WO1996031517A1 - Herbicidal heteroaryl-substituted anilides - Google Patents

Abstract

Compounds of formula (I), and their -oxides and agriculturally-suitable salts, are disclosed which are useful for controlling undesired vegetation. In said formula, Q is (Q-1), (Q-2), (Q-3), T is O or S; X is a single bond, O, S, or NR5; Y is O, S, NR6, -CH=CH-, or -CH=N-, where the -CH=N- can be attached in either possible orientation; Z is CH or N; W is CH or N; V is CH, CCH¿3? or N, provided that V is CH or CCH3 when W is CH; n is 0 or 1; and R?1-R6¿ are as defined in the disclosure. Also disclosed are compositions containing the compounds of formula (I) and a method for controlling undesired vegetation which involves contacting the vegetation or its environment with an effective amount of a compound of formula (I).

Description

TITLE

HERBICIDAL HETEROARYL-SUBSTITUTED ANILIDES

BACKGROUND OF THE INVENTION

This invention relates to certain heteroaryl-substituted anilides, their N-oxides, agriculturally-suitable salts of the anilides and compositions, and methods of their use for controlling undesirable vegetation.

The control of undesired vegetation is extremely important in achieving high crop efficiency. Achievement of selective control of the growth of weeds especially in such useful crops as rice, soybean, sugar beet, com (maize), potato, wheat, barley, tomato and plantation crops, among others, is very desirable. Unchecked weed growth in such useful crops can cause significant reduction in productivity and thereby result in increased costs to the consumer. The control of undesired vegetation in noncrop areas is also important. Many products are commercially available for these purposes, but the need continues for new compounds which are more effective, less costly, less toxic, environmentally safer or have different modes of action.

WO 93/11097 discloses anilides of Formula i as herbicides:

wherein

Q is, among others, Q-1

R is, among others, C₁-C₂ haloalkyl, C₁-C₂ haloalkoxy, C₁-C₂ haloalkylthio,

halogen, cyano, or nitro;

Y is ΝR⁷C(O)XR³;

X is a single bond, O, S or NR⁴;

R¹ is, among others, H, C₁-C₃ alkyl, C₁-C₃ alkoxy, C₁-C₃ alkylthio, C₂-C₃

alkoxyalkyl, C₂-C₃ alkylthioalkyl, halogen, NO₂, CN, NHR⁵ or NR⁵R⁶; and R³ is, among others, C₁-C₅ alkyl optionally substituted with C₁-C₂ alkoxy, OH, 1-3 halogen, or C₁-C₂ alkylthio; CH₂(C₃-C₄ cycloalkyl); C₃-C₄ cycloalkyl optionally substituted with 1-3 CH₃'s; C₂-C₄ alkenyl; or C₂-C₄ haloalkenyl. The heteroaryl-substituted anilides of the present invention are not disclosed therein.

SUMMARY OF THE INVENTION

This invention is directed to compounds of Formula I, geometric isomers, stereoisomers, N-oxides, and agriculturally suitable salts thereof as well as agricultural compositions containing them and their use for controlling undesirable vegetation:

T is O or S;

X is a single bond, O, S, or ΝR⁵;

Y is O, S, ΝR⁶, -CH=CH-, or -CH=Ν-, where the -CH=N- can be attached in either possible orientation;

Z is CH or N;

W is CH or N;

V is CH, CCH₃ or N, provided that V is CH or CCH₃ when W is CH;

R¹ is C₁-C₅ alkyl optionally substituted with C₁-C₂ alkoxy, OH, 1-7 halogen, or C₁-C₂ alkylthio; CH₂(C₃-C₄ cycloalkyl); C₃-C₆ cycloalkyl optionally substituted with 1-3 halogen or 1-4 methyl groups; C₂-C₄ alkenyl; C₂-C₄ haloalkenyl; or phenyl optionally substituted with C₁-C₄ alkyl, C₁-C₄ haloalkyl, C₁-C₄ alkoxy, 1-2 halogen, nitro, or cyano; provided that when X is O, S, or NR⁵, then R¹ is other than C₂ alkenyl and C₂ haloalkenyl;

R² is H, halogen, C₁-C₂ alkyl, C₁-C₂ alkoxy, C₁-C₂ alkylthio, C₂-C₃ alkoxyalkyl, C₂-C₃ alkylthioalkyl, cyano, nitro, NH(C₁-C₂ alkyl), or N(C₁-C₂ alkyl)₂; R³ is H, halogen, C₁-C₂ alkyl, C₁-C₂ alkoxy, C₁-C₂ alkylthio, C₂-C₃ alkoxyalkyl,

C₂-C₃ alkylthioalkyl, cyano, nitro, NH(C₁-C₂ alkyl), or N(C₁-C₂ alkyl)₂; R⁴ is C₁-C₄ haloalkyl, C₁-C₂ haloalkoxy, C₁-C₄ haloalkylthio, C₁-C₄ alkylsulfonyl, C₁-C₂ haloalkylsulfonyl, halogen, cyano, or nitro;

R⁵ is H, CH₃, or OCH₃;

R⁶ is H or CH₃; and

n is 0 or 1.

In the above recitations, the term "alkyl", used either alone or in compound words such as "alkylthio" or "haloalkyl" includes straight-chain or branched alkyl, such as, methyl, ethyl, n-propyl, i-propyl, or the different butyl or pentyl isomers. The term "1-4 methyl groups" indicates that one to four of the available positions for that substituent may be methyl. "Alkenyl" includes straight-chain or branched alkenes such as vinyl, 1 -propenyl, 2-propenyl, and the different butenyl isomers. "Alkenyl" also includes polyenes such as 1,2-propadienyl. "Alkoxy" includes, for example, methoxy, ethoxy, n-propyloxy, isopropyloxy and the different butoxy isomers. "Alkoxyalkyl" denotes alkoxy substitution on alkyl. Examples of "alkoxyalkyl" include CH₃OCH₂,

CH₃OCH₂CH₂ and CH₃CH₂OCH₂. "Alkylthio" includes branched or straight-chain alkylthio moieties such as methylthio, ethylthio, and the different propylthio and butylthio isomers. "Alkylthioalkyl" denotes alkylthio substitution on alkyl. Examples of

"alkylthioalkyl" include CH₃SCH₂, CH₃SCH₂CH₂ and CH₃CH₂SCH₂. Examples of "alkylsulfonyl" include CH₃S(O)₂, CH₃CH₂S(O)₂, CH₃CH₂CH₂S(O)₂, (CH₃)₂CHS(O)₂ and the different butylsulfonyl isomers. "Cycloalkyl" includes, for example, cyclopropyl, cyclobutyl, cyclopentyl, and cyclohexyl. One skilled in the art will appreciate that not all nitrogen containing heterocycles can form N-oxides since the nitrogen requires an available lone pair for oxidation to the oxide; one skilled in the art will recognize those nitrogen containing heterocycles which can form N-oxides.

The term "halogen", either alone or in compound words such as "haloalkyl", includes fluorine, chlorine, bromine or iodine. The term "1-7 halogen" indicates that one to seven of the available positions for that substituent may be halogen which are independently selected; the terms "1-3 halogen" and "1-2 halogen" are defined

analogously. Further, when used in compound words such as "haloalkyl", said alkyl may be partially or fully substituted with halogen atoms which may be the same or different. Examples of "haloalkyl" include F₃C, ClCH₂, CF₃CH₂ and CF₃CCl₂. The terms "haloalkenyl", "haloalkoxy", and the like, are defined analogously to the term

"haloalkyl". Examples of "haloalkenyl" include (Cl)₂C=CHCH₂ and CF₃CH=CHCH₂. Examples of "haloalkoxy" include CF₃O, CCl₃CH₂O, HCF₂CH₂CH₂O and CF₃CH₂O. Examples of "haloalkylthio" include CCl₃S, CF₃S, CCl₃CH₂S and ClCH₂CH₂CH₂S. Examples of "haloalkylsulfonyl" include CF₃S(O)₂, CCl₃S(O)₂, CF₃CH₂S(O)₂ and CF₃CF₂S(O)₂.

The total number of carbon atoms in a substituent group is indicated by the "C_i-C_j" prefix where i and j are numbers from 1 to 5. For example, C₁-C₃ alkylsulfonyl designates methylsulfonyl through propylsulfonyl; C₂ alkoxyalkyl designates CH₃OCH₂; and C₃ alkoxyalkyl designates, for example, CH₃CH(OCH₃), CH₃OCH₂CH₂ or CH₃CH₂OCH₂.

When a group contains a substituent which can be hydrogen, for example R² or R⁵, then, when this substituent is taken as hydrogen, it is recognized that this is equivalent to said group being unsubstituted.

Compounds of this invention can exist as one or more stereoisomers. The various stereoisomers include enantiomers, diastereomers, atropisomers and geometric isomers. One skilled in the art will appreciate that one stereoisomer may be more active and/or may exhibit beneficial effects when enriched relative to the other stereoisomer(s) or when separated from the other stereoisomer(s). Additionally, the skilled artisan knows how to separate, enrich, and/or to selectively prepare said stereoisomers. Accordingly, the present invention comprises compounds selected from Formula I, N-oxides and agriculturally suitable salts thereof. The compounds of the invention may be present as a mixture of stereoisomers, individual stereoisomers, or as an optically active form.

The salts of the compounds of the invention include acid-addition salts with inorganic or organic acids such as hydrobromic, hydrochloric, nitric, phosphoric, sulfuric, acetic, butyric, fumaric, lactic, maleic, malonic, oxalic, propionic, salicylic, tartaric, 4-toluenesulfonic or valeric acids. The salts of the compounds of the invention also include those formed with organic bases (e.g., pyridine, ammonia, or triethylamine) or inorganic bases (e.g., hydrides, hydroxides, or carbonates of sodium, potassium, lithium, calcium, magnesium or barium) when the compound contains an acidic group.

Preferred compounds for reasons of better activity and/or ease of synthesis are: Preferred 1. Compounds of Formula I above, and N-oxides and

agriculturally-suitable salts thereof, wherein: R¹ is C₁-C₄ alkyl optionally substituted with methoxy or 1-3 halogen; C₃-C₄ cycloalkyl optionally substituted with one methyl group; C₂-C₄ alkenyl; or C₂-C₄ haloalkenyl;

R² is chlorine, bromine, C₁-C₂ alkyl, C₁-C₂ alkoxy, cyano, nitro,

NH(C₁-C₂ alkyl), or N(C₁-C₂ alkyl)₂; and

R³ is H.

Preferred 2: Compounds of Preferred 1 wherein:

X is a single bond; and

R⁴ is C₁-C₂ haloalkyl, C₁-C₂ haloalkoxy, C₁-C₂ haloalkylthio, chlorine, or bromine.

Preferred 3: Compounds of Preferred 2 wherein:

Q is Q-1.

Preferred 4: Compounds of Preferred 2 wherein:

Q is Q-2.

Preferred 5: Compounds of Preferred 2 wherein:

Q is Q-3.

Most preferred are compounds of Preferred 2 selected from the group:

3-methyl-N-[4-methyl-2-[2-(trifluoromethyl)thiazolo[3,2- b] [1,2,4]triazol-6- yl]phenyl]butanamide;

N-[4-methyl-2-[2-(trifluoromethyl)thiazolo[3,2-b][1,2,4]triazol-6- yl]phenyl]cyclopropanecarboxamide;

2-methyl-N-[4-methyl-2-[3-(trifluoromethyl)-1H-pyrazol-1- yl]phenyl]propanamide;

N-[4-methyl-2-[3-(trifluoromethyl)-1H-pyrazol-1- yl]phenyl]cyclopropanecarboxamide;

3-methyl-N-[4-methyl-2-[3-(trifluoromethyl)- 1H-pyrazol- 1 - yl]phenyl]butanamide;

2-methyl-N-[4-methyl-2-[[3-(trifluoromethyl)-1H-pyrazol-1- yl]methyl]phenyl]propanamide; and

2,2-dimethyl-N-[4-methyl-2-[3-(trifluoromethyl)-1,2,4-triazolo[4,3-b]pyridazin-

6-yl]phenyl]propanamide.

