Pyrimidinyloxybenzene derivatives as herbicides

Abstract

The present application relates to pyrimidinyloxybenzene derivatives as herbicides. The present invention discloses compounds of formula (1), including all stereoisomers, N-oxides and salts thereof, wherein Q, Z, R 2 , R 3 and m are defined in the disclosure. The present invention also discloses compositions comprising compounds of formula (1) and methods for controlling undesirable vegetation, the methods comprising contacting the undesirable vegetation or its environment with an effective amount of a compound or composition of the present invention.

Description

[0001] This application is a divisional application of an invention patent application, the application date of the parent case is January 9, 2015, the application number is 201580004764.0 (PCT / US2015 / 010823), and the name of the invention is "Pyrimidinyloxybenzene derivatives as herbicides". Technical Field

[0002] The present invention relates to certain pyrimidinyloxybenzene derivatives, their N-oxides, salts and compositions, and methods of using them to control undesirable vegetation. Background Art

[0003] In order to obtain high crop efficiency, it is extremely important to control undesirable vegetation. Realizing the growth of selectively controlled weeds is very desirable, particularly in useful crops, such as rice, soybean, sugar beet, corn, potato, wheat, barley, tomato and plantation crops etc. Uncontrolled weed growth in such useful crops can cause a significant reduction in output, resulting in rising consumer costs thus. Controlling undesirable vegetation in non-cultivated areas is also extremely important. Many products used for these purposes are commercially available, but continue to need more effective, more economical, less toxic, safer to the environment or novel compounds with different action sites.

[0004] JP 61236766 A (Sumitomo, 1986) discloses certain carbon-linked pyrimidinyloxybenzene derivatives as herbicides. WO 94 / 17059 (Nippon Soda, 1994) discloses certain carbon-linked pyrimidinyloxybenzene derivatives as herbicides. Summary of the invention

[0005] The present invention relates to compounds of formula 1 (including all stereoisomers), (N-oxides and salts thereof), agricultural compositions containing them, and their use as herbicides:

[0006]

[0007] Q is a 5- or 6-membered aromatic heterocyclic ring, which is bonded to the rest of Formula 1 via a carbon atom and is optionally substituted by 1 to 4 R 1 replace;

[0008] Z is O or S;

[0009] Each R 1are independently halogen, cyano, nitro, SF5, CHO, C(=O)NH2, C(=S)NH2, SO2NH2, C1-C4 alkyl, C2-C4 alkenyl, C2-C4 alkynyl, C1-C4 haloalkyl, C2-C4 haloalkenyl, C2-C4 haloalkynyl, C3-C6 cycloalkyl, C3-C6 halocycloalkyl, C4–C8 alkylcycloalkyl, C4–C8 cycloalkylalkyl, C2–C6 alkylcarbonyl, C2–C6 haloalkylcarbonyl, C2–C6 alkoxycarbonyl, C3-C7 cycloalkylcarbonyl, C2–C8 alkylaminocarbonyl, C3-C 10 dialkylaminocarbonyl, C1-C4 alkoxy, C3-C4 alkenyloxy, C3-C4 alkynyloxy, C1-C4 haloalkoxy, C3-C4 haloalkenyloxy, C3-C4 haloalkynyloxy, C3–C6 cycloalkoxy, C3–C6 halocycloalkoxy, C4–C8 cycloalkylalkoxy, C2-C6 alkoxyalkyl, C2-C6 haloalkoxyalkyl, C2-C6 alkoxyhaloalkyl, C2–C6 alkoxyalkoxy, C2-C4 alkylcarbonyloxy, C2-C6 cyanoalkyl, C2-C6 cyanoalkoxy, C1-C4 hydroxyalkyl, C2-C4 alkylthioalkyl, SO n R 1A 、Si(CH3)3 or B(-OC(R 1B )2C(R 1B )2O-); or a benzene ring optionally substituted with up to 5 substituents independently selected from R 1C or a 5- or 6-membered heteroaromatic ring comprising ring members selected from carbon atoms and up to 4 heteroatoms independently selected from up to 2 O, up to 2 S, and up to 4 N atoms, each ring optionally substituted with up to 3 substituents independently selected from R on the carbon atom ring members 1C and R on the nitrogen ring member 1D ;

[0010] R 2 is halogen, cyano, nitro, C1-C4 alkoxy, C1-C4 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, SO n R 2A , C1-C4 haloalkyl or C3-C6 cycloalkyl;

[0011] Each R 3and independently halogen, cyano, hydroxyl, nitro, amino, CHO, C(═O)NH2, C(═S)NH2, SO2NH2, C1-C4 alkyl, C2-C4 alkenyl, C2-C4 alkynyl, C1-C4 haloalkyl, C2-C4 haloalkenyl, C2-C4 haloalkynyl, C3-C6 cycloalkyl, C3-C6 halocycloalkyl, C4–C8 alkylcycloalkyl, C4–C8 cycloalkylalkyl, C2–C6 alkylcarbonyl, C2–C6 haloalkylcarbonyl, C2–C6 alkoxycarbonyl, C3-C7 cycloalkylcarbonyl, C1-C4 alkoxy, C3-C 4-Alkenyloxy, C3-C4 Alkynyloxy, C1-C4 Haloalkoxy, C3-C4 Haloalkenyloxy, C3-C4 Haloalkynyloxy, C3–C6 Cycloalkoxy, C3–C6 Halocycloalkoxy, C4–C8 Cycloalkylalkoxy, C2-C6 Alkoxyalkyl, C2-C6 Haloalkoxyalkyl, C2-C6 Alkoxyhaloalkyl, C2–C6 Alkoxyalkoxy, C2-C4 Alkylcarbonyloxy, C2-C6 Cyanoalkyl, C2-C6 Cyanoalkoxy, C2-C4 Alkylthioalkyl, Si(CH3)3, C≡CSi(CH3)3, C(=O)N(R 3A )(R 3B )、C(=NOR 3C )H、C(=NR 3D )H、SO n R 3E ; or a benzene ring optionally substituted with up to 5 substituents independently selected from R 3F or a 5- or 6-membered heteroaromatic ring comprising ring members selected from carbon atoms and up to 4 heteroatoms independently selected from up to 2 O, up to 2 S, and up to 4 N atoms, each ring optionally substituted with up to 3 substituents independently selected from R on the carbon atom ring members 3F and R on the nitrogen ring member 3G ; or pyrimidinyloxy;

[0012] m is 0, 1, 2 or 3;

[0013] Each n is independently 0, 1 or 2;

[0014] Each R 1A , R 2A and R 3E are independently C1-C4 alkyl, C1-C4 haloalkyl, C1-C4 alkylamino or C2-C6 dialkylamino;

[0015] Each R 1B are independently H or C1-C4 alkyl;

[0016] Each R 1Care independently hydroxy, halogen, cyano, nitro, C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 alkoxy or C1-C6 haloalkoxy;

[0017] Each R 1D are independently cyano, C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 alkoxy or C2-C6 alkylcarbonyl;

[0018] Each R 3A are independently C1-C4 alkyl or C1-C4 haloalkyl;

[0019] Each R 3B are independently H, C1-C4 alkyl or C1-C4 haloalkyl;

[0020] Each R 3C are independently H or C1-C4 alkyl;

[0021] Each R 3D are independently H, amino, C1-C4 alkyl or C1-C4 alkylamino;

[0022] Each R 3F are independently hydroxy, halogen, cyano, nitro, C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 alkoxy or C1-C6 haloalkoxy; and

[0023] Each R 3G are independently cyano, C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 alkoxy or C2-C6 alkylcarbonyl;

[0024] More specifically, the present invention relates to a compound of formula 1 (including all stereoisomers), an N-oxide thereof or a salt thereof. The present invention also relates to a herbicide composition comprising a compound of the present invention (i.e., a herbicidally effective amount) and at least one component selected from a surfactant, a solid diluent and a liquid diluent. The present invention also relates to a method for controlling the growth of undesirable vegetation, the method comprising contacting the vegetation or its environment with a herbicidally effective amount of a compound of the present invention (e.g., in the form of a composition as described herein).

[0025] The present invention also includes a herbicide mixture comprising (a) a compound selected from Formula 1, N-oxides and salts thereof, and (b) at least one additional active ingredient selected from ((b1) to (b16); and salts of compounds of ((b1) to (b16). DETAILED DESCRIPTION

[0026] As used herein, the terms "comprises," "including," "comprising," "covering," "having," "containing," "encompassing," "containing," "characterized by," or any other variations thereof, are intended to cover a non-exclusive inclusion, subject to any expressly specified limitation. For example, a composition, mixture, process, or method that comprises a list of elements is not necessarily limited to only those elements but may include other elements not expressly listed or other elements inherent to such composition, mixture, process, or method.

[0027] The transitional phrase "consisting of" excludes any unspecified elements, steps, or ingredients. If in a claim, such words limit the claim to include nothing other than those stated except for the impurities that normally accompany it. When the phrase "consisting of" appears in a clause of the body of a claim, rather than immediately preceding it, it is limited only to the elements mentioned in that clause; other elements are not excluded from the claim as a whole.

[0028] The transitional phrase "consisting essentially of is used to qualify compositions or methods that include materials, steps, parts, components, or elements in addition to those literally disclosed, provided that these additional materials, steps, parts, components, or elements do not materially affect the basic characteristics and one or more novel characteristics of the claimed invention. The term "consisting essentially of" is intermediate between "comprising" and "consisting of."

[0029] When applicants use open-ended terms such as "comprising" to define an invention or a portion thereof, it should be readily understood that (unless otherwise indicated) the description should be interpreted as also using the terms "consisting essentially of" or "consisting of" to describe this invention.

[0030] In addition, unless expressly stated to the contrary, "or" refers to an inclusive "or" rather than an exclusive "or". For example, condition A or B satisfies any of the following: A is true (or exists) and B is false (or does not exist), A is false (or does not exist) and B is true (or exists), and both A and B are true (or exist).

[0031] In addition, the indefinite article "a" or "an" before an element or component of the present invention is intended to be non-limiting in relation to the number of instances (i.e., occurrences) of an element or component. Therefore, "a" or "an" should be understood to include one or at least one, and the singular form of an element or component also includes plural references unless there is a number that clearly indicates a singular number.

[0032] As referred to herein, the term "seedling" used alone or in combination of words refers to a plant seedling that develops from the embryo of a seed.

[0033] As used herein, the term "broadleaf" may be used alone or in a phrase such as "broadleaf crops" to refer to dicots or dicots, which is a term used to describe a class of angiosperms characterized by a plumule with two cotyledons. As used herein, the term "alkylating agent" refers to a compound in which a carbon-containing group is bound to a leaving group such as a halogen or sulfonate through a carbon atom, and the leaving group can be displaced by a nucleophile bonding to the carbon atom. Unless otherwise indicated, the term "alkylating" does not limit the carbon-containing group to an alkyl group; the carbon-containing groups in the alkylating agent include Q, R 1 and R 3 Specify the substituents bonded to the various carbons.

[0034] In the above description, the term "alkyl" used alone or in a compound word such as "alkylthio" or "haloalkyl" includes straight-chain or branched alkyl, such as methyl, ethyl, n-propyl, iso-propyl or different butyl, pentyl or hexyl isomers. "Alkenyl" includes straight-chain or branched olefins, such as vinyl, 1-propenyl, 2-propenyl and different butenyl, pentenyl and hexenyl isomers. "Alkenyl" also includes polyenes, such as 1,2-propadienyl and 2,4-hexadienyl. "Alkynyl" includes straight-chain or branched alkynes, such as ethynyl, 1-propynyl, 2-propynyl and different butynyl, pentynyl and hexynyl isomers.

[0035] "Alkoxy" includes, for example, methoxy, ethoxy, n-propoxy, isopropoxy, and different butoxy, pentoxy and hexoxy isomers. "Alkoxyalkyl" means an alkoxy substitution on an alkyl group. Examples of "alkoxyalkyl" include CH3OCH2, CH3OCH2CH, CH3CH2OCH2, CH3CH2CH2CH2OCH2, and CH3CH2OCH2CH2. "Alkenyloxy" includes straight-chain or branched alkenyloxy moieties. Examples of "alkenyloxy" include H2C=CHCH2O, (CH3)2C=CHCH2O, (CH3)CH=CHCH2O, (CH3)CH=C(CH3)CH2O, and CH2=CHCH2CH2O. "Alkynyloxy" includes straight-chain or branched alkenyloxy moieties. Examples of "alkynyloxy" include HC≡CCH2O, CH3C≡CCH2O, and CH3C≡CCH2CH2O. "Alkylthio" includes branched or straight-chain alkylthio moieties, such as methylthio, ethylthio, and different propylthio, butylthio, pentylthio and hexylthio isomers. "Alkylthioalkyl" represents an alkylthio substituent on an alkyl group. Examples of "alkylthioalkyl" include CH3SCH2, CH3SCH2CH2, CH3CH2SCH2, CH3CH2CH2CH2SCH2 and CH3CH2SCH2CH2. "Alkylthioalkoxy" represents an alkylthio substitution on an alkoxy group. "Cyanoalkyl" represents an alkyl group substituted by a cyano group. Examples of "cyanoalkyl" include NCCH2, NCCH2CH2 and CH3CH(CN)CH2. "Alkylamino", "dialkylamino" and the like are similar to the above example definitions.

[0036] "Cycloalkyl" includes, for example, cyclopropyl, cyclobutyl, cyclopentyl and cyclohexyl. The term "halogen" alone or in compound words such as "haloalkyl" or when used to describe, for example, "alkyl substituted with halogen" includes fluorine, chlorine, bromine or iodine. In addition, when used in compound words such as "haloalkyl" or when used to describe, for example, "alkyl substituted with halogen", the alkyl may be partially or completely substituted with halogen atoms (which may be the same or different). Examples of "haloalkyl" or "alkyl substituted with halogen" include F3C, ClCH2, CF3CH2 and CF3CCl2. The term "haloalkoxy" and the like are defined similarly to the term "haloalkyl". Examples of "haloalkoxy" include CF3O-, CCl3CH2O-, HCF2CH2CH2O- and CF3CH2O-. "Alkylcarbonyl" represents a straight-chain or branched alkyl moiety bonded to a C(=O) moiety. Examples of "alkylcarbonyl" include CH3C(=O)-, CH3CH2CH2C(=O)-, and (CH3)2CHC(=O)-. Examples of "alkoxycarbonyl" include CH3OC(=O)-, CH3CH2OC(=O)-, CH3CH2CH2OC(=O)-, (CH3)2CHOC(=O)-, and different butoxy- or pentoxycarbonyl isomers.

[0037] The total number of carbon atoms in a substituent group is represented by the “C i –C j " prefix represents, wherein i and j are numbers from 1 to 6. For example, C1-C4 alkanesulfonyl represents methylsulfonyl to butylsulfonyl; C2 alkoxyalkyl represents CH3OCH2-; C3 alkoxyalkyl represents, for example, CH3CH(OCH3)-, CH3OCH2CH2- or CH3CH2OCH2-; and C4 alkoxyalkyl represents various isomers of alkyl groups containing a total of four carbon atoms substituted with alkoxy groups, examples of which include CH3CH2CH2OCH2- and CH3CH2OCH2CH2-.

[0038] When a compound is substituted with substituents having a subscript indicating that the number of substituents may exceed one, the substituents (when there are more than one) are independently selected from the defined substituents (e.g. (R 3 )n, n is 0, 1, 2 or 3). In addition, when a subscript indicates a range, such as (R) i–j , then the number of substituents may be selected from integers between i and j, inclusive. When a group contains a substituent that may be hydrogen (e.g., when m=0), then when the substituent is considered to be hydrogen, it is recognized that this is equivalent to the group being unsubstituted. When a variable group is shown to be optionally attached to a position, (e.g., attached to Q (R 1 ) n, wherein n can be 0), even if not described in the variable group definition, hydrogen can be at the position. When one or more positions on the group are referred to as "not substituted" or "unsubstituted", hydrogen atoms are attached to occupy any free valences.

[0039] Unless otherwise indicated, a "ring" as a component of Formula 1 (e.g., a substituent Q) is carbocyclic or heterocyclic. The term "ring member" refers to the atoms or heteroatoms that form the backbone of the ring. When a fully unsaturated carbocyclic ring satisfies Huckel's rule, then the ring is also referred to as an "aromatic ring." A "saturated carbocyclic ring" refers to a ring having a backbone consisting of carbon atoms connected to each other by single bonds; unless otherwise indicated, the remaining carbon valences are occupied by hydrogen atoms.

[0040] The term "heterocyclic ring", "heterocycle" means a ring in which at least one atom forming the backbone of the ring is not carbon (e.g., nitrogen, oxygen or sulfur). Typically, the heterocyclic ring contains no more than 4 nitrogens, no more than 2 oxygens and no more than 2 sulfurs. Unless otherwise indicated, the heterocyclic ring can be a saturated, partially unsaturated or fully unsaturated ring. When the fully unsaturated heterocyclic ring satisfies Huckel's rule, the ring is also referred to as a "heteroaromatic ring" or "aromatic heterocyclic ring". Unless otherwise indicated, the heterocyclic ring can be connected via any available carbon or nitrogen by replacing the hydrogen on the carbon or nitrogen.

[0041] "Aromatic" means that the ring atoms are substantially in the same plane and have p-orbitals perpendicular to the plane of the ring and (4n+2) pi electrons (where n is a positive integer) are associated with the ring to comply with Huckel's rule.

[0042] The term "optionally substituted" in relation to a heterocyclic ring refers to a group that is unsubstituted or has at least one non-hydrogen substituent that does not destroy the biological activity possessed by the unsubstituted analog. As used herein, unless otherwise indicated, the following definitions apply. The term "optionally substituted" is used interchangeably with the phrase "substituted or unsubstituted" or with the term "(un)substituted". Unless otherwise indicated, an optionally substituted group may have a substituent at each substitutable position of the group, and each substitution is independent of one another.

[0043] Unless otherwise indicated, when Q is a 5- or 6-membered (nitrogen-containing) heterocycle, it may be attached to the remainder of Formula 1 via any available carbon or nitrogen ring atom. As described above, Q may be (among other things) a phenyl group optionally substituted with one or more substituents selected from the substituents defined in the Summary of the Invention. An example of a phenyl group optionally substituted with one to five substituents is the ring illustrated as U-1 in Example 1, wherein R v R is defined as Q in the Summary of the Invention 1 , and r is an integer (0 to 4).

[0044] As described above, Q may be, among other things, a saturated or unsaturated 5- or 6-membered aromatic heterocyclic ring which may be optionally substituted with one or more substituents independently selected from the substituents defined in the Summary of the Invention. Examples of 5- or 6-membered unsaturated aromatic heterocyclic rings which may be optionally substituted with one or more substituents include rings U-2 to U-61 shown in Example 1, wherein R v As described in the invention, Q (i.e. R 1 ), and r is an integer from 0 to 4, which is limited by the number of available positions on each U group. Since U-29, U-30, U-36, U-37, U-38, U-39, U-40, U-41, U-42 ​​and U-43 have only one available position, for these U groups, r is limited to an integer of 0 or 1, and r being 0 means that the U group is unsubstituted, and in the case of (R v ) r There is one hydrogen at the position shown.

[0045] Example 1

[0046]

[0047]

[0048] Although R is shown in structures U-1 to U-61 v groups, but it should be noted that since they are optional substituents, they do not have to be present. It should be noted that when R v When H is present, when attached to an atom, this is as if the atom were unsubstituted. The nitrogen atom may be H or R v substitution, the nitrogen atom needs to be substituted to fill its valence. It should be noted that when (R v ) r When the connection point to the U group is shown as floating, (R v ) r Any available carbon or nitrogen atom of the U group can be attached. It should be noted that when the attachment point on the U group is shown as floating, the U group can be attached to the remainder of Formula 1 via any available carbon or nitrogen in the U group by replacing a hydrogen atom. It should be noted that some U groups can only be attached by less than 4 R atoms. v The substituted moieties are substituted with 1-(2- to 3-6-yl)-1-nitropropene.

[0049] A variety of synthetic methods are known in the art for the preparation of aromatic and non-aromatic heterocyclic rings and ring systems; for extensive reviews see the eight-volume set Comprehensive Heterocyclic Chemistry, eds. AR Katritzky and CW Rees, Pergamon Press, Oxford, 1984, and the twelve-volume set Comprehensive Heterocyclic Chemistry II, eds. AR Katritzky, CW Rees and EF V Scriven, Pergamon Press, Oxford, 1996.

[0050] The compounds of the present invention may exist as one or more stereoisomers. Various stereoisomers include enantiomers, diastereomers, atropisomers and geometric isomers. Stereoisomers are isomers that are identical in structure but different in the arrangement of their atoms in space, and include enantiomers, diastereomers, cis-trans isomers (also known as geometric isomers) and atropisomers. Atropisomers arise from restricted rotation around a single bond, where the rotation barrier is high enough to allow separation of isomeric substances. Those skilled in the art will know that when a stereoisomer is enriched relative to other stereoisomers, or when it is separated from other stereoisomers, it may be more active and / or may exhibit beneficial effects. In addition, those skilled in the art know how to separate, enrich and / or selectively prepare the stereoisomers. The compounds of the present invention may exist as a mixture of stereoisomers, a single stereoisomer or as an optically active form.

[0051] The compounds of formula 1 are usually present in more than one form, so formula 1 includes all crystalline and non-crystalline forms of the compounds they represent. Non-crystalline forms include solid embodiments such as waxes and gums, and liquid embodiments such as solutions and melts. Crystalline forms include embodiments representing essentially single crystal forms, and embodiments representing mixtures of polymorphs (i.e., different crystal forms). The term "polymorph" refers to a specific crystal form of a compound that can be crystallized in different crystal forms, which have different molecular arrangements and / or molecular conformations in the crystal lattice. Due to the presence or absence of co-crystallized water or other molecules that may be weakly or strongly bound in the crystal lattice, although polymorphs may have the same chemical composition, they may also have different compositions. Polymorphs may have different chemical, physical and biological properties, such as crystal shape, density, hardness, color, chemical stability, melting point, hygroscopicity, suspendability, dissolution rate and bioavailability. Those skilled in the art will appreciate that a polymorph of a compound of Formula 1 may exhibit beneficial effects (e.g., suitability for preparing a usable formulation, improved biological performance) relative to another polymorph or mixture of polymorphs of the same compound of Formula 1. The preparation and separation of a particular polymorph of a compound of Formula 1 may be accomplished by methods known to those skilled in the art, including, for example, crystallization using a selected solvent and temperature. For an extensive discussion of polymorphism, see Polymorphism in the Pharmaceutical Industry, edited by R. Hilfiker, Wiley-VCH, Weinheim, 2006.

[0052] Those skilled in the art will appreciate that not all nitrogen-containing heterocycles can form N-oxides, since nitrogen requires an available lone pair of electrons for oxidation to the oxide; those skilled in the art will recognize those nitrogen-containing heterocycles that can form N-oxides. Those skilled in the art will also know that tertiary amines can form N-oxides. Synthetic methods for preparing N-oxides of heterocycles and tertiary amines are well known to those skilled in the art and include oxidation of heterocyclic compounds and tertiary amines with peroxyacids such as peracetic acid and meta-chloroperbenzoic acid (MCPBA), hydrogen peroxide, alkyl hydroperoxides such as tert-butyl hydroperoxide, sodium perborate, and dioxiranes such as dimethyldioxirane. These methods for preparing N-oxides have been extensively described and reviewed in the literature, see, for example: T.L. Gilchrist in Comprehensive Organic Synthesis, Vol. 7, pp. 748–750, ed. S.V. Ley, Pergamon Press; M. Tisler and B. Stanovnik in Comprehensive Heterocyclic Chemistry, Vol. 3, pp. 18–20, ed. A.J. Boulton and A. McKillop, Pergamon Press; M.R. Grimmett and B.R.T. Keene in Advances in Heterocyclic Chemistry, Vol. 43, pp. 149–161, ed. A.R. Katritzky, Academic Press; M. Tisler and B. Stanovnik in Advances in Heterocyclic Chemistry, Vol. 9, pp. 285–291, ed. A.R. Katritzky and A.J. Boulton, Academic Press; and G.W.H. Cheeseman and E.S.G. Verstiuk in Advances in Heterocyclic Chemistry, Vol. 43, pp. 149–161, ed. A.R. Katritzky, Academic Press. Chemistry, Volume 22, Pages 390–392, AR Katritzky and AJ Boulton, eds., Academic Press.

[0053] Those skilled in the art recognize that, because the salt of the compound is in balance with their corresponding non-salt form under environmental and physiological conditions, the salt shares biological use with the non-salt form. Therefore, the salt of a variety of formula 1 compounds can be used to control undesirable vegetation (i.e., suitable for agriculture). The salt of the compound of formula 1 includes an acid-addition salt formed with an inorganic acid or an organic acid, such as hydrobromic acid, hydrochloric acid, nitric acid, phosphoric acid, sulfuric acid, acetic acid, butyric acid, fumaric acid, lactic acid, maleic acid, malonic acid, oxalic acid, propionic acid, salicylic acid, tartaric acid, 4-toluenesulfonic acid or valeric acid. When the compound of formula 1 includes an acidic part such as a carboxylic acid or phenol, the salt also includes those formed with an organic base or an inorganic base such as pyridine, triethylamine or ammonia or sodium, potassium, lithium, calcium, magnesium or barium amide, hydride, hydroxide or carbonate. Therefore, the present invention includes compounds selected from formula 1, its N-oxides and its salts suitable for agriculture.

[0054] Embodiments of the present invention as described in the Summary of the Invention include (wherein Formula 1 as used in the following embodiments includes N-oxides and salts thereof):

[0055] Embodiment 1 The compound of formula 1, wherein Q is selected from

[0056]

[0057]

[0058]

[0059] wherein r is 0, 1, 2, or 3; and s is 0 or 1.

[0060] Embodiment 2 The compound of Embodiment 1, wherein Q is selected from Q-1 to Q-42.

[0061] Embodiment 3 The compound of Embodiment 2, wherein Q is selected from Q-7 to Q-24.

[0062] Embodiment 4 The compound of Embodiment 3, wherein Q is selected from Q-16 and Q-18.

[0063] Embodiment 5 The compound of Embodiment 4, wherein Q is Q-16.

[0064] Embodiment 6 The compound of Embodiment 4, wherein Q is Q-18.

[0065] Embodiment 7 The compound of Embodiment 1, wherein Q is selected from Q-43 to Q-55.

