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NZ613477B2 - Arylalkyl esters of 4-amino-6-(substituted phenyl)picolinates and 6-amino-2-(substituted phenyl)-4-pyrimidinecarboxylates and their use as herbicides - Google Patents
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NZ613477B2 - Arylalkyl esters of 4-amino-6-(substituted phenyl)picolinates and 6-amino-2-(substituted phenyl)-4-pyrimidinecarboxylates and their use as herbicides - Google Patents

Arylalkyl esters of 4-amino-6-(substituted phenyl)picolinates and 6-amino-2-(substituted phenyl)-4-pyrimidinecarboxylates and their use as herbicides Download PDF

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NZ613477B2
NZ613477B2 NZ613477A NZ61347712A NZ613477B2 NZ 613477 B2 NZ613477 B2 NZ 613477B2 NZ 613477 A NZ613477 A NZ 613477A NZ 61347712 A NZ61347712 A NZ 61347712A NZ 613477 B2 NZ613477 B2 NZ 613477B2
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compound
mmol
mhz
compounds
amino
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NZ613477A
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NZ613477A (en
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Joseph D Eckelbarger
Jeffrey B Epp
Katherine A Guenthenspberger
Christian T Lowe
Paul R Schmitzer
Thomas L Siddall
Carla N Yerkes
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Dow Agrosciences Llc
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Priority claimed from PCT/US2012/022286 external-priority patent/WO2012103042A1/en
Publication of NZ613477A publication Critical patent/NZ613477A/en
Publication of NZ613477B2 publication Critical patent/NZ613477B2/en

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    • A—HUMAN NECESSITIES
    • A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
    • A01N—PRESERVATION OF BODIES OF HUMANS OR ANIMALS OR PLANTS OR PARTS THEREOF; BIOCIDES, e.g. AS DISINFECTANTS, AS PESTICIDES OR AS HERBICIDES; PEST REPELLANTS OR ATTRACTANTS; PLANT GROWTH REGULATORS
    • A01N43/00—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds
    • A01N43/34—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having rings with one nitrogen atom as the only ring hetero atom
    • A01N43/40—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having rings with one nitrogen atom as the only ring hetero atom six-membered rings
    • A—HUMAN NECESSITIES
    • A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
    • A01N—PRESERVATION OF BODIES OF HUMANS OR ANIMALS OR PLANTS OR PARTS THEREOF; BIOCIDES, e.g. AS DISINFECTANTS, AS PESTICIDES OR AS HERBICIDES; PEST REPELLANTS OR ATTRACTANTS; PLANT GROWTH REGULATORS
    • A01N43/00—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds
    • A01N43/48—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having rings with two nitrogen atoms as the only ring hetero atoms
    • A01N43/54—1,3-Diazines; Hydrogenated 1,3-diazines
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D213/00—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
    • C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
    • C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
    • C07D213/60—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
    • C07D213/72—Nitrogen atoms
    • C07D213/73—Unsubstituted amino or imino radicals
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D213/00—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
    • C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
    • C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
    • C07D213/60—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
    • C07D213/78—Carbon atoms having three bonds to hetero atoms, with at the most one bond to halogen, e.g. ester or nitrile radicals
    • C07D213/79—Acids; Esters
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D239/00—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings
    • C07D239/02—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings
    • C07D239/24—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings having three or more double bonds between ring members or between ring members and non-ring members
    • C07D239/28—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings having three or more double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, directly attached to ring carbon atoms
    • C07D239/32—One oxygen, sulfur or nitrogen atom
    • C07D239/34—One oxygen atom
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D239/00—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings
    • C07D239/02—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings
    • C07D239/24—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings having three or more double bonds between ring members or between ring members and non-ring members
    • C07D239/28—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings having three or more double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, directly attached to ring carbon atoms
    • C07D239/32—One oxygen, sulfur or nitrogen atom
    • C07D239/42—One nitrogen atom
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D239/00—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings
    • C07D239/02—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings
    • C07D239/24—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings having three or more double bonds between ring members or between ring members and non-ring members
    • C07D239/28—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings having three or more double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, directly attached to ring carbon atoms
    • C07D239/46—Two or more oxygen, sulphur or nitrogen atoms
    • C07D239/47—One nitrogen atom and one oxygen or sulfur atom, e.g. cytosine
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
    • C07D405/02—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings
    • C07D405/12—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings linked by a chain containing hetero atoms as chain links

Abstract

The disclosure relates to arylalkyl esters of 4-aminopicolinic acids having structural formula (IB), wherein the variables are as defined in the specification. These compounds are suitable as herbicides for controlling weeds especially those species common to rice and wheat cropping systems and in pasture management programs. asture management programs.

Description

ARYLALKYL ESTERS OF 4-AMINO(SUBSTITUTED PHENYL)PICOLINATES AND 6-AMINO(SUBSTITUTED PHENYL)PYRIMIDINECARBOXYLATES AND THEIR USE AS HERBICIDES This invention relates to certain novel esters of 4-amino(substituted phenyl)- picolinic acids and 6-amino(substituted phenyl)pyrimidinecarboxylic acids and to the use of these compounds as herbicides for control of weeds especially those s common to rice and wheat cropping systems and in pasture management programs.
A number of picolinic acids and their pesticidal properties have been described in the art. U.S. Patent 6,784,137 B2 and U.S. Patent 7,314,849 B2 disclose a genus of 4-amino arylpicolinic acids and their derivatives and their use as selective herbicides, particularly for rice and cereals such as wheat and barley. A1, A1, U.S.
Patent 7,863,220 B2, U.S. Patent 7,300,907 B2, U.S. Patent 220 B2, and U.S. Patent 7,786,044 B2 disclose certain 6-aminosubstitutedpyrimidinecarboxylic acids and their tives and their use as herbicides. It has now been ered that certain esters of 4- amino(substituted phenyl)picolinic acids and of 6-amino(substituted phenyl) pyrimidinecarboxylic acids can provide superior weed control especially in rice and wheat cropping systems and in pasture management programs.
Certain arylalkyl esters of 4-amino(substituted phenyl)picolinic acids and of 6- amino(substituted phenyl)pyrimidinecarboxylic acids are superior herbicides with a broad spectrum of broadleaf, grass, and sedge weed l especially in rice and wheat cropping systems and in pasture management programs. The compounds further possess excellent logical or environmental profiles.
The invention es compounds of Formula IA: wherein Y represents C1-C8 alkyl, C3-C6 lkyl, or phenyl substituted with l — 4 substituents independently selected from halogen, C1-C3 alkyl, C3-C6 cycloalkyl, C1-C3 alkoxy, C1-C3 haloalkyl, C1-C3 haloalkoxy, cyano, nitro, NRIRZ, or where two adjacent substituents are taken together as —O(CH2)nO— or —O(CH2)n— wherein n=1 or 2; Z represents halogen, C1-C3 alkoxy, or C2-C4 alkenyl; R1 and R2 independently represent H, C1-C6 alkyl, or C1-C6 acyl; R3 represents unsubstituted or substituted C7-C11 arylalkyl. red compounds include those in which Y represents substituted phenyl, Z represents Cl, -CH=CH2 or OCH3, R1 and R2 represent H, R3 represents unsubstituted or 0rth0-, meta-, or onosubstituted benzyl.
The invention also es compounds of Formula IB: 1 2 R\N/R X Z / O Y N \R3 wherein X = H or F; Y represents halogen, C1-C8 alkyl, C3-C6 cycloalkyl, or phenyl substituted with l — 4 substituents independently selected from halogen, C1-C3 alkyl, C3-C6 cycloalkyl, C1-C3 alkoxy, C1-C3 haloalkyl, C1-C3 haloalkoxy, cyano, nitro, NRIRZ, or where two adjacent substituents are taken together as )nO— or —O(CH2)n— n n=1 or 2; Z represents halogen or C2-C4 alkenyl; R1 and R2 independently represent H, C1-C6 alkyl, or C1-C6 acyl; R3 represents unsubstituted or substituted C7-C11 kyl.
Preferred compounds include those in which X represents H or F, Y represents substituted phenyl, Z represents Cl, R1 and R2 represent H, R3 represents unsubstituted or 0rth0-, meta-, or para-monosubstituted benzyl.
The invention includes herbicidal compositions comprising an herbicidally effective amount of a compound of a IA or IB in a mixture with an agriculturally acceptable adjuvant or carrier. The invention also includes a method of use of the compounds and compositions of the present invention to kill or control undesirable vegetation by application of an idal amount of the compound to the vegetation or to the locus of the vegetation as well as to the soil prior to nce of the vegetation or to the irrigation or flood water, prior to, or after emergence. The invention further includes a method for the selective postemergent control of undesirable vegetation in the presence of rice, wheat or forage, which comprises applying to said undesirable vegetation an herbicidally effective amount of a compound of the present invention. The ion also es a method of making the compounds of the present invention.
The herbicidal compounds of the present invention are arylyalkyl esters of 4-amino (substituted )picolinic acids and 6-amino(substituted phenyl)pyrimidine- carboxylic acids and their derivatives. The picolinic acids from which the esters of Formula IB are d are a new class of compounds having herbicidal activity. A number of picolinic acid compounds are described in U.S. Patent 6,784,137 B2 and U.S. Patent 7,314,849 B2, including inter alia, 4-aminochloro(4-chlorofluoromethoxyphenyl )picolinic acid, ochlorofluoro(4-chlorofluoro methoxyphenyl)picolinic acid and 4-amino-3 -chloro(2,4-dichloro methoxyphenyl)picolinic acid. The pyrimidinecarboxylic acids from which the esters of Formula IA are derived are also a new class of compounds having herbicidal activity. A number of pyrimidinecarboxylic acid compounds are bed in A1, WO 2007/082076 A1, U.S. Patent 7,863,220 B2, U.S. Patent 7,300,907 B2, U.S. Patent 220 B2, and U.S. Patent 7,786,044 B2. These picolinic acids and dinecarboxylic acids control annual grass weeds, broadleaf weeds, and sedges in rice and wheat, but arylalkyl esters of the present invention trate greater efficacy than the known esters, especially against weeds ent in rice and wheat cropping systems and in pasture management programs.
Preferred ester groups are those which produce greater levels of weed control than an acid equivalent rate of the methyl esters. Preferred ester groups include the unsubstituted benzyl ester and 0rth0-, meta-, and onosubstituted benzyl esters.
The arylalkyl esters of the 6-amino(substituted )pyrimidinecarboxylic acids can be ed by reacting the dinecarboxylic acid with an arylalkyl halide in the presence of a base.
R1N\/R2 Scheme 1 R1N\/R2 YIEOHHEH/—>R3YfiI'(OR3 [1 LA The arylalkyl esters of the picolinic acids can be prepared by coupling of picolinic acid with an alcohol using any number of suitable activating agents such as those used for peptide couplings such as dicyclohexylcarbodiimide (DCC) or carbonyl diimidazole (CD1) or by reacting the corresponding acid with an appropriate arylalkyl alcohol in the presence of an acid st. Alternatively, the arylalkyl esters can be prepared by reacting the picolinic acid with an arylalkyl halide in the presence of a base.
Scheme 2 R \N/R1 2 Rl\N/R2 X R3 X Z z \ HO/ 01‘ \ OH ——> / OR3 Y N/ Y N 0 Hal 0 H [B It is recognized that some reagents and reaction conditions disclosed herein or in the chemical literature for preparing compounds of Formula IA or IE may not be compatible with certain functionalities present in the intermediates. In these instances, the incorporation of protection/deprotection sequences or functional group interconversions into the synthesis will aid in obtaining the desired products. The use and choice of the protecting groups will be apparent to one skilled in chemical synthesis.
The terms "alkyl," "alkenyl" and "alkynyl," as well as derivative terms such as "alkoxy,99 ‘6acyl" and "alkylthio," as used , include within their scope straight chain and branched chain moieties. Unless specifically stated otherwise, each may be unsubstituted or substituted with one or more substituents selected from but not limited to halogen, alkoxy, alkylthio, or aminoalkyl, provided that the substituents are sterically compatible and the rules of chemical bonding and strain energy are satisfied. The terms "alkenyl" and "alkynyl" are intended to include one or more unsaturated bonds.
The term lkyl," as used herein, refers to a phenyl substituted alkyl group having a total of 7 to 11 carbon atoms, such as benzyl (—CH2C6H5), 2—methylnaphthyl (—CH2C10H7) and l- or 2—phenethyl (—CHZCH2C6H5 or —CH(CH3)C6H5). The phenyl group may itself be tituted or substituted with one or more substituents independently selected from n, nitro, cyano, C1-C6 alkyl, C1-C6 alkoxy, halogenated C1-C6 alkyl, halogenated C1-C6 , C1-C6 alkylthio, C(O)OC1-C6alkyl, or where two adjacent substituents are taken together as —O(CH2)nO— wherein n=1 or 2, provided that the substituents are sterically compatible and the rules of chemical g and strain energy are satisfied.
Unless specifically limited otherwise, the term n es fluorine, chlorine, bromine, and iodine.