This invention also relates to herbicidal compositions comprising herbicidally effective amounts of the compounds of the invention and at least one of a surfactant, a solid diluent or a liquid diluent. The preferred compositions of the present invention are those which comprise the above preferred compounds. This invention also relates to a method for controlling undesired vegetation comprising applying to the locus of the vegetation herbicidally effective amounts of the compounds of the invention (e.g., as a composition described herein). The preferred methods of use are those involving the above preferred compounds.

DETAILS OF THE INVENTION

The compounds of Formula I can be prepared by one or more of the following methods and variations as described in Schemes 1-34. The definitions of Q, T, X, Y, Z, W, V, R ¹-R⁶ and n in the compounds of Formulae 1-48 below are as defined above in the Summary of the Invention. Compounds of Formulae la-Ic are various subsets of the compounds of Formula I, and all substituents for Formulae la-Ic are as defined above for Formula I.

Scheme 1 illustrates the preparation of compounds of Formula la where T = O whereby substituted phenyl compounds of Formula la wherein X² is trialkyltin (e.g., Me₃Sn), trialkylsilyl (e.g., Me₃Si), or a boronic acid derivative (e.g., B(OH)₂) are coupled with heterocycles of Formula 2a wherein X¹ is chlorine, bromine, iodine or trifluoromethylsulfonyloxy (OTf). The coupling is carried out by methods known in the art: for example, see Tsuji, J., Organic Synthesis with Palladium Compounds,

Springer- Veriag, Berlin (1980); Negishi, E., Ace. Chem. Res. (1982), 15, 340; Stille, J. K., Angew. Chem. (1986), 98, 504; Yamamoto, A. and Yamagi, A., Chem. Pharm. Bull. (1982), 30, 1731 and 2003; Dondoni et al., Synthesis (1987), 185; Dondoni et al., Synthesis (1987), 693; Hoshino et al., Bull. Chem. Soc. Jpn. (1988), 61, 3008; Sato, M. et al., Chem. Lett. (1989), 1405; Miyaura et al., Synthetic Commun. (1981), 11, 513; Siddiqui and Sniekus, Tetrahedron Lett. (1988), 29, 5463; Sharp at al., Tetrahedron Lett. (1987), 28, 5093; Hatanaka et al., Chem. Lett. (1989), 1711; Bailey, T. R.,

Tetrahedron Lett. (1986), 27, 4407; Echavarren, A. M. and Stille, J. K., J. Am. Chem. Soc. (1987), 109, 5478; and Ali et al., Tetrahedron Lett. (1992), 48, 8117. The coupling of la and 2a is carried out by heating the mixture in the presence of a transition metal catalyst such as tetrakis(triphenylphosphine) palladium(0) or bis(triphenylphosphine)- palladium (II) dichloride in a solvent such as toluene, acetonitrile, glyme, or tetrahydrofuran optionally in the presence of an aqueous inorganic base such as sodium hydrogen carbonate or an organic base such as triethylamine. One skilled in the art will recognize that when 2a contains more than one reactive substituent, then the stoichiometric ratios of reagents will need to be adjusted to minimize bis-coupling.

Conversely, the anilides of Formula la where T = O can be prepared by reversing the reactivity of the two substrates. Substituted phenyl compounds of Formula 1b wherein X² is chlorine, bromine, iodine or trifluoromethylsulfonyloxy (OTf) can be coupled with heteroaromatic compounds of Formula 2b wherein X¹ is trialkyltin (e.g., Me₃Sn), trialkylsilyl (e.g., Me₃Si), or a boronic acid derivative (e.g., B(OH)₂). The procedure for conducting the coupling is the same as those described and referenced above.

By methods also reported in the above cited literature, compounds of Formula la and 2b are prepared by treating the corresponding halide (i.e., wherein X¹ and X² is bromine or iodine) with a metalating agent such as n-butyllithium followed by quenching with a trialkyltin halide, trialkylsilyl halide, boron trichloride, or trialkyl borate.

Some compounds of Formula la can also be prepared from the corresponding ort ho-unsubstituted compound (i.e., wherein X² is hydrogen) by treatment with a base such as n-butyllithium followed by quenching with a trialkyltin halide, trialkylsilyl halide, or trialkyl borate as reported in the same literature references. This preparation requires that -NHC(=O)XR¹ is an ortho-metalaύon directing group known in the art (e.g., trimethylacetylamido): see for example, Fuhrer, W., J. Org. Chem. (1979), 44, 1133.

Anilides and heteroaromatics of Formulae 1 and 2 wherein X¹ and X² are chlorine, bromine, iodine, OTf, and hydrogen are either known or readily prepared by procedures and techniques well known in the art, for example: D. E. Pereira, et al., Tetrahedron (1987), 43, 4931-4936; K. Senga, et al., J. Med. Chem. (1981), 24, 610-613;

T. Novinson, et al., J. Med. Chem. (1976), 19, 512-516; Makisumi, K., Chem. Pharm. Bull. (1959), 7, 907, 909; Sirakawa, Yakugaku Zasshi (1959), 79, 903, 907;

J. J. Kaminski, et al., J. Med. Chem. (1987), 30, 2047-2051; E. S. Hand, et al., J. Org. Chem. (1980), 45, 3738-3745; Finkelstein, B. L., J. Org. Chem. (1992), 57, 5538-5540; Tschitschibabin, D. R. P. 464,481; C. Sablayrolles, et al., J. Med. Chem. (1984), 27, 206-212; Vercek et al., Tetrahedron Lett. (1974), 4539; and S. Polanc, et al., J. Org. Chem. (1974), 39, 2143-2147.

Compounds of Formula la can also be prepared by one skilled in the art from anilines of Formula 3 by treatment with an appropriate acyl chloride or acid anhydride (T = O, X = direct bond), chloroformate (T = O, X = O), chlorothiolformates (T = O, X = S), carbamoyl chloride (T = O, X = NR⁵), isothiocyanate (T = S, X = NH), isocyanate (T = O, X = NH) or xanthyl chlorides (T = S, X = S) under conditions well known in the literature, for example: Sandier, R. S. and Karo, W., Organic Functional Group Preparations, 2nd Edition, Vol. I, p 274 and Vol. II, pp 152, 260, Academic Press (Scheme 2).

Alternatively, anilines of Formula 3 can be converted into the corresponding isocyanate by treatment with phosgene or known phosgene equivalents

(e.g., ClC(=O)OCCl₃), and then condensed with an appropriate alcohol or amine of Formula 4 to afford anilides of Formula la (Scheme 3). These techniques are well known in the literature. For example, see Sandier, R. S. and Karo, W., Organic

Functional Group Preparations, 2nd Edition, Vol. II, 152, 260, Academic Press; Lehman, G. and Teichman, H. in Preparative Organic Chemistry, 472, Hilgetag, G. and Martini, A., Eds., John Wiley & Sons, New York, (1972); Eckert, H. and Forster, B., Angew. Chem., Int. Ed. (1987), 26, 894; Babad, H. and Zeiler, A. G., Chem. Rev.

(1973), 73, 75.

In some cases, it is desirable to perform the palladium coupling reaction on an N-protected form of the aniline, for example the 2,2-dimethylpropanamide. Upon completion of the coupling reaction, the N-protecting group can be removed, for example by treatment of the 2,2-dimethylpropanamide with acid, to liberate the amino group.

Anilines of Formula 3 are readily prepared by palladium catalyzed coupling of an ørt/tø-substituted nitrophenyl compound of Formula 5a, wherein X² is as defined above, with a heteroaromatic compound of Formula 2a, wherein X¹ is as defined above, followed by catalytic or chemical reduction of the nitro group (Scheme 4). As described for Scheme 1, the reactivity of the substrates can be reversed, i.e., the coupling is carried out using an ortho-substituted nitrophenyl compound of Formula 5b and a

heteroaromatic compound of Formula 2b.

Reduction of nitro groups to amino groups is well documented in the chemical literature. See for example, Ohme, R. and Zubek, A. R. and Zubek, A. in Preparative Organic Chemistry, 557, Hilgetag, G. and Martini, A., Eds., John Wiley & Sons, New York: (1972).

In other cases, it is advantageous to prepare compounds of Formula 3, not by the cross-coupling methods described above, but rather by elaboration of a ortho-substituted nitrophenyl compound of Formula 6, under any of a number of ring closure

methodologies (Scheme 5). Subsequent reduction of the nitro compounds of Formula 7 provides compounds of Formula 3.

wherein

X³ can be any of a number of heterocycle building blocks, including, but not

limited to those shown below:

X³ = COCH₂NH₂, COCH₂-halogen,

Compounds of Formula 6 are well known in the art or may be made by simple functional group interconversions on ortho-substituted nitrophenyl compounds. Numerous methods for conversion of these X³ substituents into Q-l heterocycles are well known in the literature and can be applied by those skilled in the art for the preparation compounds of Formula 7. For example, see Katritzky, A. R. and

Rees, C. W., Comprehensive Heterocyclic Chemistry, Vol. 6, pp. 992-993, Pergamon Press, London (1984); Flament et al., Helv. Chim. Acta. (1977), 60, 1872-1882; Kasuga et al., Yakugaku Zasshi (1974), 94, 952-962; E. Abignente, et al., J. Heterocycl. Chem. (1986), 23, 1031-1034; O. Chavignon, et al., J. Heterocycl. Chem. (1992), 29, 691-697; Buchan et al., J. Org. Chem. (1977), 42, 2448-2451; Allen et al. J. Org. Chem. (1959), 24, 796-801; Balicki, R., Pol. J. Chem. (1983), 57, 1251-1261; J. P. Dusza, et al., U.S. 4178449; D. W. Hansen Jr., et al., World Patent Publication WO 91/08211; M. L. Bode, et al., J. Chem. Soc, Perkin Trans. 1 (1993), 1809-1813; I. Anitha, et al., J. Indian Chem. Soc. (1989), 66, 460-462; Y. Tominaga, et al., J. Heterocycl. Chem. (1989), 26, 477-487; S. Branko, et al., J. Heterocycl. Chem. (1993), 30, 1577; M. Mukoyama, Jpn. Kokai Tokkyo Koho JP 06 16667; Y.Tominaga, et al., Heterocycles (1988), 27, 2345-2348; P. L. Anderson, et al., J. Heterocycl. Chem. (1981), 18, 1149-1152; F. Compernolle, et al., J. Heterocycl. Chem. (1986), 23, 541-544; L. F. Miller, et al., J. Org. Chem. (1973), 38, 1955-1957; R. Faure, et al., Tetrahedron (1976), 32, 341-348; A. Terada, Eur. Pat. Appl. EP-A-353,047; Reid, D. H., J. Chem. Soc, Perkin Trans. 1 (1979), 2334-2339; J. C. Brindley, et al; J. Chem. Soc, Perkin Trans. 1 (1986),

1255-1259; R. L. Harris, et al., Aust. J. Chem. (1986), 39, 887-892; J. P. Henichart, et al., J. Heterocycl. Chem. (1986), 23, 1531-1533; I. A. Mazur, et al., Chem.

Heterocycl. Compd. (1970), 6, 474-476; I. A. Mazur, et al., Khim. Geterotsikl. Soedin. (1970), 512-514; Meakins, G. D., J. Chem. Soc, Perkin Trans. 1 (1989), 643-648; and E. Campaigne, et al., J. Heterocycl. Chem. (1978), 15, 401-411.

One skilled in the art will recognize that these same ring closure methodologies can be used to elaborate an σrtAø-substituted aniline of Formula 8, or a derivative thereof, into compounds of Formula 3 (Scheme 6). This strategy is illustrated in Examples 1 and 2.

wherein

X³ is as previously defined in Scheme 5.

Compounds of Formula 8 are well known in the art (see for example, H. Gunter, et al., Liebigs Ann. Chem. (1987), 765-770) or may be made by simple functional group interconversions on ortho-substituted anilines or a derivative thereof.