[0066] Embodiment 8 The compound of Embodiment 7, wherein Q is selected from Q-43, Q-44, Q-45, Q-48, Q-49 and Q-50.

[0067] Embodiment 9 The compound of Embodiment 8, wherein Q is selected from Q-43, Q-44 and Q-45.

[0068] Embodiment 10 The compound of Embodiment 9, wherein Q is Q-43.

[0069] Embodiment 11 The compound of Embodiment 10, wherein Q is Q-45.

[0070] Embodiment 12 A compound of Formula 1 or any one of Embodiments 1 to 11, alone or in combination, wherein Z is O.

[0071] Embodiment 13 A compound of Formula 1 or any one of Embodiments 1 to 12, alone or in combination, wherein each R 1 are independently halogen, cyano, SF5, CHO, C1-C4 alkyl, C2-C4 alkenyl, C2-C4 alkynyl, C1-C4 haloalkyl, C2-C4 haloalkenyl, C2-C4 haloalkynyl, C2-C6 alkylcarbonyl, C2-C6 haloalkylcarbonyl, C2-C6 alkoxycarbonyl, C1-C4 alkoxy, C3-C4 alkenyloxy, C3-C4 alkynyloxy, C1-C4 haloalkoxy, C3-C4 haloalkenyloxy, C3-C4 haloalkynyloxy, C2-C6 alkoxyalkyl, C2-C6 haloalkoxyalkyl, C2-C6 cyanoalkyl, C1-C4 hydroxyalkyl, C2-C4 alkylthioalkyl or SO n R 1A .

[0072] Embodiment 14 The compound of Embodiment 13, wherein each R 1 are independently halogen, cyano, CHO, C1-C4 alkyl, C2-C4 alkenyl, C2-C4 alkynyl, C1-C4 haloalkyl, C2-C4 haloalkenyl, C2-C4 haloalkynyl, C1-C4 alkoxy, C3-C4 alkenyloxy, C3-C4 alkynyloxy, C1-C4 haloalkoxy, C3-C4 haloalkenyloxy, C3-C4 haloalkynyloxy, C2-C6 alkoxyalkyl, C2-C6 haloalkoxyalkyl, C1-C4 hydroxyalkyl, C2-C4 alkylthioalkyl or SO n R 1A .

[0073] Embodiment 15 The compound of Embodiment 14, wherein each R 1 are independently halogen, cyano, C1-C4 alkyl, C1-C4 haloalkyl, C1-C4 alkoxy, C1-C4 haloalkoxy or SO n R 1A .

[0074] Embodiment 16: The compound of Embodiment 15, wherein each R 1are independently halogen, C1-C4 alkyl, C1-C4 haloalkyl or C1-C4 haloalkoxy.

[0075] Embodiment 17 The compound of Embodiment 16, wherein each R 1 are independently halogen, C1-C4 haloalkyl or C1-C4 haloalkoxy.

[0076] Embodiment 18 The compound of Embodiment 17, wherein each R 1 are independently halogen or C1-C4 haloalkyl.

[0077] Embodiment 19 The compound of Embodiment 18, wherein each R 1 are independently F, Cl, Br, CF3, CHF2 or CH2F.

[0078] Embodiment 20 A compound of Formula 1 or any one of Embodiments 1 to 19, alone or in combination, wherein r is 0, 1 or 2.

[0079] Embodiment 20a. The compound of Embodiment 20, wherein r is 1.

[0080] Embodiment 21 A compound of Formula 1 or any one of Embodiments 1 to 19, alone or in combination, wherein s is 1.

[0081] Embodiment 21a. A compound of formula 1 or any one of embodiments 1 to 20a, alone or in combination, wherein when Q is Q-16 and r is 1, then R 1 Attached at position 5 of the Q-16 ring.

[0082] Embodiment 21b. A compound of formula 1 or any one of embodiments 1 to 20a, alone or in combination, wherein when Q is Q-18 and r is 1, then R 1 Attached at position 3 of Q-18 ring.

[0083] Embodiment 22 A compound of Formula 1 or any one of Embodiments 1 to 21b, alone or in combination, wherein R 2 is halogen, C1-C4 alkyl or C1-C4 haloalkyl.

[0084] Embodiment 23 The compound of Embodiment 22, wherein R 2 It is halogen or C1-C4 alkyl.

[0085] Embodiment 24 The compound of Embodiment 23, wherein R 2 is halogen or CH3.

[0086] Embodiment 25 The compound of Embodiment 24, wherein R2 It is a halogen.

[0087] Embodiment 26 The compound of Embodiment 25, wherein R 2 is F, Cl or Br.

[0088] Embodiment 27 A compound of Formula 1 or any one of Embodiments 1 to 26, alone or in combination, wherein m is 0, 1 or 2.

[0089] Embodiment 28 The compound of Embodiment 27, wherein m is 0 or 1.

[0090] Embodiment 29 The compound of Embodiment 28, wherein m is 1.

[0091] Embodiment 30 The compound of Embodiment 27, wherein m is 0 (i.e., the 3-, 4-, 5-, and 6-positions are not R 3 replaced).

[0092] Embodiment 31 A compound of Formula 1 or any one of Embodiments 1 to 30, alone or in combination, wherein each R 3 are independently halogen, cyano, CHO, C1-C4 alkyl, C2-C4 alkenyl, C2-C4 alkynyl, C1-C4 haloalkyl, C2-C4 haloalkenyl, C2-C4 haloalkynyl, C3-C6 cycloalkyl, C3-C6 halocycloalkyl, C4–C8 alkylcycloalkyl, C2–C6 alkylcarbonyl, C2–C6 haloalkylcarbonyl, C2–C6 alkoxycarbonyl, C1-C4 alkoxy, C3-C4 alkenyloxy, C3-C4 alkynyloxy, C1-C4 haloalkoxy, C3-C4 haloalkenyloxy, C3-C4 haloalkynyloxy, C3–C6 cycloalkyloxy, C3–C6 halocycloalkyloxy, C2-C6 alkoxyalkyl, C2-C6 haloalkoxyalkyl, C2-C4 alkylcarbonyloxy, C2-C6 cyanoalkyl, C(=O)N(R 3A )(R 3B )、C(=NOR 3C )H、SO n R 3E ; or a benzene ring optionally substituted with up to 5 substituents independently selected from R 3F or a 5- or 6-membered heteroaromatic ring comprising ring members selected from carbon atoms and up to 4 heteroatoms independently selected from up to 2 O, up to 2 S, and up to 4 N atoms, each ring optionally substituted with up to 3 substituents independently selected from R on the carbon atom ring members; 3F and R on the nitrogen ring member 3G .

[0093] Embodiment 32 The compound of Embodiment 31, wherein each R 3 are independently halogen, cyano, CHO, C1-C4 alkyl, C2-C4 alkenyl, C2-C4 alkynyl, C1-C4 haloalkyl, C2-C4 haloalkenyl, C2-C4 haloalkynyl, C3-C6 cycloalkyl, C3-C6 halocycloalkyl, C2-C6 alkylcarbonyl, C2-C6 haloalkylcarbonyl, C2-C6 alkoxycarbonyl, C1-C4 alkoxy, C1-C4 haloalkoxy, C2-C6 alkoxyalkyl, C2-C6 haloalkoxyalkyl, C2-C6 cyanoalkyl, SO n R 3E or a 5- or 6-membered heteroaromatic ring comprising ring members selected from carbon atoms and up to 4 heteroatoms independently selected from up to 2 O, up to 2 S, and up to 4 N atoms, each ring optionally substituted with up to 3 substituents independently selected from R on the carbon atom ring members 3F and R on the nitrogen ring member 3G .

[0094] Embodiment 33 The compound of Embodiment 32, wherein each R 3 are independently halogen, cyano, C1-C4 alkyl, C2-C4 alkenyl, C2-C4 alkynyl, C1-C4 haloalkyl, C2-C6 alkylcarbonyl, C2-C6 haloalkylcarbonyl, C2-C6 alkoxycarbonyl, C1-C4 alkoxy, C1-C4 haloalkoxy, C2-C6 alkoxyalkyl or C2-C6 haloalkoxyalkyl.

[0095] Embodiment 34 The compound of Embodiment 33, wherein each R 3 are independently halogen, cyano, C1-C4 alkyl or C1-C4 haloalkyl.

[0096] Embodiment 35 The compound of Embodiment 34, wherein each R 3 are independently halogen or cyano.

[0097] Embodiment 36 The compound of Embodiment 35, wherein each R 3 are independently halogen.

[0098] Embodiment 37 A compound of Formula 1 or any one of Embodiments 1 to 36, alone or in combination, wherein R 3 The bond is to the remainder of Formula 1 at the 3-position.

[0099] Embodiment 38 A compound of Formula 1 or any one of Embodiments 1 to 37, alone or in combination, wherein each R 1A are independently C1-C4 alkyl or C1-C4 haloalkyl.

[0100] Embodiment 39. The compound of Embodiment 38, wherein each R 1A are independently C1-C4 haloalkyl.

[0101] Embodiment 40. A compound of formula 1 or any one of embodiments 1 to 39, alone or in combination, wherein each R 3E are independently C1-C4 alkyl.

[0102] Embodiment 41. A compound of formula 1 or any one of embodiments 1 to 40, alone or in combination, wherein each R 3A are independently C1-C4 alkyl.

[0103] Embodiment 42. A compound of formula 1 or any one of embodiments 1 to 41, alone or in combination, wherein each R 3B are independently H or C1-C4 alkyl.

[0104] Embodiment 43. A compound of formula 1 or any one of embodiments 1 to 42, alone or in combination, wherein each R 3C are independently H or C1-C4 alkyl.

[0105] Embodiment 44. A compound of formula 1 or any one of embodiments 1 to 43, alone or in combination, wherein each R 3D are independently H or C1-C4 alkyl.

[0106] Embodiment 45. A compound of Formula 1 or any one of Embodiments 1 to 44, alone or in combination, wherein each n is independently 0 or 2.

[0107] Embodiment 46. The compound of Embodiment 45, wherein n is 2.

[0108] Embodiment 47. The compound of Embodiment 45, wherein n is 0.

[0109] Embodiment 48. A compound of formula 1 or any one of embodiments 1 to 47, alone or in combination, provided that i) when Q is 5-chloro-2-pyridyl; Z is O; and R 3 When it is 4-chloro, then R 2 is not Cl or Br; ii) when Q is 4-CF3-2-pyrimidinyl; Z is O; and m is 0, then R 2 is not Cl or Br; and iii) when Q is 6-CF3-2-pyridyl; Z is O; and m is 0, then R 2 Not Br.

[0110] Embodiments of the invention and Embodiment AAA as described in the Summary of the Invention also include the following:

[0111] Embodiment 1P The compound of formula 1 (including all stereoisomers), its N-oxide and salt thereof, agricultural composition containing them, and their use as herbicides are as described in the Summary of the Invention.

[0112] Embodiment 2P The compound of Embodiment 1, wherein Q is a 5- or 6-membered aromatic heterocyclic ring, which is bound to the rest of Formula 1 via a carbon atom and is optionally substituted by 1 to 3 R 1 replace.

[0113] Embodiment 3P A compound of Embodiment 2, wherein Q is selected from

[0114]

[0115]

[0116] r is 0, 1, 2, or 3; and

[0117] s is 0 or 1.

[0118] Embodiment 4P A compound according to any one of Embodiments 1 to 3, wherein Q is a 5-membered aromatic heterocyclic ring, said ring being bound to the rest of Formula 1 via a carbon atom, and optionally substituted by R 1 is substituted and is selected from Q-1 to Q-41.

[0119] Embodiment 5P A compound of Embodiment 4 wherein Q is selected from Q-7 to Q-24.

[0120] Embodiment 6P A compound of Embodiment 5 wherein Q is selected from the group consisting of Q-9, Q-11, Q-12, Q-16, Q-18, Q-22, Q-23, Q-24, and Q-25.

[0121] Embodiment 7P A compound of Embodiment 6 wherein Q is selected from the group consisting of Q-11, Q-18 and Q-22.

[0122] Embodiment 8P A compound according to any one of Embodiments 1 to 3, wherein Q is a 6-membered aromatic heterocyclic ring, the ring being bound to the rest of Formula 1 via a carbon atom, and optionally substituted by R 1 is substituted and is selected from Q-42 to Q-54.

[0123] Embodiment 9P A compound of Embodiment 8 wherein Q is selected from the group consisting of Q-42, Q-43, Q-44, Q-47, Q-48 and Q-49.

[0124] Embodiment 10P The compound of Embodiment 9 wherein Q is selected from the group consisting of Q-42, Q-43, Q-47 and Q-48.

[0125] Embodiment 11P The compound of Embodiment 10 wherein Q is selected from the group consisting of Q-42, Q-47 and Q-48.

[0126] Embodiment 12P A compound of Embodiment 11 wherein Q is selected from Q-42.

[0127] Embodiment 13P The compound of Embodiment 12, wherein Q is

[0128]

[0129] Embodiment 14P A compound of any one of Embodiments 1 to 3 wherein Q is selected from the group consisting of Q-7 to Q-24, Q-42, Q-43, Q-44, Q-47, Q-48, and Q-49.

[0130] Embodiment 15P A compound of Embodiment 14 wherein Q is selected from Q-9, Q-11, Q-12, Q-16, Q-18, Q-22, Q-23, Q-24, Q-25, Q-42, Q-43, Q-47, and Q-48.

[0131] Embodiment 16P A compound of Embodiment 1 wherein Q is substituted with 1 to 3 R 1 Substituted phenyl.

[0132] Embodiment 17P The compound of Embodiment 16, wherein Q is 1 Substituted phenyl.

[0133] Embodiment 18P The compound of Embodiment 17, wherein Q is replaced by 1 R at the 3- or 4-position 1 Substituted phenyl (ie, in the meta or para position relative to the attachment of the phenyl to the remainder of Formula 1).

[0134] Embodiment 19P A compound of Embodiment 1, wherein when Q is 1 In the case of substituted phenyl, m is 1, 2 or 3.

[0135] Embodiment 20P A compound of Embodiment 1, wherein when Q is 1 In the case of substituted phenyl, m is 1 or 2.

[0136] Embodiment 21P A compound of Embodiment 1 wherein Q is not 1 Substituted phenyl.

[0137] Embodiment 22P A compound according to any one of Embodiments 1 to 21, wherein R 1is halogen, cyano, CHO, C1-C4 alkyl, C2-C4 alkenyl, C2-C4 alkynyl, C1-C4 alkoxy, C3-C4 alkenyloxy, C3-C4 alkynyloxy, C1-C4 haloalkyl, C1-C4 haloalkoxy, C2-C4 alkoxyalkyl, C2-C4 alkylthioalkyl or SO n R 1A .

[0138] Embodiment 23P The compound of Embodiment 22, wherein R 1 It is halogen, cyano, C1-C4 alkyl, C1-C4 alkoxy, C1-C4 haloalkyl, C1-C4 haloalkoxy, or SCF3.

[0139] Embodiment 24P The compound of Embodiment 23, wherein R 1 is halogen, C1-C4 alkyl or C1-C4 haloalkyl or C1-C4 haloalkoxy.

[0140] Embodiment 25P The compound of Embodiment 24, wherein R 1 is halogen, C1-C4 haloalkyl or C1-C4 haloalkoxy.

[0141] Embodiment 26P The compound of Embodiment 25, wherein R 1 It is Cl, Br, CF3 or OCF3.

[0142] Embodiment 27P A compound of any one of Embodiments 1 to 22 wherein each n is independently 0, 1 or 2.

[0143] Embodiment 28P A compound of Embodiment 27 wherein each n is independently 0.

[0144] Embodiment 29P A compound of Embodiment 28 wherein each n is independently 2.

[0145] Embodiment 30P A compound according to any one of Embodiments 1 to 29, wherein R 2 is halogen, C1-C4 alkyl or C1-C4 haloalkyl.

[0146] Embodiment 31P The compound of Embodiment 30, wherein R 2 It is halogen or C1-C4 alkyl.

[0147] Embodiment 32P The compound of Embodiment 31, wherein R 2 is halogen or CH3.

[0148] Embodiment 33P The compound of Embodiment 32, wherein R 2 It is a halogen.

[0149] Embodiment 34P The compound of Embodiment 33, wherein R 2 is F, Cl or Br.

[0150] Embodiment 35P A compound of any one of Embodiments 1 to 34 wherein m is 0, 1 or 2.

[0151] Embodiment 36P A compound of Embodiment 35 wherein m is 0 or 1.

[0152] Embodiment 37P A compound of Embodiment 36 wherein m is 1.

[0153] Embodiment 38P The compound of Embodiment 37, wherein m is 0 (i.e., the 3-, 4-, 5-, and 6-positions of the phenyl ring are not replaced by R 3 replace).

[0154] Embodiment 39P A compound of any one of Embodiments 1 to 37, wherein each R 3 are independently halogen, cyano, hydroxyl, nitro, amino, CHO, C1-C4 alkyl, C2-C4 alkenyl, C2-C4 alkynyl, C(=O)N(R 3A )(R 3B )、C(=NOR 3C )H、C(=N)(R 3D )H, C1-C4 alkoxy, C2-C4 cyanoalkoxy, C2-C4 alkylcarbonyl, C2-C4 alkoxycarbonyl, C2-C4 alkylcarbonyloxy, C2-C4 alkoxyalkyl, C1-C4 haloalkyl, C1-C4 haloalkoxy, SO n R 3E Or C3-C6 cycloalkyl.

[0155] Embodiment 40P The compound of Embodiment 39, wherein each R 3 are independently halogen, cyano, amino, C1-C4 alkyl, C2-C4 alkenyl, C2-C4 alkynyl, C1-C4 alkoxy, C2-C4 alkoxycarbonyl, C2-C4 alkylcarbonyloxy, C2-C4 alkoxyalkyl or C1-C4 haloalkyl.

[0156] Embodiment 41P A compound of Embodiment 40, wherein each R 3 are independently halogen, cyano, amino or C1-C4 alkyl.

[0157] Embodiment 42P A compound of Embodiment 41 wherein each R 3 are independently cyano.

[0158] Embodiment 43P. A compound of any one of Embodiments 1 to 37 or 39 to 42, wherein each R 3The bond to the remainder of Formula 1 is at the 3-, 4- or 6-position.

[0159] Embodiment 44P. The compound of Embodiment 43, wherein each R 3 The bond to the remainder of Formula 1 is at the 3- or 4-position.

[0160] Embodiment 45P. The compound of Embodiment 44, wherein R 3 The bond is to the remainder of Formula 1 at the 3-position.

[0161] Embodiment 46P. A compound of any one of Embodiments 1 to 22 or 27 or 29 to 45, wherein R 1A It is C1-C4 alkyl or C1-C4 haloalkyl.

[0162] Embodiment 47P. The compound of Embodiment 46, wherein R 1A It is a C1-C4 haloalkyl group.

[0163] Embodiment 48P. A compound of any one of Embodiments 1 to 37 or 39, wherein R 3E It is a C1-C4 alkyl group.

[0164] Embodiment 49P. A compound of any one of Embodiments 1 to 37 or 39, wherein R 3A It is a C1-C4 alkyl group.

[0165] Embodiment 50P. A compound of any one of Embodiments 1 to 37 or 39, wherein R 3B It is H or C1-C4 alkyl.

[0166] Embodiment 51P. A compound of any one of Embodiments 1 to 37 or 39, wherein R 3C It is H or C1-C4 alkyl.

[0167] Embodiment 52P. A compound of any one of Embodiments 1 to 37 or 39, wherein R 3D It is H or C1-C4 alkyl.

[0168] Embodiment 53P. A compound of any one of Embodiments 1 to 52, wherein Z is O.

[0169] Embodiment 54P. A compound of any one of Embodiments 1 to 53, wherein when m is 1, R 3 Located at the 3-, 5- or 6-position (ie, the 3-, 5- and 6-position of the benzene ring).

[0170] Embodiment 55P. The compound of any one of Embodiments 1 to 53, wherein when m is 1, R at the 4-position 3 Not Cl.

[0171] Embodiments of the present invention, including embodiments 1-48 and 1P-55P above and any other embodiments described herein, can be combined in any manner, and the variable descriptions in the embodiments relate not only to compounds of formula 1, but also to starting compounds and intermediate compounds that can be used to prepare compounds of formula 1. In addition, embodiments of the present invention, including embodiments 1-48 and 1P-55P above and any other embodiments described herein, and any combination thereof, relate to compositions and methods of the present invention.

[0172] The compound of embodiment AAA formula 1, wherein

[0173] Q is a 5- or 6-membered aromatic heterocyclic ring, which is bonded to the rest of Formula 1 via a carbon atom and is optionally substituted by 1 to 4 R 1 replace; or

[0174] Q is 1 to 4 R 1 Substituted phenyl;

[0175] Z is O or S;

[0176] R 1 is halogen, cyano, CHO, C1-C4 alkyl, C2-C4 alkenyl, C2-C4 alkynyl, C1-C4 alkoxy, C3-C4 alkenyloxy, C3-C4 alkynyloxy, C1-C4 haloalkyl, C1-C4 haloalkoxy, C2-C4 alkoxyalkyl, C2-C4 alkylthioalkyl, SO n R 1A , C2-C6 dialkylamino, C1-C4 cyanoalkyl, C1-C4 hydroxyalkyl, CH(=NOH) or C3-C6 cycloalkyl; or unsubstituted phenyl; or unsubstituted pyridyl;

[0177] R 2 is halogen, cyano, nitro, C1-C4 alkoxy, C1-C4 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, SO n R 2A or C1-C4 haloalkyl;

[0178] Each R 3 are independently halogen, cyano, hydroxyl, nitro, amino, CHO, C1-C4 alkyl, C2-C4 alkenyl, C2-C4 alkynyl, C(=O)N(R 3A )(R 3B )、C(=NOR 3C )H、C(=N)(R 3D)H, C1-C4 alkoxy, C2-C4 cyanoalkoxy, C2-C4 alkylcarbonyl, C2-C4 alkoxycarbonyl, C2-C4 alkylcarbonyloxy, C2-C4 alkoxyalkyl, C1-C4 haloalkyl, C1-C4 haloalkoxy, SO n R 3E or C3-C6 cycloalkyl; or phenyl optionally substituted by cyano, halogen or C1-C4 alkyl;

[0179] m is 0, 1, 2 or 3;

[0180] Each R 1A , R 2A and R 3E are independently C1-C4 alkyl, C1-C4 haloalkyl, C1-C4 alkylamino or C2-C6 dialkylamino;

[0181] R 3A is C1-C4 alkyl or C1-C4 haloalkyl;

[0182] R 3B is H, C1-C4 alkyl or C1-C4 haloalkyl;

[0183] R 3C are independently H or C1-C4 alkyl;

[0184] R 3D are independently H or C1-C4 alkyl; and

[0185] n is 0, 1, or 2;

[0186] Provided that the compound of formula 1 is not 5-chloro-2-[(4'-methyl[1,1'-biphenyl]2-yl)oxy]-pyrimidine (CAS#107492-74-0), 5-chloro-2-[(4'-chloro[1,1'-biphenyl]2-yl)oxy]-pyrimidine (CAS#107492-72-8), 5-chloro-2-[(3'-chloro[1,1'-biphenyl]2-yl)oxy]-pyrimidine (CAS#107492-76-2) and 5-chloro-2-[[3'-(trifluoromethyl)[1,1'-biphenyl]2-yl]oxy]-pyrimidine (CAS#107492-75-1); and provided that i) when Q is 5-chloro-2-pyridyl; Z is O; and R 3 When it is 4-chloro, then R 2 is not Cl or Br; ii) when Q is 4-CF3-2-pyrimidinyl; Z is O; and m is 0, then R 2 is not Cl or Br; and iii) when Q is 6-CF3-2-pyridyl; Z is O; and m is 0, then R 2 Not Br.

