2230, ESIMS ¾ NMR (600 MHz, DMSO-ifc) δ 9.97
163-
Fl l 2130, 1446, 1023, m/z 183 (br, 1H), 8.15 (m, 1H), 7.92 (s, 2H), 166
998 cm 1 ([M-H]") 6.28 (s, 1H)
lH NMR (400 MHz, DMSO-ifc) δ 9.34 (s, 1H), 7.67 (d, / = 8.1 Hz, 1H), 7.50
ESIMS
109- (td, / = 7.6, 1.2 Hz, 1H), 7.39 - 7.24 (m,
F12 - m/z 325
111 3H), 6.94 (dd, / = 8.2, 2.2 Hz, 1H), 6.75
([M+H]+)
(d, J = 2.1 Hz, 1H), 6.19 (s, 1H), 3.72 (s, 3H)
¾ NMR (400 MHz, DMSO-ifc) δ 10.03 (s, 1H), 7.85 (dd, / = 8.2, 5.7 Hz, 1H),
IR (ATR) 2257, 7.55 (dd, / = 8.9, 2.2 Hz, 1H), 7.37
98-
F13 2130, 1440, 1023, - (ddd, / = 10.0, 8.1, 2.3 Hz, 1H), 6.28 (s, 103
956 cm 1 1H);
13C NMR (101 MHz, DMSO-ifc) δ 191.3, 164.1, 161.6, 149.8, 149.8, 131.7, Commp
pound IR (cm4) MASS NMR Data
(°C)
No.
131.6, 118.2, 116.0, 115.3, 115.1, 107.9,
107.6, 65.1, 65.1, 19.0, 12.3;
19F NMR (376 MHz, DMSO-ifc) δ
-107.67
¾ NMR (400 MHz, DMSO-ifc) δ 9.43
(s, 1H), 7.91 (dt, 7 = 7.8, 0.9 Hz, 1H),
7.82 (dq, 7 = 1.5, 0.9 Hz, 1H), 7.74 -
113-
F14 - - 7.65 (m, 1H), 5.31 (q, 7 = 6.6 Hz, 1H), 116
1.45 (d, 7 = 6.6 Hz, 3H)
19F NMR (376 MHz, DMSO-ifc) δ
-60.81
lH NMR (400 MHz, DMSO-ifc) δ 9.21 (s, 1H), 7.66 (d, 7 = 8.1 Hz, 1H), 7.39 -
ESIMS
121- 7.32 (m, 2H), 7.29 (tt, 7 = 7.8, 1.4 Hz,
F15 - m/z 241
123 3H), 6.92 (ddd, 7 = 8.2, 2.2, 0.6 Hz,
([M+H]+)
1H), 6.67 (dt, 7 = 2.2, 0.7 Hz, 1H), 6.10 (s, 1H), 3.71 (s, 3H)
lH NMR (400 MHz, CDCh) δ 7.73 (dt, 7 = 7.4, 1.0 Hz, 1H), 7.49 (td, 7 = 7.5, 1.2 Hz, 1H), 7.37 (tt, 7 = 7.3, 0.8 Hz,
EIMS m/z 1H), 7.30 (dq, 7 = 7.6, 0.8 Hz, 1H), 5.34
F16 - - 146 (q, 7 = 6.7 Hz, 1H), 5.16 (s, 1H), 1.53
([M-H]") (d, 7 = 6.6 Hz, 3H);
13C NMR (101 MHz, CDCh) δ 158.44, 131.07, 130.40, 127.30, 120.96, 78.25, 22.27
¾ NMR (400 MHz, DMSO-ifc) δ 9.84
ESIMS (s, 1H), 8.11 (t, 7 = 1.2 Hz, 1H), 8.00
188-
F17 - m/z 184 (dd, 7 = 8.0, 1.6 Hz, 1H), 7.68 (dt, 7 = 190
([M+H]+) 8.0, 0.9 Hz, 1H), 6.05 (dd, 7 = 2.3, 0.8
Hz, 1H), 3.73 (d, 7 = 2.3 Hz, 1H)
¾ NMR (300 MHz, DMSO-ifc) δ 9.90
ESIMS (s, 1H), 7.97 (d, 7 = 7.6 Hz, 1H), 7.86
163-
F18 - m/z 302 (d, 7 = 7.2 Hz, 1H), 7.77 - 7.66 (m, 2H), 165
([M-H]") 7.40 (dd, 7 = 8.4, 2.2 Hz, 1H), 7.10 (d, 7
= 8.5 Hz, 1H), 6.59 (s, 1H)
lH NMR (400 MHz, DMSO-ifc) δ 9.21 (s, 1H), 7.61 (dd, 7 = 8.1, 0.6 Hz, 1H),
7.01 - 6.87 (m, 2H), 5.77 (qd, 7 = 2.2,
129- 1.2 Hz, 1H), 3.81 (s, 3H), 1.84 (d, 7 =
F19 - - 131 2.3 Hz, 3H);
13C NMR (101 MHz, DMSO-ifc) δ 162.10, 156.96, 131.67, 114.96, 106.28, 82.02, 77.72, 69.58, 55.28, 3.12 Commp
pound IR (cm-1) MASS NMR Data
(°C)
No.