In some instances, it may be necessary, or more convenient, to introduce the desired substituents after the coupling reaction was performed. This can be

accomplished by electrophilic substitution (Scheme 7), or nucleophilic substitution and functional group modifications (Schemes 8 and 9) using procedures well documented in the literature.

l

Variation of the substituent R⁴ on the heterocycle Q- 1 of compounds of

Formula la may be achieved by one of three ways. First, one skilled in the art may simply select the appropriate heteroaromatic compound of Formula 2a,b for the palladium coupling in Schemes 1 and 4 to give examples with a variety of values for R⁴. Alternatively, it may at times be convenient to vary R⁴ by performing various functional group transformations on compounds of Formula 9, which can be prepared by the same methods for the preparation of the aryl-substituted heterocycles of Formula la, as shown in Scheme 8. Alternatively, it may at times be convenient to vary R⁴ by performing various functional group transformations on compounds of Formula 10, which can be prepared by the same methods for the preparation of the ørtλo-substituted nitrophenyl compounds of Formula 7, and then converting the product to compounds of Formula la (using methods discussed previously) as shown in Scheme 9. Methods to perform these transformations are well known in the literature. Some examples include conversion of chloro to bromo (L. J. Street, et al., J. Med. Chem. (1992), 35, 295-304), bromo to trifluoromethyl (J. Wrobel, et al., J. Med. Chem. (1989), 32(11), 2493-2500), cyano (Ellis, G. P., T. M. Romney- Alexander, Chem. Rev. (1987), 87, 779-794), aldehyde to difluoromethyl (Middleton, W. J., J. Org. Chem. (1975), 40, 574-578), thiol to trifluoromethylthio (Popov, V. I., Boiko, V. N., Yagupolskii, L. M., J. Fluor. Chem. (1982), 21, 365-369) and amino to a variety of substituents via the diazonium salts. Electrophilic aromatic substitution or metallation chemistry are also useful methods for incorporating certain substituents.

3 ₂

As shown in Scheme 10, compounds of Formula la where T = S can be prepared by one skilled in the art from compounds of Formula la where T = O by treatment with P₂S₅ or Lawesson's reagent under conditions well known in the literature, for example: T. P. Sychera, et al., J. Gen. Chem. U.S.S.R. (1962), 32, 2839; K. Yoshino, et al., J. Heterocycl. Chem. (1989), 26, 1039-1043; E. C. Taylor Jr., et al., J. Amer. Chem. Soc. (1953), 75, 1904; and O. P. Goel, et al., Synthesis-Stuttgart (1987), 2, 162-164.

Alternatively, anilines of Formula 3 can be converted into the corresponding isothiocyanate by treatment with thiophosgene or known thiophosgene equivalents (e.g., 1, 1'-thiocarbonyldiimidazole) and then condensed with an appropriate alcohol or amine of Formula 4 or a Grignard-reagent to afford compounds of Formula la where T = S (Scheme 11). These techniques are well known in the literature. For example, see Y. M. Zhang, et al., Tetrahedron Lett. (1987), 28, 3815-3816; Ares, J. J., Synthetic Commun. (1991), 21, 625-623; S. Roy, et al., Indian. J. Chem. B (1994), 33, 291-292; J. Garin, et al., J. Heterocycl. Chem. (1991), 28, 359-363; and I. Sircar, et al., J. Med. Chem. (1985), 28, 1405.

As shown in Scheme 12, compounds of Formula lb can be prepared by one skilled in the art from anilines of Formula 11 by treatment with an appropriate acyl chloride or acid anhydride (T = O, X = direct bond), chloroformate (T = O, X = O), chlorothiolformates (T = O, X = S), carbamoyl chloride (T = O, X = NR⁵),

isothiocyanate (T = S, X = NH) isocyanate (T = O, X = NH), or xanthyl chlorides (T = S, X = S) as described for Scheme 2.

Alternatively, anilines of Formula 11 can be converted into die corresponding isocyanate and then condensed with an appropriate alcohol or amine to afford anilides of Formula lb (Scheme 13). These techniques were described for Scheme 3.

Anilines of Formula 11 can be prepared by the reduction of compounds of

Formula 12 by methods well documented in the literature (Scheme 14). See for example, Ohme, R. and Zubek, A. R. and Zubek, A. in Preparative Organic Chemistry, 557; Hilgetag, G. and Martini, A. Eds., John Wiley & Sons, New York: (1972).

Many compounds of Formula 12 can be prepared by the introduction of the Q-2 substituent by displacement of an appropriate leaving group (X⁵) by the appropriate heterocycle of Formula 14 (Scheme 15).

In other cases, it is advantageous to prepare compounds of Formulae lb, 11, or 12 by elaboration of an appropriate substituent, X⁶ ortho to the amido, amino or nitro group, respectively. This strategy is illustrated in Scheme 16 for the preparation of compounds of Formula 12.

wherein X⁶ can be any number of substituents useful in the synthesis of nitrogen heterocycles, including, but not limited to those shown below:

X³ = NO₂, NH₂, NHNH₂, X⁵, CH₂X⁵, CHO, CO₂H, COCl, CN; and

X⁵ = Cl, Br, I, OTf.

Compounds of Formula 15 are well known in the art or may be made by simple functional group interconversions on ortho-substituted nitrobenzenes.

Some of the numerous methods for conversion of these X⁶ substituents into the

5-membered nitrogen heterocycles of Q-2 shown in Scheme 16 and the direct displacement reactions of Scheme 15 are illustrated below. Scheme 17 shows a direct displacement reaction with an appropriately substituted pyrrole of Formula 14. For example, see: Katritzky, A. R. and Rees, C. E., Eds., Comprehensive Heterocyclic Chemistry, Vol. 4, p. 235 ff., Pergamon Press, London (1984); Smith, L. R., Chem. Heterocycl. Compd. (1972), 25-2, 127; Santaniello, E., Farachi, C., Ponti, F., Synthesis (1979), 617; Jones, R. A. and Bean, G. P., The Chemistry of Pyrroles, Academic Press, London, 1977, Chapter 4, pp. 205-11;

Rubottom, G. M. and Chabala, J. C., Org. Synth. (1974), 54, 60.

The synthesis of the pyrrole ring system by ring construction is illustrated in Scheme 18 by one of the best procedures. This procedure and others are extensively reviewed in the literature: Katritzky, A. R. and Rees, C. E., Eds., Vol. 4, pp. 313-352, derivatives, pp 353-368, Pergamon, (1984); Kiedy, J. S., Huang, S., J. Heterocycl. Chem. (1987), 24, 1137; Hamdan, A., Wasley, J. W. F., Synth. Commun. (1983), 13, 741; Josey, A. D., Org. Synth. Coll. Vol. V(1973), 716.

Scheme 19 shows an alkylation reaction of an imidazole by compounds of Formula 13.

The reactions of Scheme 19 can be run by the methods of Ginda, W. C. and Mathre, D. J., J. Org. Chem. (1980), 45, 3172; Mathias, L. R. and Burkett, D., Tetrahedron Lett. (1979), 4709; Dorr, H. J. M. and Metzger, J., Bull. Soc. Chim. Fr. (1976), 1861; A. F. Pozharskii, et al., Zh. Obshch. Khim (1963), 33, 1005; (1964), 34, 1371; (Chem. Abstr. 59: 7515; 61: 1849; 65: 88955; 65: 13684).

The preparation of imidazole compounds of Formula 19 (wherein n = 0) by ring construction methods are well known in the literature. An illustrative example is shown in Scheme 20.

The method of Scheme 20 and many others are taught and reviewed in

Katritzky, A. R. and Boulton, A. J., Advances in Heterocyclic Chemistry, Vol. 12, pp 166-183, Academic, New York, 1970; Bacon, R. G. R. and Hamilton, S. D., J. Chem. Soc. Perkin Trans. I (1974), 1970, and Katritzky, A. R. and Rees, C. E., Comprehensive Heterocyclic Chemistry Vol. 5, pp 457-482, Pergamon, London, 1984.

Pyrazole compounds of Formula 23 can be prepared by direct displacement reactions as shown in Scheme 21.

N-alkylation and N-arylation are taught by Dorr, H. J. M., Elguero, J., Espada, M. and Hassanaly, P., An Quim. (1978), 74, 1137; Khan, M. A. and Lynch, B. M., J.

Heterocycl. Chem. (1970), 7, 1237; Elguero, J., Espada, M., Mathier, D. and

Lun, R. P. T., An Quim, (1979), 75, 729; Guida, W. C. and Mathre, D. J., J. Org. Chem. (1980), 45, 3172; J. Elguero, et al., Bull. Chem. Soc. Fr. (1970), 1121; (1968), 707, 5019; (1967), 1966, 619, 775, 2833, 3727; Khan, M. A., Rec Chem. Prog. (1970), 31, 43.

A synthesis of an N-aryl pyrazole by a ring construction method is illustrated in Example 3. Numerous other methods are reviewed in Katritzky, A. R. and Rees, C. E., Comprehensive Heterocyclic Chemistry, Vol. 5, p 272 ff.

The preparations of the 2-substituted-1,2,3-triazoles of this invention are reviewed by Katritzky, A. R. and Rees, C. E., Comprehensive Heterocyclic Chemistry, Vol. 5, p 690 ff., Pergamon, London, 1984; and Elderfield, R. E., Ed. Heterocyclic Compounds, Vol. 7, p 384, John Wiley & Sons, New York, 1961. One of the various syntheses is illustrated in Scheme 22.

This procedure and others are taught by Coles, R. F. and Hamilton, C. F., J. Am. Chem. Soc. (1946), 68, 1179; Riebsomer, J. L., J. Org. Chem. (1948), 13, 815; Stolle, R., Ber. (1926), 59, 1742; Finley, K. T., Chem. Heterocycl. Compd. (1980), 39, 1;

Carboni, R. A., Kauer, J. C., Hatcher, W. R., Harder, R. J., J. Amer. Chem. Soc. (1967), 89, 2626.

The preparation of the 1 -substituted -1,2,4-triazoles of Formula 28 by direct displacement reactions on compounds of Formula 13 are reviewed and taught in

Schofield, K., Grimmett, M. R. and Keene, B. R., Heteroaromatic Nitrogen

Compounds: TheAzoles, pp 735-757, Cambridge University, Cambridge, 1976; Potts, K. T., Chem. Rev. (1961), 61, 87; Kahn, M. A. and Polya, J. B., J. Chem. Soc. (C) (1970), 85.

Alternatively, the 1,2,4-triazole compounds of Formula 28 can be prepared by ring construction methods well known in the literature. An illustrative example is given in Scheme 23.

The method of Scheme 23 and many others are taught and reviewed in

Katritzky, A. R. and Rees, C. E., Comprehensive Heterocyclic Chemistry, Vol. 5, p 762 ff., Pergamon, London, 1984; K. Matsumoto, et al., Synthesis (1975), 609; Huisgen, R., Grashey, R., Aufderhaar, E., Kung, Z., Chem. Ber. (1965), 98, 642, Grundman, C. and Ratz, R., J. Org. Chem. (1956), 21, 1037.

The preparation of the 2-substituted tetrazoles of Formula 33 by direct

displacement on a compound of Formula 13 is reviewed and taught by Katritzky, A. R. and Rees, C. E., Comprehensive Heterocyclic Chemistry, Vol. 5, p 817 ff.; Pergamon, London, 1984; general alkylation - Butler, R. N., Garvin, V. C., and McEvoy, T. M., J. Chem. Res. (S) (1981), 174; benzylation - Doderhack, D., Chem. Ber. (1975), 108, 887; with activated aryl halides - Komecke, A., Lepom, P., and Lippmann, E., Z Chem. (1978), 81, 214.

The preparation of 2-substituted tetrazoles of Formula 33 by ring construction methods are well known in the literature. Dlustrative examples are shown in Scheme 24.

U. Saha, et al., J. Inst. Chem (India) (1980), 52, 196; Baldwin, J. E., J. Heterocycl. Chem. (1968), 5, 565; Hong, S.-Y. and Baldwin, J. E., Tetrahedron (1968), 24, 3787; Ito, S., Tanaka, Y., Kakehi, A. and Kondo, K., Bull. Chem. Soc. Jpn. (1976), 49, 1920.

Variation of the substituent R⁴ on the heterocycle Q-2 of compounds of

Formula lb may be achieved by one of two ways. First, one skilled in the art may simply select the appropriate heteroaromatic compound of Formula 14, in Scheme 15 to give examples with a variety of values for R⁴. Alternatively, it may at times be convenient to vary R⁴ by performing various functional group transformations on compounds of Formula 37, which can be prepared by the same methods for the preparation of the aryl-substituted heterocycles of Formula lb, as shown in Scheme 25. Methods to perform these transformations are well known in the literature and were described in the discussion for Schemes 8 and 9.