[0187] Embodiment AA: A compound of Embodiment AAA or a compound of Formula 1 as described in the Summary of the Invention, wherein

[0188] Q is a 5- or 6-membered aromatic heterocyclic ring, which is bonded to the rest of Formula 1 via a carbon atom and is optionally substituted by 1 to 4 R 1 replace;

[0189] Z is O or S;

[0190] Each R 1 are independently halogen, cyano, nitro, SF5, CHO, C(=O)NH2, C(=S)NH2, SO2NH2, C1-C4 alkyl, C2-C4 alkenyl, C2-C4 alkynyl, C1-C4 haloalkyl, C2-C4 haloalkenyl, C2-C4 haloalkynyl, C3-C6 cycloalkyl, C3-C6 halocycloalkyl, C4–C8 alkylcycloalkyl, C4–C8 cycloalkylalkyl, C2–C6 alkylcarbonyl, C2–C6 haloalkylcarbonyl, C2–C6 alkoxycarbonyl, C3-C7 cycloalkylcarbonyl, C2–C8 alkylaminocarbonyl, C3-C 10 dialkylaminocarbonyl, C1-C4 alkoxy, C3-C4 alkenyloxy, C3-C4 alkynyloxy, C1-C4 haloalkoxy, C3-C4 haloalkenyloxy, C3-C4 haloalkynyloxy, C3–C6 cycloalkoxy, C3–C6 halocycloalkoxy, C4–C8 cycloalkylalkoxy, C2-C6 alkoxyalkyl, C2-C6 haloalkoxyalkyl, C2-C6 alkoxyhaloalkyl, C2–C6 alkoxyalkoxy, C2-C4 alkylcarbonyloxy, C2-C6 cyanoalkyl, C2-C6 cyanoalkoxy, C1-C4 hydroxyalkyl, C2-C4 alkylthioalkyl, SO n R 1A 、Si(CH3)3 or B(-OC(R 1B )2C(R 1B )2O-); or a benzene ring optionally substituted with up to 5 substituents independently selected from R 1C or a 5- or 6-membered heteroaromatic ring comprising ring members selected from carbon atoms and up to 4 heteroatoms independently selected from up to 2 O, up to 2 S, and up to 4 N atoms, each ring optionally substituted with up to 3 substituents independently selected from R on the carbon atom ring members 1C and R on the nitrogen ring member 1D ;

[0191] R 2 is halogen, cyano, nitro, C1-C4 alkoxy, C1-C4 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, SO n R2A , C1-C4 haloalkyl or C3-C6 cycloalkyl;

[0192] Each R 3 and independently halogen, cyano, hydroxyl, nitro, amino, CHO, C(═O)NH2, C(═S)NH2, SO2NH2, C1-C4 alkyl, C2-C4 alkenyl, C2-C4 alkynyl, C1-C4 haloalkyl, C2-C4 haloalkenyl, C2-C4 haloalkynyl, C3-C6 cycloalkyl, C3-C6 halocycloalkyl, C4–C8 alkylcycloalkyl, C4–C8 cycloalkylalkyl, C2–C6 alkylcarbonyl, C2–C6 haloalkylcarbonyl, C2–C6 alkoxycarbonyl, C3-C7 cycloalkylcarbonyl, C1-C4 alkoxy, C3-C 4-Alkenyloxy, C3-C4 Alkynyloxy, C1-C4 Haloalkoxy, C3-C4 Haloalkenyloxy, C3-C4 Haloalkynyloxy, C3–C6 Cycloalkoxy, C3–C6 Halocycloalkoxy, C4–C8 Cycloalkylalkoxy, C2-C6 Alkoxyalkyl, C2-C6 Haloalkoxyalkyl, C2-C6 Alkoxyhaloalkyl, C2–C6 Alkoxyalkoxy, C2-C4 Alkylcarbonyloxy, C2-C6 Cyanoalkyl, C2-C6 Cyanoalkoxy, C2-C4 Alkylthioalkyl, Si(CH3)3, C≡CSi(CH3)3, C(=O)N(R 3A )(R 3B )、C(=NOR 3C )H、C(=NR 3D )H、SO n R 3E ; or a benzene ring optionally substituted with up to 5 substituents independently selected from R 3F or a 5- or 6-membered heteroaromatic ring comprising ring members selected from carbon atoms and up to 4 heteroatoms independently selected from up to 2 O, up to 2 S, and up to 4 N atoms, each ring optionally substituted with up to 3 substituents independently selected from R on the carbon atom ring members 3F and R on the nitrogen ring member 3G ; or pyrimidinyloxy;

[0193] m is 0, 1, 2 or 3;

[0194] Each n is independently 0, 1 or 2;

[0195] Each R 1A , R 2A and R 3E are independently C1-C4 alkyl, C1-C4 haloalkyl, C1-C4 alkylamino or C2-C6 dialkylamino;

[0196] Each R1B are independently H or C1-C4 alkyl;

[0197] Each R 1C are independently hydroxy, halogen, cyano, nitro, C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 alkoxy or C1-C6 haloalkoxy;

[0198] Each R 1D are independently cyano, C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 alkoxy or C2-C6 alkylcarbonyl;

[0199] Each R 3A are independently C1-C4 alkyl or C1-C4 haloalkyl;

[0200] Each R 3B are independently H, C1-C4 alkyl or C1-C4 haloalkyl;

[0201] Each R 3C are independently H or C1-C4 alkyl;

[0202] Each R 3D are independently H, amino, C1-C4 alkyl or C1-C4 alkylamino;

[0203] Each R 3F are independently hydroxy, halogen, cyano, nitro, C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 alkoxy or C1-C6 haloalkoxy; and

[0204] Each R 3G are independently cyano, C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 alkoxy or C2-C6 alkylcarbonyl;

[0205] Embodiment A. The compound of Embodiment AA, wherein

[0206] Q is selected from Q-1 to Q-55, wherein r is 0, 1, 2 or 3; and s is 0 or 1;

[0207] Each R 1are independently halogen, cyano, SF5, CHO, C1-C4 alkyl, C2-C4 alkenyl, C2-C4 alkynyl, C1-C4 haloalkyl, C2-C4 haloalkenyl, C2-C4 haloalkynyl, C2-C6 alkylcarbonyl, C2-C6 haloalkylcarbonyl, C2-C6 alkoxycarbonyl, C1-C4 alkoxy, C3-C4 alkenyloxy, C3-C4 alkynyloxy, C1-C4 haloalkoxy, C3-C4 haloalkenyloxy, C3-C4 haloalkynyloxy, C2-C6 alkoxyalkyl, C2-C6 haloalkoxyalkyl, C2-C6 cyanoalkyl, C1-C4 hydroxyalkyl, C2-C4 alkylthioalkyl or SO n R 1A ;

[0208] R 3 are independently halogen, cyano, CHO, C1-C4 alkyl, C2-C4 alkenyl, C2-C4 alkynyl, C1-C4 haloalkyl, C2-C4 haloalkenyl, C2-C4 haloalkynyl, C3-C6 cycloalkyl, C3-C6 halocycloalkyl, C4–C8 alkylcycloalkyl, C2–C6 alkylcarbonyl, C2–C6 haloalkylcarbonyl, C2–C6 alkoxycarbonyl, C1-C4 alkoxy, C3-C4 alkenyloxy, C3-C4 alkynyloxy, C1-C4 haloalkoxy, C3-C4 haloalkenyloxy, C3-C4 haloalkynyloxy, C3–C6 cycloalkyloxy, C3–C6 halocycloalkyloxy, C2-C6 alkoxyalkyl, C2-C6 haloalkoxyalkyl, C2-C4 alkylcarbonyloxy, C2-C6 cyanoalkyl, C(=O)N(R 3A )(R 3B )、C(=NOR 3C )H、SO n R 3E ; or a benzene ring optionally substituted with up to 5 substituents independently selected from R 3F or a 5- or 6-membered heteroaromatic ring comprising ring members selected from carbon atoms and up to 4 heteroatoms independently selected from up to 2 O, up to 2 S, and up to 4 N atoms, each ring optionally substituted with up to 3 substituents independently selected from R on the carbon atom ring members 3F and R on the nitrogen ring member 3G ;

[0209] Z is O; and

[0210] m is 0, 1 or 2.

[0211] Embodiment B. The compound of Embodiment A, wherein

[0212] Each R 1are independently halogen, cyano, CHO, C1-C4 alkyl, C2-C4 alkenyl, C2-C4 alkynyl, C1-C4 haloalkyl, C2-C4 haloalkenyl, C2-C4 haloalkynyl, C1-C4 alkoxy, C3-C4 alkenyloxy, C3-C4 alkynyloxy, C1-C4 haloalkoxy, C3-C4 haloalkenyloxy, C3-C4 haloalkynyloxy, C2-C6 alkoxyalkyl, C2-C6 haloalkoxyalkyl, C1-C4 hydroxyalkyl, C2-C4 alkylthioalkyl or SO n R 1A ;

[0213] R 2 is halogen, C1-C4 alkyl or C1-C4 haloalkyl;

[0214] Each R 3 are independently halogen, cyano, CHO, C1-C4 alkyl, C2-C4 alkenyl, C2-C4 alkynyl, C1-C4 haloalkyl, C2-C4 haloalkenyl, C2-C4 haloalkynyl, C3-C6 cycloalkyl, C3-C6 halocycloalkyl, C2-C6 alkylcarbonyl, C2-C6 haloalkylcarbonyl, C2-C6 alkoxycarbonyl, C1-C4 alkoxy, C1-C4 haloalkoxy, C2-C6 alkoxyalkyl, C2-C6 haloalkoxyalkyl, C2-C6 cyanoalkyl, SO n R 3E or a 5- or 6-membered heteroaromatic ring comprising ring members selected from carbon atoms and up to 4 heteroatoms independently selected from up to 2 O, up to 2 S, and up to 4 N atoms, each ring optionally substituted with up to 3 substituents independently selected from R on the carbon atom ring members 3F and R on the nitrogen ring member 3G ;and

[0215] m is 0 or 1.

[0216] Embodiment C1. The compound of Embodiment B, wherein

[0217] Q is selected from Q-7 to Q-24;

[0218] Each R 1 are independently halogen, cyano, C1-C4 alkyl, C1-C4 haloalkyl, C1-C4 alkoxy, C1-C4 haloalkoxy or SO n R 1A ;

[0219] R 2 is halogen or C1-C4 alkyl;

[0220] Each R 3are independently halogen, cyano, C1-C4 alkyl, C2-C4 alkenyl, C2-C4 alkynyl, C1-C4 haloalkyl, C2-C6 alkylcarbonyl, C2-C6 haloalkylcarbonyl, C2-C6 alkoxycarbonyl, C1-C4 alkoxy, C1-C4 haloalkoxy, C2-C6 alkoxyalkyl or C2-C6 haloalkoxyalkyl; and

[0221] Each R 1A are independently C1-C4 alkyl or C1-C4 haloalkyl.

[0222] Embodiment C2. The compound of Embodiment B, wherein

[0223] Q is selected from the group consisting of Q-43, Q-44, Q-45, Q-48, Q-49, and Q-50;

[0224] Each R 1 are independently halogen, cyano, C1-C4 alkyl, C1-C4 haloalkyl, C1-C4 alkoxy, C1-C4 haloalkoxy or SO n R 1A ;

[0225] R 2 is halogen or C1-C4 alkyl;

[0226] Each R 3 are independently halogen, cyano, C1-C4 alkyl, C2-C4 alkenyl, C2-C4 alkynyl, C1-C4 haloalkyl, C2-C6 alkylcarbonyl, C2-C6 haloalkylcarbonyl, C2-C6 alkoxycarbonyl, C1-C4 alkoxy, C1-C4 haloalkoxy, C2-C6 alkoxyalkyl or C2-C6 haloalkoxyalkyl; and

[0227] Each R 1A are independently C1-C4 alkyl or C1-C4 haloalkyl.

[0228] Embodiment D1. The compound of Embodiment C1, wherein

[0229] Q is selected from Q-16 and Q-18;

[0230] Each R 1 are independently halogen, C1-C4 alkyl, C1-C4 haloalkyl or C1-C4 haloalkoxy;

[0231] R 2 is halogen or CH3; and

[0232] Each R 3 are independently halogen, cyano, C1-C4 alkyl or C1-C4 haloalkyl.

[0233] Embodiment D2. The compound of Embodiment C2, wherein

[0234] Q is selected from Q-43, Q-44 and Q-45;

[0235] Each R 1 are independently halogen, C1-C4 alkyl, C1-C4 haloalkyl or C1-C4 haloalkoxy;

[0236] R 2 is halogen or CH3; and

[0237] Each R 3 are independently halogen, cyano, C1-C4 alkyl or C1-C4 haloalkyl.

[0238] Specific embodiments include compounds of Formula 1 selected from:

[0239] 5-chloro-2-[2-(5-chloro-2-pyridyl)phenoxy]pyrimidine (Compound 1),

[0240] 5-chloro-2-[2-[5-(fluoromethyl)-3-isoxazolyl]phenoxy]pyrimidine (Compound 32),

[0241] 2-[2-(3-bromo-5-isoxazolyl)phenoxy]-5-chloropyrimidine (Compound 12),

[0242] 5-chloro-2-[2-[5-(trifluoromethyl)-2-pyridyl]phenoxy]pyrimidine (Compound 27),

[0243] 5-chloro-2-[3-chloro-2-(5-chloro-2-pyridyl)phenoxy]pyrimidine (Compound 23),

[0244] 4-[2-[(5-bromo-2-pyrimidinyl)oxy]phenyl]-2-(trifluoromethyl)pyrimidine (Compound 21),

[0245] 2-[2-(2-bromo-5-thiazolyl)phenoxy]-5-(trifluoromethyl)pyrimidine (Compound 15),

[0246] 5-chloro-2-[4-methyl-2-[2-(trifluoromethyl)-4-pyridinyl]phenoxy]pyrimidine (Compound 24),

[0247] 5-chloro-2-[2-[5-(difluoromethyl)-3-isoxazolyl]phenoxy]pyrimidine (Compound 35),

[0248] 5-chloro-2-[2-[3-(difluoromethyl)-5-isoxazolyl]phenoxy]pyrimidine (Compound 53),

[0249] 5-chloro-2-[2-[5-(difluoromethyl)-3-isoxazolyl]-3-fluorophenoxy]pyrimidine (Compound 55),

[0250] 5-bromo-2-[2-[5-(difluoromethyl)-3-isoxazolyl]phenoxy]pyrimidine (Compound 62),

[0251] 5-chloro-2-[2-[3-(trifluoromethyl)-5-isoxazolyl]phenoxy]pyrimidine (Compound 63),

[0252] 5-chloro-2-[2-[3-(difluoromethyl)-5-isoxazolyl]-3-fluorophenoxy]pyrimidine (Compound 144),

[0253] 5-bromo-2-[2-[3-(difluoromethyl)-5-isoxazolyl]-3-fluorophenoxy]pyrimidine (Compound 145),

[0254] 5-chloro-2-[2-[5-(trifluoromethyl)-3-isoxazolyl]-3-fluorophenoxy]pyrimidine (Compound 168), and

[0255] 5-Chloro-2-[2-[5-(trifluoromethyl)-3-isoxazolyl]phenoxy]pyrimidine (Compound 200).

[0256] Embodiments of the invention and Embodiment AAA as described in the Summary of the Invention also include the following:

[0257] The compound of embodiment Ap of the invention, wherein

[0258] Q is a 5- or 6-membered aromatic heterocyclic ring, which is bonded to the rest of Formula 1 via a carbon atom and is optionally substituted by 1 to 3 R 1 replace; or

[0259] Q is 1 to 3 R 1 Substituted phenyl;

[0260] R 1 is halogen, cyano, CHO, C1-C4 alkyl, C2-C4 alkenyl, C2-C4 alkynyl, C1-C4 alkoxy, C3-C4 alkenyloxy, C3-C4 alkynyloxy, C1-C4 haloalkyl, C1-C4 haloalkoxy, C2-C4 alkoxyalkyl, C2-C4 alkylthioalkyl or SO n R 1A ;

[0261] Each n is independently 0, 1 or 2

[0262] R 2 is halogen, C1-C4 alkyl or C1-C4 haloalkyl;

[0263] m is 0, 1 or 2;

[0264] Each R 3 are independently halogen, cyano, hydroxyl, nitro, amino, CHO, C1-C4 alkyl, C2-C4 alkenyl, C2-C4 alkynyl, C(=O)N(R 3A )(R 3B )、C(=NOR 3C )H、C(=N)(R 3D )H, C1-C4 alkoxy, C2-C4 cyanoalkoxy, C2-C4 alkylcarbonyl, C2-C4 alkoxycarbonyl, C2-C4 alkylcarbonyloxy, C2-C4 alkoxyalkyl, C1-C4 haloalkyl, C1-C4 haloalkoxy, SO n R 3E or C3-C6 cycloalkyl;

[0265] Each R 3 It is linked to the rest of Formula 1 at the 3-, 4- or 6-position.

[0266] R 1A is C1-C4 alkyl or C1-C4 haloalkyl;

[0267] R 3E is a C1-C4 alkyl group;

[0268] R 3A is a C1-C4 alkyl group;

[0269] R 3B is H or C1-C4 alkyl;

[0270] R 3C is H or C1-C4 alkyl; and

[0271] R 3D is H or C1–C4 alkyl.

[0272] Embodiment Bp The compound of Embodiment A, wherein

[0273] Q is selected from Q-1 to Q-54 (i.e., as described in Embodiment 3);

[0274] Z is O;

[0275] R 1 is halogen, cyano, C1-C4 alkyl, C1-C4 alkoxy, C1-C4 haloalkyl, C1-C4 haloalkoxy, or SCF3;

[0276] R 2 is halogen or C1-C4 alkyl;

[0277] m is 0 or 1;

[0278] Each R 3 are independently halogen, cyano, amino, C1-C4 alkyl, C2-C4 alkenyl, C2-C4 alkynyl, C1-C4 alkoxy, C2-C4 alkoxycarbonyl, C2-C4 alkylcarbonyloxy, C2-C4 alkoxyalkyl or C1-C4 haloalkyl; and

[0279] Each R 3 It is linked to the rest of Formula 1 at the 3- or 4-position.

[0280] The compound of Embodiment Cp Embodiment B, wherein

[0281] Q is a 5-membered aromatic heterocyclic ring, which is bonded to the rest of Formula 1 via a carbon atom, and is optionally 1 substituted, and is selected from Q-1 to Q-41;

[0282] R 1 is halogen, C1-C4 haloalkyl or C1-C4 haloalkoxy;

[0283] R 2 is halogen or CH3; and

[0284] Each R 3 are independently halogen, cyano, amino or C1-C4 alkyl.

[0285] The compound of Embodiment D or Embodiment C, wherein

[0286] Q is a 6-membered aromatic heterocyclic ring, which is bonded to the rest of Formula 1 via a carbon atom, and is optionally replaced by R 1 substituted and selected from Q-42 to Q-54;

[0287] R 1 is halogen, C1-C4 haloalkyl or C1-C4 haloalkoxy;

[0288] R 2 is halogen or CH3; and

[0289] Each R 3 are independently halogen, cyano, amino or C1-C4 alkyl.

[0290] Embodiment Ep. The compound of Embodiment D, wherein

[0291] Q is selected from the group consisting of Q-42, Q-43, Q-44, Q-47, Q-48, and Q-49;

[0292] R 1 Cl, Br, CF3 or OCF3;

[0293] R 2 is a halogen; and

[0294] Each R 3 are independently cyano.

[0295] Specific embodiments include compounds of formula 1 selected from:

[0296] 5-Chloro-2-[2-(5-chloro-2-pyridyl)phenoxy]pyrimidine (Compound 1);

[0297] 5-Chloro-2-[2-[5-(fluoromethyl)-3-isoxazolyl]phenoxy]pyrimidine (Compound 32);

[0298] 2-[2-(3-bromo-5-isoxazolyl)phenoxy]-5-chloropyrimidine (Compound 12);

[0299] 5-Chloro-2-[[4'-(trifluoromethoxy)[1,1'-biphenyl]-2-yl]oxy]pyrimidine (Compound 42);

[0300] 5-Chloro-2-[2-[5-(trifluoromethyl)-2-pyridinyl]phenoxy]pyrimidine (Compound 27);

[0301] 5-Chloro-2-[3-chloro-2-(5-chloro-2-pyridyl)phenoxy]pyrimidine (Compound 23);

[0302] 4-[2-[(5-bromo-2-pyrimidinyl)oxy]phenyl]-2-(trifluoromethyl)pyrimidine (Compound 21);

[0303] 2-[2-(2-bromo-5-thiazolyl)phenoxy]-5-(trifluoromethyl)pyrimidine (Compound 15); and

[0304] 5-Chloro-2-[4-methyl-2-[2-(trifluoromethyl)-4-pyridinyl]phenoxy]pyrimidine (Compound 24).

[0305] The present invention also relates to a method for controlling undesirable vegetation, the method comprising applying a herbicidally effective amount of a compound of the present invention (e.g., in the form of a composition described herein) to the location of the vegetation. It is noteworthy that the embodiments related to the method of use are those of the compounds of the above embodiments. The compounds of the present invention are particularly useful for selectively controlling weeds in crops such as wheat, barley, corn, soybeans, sunflowers, cotton, rapeseed and rice, as well as specialty crops such as sugarcane, citrus, fruit and nut crops.

[0306] Also noteworthy as an embodiment is the herbicidal composition of the present invention comprising a compound of the above-described embodiment.

[0307] The present invention also includes a herbicide mixture, the herbicide mixture comprising (a) a compound selected from Formula 1, its N-oxide and salt, and (b) at least one additional active ingredient selected from the following: (b1) photosynthetic system II inhibitors, (b2) acetohydroxyacid synthase (AHAS) inhibitors, (b3) acetyl-CoA carboxylase (ACCase) inhibitors, (b4) auxin mimetics, and (b5) 5-enol-pyruvylshikimate-3-phosphate (EPSP) synthase inhibitors, (b6) photosynthetic system I electron diverters, (b7) protoporphyrinogen oxidase (PPO) inhibitors, (b8) glutamine synthetase (GS) inhibitors, (b9) very long chain fatty acid (VLCFA) elongase inhibitors. preparations, (b10) auxin transport inhibitors, (b11) phytoene desaturase (PDS) inhibitors, (b12) 4-hydroxyphenyl-pyruvate dioxygenase (HPPD) inhibitors, (b13) homogentisate solanine transferase (HST) inhibitors, (b14) cellulose biosynthesis inhibitors, (b15) other herbicides, including mitotic disruptors, organic arsenic compounds, sulfamethoxam, avenate, bromobutyric acid, chlorfenapyr, cyproconazole, benzylpyruvate, dazomethan, saprol, methylthiazol, ethoprop, phosphine-adjusting, phosphine-ammonium, metamidine, oxazolidinone, oleic acid, nonanoic acid and barnyardgra, and (b16) herbicide safeners; and salts of compounds (bl) to (bl6).

[0308] "Photosystem II inhibitors" (b1) are compounds that bind to the D-1 protein at the QB-binding site, thereby blocking the transfer of electrons from QA to QB in the chloroplast thylakoid membrane. The blocked electrons through photosystem II are transferred through a series of reactions to form toxic compounds that damage the cell membrane and cause chloroplast swelling, membrane leakage, and ultimately cell rupture. The QB-binding site has three different binding sites: binding site A binds triazines such as atrazine, triazinones such as hexazinone, and uracils such as herbicide, binding site B binds phenylureas such as diuron, and binding site C binds benzothiadiazoles such as bentazon, nitriles such as bromoxynil, and phenyl-pyridazines such as daconil. Examples of photosystem II inhibitors include ametryn, amitriptyline, atrazine, thiamethoxam, herbicide, bromophenoxime, bromoxynil, chlorbromid, herbicide, chlorotoluron, cypermethrin, benzyluron, cyanazine, cypermethrin, betamethoxam, dichlorvos, oxazolidinone, isopentanol, diuron, sulfathiocarb, fenucyanuron, fluuron, hexazinone, ioxynil, isoproturon, isoxaluron, lenacil, linuron, metamitron, methylbenzenethiocarb, thiamethoxam, methicillin, chloranil, chlorpyrifos, chloranil, chlorfenapyr ...

[0309] "AHAS inhibitors" (b2) are compounds that inhibit acetohydroxyacid synthase (AHAS), also known as acetolactate synthase (ALS), thereby killing plants by inhibiting the production of branched aliphatic amino acids such as valine, leucine and isoleucine required for protein synthesis and cell growth. Examples of AHAS inhibitors include amidosulfuron, tetrazosulfuron, benzylsulfuron, bispyribac-sodium, clorac-sulfuron, chlorsulfuron, cysulfuron, cyclamoxal, bispyribac-sodium, ethoxysulfuron, fluazifop-methyl, fluazifop-methyl, fluazifop-methyl sodium, foramsulfuron, halopersulfuron, imazamox, imazamox, imazamox, imazamox, imazamox, imazamox, Imazethapyr, imazethapyr, iodosulfuron-methyl (including sodium salt), iofensulfuron (2-iodo-N-[[(4-methoxy-6-methyl-1,3,5-triazine-2-yl)amino]carbonyl]benzenesulfonamide), methyldisulfuron, bis-ether clorosulfuron-methyl (3-chloro-4-(5,6-dihydro-5-methyl-1,4,2-dioxazin-3-yl)-N-[[(4,6-dimethoxy-2-pyrimidinyl)amino]carbonyl]-1-methyl-1H-pyrazole-5-sulfonamide), sulfamethoxazole, nicosulfuron, oxasulfuron-methyl, penoxsulam, primisulfuron, propensulfuron-methyl, propazinesulfuron (2-chloro-N-[[(4,6-dimethoxy-2-pyrimidinyl)amino]carbonyl]-6-propylimidazo[1,2-b]pyridazine-3-sulfonamide), prosulfuron, pyrazosulfuron Sulfurcarbon, pyrimidinesulfuron, cypermethrin, oxaflutamide, pyrimidinesulfuron, pyrimidinesulfuron, sulfasulfuron-methyl, thiosulfuron-methyl, thiosulfuron-methyl, thiosulfuron-methyl, fluazifop-methyl (N-[2-[(4,6-dimethoxy-1,3,5-triazine-2-yl)carbonyl]-6-fluorophenyl]-1,1-difluoro-N-methylmethanesulfonamide), bensulfuron-methyl, bensulfuron-methyl, trifloxysulfuron (including sodium salt), and fluazifop-methyl.

[0310] "ACCase inhibitors" (b3) are compounds that inhibit acetyl-CoA carboxylase, which is used to catalyze the early steps of lipid and fatty acid synthesis in plants. Lipids are essential components of cell membranes, and new cells cannot be produced without them. Inhibition of acetyl-CoA carboxylase and the subsequent lack of lipid production lead to loss of cell membrane integrity, especially in active growth areas such as meristems. Eventually, seedling and rhizome growth ceases, and seedling meristems and flagella begin to wilt. Examples of ACCase inhibitors include fenoxam, butyrac, clethodim, clodinafop-butyl, cyhalofop-butyl, diclofodinate, fenoxaprop-butyl, fluazifop-butyl, cyhalofop-butyl, pinoxaden, cypermethrin, cypermethrin, quinazolin, quizalofop-butyl, sethoxydim, chlorpyrifos and oxazolidinone, including split forms such as fenoxaprop-butyl, fluazifop-butyl, fluazifop-butyl and quizalofop-butyl and ester forms such as propargyl clodinafop-butyl, cyhalofop-butyl, diclofodinate methyl and fenoxaprop-butyl ethyl.

[0311] Auxins are plant hormones that regulate the growth of various plant tissues. "Auxin mimetics" (b4) are compounds that mimic the plant growth hormone auxin, thus causing uncontrolled and disordered growth, leading to plant death in susceptible species. Examples of auxin mimetics include cyprodinil (6-amino-5-chloro-2-cyclopropyl-4-pyrimidinecarboxylic acid) and its methyl and ethyl esters and their sodium and potassium salts, aminopyralid, chlorpyrifos, chlorpyrifos, barnyardgrass, clopyralid, dicamba, 2,4D, 2,4DB, 2,4-dichlorvos, fluroxypyr, fluazifop-butyl (4-amino-3-chloro-6-(4-chloro-2-fluoro-3-methoxyphenyl)propene )-2-picolinic acid), halofopyridine (methyl 4-amino-3-chloro-6-(4-chloro-2-fluoro-3-methoxyphenyl)-2-picolinate), MCPA, MCPB, chloropropionic acid, picloram, quinclorac, quinmeclorac, 2,3,6TBA, triclopyr, and methyl 4-amino-3-chloro-6-(4-chloro-2-fluoro-3-methoxyphenyl)-5-fluoro-2-picolinate.