The compounds of Formula IA or IE have been found to be useful as pre-emergence and post-emergence herbicides for rice and cereals cropping systems and for e management programs. The term herbicide is used herein to mean an active ingredient that kills, ls or otherwise adversely modifies the growth of plants. An herbicidally effective or vegetation controlling amount is an amount of active ingredient which causes an adversely modifying effect and es deviations from natural pment, killing, regulation, desiccation, ation, and the like. The terms plants and vegetation include germinating seeds, emerging seedlings, above and below ground plant parts such as shoots, roots, tubers, rhizomes and the like, and established vegetation.
Herbicidal activity is exhibited by the compounds of the present invention when they are applied directly to the plant or to the locus of the plant at any stage of growth or before planting or emergence. The effect observed depends upon the plant s to be controlled, the stage of growth of the plant, the application parameters of dilution and spray drop size, the le size of solid components, the environmental conditions at the time of use, the specific compound employed, the specific adjuvants and rs employed, the soil type, water quality, and the like, as well as the amount of chemical d. These and other factors can be adjusted as is known in the art to e selective herbicidal action.
Generally, it is preferred to apply the compounds of Formula IA or IE postemergence via spray or water application to relatively immature undesirable vegetation to achieve the maximum control of weeds.
Application rates of l to 500 grams per hectare (g/ha) are generally employed in foliar-applied and water-applied postemergence operations. Preferred application rates are 10 to 300 g/ha. For preemergence applications, rates of 5 to 500 g/ha are generally employed. red application rates are 30 to 300 g/ha. The higher rates designated generally give non-selective control of a broad variety of undesirable vegetation. The lower rates typically give selective control and can be ed in the locus of crops.
The herbicidal nds of the present invention are often applied 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 ated with the other herbicide or herbicides, tank mixed with the other herbicide or ides 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 invention include: 2,4-D salts, esters and amines, acetochlor, acifluorfen, alachlor, ulfuron, aminopyralid, aminotriazole, ammonium thiocyanate, anilifos, atrazine, azimsulfuron, benfuresate, bensulfuron-methyl, bentazon, benthiocarb, benzobicyclon, benzofenap, x, bispyribac-sodium, bromobutide, lor, cafenstrole, carfentrazone-ethyl, nafoppropyrgyl , chlorimuron, chlorpropham, cinosulfuron, clethodim, clomazone, clomeprop, clopyralid, cloransulam-methyl, cyclosulfamuron, cycloxydim, cyhalofop-butyl, cumyluron, daimuron, diclosulam, diflufenican, diflufenzopyr, dimepiperate, dimethametryn, diquat, pyr, EK2612, EPTC, esprocarb, ET-75l, ethoxysulfuron, ethbenzanid, fenoxaprop, fenoxaprop-ethyl, fenoxaprop-ethyl + isoxadifen-ethyl, fentrazamide, flazasulfuron, florasulam, fluazifop, fluazifop-P-butyl, flucetosulfuron, flufenacet, flufenpyr-ethyl, flumetsulam, flumioxazin, flupyrsulfuron, fluroxypyr, fomesafen, foramsulfuron, glufosinate, glufosinate-P, sate, halosulfuron-methyl, haloxyfop-methyl, haloxyfop-R, haloxyfop- R-methyl, imazamethabenz, imazamox, imazapic, imazapyr, imazaquin, imazethapyr, imazosulfuron, indanofan, l, ipfencarbazone, isoxaben, MCPA, MCPB, mefenacet, mesosulfuron, mesotrione, metamifop, metazosulfuron, chlor, lam, metsulfuron, molinate, lfuron, MSMA, orthosulfamuron, oryzalin, oxadiargyl, oxadiazon, oxazichlomefone, oxyfluorfen, paraquat, pendimethalin, penoxsulam, pentoxazone, pethoxamid, picloram, piperophos, pretilachlor, profoxydim, prohexadione- calcium, propachlor, propanil, propisochlor, propyzamide, propyrisulfuron, prosulfuron, pyrabuticarb, pyraclonil, pyrazogyl, pyrazolynate, pyrazosulfuron-ethyl, pyrazoxyfen, pyribenzoxim, pyridate, pyriftalid, pyriminobac-methyl, pyrimisulfan, primisulfuron, pyroxsulam, quinoclamine, quinclorac, quizalofop-P—ethyl, 8-3252, sethoxydim, simazine, simetryne, s-metolachlor, sulcotrione, sulfentrazone, sulfosate, tefuryltrione, thenylchlor, thiazopyr, thiobencarb, triclopyr, triclopyr-esters and amines, trifluralin, trinexapac-ethyl, tritosulfuron, and other 4-amino(substituted phenyl)picolinates and 6-amino-2—(substituted phenyl)pyrimidinecarboxylates and their salts and esters.
The compounds of the present invention can additionally be employed to control undesirable vegetation in many crops that have been made nt to or resistant to them or to other herbicides by genetic manipulation or by mutation and selection. The herbicidal compounds of the present invention can, further, be used in conjunction with sate, glufosinate, dicamba, imidazolinones, aryloxyphenoxypropionates or 2,4-D on glyphosate- tolerant, inate-tolerant, dicamba-tolerant, imidazolinone-tolerant, aryloxyphenoxy- propionate tolerant or 2,4-D-tolerant crops. It is generally preferred to use the compounds of the invention in combination with herbicides that are selective for the crop being treated and which complement the spectrum of weeds controlled by these nds at the application rate employed. It is further lly preferred to apply the compounds of the invention and other complementary herbicides at the same time, either as a combination formulation or as a tank mix. rly the herbicidal compounds of the t invention can be used in conjunction with acetolactate synthase (ALS) inhibitors on acetolactate synthase inhibitor tolerant crops or with 4-hydroxyphenyl te dioxygenase (HPPD) inhibitors on 4- yphenyl pyruvate dioxygenase tor tolerant crops.
The compounds of the present invention can generally be employed in ation with known herbicide rs, such as benoxacor, benthiocarb, nolide, cloquintocet (mexyl), rinil, cyprosulfamide, daimuron, dichlormid, dicyclonon, dietholate, dimepiperate, oton, fenchlorazole-ethyl, fenclorim, flurazole, fluxofenim, furilazole, harpin proteins, isoxadifen-ethyl, mefenpyr-diethyl, mephenate, MG 191, MON 4660, naphthalic ide (NA), oxabetrinil, R29148 and N—phenyl-sulfonylbenzoic acid amides, to e their selectivity. They can additionally be employed to control undesirable vegetation in many crops that have been made tolerant to or resistant to them or to other herbicides by genetic manipulation or by mutation and selection. For example, corn, wheat, rice, soybean, sugar beet, cotton, canola, and other crops that have been made nt or resistant to nds that are acetolactate synthase tors in sensitive plants can be treated. Many glyphosate- and glufosinate-tolerant crops can be treated as well, alone or in combination with these herbicides. Some crops have been made tolerant to c herbicides and ACCase herbicides such as 2,4-(dichlorophenoxy)acetic acid (2,4-D) and dicamba and aryloxyphenoxypropionates. These herbicides may be used to treat such resistant crops or other auxin tolerant crops. Some crops have been made tolerant to 4- hydroxyphenyl pyruvate dioxygenase inhibiting herbicides, and these herbicides may be used to treat such resistant crops.
While it is possible to utilize the compounds of Formula IA or IE directly as herbicides, it is preferable to use them in mixtures containing an herbicidally effective amount of the compound along with at least one agriculturally acceptable nt or carrier.
Suitable adjuvants or carriers should not be phytotoxic to valuable crops, particularly at the concentrations employed in applying the compositions for ive weed l in the presence of crops, and should not react chemically with the compounds of Formula IA or IE 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 normally 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 ltural adjuvants and carriers that are useful in preparing the herbicidal mixtures of the invention 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 olyglycoside; phosphated alcohol ethoxylate; natural primary alcohol (Cu-C16) ethoxylate; di-sec-butylphenol EO-PO block copolymer; polysiloxane-methyl cap; nonylphenol ethoxylate + urea ammonium nitrate; emulsified methylated seed oil; tridecyl alcohol (synthetic) late (8E0); tallow amine ethoxylate (15 E0); PEG(400) dioleate- Liquid carriers that can be employed include water and organic ts. The c solvents typically used include, but are not limited to, petroleum fractions or hydrocarbons such as l 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 cohols (4-6 y containing), such as l hexyl 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 rboxylic acids and the like. ic organic solvents e toluene, xylene, petroleum naphtha, crop oil, acetone, methyl ethyl ketone, cyclohexanone, trichloroethylene, perchloroethylene, ethyl acetate, amyl acetate, butyl e, propylene glycol monomethyl ether and diethylene glycol monomethyl ether, methyl alcohol, ethyl alcohol, isopropyl alcohol, amyl alcohol, ethylene glycol, propylene , glycerine, N—methyl-2—pyrrolidinone, N,N—dimethyl alkylamides, dimethyl sulfoxide, liquid fertilizers and the like. Water is generally the carrier of choice for the dilution of concentrates .
Suitable solid carriers include talc, pyrophyllite clay, silica, lgus 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.
It is usually desirable to incorporate one or more surface-active agents into the compositions of the present invention. Such surface-active agents are advantageously employed in both solid and liquid compositions, especially 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 cheon’s ents 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 nolammonium lauryl sulfate; alkylarylsulfonate salts, such as calcium dodecylbenzenesulfonate; alkylphenol-alkylene oxide addition products, such as nonylphenol-Clg ethoxylate; alcohol-alkylene oxide addition products, such as yl alcohol-C16 ethoxylate; soaps, such as sodium stearate; alkylnaphthalene-sulfonate salts, such as sodium dibutyl- naphthalenesulfonate; 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 ne oxide and propylene oxide; salts of mono and l ate 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, particularly 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 ltural compositions include compatibilizing agents, antifoam agents, sequestering , neutralizing agents and buffers, corrosion inhibitors, dyes, odorants, ing agents, penetration aids, sticking agents, dispersing agents, thickening agents, freezing point depressants, antimicrobial agents, and the like. The itions may also contain other compatible components, for example, other herbicides, plant growth regulants, ides, insecticides, and the like and can be formulated with liquid fertilizers or solid, ulate fertilizer carriers such as um nitrate, urea and the like.
The concentration of the active ingredients in the herbicidal compositions of this invention is generally from 0.001 to 98 percent by . trations from 0.01 to 90 percent by weight are often employed. In compositions ed to be employed as concentrates, the active ient is generally present in a concentration from 5 to 98 weight percent, preferably 10 to 90 weight percent. Such compositions are typically diluted with an inert r, such as water, before application. The diluted compositions usually applied to weeds or the locus of weeds generally contain 0.0001 to 1 weight t active ient and preferably contain 0.001 to 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 water or paddy flood water, and by other tional means known to those skilled in the art.
The following Examples are presented to illustrate the various aspects of this invention and should not be construed as limitations to the claims.
Examples General: Microwave heating was carried out us1ng a Biotage Initiator. . . . . .. TM . microwave reactor. The microwave reactions were conducted in closed reaction vessels with magnetic stirring and with the temperature controlled via infrared (IR) detection.
Example 1. Preparation of benzyl 4-aminochloro(4-chlorofluoromethoxyphenyl)- -fluoropicolinate (Compound 1) To a solution of 4-aminochloro(4-chlorofluoromethoxyphenyl) fluoropicolinic acid (prepared by the s bed in U. S. Patent 7,314,849 B2; 100 milligrams (mg), 0.29 millimoles (mmol)) in tetrahydrofuran (THF; 1 milliliter (mL)) was added carbonyl diimidazole (51 mg, 0.32 mmol). The on mixture was stirred at ambient temperature for 30 s (min) when carbon e (C02) evolution ceased. Benzyl alcohol (62 mg, 0.58 mmol) was added, and the reaction mixture was heated in a benchtop microwave at 90 0C for 20 min. The reaction mixture was purified by silica gel chromatography (applied directly to an Isco 40 gram (g) RediSep® column eluting with 0- 100% diethyl ether (EtZO) in hexanes) to yield a white solid (147 mg, 78%): mp 132—133 0C, 1H NMR (400 MHz, DMSO-dg) 5 7.50 — 7.33 (m, 6H), 7.29 (dd, J: 8.5, 7.1 Hz, 1H), 7.13 (s, 2H), 5.37 (s, 2H), 3.92 (s, 3H); ESIMS m/z 439 ([M+H]+).
Example 2. Preparation of 4-chlorobenzyl 4-aminochloro(4-chlorofluoro methoxyphenyl)fluoropicolinate (Compound 2) WO 03042 A suspension of 4-aminochloro(4-chlorofluoromethoxyphenyl) fluoropicolinic acid (150 mg, 0.43 mmol), 1-(bromomethyl)methylbenzene (159 mg, 0.86 mmol), potassium carbonate (K2CO3; 118 mg, 0.86 mmol) and sodium iodide (NaI; 6 mg, 0.04 mmol) in N,N—dimethylformamide (DMF; 1 mL) was heated in a benchtop microwave at 100 0C for 5 min. The reaction mixture was then diluted with Eth, washed with brine, dried over sodium sulfate (Nast4) and concentrated in vacuo. The residue was purified by silica gel chromatography (eluting with a 0-70% ethyl acetate (EtOAc)/hexanes gradient) to yield a white solid (148 mg, 73%): mp 143 OC;1H NMR (400 MHz, 6) 5 7.50 — 7.42 (m, 5H), 7.28 (dd, J: 8.5, 7.1 Hz, 1H), 7.08 (s, 2H), 5.37 (s, 2H), 3.93 (d, J: 0.8 Hz, 3H); ESIMS m/z 475 +).