¾ NMR (300 MHz, DMSO-ifc) δ 13.19 (s, IH), 9.80 (s, IH), 7.99 - 7.93 (m,
ESIMS
210- IH), 7.89 (d, / = 7.7 Hz, IH), 7.76 (dd,
F20 - m/z 321
212 / = 9.2, 1.7 Hz, 2H), 7.39 (dd, / = 8.4,
([M-H]-)
2.2 Hz, IH), 7.12 (d, / = 8.4 Hz, IH), 6.61 (s, IH)
lH NMR (400 MHz, DMSO-ifc) δ 9.60
ESIMS (s, IH), 8.01 (s, IH), 7.86 (m, IH), 7.81
150-
F21 - m/z 286.2 (dd, / = 7.6, 8.0 Hz, IH), 7.65 (dt, / = 155
([M-H]") 1.8, 0.8 Hz, IH), 7.43 (m, 3H), 7.33 (m,
2H), 6.26 (s, IH)
IR (thin film)
547.17, 505.64,
562.89, 636.38,
674.45, 711.68,
796.08, 818.76,
833.95, 864.69,
899.59, 960.36,
990.22, 1025.21, lH NMR (400 MHz, DMSO-ifc) δ 9.31 1040.61, 1094.56, (s, IH), 7.62 (dd, / = 8.0, 0.7 Hz, IH),
189-
F22 1140.53, 1192.44, - 7.03 - 6.86 (m, 2H), 5.83 (dt, / = 2.4, 190
1214.17, 1238.86, 0.7 Hz, IH), 3.81 (s, 3H), 3.62 (d, / = 1281.48, 1335.09, 2.3 Hz, IH)
1435.15, 1456.69,
1500.87, 1525.87,
1577.04, 1616.24,
2120.89, 2846.47,
2951.41, 2978.09,
3017.34, 3263.86,
3359.50 cm 1
lH NMR (300 MHz, DMSO-ifc) δ 9.47
145- (s, IH), 7.95 (s, IH), 7.87 (d, / = 7.5 Hz,
F23 - - 147 IH), 7.78 (d, / = 7.5 Hz, IH), 5.27 (q, /
= 6.6 Hz, IH), 1.42 (d, / = 6.6 Hz, 3H)
¾ NMR (400 MHz, DMSO-ifc) δ 13.15
ESIMS (s, IH), 9.71 (s, IH), 7.94 - 7.91 (m,
187-
F24 - m/z 287 IH), 7.87 (dd, / = 7.6, 0.8 Hz, IH), 7.67 189
([M-H] ) (t, 7 = 1.1 Hz, IH), 7.46 - 7.40 (m, 2H),
7.37 - 7.32 (m, 2H), 6.29 (s, IH)
¾ NMR (400 MHz, DMSO-ifc) δ 9.80 (s, IH), 7.71 (d, / = 8.2 Hz, IH), 7.18 (dt, / = 2.2, 0.7 Hz, IH), 7.08 (ddd, / =
ESIMS
148- IR (ATR) 1605, 8.2, 2.2, 0.6 Hz, IH), 6.21 (t, / = 0.7 Hz,
F25 m/z 188.1
151 1408, 1290 cm 1 IH), 3.84 (s, 3H);
([M-H] )
13C NMR (101 MHz, DMSO-ifc) δ 162.5, 151.4, 132.2, 118.2, 116.4, 106.4, 66.8, 55.4 Commp
pound IR (cm-1) MASS NMR Data
(°C)
No.