[0312] "EPSP (5-enol-pyruvylshikimate-3-phosphate) synthase inhibitors" (b5) are compounds that inhibit the enzyme, 5-enol-pyruvylshikimate-3-phosphate synthase, which is involved in the synthesis of aromatic amino acids such as tyrosine, tryptophan and phenylalanine. EPSP inhibitor herbicides are readily absorbed through plant leaves and transported to the growing points in the phloem. Glyphosate is a relatively non-selective post-emergence herbicide belonging to this class. Glyphosate includes esters and salts such as ammonium, isopropylammonium, potassium, sodium (including sodium sesquisodium) and trimethylsulfonium (otherwise known as glufosinate).

[0313] "Photosystem I electron diverters" (b6) are compounds that accept electrons from Photosystem I and, after several cycles, generate hydroxyl radicals. These radicals are extremely reactive and tend to damage unsaturated lipids, including membrane fatty acids and chlorophyll. This destroys cell membrane integrity, making cells and organelles "leaky," leading to rapid wilting and drying of leaves, and ultimately plant death. Examples of this second class of photosynthesis inhibitors include diquat.

[0314] "PPO inhibitors" (b7) are compounds that inhibit the enzyme protoporphyrinogen oxidase, which rapidly leads to the formation of highly reactive compounds in plants that damage cell membranes, thereby causing cell fluid exudation. Examples of PPO inhibitors include trifluorfen, azopyralid, bispyribac, fluazifop-butyl, foramsulfuron, triadimefon, indolesulfuron, isopropylpyraclostrobin, flupyridazine, fluamid, fluazifop-butyl, fluazifop-butyl, fluazifop-butyl, flufenacet, flumioxazolidinone, fluazifop-butyl, flufenacet-butyl, fluazifop-butyl, flufenacet-butyl, fluazifop-butyl, flufenacet-butyl, lactofen, oxadiazine, oxadiazine, oxyfluorfen, cypermethrin, fluazifop-butyl, flufenacet-butyl ... -[2-[[2-chloro-5-[3,6-dihydro-3-methyl-2,6-dioxo-4-(trifluoromethyl)-1(2H)-pyrimidinyl]-4-fluorophenyl]thio]-1-oxopropyl]-β-alanine methyl ester) and 3-[7-fluoro-3,4-dihydro-3-oxo-4-(2-propyn-1-yl)-2H-1,4-benzoxazin-6-yl]dihydro-1,5-dimethyl l-6-thioxo-1,3,5-triazine-2,4(1H,3H)-dione.

[0315] "GS (glutamine synthase) inhibitors" (b8) are compounds that inhibit the activity of glutamine synthase, an enzyme used by plants to convert ammonia to glutamine. As a result, ammonia accumulates and glutamine levels decrease. Plant damage may occur due to the combined effects of ammonia toxicity and deficiencies in amino acids required for other metabolic processes. GS inhibitors include glufosinate and its esters and salts, such as glufosinate-ammonium and other glufosinate derivatives, glufosinate-P ((2S)-2-amino-4-(hydroxymethylphosphinyl)butyric acid) and bialaphos.

[0316] "VLCFA (very long chain fatty acid) elongase inhibitors" (b9) are herbicides of various chemical structures that inhibit elongase. Elongase is an enzyme located in or near the chloroplasts that is involved in the biosynthesis of VLCFAs. In plants, very-long-chain fatty acids are the main constituents of hydrophobic polymers that prevent dehydration of the leaf surface and provide stability to pollen grains. Such herbicides include acetochlor, alachlor, safamidophos, butachlor, benzophenone, dimethochlor, dimethenamid, bispyribac, fenoxasulfone (3-[[(2,5-dichloro-4-ethoxyphenyl)methyl]sulfonyl]-4,5-dihydro-5,5-dimethylisoxazole), tetrazopyralid, flufenacet, indole, mefenacet, metazachlor, isopropylamine, naproxenamide, naproxenamide, naproxenamide-M ((2R)-N,N-diethyl-2-(1-naphthyloxy)propionamide), pethodiolachlor, pyraclostrobin, pretilachlor, chlorfenapyr, isopropylamine, roxasulfone, and dimethenamid, including resolved forms such as S-isopropylamine and chloroacetamide and oxyacetamide.

[0317] "Auxin transport inhibitors" (b10) are chemicals that inhibit auxin transport in plants, such as by binding to auxin-carrier proteins. Examples of auxin transport inhibitors include diflufenicol, naphthamide (also known as N-(1-naphthyl)-o-carbamoylbenzoic acid and 2-[(1-naphthylamino)carbonyl]benzoic acid).

[0318] "PDS (phytoene dehydrogenase inhibitor)" (b11) is a compound that inhibits the carotenoid biosynthesis pathway in the phytoene dehydrogenase step. Examples of PDS inhibitors include fluazifop, diflufenicol, fluazifop, fluridone, fluchloridone, furazolidone, fluazifop, and flufenac.

[0319] "HPPD (4-hydroxyphenyl-pyruvate dioxygenase) inhibitors" (b12) are chemical substances that inhibit the biosynthesis of 4-hydroxyphenyl-pyruvate dioxygenase synthesis. Examples of HPPD inhibitors include cypermethrin, pyraclostrobin, flupyraclostrobin (4-hydroxy-3-[[2-[(2-methoxyethoxy)methyl]-6-(trifluoromethyl)-3-pyridinyl]carbonyl]bicyclo[3.2.1]oct-3-en-2-one), fenquinotrione (2-[[8-chloro-3,4-dihydro-4-(4-methoxyphenyl)-3-oxo-2-quinoxalinyl]carbonyl]-1,3-cyclohexanedione), isoxaflutole, isoxaflutole, mesotrione, pyraclostrobin, pyrazolamide, pyrazolamide, pyrazolidine ... -(2,6-diethyl-4-methylphenyl)-5-hydroxy-2,6-dimethyl-3(2H)-pyridazinone, 4-(4-fluorophenyl)-6-[(2-hydroxy-6-oxo-1-cyclohexen-1-yl)carbonyl]-2-methyl-1,2,4-triazine-3,5(2H,4H)-dione, 5[(2-hydroxy-6-oxo-1-cyclohexen-1-yl)carbonyl]- 2-(3-methoxyphenyl)-3-(3-methoxypropyl)-4(3H)-pyrimidinone, 2-methyl-N-(4-methyl-1,2,5-oxadiazol-3-yl)-3-(methylsulfinyl)-4-(trifluoromethyl)benzamide, and 2-methyl-3-(methylsulfonyl)-N-(1-methyl-1H-tetrazol-5-yl)-4-(trifluoromethyl)benzamide.

[0320] HST (homogeneic acid solenesyltranserase) inhibitors (b13) disrupt the ability of plants to convert homogentisic acid into 2-methyl-6-solanyl-1,4-benzoquinone, thereby disrupting carotenoid biosynthesis. Examples of HST inhibitors include fluazifop, chlorpyrifos, 3-(2-chloro-3,6-difluorophenyl)-4-hydroxy-1-methyl-1,5-naphthyridin-2(1H)-one, 7-(3,5-dichloro-4-pyridyl)-5-(2,2-difluoroethyl)-8-hydroxypyrrolo[2,3-b]pyrazin-6(5H)-one, and 4-(2,6-diethyl-4-methylphenyl)-5-hydroxy-2,6-dimethyl-3(2H)-pyridazinone.

[0321] HST inhibitors also include compounds of formula A and B.

[0322]

[0323] Where R d1 is H, Cl or CF3; R d2 is H, Cl or Br; R d3 is H or Cl; R d4 is H, Cl or CF3; R d5 is CH3, CH2CH3 or CH2CHF2; and R d6 is OH or -OC(=O)-i-Pr; and R e1 is H, F, Cl, CH3 or CH2CH3; R e2 is H or CF3; R e3 is H, CH3 or CH2CH3; R e4 is H, F or Br; R e5 is Cl, CH3, CF3, OCF3 or CH2CH3; R e6 is H, CH3, CH2CHF2 or C≡CH; R e7 is OH, -OC(=O)Et, -OC(=O)-i-Pr or -OC(=O)-t-Bu; and A e8 is N or CH.

[0324] Cellulose biosynthesis inhibitors (b14) inhibit the biosynthesis of cellulose in certain plants. They are most effective when used as a pre-application or early post-application on young or rapidly growing plants. Examples of cellulose biosynthesis inhibitors include chlorpyrifos, dichlobenil, fluazifop, triazine, indole, chloranil ... 2 -[(1R,2S)-2,3-dihydro-2,6-dimethyl-1H-inden-1-yl]-6-(1-fluoroethyl)-1,3,5-triazine-2,4-diamine), isoxazolidinone and triazine fluazifop-amid.

[0325] Other herbicides (b15) include herbicides that work through a variety of different modes of action, such as mitotic disruptors (e.g., oxazolidinone-M-methyl and oxazolidinone-M-isopropyl), organic arsenic compounds (e.g., DSMA and MSMA), 7,8-dihydrofolate synthesis inhibitors, chloroplast isoprenoid synthesis inhibitors, and cell wall biosynthesis inhibitors. Other herbicides include those herbicides with unknown modes of action or that do not belong to the specific categories listed in (b1) to (b14) or that work through a combination of the modes of action listed above. Examples of other herbicides include fenthiocarb, sulfamethoxam, chlorfenapyr, bromobutyric acid amine, cyproconazole, clomazone, benzylpyridinium, cyclopyrimorate (6-chloro-3-(2-cyclopropyl-6-methylphenoxy)-4-pyridazinyl 4-morpholine carboxylate), fenthiocarb, difenac, ethoxybencarb, fluazifop, fluazifop, chlorfenapyr, chlorfenapyr, dazomethane, saprol, triazolam (1-( The compounds included 2,4-dichlorophenyl)-N-(2,4-difluorophenyl)-1,5-dihydro-N-(1-methylethyl)-5-oxo-4H-1,2,4-triazole-4-amide), metamidine, methylthiazol-methyl, oleic acid, oxazithromycin, nonanoic acid, barnyardgrass and 5-[[(2,6-difluorophenyl)methoxy]methyl]-4,5-dihydro-5-methyl-3-(3-methyl-2-thienyl)isoxazole.

[0326] "Herbicide safeners" (b16) are substances added to herbicide formulations to eliminate or reduce the phytotoxic effects of the herbicide on certain crops. These compounds protect the crop from damage by the herbicide, but generally do not prevent the herbicide from controlling undesirable vegetation. Examples of herbicide safeners include, but are not limited to, fenthiocarb, fenthiocarb, benthiocarb, cyproconazole, cyproconazole, cyproconazole, dimethoate, dichloropropene, dicyclonon, fenthiocarb, fenthiocarb, fenthiocarb, fluazifop, fenthiocarb, isoxadiazole, mefenacet, mephenate, mefenacet, naphthalene dicarboxylic anhydride, fenthiocarb, N-(carbamoyl)-2-methylbenzenesulfonamide and N-(aminocarbonyl)-2-fluorobenzenesulfonamide, 1-bromo-4-[(chloromethyl)sulfonyl]benzene, 2-(dichloromethyl)-2-methyl-1,3-dioxolane (MG 191), 4-(dichloroacetyl)-1-oxa-4-azaspiro[4.5]decane (MON 4660).

[0327] The compounds of Formula 1 can be prepared by general methods known in the art of synthetic organic chemistry. The compounds of Formula 1 can be prepared using one or more of the following methods and variations as described in Schemes 1-9. Unless otherwise indicated, Q, R 1 , R 2 and R 3The definition of is as defined above in the Summary of the Invention. Unless otherwise indicated, compounds of Formulas 1A-1C, 2A-2F, 4A and 8A are various subsets of compounds of Formulas 1, 2, 4 and 8, and all substituents of Formulas 1A-1C, 2A-2F, 4A and 8A are as defined above in Formula 1.

[0328] Compounds of Formula 1 may be prepared using one or more of the following methods and variations as described in Schemes 1-9. Unless otherwise indicated, Q, R 1 , R 2 and R 3 The definition of is as defined above in the Summary of the Invention.

[0329] As shown in Scheme 1, the compound of Formula 1 can be prepared by nucleophilic substitution by heating the compound of Formula 2 with the compound of Formula 3 (wherein LG is halogen or SO2Me) in a suitable solvent such as acetonitrile, tetrahydrofuran or N,N-dimethylformamide in the presence of a base such as potassium carbonate or cesium carbonate at a temperature in the range of 50 to 110° C. The reaction is usually carried out at a temperature in the range of 50 to 110° C.

[0330] Solution 1

[0331]

[0332] Alternatively, as shown in Scheme 2, formula 5 boron compounds or formula 6 tin compounds can be coupled with formula 4 intermediates under Suzuki or Stille conditions to obtain formula 1 compounds. Suzuki coupling is usually carried out in the presence of Pd (0) or Pd (II) salts, suitable ligands and bases. Suitable bases for this conversion include potassium carbonate or cesium carbonate, and Pd (II) salts such as Pd (OAc) 2 or PdCl 2 can be used with ligands such as triphenylphosphine or 1,1'-bis (diphenylphosphino) ferrocene (dppf). Suzuki coupling conditions are recorded in detail in the literature (see, for example, Angewandte Chemie International Edition, 2006, 45, 3484, and Tetrahedron Letters, 2002, 58 (14), 2885). The boron intermediate of formula 5 is commercially available or can be prepared from the corresponding halide or triflate by methods known in the literature (see, for example, PCT Patent Publication WO 2007 / 043278, U.S. Pat. No. 8,080,566, Organic Letters 2011, 13(6), 1366, and Organic Letters 2012, 14(2), 600). Stille coupling is usually carried out in the presence of Pd(0) or Pd(II) salt, ligand and Cu(I) salt such as copper(I) iodide. The reaction can be carried out in a solvent such as dioxane, 1,2-dimethoxyethane or toluene at a temperature ranging from ambient temperature to reflux. For conditions and reagents used in Stille coupling, see Chemical Reviews 2007, 107(1), 133–173.

[0333] Solution 2

[0334]

[0335] As shown in Scheme 3, a compound of Formula 2C (i.e., a compound of Formula 2, wherein Z is O) can be prepared by reacting a compound of Formula 2B (i.e., a compound of Formula 2A, wherein Z is O; and R A As described by Das et al. in Tetrahedron 2003, 59, 1049-1054 and the methods cited therein, the methoxyl radical (i.e., when R A When R is CH3) deprotection agents such as BBr3, AlCl3 and HBr in acetic acid. Suitable acetoxy groups (i.e., when R is CH3) can be used at room temperature. AWhen the deprotecting agent is -C(=O)CH3, it includes a methanol solution of potassium carbonate or an aqueous methanol solution of ammonium acetate. Alternatively, the compound of formula 2B can be reacted with Amberlyst The compound of formula 2C is prepared by mixing with a methanol solution of 2-hydroxy-2-nitropropene (as described by Das et al. in Tet. Lett. 2003, 44, 5465-5468) or with an ethanol solution of sodium acetate (as described by Narender, T et al. in Synthetic Communications 2009, 39 (11), 1949-1956) to obtain the compound of formula 2C. Other useful phenol protecting groups suitable for preparing the compound of formula 2C can be found in Greene, TW; Wuts, PGM Protective Groups in Organic Synthesis 4th Edition; Wiley: Hoboken, New Jersey, 1991.

[0336] Solution 3

[0337]

[0338] The intermediate of formula 2B can be prepared from the intermediate of formula 7 by various methods known to those skilled in the art as shown in Scheme 4. The compound of formula 2B can be obtained by coupling the precursor of formula 7 (wherein J is Br, Cl, I or triflate) with a borate ester or a heterocycle containing a trialkyltin group (i.e., a compound of formula 5 or formula 6, using the Suzuki conditions or Stille conditions of Scheme 2). Alternatively, using the method shown in Scheme 2, the compound of formula 7 (wherein J is a borate ester or a trialkyltin group) can be coupled with a halogen-substituted heterocycle QX to obtain the compound of formula 2B. The skilled pharmacist will recognize that by careful selection of groups X and J in the reaction involving the compound of formula 7 and QX, intermediate 2B can be synthesized using various cross-coupling methods, such as the Kumada coupling, Hiyama coupling or Negishi coupling described in "Metal-Catalyzed Cross-Coupling Reactions" (Editors A. de Meijere and F. Diederich, Wiley-VCH, Weinheim, 2004, Volumes 1 and 2).

[0339] When J in Formula 7 is an alkene, alkyne, oxime, nitrile or ketone, the various heterocycles may be prepared using the methods described by Katritsky in Advances in Heterocyclic Chemistry, Vol. 1-104 (Elsevier). In cases where a regioisomeric mixture is prepared, the desired product may be isolated using conventional separation techniques known in the art.

[0340] Solution 4

[0341]

[0342] As shown in Scheme 5, compounds of Formula 4A can be prepared by coupling a phenol of Formula 9 with a compound of Formula 3 under nucleophilic substitution conditions as described in Scheme 1.

[0343] Solution 5

[0344]

[0345] As shown in Scheme 6, the compound of Formula 1B (i.e., the compound of Formula 1, wherein Z is O; and m at the 3-position is 1) can be prepared by "CH activation" of the compound of Formula 1A (the compound of Formula 1, wherein Z is O; and m is 0). For example, palladium (II) acetate with N-halosuccinimide, PhI (OAc) 2, N-fluoropyridine tetrafluoroborate, or with a lower alkyl boronic acid can be used to introduce R such as I, Br, Cl, -OAc, F and a lower alkyl substituent, respectively. 3 Variables. These methods are reviewed in detail in Chemical Reviews 2010, 110, 575-1211 and the selective activation of C-H bonds in the references cited therein. The "C-H activation" method can also be found in a series of "C-H activation" reviews in Nature Chemistry 2013, 5, 369-375 and Accounts of Chemical Research 2012, 45, 777–958 by Wencel-Delord et al. and the references cited therein. Subsequently, the iodide and bromide of Formula 1B can be further functionalized by various cross-coupling methods described in Volumes 1 and 2 of "Metal-Catalyzed Cross-Coupling Reactions" (Wiley-VCH, Weinheim, 2004), edited by A. de Meijere and F. Diederich.

[0346] Solution 6

[0347]

[0348] As shown in Scheme 7, using palladium(II) acetate and (diacetoxyiodo)benzene as described above in Scheme 6, a "CH activation" based chemistry can also be used to prepare compounds of Formula 2D (i.e., compounds of Formula 2, wherein Z is O; R A is -C(O)CH3; and m at the 3-position is 1). The compound of formula 2D can then be converted via the methods disclosed in Schemes 1 and 6 to obtain the compound of formula 1.

[0349] Solution 7

[0350]

[0351] Similarly, as shown in Scheme 8, a chemical reaction based on "CH activation" can be used to prepare a compound of formula 2F (i.e., a compound of formula 2A, wherein Z is S). The compound of formula 8 can first be converted to a compound of formula 8A (i.e., a compound of formula 6, wherein the ortho-position "H" is X; and X is Br or I) by stepwise introduction of substituents using "CH activation". The iodide and bromide of formula 8A can then be further functionalized by copper-mediated cross-coupling with thiourea, as described by Qi, Junsheng in Chin. J. Chem. 2010, 28, 1441-1443, to provide an aryl thiol after acid deprotection. The palladium-catalyzed cross-coupling reaction of an aryl halide can give a protected thiol, which can then be deprotected under acidic conditions or alkaline conditions (e.g., cesium fluoride) to provide a compound of formula 2F. These conditions are discussed in Organ, Michael G., Angew Chem. Int. Ed. 2012, 51, 3314-3322 and references cited therein. In addition, related conditions can be found in Takashiro Itoh, J. Org. Chem. 2006, 71, 2203-2206. The compound of formula 2F can then be converted to obtain the compound of formula 1 via the methods disclosed in Schemes 1 and 7.

[0352] Solution 8

[0353]

[0354] In Scheme 9, for acidic phenols, phenol 2E is reacted with a solution of N,N-dimethylthiocarbamoyl chloride in N,N-dimethylformamide in the presence of a strong tertiary amine base such as 1,4-diazabicyclo[2.2.2]octane or N-methylmorpholine (for less acidic phenols, deprotonation with sodium hydride may be advantageous before) to form an N,N-dimethylthiocarbamic acid O-aryl ester of formula 10. Newman-Kwart rearrangement of the compound of formula 10 at a temperature in the range of 200 to 300°C provides the intermediate dimethylthiocarbamic acid S-aryl ester of formula 11. One-pot deprotection of the compound of formula 11 is easily achieved using 10% aqueous sodium hydroxide or potassium hydroxide in methanol to provide the corresponding aryl thiol. Subsequent reaction with the compound of formula 3 at room temperature or slightly above room temperature affords the product of formula 1C (i.e., the compound of formula 1, wherein Z is S). The Newman-Kwart rearrangement method is described in Lloyd-Jones, Guy C. Synthesis 2008, 661-689.

[0355] Solution 9

[0356]

[0357] Those skilled in the art recognize that various functional groups can be converted into other to provide different compounds of formula 1. For a valuable resource showing that functional groups are converted into each other in a simple and direct manner, see Larock, RC, Comprehensive Organic Transformations: A Guide to Functional Group Preparations, Second Edition, Wiley-VCH, New York, 1999. For example, the intermediate used to prepare the compound of formula 1 may include an aromatic nitro group, which can be reduced to an amino group and then converted into various halides via reactions well known in the art, such as the Sandmeyer reaction, to provide compounds of formula 1. In many cases, the above reactions may also be performed in an alternative order.

[0358] It should be recognized that some of the reagents and reaction conditions for preparing the compounds of Formula 1 described above may be incompatible with certain functional groups present in the intermediates. In these cases, adding the protection / deprotection sequence or the functional group tautomer to the synthesis will help to obtain the desired product. The use and selection of protecting groups will be apparent to those skilled in the art of chemical synthesis (see, for example, Greene, TW, Wuts, PGM Protective Groups in Organic Synthesis 4th Edition; Wiley: Hoboken, New Jersey, 1991). Those skilled in the art will recognize that in some cases, after introducing the specified reagent as shown in any individual scheme, it may be necessary to implement additional conventional synthesis steps not described in detail to complete the synthesis of the compound of Formula 1. Those skilled in the art will also recognize that it may be necessary to implement the combination of the steps shown in the above scheme in an order different from the specific order presented when preparing the compound of Formula 1.

[0359] Those skilled in the art will also recognize that the compounds of Formula 1 and intermediates described herein can undergo a variety of electrophilic, nucleophilic, free radical, organometallic, oxidation, and reduction reactions to add substituents or modify existing substituents.

[0360] Without further elaboration, it is believed that one skilled in the art can utilize the present invention to its maximum extent using the foregoing. Therefore, the following examples should be understood to be merely illustrative and not to limit the disclosure of the present invention in any way. The steps in the following examples illustrate the process of each step in the overall synthetic transformation, and the starting materials for each step may not necessarily be prepared by the specific preparation steps whose processes are described in other embodiments or steps. Percentages are all by weight, except for chromatographic solvent mixtures or unless otherwise specified. Unless otherwise specified, the parts and percentages of chromatographic solvent mixtures are all by volume. In CDCl3, the units are recorded in ppm from the low field of tetramethylsilane. 1 H NMR spectrum; "s" indicates a singlet, "d" indicates a doublet, "t" indicates a triplet, "q" indicates a quartet, "m" indicates a multiplet, "dd" indicates two doublets, "dt" indicates two triplets, and "bs" indicates a broad singlet.

[0361] Those skilled in the art recognize that various functional groups can be converted to others to provide different compounds of Formula 1. For a valuable resource that illustrates functional group interconversions in a simple and intuitive manner, see Larock, RC, Comprehensive Organic Transformations: A Guide to Functional Group Preparations, Second Edition, Wiley-VCH, New York, 1999. For example, the intermediates used to prepare compounds of Formula 1 may contain aromatic nitro groups, which can be reduced to amino groups and then converted to various halides via reactions well known in the art, such as the Sandmeyer reaction, to provide compounds of Formula 1. In many cases, the above reactions can also be performed in an alternative order.

[0362] It should be recognized that some of the reagents and reaction conditions for preparing the compounds of Formula 1 described above may be incompatible with certain functional groups present in the intermediates. In these cases, adding the protection / deprotection sequence or the functional group tautomer to the synthesis will help to obtain the desired product. The use and selection of protecting groups will be obvious to those skilled in the art of chemical synthesis (see, for example, Greene, TW; Wuts, PGM Protective Groups in Organic Synthesis 2nd Edition; Wiley: New York, 1991). Those skilled in the art will recognize that in some cases, after introducing the specified reagent as shown in any individual scheme, it may be necessary to implement additional conventional synthesis steps not described in detail to complete the synthesis of the compound of Formula 1. Those skilled in the art will also recognize that it may be necessary to implement the combination of the steps shown in the above scheme in an order different from the specific order presented when preparing the compound of Formula 1.

[0363] Those skilled in the art will also recognize that the compounds of Formula 1 and intermediates described herein can undergo a variety of electrophilic, nucleophilic, free radical, organometallic, oxidation, and reduction reactions to add substituents or modify existing substituents.

[0364] Without further elaboration, it is believed that one skilled in the art can utilize the present invention to its maximum extent using the foregoing. Therefore, the following examples should be understood to be merely illustrative and not to limit the disclosure of the present invention in any way. The steps in the following examples illustrate the process of each step in the entire synthetic transformation, and the starting material for each step may not necessarily be prepared by the specific preparation steps whose process is described in other embodiments or steps. Percentages are all by weight, except for chromatographic solvent mixtures or unless otherwise specified. Unless otherwise specified, the parts and percentages of chromatographic solvent mixtures are all by volume. Unless otherwise specified, in CDCl3, the low field ppm number from tetramethylsilane at 500MHz is recorded as a unit. 1 H NMR spectrum; "s" indicates a singlet, "d" indicates a doublet, "t" indicates a triplet, "q" indicates a quartet, "m" indicates a multiplet, "dd" indicates two doublets, and "dt" indicates two triplets.

[0365] Synthesis Example 1

[0366] Synthesis of 3-[2-[(5-chloro-2-pyrimidinyl)oxy]phenyl]-5-isoxazolemethanol (Compound 31)

[0367] Step A: 5-chloro-2-[2-[5-[[[(1,1-dimethylethyl)diphenylsilyl]oxy]methyl]-3-isothiazolinyl Synthesis of [oxazolyl]phenoxy]pyrimidine

[0368] To a solution of 3-(2-methoxyphenyl)-5-isoxazolemethanol (prepared as described in Bioorganic Med. Chem. 2004, 12, 3965) (0.500 mg, 0.243 mmol) in tetrahydrofuran (25 mL) was added tert-butyldiphenylsilyl chloride (0.804 mg, 2.92 mmol) followed by imidazole (0.199 mg, 2.92 mmol). After 2 h, the solvent was removed in vacuo. Purification by chromatography on silica gel using 0 to 100% ethyl acetate in hexanes afforded the intermediate 5-[[[(1,1-dimethylethyl)diphenylsilyl]oxy]methyl]-3-(2-methoxyphenyl)isoxazole and the material was used without further purification.