Compounds 3-16 in Table 1 were synthesized as in Example 2.
Example 3. Preparation of chlorobenzyl 4-aminochloro(4-chlorofluoro methoxyphenyl)picolinate (Compound 17) 4-Aminochloro(4-chlorofluoromethoxyphenyl)picolinic acid (prepared by the methods described in U. S. Patent 7,314849 B2; 828 mg, 2.5 mmol) was dissolved in DMF (4 mL). Sodium hydride (NaH, 60% disperson in mineral oil; 154 mg, 3.85 mmol) was added portion wise. To the mixture was added 2,4-dichloro(chloromethyl)benzene (586 mg, 3.0 mmol). The reaction mixture was d to stir for 24 hours (h). Water was added to the reaction e, and the aqueous phase was extracted with EtOAc (x3). The combined organic extracts were washed with brine, dried with Nast4, filtered, and concentrated. Purification by normal phase chromatography gave a white solid (440 mg, %): mp 165—168 0C, 1H NMR (400 MHz, CDC13) 5 7.68 (dd, J: 8.6, 7.8 Hz, 1H), 7.54 (d, J: 8.3 Hz, 1H), 7.43 (d, J: 2.1 Hz, 1H), 7.28 (d, J: 2.1Hz, 1H), 7.23 (d, J: 1.8 Hz, 1H), 7.21 (d, J = 1.6 Hz, 1H), 5.50 (s, 2H), 4.83 (s, 2H), 3.97 (d, J = 0.8 Hz, 3H); ESIMS m/z 489 ([M-H]).
Compounds 18 and 19 in Table l were sized as in Example 3.
Example 4. Preparation of 4-trifluoromethoxybenzyl 4-aminochloro(4-chlorofluoro- 3-methoxyphenyl)fluoropicolinate (Compound 20) A suspension of 4-aminochloro(4-chloro-2—fluoromethoxyphenyl) fluoropicolinic acid (200 mg, 0.573 mmol), l-(bromomethyl)(trifluoromethoxy)benzene (161 mg, 0.630 mmol) and K2C03 (l 19 mg, 0.859 mmol) in DMF (2 mL) was heated at 50 OC overnight. The reaction mixture was then concentrated in vacuo. The residue was purified by silica gel chromatography (eluting with 0-80% EtOAc/hexane gradient) to yield a white solid (154 mg, : mp 155—156 0C; 1H NMR (400 MHZ, g) 5 7.60 (d, J = 8.7 Hz, 2H), 7.47 (dd, J: 8.5, 1.5 Hz, 1H), 7.41 (d, J: 8.0 Hz, 2H), 7.29 (dd, J: 8.5, 7.1 Hz, 1H), 7.14 (s, 2H), 5.41 (s, 2H), 3.95 — 3.90 (m, 3H); ESIMS m/z 523 ([M+H]+), 52l ([M—H]'). l5 Compounds 21-34 in Table l were synthesized as in Example 4.
Example 5. Preparation of benzyl 6-amino(4-chlorofluoro-3 -methoxyphenyl) Vinylpyrimidinecarboxylate (Compound 35) 6-Amino(4-chlorofluoromethoxyphenyl)Vinylpyrimidinecarboxylic acid (prepared by the methods described in U.S. Pat. 7,786,044 B2; 0.150 g, 0.463 mmol), (bromomethyl)benzene (0.103 g, 0.602 mmol), and lithium carbonate (leCOg; 0.044 g, 0.602 mmol) were combined in DMF (1.5 mL) and heated at 60 OC overnight. The cooled reaction mixture was concentrated and then partitioned between EtOAc and water. The organic phase was dried, concentrated and purified by column tography (eluting with an EtOAc/hexanes gradient) to yield benzyl 6-amino(4-chlorofluoromethoxyphenyl) Vinylpyrimidinecarboxylate as a white solid (0.154 g, 80%): mp 119—121 0C; 1H NMR (400 MHz, CDClg) 5 7.67 (dd, J: 8.5, 7.5 Hz, 1H), 7.49 — 7.42 (m, 2H), 7.42 — 7.32 (m, 3H), 7.21 (dd, J: 8.6, 1.7 Hz, 1H), 6.70 (dd, J: 17.8, 11.6 Hz, 1H), 5.60 (dd, J: 7.7, 1.0 Hz, 1H), 5.57 (s, 1H), 5.39 (s, 2H), 5.35 (s, 2H), 4.00 (d, J: 0.8 Hz, 3H); ESIMS m/z 414 ([M+Hl+). e 6. Preparation of oxybenzyl 4-aminochloro(4-chlorofluoro methoxyphenyl)picolinate (Compound 36) To a solution of 4-aminochloro(4-chlorofluoromethoxyphenyl)picolinic acid (600 mg, 1.81 mmol) in THF (10 mL) was added triphenylphosphine (475 mg, 1.81 mmol), diethyl arboxylate (0.29 mL, 1.81 mmol), and 4-methoxybenzyl l (0.34 mL, 2.72 mmol). The reaction mixture was stirred for 48 h. onal triphenylphosphine (475 mg, 1.81 mmol) was added to the reaction, and the reaction mixture was stirred for 24 h.
The on mixture was concentrated to dryness and was ed by silica gel chromatography (eluting with a 0-100% EtOAc/hexane gradient) to provide an off-white solid (170 mg, 26%): mp 73—83OC; 1H NMR (400 MHz, CDC13) 5 7.66 (dd, J = 8.6, 7.8 Hz, 1H), 7.45 — 7.38 (m, 2H), 7.22 (dd, J: 8.7, 1.8 Hz, 1H), 7.16 (d, J: 1.7 Hz, 1H), 6.94 — 6.87 (m, 2H), 5.38 (s, 2H), 4.80 (s, 2H), 3.96 (d, J: 0.8 Hz, 3H), 3.81 (s, 3H); ESIMS m/z 451 +), 449 ([M—H]').
Compound 37 in Table 1 was synthesized as in Example 6.
Example 7. Preparation of benzyl 4-amino-3 -chloro(2,4-dichloro-3 -methoxyphenyl)- picolinate (Compound 38) Methyl 4-aminochloro(2,4-dichloromethoxyphenyl)picolinate (Compound C, prepared by the methods described in U. S. Patent 7,314849 B2; 500 mg, 1.4 mmol) was dissolved in benzyl alcohol (10 mL), treated with titanium(IV) isopropoxide (ca 100 uL) and heated at 85—90 0C. After 2 h, another n of titanium(IV) isopropoxide (100 uL) was added and heating was continued for another 18 h. The volatiles were removed under high vacuum, and the residue was purified by silica gel chromatography (eluting with 5% EtzO— % dichloromethane (CH2C12)—65% hexane). The material was further purified by reverse phase high mance liquid chromatography (RP-HPLC; eluting with 70% acetonitrile) to give the title compound (375 mg, 61%): mp 107—108 0C; 1H NMR (400 MHZ, CDC13) 5 7.50 — 7.26 (m, 8H), 6.97 (s, 1H), 5.42 (s, 2H), 4.85 (s, 2H), 3.91 (s, 3H); ESIMS m/z 437 ([M+H]+).
Compound 39 in Table 1 was synthesized as in Example 7.
Example 8. Preparation of benzyl 4-aminochloro(4-chlorofluoro(1- fluoroethyl)phenyl)fluoropicolinate (Compound 40) Step A. Methyl 4-aminochloro(4-chlorofluoro(1-fluoroethyl)phenyl) fluoropicolinate (Compound H). 2-(4-Chloro-2—fluoro(1-fluoroethyl)phenyl)-4,4,5,5- tetramethyl-1,3,2-dioxaborolane (510 mg, 1.7 mmol, 1.0 equivalent (equiv)) and methyl 4- amino-3,6-dichlorofluoropicolinate (prepared by the methods described in U.S. Patent 6,784,137 B2; 400 mg, 1.7 mmol, 1.0 equiv) were sequentially added to a 5 mL Biotage ave vessel, followed by cesium fluoride (CsF; 510 mg, 3.3 mmol, 2.0 equiv), palladium(II) acetate (19 mg, 0.084 mmol, 0.05 , and sodium 3,3‘,3"- phosphinetriyltribenzenesulfonate (95 mg, 0.17 mmol, 0.10 equiv). A 3:1 mixture of water— acetonitrile (3.2 mL) was added and the resulting brown mixture was heated in a benchtop microwave at 1500C for 5 min. The cooled reaction mixture was d with water (150 mL) and extracted with CHzClz (4 x 50 mL). The ed organic extracts were dried with ium sulfate (MgSO4), gravity filtered, and concentrated by rotary evaporation. The residue was purified by reverse phase column tography (eluting with a 5% acetonitrile to 100% acetonitrile gradient) to afford the desired t, methyl 4-aminochloro(4- chloro-2—fluoro(1-fluoroethyl)phenyl)fluoropicolinate as a tan semisolid (220 mg, %): IR (thin film) 3475 (w), 3353 (m), 3204 (w), 3001 (w), 2955 (w), 1738 (s), 1711 (s), 1624 (s)cm'1; 1H NMR (300 MHz,CDC13) 5 7.50 (m, 1H), 7.30 (m, 1H), 7.21 (d, J = 2 Hz, 1H), 6.16 (dq, J: 46, 7 Hz, 1H), 4.96 (br s, 2H), 3.97 (s, 3H), 1.75 (dd, J: 23, 7 Hz, 3H); ESIMS m/z 379 ([M+H]+).
WO 03042 Step B. 4-Aminochloro(4-chloro-2—fluoro(1-fluoroethyl)phenyl) fluoropicolinic acid. A 2 molar (M) on of aqueous sodium hydroxide (NaOH; 580 uL, 1.2 mmol, 4.0 equiv) was added to a stirred suspension of methyl 4-aminochloro(4- chlorofluoro(1-fluoroethyl)phenyl)fluoropicolinate (110 mg, 0.29 mmol, 1.0 equiv) in methyl alcohol (1.9 mL) at 23 OC. The resulting homogeneous pale yellow solution was stirred at 23 0C for 20 h. The reaction e was adjusted to approximately pH=4 via dropwise addition of trated hydrochloric acid (HCl) and concentrated via rotary ation. The residue was slurried in water and vacuum filtered to afford the desired product, 4-amino-3 -chloro(4-chloro-2—fluoro(1-fluoroethyl)phenyl)fluoropicolinic acid as a white powder (55 mg, 50%): IR (thin film) 3319 (m), 3193 (w), 2983 (w), 1719 (m), 1629 (s)cm'1; 1H NMR (300 MHz, g) 5 7.58 (t, J: 9 Hz, 1H), 7.49 (d, J = 9 Hz, 1H), 6.99 (br s, 2H), 6.15 (dq, J: 44, 7 Hz, 1H), 1.71 (dd, J: 23, 7 Hz, 3H); ESIMS m/z 365 ([M+H]+).
Step C. Benzyl 4-aminochloro(4-chloro-2—fluoro(1-fluoroethyl)phenyl) fluoropicolinate. Triethylamine (190 uL, 1.4 mmol, 2.0 equiv) and benzyl bromide (120 uL, 1.0 mmol, 1.5 equiv) were sequentially added to a stirred solution of 4-amino-3 -chloro(4- chloro-2—fluoro(1-fluoroethyl)phenyl)fluoropicolinic acid (0.25 g, 0.69 mmol, 1.0 equiv) in THF (3.4 mL) at 23 OC. The resulting cloudy pale yellow solution was stirred at 23 0C for 18 h. The reaction mixture was diluted with water (150 mL) and extracted with CH2C12 (3 x 70 mL). The combined c layers were dried (MgSO4), gravity filtered, and concentrated by rotary evaporation. The residue was purified by reverse phase column chromatography (eluting with a 5% acetonitrile to 100% acetonitrile gradient) to afford the desired product, benzyl 4-amino-3 -chloro(4-chlorofluoro(1-fluoroethyl)phenyl) fluoropicolinate as a yellow semisolid (160 mg, 52%): IR (thin film) 3485 (m), 3393 (m), 3196 (w), 3035 (w), 2983 (w), 1737 (s), 1622 (s) cm'l; 1H WR (300 MHz, CDC13) 5 7.23 — 7.57 (m, 7H), 6.18 (dq, J: 45, 6 Hz, 1H), 5.45 (s, 2H), 4.94 (br s, 2H), 1.78 (ddd, J: 23,7, 1 Hz, 3H); ESIMS m/z 453 ([M+H]+).