¾ NMR (400 MHz, DMSO-ifc) δ 9.51 (s, 1H), 7.97 (dt, / = 1.4, 0.8 Hz, 1H), 7.88 (dd, / = 7.6, 0.8 Hz, 1H), 7.80
ESIMS
169- (ddd, / = 7.5, 1.3, 0.7 Hz, 1H), 4.66 (d, /
F26 - m/z 198
172 = 7.8 Hz, 1H), 0.97 (qt, / = 8.0, 4.8 Hz,
([M-H]-)
1H), 0.76 - 0.65 (m, 1H), 0.64 - 0.53 (m, 1H), 0.48 (dddd, / = 8.8, 7.7, 5.7, 4.2 Hz, 1H), 0.42 - 0.32 (m, 1H) lH NMR (400 MHz, DMSO-ifc) δ 9.27
ESIMS (s, 1H), 7.66 (d, 7 = 8.1 Hz, 1H), 7.46 -
131-
F27 - m/z 275 7.37 (m, 2H), 7.37 - 7.27 (m, 2H), 6.98 133
([M+H]+) - 6.87 (m, 1H), 6.73 - 6.63 (m, 1H),
6.12 (s, 1H), 3.72 (s, 3H)
¾ NMR (400 MHz, DMSO-ifc) δ 9.58 (s, 1H), 7.77 (m, 1H), 7.27 (m, 2H), 5.91 (m, 1H), 3.68 (d, 1H);
13C NMR (101 MHz, DMSO-ifc) δ
127- IR (ATR) 3298,
F28 - 165.7, 163.2, 156.5, 156.4, 132.8,
129 2123, 1436 cm"1
132.71, 115.8, 115.5, 109.0, 108.8, 81.4, 77.0, 68.9, 68.9;
19F NMR (376 MHz, DMSO-ifc) δ -108.9
¾ NMR (400 MHz, DMSO-ifc) δ 8.90 (s, 1H), 7.58 (d, / = 8.1 Hz, 1H), 6.95
ESIMS
72- (dt, / = 2.2, 0.7 Hz, 1H), 6.89 (ddd, / =
F29 - m/z 176
75 8.1, 2.2, 0.6 Hz, 1H), 5.13 (q, / = 6.6
([M-H]")
Hz, 1H), 3.79 (s, 3H), 1.39 (d, / = 6.5 Hz, 3H)
¾ NMR (400 MHz, DMSO-ifc) δ 13.09
ESIMS
221- (s, 1H), 9.34 (s, 1H), 7.96 - 7.88 (m,
F30 - m/z 192
223 2H), 7.80 (d, / = 7.6 Hz, 1H), 5.28 (q, /
([M-H]")
= 6.6 Hz, 1H), 1.42 (d, / = 6.6 Hz, 3H)
IR (thin film)
533.68, 605.49,
656.40 636.83,
752.77, 734.22,
787.54, 815.42,
876.97, 927.99, lH NMR (400 MHz, DMSO-ifc) δ 9.06 914.62, 959.44, (s, 1H), 7.02 (d, / = 7.8 Hz, 1H), 6.82
125-
F31 1026.74, 1039.06, - (dd, / = 7.8, 1.0 Hz, 1H), 6.05 - 5.94 127
1067.93, 1152.59, (m, 2H), 5.15 (qd, / = 6.5, 1.0 Hz, 1H), 1103.84, 1235.78, 1.36 (d, 7 = 6.5 Hz, 3H) 1210.93, 1261.54,
1322.12, 1334.75,
1367.99, 1455.29,
1423.54, 1502.68,
1644.42, 2923.57, Commp
pound IR (cm4) MASS NMR Data
(°C)
No.