[0369] To a solution of 5-[[[(1,1-dimethylethyl)diphenylsilyl]oxy]methyl]-3-(2-methoxyphenyl)isoxazole (3.10 g, 0.699 mmol) in dichloromethane (35 mL) was added a 1.0 M solution of boron tribromide (34.9 mL) at 0°C and the reaction was stirred at this temperature for 1 h. The reaction was quenched with saturated sodium bicarbonate solution. The phases were separated and the aqueous layer was washed with additional dichloromethane. The combined organic phases were mixed, dried over MgSO4, and concentrated in vacuo. Purification by chromatography on silica gel using 0 to 100% ethyl acetate in hexanes gave 2-[5-[[[(1,1-dimethylethyl)diphenylsilyl]oxy]methyl]-3-isoxazolyl]phenol which was used in the next step without further purification.

[0370] To a solution of 2-[5-[[[(1,1-dimethylethyl)diphenylsilyl]oxy]methyl]-3-isoxazolyl]phenol (2.78 g, 6.47 mmol) in acetonitrile (60 mL) was added 2,5-dichloropyrimidine (1.15 g, 7.70 mmol) and potassium carbonate (2.24 g, 16.2 mmol) and the reaction was heated at 80 °C for 6 h. The reaction mixture was allowed to warm to room temperature and the solvent was removed in vacuo. Purification by chromatography on silica gel using 0 to 100% ethyl acetate in hexanes gave the title product (2.27 g).

[0371] 1 H NMRδ8.41(s,2H),8.00–7.97(m,1H),7.67–7.61(m,4H),7.56–7.50(m,1H),7.47–7.36(m,7H),7.28–7.26(m,1H),6.56(t,1H),1.05(s,9H). MS(AP + )=542.

[0372] Step B: Synthesis of 3-[2-[(5-chloro-2-pyrimidinyl)oxy]phenyl]-5-isoxazolemethanol

[0373] To a solution of 5-chloro-2-[5-[[[(1,1-dimethylethyl)diphenylsilyl]oxy]methyl]-3-isoxazolyl]phenoxy]pyrimidine (i.e., the product of step A) (2.27 g, 4.19 mmol) in tetrahydrofuran (15 mL), acetic acid (0.50 mL) was added, followed by a solution of 75% tetrabutylammonium fluoride in water (2.9 mL), and the reaction was stirred for 2 h. The reaction was quenched with a saturated sodium bicarbonate solution, and the phases were separated, and the aqueous phase was further washed with ethyl acetate. The combined organic phases were mixed, dried with MgSO4, and concentrated in vacuo. Purification by chromatography was performed using a hexane solution of 0 to 100% ethyl acetate on silica gel to obtain the title product, which was a compound of the present invention (1.21 g).

[0374] 1 H NMRδ8.45(s,2H),7.99–7.95(m,1H),7.56–7.52(m,1H),7.42–7.38(m,1H),7.28–7.25(m,1H),6.64–6.61(m,1H),4.77–4.73(m,2H).

[0375] Synthesis Example 2

[0376] Synthesis of 3-[2-[(5-chloro-2-pyrimidinyl)oxy]phenyl]-5-isoxazolecarboxaldehyde (Compound 33)

[0377] Step A: Synthesis of 3-[2-[(5-chloro-2-pyrimidinyl)oxy]phenyl]-5-isoxazolecarboxaldehyde

[0378] Chlorochromic acid pyridinium salt (263mg, 1.22mmol) and silica gel (200mg) are merged, and mixed with solid form.Then the mixture is added to the stirred 3-[2-[(5-chloro-2-pyrimidinyl) oxygen base] phenyl]-5-isoxazole methanol (i.e. the product obtained in step A of embodiment 1) (309mg, 1.02mmol) in dichloromethane (5.0mL) solution, and the reaction is stirred for 18h.The solution is filtered to remove silica gel, and the organic phase is washed with 1M hydrochloric acid solution.Organic phase MgSO4 is dried and concentrated in vacuo.Adopting chromatography, using the hexane solution wash-out of 0 to 100% ethyl acetate on silica gel, obtain title product, be the compounds of this invention (0.307g).

[0379] 1 H NMRδ9.95(s,1H),8.46(s,2H),8.06–8.01(m,1H),7.61–7.56(m,1H),7.47–7.41(m,1H),7.38(s,1H),7.32–7.29(m,1H). MS(AP + )=302.

[0380] Synthesis Example 3

[0381] Synthesis of 5-chloro-2-[2-[5-(difluoromethyl)-3-isoxazolyl]phenoxy]pyrimidine (Compound 35)

[0382] Step A Synthesis of 5-chloro-2-[2-[5-(difluoromethyl)-3-isoxazolyl]phenoxy]pyrimidine

[0383] To a stirred solution of 3-[2-[(5-chloro-2-pyrimidinyl)oxy]phenyl]-5-isoxazolecarboxaldehyde (i.e., the product of Example 2, Step A) (100 mg, 0.332 mmol) in dichloromethane (3.0 mL) was added at -78°C. (161 mg, 0.729 mmol), and the reaction was returned to ambient temperature. After the raw material was exhausted as confirmed by thin layer chromatography, the solvent was removed in vacuo. Purification by chromatography, eluting with 0 to 100% ethyl acetate in hexane on silica gel, obtained the title product, which is the compound of the present invention (36.3 mg).

[0384] 1 H NMRδ8.46(s,2H),8.01–7.96(m,1H),7.59–7.54(m,1H),7.44–7.38(m,1H),7.31–7.27(m,1H),6.98–6.96(s,1H),6.83–6.60(m,1H). MS(ESI + )=324.

[0385] Synthesis Example 4

[0386] Synthesis of 2-[2-(3-bromo-5-isoxazolyl)phenoxy]-5-chloropyrimidine (Compound 12)

[0387] Step A: Synthesis of 3-bromo-5-(2-methoxyphenyl)isoxazole

[0388] To 1-ethynyl-2-methoxybenzene (0.78g, 5.92mmol) in dichloromethane (10mL) solution, add dibromoformaldehyde oxime (1.00g, 4.93mmol). The mixture is cooled to 0 ℃ and potassium bicarbonate (1.48g, 14.8mmol) is added, then heated at 40 ℃ for 18h. Water is added in the reaction mixture, phase separation, and the water layer is washed again with dichloromethane. The combined organic phase is dried over MgSO4, concentrated in vacuo, and purified by chromatography, eluted with a hexane solution of 0 to 100% ethyl acetate on silica gel, to obtain the title product, which is the compound of this invention (1.04g).

[0389] 1 H NMR δ7.94(dd,1H),7.47–7.42(m,1H),7.09(dd,1H),7.02(dd,1H),6.85(s,1H),3.97(s,3H). MS(AP +)=254.

[0390] Step B: Synthesis of 2-(3-bromo-5-isoxazolyl)phenol

[0391] To a solution of 3-bromo-5-(2-methoxyphenyl)isoxazole (ie, the product of step A) (0.50 g, 1.97 mmol) in dichloromethane (20 mL) at -78 ° C, a 1M solution of boron tribromide in dichloromethane (9.86 mmol) was added, and the solution was allowed to warm to room temperature and stirred for 18 h. Dichloroethane (20 mL) was added, and the reaction mixture was concentrated to remove excess dichloromethane. A solution of boron tribromide in dichloromethane (9.86 mmol) was added again, and the reaction was heated to 80 ° C until the reaction was confirmed to be complete by thin layer chromatography. The reaction mixture was cooled to ambient temperature and quenched with a saturated sodium bicarbonate solution. The phases were separated, and the aqueous layer was washed again with dichloromethane. The combined organic phases were dried over MgSO4, concentrated in vacuo, and purified by chromatography, eluting on silica gel with a hexane solution of 0 to 100% ethyl acetate to obtain the title product (0.395 g).

[0392] 1 H NMR δ7.76(dd,1H),7.39–7.33(m,1H),7.09–7.02(m,1H),6.96–6.93(m,1H),6.02(s,1H). MS(AP–)=238.

[0393] Step C: 2-[2-(3-bromo-5-isoxazolyl)phenoxy]-5-chloropyrimidine

[0394] To a solution of 2-(3-bromo-5-isoxazolyl)phenol (i.e., the product of step B) (100 mg, 0.417 mmol) in acetonitrile (5 mL), 2,5-dichloropyrimidine (75.0 mg, 0.503 mmol) and potassium carbonate (288 mg, 2.08 mmol) were added, and the solution was then stirred at ambient temperature for 18 h. The reaction was then heated at 40 ° C for 2 h, and then at 80 ° C for two hours. The solution was then cooled to ambient temperature, water was added, the phases were separated, and the aqueous layer was washed again with dichloromethane. The combined organic phases were dried over MgSO4, concentrated in vacuo, and purified by chromatography, eluting on silica gel with a hexane solution of 0 to 100% ethyl acetate to obtain the title product, which is a compound of the present invention (122 mg).

[0395] 1 H NMR δ8.49(s,2H),8.03(dd,1H),7.58–7.53(m,1H),7.43(dt,1H),7.29(dd,1H),6.74(s,1H). MS(AP + )=352.

[0396] Synthesis Example 5

[0397] Synthesis of 5-chloro-2-[2-[4-(trifluoromethyl)-2-pyridyl]phenoxy]pyrimidine (Compound 25)

[0398] Step A: Synthesis of 2-[4-(trifluoromethyl)-2-pyridyl]phenol

[0399] 2-Chloro-4-trifluoromethylpyridine (1.0 g, 5.5 mmol) and 2-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenol (1.57 g, 7.16 mmol) were mixed in dimethoxyethane (18 mL) and water (1.8 mL). Sodium carbonate (2.28 g, 16.5 mmol) and tetrakis(triphenylphosphine)palladium(0) (0.32 g, 0.27 mmol) were added to the mixture. The reaction was heated at 90 ° C for 2.5 h, and stirred at 23 ° C for 18 h. The mixture was diluted with water (20 mL) and dichloromethane (20 mL), and separated. The aqueous layer was washed with dichloromethane (10 mL). The combined dichloromethane layer was washed with saturated sodium chloride aqueous solution (10 mL), and dried over sodium sulfate. After filtration, the organic layer was evaporated, and the solid thus obtained was ground with hexane (20 mL). The filtrate was concentrated to afford 1.18 g of the title compound as a yellow solid which was used in step B without further purification.

[0400] 1 H NMR δ13.61(s,1H),8.72(d,1H),8.12(s,1H),7.83(d,1H),7.47(m,1H),7.36(s,1H),7.06(d,1H),6.96(t,1H).

[0401] Step B Synthesis of 5-chloro-2-[2-[4-(trifluoromethyl)-2-pyridyl]phenoxy]pyrimidine

[0402] 2-[4-(trifluoromethyl)-2-pyridyl]phenol (i.e., the product of step A) (0.20g, 0.84mmol) and 2,5-dichloropyrimidine (0.14g, 0.92mmol) were dissolved in acetonitrile (2mL) and treated with powdered potassium carbonate (0.34g, 2.5mmol). The mixture was heated at 80°C for 18h. After cooling, the reaction mixture was diluted with water (10mL) and ethyl acetate (10mL), and the layers were separated. The water layer was washed with ethyl acetate (10mL). The combined ethyl acetate solution was washed with saturated sodium chloride aqueous solution (10mL) and dried on MgSO4. The filtrate was evaporated under reduced pressure and eluted with a hexane solution of 10 to 20% ethyl acetate, and chromatographed by 12g silica gel. Appropriate fractions were combined and evaporated to obtain the title compound as a transparent oily compound of the invention (0.2g).

[0403] 1 H NMRδ8.75(d,1H),8.39(s,2H),7.91(s,1H),7.88(m,1H),7.54(m,1H),7.44(m,1H),7.37(d,1H),7.28(m,1H).

[0404] Synthesis Example 6

[0405] Synthesis of 5-chloro-2-[4-methyl-2-[6-(trifluoromethyl)-3-pyridyl]phenoxy]pyrimidine (Compound 22)

[0406] Step A: Synthesis of 2-(2-bromo-4-methylphenoxy)-5-chloropyrimidine

[0407] Under nitrogen atmosphere, 2-bromo-4-methylphenol (280mg, 1.5mmol) and 2,5-dichloropyrimidine (246mg, 1.65mmol) are mixed in 6mL acetonitrile. Powdered potassium carbonate (455mg, 3.3mmol) is added and the resulting mixture is heated to reflux for 6h. The reaction mixture is cooled and diluted with deionized water and ethyl acetate. The aqueous layer is separated and extracted twice with ethyl acetate. The combined organic layer is washed with salt water, dried on MgSO4, filtered, and concentrated under reduced pressure. The resulting residue is purified by medium pressure liquid chromatography, eluted with a hexane solution of 0 to 15% ethyl acetate on silica gel, and the title compound (270mg) is obtained.

[0408] 1 H NMR δ8.48(s,2H),7.47(d,1H),7.18(m,1H),7.11(m,1H),2.37(s,3H).

[0409] Step B Synthesis of 5-chloro-2-[4-methyl-2-[6-(trifluoromethyl)-3-pyridyl]phenoxy]pyrimidine

[0410] A mixture of 2-(2-bromo-4-methylphenoxy)-5-chloropyrimidine (i.e., the product of step A; 190 mg, 0.63 mmol), B-[6-(trifluoromethyl)-3-pyridyl]-boric acid (133 mg, 0.70 mmol), sodium carbonate (0.6 mL of a 2M aqueous solution, 1.26 mmol) and tetrakis(triphenylphosphine)palladium(0) (73 mg, 0.06 mmol) was heated at 90° C. for 2 h in toluene (9 mL) and ethanol (1 mL). The reaction mixture was then concentrated under reduced pressure, and the residue was purified by medium pressure liquid chromatography on silica gel eluting with 0 to 10% ethyl acetate in hexane to obtain the title compound, a compound of the present invention (190 mg).

[0411] 1H NMR δ8.77(d,1H),8.36(s,2H),8.02(m,1H),7.64(d,1H),7.31(m,2H),7.15(d,1H),2.45(s,3H).

[0412] Synthesis Example 7

[0413] Synthesis of 5-chloro-2-[2-[3-(difluoromethyl)-5-isoxazolyl]phenoxy]pyrimidine (Compound 53)

[0414] Step A: Synthesis of 2-(3-difluoromethyl-5-isoxazolyl)phenol

[0415] To a 25% solution of sodium methoxide in methanol (5 mL) and tetrahydrofuran (10 mL) was added a solution of acetophenone (1 g, 7.3 mmol) and difluoroacetate (1 g, 8.1 mmol) in tetrahydrofuran (2 mL) and heated at 60°C for 5 h. The reaction was cooled to room temperature and treated with 36% aqueous hydrochloric acid (4 mL) and stirred at 60°C for 2 h. The reaction was quenched by the addition of water (15 mL) and the organic solvent was removed in vacuo. The precipitated product, 2-difluoromethyl-4-chromenone (1.4 g), was filtered and dissolved in ethanol (5 mL). To this solution was added a solution of hydroxylamine acetate (22 mmol) in water (5 mL) and the mixture was heated at 60°C for 3 h. After the reaction was cooled to ambient temperature, water (20 mL) was added to precipitate 4,4-difluoro-1-(2-hydroxyphenyl)-butane-1,3-dione 3-oxime. The product was collected by filtration and suspended in acetic acid (5 mL) and 36% aqueous hydrochloric acid (1.8 mL) at room temperature and stirred at 80°C for 15 minutes to give the title compound as a beige solid (800 mg).

[0416] 1 H NMR δ7.82(m,1H),7.36(s,1H),7.07(m,1H),6.95(m,2H),6.82(t,1H),6.05(s,1H). MS(ESI + )=212

[0417] Step B: Synthesis of 5-chloro-2-[2-[3-(difluoromethyl)-5-isoxazolyl]phenoxy]-pyrimidine

[0418] To an anhydrous N, N-dimethylformamide (8mL) solution of 2-(3-difluoromethyl-5-isoxazolyl)phenol (i.e., the product of step A) (2.1 g, 9.71 mmol), 2,5-dichloropyrimidine (1.5 g, 10.2 mmol) and potassium carbonate (2.9 g, 21.3 mmol) were added. The reaction was heated at 90 ° C for 1 h. The solution was cooled to ambient temperature and diluted with water. The phases were separated and the aqueous phase was washed with additional ethyl acetate. The organic phases were combined, dried over magnesium sulfate and concentrated in vacuo. Purification by chromatography was performed using a hexane solution of 0 to 10% ethyl acetate on silica gel to obtain the title compound as a solid compound of the invention (2.2 g).

[0419] 1 H NMR δ8.49(s,2H),8.06(m,1H),7.57(m,1H),7.44(m,1H),7.31(m,1H),6.88(s,1H),6.74(t,1H). MS(ESI + )=324

[0420] Synthesis Example 8

[0421] Synthesis of 5-chloro-2-[2-[3-(difluoromethyl)-5-isoxazolyl]-3-fluorophenoxy]pyrimidine (Compound 144)

[0422] Step A: Synthesis of 4,4-difluoro-1-(2-fluoro-6-methoxyphenyl)butane-1,3-dione

[0423] To an anhydrous N,N-dimethylformamide solution of 1-(2-fluoro-6-methoxyphenyl)ethanone (2.6 g, 15.5 mmol) and ethyl difluoroacetate (3.9 mL, 31.0 mmol) at 0°C, sodium hydride (1.2 g, 31.0 mmol) was added. The reaction mixture was heated at 80°C for 1 h. The reaction was then cooled to 0°C, diluted with ethyl acetate, and acidified with 1N aqueous hydrochloric acid. The phases were separated and the aqueous phase was washed with additional ethyl acetate. The organic phases were combined, dried over magnesium sulfate, and concentrated in vacuo. Purification by chromatography was performed on silica gel using 0 to 15% ethyl acetate in hexane to obtain the title compound (2.5 g).

[0424] 1 H NMR δ7.39(m,1H),6.77(m,2H),6.24(s,1H),6.01(t,1H),3.87(s,3H). MS(ESI + )=247

[0425] Step B: Synthesis of 3-difluoromethyl-5-(2-fluoro-6-methoxyphenyl)isoxazole

[0426] A solution of 4,4-difluoro-1-(2-fluoro-6-methoxyphenyl)butane-1,3-dione (i.e., the product of step A) (2.5 g, 10 mmol) and hydroxylamine hydrochloride (2.1 g, 30 mmol) in ethanol (25 mL) was stirred at 80 ° C. After 1 h, the solvent was removed in vacuo. The resulting residue was diluted with water and extracted with dichloromethane. The organic phase was dried over magnesium sulfate and concentrated in vacuo. Purification by chromatography was performed using 0 to 15% ethyl acetate in hexane on silica gel to obtain the title compound (1.5 g).

[0427] 1 H NMRδ7.41(m,1H),6.69-6.98(m,4H),3.93(s,3H). MS(ESI + )=244

[0428] Step C: Synthesis of 2-(3-difluoromethyl-5-isoxazolyl)-3-fluorophenol

[0429] To a solution of 3-difluoromethyl-5-(2-fluoro-6-methoxyphenyl)isoxazole (i.e., the product of step B) (1.5g, 6.2mmol) in dichloromethane (10mL), 1.0M boron tribromide in dichloromethane (31mL, 31mmol) was added at 0°C. The reaction mixture was warmed to ambient temperature and stirred for 6h. The reaction was cooled to 0°C and slowly quenched with saturated sodium bicarbonate aqueous solution. The biphasic mixture was stirred for 1h at room temperature. The phases were separated and the aqueous phase was extracted with dichloromethane. The combined organic phases were dried and concentrated in vacuo. The crude residue was purified by chromatography on silica gel eluted with a hexane solution of 0 to 10% ethyl acetate to obtain the title compound (980mg).

[0430] 1 H NMRδ7.33(m,1H),6.66-6.99(m,4H). MS(ESI + )=230

[0431] Step D: Synthesis of 5-chloro-2-[2-[3-(difluoromethyl)-5-isoxazolyl]-3-fluorophenoxy]pyrimidine To anhydrous N, N-dimethylformamide (2mL) solution of 2-(3-difluoromethyl-5-isoxazolyl)-3-fluorophenol (i.e., the product of step C) (120mg, 0.5mmol), 2,5-dichloropyrimidine (85mg, 0.57mmol) and potassium carbonate (244mg, 1.04mmol) were added. The reaction was heated at 80°C for 4h. The mixture was cooled to ambient temperature and diluted with water. The phases were separated and the aqueous phase was washed with additional ethyl acetate. The organic phases were combined, dried over magnesium sulfate and concentrated in vacuo. Purification by chromatography was performed using a hexane solution of 0 to 15% ethyl acetate on silica gel to obtain the title compound as a solid compound of the invention (110mg).

[0432] 1 H NMR δ8.46(s,2H),7.56(m,1H),7.21(m,1H),7.13(m,1H),6.87(m,1H),6.74(t,1H). MS(ESI + )=342

[0433] Synthesis Example 9

[0434] Synthesis of 5-chloro-2-[2-[5-(difluoromethyl)-3-isoxazolyl]-3-fluorophenoxy]pyrimidine (Compound 55)

[0435] Step A: Synthesis of 4,4-difluoro-1-(2-fluoro-6-methoxyphenyl)butane-1,3-dione

[0436] A solution of 2-fluoro-6-methoxyacetophenone (6.83 g, 40.6 mmol) and ethyl difluoroacetate (7.45 g, 60 mmol) in tetrahydrofuran (35 mL) was added dropwise to a solution of tetrahydrofuran (20 mL) and 25% sodium methoxide (10.2 g, 47.2 mmol) over 15 minutes. The reaction was completed within 3 h as measured by high pressure liquid chromatography. The reaction was partially concentrated in vacuo to remove most of the tetrahydrofuran and methanol, then diluted with toluene and water. The aqueous phase was acidified with 37% hydrochloric acid (5 g), then extracted with toluene. The combined organic phases were concentrated in vacuo to obtain the title compound (7.98 g).

[0437] 1 H NMR δ7.39(td,1H)6.72-6.81(m,2H)6.25(d,1H)5.87-6.14(m,1H)3.88(s,3H).

[0438] Step B: Synthesis of 5-(difluoromethyl)-3-(2-fluoro-6-methoxyphenyl)-4H-isoxazol-5-ol

[0439] To a 35 mL methanol solution of 4,4-difluoro-1-(2-fluoro-6-methoxyphenyl)butane-1,3-dione (i.e., the product of step A) (7.98 g, 32.4 mmol) was added 50% hydroxylamine solution (2.78 g, 42.1 mmol) and 1N sodium hydroxide solution (1.50 mL, 1.50 mmol) at room temperature, and then heated at 65 ° C for 2 h. The reaction was cooled to room temperature and diluted with water and toluene. The phases were separated and the organic phase was concentrated in vacuo to obtain the title compound (7.99 g).

[0440] 1 H NMR δ7.36(td,1H)6.73-6.82(m,2H)5.79-6.05(m,1H)3.88(s,3H)3.67-3.73(m,1H)3.47-3.51(m,1H)3.34-3.42(m,1H).

[0441] Step C: Synthesis of 5-(difluoromethyl)-3-(2-fluoro-6-methoxyphenyl)isoxazole

[0442] 5-(difluoromethyl)-3-(2-fluoro-6-methoxyphenyl)-4H-isoxazole-5-ol (i.e., the product of step B) (7.99 g, 30.6 mmol) was added to toluene (80 mL), followed by p-toluenesulfonic acid monohydrate (0.700 g, 3.68 mmol). The mixture was heated under vigorous reflux (107–111° C.) for two hours, at which time high pressure liquid chromatography determined that the reaction was complete. The cooled reaction mixture was washed with saturated sodium bicarbonate solution and then with water. The organic phase was concentrated in vacuo to obtain the title compound (7.44 g).

[0443] 1 H NMR δ7.40(td,1H)6.69-6.94(m,4H)3.88(s,3H).

[0444] Step D: Synthesis of 2-[5-(difluoromethyl)-3-isoxazolyl]-3-fluorophenol

[0445] To a solution of 5-(difluoromethyl)-3-(2-fluoro-6-methoxyphenyl)isoxazole (i.e., the product of step C) (3.72 g, 15.3 mmol) in dichloromethane (15 mL) was added 1 M boron tribromide in dichloromethane (18.0 mL, 18 mmol) at 3°C ​​over 5 min. The reaction was then allowed to warm to room temperature. After 90 minutes, the reaction was complete using high pressure liquid chromatography and the reaction was treated with 10% aqueous potassium bicarbonate solution (10 mL). The phases were separated and the organic phase was concentrated in vacuo. The resulting brown solid was ground with water / methanol solution (~2 / 1) to obtain the title compound (3.34 g).

[0446] 1 H NMR δ9.63-9.75(m,1H)7.33(td,1H)7.21(ddd,1H)6.71-6.96(m,3H).

[0447] Step E: Synthesis of 5-chloro-2-[2-[5-(difluoromethyl)-3-isoxazolyl]-3-fluorophenoxy]pyrimidine

[0448] To 2-[5-(difluoromethyl)-3-isoxazolyl]-3-fluorophenol (i.e., the product of step D) (1.61g, 7.02mmol) and 5-methyl-2-methylsulfonyl pyrimidine (1.49g, 7.72mmol) in N, N-dimethylformamide (9mL) solution, potassium carbonate (4.24g, 17.5mmol) was added, and the reaction was stirred at room temperature for 24h. The reaction was diluted with water and toluene, the phases were separated, and the organic solution was removed in vacuo. 8mL of methanol was added to the resulting oil, and a tan slurry was formed, which was further diluted with methanol / water solution (20mL), and the precipitate was filtered to obtain the title compound, which was the compound of the present invention (2.24g).

[0449] 1 H NMR δ8.45(s,2H)7.54(td,1H)7.19(ddd,1H)7.14(dt,1H)6.88(dt,1H)6.61-6.85(m,1H).