Scheme 26 illustrates the preparation of compounds of Formula Ic (Formula I where Q is Q-3) whereby an appropriately substituted pyridazine of Formula 38 is reacted with a suitably substituted condensing agent such as hydrazides, anhydrides, orthoesters, β-dicarbonyl compounds and others. Much work has been published with regard to cyclizations of this type. For example see: Katritzky, A. R. and Rees, C. W., Comprehensive Heterocyclic Chemistry, Vol. 5, pp 607-668; Vol. 4, 443-495,

Pergamon, London (1984); Pollak, A., Stanovnik, V. and Tisler, M., Tetrahedron (1968), 2623; L. M. Berbel, M. L. Zamura, Tetrahedron (1965), 287; Stanovnik, B., Tisler, M., Tetrahedron (1967), 2739; Fraser, M., J. Org. Chem. (1971), 3087;

F. D. Popp, et al., J. Heterocyclic Chem. (1981), 443; Thompson, R. D., Castle, R. N., J. Heterocyclic Chem. (1981), 1523-1527; J. D. Albright, et al., J. Med. Chem. (1981), 592-600; Legraverend, M., Bisagn, C., Lhoste, J. M., J. Heterocyclic Chem. (1981), 893-898; Pollak, A., Tisler, M., Tetrahedron (1966), 2073-2079; Letsinger, R. L., Lasco, R., J. Org. Chem. (1956), 764; Ohsaua, A., Abe, Y., Igeta, H., Chem. Lett. (1979), 241.

The substituent R⁴ may often be incorporated by selection of the proper condensing agent. However, it may at times be necessary or convenient to introduce the desired substituents after the cyclization has occurred. This strategy is shown in Scheme 27. Numerous methods for such transformations are known to those skilled in the art. For example: Stanovnik, B., Tisler, M., Tetrahedron, (1967), 387-395; Kobe, J., Stanovnik, B., Tisler, M., Tetrahedron, (1968), 239-245, and methods discussed in Schemes 8 and 9. Compounds of Formula 39 can be prepared by the same methods shown in Scheme 26.

The arylpyridazines of Formula 38 can be prepared by palladium-catalyzed coupling of an arylboronic acid of Formula 40 with a pyridazine of Formula 41 as shown in Scheme 28. The pyridazines of Formula 41 are commercially available or can be prepared by methods known in the art. One skilled in the art will notice that for

X⁷ = NHNH₂, compounds of Formula 38b can be prepared by nucleophilic displacement of chlorine as shown in Scheme 28. The coupling is carried out by methods known in the literature as discussed for Scheme 1. The coupling is carried out by heating the mixture of 40 and 41 in the presence of a transition metal catalyst such as

tetrakis(triphenylphosphine)palladium (0) or bis(triphenylphosphine)palladium (II) dichloride in a solvent such as toluene, acetonitrile, glyme or tetrahydrofuran optionally in the presence of bases such as aqueous sodium carbonate or triethylamine. One skilled in the art will recognize that when X⁷ is chlorine, the stoichiometric ratios of reagents will need adjustment in order to avoid bis-coupling.

The requisite boronic acid can be prepared according to literature cited for Scheme 1 as shown in Scheme 29. This involves treating a bromide or iodide of Formula 42 with a metallating agent such as butyllithium followed by quenching with a trialkyl borate and, finally, treating with dilute acid to give the desired boronic acids of Formula 40. One skilled in the art will further note that when X⁸ = H, this constitutes an ortho-metallation for which there is ample precedent. As an example, see Fuhrer, W., J. Org. Chem. (1979), 1138.

The anilides of Formula 42 are either known or readily prepared by procedures and techniques well known in the art, for example: Houben-Weyl, Methoden der Organische Chemie, IVth Ed., Eugen Muller, Ed., George Thieme Veriag; I. J. Turchi, The

Chemistry of Heterocyclic Compounds, Vol. 45, pp 36-43, J. Wiley & Sons, New York, (1986); L. S. Wittenbrook, G. L. Smith, R. J. Timmons, J. Org. Chem. (1973), 465-471; P. Reynard, et al., Bull. Soc. Chim. Fr. (1962), 1735-1738. Compounds of Formula Ic can also be prepared by coupling of the boronic acids of Formula 40 with a heterocycle of Formula 43 as depicted in Scheme 30. One skilled in the art will recognize that the heterocycles of Formula 43 can be prepared according to procedures previously referenced for ring annulation as described for Scheme 26. This is also true with respect to the variation of substituent R⁴.

Another method for the preparation of Ic, especially where Z = CH and W = N or CH, is described in Scheme 31. For example, a suitably substituted N-aminopyrrole (44a) or N-aminoimidazole (44b) can be condensed with a β-dicarbonyl compound of Formula 45 to give the desired products. Several methods for this transformation are known in the art. For example, see Flitsch, W.; Kramer, V. LiebigsAnn. Chem. (1970) 735, 35; Blewith, H. L., Chem. Heterocyclic Compd. (1977) 30, 117; Maury, G., Chem. Heterocyclic Compd. (1977) 30, 179; Coppola, G. M.; Hardtmann, G. E.; Huegi, B. S. J; Heterocyclic Chem. (1974) 11, 51; Golubusuma, G. M.; Posntarck, G. Ν.; Chuguk, V. A. Khim. Geterotsikl. Soedin. (1974) 846; Bruckner, R.; Lavergne J.- P.; Vailfont, P., Liebigs Ann. Chem. (1979), 639; A. A. Tomaswin, et al., Ukr. Khim. (1988), 54, 612.

Numerous methods for the preparation of the required N-aminoheterocycles of Formula 44a and 44b and β-dicarbonyl compounds (45) or their equivalents (for example, compounds of Formula 46) are well known in the literature. For example, see:

Stetter, H., Jones, F., Chem. Ber. (1981), 564; M. Somei, et al., Chem. Pharm, Bull. (1978), 2522; Somei, M., Νatsume, M., Tetrahedron Lett. (1974), 461;

Schweitzer, E. L., Kopey, C. M., J. Org. Chem. (1972), 1561; Perveev, F. Y.,

Ershova, V., Zh. Org. Khim. (1961), 3554; Sitte, A., Paul, H., Hilgetag, G., Z Chem.

(1967), 341; R. Ν. Νeylor, et al., J. Chem. Soc. (1961), 4845; Frohlisch, B., Chem. Ber.

(1971), 3610; Sherif, J. E., Rene, L., Synthesis (1988), 138; J. T. Gupton, et al., J. Org. Chem. (1980), 4522; Tsuge, O., Limune, T., Horie, M., Heterocycles (1976), 13;

Kreutzenberger, A., Kreutzenberger, E., Tetrahedron (1976), 2603.

Compounds of Formula Ic can also be prepared by one skilled in the art from anilines of Formula 47 by treatment with an appropriate acyl halide or acid anhydride

(T = O, X = direct bond), chloroformates (T = O, X = O), chlorothiolformates (T = O, X = S), carbamoyl chlorides (T = O, X = NR⁵), isothiocyanates, (T = S, X = NH), isocyanates (T = O, X = NH) or xanthyl chlorides (T = S, X = S). Treatment of compounds such as amides (X = bond, T = O) with Lawesson's reagent will give thioamides (X = bond, T = S). This is illustrated in Scheme 32 and is well known to those skilled in the art. For example: Sandier, R. S., Karo, W., Organic Functional Group Preparations, 2nd Ed., Vol. 1, p 274 and Vol. 2, pp 152, 260, Academic. i

Alternatively, compounds of Formula 47 can be converted to compounds of

Formula Ic by first treating the anilines with thiophosgene or phosgene (or a phosgene equivalent such as triphosgene) followed by condensation with an appropriate alcohol, thiol, or amine, as shown in Scheme 33. These techniques are also well known in the literature. For example, see Sandier, R. S., Karo, W., Organic Functional Group Preparation, 2nd Ed., Vol. 2, pp 152, 260, Academic; Lehman, G., Teichman, H., Preparative Organic Chemistry, p 472, John Wiley & Sons, New York, (1972);

Eckert, H., Forster, B., Angew, Chem. Int. Ed. Eng. (1987), 894; Babed, H., Zeiler, A. G., Chem. Rev. (1973), 75.

R

Anilines of Formula 47 are readily prepared by palladium-catalyzed coupling of an ortho-substituted nitrophenyl compound of Formula 48 with a heterocycle of Formula 43 (described previously), followed by catalytic hydrogenation or chemical reduction of the nitro group as shown in Scheme 34. Reduction of nitro groups is well documented in the literature. See for example, Ohme, R., Zubek, A. R. in Preparative Organic Chemistry, 557, Hilgetag, G. and Martini, A., Eds. John Wiley & Sons, New York (1972).

It is recognized that some reagents and reaction conditions described above for preparing compounds of Formula I may not be compatible with certain functionalities present in the intermediates. In these instances, the incorporation of

protection/deprotection sequences or functional group interconversions into the synthesis will aid in obtaining the desired products. The use and choice of the protecting groups will be apparent to one skilled in chemical synthesis (see, for example, Greene, T. W.; Wuts, P. G. M. Protective Groups in Organic Synthesis, 2nd ed.; Wiley: New York, 1991). One skilled in the art will recognize that, in some cases, after the introduction of a given reagent as it is depicted in any individual scheme, it may be necessary to perform additional routine synthetic steps not described in detail to complete the synthesis of compounds of Formula I. One skilled in the art will also recognize that it may be necessary to perform a combination of the steps illustrated in the above schemes in an order other than that implied by the particular sequence presented to prepare the compounds of Formula I.

One skilled in the art will also recognize that compounds of Formula I and the intermediates described herein can be subjected to various electrophilic, nucleophilic, radical, organometallic, oxidation, and reduction reactions to add substituents or modify existing substituents.

Without further elaboration, it is believed that one skilled in the art using the preceding description can utilize the present invention to its fullest extent. The following Examples are, therefore, to be construed as merely illustrative, and not limiting of the disclosure in any way whatsoever. Percentages are by weight except for

chromatographic solvent mixtures or where otherwise indicated. Parts and percentages for chromatographic solvent mixtures are by volume unless otherwise indicated. ¹H NMR spectra are reported in ppm downfield from tetramethylsilane; s = singlet, d = doublet, t = triplet, p = pentet, m = multiplet, br s = broad singlet.

EXAMPLE 1

Step A: Preparation of 1-(2-amino-5-methylphenyl)-2-[[5-(trifluoromethyl)-4H- 1 ,2,4-triazol-3-yl]thio]ethanone

0.33 g (0.0144 mol) of sodium was dissolved under nitrogen in 50 mL of methanol, 2.55 g (0.0151 mol) of 5-(trifluoromethyl)-4H-1,2,4-triazole-3(2H)-thione hydrate (purchased from Lancaster) was added, and the mixture was stirred at room temperature for 1 h, after which 2.52 g (0.0137 mol) of 1-(2-amino-5-methylphenyl)-2- chloroethanone was added. After stirring overnight, the reaction mixture was evaporated to dryness. The crude product was washed with water and purified by recrystallization from chloroform to yield 2.40 g of the title compound of Step A as a powder melting at 205°C (dec). ¹Η NMR (Me₂SO-d₆): δ 2.20 (s,3Η), 4.98 (s,2H), 6.71-7.61 (m,4H).

Step B: Preparation of 4-methyl-2-[2-(trifluoromethyl)thiazolo[3,2- b] [ 1.2.4]triazol-6-yl]benzenamine

1.30 g (0.0041 mol) of the title compound of Step A was dissolved under nitrogen in 5 mL of concentrated sulfuric acid. The reaction mixture was stirred at about 100°C for 2 h. After cooling to about 0°C, 1N sodium hydroxide was added slowly until the reaction mixture reached pH 7. The crude product was filtered and washed with hexane to yield 1.0 g of the title compound of Step B as a powder melting at 132-133°C.

1H NMR (CDCl₃): δ 2.31 (s,3H), 6.78-7.29 (m,4H).