2963.39, 3252.56
cm"1
lH NMR (400 MHz, CDCh) δ 7.39 -
ESIMS
123- 7.30 (m, 3H), 7.28 - 7.25 (m, 2H), 7.21
F32 - m/z 271.2
125 (s, 1H), 6.61 (s, 1H), 6.08 (s, 1H), 4.56
([M+H]+)
(s, 1H), 3.93 (s, 3H), 3.82 (s, 3H) lH NMR (400 MHz, DMSO-ifc) δ 9.80
ESIMS
162- (s, 1H), 7.95 (dd, / = 7.6, 0.8 Hz, 1H),
F33 - m/z 234
164 7.84 - 7.76 (m, 1H), 7.69 (q, / = 1.0 Hz,
([M-H]-)
1H), 7.42 - 7.27 (m, 5H), 6.28 (s, 1H)
¾ NMR (300 MHz, DMSO-ifc) δ 13.15
ESIMS
235- (s, 1H), 9.77 (s, 1H), 7.96 - 7.87 (m,
F34 - m/z 321
237 2H), 7.73 - 7.68 (m, 3H), 7.63 (d, / =
([M-H]")
5.9 Hz, 2H), 6.42 (s, 1H)
Examples of Herbicidal Activities
Herbicidal evaluations were made visually on a scale of 0 to 100 where 0 represents no activity and 100 represents complete plant death. The data are displayed as indicated in Table A.
Table A: Percent Control Rating Conversion Table
Figure imgf000052_0001
Example A. Evaluation of Postemergent Herbicidal Activity
Post- Emergent Test I: Seeds of test species were obtained from commercial suppliers and planted into a 13 centimeter (cm) diameter-round pot containing soil-less media mix (Metro-Mix 360®, Sun Gro Horticulture). Postemergence treatments were planted 8-12 days (d) prior to application and cultured in a greenhouse equipped with supplemental light sources to provide a 16 hour (h) photoperiod at 24-29 °C. All pots were surface irrigated.
A weighed amount, determined by the highest rate to be tested, of each compound was dissolved in 1.3 milliliters (mL) acetone-dimethyl sulfoxide (DMSO; 97:3, volume per volume (v/v)) and diluted with 4.1 mL water-isopropanol-crop oil concentrate (78:20:2, v/v/v) containing 0.02% Triton X-155 to obtain concentrated stock solutions. Additional application rates were obtained by serial dilution of the high rate solution into a solution containing an appropriate volume of a 97:3 v/v mixture of acetone and DMSO and an appropriate volume of an aqueous mixture of water, isopropyl alcohol, crop oil concentrate (78:20:2, v/v/v) containing 0.02% Triton X-155.
Formulated compounds were applied using a DeVilbiss® compressed air sprayer at 2-
4 pounds per square inch (psi). Following treatment, pots were returned to the greenhouse for the duration of the experiment. All pots were subirrigated as needed to provide optimum growing conditions. All pots were fertilized one time per week by subirrigating with Peters Peat-Lite Special® fertilizer (20-10-20).
Phytotoxicity ratings were obtained 10 days after postemergence applications. All evaluations were made visually on a scale of 0 to 100 where 0 represents no activity and 100 represents complete plant death, and the data are presented as indicated in Table A. Visual assessments of plant injury were made based on growth reduction, discoloration, leaf deformity and necrosis.
Some of the compounds tested, application rates employed, plant species tested, and results are given in Table B.
Table B. Post-Emergent Test I Herbicidal Activity on Key Broadleaf and Grass Weed as well as Crop Species
Figure imgf000054_0001
Compound Rate
HELAN IPOHE AVEFA ECHCG SETFA APESV PANDI PHAMI
Number (kg/ha)
F22 1 C D G G G - - -
F22 2 C C G G F - - -
F22 4 B B F D D D - E
F23 4 C B F E E E B D
F24 4 G G G G G - G -
F25 4 C C E D D - - -
F26 4 G D F F F G - -
F27 4 G G G F - G - -
F28 0.5 C C G G G - - -
F28 1 C C G G G - - -
F28 2 C B G G F - - -
F28 4 B B E D C D - -
F29 4 G C G G - G - G
F30 4 G G G G G - G -
F31 4 C B F D - F - -
F32 4 G G G D G G - -
F33 0.5 G F G F F - - -
F33 1 G D F E D - - -
F33 2 G C E E C - - -
F33 4 E C E D D E - -
F34 4 G G G G G - G -
APESV: windgrass ( Apera spica-venti (L.) Beauv.)