Example 9. Preparation of benzyl 4-amino-3 -chloro(4-chloro-3 -ethoxyfluorophenyl) fluoropicolinate (Compound 41) Step A. Methyl 4-aminochloro(4-chloroethoxyfluorophenyl) fluoropicolinate (Compound A). 2-(4-Chloroethoxyfluorophenyl)-4,4,5,5-tetramethyl- 1,3,2-dioxaborolane (500 mg, 1.7 mmol, 1.0 equiv) and methyl 4-amino-3,6-dichloro fluoropicolinate (400 mg, 1.7 mmol, 1.0 equiv) were sequentially added to a 5 mL Biotage microwave vessel, followed by CsF (510 mg, 3.3 mmol, 2.0 equiv), palladium(H) acetate (19 mg, 0.084 mmol, 0.05 equiv), and sodium 3,3',3"-phosphinetriyltribenzene-sulfonate (95 mg, 0.17 mmol, 0.10 equiv). A 3:1 mixture of water—acetonitrile (3.2 mL) was added, and the resulting brown mixture was heated in a benchtop microwave at 150 0C for 5 min. The cooled reaction mixture was diluted with water (150 mL) and extracted with CH2C12 (4 x 50 mL). The combined organic extracts were dried ), gravity filtered, and concentrated by rotary evaporation. The residue was purified by silica gel column tography ng with 33% hexane) to afford the desired product, methyl 4-aminochloro (4-chloroethoxyfluorophenyl)fluoropicolinate as a tan powder (450 mg, 63%): mp 170—172 0C; IR (thin film) 3485 (m), 3380 (s), 2951 (w), 1739 (s), 1610 (s)cm'1; 1H NMR (300 MHz, CDClg) 5 7.20 — 7.30 (m, 2H), 4.95 (br s, 2H), 4.19 (q, J = 7 Hz, 2H), 3.98 (s, 3H), 1.43 (t, J = 7 Hz, 3H); ESIMS m/z 377 ([M+H]+).
Step B. 4-Aminochloro(4-chloroethoxyfluorophenyl)fluoropicolinic acid. A 2 M solution of aqueous NaOH (900 uL, 1.8 mmol, 4.0 equiv) was added to a stirred suspension of methyl ochloro(4-chloroethoxyfluorophenyl) fluoropicolinate (170 mg, 0.45 mmol, 1.0 equiv) in methyl alcohol (3.0 mL) at 23 OC. The resulting geneous white mixture was stirred at 23 0C for 4 h. The on mixture was adjusted to approximately pH=4 via se addition of concentrated HCl and then concentrated via rotary evaporation. The residue was slurried in water and vacuum filtered to afford the desired product, 4-aminochloro(4-chloroethoxyfluorophenyl) fluoropicolinic acid as a white powder (140 mg, 88%): mp 163—165 0C; IR (thin film) 3486 (m), 3377 (s), 3155 (W), 2981 (w), 2935 (w), 1718 (s), 1614 (s) cm]; 1H NMR (300 MHz, DMSO-dg) 5 7.45 (dd, J = 9, 2 Hz, 1H), 7.28 (dd, J: 9, 7 Hz, 1H), 7.01 (br s, 2H), 4.15 (q, J = 7 Hz, 2H), 1.33 (t, J = 7 Hz, 3H); ESIMS m/z 363 ([M+H]+).
Step C. Benzyl 4-aminochloro(4-chloroethoxyfluorophenyl) fluoropicolinate. Triethylamine (290 uL, 2.1 mmol, 2.0 equiv) and benzyl bromide (190 uL, 1.6 mmol, 1.5 equiv) were sequentially added to a stirred on of 4-aminochloro(4- chloroethoxyfluorophenyl)fluoropicolinic acid (0.38 g, 1.1 mmol, 1.0 equiv) in THF (7.0 mL) at 23 OC. The resulting cloudy brown solution was stirred at 23 0C for 18 h. The reaction mixture was diluted with water (150 mL) and extracted with CH2C12 (3 x 70 mL).
The combined organic extracts were dried (MgSO4), y filtered, and concentrated by rotary evaporation. The residue was purified by RP-HPLC (eluting with a 5% acetonitrile to 100% acetonitrile nt) to afford the desired t, benzyl 4-aminochloro(4- chloroethoxyfluorophenyl)fluoropicolinate as a white powder (230 mg, 49%): mp 122—124 0C; IR (thin film) 3477 (s), 3372 (s), 3194 (w), 3036 (w), 2992 (m), 2943 (w), 2900 (w), 1729 (s), 1616 (s)cm'1; 1H NMR (300 MHz,CDC13)5 7.49 — 7.32 (m, 5H), 7.29 — 7.21 (m, 2H), 5.43 (s, 2H), 4.91 (br s, 2H), 4.19 (q, J = 7 Hz, 2H), 1.43 (t, J = 7 Hz, 3H); ESIMS m/z 453 ([M+H]+).
Example 10. Preparation of benzyl 4-aminochloro(4-cyclopropylphenyl) icolinate (Compound 42) Step A. Ethyl ochloro(4-cyclopropylphenyl)fluoropicolinate. 4- Cyclopropylphenylboronic acid (250 mg, 1.5 mmol, 1.2 equiv) and methyl 4-amino-3,6- dichlorofluoropicolinate (300 mg, 1.3 mmol, 1.0 equiv) were sequentially added to a 5 mL Biotage microwave vessel, followed by CsF (380 mg, 2.5 mmol, 2.0 equiv), ium(H) acetate (14 mg, 0.063 mmol, 0.05 equiv), and sodium "-phosphinetriyl- tribenzenesulfonate (71 mg, 0.13 mmol, 0.10 equiv). A 3:1 mixture of water—acetonitrile (2.5 mL) was added, and the resulting brown mixture was heated in a benchtop microwave at 150 0C for 5 min. The cooled on mixture was diluted with water (150 mL) and extracted with CHzClz (4 x 50 mL). The combined organic extracts were dried (MgS O4), gravity filtered, and concentrated by rotary evaporation. The residue was ed by RP-HPLC (eluting with a 5% acetonitrile to 100% acetonitrile gradient) to afford the desired product, methyl 4-aminochloro(4-cyclopropylphenyl)fluoropicolinate as a white powder (310 mg, 78%): mp 9 0C; IR (thin film) 3475 (s), 3357 (s), 3089 (w), 3013 (w), 2954 (w), 1724 (m), 1607 (m) cm]; 1H NMR (300 MHz, CDClg) 5 7.81 (m, 2H), 7.15 (m, 2H), 4.85 (br s, 2H), 3.98 (s, 3H), 1.94 (m, 1H), 1.01 (m, 2H), 0.74 (m, 2H); ESIMS m/z 321 ([M+H]+).
Step B. ochloro(4-cyclopropylphenyl)fluoropicolinic acid. A 2 M solution of aqueous NaOH (600 uL, 1.2 mmol, 2.0 equiv) was added to a stirred suspension of methyl 4-aminochloro(4-cyclopropylphenyl)fluoropicolinate (190 mg, 0.59 mmol, 1.0 equiv) in methyl alcohol (3.0 mL) at 23 OC. The resulting heterogeneous white mixture was stirred at 23 0C for 3 h. The reaction mixture was ed to imately pH=4 via dropwise addition of concentrated HCl and then concentrated via rotary evaporation. The residue was slurried in water and vacuum filtered to afford the desired product, 4-amino chloro(4-cyclopropylphenyl)fluoropicolinic acid as a white powder (170 mg, 94% yield): mp 147—149 0C; IR (thin film) 3463 (s), 3339 (s), 3202 (m), 3084 (w), 3007 (w), 1721 (m), 1630 (s) cm'l; 1H NMR (300 MHz, DMSO-dg) 5 7.70 (m, 2H), 7.17 (m, 2H), 6.81 (br s, 2H), 1.96 (m, 1H), 0.99 (m, 2H), 0.71 (m, 2H); ESIMS m/z 307 ([M+H]+).
Step C. Benzyl 4-aminochloro(4-cyclopropylphenyl)fluoropicolinate.
Triethylamine (220 uL, 1.6 mmol, 2.0 equiv) and benzyl bromide (140 uL, 1.2 mmol, 1.5 equiv) were sequentially added to a stirred solution of 4-aminochloro(4-chloro ethoxyfluorophenyl)fluoropicolinic acid (0.24 g, 0.78 mmol, 1.0 equiv) in THF (5.2 mL) at 23 OC. The resulting cloudy pale yellow solution was stirred at 23 0C for 72 h. The reaction mixture was diluted with water (150 mL) and extracted with CH2C12 (3 x 70 mL).
The combined organic extracts were dried (MgSO4), gravity filtered, and concentrated by rotary evaporation. The residue was purified by RP-HPLC ng with a 5% acetonitrile to 100% acetonitrile gradient) to afford the desired product, benzyl 4-aminochloro(4- cyclopropylphenyl)fluoropicolinate as a white powder (180 mg, 58%): mp 129—131 0C; IR (thin film) 3389 (s), 3229 (w), 3194 (w), 3083 (w), 3068 (w), 3033 (w), 3008 (w), 1737 (s), 1616 (s)cm'1; 1H NMR (300 MHz, CDC13) 5 7.83 (m, 2H), 7.48 (m, 2H), 7.33 — 7.42 (m, 3H), 7.15 (m, 2H), 5.43 (s, 2H), 4.82 (br s, 2H), 1.94 (m, 1H), 1.01 (m, 2H), 0.75 (m, 2H); ESIMS m/z 497 ([M+H]+).
Example 11: Preparation of benzyl 4-aminobromo(4-chlorofluoromethoxy- phenyl)fluoropicolinate (Compound 43) Step A. A mixture of methyl 4,5,6-trichloropicolinate red by the s described in U. S. Patent 6,784,137 B2; 25 g, 0.10 moles (mol)) and benzyl alcohol (100 g, 0.2 mol) in a 250 mL three-neck round bottom flask was heated under en at 100 0C.
Titanium isopropoxide (0.6 g, 0.02 mol) was added. After 4 h at 100 0C, the nearly colorless solution was cooled and transferred to a 250 mL round bottom single neck flask. Excess benzyl alcohol was removed under vacuum to give a nearly white solid (31 g, 94%): mp 125—126.5 0C; 1H NMR (400 MHz, CDClg) 5 8.08 (s, 1H, ne H), 7.42 (m, 2H, phenyl), 7.31 (m, 3H, phenyl), 5.40 (s, 2H, CHzPh); 13C{1H} NMR (101 MHz, CDC13)5 162.0 (COzR), 150.4, 145.0, 144.9, 134.7, 133.1, 128.3 (phenyl CH), 125.4 (pyridine CH), 67.88 (CHzPh).
Step B. A 250 mL three-neck flask equipped with a reflux condenser and nitrogen (N2) inlet was charged with benzyl 4,5,6-trichloropicolinate (17.77 g, 56.10 mmol), 2-(4- fluoromethoxyphenyl)-1,3,2-dioxaborinane (19.20 g, 79.0 mmol) and CsF (17.04 g, 112.0 mmol). Acetonitrile (100 mL) and water (30 mL) were added. The reaction mixture WO 03042 was evacuated/backfilled with N2 (5x). Solid dichlorobis(triphenylphosphine)palladium(H) (Pd(PPh3)2Cl2; 1.724 g, 2.456 mmol) was added. The solution was evacuated/backfilled with N2 (5x) and then d at reflux for 90 min. A white solid precipitated upon cooling to room ature. The solid was filtered, washed with water and dried in air (18.66 g, 75%): 1H NMR (400 MHz, CDC13) 5 8.23 (s, 1H, pyridine H), 7.52 — 7.32 (m, 5H, phenyl), 7.27 (dd, JH_H = 8.4 Hz = 1.7 Hz, 1H, aromatic), 7.10 (dd, JH_H = 8.4 Hz, JF_H = 6.8 Hz, 1H, , JF_H aromatic), 5.44 (s, 2H, CH2Ph), 3.98 (d, J1;H = 1.3 Hz, 3H, OMe); 13C{1H} NMR (101 MHz, CDC13)5163.0, 153.7, 153.5 (d, JF_C = 253 Hz, C2’), 146.0, 144.5 (d, JF_C =13 Hz), 144.1, 135.0, 134.2, 129.9 (d, JF_C = 3 Hz), 128.5, 126.1, 125.8 (d, JF_C = 14 Hz), 125.3 (d, JF_C = 3 Hz), 124.9 (d, JF_C = 2 Hz), 67.9 (CH2), 61.5 (d, JF_C = 4 Hz, OMe). Anal. Calcd for C20H13C13FN03: C, 54.51; H, 2.97; N, 3.18. Found: C, 54.60; H, 3.08; N, 3.16.
Step C. A 250 mL three-neck flask was equipped with a distillation head, a N2 inlet, a mechanical stirrer and a thermocouple. The flask was charged with CsF (21.07 g, 139.0 mmol). Anhydrous DMSO (100 mL) was added, and the suspension was evacuated/backfilled (5x) with N2. The suspension was heated at 80 0C for 30 min. DMSO (30 mL) was distilled off under vacuum to remove any residual water. Solid benzyl 4,5- dichloro(4-chlorofluoromethoxyphenyl)picolinate (15.34 g, 34.8 mmol) was added, and the solution was ted/backfilled with N2 (5x). The reaction mixture was heated to 105 0C under N2. After 6 h at 105 0C, analysis of an aliquot by GC showed no peak for the monofluoro intermediate. The reaction mixture was allowed to cool to room temperature.