Step C: Preparation of 3-methyl-N-[4-methyl-2-[2-(trifluoromethyl)thiazolo[3,2- b] [ 1 ,2,4]triazol-6-yl]phenyl]butanamide

0.50 g (0.0017 mol) of the title compound of Step B was added to 50 mL of diethyl ether, and the suspension was cooled under nitrogen to about 0°C. 0.25 mL (0.0020 mol) of isovaleryl chloride was added, followed by 0.30 mL (0.0022 mol) of triethylamine, and the mixture was stirred at room temperature for about 4 h. The reaction mixture was filtered and the filtrate was evaporated to dryness. Water was added and the mixture was extracted with diethyl ether (3 x 25 mL), dried (MgSO₄), and evaporated to dryness. The crude product was chromatographed on silica gel eluting with ethyl acetate/hexane (2:8, and then 3:7) mixture to yield 0.04 g of the title compound of Step C, a compound of the invention, as a powder melting at 177-178°C. ¹H ΝMR (Me₂SO-d₆): δ 0.79 (d,6H), 1.9 (m,1H), 1.97 (d,2H), 2.34 (s,3H), 7.3-7.7 (m,4H), 9.3 (s,1H). EXAMPLE 2

Step A: Preparation of 1-[(5-methyl-2-nitrophenyl)methyl]-3-(trifluoromethyl)- 1H-pyrazole

5.65 g (0.030 mol) of 5-methyl-2-nitrobenzyl chloride (purchased from Aldrich Chemical Company), 5.0 g (0.036 mol) of 3-(trifluoromethyl)pyrazole (purchased from Maybridge), and 12.4 g (0.090 mol) of potassium carbonate were added to 25 mL acetonitrile. The reaction mixture was stirred under nitrogen overnight, and then was evaporated to dryness. The crude product was purified by recrystallization from methanol. The solid was washed with water, dissolved in ethyl acetate, dried (MgSO₄), and evaporated to dryness to yield 6.26 g of the title compound of Step A as a powder. Water was added to the mother liquor to yield after filtration an additional 1.2 g of the title compound of Step A as a solid melting at 70-71.5°C. ¹Η NMR (CDCl₃): δ 2.38 (s,3Η), 5.76 (s,2H), 6.60-8.07 (m,5H).

Step B: Preparation of 4-methyl-2-[[3-(trifluoromethyl)-1H-pyrazol-1- yl]methyl]benzenamine

3.2 g (0.011 mol) of the title compound of Step A was added to a solution of 15 mL acetic acid and 6 mL water. The mixture was warmed to about 65°C, the heat was shut off, and 2.1 g (0.037 mol) of iron was added in portions maintaining the temperature below 91°C. The mixture was warmed to about 75°C for 15 min., gravity filtered onto about 100 g of ice, and then extracted with methylene chloride (3 x 50 mL). The organic extracts were washed with saturated aqueous sodium bicarbonate, dried (MgSO₄), and evaporated to dryness to yield 1.8 g of the title compound of Step B as an oil. ¹Η NMR (CDCl₃): δ 2.25 (s,3Η), 5.0 (br s,2H), 5.22 (s,2H), 6.49-7.40 (m,5H). Step C: Preparation of 2-methyl-N-[4-methyl-2-[[3-(trifluoromethyl)-1H-pyrazol- 1-yl]methyl]phenyl]propanamide

0.55 g (0.0022 mol) of the title compound of Step B was dissolved under nitrogen in 50 mL of diethyl ether. The solution was cooled to about 0°C, 0.27 mL (0.0026 mol) of isobutyryl chloride was added followed by 0.39 mL (0.0028 mol) of triethylamine. The reaction mixture was stirred over 3 days and was then filtered. The filtrate was evaporated to dryness, the resulting residue was suspended in water, and the crude product was then filtered and washed with hexane to yield 0.36 g of the title compound of Step C, a compound of the invention, as a powder melting at 125-125.5°C. ¹H ΝMR (CDCl₃): δ 1.31 (d,6Η), 2.32 (s,3H), 2.7 (m.1H), 5.21 (s,2H), 6.52-7.8 (m,5H), 9.3 (br s, 1H). EXAMPLE 3

Step A: Preparation of (5-methyl-2-nitrophenyl)hydrazine

1-Fluoro-5-methyl-2-nitrobenzene (Aldrich, 20 g, 129 mmol) was treated with hydrazine hydrate (7.0 g, 140 mmol) in DMF (100 mL) at 25°C for 3 h. The mixture was drowned in water (1000 mL) and the precipitated product filtered. The filtrate was extracted with ethyl acetate and the combined product purified by flash chromatography to give 8.38 g of the title compound of Step A as a solid melting at 128-130°C. IR (mineral oil) 3320, 3330 cm^-1; ¹H NMR (300 MHz, CDCl₃): δ 2.38 (s,3H), 3.75 (s,2H), 6.5 (d,1H), 7.38 (s,1H), 8.0 (d,1H), 8.9 (br s,1H).

Step B: Preparation of 2,2,2-trifluoroethanone (5-methyl-2-nitrophenyl)hydrazone

The title compound of Step A (3.0 g, 18 mmol) in dioxane (30 mL) was heated at reflux with trifluoroacetaldehyde hydrate (3.0 g, 26 mmol) and a catalytic amount of p-toluenesulfonic acid (0.1 g) for 20 h. The product was isolated by evaporation of the solvent and recrystallization from methanol/water to give 3.87 g of the title compound of Step B as a solid melting at 159-160°C. IR (mineral oil) 3368, 1612 cm^-1; ¹H NMR (300 MHz, CDCl₃): δ 2.44 (s,3H), 6.8 (d,1H), 7.25 (s,1H), 7.65 (s,1H), 8.1 (d,1H), 11.15 (br s,1H).

Step C: Preparation of 2,2,2-trifluoro-N-(5-methyl-2- nitrophenyl]ethanehydrazonoyl bromide

A DMF solution (35 mL) of the title compound of Step B (3.8 g, 15.4 mmol) was treated with N-bromosuccinimide (2.9 g, 16.3 mmol) at 25°C for 3 h. The reaction mixture was drowned in water (250 mL) and extracted with ethyl acetate. The product, isolated by evaporation of the solvent, was slurried with hexane and purified to give 4.2 g of the title compound of Step C as a solid melting at 135-139°C. IR (mineral oil) 3264, 1618 cm^-1; ¹H ΝMR (300 MHz, CDCl₃): δ 2.46 (s,3H), 6.9 (d,1H), 7.6 (s,1H), 8.15 (d,1H), 11.3 (s,1H).

Step D: Preparation of 5-butoxy-4,5-dihydro- 1 -(5-methyl-2-nitrophenyl)- 1H- pyrazole

A benzene (75 mL) and toluene (30 mL) solution of the title compound of Step C (4.0 g, 12.25 mmol), butyl vinyl ether (6.5 g, 6.5 mmol), and triethylamine (1.3 g, 13 mmol) was heated at 90°C for 12 h. Isolation by flash chromatography

(1-chlorobutane) gave 2.3 g of the title compound of Step D as an oil. ¹Η NMR

(300 MHz, CDCl₃): δ 0.76 (t,3H), 1.05 (p,2H), 1.3 (p,2H), 2.43 (s,3H), 3.0-3.25 (m,4H), 5.8 (d,1H), 7.05 (d.1H), 7.4 (s,1H), 7.8 (d,1H). Step E: Preparation of 1-(5-methyl-2-nitrophenyl)-3-(trifluoromethyl)-1H- pyrazole

An ethyl acetate solution (25 mL) of the title compound of Step D (2.3 g, 6.7 mmol) was treated with a catalytic amount of p-toluenesulfonic acid (<0.1 g) at 25°C for 1 h. Flash chromatography gave 1.69 g of the title compound of Step E as a crystalline solid melting at 84-86°C. ¹Η NMR (300 MHz, CDCl₃): δ 2.52 (s,3H), 6.7 (d,1H), 7.4 (m,2H), 7.7 (s.1H), 7.95 (d,1H).

Alternatively, the title compound of Step E can be prepared directly from

1-fluoro-5-methyl-2-nitrobenzene. A solution of 1-fluoro-5-methyl-2-nitrobenzene (6.04 g, 39 mmol) and 3-(trifluoromethyl)pyrazole (5.05 g, 37.1 mmol) and potassium carbonate (5.63 g, 40.8 mmol) was heated in dimethyl sulfoxide (30 mL) at 50 °C for

18 h. The cooled mixture was diluted with water (100 mL) and extracted with ethyl acetate (3 x 50 mL). The combined organic layers were washed with water (2 x 50 mL) and saturated aqueous NaCl (2 x 50 mL). The organic layer was dried over magnesium sulfate and evaporated. The resulting yellow solid was triturated with hexane to give 9.5 g of the title compound of Step E melting at 84-86 °C. ¹H NMR (300 MHz, CDCl₃): δ 2.52 (s,3H), 6.75 (s,1H), 7.4 (m,2H), 7.72 (s,1H), 7.95 (d,1H).

Step F: Preparation of 4-methyl-2-[3-(trifluoromethyl)-1H-pyrazol-1- yl]benzenamine

An ethanol solution (250 mL) of the title compound of Step E ( 1.65 g, 6.1 mmol) and palladium catalyst (10% Pd/C, 0.5 g) was pressurized to 3.45 x 10⁵ Pa with hydrogen in a Paar hydrogenation apparatus at 25°C for 5 h. The reaction mixture was filtered through Celite^® and the solvent was evaporated to give, after crystallization from 1-chlorobutane, 0.77 g of the title compound of Step F as a solid melting at 66-68°C. IR (mineral oil) 3469, 3365 cm^-1; ¹Η NMR (300 MHz, CDCl₃): δ 2.28 (s,3H), 4.36 (br s,2H), 6.7 (d,1H), 6.76 (d,1H), 7.02 (d,2H), 7.75 (s,1H).

Step G: Preparation of 2-methyl-N-[4-methyl-2-[3-(trifluoromethyl)-1H-pyrazol-

1 -yl]phenyl]propanamide

To a benzene solution (30 mL) at 25°C was added the title compound of Step F (0.75 g, 3.14 mmol), pyridine (0.5 g, 6.3 mmol), and isobutyryl chloride (2.0 g,

19 mmol). The mixture was stirred at 25°C for 18 h. Water (100 mL) was added to the mixture and the products were extracted by the addition of ethyl acetate. The product was a mixture of the mono- and bis-acylated aniline. A brief treatment of the mixture with dilute sodium hydroxide in methanol and reisolation by drowning in water and ethyl acetate extraction gave 0.58 g of the title compound of Step G, a compound of the invention, as a solid melting at 99-100°C. ¹H NMR (300 MHz, CDCl₃): δ 1.2 (d,6H), 2.38 (s,3H), 2.5 (p,1H), 6.8 (s,1H), 7.2 (s,1H), 7.3 (m,1H), 7.8 (s,1H), 8.3 (d,1H).

EXAMPLE 4

Step A: Preparation of N-(2-borono-4-methylphenyl)-2,2-dimethylpropanamide A solution of 72.4 g N-(4-methylphenyl)-2,2-dimemylpropanamide in 1000 mL of dry THF was cooled to -70°C under nitrogen and 480 mL of 2.5M H-BuLi in hexanes was added dropwise over 1 h while maintaining the temperature below -60°C. Stirring was continued at -70°C for 1 h, and then the reaction was allowed to warm to room temperature with stirring overnight.

The reaction mixture was then cooled to - 10°C and 200 mL of trimethyl borate was added dropwise while maintaining the temperature below 0°C. Stirring was continued at 0°C for 2.5 h, 50 mL of water was added dropwise over 0.5 h, and then concentrated HCl was added to acidify the reaction. The solvents were removed in vacuo, 200 mL of water was added to form a slurry which was shaken (or stirred) thoroughly with ether. The white precipitate was collected by filtration, washed well with a 1 : 1 ether/hexane mixture, and then suspended in acetone and stirred for 20 min. While stirring, 600 mL of water was added slowly in portions (more water may be necessary if precipitation is not complete). The white solid was collected by filtration, washed with water, and then dried in a vacuum oven to yield 56.8 g of the title compound of Step A as a white powder. ¹H ΝMR (CDCl₃): δ 1.03 (s,9H), 2.40 (s,3H), 7.20 (d,1H), 7.80 (s,1H), 7.96 (d,1H), 9.8 (s,1H).