AVEFA: wild oats (Avenafatua)
ECHCG: bamyardgrass (Echinochloa crus-galli)
HELAN: sunflower (Helianthus annuus)
IPOHE: ivyleaf morningglory (Ipomoea hederecea)
PANDI: fall panicum (Panicum dichotomiflorum (L.) Michx.) PHAMI: littleseed canarygrass (Phalaris minor Retz.) SETFA: giant foxtail (Setaria faberi)
kg ai/ha: kilograms active ingredient per hectare

Claims

WHAT IS CLAIMED IS:
1. A compound of Formula (I):
Figure imgf000057_0001
(I)
wherein
R represents H or an agriculturally acceptable salt or ester;
Ri represents cyano; C1-C12 alkyl in which the alkyl is unsubstituted or substituted with OH, NH2, C1-C2 alkylamino, di-(Ci-C2 alkyl)amino, C1-C2 alkoxy, C1-C2 haloalkoxy, C1-C2 alkylthio or C1-C2 haloalkylthio; Ci-Cs haloalkyl; C3-C8 cycloalkyl; C2-C8 alkenyl; C2-C8 haloalkenyl; C2-C8 alkynyl; C2-C8 haloalkynyl; -C(0)OR6; -C(0)NR7R8; C8-Ci4 arylalkyl; C8-Ci4 arylalkenyl; C8-Ci4 arylalkynyl; or aryl in which the aryl is unsubstituted or substituted with one or more R9;
R2, R3, R4 and R5 independently represent H; cyano; halo; nitro; NH2; Ο-Ce alkylamino; di-(Ci-C6 alkyl)amino; C1-C12 alkyl; Ci-C8 alkoxy; Ci-C8 haloalkyl; Ci- C8 haloalkoxy; C3-C8 cycloalkyl; C2-C8 alkenyl; C2-C8 haloalkenyl; C2-C8 alkynyl; C2-C8 haloalkynyl; -C(0)OR6; -C(0)NR7Rs; aryl or aryloxy in which the aryl or aryloxy is unsubstituted or substituted with one or more R9; or where R3 and R4 are taken together as -OCH2O-, -OCH2CH2O-, -OCH2CH2- or -OCF2O-; provided that R2, R3, R4 and R5 are sterically compatible and that at least one of R2, R3, R4 and R5 is other than H;
R6, R7 and Rs independently represent H; C1-C12 alkyl; C3-C8 alkenyl; or C3-C8 alkynyl; in which the alkyl, alkenyl or alkynyl is unsubstituted or substituted with one or more OH, Ci-C4 alkoxy, Ci-C4 alkylthio, or phenyl groups, provided that R6, R7 and Rs are sterically compatible; and
R9 represents halo, C1-C12 alkyl, Ci-C8 alkoxy, Ci-C8 haloalkyl, or Ci-C8 haloalkoxy;
with the proviso that R3 is not -XYC(0)ORio, wherein
X represents O, NR11, S, SO, or SO2 where Rn is H, Ci-Ce alkyl, C3- C6 alkenyl, or C3-C6 alkynyl; Y represents Ci-C6 alkyl; C3-C6 alkenyl; or C3-C6 alkynyl; in which the alkyl, alkenyl or alkynyl is unsubstituted or substituted with one or more halogen, Ci-C6 alkyl, Ci-C6 haloalkyl, Ci-C6 alkoxy, Ci-C6 haloalkoxy, C(0)0(Ci-C6-alkyl) or phenyl which is unsubstituted or substituted by halogen, Ci-C6 alkyl, Ci-C6 haloalkyl; and
Rio represents H, Ci-C6 alkyl, C3-C6 alkenyl, C3-C6 alkynyl, (Ci-C6- alkoxy)-Ci-C6 alkyl, (Ci-C6 alkoxy)-C3-C6 alkenyl, (Ci-C6 alkoxy)-C3-C6 alkynyl, phenyl, phenyl-Ci-C6 alkyl, where the aliphatic and phenyl parts of the aforementioned radicals are unsubstituted, partly or completely halogenated.