The reaction mixture was poured into ice—water (400 g) and was extracted with EtOAc (3 x 200 mL). The combined organic extracts were washed with saturated (satd) NaHC03 solution, water (5 x 100 mL) and brine. The ts were dried (MgSO4) and concentrated under reduced pressure to give a tan solid (12.97 g). The solid was purified by flash chromatography (330 g silica column; 0—20% EtOAc-gradient) to give a white solid (9.95 g; 70%): mp 114—116 0C; 1H NMR (400 MHz, CDC13) 5 8.01 (dd, JF_H = 9.4, 5.5 Hz, 1H, ne H), 7.53 — 7.20 (m, 7H, phenyl), 5.44 (s, 2H, CH2Ph), 3.99 (d, JF_H = 1.2 Hz, 3H, OMe); 13C NMR (101 MHz, CDClg) 5 162.8 (d, JF_C = 3 Hz, CO2Bn), 156.2 (dd, JF_C = 267, 12 Hz), 153.9 (d, JF_C = 255 Hz), 148.0 (dd, JF_C = 269, 11 Hz), 145.4 (t, JF_C = 7 Hz), 144.7 (d, JF_C = 13 Hz), 144.6 (dd, JF_C = 13, 2 Hz), 135.2 (s), 130.6 (d, JF_C = 3 Hz), 125.6 (d, JF_C = 4 Hz), 125.4 (d, JF_C = 2 Hz), 122.0 (d, JF_C = 14 Hz), 115.0 (d, JF_C = 16 Hz), 67.9 (s, CH2Ph), 61.6 (d, J1;C = 5 Hz, OMe); 19F{1H} NMR (376 MHz, CDC13) 5 —123.90 (d, J1;F = 19.7 Hz, F4), -128.37 (d, JF_F = 33.5 Hz, F2’), -139.64 (dd, JF_F = 33.5, 19.7 Hz, F5). Anal.
Calcd for C20H13ClF3N03: C, 58.91; H, 3.21; N, 3.43. Found: C, 59.03; H, 3.20; N, 3.39.
Step D. Benzyl 4,5-dif1uoro(4-chlorofluoromethoxyphenyl)picolinate (4.99 g, 12.2 mmol) was slurried in DMSO (100 mL). Ammonia was bubbled through the solution for 30 min. After stirring overnight, the reaction mixture was poured into ice—water (500 mL). The product was extracted into EtOAc (3 x 150 mL). The combined organic extracts were washed with water (5 x 100 mL) and brine, dried (MgS O4) and concentrated under reduced pressure to give a white solid (4.99 g, 101%); 1H NMR (400 MHz, CDC13) 5 7.52 (d, JF_H = 6.5 Hz, 1H, ne H3), 7.45 — 7.38 (m, 2H), 7.37 — 7.17 (m, 5H), 5.38 (s, 2H, CHzPh), 4.67 (br s, 2H, NHz), 3.94 (d, J1;H = 1.1 Hz, 3H, 0M6); 13C{1H} NMR (101 MHz, CDC13) 5 164.4 (COZR), 153.9 (d, JF_C = 254 Hz), 147.6 (d, JF_C = 256 Hz), 144.4 (d, JF_C = 14 Hz), 144.0 (d, JF_C = 5 Hz), 142.2 (d, JF_C = 12 Hz), 140.4 (d, JF_C = 15 Hz), 135.6 (s), 129.5 (d, JF_C = 3 Hz), 128.5 (CH), 128.3 (CH), 128.3 (CH), 125.6 (d, JF_C = 3 Hz, CH), 125.2 (d, JF_C = 4 Hz, CH), 123.3 (dd, JF_C = 14, 4 Hz), 113.1 (d, JF_C = 4 Hz, C3), 67.3 (s, CHzPh), 61.5 (d, J1;C = 4 Hz, 0M6); 19F{1H} NMR (376 MHz, CDC13) 5 -128.54 (dd, J = 30.7, 5.2 Hz, F2’), -141.84 (dd, J = 30.8, 6.5 Hz, F5). HRMS-ESI (m/z) [M]+ calcd for C20H15C1F2N203, 404.0739; found, 404.0757.
Step E. N—Bromosuccinimide (NBS; 580 mg, 3.3 mmol, 1.1 equiv) was added to a stirred suspension of benzyl 4-amino(4-chlorofluoromethoxyphenyl)fluoro- nate (1.2 g, 3.0 mmol, 1.0 equiv) in 1,2-dichloroethane (15 mL) at 23 OC. The resulting bright yellow mixture was stirred at 23 0C for 72 h. The brown reaction e was trated by N2 stream and the residue was ed by silica gel column chromatography (eluting with 29% EtOAc/hexane) to afford the desired product, benzyl 4-aminobromo (4-chlorofluoromethoxyphenyl)fluoropicolinate as a tan powder (1.3 g, 93%): mp 6 0C; IR (thin film) 3370 (s), 3225 (w), 3190 (w), 3093 (w), 3066 (w), 3037 (w), 2948 (w), 1731 (s), 1616 (s)cm'1; 1H NMR (400 MHz, CDC13) 5 7.47 (m, 2H), 7.41 — 7.33 (m, 3H), 7.26 — 7.22 (m, 2H), 5.42 (s, 2H), 4.98 (br s, 2H), 3.96 (d, J = 1 Hz, 3H); ESIMS m/z 485 ([M+H]+).
Example 12: Preparation of (E)-benzyl 4-amino(4-chlorofluoromethoxy-phenyl) (2-chlorovinyl)fluoropicolinate (Compound 44) Step A. Tributyltin hydride (2.0 mL, 7.3 mmol, 1.0 equiv) and ethynyltrimethylsilane (2.1 mL, 15 mmol, 2.0 equiv) were combined, 2,2’-azobis(2-methylpropionitrile) (AIBN; 60 mg, 0.36 mmol, 0.05 equiv) was added, and the resulting colorless neat solution was heated to 80 OC. Upon heating, an exothermed to ~110 0C was observed. The reaction mixture was cooled back to 80 OC and d for 20 h. The on mixture was cooled to 23 0C to afford the crude desired product, (E)-trimethyl(2-(tributylstannyl)vinyl)silane, as a pale yellow oil (2.8 g, 99% crude yield): 1H NMR (400 MHz, CDClg) 5 6.96 (d, J: 22.5 Hz, 1H), 6.60 (d, J = 22.5 Hz, 1H), 1.54 — 1.44 (m, 6H), 1.35 — 1.23 (m, 6H), 0.91 — 0.82 (m, 15H), 0.03 (s, 9H).
Step B. (E)-Trimethyl(2-(tributylstannyl)vinyl)silane (1.1 g, 2.7 mmol, 1.1 equiv) was added to a stirred mixture of benzyl 4-aminobromo(4-chlorofluoro methoxyphenyl)fluoropicolinate (Compound 43; 1.2 g, 2.5 mmol, 1.0 equiv) and tetrakis(triphenylphosphine)palladium(0) (290 mg, 0.25 mmol, 0.10 equiv) in DMF (8.3 mL) at 23 OC. The reaction mixture was heated to 90 OC, resulting in a homogeneous dark yellow solution, and the reaction mixture was stirred for 20 h. The cooled reaction e was diluted with water (400 mL) and ted with Eth (4 x 100 mL). The c layer was dried (MgSO4), gravity filtered, and concentrated by rotary evaporation. The residue was purified by reverse phase column chromatography (5% acetonitrile to 100% acetonitrile gradient) to afford the desired product, (E)-benzyl 4-amino(4-chlorofluoro yphenyl)fluoro(2-(trimethylsilyl)vinyl)picolinate, as a light brown oil (460 mg, 38%): IR (thin film) 3483 (w), 3376 (m), 3206 (w), 3069 (w), 2955 (s), 2897 (w), 1732 (s), 1619 (s) cm-1; 1H NMR (400 MHz, CDCl3) 5 7.44 — 7.27 (m, 7H), 6.94 (d, J = 20 Hz, 1H), 6.28 (d, J: 20 Hz, 1H), 5.33 (s, 2H), 4.62 (br s, 2H), 3.95 (d, J: 1 Hz, 3H), 0.09 (s, 9H); ESIMS m/z 503 ([M+H]+).
WO 03042 Step C. N—Chlorosuccinimide (NCS; 190 mg, 1.4 mmol, 2.0 equiv) was added to a stirred solution of (E)-benzyl 4-amino(4-chlorofluoromethoxyphenyl)fluoro(2- (trimethylsilyl)vinyl)picolinate (350 mg, 0.70 mmol, 1.0 equiv) in DMF (7.0 mL) at 23 OC.
The homogeneous pale green solution was heated to 50 OC and d for 24 h. The cooled reaction mixture was diluted with water (400 mL) and extracted with Eth (4 x 100 mL).
The combined organic layers were dried (MgSO4), gravity ed, and concentrated by rotary evaporation. The residue was purified by reverse phase column chromatography (5% acetonitrile to 100% acetonitrile gradient) to afford the desired product, (E)-benzyl 4-amino- 6-(4-chlorofluoromethoxyphenyl)(2-chlorovinyl)fluoropicolinate as a tan powder (70 mg, 22% yield): mp 133—135 0C; IR (thin film) 3486 (s), 3345 (s), 3215 (w), 3069 (w), 3037 (w), 2953 (w), 1719 (s), 1616 (s) cm'1; 1H NMR (400 MHz, CDC13) 5 7.47 — 7.43 (m, 2H), 7.41 — 7.33 (m, 3H), 7.27 (m, 2H), 6.89 (d, J: 14 Hz, 1H), 6.45 (d, J: 14 Hz, 1H), 5.37 (s, 2H), 4.62 (br s, 2H), 3.97 (d, J = 1 Hz, 3H); ESIMS m/z 465 +).