Step B: Preparation of N-[2-(6-chloro-3-pyridazinyl)-4-methylphenyl]-2,2- dimethylpropan amide

To a stirred mixture of 8.4 g (0.056 mol) of 3,6-dichloropyridazine, 0.3 g of tetrakis(triphenylphosphine)palladium (0), and 6.6 g (0.028 mol) of the title compound of Step A was added 110 mL of a 1 molar aqueous solution of sodium carbonate. The resulting mixture was heated at reflux for 4 h. After cooling to room temperature, the reaction mixture was poured into 200 mL of saturated aqueous ΝaCl and extracted three times with 50 mL portions of ethyl acetate. The combined extracts were washed once widi water and then dried over anhydrous magnesium sulfate. The solution was filtered and evaporated to dryness. The crude product was purified by chromatography on silica gel using 20% ethyl acetate/hexane as eluent to afford 4.42 g (52%) of the title compound of Step B as a white solid melting at 144-148°C. ¹H ΝMR (CDCl₃): δ 1.31 (s,9H), 2.39 (s,3H), 7.26-734 (m,2H), 7.35(s,1H), 7.63-7.66 (m,1H), 7.86-7.89 (m,1H), 8.46-8.49 (m,1H), 11.59 (br s,1H). Step C: Preparation of N-[2-(6-hydrazino-3-pyridazinyl)-4-methylphenyl]-2,2- dimethylpropan amide

A solution of the title compound of Step B (1.0 g, 3.3 mmol) and hydrazine monohydrate (0.5 mL, 9.9 mmol) in 20 mL of n-butanol was heated at reflux for 4 h. After cooling to room temperature, the butanol was removed under vacuum and the residue so obtained was taken up in 80 mL diethyl ether. The organic solution was washed successively with 40 mL portions each of water and saturated aqueous ΝaCl, and then was dried over anhydrous magnesium sulfate. The solution was filtered and evaporated to dryness. The crude product was purified by chromatography on silica gel eluting with 5% methanol-dichloromethane to give 0.68 g (68%) of the title compound of Step C as a white solid melting at 153-156°C. ¹H ΝMR (CDCl₃): δ 1.30 (s,9H), 2.37 (s,3H), 4.00 (br s,2H), 6.27 (s,1H), 7.21-7.24 (m,2H), 7.30 (s,1H), 7.68-7.70 (m,1H), 8.44-8.46 (m,1H), 11.83 (br s,1H).

Step D: Preparation of 2,2-dimethyl-N-[4-methyl-2-[3-(trifluoromethyl)-1,2,4- triazolo[4,3-b]pyridazin-6-yl]phenyl]propanamide

A stirred solution of the title compound of Step C (0.68 g, 2.3 mmol) and 0.5 mL (3.6 mmol) of trifluoroacetic anhydride in 20 mL of pyridine was heated at reflux for 5 h. The dark solution was allowed to cool to room temperature. The volatiles were removed under reduced pressure and the residue was purified by chromatography on silica gel eluting with 50% ethyl acetate/hexane to afford 0.8 g (94%) of the title compound of Step D, a compound of the invention, as an oil. ¹H ΝMR (CDCl₃): δ 1.18 (s,9H), 2.42 (s,3H), 7.29 (s,1H), 7.37-7.40 (m,1H), 7.55-7.59 (m,1H), 7.90-7.93 (m,1H), 8.31-8.34 (m,1H), 8.77 (br s,1H).

EXAMPLE 5

Preparation of N-[4-methyl-2-[3-(trifluoromethyl)-1H-pyrazol-1- yl]phenyllcyclopropanecarboxamide

To a solution of the title compound of Step F in Example 3 (0.75 g, 3.1 mmol) and pyridine (0.49 g, 6.2 mmol) in benzene (30 mL) was added cyclopropanecarbonyl chloride (0.42 g, 4.0 mmol). The mixture was stirred at 25 °C for 18 h. The reaction mixture was diluted with ethyl acetate (25 mL) and treated with 1N aqueous

hydrochloric acid (10 mL). The organic layer was further washed with water and saturated aqueous ΝaCl (10 mL each), dried over magnesium sulfate and the solvent was then evaporated. The solid residue was triturated with hexane to give 0.72 g of the title compound of Example 5, a compound of the invention, as a solid melting at 106-107 °C. IR (mineral oil) 3300, 1674 cm^-1 ; ¹H ΝMR (300 MHz, CDCl₃): δ 0.9 (m,2H), 1.0 (m,2H), 1.4 (m,1H), 2.4 (s,3H), 6.77 (s,1H), 7.14 (s,1H), 7.2 (d,1H), 7.85 (s,1H), 8.3 (d,1H), 9.7 (s,1H).

EXAMPLE 6

Preparation of 3-methvl-N-[4-methyl-2-[3-(trifluoromethyl)-1H-pyrazol-1- yl]phenyl]butanamide

To a solution of the title compound of Step F in Example 3 (0.75 g, 3.1 mmol) and pyridine (0.49 g, 6.2 mmol) in benzene (30 mL) was added isovaleryl chloride (0.48 g, 4.0 mmol). The mixture was stirred at 25 °C for 18 h. The reaction mixture was then diluted with ethyl acetate (25 mL) and treated with IN aqueous hydrochloric acid (10 mL). The organic layer was further washed with water and saturated aqueous ΝaCl (10 mL each), dried over magnesium sulfate and the solvent was then evaporated. The solid residue was triturated with hexane to give 0.86 g of the title compound of

Example 6, a compound of the invention, as a solid melting at 102-103 °C. IR (mineral oil) 3280, 1682 cm^-1; ¹H ΝMR (300 MHz, CDCl₃): δ 0.92 (d,6H), 2.1 (m,1H), 2.2 (d,2H), 2.38 (s,3H), 6.8 (s,1H), 7.15 (s,1H), 7.2 (d,1H), 7.8 (s,1H), 8.23 (d,1H), 9.5 (s,1H).

By the procedures described herein together with methods known in the art, the following compounds of Tables 1 to 11 can be prepared. The following abbreviations are used in the Tables which follow: Me = methyl, C₆H₅ = phenyl and CΝ = cyano.

Formulation/Utility

Compounds of this invention will generally be used as a formulation or

composition with an agriculturally suitable carrier comprising at least one of a liquid diluent, a solid diluent or a surfactant. The formulation or composition ingredients are selected to be consistent with the physical properties of the active ingredient, mode of application and environmental factors such as soil type, moisture and temperature.

Useful formulations include liquids such as solutions (including emulsifiable

concentrates), suspensions, emulsions (including microemulsions and/or suspoemulsions) and the like which optionally can be thickened into gels. Useful formulations further include solids such as dusts, powders, granules, pellets, tablets, films, and the like which can be water-dispersible ("wettable") or water-soluble. Active ingredient can be

(micro)encapsulated and further formed into a suspension or solid formulation;

alternatively the entire formulation of active ingredient can be encapsulated (or

"overcoated"). Encapsulation can control or delay release of the active ingredient.

Sprayable formulations can be extended in suitable media and used at spray volumes from about one to several hundred liters per hectare. High-strength compositions are primarily used as intermediates for further formulation.

The formulations will typically contain effective amounts of active ingredient, diluent and surfactant within the following approximate ranges which add up to 100 percent by weight.

Typical solid diluents are described in Watkins, et al., Handbook of Insecticide Dust Diluents and Carriers, 2nd Ed., Dorland Books, Caldwell, New Jersey. Typical liquid diluents are described in Marsden, Solvents Guide, 2nd Ed., Interscience, New York, 1950. McCutcheon 's Detergents and Emulsifiers Annual, Allured Publ. Corp., Ridgewood, New Jersey, as well as Sisely and Wood, Encyclopedia of Surface Active Agents, Chemical Publ. Co., Inc., New York, 1964, list surfactants and recommended uses. All formulations can contain minor amounts of additives to reduce foam, caking, corrosion, microbiological growth and the like, or thickeners to increase viscosity.

Surfactants include, for example, polyethoxylated alcohols, polyethoxylated alkylphenols, polyethoxylated sorbitan fatty acid esters, dialkyl sulfosuccinates, alkyl sulfates, alkylbenzene sulfonates, organosilicones, N,N-dialkyltaurates, lignin sulfonates, naphthalene sulfonate formaldehyde condensates, polycarboxylates, and

polyoxyethylene/polyoxypropylene block copolymers. Solid diluents include, for example, clays such as bentonite, montmorillonite, attapulgite and kaolin, starch, sugar, silica, talc, diatomaceous earth, urea, calcium carbonate, sodium carbonate and bicarbonate, and sodium sulfate. Liquid diluents include, for example, water,

N,N-dimethylformamide, dimethyl sulfoxide, N-alkylpyrrolidone, ethylene glycol, polypropylene glycol, paraffins, alkylbenzenes, alkylnaphthalenes, oils of olive, castor, linseed, tung, sesame, corn, peanut, cotton-seed, soybean, rape-seed and coconut, fatty acid esters, ketones such as cyclohexanone, 2-heptanone, isophorone and 4-hydroxy-4- methyl-2-pentanone, and alcohols such as methanol, cyclohexanol, decanol and tetrahydrofurfuryl alcohol.

Solutions, including emulsifiable concentrates, can be prepared by simply mixing the ingredients. Dusts and powders can be prepared by blending and, usually, grinding as in a hammer mill or fluid-energy mill. Suspensions are usually prepared by wet-milling; see, for example, U.S. 3,060,084. Granules and pellets can be prepared by spraying the active material upon preformed granular carriers or by agglomeration techniques. See Browning, "Agglomeration", Chemical Engineering, December 4, 1967, pp 147-48, Perry's Chemical Engineer's Handbook, 4th Ed., McGraw-Hill, New York, 1963, pages 8-57 and following, and WO 91/13546. Pellets can be prepared as described in

U.S. 4, 172,714. Water-dispersible and water-soluble granules can be prepared as taught in U.S.4,144,050, U.S. 3,920,442 and DE 3,246,493. Tablets can be prepared as taught in U.S. 5,180,587, U.S. 5,232,701 and U.S. 5,208,030. Films can be prepared as taught in GB 2,095,558 and U.S. 3,299,566.

For further information regarding the art of formulation, see U.S. 3,235,361, Col. 6, line 16 through Col. 7, line 19 and Examples 10-41; U.S. 3,309,192, Col. 5, line 43 through Col. 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. 2,891,855, Col. 3, line 66 through Col. 5, line 17 and Examples 1-4; Klingman, Weed Control as a Science, John Wiley and Sons, Inc., New York, 1961, pp 81-96; and Hance et al., Weed Control Handbook, 8th Ed., Blackwell Scientific Publications, Oxford, 1989.

In the following Examples, all percentages are by weight and all formulations are prepared in conventional ways. Compound numbers refer to compounds in Index Tables A-D.

Test results indicate that the compounds of the present invention are highly active preemergent and postemergent herbicides or plant growth regulants. Many of them have utility for broad-spectrum pre- and/or postemergence weed control in areas where complete control of all vegetation is desired such as around fuel storage tanks, industrial storage areas, parking lots, drive-in theaters, air fields, river banks, irrigation and other waterways, around billboards and highway and railroad structures. Some of the compounds are useful for the control of selected grass and broadleaf weeds with tolerance to important agronomic crops which include but are not limited to barley, cotton, wheat, rape, sugar beets, corn (maize), soybeans, rice, oats, peanuts, vegetables, tomato, potato, and plantation crops including coffee, cocoa, oil palm, rubber, sugarcane, citrus, grapes, fruit trees, nut trees, banana, plantain, pineapple, hops, tea, forests such as eucalyptus and conifers, e.g., loblolly pine, and turf species, e.g.,

Kentucky bluegrass, St. Augustine grass, Kentucky fescue and Bermuda grass. Those skilled in die art will appreciate that not all compounds are equally effective against all weeds. Alternatively, the subject compounds are useful to modify plant growth.