2. A herbicidal composition comprising a compound of Formula (I):
Figure imgf000058_0001
wherein
R represents H or an agriculturally acceptable salt or ester;
Ri represents cyano; C1-C12 alkyl in which the alkyl is unsubstituted or substituted with OH, NH2, C1-C2 alkylamino, di-(Ci-C2 alkyl)amino, C1-C2 alkoxy, C1-C2 haloalkoxy, C1-C2 alkylthio or C1-C2 haloalkylthio; Ci-C8 haloalkyl; C3-C8 cycloalkyl; C2-C8 alkenyl; C2-C8 haloalkenyl; C2-C8 alkynyl; C2-C8 haloalkynyl; - C(0)OR6; -C(0)NR7R8; C8-Ci4 arylalkyl; C8-Ci4 arylalkenyl; C8-Ci4 arylalkynyl; or aryl in which the aryl is unsubstituted or substituted with one or more R9;
R2, R3, R4 and R5 independently represent H; cyano; halo; nitro; N¾; Ci-C6 alkylamino; di-(Ci-C6 alkyl)amino; C1-C12 alkyl; Ci-C8 alkoxy; Ci-C8 haloalkyl; Ci- C8 haloalkoxy; C3-C8 cycloalkyl; C2-C8 alkenyl; C2-C8 haloalkenyl; C2-C8 alkynyl; C2-C8 haloalkynyl; -C(0)OR6; -C(0)NR7Rs; aryl or aryloxy in which the aryl or aryloxy is unsubstituted or substituted with one or more R9; or where R3 and R4 are taken together as -OCH2O-, -OCH2CH2O-, -OCH2CH2- or -OCF2O-; provided that R2, R3, R4 and R5 are sterically compatible and that at least one of R2, R3, R4 and R5 is other than H; R6, 7 and Rs independently represent H; C1-C12 alkyl; C3-C8 alkenyl; or C3-C8 alkynyl; in which the alkyl, alkenyl or alkynyl is unsubstituted orsubstituted with one or more OH, C1-C4 alkoxy, C1-C4 alkylthio, or phenyl groups, provided that R6, R7 and Rs are sterically compatible; and
R9 represents halo, C1-C12 alkyl, Ci-C8 alkoxy, Ci-C8 haloalkyl, or Ci-C8 haloalkoxy;
with the proviso that R3 is not -XYC(0)ORio, wherein
X represents O, NRn, S, SO, or S02 where Rn is H, Ci-Ce alkyl, C3 C6-alkenyl, or C3-C6 alkynyl;
Y represents Ci-C6 alkyl; C3-C6 alkenyl; or C3-C6 alkynyl; in which the alkyl, alkenyl or alkynyl is unsubstituted or substituted with one or more halogen, Ci-C6 alkyl, Ci-C6 haloalkyl, Ci-C6 alkoxy, Ci-C6 haloalkoxy, C(0)0(Ci-C6 alkyl) or phenyl which is unsubstituted or substituted by halogen, Ci-C6 alkyl, Ci-C6 haloalkyl; and
Rio represents H, Ci-C6 alkyl, C3-C6 alkenyl, C3-C6 alkynyl, (Ci-C6 alkoxy)-Ci-C6 alkyl, (Ci-C6 alkoxy)-C3-C6 alkenyl, (Ci-C6 alkoxy)-C3-C6 alkynyl, phenyl, phenyl- Ci-C6 alkyl, where the aliphatic and phenyl parts of the aforementioned radicals are unsubstituted, partly or completely halogenated;
and an agriculturally acceptable adjuvant or carrier.
3. The composition or herbicidal composition of claim 1 or 2, further comprising an additional herbicidal compound.
4. The composition or herbicidal composition of any of claims 1-3, further comprising a safener.
5. The composition or herbicidal composition of any of claims 1-4, wherein R is H.
6. The composition or herbicidal composition of any of claims 1-5, wherein Ri is cyano, C1-C4 alkyl, C2-C4 alkynyl, or substituted phenyl.
7. The composition or herbicidal composition of any of claims 1-6, wherein Ri is Me, ethynyl, 4-chlorophenyl, or 2,4-dichlorophenyl.
8. The composition or herbicidal composition of any of claims 1-7, wherein R4 is cyano, trifluoromethyl, or fluoro.
9. A method for controlling undesirable vegetation, which comprises (a) contacting the undesirable vegetation or area adjacent to the undesirable vegetation, or (b) pre-emergently contacting soil or water, with a compounds of claim 1 or a herbicidal composition of claim 2.
10. The method of claim 9, wherein the herbicidal composition further comprises an additional herbicidal compound.
11. The method of claim 9 or 10, wherein the herbicidal composition further comprises a safener.
12. The method of any of claims 9-11, wherein R is H.
13. The method of any of claims 9-12, wherein Ri is cyano, C1-C4 alkyl, C2-C4 alkynyl, or substituted phenyl.
14. The method of any of claims 9-13, wherein Ri is Me, ethynyl, 4-chlorophenyl, or 2,4- dichlorophenyl.
15. The method of any of claims 9-14, wherein R4 is cyano, trifluoromethyl, or fluoro.
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