Table 1. Structures of Compounds in Examples Compound WO 03042 Compound 2012/022286 Compound 2012/022286 Compound 2012/022286 Compound 2012/022286 Compound WO 03042 Compound Table 2. Analytical Data for Compounds in Table 1 Compound mp ESIMS 1H NMR (field strength, Other NMR Appearance Number ( °C) m/z solvent) Data (400 MHz, g) 5 7.45 (dd, J = 8.5, 1.6 Hz, 1H), 7.34 (d, J = 8.0 Hz, 453 2H), 7.28 (dd, J: 8.5, 3 Whlte mm. . 139 ([M+H]+) 7.1 Hz, 1H), 7.20 (d, J: 7.9 Hz, 2H), 7.07 (s, 2H), .32 (s, 2H), 3.92 (d, J = 0.8 Hz, 3H), 2.30 (s, 3H) (400 MHz, DMSO-dg) 5 7.92 — 7.84 (m, 2H), 7.65 (d, J = 8.5 Hz, 2H), 7.47 . . 464 (dd, J: 8.5, 1.6 Hz, 1H), 4 Whlte mm 151 ([M+H]+) 7.30 (dd, J = 8.5, 7.1 Hz, 1H), 7.10 (s, 2H), 5.48 (s, 2H), 3.93 (d, J = 0.9 Hz, (400 MHz, g) 5 469 7.43 (d, J: 8.4 Hz, 1H), Whlte mm. . 183— ([M+H]+), 7.29 — 7.12 (m, 4H), 6.88 184 467 (d, J = 8.7 Hz, 2H), 4.59 ([M-H]') (d, J = 4.4 Hz, 2H), 3.90 (s, 3H), 3.71 (s, 3H) (400 MHz, DMSO-dg) 5 7.79 (d, J: 8.2 Hz, 2H), 507 7.68 (d, J: 8.1 Hz, 2H), . . 118— ([M+H]+), 7.47 (dd, J: 8.5, 1.5 Hz, 6 Whlte mm 119 505 1H), 7.31 (dd, J = 8.5, ([M-H]') 7.1 Hz, 1H), 7.15 (s, 2H), .49 (s, 2H), 3.93 (d, J = 0.7 Hz, 3H) (400 MHz, CDClg) 5 8.03 — 7.94 (m, 2H), 7.70 449 —7.59 (m, 2H), 7.51 (dd, . 170— ([M+H]+), J = 10.6, 4.8 Hz, 2H), 7 Yellow SOhd 175 447 7.22 (dd, J = 7.7, 1.6 Hz, ([M-H]') 2H), 5.63 (s, 2H), 4.95 (s, 2H), 3.96 (d, J = 0.8 Hz, PCT/U82012/022286 Compound ESIMS 1H NMR (field strength, Other NMR Appearance Number m/z solvent) Data (400 MHz, DMso—d6) 5 453 7.50 — 7.38 (m, 2H), 7.33 ([M+H]+), —7.18 (m, 4H), 7.13 (s, White Solid 451 2H), 5.39 (s, 2H), 3.92 ([M-Hl') (d, J = 0.7 Hz, 3H), 2.35 (s, 3H) (400 MHz, 6) 5 474 7.62 (dd, J = 7.0, 2.3 Hz, ([M+H]+), 1H), 7.57 — 7.37 (m, 4H), White Solid 472 7.30 (dd, J: 8.5, 7.1 Hz, ([M-Hl) 1H), 7.14 (s, 2H), 5.45 (s, 2H), 3.92 (s, 3H) (400 MHz, DMso—d6) 5 7.46 (dd, J: 8.5,1.5 Hz, 1H), 7.43 — 7.33 (m, 2H), 7.29 (dd, J: 8.5, 7.1 Hz, White Solid 1H), 7.11 (s, 2H), 7.05 ([M+H]+) (d, J = 8.0 Hz, 1H), 6.96 (td, J = 7.4, 0.9 Hz, 1H), .34 (s, 2H), 3.92 (d, J = 0.5 Hz, 3H), 3.81 (s, 3H) (400 MHz, DMso—d6) 5 7.46 (dd, J: 8.5,1.5 Hz, 1H), 7.32 — 7.21 (m, 4H), ([M+H]+), White Solid 7.17 (d, J: 7.2 Hz, 1H), 7.13 (s, 2H), 5.34 (s, 2H), ([M-Hl') 3.92 (d, J: 0.7 Hz, 3H), 2.31 (s, 3H) (400 MHz, DMso—d6) 5 474 7.55 (s, 1H), 7.51 — 7.39 147— ([M+H]+), (m, 4H), 7.30 (dd, J = 12 White Solid 148 472 8.5, 7.1 Hz, 1H), 7.15 (s, ([M-Hl) 2H), 5.40 (s, 2H), 3.93 (d, J = 0.7 Hz, 3H) Compound 1H NMR (field strength, Other NMR Appearance Number solvent) Data (400 MHz, DMso—d6) 5 7.47 (dd, J: 8.5, 1.5 Hz, 469 1H), 7.36 — 7.25 (m, 2H), +), 7.14 (s, 2H), 7.02 (d, J = White Solid 467 7.4 Hz, 2H), 6.96 — 6.88 ([M-Hl') (m, 1H), 5.35 (s, 2H), 3.93 (d, J: 0.7 Hz, 3H), 3.74 (s, 3H) (400 MHz, DMso—d6) 5 19F NMR (376 7.50 — 7.43 (m, 3H), 7.41 MHz, DMSO- 453 — 7.35 (m, 2H), 7.35 — d6) 5 —129.03 ([M+H]+), 7.26 (m, 2H), 7.07 (s, Colorless Oil (d, J: 28.1 451 2H), 6.08 (q, J = 6.5 Hz, Hz), —137.77 ') 1H), 3.93 (d, J = 0.9 Hz, (d, J: 28.1 3H), 1.61 (d, J = 6.6 Hz, (400 MHz, DMso—d6) 5 7.47 (dd, J = 8.5, 1.6 Hz, 1H), 7.36 — 7.18 (m, 6H), ([M+H]+), White Solid 7.05 (s, 2H), 4.53 (t, J = 6.8 Hz, 2H), 3.93 (d, J: ([M-Hl') 1.0 Hz, 3H), 3.02 (t, J: 6.8 Hz, 2H) (400 MHz, DMso—d6) 5 8.02 — 7.95 (m, 2H), 7.59 498 (d, J = 8.5 Hz, 2H), 7.46 ([M+H]+), (dd, J: 8.5, 1.6 Hz, 1H), White Solid 496 7.30 (dd, J: 8.5, 7.1 Hz, ([M-Hl') 1H), 7.09 (s, 2H), 5.47 (s, 2H), 3.93 (d, J: 1.0 Hz, 3H), 3.86 (s, 3H) (400 MHz, CDClg) 5 7.64 (dd, J = 8.6, 7.8 Hz, 457 1H), 7.44 — 7.32 (m, 4H), ([M+H]+), 7.22 (dd, J = 87,18 Hz, White Solid 455 1H), 7.17 (d, J: 1.6 Hz, ([M-Hl') 1H), 5.40 (s, 2H), 4.85 (s, 2H), 3.96 (d, J = 0.9 Hz, Compound 1H NMR (field th, Other NMR Appearance Number solvent) Data (400 MHz, CDC13) 5 7.71 (dd, J = 8.6, 7.8 Hz, 1H), 7.49 (dd, J: 5.4, 3.4 Hz, 2H), 7.40 — 7.34 (m, 2H), 7.33 — 7.28 (m, ([M+H]+), White Solid 1H), 7.23 (dd, J: 8.7, 1.7 Hz, 1H), 7.18 (d, J: ([M-Hl') 1.6 Hz, 1H), 6.21 (q, J: 6.6 Hz, 1H), 4.80 (s, 2H), 3.97 (d, J: 0.8 Hz, 3H), 1.72 (d, J = 6.6 Hz, 3H) (400 MHz, acetone-d6) 5 8.33 — 8.25 (m, 2H), 7.85 — 7.77 (m, 2H), 7.40 ([M+H]+), White Solid (ddd, J: 15.3, 8.5, 4.1 Hz, 2H), 6.52 (s, 1H), ([M-Hl) .59 (s, 2H), 3.99 (d, J: 1.1 Hz, 3H) (400 MHz, DMSO-dg) 5 7.48 (dd, J = 8.5, 1.6 Hz, 1H), 7.34 (s, 4H), 7.27 . . 107— 485 (dd, J: 8.5, 7.1 Hz, 1H), 22 Whlte mm 108 ([M-H]') 7.09 (s, 2H), 4.52 (t, J = 6.6 Hz, 2H), 3.93 (d, J: 0.8 Hz, 3H), 3.01 (t, J: 6.6 Hz, 2H) (400 MHz, DMSO-dg) 5 457 7.50 — 7.41 (m, 2H), 7.34 160— ([M+H]+), — 7.26 (m, 3H), 7.20 (s, 23 Whlte mm. . 161 455 1H), 7.14 (s, 2H), 5.40 (s, ([M-H]') 2H), 3.92 (d, J = 0.6 Hz, (400 MHz, DMSO-dg) 5 7.55 — 7.50 (m, 2H), 7.46 24 Whlte mm. . 143— 457 (dd, J: 8.5, 1.5 Hz, 1H), 144 ([M+H]+) 7.31 — 7.20 (m, 3H), 7.13 (s, 2H), 5.36 (s, 2H), 3.92 (s, 3H) Compound 1H NMR (field strength, Other NMR Appearance Number solvent) Data (400 MHz, DMSO-dg) 5 7.57 (dt, J = 9.4, 4.7 Hz, 457 1H), 7.45 (ddd, J: 9.4, +), 4.6, 1.7 Hz, 2H), 7.26 White Solid 455 (ddd, J: 15.6, 7.3, 2.8 ([M-H]') Hz, 3H), 7.13 (s, 2H), .42 (s, 2H), 3.92 (d, J = 0.5 Hz, 3H) (400 MHz, DMSO-dg) 5 7.84 — 7.69 (m, 3H), 7.61 507 (t, J = 7.5 Hz, 1H), 7.48 ([M+H]+), (dd, J: 8.5, 1.5 Hz, 1H), White Solid 505 7.29 (dd, J: 8.5, 7.1 Hz, ([M-H]') 1H), 7.15 (s, 2H), 5.53 (s, 2H), 3.92 (d, J = 0.6 Hz, (400 MHz, DMSO-dg) 5 7.46 (dd, J: 8.5,1.5 Hz, 1H), 7.37 (d, J = 8.1 Hz, 2H), 7.32 — 7.23 (m, 3H), ([M+H]+), White Solid 7.12 (s, 2H), 5.32 (s, 2H), 3.92 (d, J: 0.7 Hz, 3H), ([M-Hl') 2.88 (dt, J = 13.7, 6.8 Hz, 1H), 1.19 (d, J: 6.9 Hz, (400 MHz, acetone-d6) 5 8.06 (s, 1H), 8.00 — 7.90 (m, 3H), 7.65 (dd, J: 8.5, 1.7 Hz, 1H), 7.59 — ([M+H]+), White Solid 7.51 (m, 2H), 7.40 (ddd, J: 15.3, 8.5, 4.1 Hz, ([M-Hl') 2H), 6.49 (s, 2H), 5.61 (s, 2H), 4.00 (d, J: 1.1 Hz, Compound 1H NMR (field strength, Other NMR Appearance Number solvent) Data (400 MHz, acetone-d6) 5 8.19 (dd, J: 1.7, 1.2 Hz, 1H), 8.01 (dt, J: 7.8, 1.4 Hz, 1H), 7.79 (ddd, J = 7.7, 1.7, 1.2 Hz, 1H), White Solid ’ 7.58 (t, J: 7.7 Hz, 1H), 7.43 (dd, J: 8.5, 1.5 Hz, ([M H1)' 1H), 7.37 (dd, J: 8.5, 6.7 Hz, 1H), 6.50 (s, 2H), .53 (s, 2H), 4.00 (d, J: 1.1 Hz, 3H), 3.90 (s, 3H) (400 MHz, acetone-d6) 5 7.51 (d, J: 8.2 Hz, 1H), 7.43 (dd, J: 8.5,1.6 Hz, . . 485 1H), 7.37 — 7.30 (m, 2H), Whlte SOhd ([M-H]') 7.26 (dd, J = 8.1, 2.0 Hz, 1H), 6.49 (s, 2H), 5.43 (s, 2H), 4.00 (d, J = 1.1 Hz, (400 MHz, acetone-d6) 5 485 7.50 — 7.39 (m, 3H), 7.33 . . ([M+H]+), (ddd, J: 8.4, 7.9, 4.4 Hz, 31 Whlte SOhd 145 483 3H), 6.48 (s, 2H), 5.38 (s, ([M-H]') 2H), 4.00 (d, J: 1.1 Hz, (400 MHz, acetone-d6) 5 8.02 (dd, J: 7813 Hz, 1H), 7.78 (dd, J: 7.8, + 0.6 Hz, 1H), 7.65 (td, J = 32 Colorless ([M+H] )’ 161 7.6, 1.4 Hz, 1H), 7.54 — Sohd 495 7.35 (m, 3H), 6.50 (s, ([M-H]') 1H), 5.82 (s, 2H), 4.01 (d, J: 1.1 Hz, 3H), 3.91 (s, 3H) (400 MHz, CDClg) 5 7.65 — 7.15 (m, 9H), 5.45 19 F NMR (376 . . 145— 417 (d, J: 4.1 Hz, 2H), 5.40 33 Whlte Sohd + MHz, CDC13) 147 ([M+H] ) (s, 2H), 3.99 (d, J— 1.0_ -129.38(s) Hz, 3H), 3.81 (d, J: 7.2 Hz, 3H) Compound mp ESIMS 1H NMR (field strength, Other NMR Appearance Number ( °C) m/z solvent) Data (400 MHz, CDClg) 5 7.59 (dd, J = 8.6, 7.5 Hz, 1H), 7.35 — 7.15 (m, 6H), 19F NMR (376 34 Clear on 5.63 (s, 2H), 4.63 (td, J = MHz, CDClg) 7.0, 4.0 Hz, 2H), 3.98 (d, 5 -129.46 (S) J: 0.9 Hz, 3H), 3.75 (s, 3H), 3.15 — 3.07 (m, 2H) (400 MHz, CDClg) 5 7.67 (dd, J = 8.6, 7.9 Hz, 1H), 7.29 (dd, J: 15.8, 3.6 Hz, 4H), 7.25 — 7.20 ([M+H]+) 37 Yellow on ’ (m, 2H), 7.19 (d, J = 1.6 Hz, 1H), 4.81 (s, 2H), ([M_H]_) 4.62 (t, J = 7.2 Hz, 2H), 3.97 (d, J: 0.7 Hz, 3H), 3.12 (t, J: 7.1 Hz, 2H) (400 MHz, CDClg) 5 White 90— 421 7.73 — 7.11 (m, 9H), 5.45 Crystals 91.5 ([M+H]+) (s, 2H), 4.81 (s, 2H), 3.97 (d, J = 0.6 Hz, 3H) Example 13. tion of General Postemergence Herbicidal Activity Seeds or nutlets of the desired test plant species were planted in Sun Gro Metro-Mix® 360 planting mixture, which typically has a pH of 6.0 to 6.8 and an c matter content of t, in plastic pots with a surface area of 84.6 square centimeters (cmz). When required to ensure good germination and healthy plants, a fungicide treatment and/or other chemical or physical treatment was applied. The plants were grown for 7-31 days (d) in a greenhouse with an approximate 15 hour (h) photoperiod which was maintained at 23—29 °C during the day and 22—28 0C during the night. Nutrients and water were added on a regular basis and supplemental lighting was provided with overhead metal halide 1000-Watt lamps as necessary. The plants were employed for testing when they reached the first or second true leaf stage.
Treatments consisted of esters of compounds 33 and 39 and F and G. Compound F is methyl 6-amino(4-chlorofluoromethoxyphenyl)methoxypyrimidine carboxylate; and compound G is methyl 4-aminochloro(4-chlorofluoro methoxyphenyl)picolinate. A weighed , ined by the highest rate to be tested, of each test compound was placed in a 25 mL glass vial and was dissolved in 4 mL of a 97:3 v/v (volume/volume) mixture of acetone and dimethyl sulfoxide (DMSO) to obtain concentrated stock solutions. If the test compound did not dissolve readily, the mixture was warmed and/or sonicated. The concentrated stock solutions obtained were d with 20 mL of an aqueous mixture containing acetone, water, isopropyl alcohol, DMSO, Atplus 411F crop oil concentrate, and Triton® X-155 surfactant in a 48.5:39:10: 1.5: 1.0:0.02 v/v ratio to obtain spray solutions containing the highest application rates. Additional ation rates were obtained by serial dilution of 12 mL of the high rate on into a solution containing 2 mL of a 97:3 v/v (volume/volume) mixture of e and DMSO and 10 mL of an aqueous e containing acetone, water, isopropyl alcohol, DMSO, Atplus 411F crop oil concentrate, and Triton X-155 surfactant in a 48.5:39:10:1.5:1.0:0.02 v/v ratio to obtain 1/2X, 1/4X, 1/8X and 1/16X rates of the high rate. Compound requirements are based upon a 12 mL application volume at a rate of 187 liters per hectare (L/ha). Formulated compounds were applied to the plant material with an overhead Mandel track sprayer equipped with 8002E nozzles calibrated to deliver 187 L/ha over an ation area of 0.503 square meters (m2) at a spray height of 18 inches (43 cm) above the average plant canopy height. Control plants were sprayed in the same manner with the t blank.