Compounds of this invention can be used alone or in combination with other commercial herbicides, insecticides or fungicides. Compounds of this invention can also be used in combination with commercial herbicide safeners such as benoxacor, dichlormid and furilazole to increase safety to certain crops. A mixture of one or more of the following herbicides with a compound of this invention may be particularly useful for weed control: acetochlor/acifluorfen and its sodium salt, aclonifen, acrolein

(2-propenal), alachlor, ametryn, amidosulfuron, amitrole, ammonium sulfamate, anilofos, asulam, atrazine, azimsulfuron, benazolin, benazolin-ethyl, benfluralin, benfuresate, bensulfuron-methyl, bensulide, bentazone, bifenox, bromacil, bromoxynil, bromoxynil octanoate, butachlor, butralin, butylate, chlomethoxyfen, chloramben, chlorbromuron, chloridazon, chlorimuron-ethyl, chlornitrofen, chlorotoluron, chlorpropham,

chlorsulfuron, chlorthal-dimethyl, cinmethylin, cinosulfuron, clethodim, clomazone, clopyralid, clopyralid-olamine, cyanazine, cycloate, cyclosulfamuron, 2,4-D and its butotyl, butyl, isoctyl and isopropyl esters and its dimethylammonium, diolamine and trolamine salts, daimuron, dalapon, dalapon-sodium, dazomet, 2,4-DB and its dimethylammonium, potassium and sodium salts, desmedipham, desmetryn, dicamba and its diglycolammonium, dimethylammonium, potassium and sodium salts, dichlobenil, dichlorprop, diclofop-methyl, 2-[4,5-dihydro-4-methyI-4-(1-methylethyl)-5-oxo- 1H- imidazol-2-yl]-5-methyl-3-pyridinecarboxylic acid (AC 263,222), difenzoquat metilsulfate, diflufenican, dimepiperate, dimethenamid, dimethylarsinic acid and its sodium salt, dinitramine, diphenamid, diquat di bromide, dithiopyr, diuron, DNOC, endothal, EPTC, esprocarb, ethalfluralin, ethametsulfuron-methyl, ethofumesate, ethyl α,2-dichloro-5-[4-(difluoromethyl)-4,5-dihydro-3-methyl-5-oxo-1H-1,2,4-triazol-1-yl]- 4-fluorobenzenepropanoate (F8426), fenoxaprop-ethyl, fenoxaprop-P-ethyl, fenuron, fenuron-TCA, flamprop-methyl, flamprop-M-isopropyl, flamprop-M-methyl,

flazasulfuron, fluazifop-butyl, fluazifop-P-butyl, fluchloralin, flumetsulam,

flumiclorac-pentyl, flumioxazin, fluometuron, fluoroglycofen-ethyl, fiupoxam, fluridone, flurochloridone, fluroxypyr, fomesafen, fosamine-ammonium, glufosinate,

glufosinate-ammonium, glyphosate, glyphosate-isopropylammonium,

glyphosate-sesquisodium, glyphosate-trimesium, halosulfuron-methyl, haloxyfop-etotyl, haloxyfop-methyl, hexazinone, imazamethabenz-methyl, imazamox (AC 299263), imazapyr, imazaquin, imazaquin-ammonium, imazethapyr, imazethapyr-ammonium, imazosulfiiron, ioxynil, ioxynil octanoate, ioxynil-sodium, isoproturon, isouron, isoxaben, isoxaflutole (RPA 201772), lactofen, lenacil, linuron, maleic hydrazide, MCPA and its dimethylammonium, potassium and sodium salts, MCPA-isoctyl, mecoprop,

mecoprop-P, mefenacet, mefluidide, metam-sodium, methabenzthiazuron, methyl [[2- chloro-4-fluoro-5-[(tetrahydro-3-oxo- 1H,3H-[1,3,4]thiadiazolo[3,4-a]pyridazin-1- ylidene)aminojphenyl]thioacetate (KTΗ 9201), methylarsonic acid and its calcium, monoammonium, monosodium and disodium salts, methyl [[[l-[5-[2-chloro-4- (trifluoromethyl)phenoxy]-2-nitrophenyl]-2-methoxyethylidene]amino]oxy]acetate

(AKΗ-7088), memyl 5-[[[[(4,6-dimemyl-2-pyrirrύdinyl)amino]carbonyl]amino]sulfonyl]- 1-(2-pyridinyl)-1H-pyrazole-4-carboxylate (NC-330), metobenzuron, metolachlor, metosulam, metoxuron, metribuzin, metsulfiiron-methyl, molinate, monolinuron, napropamide, naptalam, neburon, nicosulfuron, norflurazon, oryzalin, oxadiazon, 3-oxetanyl 2-[[[[(4,6-dimemyl-2-pyrimidinyl)amino]carbonyl]amino]sulfonyl]benzoate (CGA 277476), oxyfluorfen, paraquat dichloride, pebulate, pendimethalin, perfluidone, phenmedipham, picloram, picloram-potassium, pretilachlor, primisulfuron-methyl, prometon, prometryn, propachlor, propanil, propaquizafop, propazine, propham, propyzamide, prosulfuron, pyrazolynate, pyrazosulfuron-ethyl, pyridate, pyrithiobac, pyrithiobac -sodium, quinclorac, quizalofop-ethyl, quizalofop-P-ethyl,

quizalofop-P-tefuryl, rimsulfuron, sethoxydim, siduron, simazine, sulcotrione

(ICIA0051), sulfentrazone, sulfometuron-methyl, TCA, TCA-sodium, tebuthiuron, terbacil, terbuthylazine, terbutryn, thenylchlor, thiafluamide (BAY 11390),

thifensulfuron-methyl, thiobencarb, tralkoxydim, tri-allate, triasulfuron,

tribenuron-methyl, triclopyr, triclopyr-butotyl, triclopyr-triethylammonium, tridiphane, trifluralin, triflusulfuron-methyl, and vernolate.

In certain instances, combinations with other herbicides having a similar spectrum of control but a different mode of action will be particularly advantageous for preventing the development of resistant weeds.

Preferred for better control of undesired vegetation (e.g., lower use rate, broader spectrum of weeds controlled, or enhanced crop safety) or for preventing the development of resistant weeds are mixtures of a compound of this invention with a herbicide selected from the group atrazine, chlorimuron-ethyl, imazaquin,

imazaquin-ammonium, imazethapyr, imazethapyr-ammonium, norflurazon, and pyrithiobac. Specifically preferred mixtures (compound numbers refer to compounds in Index Tables A-D) are selected from the group: compound 1 and atrazine; compound 1 and chlorimuron-ethyl; compound 1 and imazaquin; compound 1 and imazethapyr; compound 1 and norflurazon; compound 1 and pyrithiobac; compound 4 and atrazine; compound 4 and chlorimuron-ethyl; compound 4 and imazaquin; compound 4 and imazethapyr; compound 4 and norflurazon; compound 4 and pyrithiobac; compound 40 and atrazine; compound 40 and chlorimuron-ethyl; compound 40 and imazaquin;

compound 40 and imazethapyr; compound 40 and norflurazon; compound 40 and pyrithiobac; compound 41 and atrazine; compound 41 and chlorimuron-ethyl;

compound 41 and imazaquin; compound 41 and imazethapyr; compound 41 and norflurazon; compound 41 and pyrithiobac; compound 42 and atrazine; compound 42 and chlorimuron-ethyl; compound 42 and imazaquin; compound 42 and imazethapyr; compound 42 and norflurazon; compound 42 and pyrithiobac; compound 46 and atrazine; compound 46 and chlorimuron-ethyl; compound 46 and imazaquin;

compound 46 and imazethapyr; compound 46 and norflurazon; compound 46 and pyrithiobac; compound 133 and atrazine; compound 133 and chlorimuron-ethyl;

compound 133 and imazaquin; compound 133 and imazethapyr; compound 133 and norflurazon; and compound 133 and pyrithiobac.

A herbicidally effective amount of the compounds of this invention is determined by a number of factors. These factors include: formulation selected, method of application, amount and type of vegetation present, growing conditions, etc. In general, a herbicidally effective amount of compounds of this invention is 0.001 to 20 kg/ha with a preferred range of 0.004 to 1.0 kg/ha. One skilled in the art can easily determine the herbicidally effective amount necessary for the desired level of weed control. The following Tests demonstrate the control efficacy of the compounds of this invention against specific weeds. The weed control afforded by the compounds is not limited, however, to these species. See Index Tables A-D for compound descriptions. The following abbreviations are used in the Index Tables which follow: n - normal, i = iso, Pr = propyl, i-Pr = isopropyl, Bu = butyl, Ph = phenyl, and NO₂ = nitro. The abbreviation "dec" indicates that the compound appeared to decompose on melting. The abbreviation "Ex." stands for 'Εxample" and is followed by a number indicating in which example the compound is prepared.

* See Index Table D for ¹H NMR data.

** Protonated parent molecular ion (m/e) measured by mass spectrometry using atmospheric pressure chemical ionization in the positive ion mode (APCI+). The ion shown corresponds to the M+H+ ion calculated from the integral values of the atomic weights of the most abundant isotope of each element present.

*See Index Table D for ¹H NMR data.

INDEX TABLE D

Cmpd No. ¹H NMR Data (CDCl₃ solution unless indicated otherwise)^a

80 δ 1.5 (d,1H), 1.8 (s,3H), 2.3 (s,3H), 2.4 (d.1H).5.2 (d.1H), 5.3 (d.1H),

6.5-7.7 (m,5H), 9.8 (brs, 1H).

116 δ 2.35 (s,3H), 5.2 (s,2H), 6.5-7.8 (m,5H), 11.1 (br s,1H).

133 δ 1.18 (s,9H), 2.42 (s,3H), 7.29 (s.1H), 7.37-7.40 (m.1H), 7.55-7.59

(m,1H), 7.90-7.93 (m,1H), 8.31-8.34 (m,1H), 8.77 (br s,1H).

^{1 1}H NMR data are in ppm downfϊeld from tetramethylsilane. Couplings are designated by (s)-singlet, (d)-doublet, (m)-multiplet, (br s)-broad singlet.

BIOLOGICAL EXAMPLES OF THE INVENTION TEST A

Seeds of barnyardgrass (Echinochloa crus-galli), cocklebur (Xanthium

strumarium), crabgrass (Digitaria spp.), downy brome (Bromus tectorum), giant foxtail (Setaria faberiϊ), momingglory (Ipomoea spp.), sorghum (Sorghum bicolor), velvetleaf (Abutilon theophrasti), and wild oat (Avenafatuά) were planted into a sandy loam soil and sprayed preemergence (PRE) or treated by soil drench (PDRN) with test chemicals formulated in a non-phytotoxic solvent mixture which includes a surfactant. At the same time, these crop and weed species were also sprayed postemergence (POST) or sprayed to runoff (STRO) with test chemicals formulated in the same manner. Plants ranged in height from two to eighteen cm and were in the two to three leaf stage for the postemergence treatment. Treated plants and untreated controls were maintained in a greenhouse for approximately eleven days, after which all treated plants were compared to untreated controls and visually evaluated for injury. Plant response ratings, summarized in Table A, are based on a 0 to 10 scale where 0 is no effect and 10 is complete control. A dash (-) response means no test results.

TEST B

Seeds of barley (Hordeum vulgare), barnyardgrass (Echinochloa crus-galli), bedstraw (Galium aparine), blackgrass (Alopecurus myosuroides), chickweed (Stellaria media), cocklebur (Xanthium strumarium), corn (Zea mays), cotton (Gossypium hirsutum), crabgrass (Digitaria sanguinalis), downy brome (Bromus tectorum), giant foxtail (Setaria faberii), lambsquarters (Chenopodium album), momingglory (Ipomoea hederacea), rape (Brassica napus), rice (Oryza sativa), sorghum (Sorghum bicolor), soybean (Glycine max), sugar beet (Beta vulgaris), velvetleaf (Abutilon theophrastϊ), wheat (Triticum aestivum), wild buckwheat (Polygonum convolvulus), wild oat (Avena fatua) and purple nutsedge (Cyperus rotundus) tubers were planted and treated preemergence with test chemicals formulated in a non-phytotoxic solvent mixture which includes a surfactant.

At the same time, these crop and weed species were also treated with

postemergence applications of test chemicals formulated in the same manner. Plants ranged in height from two to eighteen cm (one to four leaf stage) for postemergence treatments. Treated plants and controls were maintained in a greenhouse for twelve to sixteen days, after which all species were compared to controls and visually evaluated. Plant response ratings, summarized in Table B, are based on a scale of 0 to 10 where 0 is no effect and 10 is complete control. A dash (-) response means no test result.

.

TEST C

The compounds evaluated in this test were formulated in a non-phytotoxic solvent mixture which includes a surfactant and applied to the soil surface before plant seedlings emerged (preemergence application), to water that covered the soil surface (flood application), and to plants that were in the one-to-four leaf stage (postemergence application). A sandy loam soil was used for the preemergence and postemergence tests, while a silt loam soil was used in the flood test. Water depth was approximately 2.5 cm for the flood test and was maintained at this level for the duration of the test.