[0450] Synthesis Example 10

[0451] Preparation of 5-chloro-2-[3-cyano-2-[4-(trifluoromethyl)-2-pyridinyl]phenoxy]pyrimidine (Compound 158)

[0452] Under nitrogen atmosphere, 4.27mL N,N-dimethylformamide solution of 5-chloro-2-[2-[4-(trifluoromethyl)-2-pyridyl]phenoxy]pyrimidine (i.e., the product of step B of Example 5) (0.30g, 0.853mmole) was treated with copper (II) bromide (0.19g, 0.853mmole), palladium (II) acetate (9mg, 0.0426mmole) and potassium ferrocyanide (0.06g, 0.17mmole). The mixture was heated at 130°C for 18 hours. The mixture was then cooled, diluted with ether and water, filtered through a diatomaceous earth pad, and rinsed with ethyl acetate and water. The phases were separated, and the aqueous phase was extracted twice with ether. The combined organic phases were washed twice with water and saturated sodium chloride aqueous solution, dried over magnesium sulfate, and concentrated to obtain 0.21g of crude product. The crude product was purified using a 12 g Teledyne Isco silica gel column eluting with a 10 to 30% EtOAc-hexanes gradient to afford the title compound as a solid (0.23 g).

[0453] 1 H NMR δ8.86(d,1H),8.40(s,2H),7.78(d&s,2H),7.62(t,1H),7.52(d,1H),7.50(d,1H).

[0454] Synthesis Example 11

[0455] Synthesis of 5-chloro-2-[2-[5-(trifluoromethyl)-2-pyridyl]phenoxy]pyrimidine (Compound 27)

[0456] Step A: Synthesis of 2-[5-(trifluoromethyl)-2-pyridyl]phenol

[0457] 2-Chloro-5-(trifluoromethyl)pyridine (1.0 g, 5.50 mmole) and 2-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenol (1.57 g, 7.16 mmole) were mixed in 16 mL 1,2-dimethoxyethane and 1.8 mL deionized water under a nitrogen atmosphere. Solid sodium carbonate (2.28 g, 16.5 mmole) was added, followed by tetrakis(triphenylphosphine)palladium(0) (0.32 g, 0.27 mmole). The reaction was heated to reflux for about ninety minutes. The reaction was cooled, diluted with dichloromethane, and filtered through a diatomaceous earth pad, rinsed with dichloromethane, and then rinsed with deionized water. The phases were separated. The aqueous phase was extracted twice with dichloromethane. The combined organic phase was washed with a saturated sodium chloride aqueous solution, dried over magnesium sulfate, filtered and concentrated to obtain a solid. The solid was filtered off from the hexanes to give 34 mg. A second crop was obtained from the hexanes filtrate to give 506 mg of the title compound as a light orange-brown solid.

[0458] 1 H NMR δ8.81(s,1H),8.04(m,2H),7.83(d,1H),7.38(t,1H),7.07(d,1H),6.98(t,1H).

[0459] Step B: Synthesis of 5-chloro-2-[2-[5-(trifluoromethyl)-2-pyridinyl]phenoxy]-pyrimidine

[0460] 2-[5-(trifluoromethyl)-2-pyridyl]phenol (i.e., the product of step A) (0.20g, 0.836mmole) and 2,5-dichloropyrimidine (0.14g, 0.919mmole) mixture of 2.0mL N,N-dimethylformamide solution were stirred under a nitrogen atmosphere. Powdered potassium carbonate (0.35g, 2.51mmole) was added, and the mixture was heated at 80°C overnight. The reaction was cooled and then diluted with deionized water and ether. The phases were separated. The aqueous phase was extracted twice with ether. The combined organic phase was washed three times with deionized water, dried over sodium sulfate, filtered and concentrated to 0.37g solid. The solid was filtered out from hexane and some ether to obtain 103mg of the title compound, which is a compound of the present invention.

[0461] 1 H NMRδ8.84(s,1H),8.40(s,2H),7.92(d,1H),7.87(s&d,2H),7.54(t,1H),7.45(t,1H),7.27(d,1H).

[0462] Synthesis Example 12

[0463] Preparation of 5-chloro-2-[2-[5-(trifluoromethyl)-2-pyridinyl]-3-chlorophenoxy]pyrimidine (Compound 160)

[0464] 5-Chloro-2-[2-[5-(trifluoromethyl)-2-pyridyl]phenoxy]-pyrimidine (i.e., the product of step B of Example 11) (0.14 g, 0.398 mmole) was dissolved in 2 mL of acetic acid. Palladium acetate (0.01 g, 0.039 mmole) and N-chlorosuccinimide (0.11 g, 0.796 mmole) were added, and the mixture was heated at 100° C. for three hours. The mixture was cooled to room temperature overnight and then diluted with toluene and ethyl acetate. The mixture was filtered through a diatomaceous earth pad, rinsed with toluene, and then with ethyl acetate. The filtrate was washed twice with a saturated aqueous sodium bicarbonate solution, a saturated aqueous sodium chloride solution, dried over magnesium sulfate, and concentrated to a crude product. The crude product was purified with a 12 g Teledyne Isco silica gel column, eluted with a 10 to 30% EtOAc-hexane gradient to obtain the title compound as a solid compound of the present invention (40 mg).

[0465] 1 H NMR δ8.82(s,1H),8.41(s,2H),7.93(d,1H),7.52(d,1H),7.47(m,2H),7.19(m,1H).

[0466] Synthesis Example 13

[0467] Synthesis of 5-bromo-2-[2-[5-(difluoromethyl)-3-isoxazolyl]phenoxy]pyrimidine (Compound 62)

[0468] Step A: Synthesis of 5-(difluoromethyl)-3-(2-methoxyphenyl)isoxazole

[0469] In the methanol (15mL) solution of acetophenone (3.0g, 20mmol), add the methanol solution (5.0mL) of 30% sodium methoxide, and stir the reaction for five minutes. Then add ethyl difluoroacetate (2.97g, 24mmol), and the reaction is heated to reflux for 18h. Make the reaction cool to room temperature, and vacuum remove solvent. Add 1M hydrochloric acid and ethyl acetate to the residue, separate the phases, use magnesium sulfate to dry the organic phase and vacuum remove solvent. Adopt chromatography purification, use 0 to 100% ethyl acetate hexane solution wash-out on silica gel, obtain the desired product, it is directly used. The ethanol (30mL) solution of 4,4-difluoro-1-(2-methoxyphenyl) fourth-1,3-dione obtained from the previous step is added dropwise to the 1M sodium hydroxide (21mL) solution of hydroxylamine hydrochloride (1.4g, 20mmol). Then the reaction is heated to reflux for 2h, then cooled to room temperature. The product was precipitated from solution by addition of water and collected via vacuum filtration to afford the desired product which was used directly (AP+244, 1HNMR δ ppm 7.79 (d, 1H) 7.38-7.46 (m, 1H) 6.93-7.04 (m, 2H) 5.76-6.04 (m, 1H) 3.88 (s, 3H) 3.67-3.80 (m, 1H) 3.49-3.55 (m, 1H)). The 5-(difluoromethyl)-3-(2-methoxyphenyl)-4H-isoxazol-5-ol solution from the previous step was then taken up in trifluoroacetic acid (20 mL) and heated at 70°C for 18 h. The reaction was cooled to room temperature and the solvent was removed in vacuo. The resulting residue was dissolved in dichloromethane and washed with saturated sodium bicarbonate solution. The phases were separated, the organic phase was dried over magnesium sulfate and the solvent was removed in vacuo. Purification by chromatography on silica gel using 0 to 100% ethyl acetate in hexanes gave the title compound (2.0 g, AP + =226).

[0470] 1 H NMR δ7.91(dd,1H)7.42-7.50(m,1H)6.98-7.12(m,3H)6.66-6.93(m,1H)3.92(s,3H).

[0471] Step B: Synthesis of 2-[5-(difluoromethyl)-3-isoxazolyl]phenol

[0472] To a solution of 5-(difluoromethyl)-3-(2-methoxyphenyl)isoxazole (i.e., the product of Step A) (2.01 g, 8.92 mmol) in dichloromethane (50 mL) was added 1 M boron tribromide in dichloromethane (13.3 mL, 13.3 mmol) at 0° C., and the reaction was allowed to warm to room temperature over three hours. The solvent was removed in vacuo, and the title compound was purified by chromatography on silica gel eluting with 0 to 10% ethyl acetate in hexanes to obtain the title compound (1.66 g, AP-=210).

[0473] 1 H NMR δ9.14(s,1H)7.51(dd,1H)7.39(ddd,1H)7.11(dd,1H)6.97-7.04(m,2H)6.70-6.95(m,1H).

[0474] Step C: Synthesis of 5-bromo-2-[2-[5-(difluoromethyl)-3-isoxazolyl]phenoxy]-pyrimidine

[0475] To 2-[5-(difluoromethyl)-3-isoxazolyl]phenol (ie, the product of step B) (427 mg, 2.01 mmol) and 5-bromo-2-chloro-pyrimidine (468 mg, 2.42 mmol) in acetonitrile (10 mL) solution, potassium carbonate (695 mg, 5.03 mmol) was added, and the reaction was heated at 80 ° C. for 18 h. The solvent was removed in vacuo, and purified by chromatography on silica gel eluting with 0 to 10% ethyl acetate in hexane to obtain the title compound as a solid compound of the present invention (555 mg, mp = 88.9-92.8 ° C).

[0476] 1 H NMR δ8.53(s,2H)7.98(dd,1H)7.53-7.60(m,1H)7.41(td,1H)7.28(dd,1H)6.97(t,1H)6.59-6.84(m,1H).

[0477] Synthesis Example 14

[0478] Synthesis of 5-chloro-2-[2-[5-(trifluoromethyl)-3-isoxazolyl]-3-fluorophenoxy]pyrimidine (Compound 168)

[0479] Step A: Synthesis of 5-(difluoromethyl)-3-(2-methoxyphenyl)-4H-isoxazol-5-ol

[0480] To a solution of 2-fluoro-6-methoxyacetophenone (1.0 g, 5.9 mmol) in tetrahydrofuran (2 mL), a 30% solution of sodium methoxide in methanol (1.4 mL) was added. A solution of ethyl trifluoroacetate (0.805 g, 6.49 mmol) in tetrahydrofuran (1 mL) was added dropwise to the mixture, and the reaction was stirred at room temperature for 2 h. 1 M hydrochloric acid solution and ethyl acetate were added to the reaction, the phases were separated, and the aqueous phase was washed again with ethyl acetate. The combined organic phases were dried over magnesium sulfate and concentrated in vacuo to obtain the desired product (AP-=263), which was then used directly in the next step. Next, to a solution of 4,4,4-trifluoro-1-(2-fluoro-6-methoxyphenyl)butane-1,3-dione (from the previous step) in ethanol (14 mL), a 1 M sodium hydroxide solution (7 mL) was added, followed by hydroxylamine hydrochloride (410 mg, 5.9 mmol), and the reaction was stirred at room temperature overnight. The solvent was removed in vacuo and the residue was purified by chromatography on silica gel eluting with 0 to 10% ethyl acetate in hexanes and 0 to 20% methanol in dichloromethane to give the product (AP+=280, 1H NMR δ ppm 7.37 (td, 1H) 6.74-6.83 (m, 2H) 3.89 (s, 3H) 3.79 (d, 1H) 3.50 (dd, 1H)), which was used directly in the next step. To a solution of 3-(2-fluoro-6-methoxy-phenyl)-5-(trifluoromethyl)-4H-isoxazol-5-ol (from the previous step) in dichloromethane (20 mL) was added 1 M dichloromethane solution of boron tribromide (11.8 mL, 11.8 mmol) at 0°C, and the reaction was allowed to warm to room temperature over 2 h. The solvent was removed in vacuo. The residue was dissolved in dichloromethane and washed with saturated sodium bicarbonate solution, and the aqueous phase was washed with dichloromethane. The combined organic phases were dried over magnesium sulfate, concentrated in vacuo, and purified by chromatography on silica gel eluting with 0 to 100% ethyl acetate in hexanes to afford the title compound (606 mg, AP-=264).

[0481] 1 H NMR δ9.86(s,1H)7.32(td,1H)6.84-6.90(m,1H)6.68(ddd,1H)3.86-3.94(m,1H)3.75(dd,1H)3.56(s,1H).

[0482] Step B: Synthesis of 5-chloro-2-[2-[5-(trifluoromethyl)-3-isoxazolyl]-3-fluorophenoxy]pyrimidine

[0483] To a solution of 3-(2-fluoro-6-hydroxyphenyl)-5-(trifluoromethyl)-4H-isoxazol-5-ol (ie, the product of step A) (606 mg, 2.29 mmol) in dimethyl sulfoxide (15 mL) was added 5-chloro-2-methylsulfonyl-pyrimidine (527 mg, 2.74 mmol), followed by cesium carbonate (1.1 g, 3.43 mmol), and the reaction was stirred for 18 h. The reaction was partitioned between water and ethyl acetate, the phases were separated, and the aqueous layer was washed again with ethyl acetate. The combined organic phases were dried over magnesium sulfate and concentrated in vacuo. The residue was purified by chromatography on silica gel eluting with 0 to 10% ethyl acetate to obtain the title compound, which is a compound of the present invention (198 mg, AP + =360).

[0484] 1 H NMR δ8.46(s,2H)7.56(td,1H)7.21(ddd,1H)7.15(dt,1H)7.02(dd,1H).

[0485] Synthesis Example 15

[0486] Synthesis of 5-chloro-2-[2-[3-(trifluoromethyl)-5-isoxazolyl)phenoxy]pyrimidine (Compound 63)

[0487] Step A: Synthesis of 2-(trifluoromethyl)-4H-1-benzopyran-4-one

[0488] 2-Hydroxyacetophenone (10g, 66.7mmol) is dissolved in trifluoroacetic anhydride (19mL, 133.3mmol) and pyridine (10.8mL, 133.3mmol). The reaction mixture is heated at 70°C and stirred for 12h. After cooling, the reaction mixture is diluted with 1M hydrochloric acid and dichloromethane and washed with water. The organic phase is dried over magnesium sulfate and concentrated in vacuo. Purification is performed via chromatography using 0 to 5% ethyl acetate in hexane solution on silica gel to obtain the title compound (10.5g) as a light yellow solid.

[0489] 1 H NMR δ8.21(m,1H),7.76(m,1H),7.77(d,1H),7.46(m,1H),6.73(s,1H). MS(ESI + )=215

[0490] Step B: Synthesis of 2-[3-(trifluoromethyl)-5-isoxazolyl]phenol

[0491] To a solution of 2-(trifluoromethyl)-4H-1-benzopyran-4-one (i.e., the product of step A) (10.5 g, 48.8 mmol) in ethanol (50 mL) was added a solution of hydroxylamine acetate (146 mmol) in water (50 mL). The mixture was heated at 60 ° C for 4 h. After the reaction was cooled to ambient temperature, water (200 mL) was added to precipitate 4,4,4-trifluoro-1-(2-hydroxyphenyl)-butane-1,3-dione 3-oxime.

[0492] 1 H NMR δ9.30(s,1H),7.37(m,1H),7.19(m,1H),7.06(m,1H),6.94(m,1H),3.87(d,1H),3.69(d,1H).

[0493] The product was collected by filtration and suspended in acetic acid (30 mL) and 36% aqueous hydrochloric acid (10.8 mL) at room temperature. The mixture was stirred at 80°C for 30 min to give the title compound (4.6 g) as a white solid.

[0494] 1 H NMR δ7.88(m,1H),7.37(m,1H),7.08(m,1H),7.01(s,1H),6.95(m,1H). MS(ESI + )=230

[0495] Step C: Synthesis of 5-chloro-2-[2-[3-(trifluoromethyl)-5-isoxazolyl)phenoxy]-pyrimidine

[0496] To an anhydrous N, N-dimethylformamide (10 mL) solution of 2-[3-(trifluoromethyl)-5-isoxazolyl]phenol (i.e., the product of step B) (2.2 g, 9.4 mmol), 2,5-dichloropyrimidine (1.5 g, 10.3 mmol) and potassium carbonate (2.9 g, 20.6 mmol) were added. The reaction was heated at 80 ° C for 2 h. The solution was cooled to ambient temperature and diluted with water. The phases were separated and the aqueous phase was washed with additional ethyl acetate. The organic phases were combined, dried over magnesium sulfate and concentrated in vacuo. Purification by chromatography was performed using a hexane solution of 0 to 5% ethyl acetate on silica gel to obtain the title compound as a solid compound of the invention (2.1 g).

[0497] 1 H NMR δ8.49(s,2H),8.08(m,1H),7.58(m,1H),7.45(m,1H),7.32(m,1H),6.91(s,1H). MS(ESI + )=342. Melting point: 114-115℃

[0498] Synthesis Example 16

[0499] Synthesis of 5-bromo-2-[2-[3-(difluoromethyl)-5-isoxazolyl]-3-fluorophenoxy]pyrimidine (Compound 145)

[0500] Step A: Synthesis of 4,4-difluoro-1-(2-fluoro-6-methoxyphenyl)butane-1,3-dione

[0501] To an anhydrous N,N-dimethylformamide solution of 1-(2-fluoro-6-methoxyphenyl)ethanone (2.6 g, 15.5 mmol) and ethyl difluoroacetate (3.9 mL, 31.0 mmol) at 0°C, sodium hydride (1.2 g, 31.0 mmol) was added. The reaction mixture was heated at 80°C for 1 h. The reaction was then cooled to 0°C, diluted with ethyl acetate and acidified with 1N aqueous hydrochloric acid. The phases were separated and the aqueous phase was washed with additional ethyl acetate. The organic phases were combined and dried over magnesium sulfate and concentrated in vacuo. Purification by chromatography was performed on silica gel using 0 to 15% ethyl acetate in hexane to obtain the title compound (2.5 g).

[0502] 1 H NMR δ7.39(m,1H),6.77(m,2H),6.24(s,1H),6.01(t,1H),3.87(s,3H). MS(ESI + )=247

[0503] Step B: Synthesis of 3-(difluoromethyl)-5-(2-fluoro-6-methoxyphenyl)isoxazole

[0504] A solution of 4,4-difluoro-1-(2-fluoro-6-methoxyphenyl)butane-1,3-dione (i.e., the product of step A) (2.5 g, 10 mmol) and hydroxylamine hydrochloride (2.1 g, 30 mmol) in ethanol (25 mL) was stirred at 80 ° C. The solvent was removed in vacuo after 1 h. The resulting residue was diluted with water and extracted with dichloromethane. The organic phase was dried over magnesium sulfate and concentrated in vacuo. Purification by chromatography was performed on silica gel using 0 to 15% ethyl acetate in hexane to obtain the title compound (1.5 g).

[0505] 1 H NMRδ7.41(m,1H),6.69-6.98(m,4H),3.93(s,3H). MS(ESI + )=244

[0506] Step C: Synthesis of 2-[3-(difluoromethyl)-5-isoxazolyl]-3-fluorophenol

[0507] 1.0M boron tribromide in dichloromethane (31mL, 31mmol) was added to a solution of 3-(difluoromethyl)-5-(2-fluoro-6-methoxyphenyl)isoxazole (i.e., the product of step B) (1.5g, 6.2mmol.) in dichloromethane (10mL) at 0°C. The reaction mixture was warmed to ambient temperature and stirred for 6h. The reaction was cooled to 0°C and slowly treated with saturated sodium bicarbonate aqueous solution. The biphasic mixture was stirred for 1h at room temperature. The phases were separated and the aqueous phase was extracted with dichloromethane. The combined organic phases were dried and concentrated in vacuo. The crude residue was purified by chromatography on silica gel eluted with 0 to 10% ethyl acetate in hexane to obtain the title compound (980mg).

[0508] 1 H NMRδ7.33(m,1H),6.66-6.99(m,4H). MS(ESI + )=230

[0509] Step D: Synthesis of 5-bromo-2-[2-[3-(difluoromethyl)-5-isoxazolyl]-3-fluorophenoxy]pyrimidine To 2-[3-(difluoromethyl)-5-isoxazolyl]-3-fluorophenol (i.e., the product of step C) (229 mg, 1 mmol) in anhydrous N, N-dimethylformamide (2.5 mL) solution, 5-bromo-2-chloropyrimidine (212 mg, 1.1 mmol) and potassium carbonate (304 mg, 2.2 mmol) were added. The reaction was heated at 80 ° C for 1 h. The solution was cooled to ambient temperature and diluted with water. The phases were separated and the aqueous layer was washed with additional ethyl acetate. The organic phases were combined, dried over magnesium sulfate and concentrated in vacuo. Purification by chromatography was performed using a hexane solution of 0 to 15% ethyl acetate on silica gel to obtain the title compound as a solid compound of the invention (320 mg).

[0510] 1 H NMR δ8.54(s,2H),7.54(m,1H),7.20(m,1H),7.13(m,1H),6.86(m,1H),6.75(t,1H). MS(ESI + )=387

[0511] The following compounds of Tables 1 to 1584 can be prepared by methods described herein and methods known in the art. The following abbreviations used in the tables correspond to: t means tertiary, s means secondary, n means normal, i means iso, c means cyclo, Me means methyl, Et means ethyl, Pr means propyl, Bu means butyl, i-Pr means isopropyl, Bu means butyl, c-Pr means cyclopropyl, c-Bu means cyclobutyl, Ph means phenyl, OMe means methoxy, OEt means ethoxy, SMe means methoxy, SEt means ethylthio, NHMe means methoxyamino, -CN means cyano, Py means pyridyl, -NO2 means nitro, tzl means triazole, pzl means pyrazole, izl means imidazole, odzl means oxadiazole, tdzl means thiadiazole, and SO2Me means methylsulfonyl.

[0512] Table 1

[0513]

[0514] R 2 =Cl; Z = O; and R 3 =H(m=0);

[0515] And Q is:

[0516]

[0517]

[0518]

[0519]

[0520]

[0521]

[0522]

[0523]

[0524] This disclosure also includes Tables 2 to 1584. Each table is constructed in the same manner as Table 1 above, except that the row headings in Table 1 (i.e., "R 2 =Cl; Z = O; and R3 =H(m=0)") is replaced by the corresponding row heading shown below. For example, the first entry in Table 2 is a compound of Formula 1, wherein R 1 For H, R 2 is Cl, Z is O, R 3 is H (m=0), and Q is isoxazol-5-yl (ie, unsubstituted isoxazole is attached to the remainder of Formula 1 at the 5-position). The remainder of Table 2 is constructed in the same manner, and the remainder of Tables 3 to 1584 are constructed in the same manner.

[0525]

[0526]

[0527]

[0528]

[0529]

[0530]

[0531]

[0532]

[0533]

[0534]

[0535]

[0536]

[0537]

[0538]

[0539]

[0540]

[0541]

[0542]

[0543]

[0544]

[0545]

[0546]

[0547]

[0548]

[0549]

[0550]

[0551]

[0552] The compounds of the present invention can generally be used as herbicidal active ingredients in compositions, i.e. formulations, having at least one additional component used as a carrier, selected from surfactants, solid diluents and liquid diluents. The formulation or composition ingredients are selected to conform to the physical properties of the active ingredient, the mode of application and environmental factors such as soil type, moisture and temperature.

[0553] Available preparations include both liquid compositions and solid compositions.Liquid compositions include solutions (including emulsifiable concentrates), suspensions, emulsions (including microemulsions, oil-in-water emulsions, concentrates that can flow and / or suspoemulsions) etc., which can optionally be thickened into gels.The general type of aqueous liquid compositions is soluble concentrates, suspension concentrates, capsule suspensions, concentrated emulsions, microemulsions, oil-in-water emulsions, flowable concentrates and suspoemulsions.The general type of non-aqueous liquid compositions is emulsifiable concentrates, microemulsions, dispersible concentrates and oil dispersions.

[0554] The general types of solid compositions are dusts, powders, granules, pellets, pellets, pastilles, tablets, filled films (including seed coatings), etc., which may be water-dispersible ("wettable") or water-soluble. Films and coatings formed by film-forming solutions or flowable suspensions are particularly useful for seed treatment. The active ingredient may be (micro)encapsulated and further formed into a suspension or solid formulation; alternatively, the entire active ingredient formulation may be encapsulated (or "coated"). Encapsulation may control or delay the release of the active ingredient. Emulsifiable granules combine the advantages of both emulsifiable concentrates and dry granular formulations. High-strength compositions are primarily used as intermediates for further formulations.

[0555] Sprayable formulations are usually dispersed in suitable media before spraying. Such liquid and solid formulations are formulated in spray media, usually water, but are easy to dilute in another suitable medium such as aromatic or paraffinic hydrocarbons or vegetable oils occasionally. The spray volume can be in the scope of about one liter per hectare to several thousand liters, but more typically in the scope of about ten liters per hectare to several hundred liters. Sprayable formulations can be mixed with water or another suitable medium in a tank, for processing leaves by air or ground application, or are applied to the growth medium of plants. Liquid and dry formulations can be directly quantitatively added in the drip irrigation system, or quantitatively added in the furrow during the planting period.

[0556] The formulation will generally contain effective amounts of active ingredient, diluent and surfactant within the following approximate ranges, totaling 100% by weight.

[0557]

[0558]

[0559] Solid diluents include, for example, clays such as bentonite, montmorillonite, attapulgite and kaolin, gypsum, cellulose, titanium dioxide, zinc oxide, starch, dextrin, sugars (e.g., lactose, sucrose), silicon dioxide, talc, mica, diatomaceous earth, urea, calcium carbonate, sodium carbonate and bicarbonate, and sodium sulfate. Typical solid diluents are described in Watkins et al., Handbook of Insecticide Dust Diluents; S and Carriers, 2nd Edition, Dorland Books, Caldwell, New Jersey.