The treated plants and control plants were placed in a ouse as described above and d by sub-irrigation to prevent wash-off of the test compounds. After 14 d, the condition of the test plants as compared with that of the untreated plants was determined visually and scored on a scale of 0 to 100 percent where 0 corresponds to no injury and 100 corresponds to complete kill.
Some of the compounds tested, application rates employed, plant species tested, and results are given in Tables 3 and 4.
Table 3: ty of idal Compounds in Post-emergent Applications at Various Rates (14 Days After Application (DAA)) Application Compound Rate Number (g ai/ha) G 35 G 17.5 G 8.75 39 35 39 17.5 39 8.75 IPOHE = Ipomoea cea (Morningglory, ivyleaf) ORYSA = Oryza sativa (Rice) STEME = Stellaria media (Chickweed, common) TRZAS = Triticum aestivum (Wheat, spring) VIOTR = Viola tricolor (Pansy, wild) g ai/ha = grams active ingredient per hectare DAA = days after application Exam le 14. Evaluation of Postemer ence idal Activit in Cereal Cro s Seeds of the desired test plant species were d in Sun Gro Metro-Mix® 360 planting mixture, which typically has a pH of 6.0 to 6.8 and an organic matter content of 30 percent, in plastic pots with a surface area of 84.6 cmz. When required to ensure good germination and healthy plants, a fungicide treatment and/or other chemical or physical ent was applied. The plants were grown for 7-36 din a greenhouse with an approximate 14 h photoperiod which was maintained at 18 °C during the day and 17 0C during the night. Nutrients and water were added on a regular basis and supplemental lighting was provided with overhead metal halide 1000-Watt lamps as necessary. The plants were employed for testing when they reached the second or third true leaf stage.
Treatments ted of esters of compounds 33, 34, 39, 40 and 42 and B, F, G and H. Compound B is methyl 4-aminochloro(4-cyclopropylphenyl)fluoropicolinate; compound F is methyl 6-amino(4-chlorofluoromethoxyphenyl) methoxypyrimidinecarboxylate; compound G is methyl 4-aminochloro(4-chloro fluoromethoxyphenyl)picolinate; and compound H is methyl 4-aminochloro(4- chlorofluoro(1-fluoroethyl)phenyl)fluoropicolinate. A weighed amount, ined by the highest rate to be tested, of each test compound was placed in a 25 mL glass vial and was dissolved in 8 mL of a 97:3 v/v mixture of acetone and DMSO to obtain concentrated stock solutions. If the test compound did not dissolve readily, the e was warmed and/or sonicated. The concentrated stock solutions obtained were diluted with 16 mL of an aqueous e ning acetone, water, isopropyl alcohol, DMSO, Agri-dex crop oil concentrate, and ® X-77 surfactant in a 64.7:26.0:6.7:2.0:0.7:0.01 v/v ratio to obtain spray solutions containing the highest application rates. Additional application rates were obtained by serial dilution of 12 mL of the high rate solution into a solution containing 4 mL of a 97:3 v/v mixture of e and DMSO and 8 mL of an aqueous mixture containing acetone, water, isopropyl alcohol, DMSO, Agri-dex crop oil concentrate, and Triton® X-77 surfactant in a 9.0:10.0:1.5:1.0:0.02 v/v ratio to obtain 1/2X, 1/4X, 1/8X and 1/16X rates of the high rate. Compound requirements are based upon a 12 mL application volume at a rate of 187 L/ha. Formulated compounds were applied to the plant material with an overhead Mandel track sprayer equipped with 8002E nozzles calibrated to deliver 187 L/ha over an application area of 0.503 m2 at a spray height of 18 inches (43 cm) above average plant canopy height. l plants were sprayed in the same manner with the blank.
The treated plants and control plants were placed in a greenhouse as described above and watered by sub-irrigation to t ff of the test compounds. After 20-22 d, the condition of the test plants as ed with that of the untreated plants was determined visually and scored on a scale of 0 to 100 percent where 0 corresponds to no injury and 100 corresponds to complete kill.
Some of the compounds tested, application rates employed, plant species tested, and results are given in Tables 5-10.
Table 5: Activity of Herbicidal Compounds in Wheat Cropping Systems (35 g ae/ha and 21 DAA) 4")Visual In'ur ‘7 Compound Number POLCO SINAR B 62 70 42 95 93 Table 6: Activity of Herbicidal Compounds in Wheat Cropping Systems (35 g ae/ha and 21 DAA) Visual In'urJ y( ‘7a) Compound Number SINAR KCHSC SASKR MATCH POLCO G 80 87 75 Table 7: ty of Herbicidal Compounds in Wheat Cropping Systems at various rates (21 DAA) Application Visual Compound Rate Number (g ae/ha) G 17.5 G 8.75 39 17.5 39 8.75 Table 8: Activity of idal Compounds in Wheat Cropping Systems (8.75 g ae/ha and 21 DAA) Compound Visual Injury (%) Number SINAR VERPE Table 9: Activity of Herbicidal Compounds in Wheat ng Systems (35 g ae/ha and 21 DAA) Visual In'urJ y( ‘7a) Compound Number MATCH AVEFA F 10 20 33 40 40 Table 10: Activity of Herbicidal Compounds in Wheat Cropping Systems (17.5 g ae/ha and 21 DAA) V's all ' 1 11 um y(r ‘7a) Compound Number LOLMU SETVI F 60 85 33 80 93 34 70 80 AVEFA = Avenafatua (Oat, wild) CIRAR = m arvense (Thistle, Canada) KCHSC = Kochia scoparia (Kochia) LOLMU = Lolium multiflorum (Ryegrass, Italian) MATCH = Matricaria chamomilla (Mayweed, wild) PESGL = Pennisetum glaucum (Foxtail, yellow) POLCO = Polygonum convolvulus (Buckwheat, wild) SASKR = Salsola kali (Thistle, Russian) SETVI = Setaria s (Foxtail, green) SINAR = Brassica sinapis (Mustard, wild) VERPE = ca persica (Speedwell, birdseye) g ae/ha = grams acid equivalent per hectare DAA = days after application Example 15. Evaluation of Postemergence Herbicidal Activity in Pastures Seeds of the d test plant species were planted in Sun Gro Metro-Mix® 360 planting mixture, which typically has a pH of 6.0 to 6.8 and an organic matter content of 30 percent, in c pots with a surface area of 139.7 cmz. When required to ensure good germination and y plants, a fungicide treatment and/or other chemical or physical treatment was applied. The plants were grown with an approximate 14 h photoperiod which was maintained at 24 °C during the day and 21 0C during the night. Nutrients and water were added on a regular basis and supplemental ng was provided with overhead metal halide 1000-Watt lamps as necessary. The plants were employed for testing when they reached the four or six true leaf stage, depending on species.
Treatments consisted of esters of compounds 39 and G. Compound G is methyl 4- aminochloro(4-chlorofluoromethoxyphenyl)picolinate. A weighed amount, determined by the highest rate to be tested, of each test compound was placed in a 25 mL glass vial and was dissolved in 8 mL of a 97:3 v/v mixture of acetone and DMSO to obtain concentrated stock solutions. If the test compound did not dissolve readily, the mixture was warmed and/or sonicated. The trated stock solutions obtained were diluted with 16 mL of an aqueous mixture containing acetone, water, pyl l, DMSO, Agri-dex crop oil concentrate, and Triton® X-77 surfactant in a 64.7:26.0:6.7:2.0:0.7:0.01 v/v ratio to obtain spray solutions containing the t application rates. Additional application rates were obtained by serial dilution of 12 mL of the high rate solution into a solution containing 4 mL of a 97:3 v/v mixture of acetone and DMSO and 8 mL of an s mixture ning acetone, water, isopropyl alcohol, DMSO, Agri-dex crop oil concentrate, and Triton® X-77 surfactant in a 48.5:39.0:10.0:1.5:1.0:0.02 v/v ratio to obtain 1/2X, 1/4X, 1/8X and 1/16X rates of the high rate. Compound requirements are based upon a 12 mL application volume at a rate of 187 L/ha. Formulated compounds were d to the plant material with an overhead Mandel track sprayer equipped with 8002E nozzles calibrated to deliver 187 L/ha over an application area of 0.503 m2 at a spray height of 18 inches (43 cm) above average plant canopy height. Control plants were d in the same manner with the blank.
The treated plants and control plants were placed in a greenhouse as described above and watered by rigation to prevent wash-off of the test compounds. After 35 d, the condition of the test plants as compared with that of the untreated plants was ined visually and scored on a scale of 0 to 100 percent where 0 corresponds to no injury and 100 corresponds to complete kill.
Some of the compounds tested, application rates employed, plant species tested, and results are given in Tables 11 and 12.
WO 03042 2012/022286 Table 11: Activity of Herbicidal Compounds in Pasture Cropping Systems at various rates (35 DAA) Application Visual Compound Rate ' Number (g ae/ha) G 35 G 17.5 39 35 39 17.5 Table 12: Activity of Herbicidal Compounds in Pasture Cropping Systems at Various Rates (35 DAA) Application Visual Compound Rate In'ur (%) Number CIRAR = Cirsium arvense (Thistle, Canada) SOOSS = Solidago L. spec (Goldenrod) g ae/ha = g acid equivalent per hectare DAA = days after application Example 16. Evaluation of Postemergence -Applied Herbicidal Activity in Direct Seeded Rice Seeds or nutlets of the desired test plant species were planted in a soil matrix prepared by mixing a loam soil (43 percent silt, 19 percent clay, and 38 percent sand, with a pH of 8.1 and an organic matter content of 1.5 percent) and river sand in an 80 to 20 ratio. The soil matrix was ned in plastic pots with a e area of 139.7 cmz. When required to ensure good germination and healthy plants, a fungicide treatment and/or other chemical or physical treatment was d. The plants were grown for 10-17 d in a greenhouse with an approximate 14-h photoperiod which was maintained at 29 0C during the day and 26 0C during the night. Nutrients and water were added on a regular basis and supplemental lighting was provided with overhead metal halide 1000-Watt lamps as necessary. The plants were employed for testing when they reached the second or third true leaf stage.
Treatments consisted of esters of compounds 1-4, 6-8, 10, 11, 13-16, 20-31, 35, 38, 41 and 42 and A-E. Compound A is methyl 4-aminochloro(4-chloroethoxy fluorophenyl)fluoropicolinate; compound B is methyl ochloro(4- cyclopropylphenyl)fluoropicolinate; compound C is methyl 4-aminochloro(2,4- dichloromethoxyphenyl)picolinate; compound D is methyl 6-amino(4-chlorofluoro- 3-methoxyphenyl)vinylpyrimidinecarboxylate; and compound E is methyl 4-amino chloro(4-chlorofluoromethoxyphenyl)fluoropicolinate. Weighed amounts of cal grade nds were placed in 25 mL glass vials and dissolved in a volume of 97:3 v/v acetone—DMSO to obtain 12X stock solutions. If the test compound did not dissolve readily, the mixture was warmed and/or sonicated. The concentrated stock solutions were added to the spray solutions so that the final e and DMSO concentrations were 16.2% and 0.5%, respectively. Spray solutions were diluted to the appropriate final concentrations with the addition of 10 mL of an aqueous mixture of 1.5% (v/v) ex crop oil trate. Generally, multiple concentrations of spray solutions were formulated and tested utilizing the same stock solution. The final spray solutions contained 1.25% (v/v) Agri- deX crop oil concentrate. Compound requirements are based upon a 12 mL application volume at a rate of 187 L/ha. Spray solutions were applied to the plant material with an overhead Mandel track sprayer ed with 8002E nozzles calibrated to deliver 187 L/ha over an ation area of 0.503 square meters (m2) at a spray height of 18 inches (43 cm) above average plant canopy . Control plants were sprayed in the same manner with the solvent blank.
The treated plants and control plants were placed in a greenhouse as described above and watered by sub-irrigation to prevent wash-off of the test compounds. After 3 weeks, the condition of the test plants, compared with that of the untreated plants, was ined visually and scored on a scale of 0 to 100 percent where 0 corresponds to no injury and 100 corresponds to complete kill.
By applying the well-accepted probit is as described by J. Berkson in Journal of the American Statistical Society, 48, 565 (1953) and by D. Finney in "Probit Analysis" Cambridge University Press (1952), the data gathered can be used to calculate GR50 and GRgo values, which are defined as growth reduction factors that correspond to the effective dose of herbicide required to kill or control 50 percent or 80 percent, tively, of a target plant.
Some of the application rates and ratios employed, plant species tested, and s are given in Tables 13-18.