[0560] Liquid diluents include, for example, water, N,N-dimethylalkaneamides (e.g., N,N-dimethylformamide), limonene, dimethyl sulfoxide, N-alkylpyrrolidones (e.g., N-methylpyrrolidone), alkyl phosphates (e.g., triethyl phosphate), ethylene glycol, triethylene glycol, propylene glycol, dipropylene glycol, polypropylene glycol, propylene glycol carbonate, butylene glycol carbonate, paraffins (e.g., white mineral oil, normal paraffins, isoparaffins), alkylbenzenes, alkylnaphthalenes, glycerol, triacetin, sorbitol, aromatic hydrocarbons, dearomatized aliphatic compounds, alkylbenzenes, alkylnaphthalenes, ketones (such as cyclohexanone, 2-heptanone, isophorone and 4- The liquid diluents may also include saturated and unsaturated fatty acids (typically C6–C8 fatty acids). 22 ) glycerides, such as oils of plant seeds and fruits (e.g. olive oil, castor oil, linseed oil, sesame oil, cereal (corn) oil, peanut oil, sunflower seed oil, grape seed oil, safflower oil, cottonseed oil, soybean oil, rapeseed oil, coconut oil and palm kernel oil), animal fats (e.g. tallow, lard, lard, cod liver oil, fish oil), and mixtures thereof. Liquid diluents also include alkylated (e.g. methylated, ethylated, butylated) fatty acids, which can be obtained by hydrolysis of glycerides derived from plants and animals and can be purified by distillation. Typical liquid diluents are described in Marsden, Solvents Guide, 2nd Edition, Interscience, New York, 1950.

[0561] The solid compositions and liquid compositions of the present invention generally contain one or more surfactants. When added to a liquid, a surfactant (also referred to as a "surfactant") generally changes, most generally reduces, the surface tension of the liquid. Depending on the nature of the hydrophilic and lipophilic groups in the surfactant molecule, the surfactant can be used as a wetting agent, dispersant, emulsifier or defoamer.

[0562] Surfactants can be classified as nonionic surfactants, anionic surfactants or cationic surfactants. Nonionic surfactants that can be used in the compositions of the present invention include, but are not limited to, alcohol alkoxylates, such as those based on natural alcohols and synthetic alcohols (which can be branched or linear) and made from alcohols and ethylene oxide, propylene oxide, butylene oxide or mixtures thereof; amine ethoxylates, alkanolamides and ethoxylated alkanolamides; alkoxylated triglycerides, such as ethoxylated soybean oil, castor oil and rapeseed oil; alkylphenol alkoxylates, such as octylphenol ethoxylate, nonylphenol ethoxylate, dinonylphenol ethoxylate and dodecylphenol ethoxylate (made from phenol and ethylene oxide, propylene oxide, butylene oxide or mixtures thereof); block polymers made from ethylene oxide or propylene oxide and trans block polymers in which the terminal blocks are made from propylene oxide. ; ethoxylated fatty acids; ethoxylated fatty acid esters and oils; ethoxylated methyl esters; ethoxylated tristyrylphenols (including those made from ethylene oxide, propylene oxide, butylene oxide or mixtures thereof); fatty acid esters, glycerides, lanolin-based derivatives, polyethoxylated esters (such as polyethoxylated sorbitan fatty acid esters, polyethoxylated sorbitan fatty acid esters and polyethoxylated glycerol fatty acid esters); other sorbitan derivatives, such as sorbitan esters; polymeric surfactants, such as random copolymers, block copolymers, alkyd peg (polyethylene glycol) resins, graft or comb polymers and star polymers; polyethylene glycol (PEG); polyethylene glycol fatty acid esters; silicone-based surfactants; and sugar derivatives, such as sucrose esters, alkyl polyglycosides and alkyl polysaccharides.

[0563] Useful anionic surfactants include, but are not limited to, alkylaryl sulfonic acids and their salts; carboxylated alcohol or alkylphenol ethoxylates; diphenyl sulfonate derivatives; lignin and lignin derivatives, such as lignin sulfonates; maleic acid or succinic acid or their anhydrides; olefin sulfonates; phosphates, such as phosphates of alcohol alkoxylates, phosphates of alkylphenol alkoxylates, and phosphates of styrylphenol ethoxylates; protein-based surfactants; sarcosine derivatives; styrylphenol ether sulfates; sulfates and sulfonates of oils and fatty acids; sulfates and sulfonates of ethoxylated alkylphenols; sulfates of alcohols; sulfates of ethoxylated alcohols; sulfonates of amines and amides, such as N,N-alkyltaurates; sulfonates of benzene, isopropylbenzene, toluene, xylene, and dodecylbenzene and tridecylbenzene; sulfonates of polycondensed naphthalene; sulfonates of naphthalene and alkylnaphthalene; sulfonates of petroleum fractions; sulfosuccinamates; and sulfosuccinates and their derivatives, such as dialkyl sulfosuccinates.

[0564] Useful cationic surfactants include, but are not limited to, amides and ethoxylated amides; amines such as N-alkylpropylenediamine, tripropylenetriamine, and dipropylenetetramine, as well as ethoxylated amines, ethoxylated diamines, and propoxylated amines (prepared from amines and ethylene oxide, propylene oxide, butylene oxide, or mixtures thereof); amine salts such as amine acetates and diamine salts; quaternary ammonium salts such as quaternary ammonium salts, ethoxylated quaternary ammonium salts, and diquaternary ammonium salts; and amine oxides such as alkyldimethylamine oxides and bis-(2-hydroxyethyl)-alkylamine oxides.

[0565] Also useful in the compositions of the present invention are mixtures of nonionic and anionic surfactants, or mixtures of nonionic and cationic surfactants. Nonionic, anionic and cationic surfactants and their recommended uses are disclosed in a number of published references, including McCutcheon's Emulsifiers and Detergents, North American and International Annual Editions, published by McCutcheon's Division, The Manufacturing Confectioner Publishing Co.; Sisely and Wood, Encyclopedia of Surface Active Agents, Chemical Publ. Co., Inc., New York, 1964; and AS Davidson and B. Milwidsky, Synthetic Detergents, Seventh Edition, John Wiley and Sons, New York, 1987.

[0566] The compositions of the present invention may also contain formulation aids and additives known to those skilled in the art as formulation aids (some of which may also be considered to function as solid diluents, liquid diluents, or surfactants). Such formulation aids and additives may control: pH (buffers), foaming during processing (defoamers, such as polyorganosiloxanes), sedimentation of active ingredients (suspending agents), viscosity (thixotropic thickeners), microbial growth in containers (antimicrobial agents), product freezing (antifreeze agents), color (dye / pigment dispersions), elution (film formers or adhesives), evaporation (evaporation inhibitors), and other formulation attributes. Film formers include, for example, polyvinyl acetate, polyvinyl acetate copolymers, polyvinyl pyrrolidone-vinyl acetate copolymers, polyvinyl alcohol, polyvinyl alcohol copolymers, and waxes. Examples of formulation aids and additives include McCutcheon's Volume 2: Functional Materials, North American and International Yearbook Edition, published by The Manufacturing Confectioner Publishing Co., a division of McCutcheon; and those listed in PCT Publication WO 03 / 024222.

[0567] The compound of formula 1 and any other active ingredient are usually incorporated into the composition of the present invention by dissolving the active ingredient in a solvent or by grinding the active ingredient in a liquid or dry diluent. Solutions including emulsifiable concentrates can be prepared by simply mixing the ingredients. If the solvent of the liquid composition intended for use as an emulsifiable concentrate is immiscible with water, an emulsifier is usually added to emulsify the solvent containing the active substance when diluted with water. A media grinder can be used to wet-grind an active ingredient slurry with a particle size of up to 2,000 μm to obtain particles with an average diameter of less than 3 μm. The aqueous slurry can be prepared as a finished suspension concentrate (see, for example, US3,060,084) or further processed by spray drying to form water-dispersible particles. Dry formulations generally require a dry grinding process that produces an average particle size in the range of 2 to 10 μm. Dusts and powders can be prepared by blending, and are usually prepared by grinding (such as with a hammer mill or fluid energy mill). Granules and granules can be prepared by spraying the active substance on a preformed granular carrier or by agglomeration techniques. See Browning's "Agglomeration" (Chemical Engineering, December 4, 1967, pages 147-48), Perry's Chemical Engineer's Handbook 4th edition (McGraw-Hill, New York, 1963, pages 8-57 et seq.), and WO 91 / 13546. Pellets can be prepared as described in US 4,172,714. Water-dispersible and water-soluble granules can be prepared according to the teachings of US 4,144,050, US 3,920,442, and DE 3,246,493. Tablets can be prepared according to the teachings of US 5,180,587, US 5,232,701, and US 5,208,030. Films can be prepared according to the teachings of GB 2,095,558 and US 3,299,566.

[0568] For further information in the field of formulation, see "The Formulator's Toolbox - Product Forms for Modern Agriculture" in TS Woods, Pesticide Chemistry and Bioscience, The Food-Environment Challenge, edited by T. Brooks and TR Roberts, Proceedings of the 9th International Congress on Pesticide Chemistry, The Royal Society of Chemistry, Cambridge, 1999, pp. 120-133. See also U.S. Pat. No. 3,235,361, column 6, lines 16 to column 7, line 19, and Examples 10-41; U.S. Pat. No. 3,309,192, column 5, lines 43 to column 7, line 62, and Examples 8, 12, 15, 39, 41, 52, 53, 58, 132, 138-140, 162-164, 166, 167, and 169-182; U.S. Pat. No. 2,891,855, column 3, lines 66 to column 5, line 17, and Examples 1-4; Klingman, Weed Control as a Science, John Wiley and Sons, Inc., New York, 1961, pages 81-96; Hance et al., Weed Control Handbook, 8th edition, Blackwell Scientific Publications, Oxford, 1989; and Developments in formulation technology, PJB Publications, Richmond, UK, 2000.

[0569] In the following examples, all percentages are by weight and all formulations are prepared in a conventional manner. The compound numbers refer to the compounds in Index Table A. Without further study, it is believed that those skilled in the art can utilize the present invention to its maximum extent based on the above description. Therefore, the following examples should be understood to be merely exemplary and not to limit the present disclosure in any way. Unless otherwise stated, percentages are by weight.

[0570] Example A

[0571] High concentration concentrate

[0572] Compound 1 98.5%

[0573] Silica Aerogel 0.5%

[0574] Synthetic amorphous fine silica 1.0%

[0575] Example B

[0576] Wettable powder

[0577]

[0578] Example C

[0579] Granules

[0580] Compound 15 10.0%

[0581] Attapulgite particles (low volatile matter, 0.71 / 0.30mm; 90.0%

[0582] USS No. 25–50 mesh)

[0583] Example D

[0584] Extrusion pellets

[0585]

[0586] Example E

[0587] EC

[0588] Compound 23 10.0%

[0589] Polyoxyethylene sorbitan hexaoleate 20.0%

[0590] C6–C 10 Fatty acid methyl ester 70.0% Example F

[0591] microemulsion

[0592]

[0593] Example G

[0594] Suspension concentrates

[0595]

[0596] Example H

[0597] water emulsion

[0598]

[0599]

[0600] Embodiment 1

[0601] oil dispersion

[0602]

[0603] Example J

[0604] Suspoemulsion

[0605]

[0606] The test results show that the compounds of the present invention are highly active pre-emergence and / or post-emergence herbicides and / or plant growth regulators. The compounds of the present invention are generally used for post-emergence weed control (i.e., application after weed seedlings sprout from soil) and pre-emergence weed control (i.e., application before weed seedlings sprout from soil). In areas where it is desired to fully control all vegetation, such as around fuel tanks, industrial storage areas, parking lots, open-air drive-in cinemas, airports, riverbanks, irrigation and other waterways, billboards and highways and railway structures, many of them have utility for broad-spectrum pre-emergence and / or post-emergence weed control. Due to selective metabolism in crops and weeds, or by selective activity of physiological inhibition sites in crops and weeds, or by selective placement on or in the environment of a mixture of crops and weeds, many compounds of the present invention can be used for selective control of grass and broad-leaved weeds in crop / weed mixtures. Those skilled in the art will recognize that in a compound or a group of compounds, the preferred combination of these selectivity factors can be easily determined by implementing conventional biological and / or biochemical analysis. The compounds of the present invention can show tolerance to important crops, including but not limited to alfalfa, barley, cotton, wheat, rapeseed, sugar beet, corn (corn), sorghum, soybean, rice, oats, peanuts, vegetables, tomatoes, potatoes, perennial crops (including coffee, cocoa, oil palm, rubber, sugar cane, citrus, grapes, fruit trees, nut trees, bananas, plantains, pineapples, dry hops), tea and forest trees such as eucalyptus and conifers (e.g., loblolly pine), and lawn species (such as Kentucky bluegrass, St. Augustine grass, Kentucky Fisk grass and Bermuda grass). The compounds of the present invention can be used for genetically transformed crops or cultivated as crops combined with resistance to herbicides, expressing proteins toxic to invertebrate pests (such as Bacillus thuringiensis toxins) and / or expressing crops of other usable traits. Those skilled in the art will know that not all compounds have the same effect on all weeds. Alternatively, the subject compounds can be used to change plant growth.

[0607] Since the compounds of the present invention have both pre-emergence and post-emergence herbicidal activity to control the undesirable vegetation by killing or injuring the vegetation or slowing down its growth, the compounds can be effectively applied by a variety of methods, which involve contacting the leaves or other parts of the undesirable vegetation, or the environment of the undesirable vegetation such as soil or water (where the undesirable vegetation grows), with a herbicidally effective amount of the compounds of the present invention, or a composition comprising the compounds and at least one surfactant, solid diluent or liquid diluent, or the environment of the undesirable vegetation such as soil or water (where the undesirable vegetation grows), or the environment surrounding the seeds or other propagules of the undesirable vegetation.

[0608] The herbicidally effective amount of the compounds of the present invention is determined by a number of factors. These factors include: the selected formulation, the method of application, the amount and type of vegetation present, growth conditions, etc. Generally speaking, the herbicidally effective amount of the compounds of the present invention is about 0.001 to 20 kg / ha, with a preferred range of about 0.004 to 1 kg / ha. Those skilled in the art can easily determine the herbicidally effective amount required for the desired level of weed control.

[0609] The compounds of the present invention can be used to treat all plants and plant parts. Plant varieties and cultivars can be obtained by conventional propagation and breeding methods or by genetic engineering methods. Genetically modified plants (transgenic plants) are those in which a heterologous gene (transgene) has been stably integrated into the genome of the plant. A transgene defined by its specific position in the plant genome is referred to as a transformation event or a transgenic event.

[0610] Genetically modified plant cultivars that can be treated according to the present invention include those that resist one or more biological stresses (pests, such as nematodes, insects, mites, fungi, etc.) or abiotic stresses (drought, low temperature, soil salinization, etc.), or they contain other desired characteristics. Plants can be genetically modified to show traits, such as herbicide tolerance, insect tolerance, modified oil characteristics or drought tolerance. Available genetically modified plants comprising a single gene conversion event or a combination of multiple conversion events are listed in Example C. Additional information about the genetic modifications listed in Example C can be obtained from, for example, publicly available databases maintained by the U.S. Department of Agriculture.

[0611] The following abbreviations 1 to 37 are used for the properties of Example C. "-" indicates that the entry is not applicable.

[0612]

[0613] Example C

[0614]

[0615]

[0616]

[0617]

[0618]

[0619]

[0620]

[0621] *Argentine (Brassica napus), **Polish (Turnip), #Eggplant

[0622] Treatment of genetically modified plants with the compounds of the invention may result in superadditive or synergistic effects. For example, reduced application rates, expanded activity profiles, increased tolerance to biotic / abiotic stresses, or enhanced storage stability may be greater than would be expected from the additive effects of simply applying the compounds of the invention to the genetically modified plants.

[0623] The compound of the present invention can also be mixed with one or more other biologically active compounds or agents to form a multi-component pesticide, giving even a wider spectrum of agricultural protection, and the other biologically active compounds or agents include herbicides, herbicide safeners, fungicides, insecticides, nematicides, bactericides, acaricides, growth regulators such as insect molting inhibitors and rooting stimulants, chemical sterilants, chemical semiochemicals, repellents, attractants, pheromones, feeding stimulants, plant nutrients, other biologically active compounds or insect pathogenic bacteria, viruses or fungi. The mixture of the compound of the present invention and other herbicides can expand the range of activity against other weed species and inhibit the proliferation of any resistant biological type. Therefore, the present invention also relates to a composition comprising a compound (herbicidally effective amount) of Formula 1 and at least one additional biologically active compound or agent (biologically effective amount), and the composition may also include at least one of a surfactant, a solid diluent or a liquid diluent. Other biologically active compounds or agents can be formulated into a composition comprising at least one of a surfactant, a solid or a liquid diluent. For the mixtures of the present invention, one or more other biologically active compounds or agents can be formulated together with the compound of Formula 1 to form a premix, or one or more other biologically active compounds or agents can be formulated separately from the compound of Formula 1 and the formulations mixed together (e.g., in a spray tank) prior to administration, or alternatively, applied sequentially.

[0624] Mixtures of one or more of the following herbicides with the compounds of the invention can be particularly useful for weed control: acetochlor, acifluorfen and its sodium salt, fenpyroxil, acrolein (2-propenal), alachlor, fenpyroxil, ametryn, amitriptyline, amidosulfuron, cyproconazole and its esters (e.g., methyl esters, ethyl esters) and salts (e.g., sodium salts, potassium salts), aminopyralid, cyproconazole, ammonium sulfamate, cyproconazole, sulfamethoxam, atrazine, tetrazosulfuron, flubutyric acid, fenpyroxil, fenpyroxil ethyl, bencarbazone, fluazifop, furosulfuron, benzylsulfuron, dimethoate, bentazon, bicyclam, pyraclostrobin, flupyroxil, bialaphos, bispyribac-butyl and its sodium salt, bromobutyric acid, bromophenoxime, bromoxynil, bromoxynil octanoate, fluazifop, flupropamide oxadiazine, chlorpyrifos, butyralid, butoxycycline, sudaramide, mesotrione, long-kill grass, triadimefon, catechin, chlorbromid, chlormethyldan, chlorpyrifos, chlorsulfuron, chlorotoluron, chlorpropamide, dimethyl chlorthalate, cypermethrin, indolone, cyproconazole, ethersulfuron, chloracylphosphine, cyclobenzophenone, clethodim, clodinafop-butyl, clomazone, barnyardgrass, clopyralid, clopyralid ethanolamine salt, clopyralid sulfamethoxam, benzylpyridin, cyanazine, cyproconazole, cyclopyrimorate, cyprosulfuron, cyfluthrin, 2,4-D and its butoxyethyl, butyl, isooctyl, and isopropyl esters and its dimethylammonium salt, diethanolamine salt and triethanolamine salt, mesotrione, dalapon, dalapon sodium, dazomethane 、2,4-DB and its dimethylammonium salt, potassium salt and sodium salt, betaine, dichlorvos, dicamba and its diethylene glycol ammonium salt, dimethylammonium salt, potassium salt and sodium salt, dichlorvos nitrile, 2,4-dichlorprop, dichlorvos butyl, diclosulam, difenac dimethyl sulfate, fluazifop, flufenazol, oxazolidinone, piperone, dimethochlor, isopentyl ethyl, dimethochlor, dimethochlor succinate, thiamethoxam, dimethylarsonic acid and its sodium salt, dimethosulfuron, telofenol, fenamid, diquat, fluthiopyr, diuron, DNOC, grass, EPTC, dichlorvos, diflunisal, ethiprole, ethosulfuron, fluurol, ethosulfuron, ethosulfuron, oxazolidinone ethyl, oxazolidinone ethyl, fenoxasulfone, fenquinotrione, tetrazopyralid, fenpyralid, fenpyralid-TCA, fluazifop-methyl, fluazifop-M-isopropyl, fluazifop-M-methyl, fluazifop-butyl, fluazifop-butyl, fluazifop-butyl, fluazifop-butyl, fluazifop-butyl, fluazifop-butyl, fluazifop-butyl, fluazifop-butyl, fluazifop-butyl, fluazifop-butyl, fluazifop-butyl, fluazifop-butyl, fluazifop-butyl, fluazifop-butyl, fluazifop-butyl, fluazifop-butyl, fluazifop-butyl and its sodium salt ...sodium salt (including sesquisodium salt) and trimethylsulfonium (or known as glufosinate), haloxyfop-butyl, haloxyfop-methyl, haloxyfop-methyl, haloxyfop-ethyl, hexazinone, imazamethoate, imazapic acid, imazapic acid, imazapic acid, imazapic acid, imazapic acid, imazapic acid, imazapic acid, imazapic acid, imazapic acid, imazapic acid, imazapic acid, imazapic acid, imazapic acid, indocyanine, triazine indocyanine, iodosulfuron, ioboxynil, ioboxynil octanoate, ioboxynil sodium, triazole, isoproturon, isoxachlor, isoxaflutamide, isoxaflutamide, isoxaflutamide, lactofen, cypermethrin, linuron, maleic hydrazide, MCPA and its salts (such as MCPA-dimethylammonium, MCPA-potassium and MCPA-sodium, esters (such as MCPA-2 ethylhexyl ester, MCPA-butoxyethyl ester) and thioesters (such as Such as MCPA-ethylthioester), MCPB and its salts (such as MCPB-sodium salt) and esters (such as MCPB-ethyl ester), 2-methyl-4-chloropropionic acid, 2-methyl-4-chloropropionic acid, benzathine, chloranil, mesosulfuron, mesotrione, metamifenamid, metamitron, metazachlor, pyrazosulfuron, methylbenthiocarb, methylarsonic acid and its calcium salt, monoammonium salt, monosodium salt and disodium salt, methylthiazon, pyranuron, sulfamethoxam, sulfamethoxam, sulfamethoxam, sulfamethoxam, methoxythiazon, methotrexate, chloranil, naphthamide, naphthamide, naphthamide, naphthamide, naphthamide, naphthamide, naphthamide, nicosulfuron, fluazifop, pyranocarb, pyrazosulfuron, pyrazosulfuron, methylbenthiocarb, methylarsonic acid and its calcium salt, monoammonium salt, monosodium salt and disodium salt, methylthiazon, pyranuron, sulfamethoxam ... ketone, oxyfluorfen, cypermethrin, nonanoic acid, dimethoate, pendimethalin, penoxsulam, cypermethrin, cypermethrin, yellow grass sulfamate, pethoxyamid, betaine, picloram, picloram potassium, pyralid, pinoxaden, pyralid, pretilachlor, methyl cypermethrin, aminopropyrin, cypermethrin, promethone, promethazine, promethazine, propoxychlor, propoxychlor, propoxychlor, propoxychlor, propoxychlor, promethazine, isopropoxychlor, propoxysulfone, propoxysulfone, propoxysulfone, penthiocarb, prosulfuron, pyraclonil, pyraclostrobin, pyrazogyl, pyrazol, pyrazoline, pyrazoline, pyrazoline, pyrazoline, pyrazoline, pyrazoline, pyrazoline, pyrazoline, pyrazoline, pyrazoline, pyrazoline, pyrazoline, pyrazoline, pyrazoline, pyrazoline, pyrazoline, pyrazoline, pyrazoline, pyrazoline , sodium sulfamethoxam, rock grass-killing sulfone, methoxysulfone, quick-kill barnyard, quinclorac, algae quinone, quizalofop-ethyl, quizalofop-ethyl ethyl, quizalofop-ethyl, sulfamethoxam, bensulfuron, sethoxydim, cypermethrin, simazine, cypermethrin, sulfotrione, sulfotrione, sulfotrione, sulfotrione, sulfotrione, 2,3,6-TBA, TCA, sodium TCA, grass-killing amine, butyryl, furfuryl ester ketone, cypermethrin, demeton, terbuthyl, methoxytobacil, terbuthyl, bensulfuron, methoxysulfone, terbuthyl, bensulfuron, methoxysulfone, thiamethoxam, thiazolin, thiazolin, thiazolin, thiazolin, thiazolin, thiazolin, thiazolin, tiafenacil, thiazolin, pyraclostrobin, oxime, wild wheat, fluazifop-sulfuron, ether bensulfuron, triazifop-sulfuron, bensulfuron methyl, triclopyr, triclopyr-butoxyethyl, triclopyr triethylammonium salt,Cyclopentanil, cypermethrin, trifloxysulfuron, fluralin, flufensulfuron, cypermethrin, 3-(2-chloro-3,6-difluorophenyl)-4-hydroxy-1-methyl-1,5-naphthyridin-2(1H)-one, 5-chloro-3-[(2-hydroxy-6-oxo-1-cyclohexene-1-yl)carbonyl]-1-(4-methoxyphenyl)-2(1H)-quinoxalinone, 2-chloro-N-(1-methyl-1H-tetrazol-5-yl)-6-(trifluoromethyl)- 7-(3,5-dichloro-4-pyridyl)-5-(2,2-difluoroethyl)-8-hydroxypyrido[2,3-b]pyrazin-6(5H)-one), 4-(2,6-diethyl-4-methylphenyl)-5-hydroxy-2,6-dimethyl-3(2H)-pyridazinone), 5-[[(2,6-difluorophenyl)methoxy]methyl]-4,5-dihydro-5-methyl-3-(3-methyl-2- thienyl)isoxazole (formerly oxathiapiprolin), 3-[7-fluoro-3,4-dihydro-3-oxo-4-(2-propyn-1-yl)-2H-1,4-benzoxazin-6-yl]dihydro-1,5-dimethyl-6-thioxo-1,3,5-triazine-2,4(1H,3H)-dione, 4-(4-fluorophenyl)-6[(2-hydroxy-6-oxo-1-cyclohexen-1-yl)carbonyl]-2-methyl-1,2,4-triazine -3,5(2H,4H)-dione, 4-amino-3-chloro-6-(4-chloro-2-fluoro-3-methoxyphenyl)-5-fluoro-2-picolinic acid methyl ester, 2-methyl-3-(methylsulfonyl)-N-(1-methyl-1H-tetrazol-5-yl)-4(trifluoromethyl)benzamide, and 2-methyl-N-(4-methyl-1,2,5-oxadiazol-3-yl)-3(methylsulfinyl)-4-(trifluoromethyl)benzamide. Other herbicides include bioherbicides such as Alternaria destruens Simmons, Colletotrichum gloeosporiodes (Penz.) Penz. & Sacc., Drechsieramonoceras (MTB-951), Myrothecium verrucaria (Albertini & Schweinitz) Ditmar Fries, Phytophthora palmivora (Butl.) and Pucciniathlaspeos Schub.

[0625] The compounds of the present invention may also be used in combination with plant growth regulators such as avermectin, N-(phenylmethyl)-1H-purin-6-amine, propionyl brassinolide, gibberellic acid, gibberellins A4 and A7, hypersensitive protein, mepiquat, prohexadione-calcium, jasmone, sodium nitrophenolate and trinexapac-ethyl, and plant growth regulating organisms such as Bacillus cereus strain BP01.

[0626] General references to agricultural protectants (i.e., herbicides, herbicide safeners, insecticides, fungicides, nematicides, miticides, and biological agents) include The Pesticide Manual, 13th edition, edited by CDS Tomlin, British Crop Protection Council, Farnham, Surrey, UK, 2003, and The BioPesticide Manual, 2nd edition, edited by LG Copping, British Crop Protection Council, Farnham, Surrey, UK, 2001.

[0627] For embodiments in which one or more of these various admixture components are used, the weight ratio of these various admixture components (total amount) to the compound of Formula 1 is generally between about 1:3000 and about 3000:1. Of note are weight ratios between about 1:300 and about 300:1 (e.g., ratios between about 1:30 and about 30:1). One skilled in the art can readily determine by simple experimentation the biologically effective amount of the active ingredient required to obtain the desired range of biological activity. Clearly, the inclusion of these additional components can extend the weed control spectrum beyond the range of weed control by the compound of Formula 1 alone.

[0628] In some cases, the combination of the compounds of the present invention and other biologically active (especially herbicidal) compounds or agents (i.e., active ingredients) can obtain an effect greater than the cumulative (i.e., synergistic) effect on weeds, and / or an effect less than the cumulative (i.e., safening) effect can be obtained for crops or other desired plants. It has always been desirable to reduce the amount of active ingredients released into the environment while ensuring effective pest control. The ability to use larger amounts of active ingredients to provide more effective weed control without causing excessive crop damage is also desirable. When the herbicidal active ingredient produces a synergistic effect on weeds at an application rate to obtain an agronomically satisfactory weed control level, such a combination can advantageously reduce crop production costs and reduce environmental loads. When the safening of herbicidal active ingredients occurs on crops, such a combination can advantageously improve crop protection by reducing weed competition.

[0629] It is noteworthy that the combination of the compound of the present invention and at least one other herbicidal active ingredient. It is particularly noteworthy that such combinations in which the other herbicidal active ingredients have a different site of action from the compounds of the present invention. In some cases, the combination with at least one other herbicidal active ingredient with a similar control range but a different site of action will be particularly beneficial for resistance management. Therefore, the present composition may also include at least one additional herbicidal active ingredient (herbicidally effective amount) with a similar control range but a different site of action.

[0630] The compounds of the present invention can also be used in combination with herbicide safeners such as diacylglycerol, chlorpyrifos, chlorpyrifos-butyl, benzylpyridin, chlorpyrifos-butyl, cyproconazole, cyproconazole, dimethoate, dichloropropene, dicyclonon, thiophene, chlorpyrifos, chlorpyrifos, chlorpyrifos-butyl, chlorpyrifos-butyl, fluazifop, chlorpyrifos-butyl, isoxadiazole, isoxadiazole, pyraclostrobin, 4-chlorophenyl methylcarbamate, chlorpyrifos naphthalene dicarboxylic anhydride (1,8-naphthalene dicarboxylic anhydride), chlorpyrifos-butyl, N-(aminocarbonyl)-2-methylbenzenesulfonamide, N-(aminocarbonyl)-2-fluorobenzenesulfonamide, 1-bromo-4-[(chloromethyl)sulfonyl]benzene (BCS), 4-(dichloroacetyl)-1-oxa-4-azospiro[4.5]decane (MON 4660), 2-(dichloromethyl)-2-methyl-1,3-dioxolane (MG 191), 1,6-dihydro-1-(2-methoxyphenyl)-6-oxo-2-phenyl-5-pyrimidinecarboxylic acid ethyl ester, 2-hydroxy-N,N-dimethyl-6-(trifluoromethyl)pyridine-3-carboxamide, and 1-(3,4-dimethylphenyl)-l,6-dihydro-6-oxo-2-phenyl-5-pyrimidinecarboxylic acid 3-oxo-1-cyclohexene-l-yl ester to improve the safety of certain crops. The herbicide safener with a detoxifying effective amount can be applied simultaneously with the compounds of the present invention, or applied as a seed treatment. Therefore, one aspect of the present invention relates to a herbicide mixture comprising a compound of the present invention and a detoxifying effective amount of a herbicide safener. Seed treatment is particularly useful for selective weed control because it limits the detoxifying entity to crop plants. Therefore, a particularly useful embodiment of the present invention is a method for selectively controlling the growth of undesirable vegetation in crops, the method comprising contacting the crop part with a herbicidally effective amount of a compound of the present invention, wherein the seed (growing the crop from it) is treated with an antidote effective amount of a safener. The antidote effective amount of the safener can be easily determined by a person skilled in the art by simple experiments.

[0631] Of note are compositions comprising (a herbicidally effective amount of) a compound of the present invention, (an effective amount of) at least one additional active ingredient selected from other herbicides and herbicide safeners, and at least one component selected from surfactants, solid diluents and liquid diluents.

[0632] Table A1 lists specific combinations of components (a) and (b), illustrating the mixtures, compositions and methods of the present invention. Compound 1 in the component (a) column is indicated in Index Table A. The second column of Table A1 lists specific component (b) compounds (e.g., "2,4-D" in the first row). The third, fourth and fifth columns of Table A1 list the weight ratio ranges (i.e., (a): (b)) relative to the application rate of component (b) when the component (a) compound is typically applied to field-grown crops. Thus, for example, the first row of Table A1 specifically discloses that the combination of component (a) (i.e., compound 1 in Index Table A) and 2,4-D is typically applied in a weight ratio between 1:168–6:1. The remaining rows of Table A1 can be interpreted similarly.

[0633] Table A1

[0634]

[0635]

[0636]

[0637]

[0638]

[0639]

[0640] Table A2 is constructed the same as in Table A1 above, except that the entry "Component (a)" under the column heading is replaced by the column entry for the corresponding component (a) shown below. Compound 1 in the "Component (a)" column is identified in Index Table A. Thus, for example, the entries under the "Component (a)" column heading in Table A2 are all listed as "Compound 12" (i.e., Compound 12 identified in Index Table A), and the first row under the column heading in Table A2 specifically discloses a mixture of Compound 12 and 2,4-D. Tables A3 to A9 are similarly constructed.

[0641]

[0642] For better control of undesirable vegetation (e.g. due to reduced use rates, broadened weed control spectrum, or enhanced crop safety, for example, due to synergistic effects) or to prevent the development of weed resistance, mixtures of the compounds of the invention with a herbicide selected from the group consisting of chlorimuron-methyl, nicosulfuron-methyl, diuron, hexazinone, thiasulfuron-methyl and S-isopropylamine are preferred.

[0643] The compounds of the invention are useful for controlling weed species that are tolerant to herbicides with an AHAS-inhibitor or (b2) [compounds that inhibit acetohydroxyacid synthase (AHAS), also known as acetolactate synthase (ALS)] mode of action.

[0644] The following tests demonstrate the control efficacy of the compounds of the present invention on specific weeds. However, the weed control provided by the compounds is not limited to these species. See Index Table A for a description of the compounds. Mass spectra were obtained using atmospheric pressure chemical ionization (APCI). + ) or electrospray ionization (ESI), observed by a mass spectrometer, and reported as the molecular weight of the most isotopically abundant parent ion (M+1) formed by the addition of H+ (molecular weight 1) to the molecule. The following abbreviations are used in Index Table A as follows: Ph is phenyl, pyridyl is pyridyl, OEt is ethoxy, CN is cyano, CHO is formyl, t-Bu is tert-butyl, i-Pr is iso-propyl, c-Pr is cyclopropyl, Me is methyl, Et is ethyl, and C(=O)CH3 is acetyl. The abbreviation "Ex." stands for "Example" and is followed by a number indicating the example in which the compound was prepared.

[0645] Index Table A

[0646]

[0647]

[0648]

[0649]

[0650]

[0651]

[0652]

[0653] a ES+, b AP–, c M+Na.

[0654] * 1 See Index Table B for H NMR data.

[0655] and 4-Br-1H-pyrazol-1-yl

[0656] Index Table B

[0657]

[0658] zUnless otherwise specified, 1 H NMR data are in ppm downfield from tetramethylsilane at 500 MHz. Couplings are indicated by (s)-singlets, (d)-doublets, and (m)-multipletts.

[0659] Biological Embodiments of the Invention

[0660] Test A

[0661] Seeds of plant species selected from Bromus tectorum, common cocklebur (Xanthium strumarium), wild oats (Avena fatua), barnyard grass (Echinochloa crus-galli), big crabgrass (Digitaria sanguinalis), giant foxtail (Setaria faberii), morning glory (Ipomoea genus), velvetleaf (Abutilon theophrasti), and sorghum (Sorghum vulgare) are planted in silt loam and treated pre-emergence by soil drench with the test compound formulated in a non-phytotoxic solvent mixture containing a surfactant. At the same time, these materials are also sprayed post-emergence to overflow treatment using the test compound formulated in the same manner.

[0662] Post-emergence treatments were performed using plants ranging in height from 2 to 18 cm and at the one- to two-leaf stage. Treated plants and untreated controls were maintained in a greenhouse for approximately 11 days, after which all treated plants were compared to untreated controls and visually assessed for injury. The plant response scores summarized in Table A were based on a scale of 0 to 100, with 0 being no effect and 100 being complete control. A dash (-) response indicated no test results.

[0663]

[0664] Test B

[0665] Seeds of a plant species selected from barnyardgrass (Echinochloa crus-galli), Kochia scoparia, ragweed (Ambrosia elatior), Italian ryegrass (Lolium multiflorum), large crabgrass (Digitaria sanguinalis), giant foxtail (Setaria faberii), morning glory (Ipomoea spp.), wild amaranth (Amaranthus retroflexus), velvetleaf (Abutilon theophrasti), wheat (Triticum aestivum), and corn (Zea mays) are planted in a blend of loam and sand and treated pre-emergence with a directed soil spray using the test compound formulated in a non-phytotoxic solvent mixture containing a surfactant.

[0666] At the same time, the plants selected from these crops and weed species and black grass (Alopecurus myosuroides) and catchweed (Galium aparine) were planted in pots comprising the same loam and sand blend, and the test compound prepared in the same manner was used to apply the treatment after emergence. The plants with a height range of 2 to 10 cm and in the one-leaf to two-leaf stage were used to carry out the post-emergence treatment. The treated plants and untreated controls were kept in a greenhouse for about 10 days, and then all the treated plants were compared with the untreated controls, and visually assessed for damage. The plant reaction scores summarized in Table B are based on a scale of 0 to 100, wherein 0 is no effect, and 100 is complete control. The dash (–) reaction indicates that there is no test result.

[0667]

[0668]

[0669]

[0670]

[0671]

[0672]

[0673]

[0674]

[0675]

[0676]

[0677]

[0678]

[0679]

[0680]

[0681]

[0682]

[0683]

[0684]

[0685]

[0686]

[0687]

[0688]

[0689]

[0690]

[0691] Test C

[0692] Plant species selected from rice (Oryza sativa), Cyperus difformis, Heteranthera limosa, and Echinochloa crus-galli were grown to the 2-leaf stage for testing in a flooded paddy field test. For treatment, the test pots were filled with water to 3 cm above the soil surface, and the test compound was applied directly to the field water for treatment, and then the water depth was maintained during the test period.

[0693] Treated plants and controls were maintained in the greenhouse for approximately 13 to 15 days, after which all species were compared to controls and visually assessed. Plant response scores summarized in Table C were based on a 0 to 100 scale, with 0 being no effect and 100 being complete control. Responses with a dash (-) indicate no test results.

[0694]

[0695]

[0696]

[0697] Test D

[0698] The selected from black grass (Alopecurus myosuroides), Italian ryegrass (Lolium multiflorum), winter wheat (Triticum aestivum), catchweed bedstraw (Galium aparine), corn (Zeamays), big crabgrass (Digitaria sanguinalis), giant foxtail grass (Setaria faberii), Johnson grass (Sorghum halepense), quinoa (Chenopodium album), morning glory (Ipomoea coccinea), oil sedge (Cyperus esculentus), wild amaranth (Amaranthus retroflexus), ragweed (Ambrosia elatior), soybean (Glycine max), barnyard grass (Echinochloa crus-galli), rapeseed (Brassicanapus), common waterhemp (Amaranthus Seeds of the plant species of Atractylodes rudis, and Abutilion theophrasti were planted in a blend of silt loam and sand and treated pre-emergence with the test compound formulated in a non-phytotoxic solvent mixture containing a surfactant.

[0699] At the same time, plants selected from these crop and weed species and Kochia scoparia, wild oats (Avenafatua), and common chickweed (Stellaria media) are grown in a field comprising Plants were grown in pots in a planting medium (Scotts Company, 14111 Scottslawn Road, Marysville, Ohio 43041) containing peat moss, vermiculite, a wetting agent and starter nutrients and treated post-emergence with the test compound formulated in the same manner. Plants ranging from 2 to 18 cm in height (one to four leaf stages) were used for post-emergence treatments.

[0700] Plant species in the flooded paddy field test consisted of rice (Oryza sativa), Cyperus difformis, Heteranthera limosa, and Echinochloacrus-galli grown to the 2-leaf stage for testing. For treatment, the test pots were filled with water to 3 cm above the soil surface, and the test compounds were applied directly to the field water for treatment, and then the water depth was maintained during the test period.

[0701] Treated plants and controls were maintained in a greenhouse for 13 to 15 days, after which all species were compared to controls and visually assessed. Plant response scores summarized in Table D were based on a 0 to 100 scale, with 0 being no effect and 100 being complete control. Responses with a dash (-) indicate no test results.

[0702]

[0703]

[0704]

[0705]

[0706]

[0707]

[0708]

[0709]

[0710]

[0711]

[0712]

[0713]

[0714]

[0715]

[0716]

[0717] Test E

[0718] The selected herbs are annual bluegrass (Poa annua), blackgrass (Alopecurus myosuroides), canary grass (Phalaris minor), common chickweed (Stellaria media), catchweed bedstraw (Galium aparine), hairy white dew grass (Bromus tectorum), field poppy (Papaver rhoeas), field violet (Viola arvensis), green foxtail (Setaria viridis), henbit deadnettle (Lamium amplexicaule), Italian ryegrass (Lolium multiflorum), Kochia scoparia, quinoa (Chenopodium album), rapeseed (Brassica napus), wild amaranth (Amaranthus retroflexus), scentless chamomile (Matricaria inodora), bird's-eye speedwell (Veronica persica), spring barley (Hordeum vulgare), spring wheat (Triticum aestivum), wild buckwheat (Polygonum convolvulus), wild mustard (Sinapisarvensis), wild oats (Avena fatua), wild radish (Raphanus raphanistrum), wind shear grass (Aperaspica-venti), winter barley (Hordeum vulgare), and winter wheat (Triticum aestivum) were planted in silt loam soil and treated pre-emergence with the test compound formulated in a non-phytotoxic solvent mixture containing a surfactant. Plants were potted in potting medium (Scotts Company, 14111 Scottslawn Road, Marysville, Ohio 43041) containing peat moss, vermiculite, a wetting agent and starter nutrients and treated post-emergence with the test compound formulated in the same manner. Plant heights ranged from 2 to 18 cm (1- to 4-leaf stages).

[0719] Treated plants and controls were maintained in a controlled growth environment for 7 to 21 days, after which all species were compared to controls and visually assessed. Plant response scores summarized in Table E were based on a 0 to 100 scale, with 0 being no effect and 100 being complete control. Responses with a dash (-) indicate no test results.

[0720]

[0721]

[0722]

[0723]

[0724]

[0725]

[0726] Test F

[0727] The grass is selected from the group consisting of Zea mays, Glycine max, Abutilon theophrasti, Chenopodium album, Euphorbia heterophylla, Amaranthus palmeri, Amaranthus rudis, Brachiaria decumbens, Digitaria sanguinalis, Digitaria horizontalis, Panicum dichotomiflorum, Setaria faberii, Setaria viridis, Eleusine indica, Sorghum halepense, Ambrosia elatior, Echinochloa crus-galli, Southern sandbur, Cenchrus Seeds of the plant species of Echinatus, Sida rhombifolia, Lolium multiflorum, Virginia (VA) dayflower, Commelina virginica, Convolvulus arvensis, common cocklebur, Xanthium strumarium, Ipomoea coccinea, eastern black nightshade, Solanum ptycanthum, Kochia scoparia, Cyperus esculentus and Bidens pilosa are planted in silt loam soil and treated pre-emergence with the test compound formulated in a non-phytotoxic solvent mixture comprising a surfactant.

[0728] At the same time, plants from these crops and weed species as well as waterhemp_RES1 (ALS & triazine resistant Amaranthus rudis) and waterhemp_RES2 (ALS & HPPD resistant Amaranthus rudis) were treated with a post-emergence application of the test compound formulated in the same manner. Plant heights for post-emergence treatments ranged from 2 to 18 cm (1- to 4-leaf stage).

[0729] Treated plants and controls were maintained in the greenhouse for 14 to 21 days, after which all species were compared to controls and visually assessed. Plant response scores summarized in Table F were based on a 0 to 100 scale, with 0 being no effect and 100 being complete control. Responses with a dash (-) indicate no test results.

[0730]

[0731]

[0732]

[0733]

[0734]

[0735]

[0736]

[0737] Test G

[0738] For each application rate, three plastic pots (about 16 cm in diameter) were partially filled with sterilized Tama silt loam soil containing sand, silt and clay in a ratio of 35:50:15 and 2.6% organic matter. The following are individual plants in each of the three pots. For each application rate, seeds of Monochoria vaginalis, Cyperus difformis, Scirpus juncoides and Ammannia coccinea (purple redstem) from the United States were sown in a 16-cm pot. For each application rate, seeds of Cyperus iria, Leptochloa fascicularis, a cluster of 9 or 10 water-seeded rice seedlings (Indica rice, Oryza sativa), and two clusters of 3 or 4 transplanted rice seedlings (Oryza sativa cv. 'Japonica-M202') from the United States were planted in a 16 cm pot. For each application rate, seeds of Echinochloa crus-galli and Echinochloa oryzicola were planted in a 16 cm pot. Planting was sequential so that the crop and weed species were at the 2.0 to 2.5 leaf stage at the time of treatment.

[0739] The potted plants were grown in a greenhouse with a day / night temperature set at 30 / 27°C and supplemental balanced lighting provided to maintain a 16-hour photoperiod. The test pots were kept in the greenhouse until the end of the test.

[0740] During treatment, the test pots were filled with water to 3 cm above the soil surface, and the test compound was applied directly to the field water for treatment, and then the water depth was maintained during the test. The treatment effect of rice and weeds was visually evaluated by comparison with untreated controls after 21 days. The plant response scores summarized in Table G are based on a scale of 0 to 100, where 0 is no effect and 100 is complete control. The response of a dash (-) indicates no test result.

[0741]

[0742]

Claims

1. A method for preparing a compound of formula 1, in Q is and connected to Formula 1 through a carbon atom at the 5-position; r is 1; Z is O; R 1 is halogen, cyano, CHO, C1-C4 alkyl, C2-C4 alkenyl, C2-C4 alkynyl, C1-C4 alkoxy, C3-C4 alkenyloxy, C3-C4 alkynyloxy, C1-C4 haloalkyl, C1-C4 haloalkoxy, C2-C4 alkoxyalkyl, C2-C4 alkylthioalkyl or SO n R 1A ; Each n is independently 0, 1 or 2; R 2 is halogen, C1-C4 alkyl or C1-C4 haloalkyl; m is 0, 1 or 2; Each R 3 are independently halogen, cyano, hydroxyl, nitro, amino, CHO, C1-C4 alkyl, C2-C4 alkenyl, C2-C4 alkynyl, C(=O)N(R 3A )(R 3B )、C(=NOR 3C )H、C(=N)(R 3D )H, C1-C4 alkoxy, C2-C4 cyanoalkoxy, C2-C4 alkylcarbonyl, C2-C4 alkoxycarbonyl, C2-C4 alkylcarbonyloxy, C2-C4 alkoxyalkyl, C1-C4 haloalkyl, C1-C4 haloalkoxy, SO n R 3E or C3-C6 cycloalkyl; Each R 3 connected to Formula 1 at the 3-, 4-, or 6-position; R 1A is C1-C4 alkyl or C1-C4 haloalkyl; R 3E is a C1-C4 alkyl group; R 3A is a C1-C4 alkyl group; R 3B is H or C1-C4 alkyl; R 3C is H or C1-C4 alkyl; and R 3D is H or C1-C4 alkyl, The method comprises heating a compound of formula 2 in the presence of a base in a suitable solvent: in Q is and connected to Formula 1 through a carbon atom at the 5-position, r is 1; Z is O; R A is H; R 1 is halogen, cyano, CHO, C1-C4 alkyl, C2-C4 alkenyl, C2-C4 alkynyl, C1-C4 alkoxy, C3-C4 alkenyloxy, C3-C4 alkynyloxy, C1-C4 haloalkyl, C1-C4 haloalkoxy, C2-C4 alkoxyalkyl, C2-C4 alkylthioalkyl or SO n R 1A ; Each R 3 are independently halogen, cyano, hydroxyl, nitro, amino, CHO, C1-C4 alkyl, C2-C4 alkenyl, C2-C4 alkynyl, C(=O)N(R 3A )(R 3B )、C(=NOR 3C )H、C(=N)(R 3D )H, C1-C4 alkoxy, C2-C4 cyanoalkoxy, C2-C4 alkylcarbonyl, C2-C4 alkoxycarbonyl, C2-C4 alkylcarbonyloxy, C2-C4 alkoxyalkyl, C1-C4 haloalkyl, C1-C4 haloalkoxy, SO n R 3E or C3-C6 cycloalkyl; Each R 3 connected to Formula 2 at the 3-, 4-, or 6-position; R 1A is C1-C4 alkyl or C1-C4 haloalkyl; R 3E is a C1-C4 alkyl group; R 3A is a C1-C4 alkyl group; R 3B is H or C1-C4 alkyl; R 3C is H or C1-C4 alkyl; and R 3D is H or C1-C4 alkyl, With the compound of formula 3: in LG is a halogen or SO2CH3; and R 2 is halogen, C1-C4 alkyl, or C1-C4 haloalkyl.

2. The method according to claim 1, wherein in the compound of formula 1, R 1 is halogen, cyano, C1-C4 alkyl, C1-C4 alkoxy, C1-C4 haloalkyl, C1-C4 haloalkoxy or SCF3; R 2 is halogen or C1-C4 alkyl; Each R 3 are independently halogen, cyano, amino, C1-C4 alkyl, C2-C4 alkenyl, C2-C4 alkynyl, C1-C4 alkoxy, C2-C4 alkoxycarbonyl, C2-C4 alkylcarbonyloxy, C2-C4 alkoxyalkyl or C1-C4 haloalkyl; m is 0 or 1; and Each R 3 connected to Formula 1 at the 3- or 4-position, and In the compound of formula 2, R 1 is halogen, cyano, C1-C4 alkyl, C1-C4 alkoxy, C1-C4 haloalkyl, C1-C4 haloalkoxy or SCF3; Each R 3 are independently halogen, cyano, amino, C1-C4 alkyl, C2-C4 alkenyl, C2-C4 alkynyl, C1-C4 alkoxy, C2-C4 alkoxycarbonyl, C2-C4 alkylcarbonyloxy, C2-C4 alkoxyalkyl or C1-C4 haloalkyl; m is 0 or 1; and Each R 3 connected to Formula 1 at the 3- or 4-position, and In the compound of formula 3, R 2 It is halogen or C1-C4 alkyl.

3. The method according to claim 2, wherein in the compound of formula 1, R 1 is halogen, C1-C4 haloalkyl or C1-C4 haloalkoxy; R 2 is halogen or CH3; Each R 3 are independently halogen, cyano, amino, C1-C4 alkyl, C2-C4 alkenyl, C2-C4 alkynyl, C1-C4 alkoxy, C2-C4 alkoxycarbonyl, C2-C4 alkylcarbonyloxy, C2-C4 alkoxyalkyl or C1-C4 haloalkyl; m is 0 or 1; and Each R 3 connected to Formula 1 at the 3- or 4-position, and In the compound of formula 2, R 1 is halogen, C1-C4 haloalkyl or C1-C4 haloalkoxy; R 2 is halogen or CH3; Each R 3 are independently halogen, cyano, amino, C1-C4 alkyl, C2-C4 alkenyl, C2-C4 alkynyl, C1-C4 alkoxy, C2-C4 alkoxycarbonyl, C2-C4 alkylcarbonyloxy, C2-C4 alkoxyalkyl or C1-C4 haloalkyl; m is 0 or 1; and Each R 3 connected to Formula 1 at the 3- or 4-position, and In the compound of formula 3, R 2 It is halogen or C1-C4 alkyl.

4. The method according to claim 1, wherein in the compound of formula 3, LG is a halogen.

5. The method according to claim 2, wherein in the compound of formula 3, LG is halogen.

6. The method according to claim 1, wherein in the compound of formula 3, LG is SO2CH3.

7. The method according to claim 2, wherein in the compound of formula 3, LG is SO2CH3.

8. The method according to claim 1, wherein the compound of formula 1 is selected from: 2-[2-(3-bromo-5-isoxazolyl)phenoxy]-5-chloropyrimidine, 5-chloro-2-[2-[3-(difluoromethyl)-5-isoxazolyl]phenoxy]pyrimidine, 5-chloro-2-[2-[3-(trifluoromethyl)-5-isoxazolyl]phenoxy]pyrimidine, 5-chloro-2-[2-[3-(difluoromethyl)-5-isoxazolyl]-3-fluorophenoxy]pyrimidine, 5-bromo-2-[2-[3-(difluoromethyl)-5-isoxazolyl]-3-fluorophenoxy]pyrimidine, 5-chloro-2-[2-[3-(trifluoromethyl)-5-isoxazolyl]-3-chlorophenoxy]pyrimidine, 5-chloro-2-[2-[3-(trifluoromethyl)-5-isoxazolyl]-3-fluorophenoxy]pyrimidine, 5-chloro-2-[2-[3-(difluoromethyl)-5-isoxazolyl]-3-chlorophenoxy]pyrimidine, 5-bromo-2-[2-[3-(difluoromethyl)-5-isoxazolyl]-3-chlorophenoxy]pyrimidine, 5-bromo-2-[2-[3-(trifluoromethyl)-5-isoxazolyl]-3-chlorophenoxy]pyrimidine, and 5-chloro-2-[2-[3-(difluoromethyl)-5-isoxazolyl]-3-bromophenoxy]pyrimidine.

9. The compound is 2-(3-difluoromethyl-5-isoxazolyl)-3-fluorophenol.

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