Table 13: Activity of Herbicidal Compounds in Rice Cropping Systems (17.5 g ae/ha and 21 DAA; visual injury may represent data gathered in le trials) Visual Injury (%) Compound Number ECHCG ECHCO AESSE SEBEX CYPES CYPIR SCPJU A 60 50 0 20 60 80 20 41 95 95 100 99 100 100 90 Table 14: Activity of Herbicidal Compounds in Rice Cropping Systems (8.75 g ae/ha and 21 DAA; visual injury may represent data gathered in multiple trials) Visual Injury (%) Compound Number ECHCO CYPIR 42 85 100 Table 15: Activity of Herbicidal Compounds in Rice Cropping Systems (8.75 g ae/ha and 21 DAA; visual injury may represent data gathered in le trials) Visual Injury (%) Compound Number ECHCO BRAPP CYPDI SCPJU C 84 74 96 90 38 90 90 100 100 Table 16: Activity of Herbicidal Compounds in Rice Cropping Systems (8.75 g ae/ha and 21 DAA; visual injury may represent data gathered in multiple trials) Visual Injury (%) Compound Number ECHCG ECHCO D 87 95 Table 17: Activity of Herbicidal Compounds in Rice Cropping Systems (8.75 g ae/ha and 21 DAA; Visual injury may represent data gathered in multiple trials) nd Visualyguury Nunflwr CYPDI SCPJU E 89 61 1 100 93 8 99 99 100 100 26 100 100 100 91 11 99 97 23 100 100 13 95 80 29 100 100 3 100 99 2 100 100 24 100 100 6 100 100 16 94 85 4 80 80 100 100 21 100 100 27 100 100 31 100 100 99 0 100 90 22 100 90 28 100 100 7 70 60 14 95 50 Table 18: Growth Reduction Calculations for Compounds in Rice Cropping Systems Compound Species GRSO GRSO GR90 Number g ae/ha ECHCG E 3 .7 17 .1 38.1 1 <4.38 <4.38 6.1 POLPY E 30.7 >70 >70 BRAPP E ECHCO E AESSE = Aeschynomene ive SW./L. tive jointvetch) BRAPP = Brachiaria plalyphylla (GRISEB.) NASH (broadleaf signalgrass) CYPDI = Cyperus diflormis L. (small-flower flatsedge) CYPES = Cyperus esculentus L. (yellow nutsedge) CYPIR = Cyperus iria L. (rice flatsedge) ECHCG = Echinochloa crus-galli (L.) P.BEAUV. (barnyardgrass) ECHCO = Echinochloa colonum (L.) LINK (junglerice) POLPY = num pensylvam'cum L. ylvania smartweed) SCPJU = Scirpus juncoides ROXB. (Japanese bulrush) SEBEX = Sesbania exaltata (RAE) CORY/RYDB. (hemp sesbania) g ae/ha = gram acid equivalent per hectare DAA = days after application GR50 = concentration of compound needed to reduce the growth of a plant by 50% relative to ted plant GRgo = concentration of compound needed to reduce the growth of a plant by 80% ve to untreated plant GR90 = concentration of compound needed to reduce the growth of a plant by 90% relative to ted plant Example 17. Evaluation of In-Water Applied Herbicidal Activity in Transplanted Paddy Rice Weed seeds or nutlets of the desired test plant species were planted in puddled soil (mud) prepared by mixing a non-sterilized mineral soil (28 percent silt, 18 t clay, and 54 percent sand, with a pH of 7.3 to 7.8 and an organic matter content of 1.0 t) and water at a ratio of 100 kilograms (kg) of soil to 19 liters (L) of water. The prepared mud was dispensed in 250 mL aliquots into 480 mL non-perforated plastic pots with a surface area of 91.6 cm2 leaving a headspace of 3 cm in each pot. Rice seeds were planted in Sun Gro MetroMix 306 planting mixture, which typically has a pH of 6.0 to 6.8 and an organic matter content of 30 percent, in plastic plug trays. Seedlings at the second or third leaf stage of growth were transplanted into 650 mL of mud ned in 960 mL non-perforated plastic pots with a surface area of 91.6 cm2 four days prior to herbicide application. The paddy was created by filling the 3 cm headspace of the pots with water. When required to ensure good germination and healthy plants, a fungicide treatment and/or other chemical or physical treatment was applied. The plants were grown for 4-14 d in a greenhouse with an approximate 14-h photoperiod which was maintained at 29 0C during the day and 26 0C during the night. Nutrients were added as Osmocote (17:6: 10, Nitrogen:Phosphorus:Potassium (N:P:K) + minor nutrients) at 2 grams (g) per cup. Water was added on a regular basis to maintain the paddy flood, and supplemental lighting was provided with overhead metal halide 1000-Watt lamps as necessary. The plants were employed for g when they reached the second or third true leaf stage.
Treatments consisted of esters of compounds 1-4, 6-33, 35-39, 41 and 42 and A-G.
Compound A is methyl 4-aminochloro(4-chloroethoxyfluorophenyl) fluoropicolinate; compound B is methyl 4-aminochloro(4-cyclopropylphenyl) icolinate; compound C is methyl 4-aminochloro(2,4-dichloro methoxyphenyl)picolinate; compound D is methyl o(4-chlorofluoro methoxyphenyl)vinylpyrimidinecarboxylate; compound E is methyl 4-aminochloro- 6-(4-chlorofluoromethoxyphenyl)fluoropicolinate; compound F is methyl 6-amino- 2-(4-chlorofluoromethoxyphenyl)methoxypyrimidinecarboxylate; and compound G is methyl 4-aminochloro(4-chlorofluoromethoxyphenyl)picolinate. Weighed amounts of cal grade compounds were placed in individual 120 mL glass vials and were dissolved in 20 mL of acetone to obtain concentrated stock solutions. If the test compound did not ve readily, the mixture was warmed and/or sonicated. The trated stock solutions obtained were diluted with 20 mL of an aqueous mixture containing 2.5% Agri-dex crop oil concentrate (v/v). The final application ons contained 1.25% (v/v) Agri-dex crop oil concentrate. lly, multiple concentrations were tested utilizing the same stock solution. Applications were made by injecting an appropriate amount of the application solution into the aqueous layer of the paddy. Control plants were treated in the same manner with the t blank.
The treated plants and control plants were placed in a greenhouse as described above and water was added as needed to maintain a paddy flood. After 3 weeks the condition of the -5 1- 2012/022286 test plants, compared with that of the untreated plants, was determined visually and scored on a scale of 0 to 100 percent where 0 corresponds to no injury and 100 corresponds to complete kill.
By applying the ccepted probit analysis as described by J. Berkson in Journal of the American Statistical Society, 48, 565 (1953) and by D. Finney in "Probit Analysis" Cambridge University Press (1952), the data gathered can be used to calculate GR50 and GRgo values, which are defined as growth reduction factors that correspond to the effective dose of herbicide ed to kill or control 50 percent or 80 percent, respectively, of a target plant.
Some of the compounds tested, application rates employed, plant species tested, and results are given in Tables 19-28.
Table 19: Activity of Herbicidal Compounds in Rice Cropping Systems (35 g ae/ha and 21 DAA; visual injury may represent data gathered in multiple trials) Visual Injury (%) Compound Number ECHCG SCPJU 41 95 100 Table 20: Activity of Herbicidal Compounds in Rice Cropping Systems (17.5 g ae/ha and 21 DAA; visual injury may ent data ed in multiple trials) Compound In'ur (%) WO 03042 2012/022286 Table 21: Activity of Herbicidal Compounds in Rice Cropping Systems (35 g ae/ha and 21 DAA; visual injury may represent data gathered in multiple trials) Visual Injury (%) Number ECHCG SCPJU F 0 50 33 40 100 Table 22: Activity of Herbicidal Compounds in Rice Cropping s (35 g ae/ha and 21 DAA; visual injury may represent data gathered in multiple trials) Visual Injury (%) Compound ECHCG SCPJU Number Table 23: Activity of Herbicidal Compounds in Rice Cropping Systems (35 g ae/ha and 21 DAA; visual injury may represent data gathered in multiple trials) Visual Compound Injury (%) Number ECHCG D 54 76 Table 24: Activity of Herbicidal Compounds in Rice Cropping Systems (35 g ae/ha and 21 DAA; visual injury may represent data gathered in multiple trials) Visual Compound Injury Number ( %) FIMMI G 61 39 100 36 100 Table 25: Activity of Herbicidal Compounds in Rice Cropping Systems (35 g ae/ha and 21 DAA; Visual injury may represent data gathered in multiple trials) Visual Compound Number G 47 Table 26: ty of Herbicidal Compounds in Rice Cropping Systems (35 g ae/ha and 21 DAA; Visual injury may represent data ed in multiple trials) Visual Injury Compound (‘70) Number ECHCG (} 74 39 100 18 100 17 98 19 90 37 98 Table 27: ty of Herbicidal Compounds in Rice Cropping Systems (17.5 g ae/ha and 21 DAA; Visual injury may represent data gathered in multiple trials) Compound Visual Injury (%) 87 99 1 427 Table 28: Growth Reduction Calculations for Compounds in Rice Cropping Systems Com ound Secies Nurlliber GR80 GR90 gae/ha ECHCG E 58.5 78.7 1 21.8 31.2 SCPJU E m20.0 29.5 1 4.4 10.8 LEFCH E 99.4 130.0 1 78.6 99.1 FIMMI E 21.7 26.8 1 <17.5 <17.5 CYPRO = Cyperus rotundus L. (purple nutsedge) ECHCG = Echinochloa crus—gallz‘ (L.) V. (barnyardgrass) FIMMI = Fimbristylis miliacea (L.) VAHL (globe rush) LEFCH : Lepz‘ochloa chinensis (L.) NEES (Chinese sprangletop) SCPJU = Scirpusjuncoides ROXB. (Japanese bulrush) g ae/ha = gram acid equivalent per e DAA = days after ation GRso : concentration of compound needed to reduce the growth of a plant by 50% relative to untreated plant GRgo = concentration of compound needed to reduce the growth of a plant by 80% relative to untreated plant GRgO = concentration of compound needed to reduce the growth of a plant by 90% relative to untreated plant As used herein, except where the context requires otherwise, the term "comprise" and II N variations of the term, such as "comprising , comprises" and "comprised", are not intended to exclude other additives, components, integers or steps.
Reference to any prior art in the specification is not, and should not be taken as, an ledgment or any form of suggestion that this prior art forms part of the common general knowledge in New Zealand or any other jurisdiction. —56- 1000909427

Claims (12)

WHAT IS CLAIMED IS:
1. A compound of Formula IB: 1 2 R\N,R X z / O Y N \R3 wherein 5 X represents H or F; Y represents halogen, C1—C8 alkyl, C3-C6 cycloalkyl, or phenyl substituted with 1 — 4 substituents independently selected from halogen, C1—C3 alkyl, C3—C6 cycloalkyl, C1—C3 alkoxy, C1—C3 kyl, C1—C3 haloalkoxy, cyano, nitro, NRIRZ, or where two adjacent substituents are taken together as —O(CH2)nO— or 70(CH2)n— wherein n=1 or 2; 10 Z represents halogen or C2-C4 alkenyl; R1 and R2 independently represent H, C1-C6 alkyl, or C1—C6 acyl; R3 represents unsubstituted or substituted C7—C11 arylalkyl.
2. The compound of Claim 1 in which X represents H.
3. The compound of Claim 1 in which X represents F. 15
4. The compound of any one of Claims 1 to 3 in which Y represents tuted phenyl.
5. The nd of any one of Claims 1 to 4 in which Z represents Cl.
6. The compound of any one of Claims 1 to 5 in which R1 and R2 represent H.
7. The compound of any one of Claims 1 to 6 in which R3 ents a benzyl. 1000909427
8. The compound of any one of Claims 1 to 7 in which R3 ents an unsubstituted or 0rth0-, meta— or para—monosubstituted benzyl.
9. An herbicidal composition comprising an herbicidally effective amount of a compound of Formula IB, according to any one of Claims 1 to 8, in a mixture with an agriculturally acceptable adjuvant or carrier.
10. A method of controlling undesirable vegetation which comprises contacting the vegetation via foliar or water application or the locus thereof with or applying to the soil or water to prevent the emergence of vegetation an herbicidally effective amount of a nd of Formula IB, according to any one of Claims 1 to 8. 10
11. A method for the selective postemergent control of undesirable vegetation in the presence of rice, wheat or forage which comprises applying to said undesirable vegetation an herbicidally effective amount of a nd of Formula 1B, according to any one of Claims 1 to 8, or an idal ition thereof.
12. The compound of Claim 1, substantially as herein described. —58—
NZ613477A 2011-01-25 2012-01-24 Arylalkyl esters of 4-amino-6-(substituted phenyl)picolinates and 6-amino-2-(substituted phenyl)-4-pyrimidinecarboxylates and their use as herbicides NZ613477B2 (en)

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US201161435925P 2011-01-25 2011-01-25
US61/435,925 2011-01-25
PCT/US2012/022286 WO2012103042A1 (en) 2011-01-25 2012-01-24 Arylalkyl esters of 4-amino-6-(substituted phenyl)picolinates and 6-amino-2-(substituted phenyl)-4-pyrimidinecarboxylates and their use as herbicides

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NZ613477B2 true NZ613477B2 (en) 2015-05-28

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