Plant species in the preemergence and postemergence tests consisted of

barnyardgrass (Echinochloa crus-galli), barley (Hordeum vulgare), bedstraw (Galium aparine), blackgrass (Alopecurμs myosuroides), chickweed (Stellaria media), cocklebur (Xanthium strumarium), corn (Zea mays), cotton (Gossypium hirsutum), crabgrass (Digitaria sanguinalis), downy brome (Bromus tectorum), giant foxtail (Setaria faberiϊ), johnsongrass (Sorghum halepense), lambsquarters (Chenopodium album), momingglory (Ipomoea hederacea), pigweed (Amaranthus retroflexus), rape (Brassica napus), ryegrass (Lolium multiflorum), soybean (Glycine max), speedwell (Veronica persica), sugar beet (Beta vulgaris), velvetleaf (Abutilon theophrastϊ), wheat (Triticum aestivum), wild buckwheat (Polygonum convolvulus), and wild oat (Avenafatua). All plant species were planted one day before application of the compound for the preemergence portion of this test. Plantings of these species were adjusted to produce plants of appropriate size for the postemergence portion of the test. Plant species in the flood test consisted of rice (Oryza sativa), umbrella sedge (Cyperus difformis), duck salad (Heteranthera limosa), barnyardgrass (Echinochloa crus-galli) and late watergrass (Echinochloa oryzicola) grown to the 2 leaf stage for testing.

All plant species were grown using normal greenhouse practices. Visual evaluations of injury expressed on treated plants, when compared to untreated controls, were recorded approximately fourteen to twenty one days after application of the test compound. Plant response this ratings, summarized in Table C, were recorded on a 0 to 100 scale where 0 is no effect and 100 is complete control. A dash (-) response means no test result.

TEST D

Seeds of barnyardgrass (Echinochloa crus-galli), bindweed (Convolvulus arvensis), black nightshade (Solanum ptycanthum dunal), cassia (Cassia obtusifolia), cocklebur (Xanthium strumarium), common ragweed (Ambrosia artemisiifolia), corn (Zea mays), cotton (Gossypium hirsutum), crabgrass (Digitaria spp.), fall panicum (Panicum dichotomiflorum), giant foxtail (Setaria faberiϊ), green foxtail (Setaria viridis), jimsonweed (Datura stramonium), johnsongrass (Sorghum halepense), lambsquarter (Chenopodium album), momingglory (Ipomoea spp.), pigweed

(Amaranthus retroflexus), prickly sida (Sida spinosa), shattercane (Sorghum vulgare), signalgrass (Brachiaria platyphylla), smartweed (Polygonum pensylvanicum), soybean (Glycine max), sunflower (Heltanthus annuus), velvetleaf (Abutilon theophrastϊ), wild proso (Panicum miliaceum), woolly cupgrass (Eriochloa villosa), yellow foxtail (Setaria lutescens) and purple nutsedge (Cyperus rotundus) tubers were planted into a sandy loam or clay loam soil. These crops and weeds were grown in the greenhouse until the plants ranged in height from two to eighteen cm (one to four leaf stage), then treated postemergence with the test chemicals formulated in a non-phytotoxic solvent mixture which includes a surfactant. Pots receiving preemergence treatments were planted immediately prior to test chemical application. Pots treated in this fashion were placed in the greenhouse and maintained according to routine greenhouse procedures.

Treated plants and untreated controls were maintained in the greenhouse approximately 14-21 days after application of the test compound. Visual evaluations of plant injury responses were then recorded. Plant response ratings, summarized in Table D, are reported on a 0 to 100 scale where 0 is no effect and 100 is complete control.

TEST E

Compounds evaluated in this test were formulated in a non-phytotoxic solvent mixture which includes a surfactant and applied to the soil surface before plant seedlings emerged (preemergence application) and to plants that were grown for various periods of time before treatment (postemergence application). A sandy loam soil was used for the preemergence test while a mixture of sandy loam soil and greenhouse potting mix in a 60:40 ratio was used for the postemergence test. Test compounds were applied within approximately one day after planting seeds for the preemergence test. Plantings of these crops and weed species were adjusted to produce plants of appropriate size for the postemergence test. All plant species were grown using normal greenhouse practices. Crop and weed species include american black nightshade (Solanum americanum), arrowleaf sida (Sida rhombifolia), barnyardgrass (Echinochloa crus-galli), cocklebur (Xanthium strumarium), common lambsquarters (Chenopodium album), common ragweed (Ambrosia artemisiifoliά), corn (Zea mays), cotton (Gossypium hirsutum), eastern black nightshade (Solanum ptycanthum), fall panicum (Panicum

dichotomiflorum), field bindweed (Convolvulus arvensis), Florida beggarweed

(Desmodium purpureum), giant foxtail (Setaria faberiϊ), hairy beggarticks (Bidens pilosa), ivy leaf momingglory (Ipomoea hederacea), johnsongrass (Sorghum halepense), ladysthumb (Polygonum persicaria), large crabgrass (Digitaria sanguinalis), purple nutsedge (Cyperus rotundus), redroot pigweed (Amaranthus retroflexus), soybean

(Glycine max), Surinam grass (Brachiaria decumbens), velvetleaf (Abutilon theophrastϊ) and wild poinsettia (Euphorbia heterophylla).

Treated plants and untreated controls were maintained in a greenhouse for approximately 14 to 21 days, after which all treated plants were compared to untreated controls and visually evaluated. Plant response ratings, summarized in Table E, are based upon a 0 to 100 scale where 0 is no effect and 100 is complete control. A dash response (-) means no test result.

TEST F

Plastic pots were partially filled with silt loam soil. The soil was then saturated with water. Rice (Oryza sativa) seed or seedlings at the 2.0 to 3.5 leaf stage; seeds tubers or plant parts selected from barnyardgrass (Echinochloa crus-gallϊ), duck salad (Heteranthera limosa), early watergrass (Echinochloa oryzoides), junglerice

(Echinochloa colonum), late watergrass (Echinochloa oryzicola), redstem (Ammonia spp.), rice flatsedge (Cyperus iriά), smallflower flatsedge (Cyperus difformis) and tighthead sprangletop (Leptochloafasicularis), were planted into this soil. Plantings and waterings of these crops and weed species were adjusted to produce plants of appropriate size for the test. At the two leaf stage, water levels were raised to 3 cm above the soil surface and maintained at this level throughout the test. Chemical treatments were formulated in a non-phytotoxic solvent mixture which includes a surfactant and applied directly to the paddy water, by pipette, or to the plant foliage, by an air-pressure assisted, calibrated belt conveyer spray system.

Treated plants and controls were maintained in a greenhouse for approximately

21 days, after which all species were compared to controls and visually evaluated. Plant response ratings, summarized in Table F, are reported on a 0 to 100 scale where 0 is no effect and 100 is complete control. A dash (-) response means no test result.

TEST G

Seeds, tubers, or plant parts of alexandergrass (Brachiaria plantaginea), alfalfa (Medicago sativa), bermudagrass (Cynodon dactyloή), broadleaf signalgrass (Brachiaria platyphylla), common purslane (Portulaca oleracea), common ragweed (Ambrosia elatior), cotton (Gossypium hirsutum), dallisgrass (Paspalum dilatatum), goosegrass (Eleusine indica), guineagrass (Panicum maximum), itchgrass (Rottboellia exaltata), johnsongrass (Sorghum halepense), large crabgrass (Digitaria sanguinalis), peanuts (Arachis hypogaea), pitted momingglory (Ipomoea lacunosά), purple nutsedge (Cyperus rotundus), sandbur (Cenchrus echinatus), sourgrass (Trichachne insularis), Surinam grass (Brachiaria decumbens) and Texas panicum (Panicum Texas) were planted into greenhouse pots or flats containing greenhouse planting medium. Plant species were grown in separate pots or individual compartments. Test chemicals were formulated in a non-phytotoxic solvent mixture which includes a surfactant and applied preemergence and postemergence to the plants. Preemergence applications were made within one day of planting the seed or plant part. Postemergence applications were applied when the plants were in the two to four leaf stage (three to twenty cm).

Untreated control plants and treated plants were placed in the greenhouse and visually evaluated for injury 13 to 21 days after herbicide application. Plant response ratings, summarized in Table G, are based on a 0 to 100 scale where 0 is no injury and 100 is complete control. A dash (-) response means no test result.

TEST H

Compounds evaluated in this test were formulated in a non-phytotoxic solvent mixture which includes a surfactant and applied to the soil surface before plant seedlings emerged (preemergence application) and to plants that were in the one-to four leaf stage (postemergence application). A sandy loam soil was used for the preemergence test while a mixture of sandy loam soil and greenhouse potting mix in a 60:40 ratio was used for the postemergence test. Test compounds were applied within approximately one day after planting seeds for the preemergence test.

Plantings of these crops and weed species were adjusted to produce plants of appropriate size for the postemergence test. All plant species were grown using normal greenhouse practices. Crop and weed species include annual bluegrass (Poa annua), black nightshade (Solanum nigrum), blackgrass (Alopecurus myosuroides), chickweed (Stellaria media), deadnettle (Lamium amplexicaule), downy brome (Bromus tectorum), field violet (Viola arvensis), galium (Galium aparine), green foxtail (Setaria viridis), jointed goatgrass (Aegilops cylindrica), kochia (Kochia scoparia), lambsquarters

(Chenopodium album), littleseed canarygrass (Phalaris minor), rape (Brassica napus), redroot pigweed (Amaranthus retrqflexus), ryegrass (Lolium multiflorum), scentless chamomile (Matricaria inodora), speedwell (Veronica persica), spring barley (Hordeum vulgare cv. 'Klages'), spring wheat (Triticum aestivum cv. ΕRA'), sugar beet (Beta vulgaris cv. 'US 1'), sunflower (Helianthus annuus cv. Ttussian Giant'), wild buckwheat (Polygonum convolvulus), wild mustard (Sinapis arvensis), wild oat (Avenafatua), windgrass (Apera spica-ventϊ), winter barley (Hordeum vulgare cv. 'Igri') and winter wheat (Triticum aestivum cv. Talent'). Wild oat was treated at two growth stages. The first stage (1) was when the plant had two to three leaves. The second stage (2) was when the plant had approximately four leaves or in the initial stages of tillering.

Treated plants and untreated controls were maintained in a greenhouse for approximately 21 to 28 days, after which all treated plants were compared to untreated controls and visually evaluated. Plant response ratings, summarized in Table H, are based upon a 0 to 100 scale where 0 is no effect and 100 is complete control. A dash response (-) means no test result.

TEST I

Compounds evaluated in this test were formulated in a non-phytotoxic solvent mixture which includes a surfactant and applied to the soil surface before plant seedlings emerged (preemergence application) and to plants that were grown for various periods of time before treatment (postemergence application). A sandy loam soil was used for the preemergence test while a mixture of sandy loam soil and greenhouse potting mix in a 60:40 ratio was used for the postemergence test. Test compounds were applied within approximately one day after planting seeds for the preemergence test, and 13 days after the last postemergence planting.

Plantings of these crops and weed species were adjusted to produce plants of appropriate size for the postemergence test. All plant species were grown using normal greenhouse practices. Crop and weed species include alexandergrass (Brachiaria plantaginea), american black nightshade (Solanum americanum), apple-of-Peru

(Nicandra physaloides), arrowleaf sida (Sida rhombifolia), brazilian sicklepod (Cassia tora Brazilian), brazilian signalgrass (Brachiaria decumbens), capim-colchao (Digitaria horizontalis), cristalina soybean (Glycine max Cristalina), florida beggarweed

(Desmodium purpureum), hairy beggarticks (Bidens pilosa), slender amaranth

(Amaranthus viridis), southern sandbur (Cenchrus echinatus), tall momingglory (Ipomoea purpurea), tropical spiderwort (Commelina benghalensis), W20 Soybean (Glycine max W20), W4-4 Soybean (Glycine max W4-4) and wild poinsettia

(Eupohorbia heterophylla).

Treated plants and untreated controls were maintained in a greenhouse for approximately 13 days, after which all treated plants were compared to untreated controls and visually evaluated. Plant response ratings, summarized in Table I, are based upon a 0 to 100 scale where 0 is no effect and 100 is complete control. A dash response (-) means no test result.

Claims

CLAIMS What is claimed is:

1. A compound selected from Formula I, N-oxides and agriculturally-suitable salts thereof,

T is O or S;

X is a single bond, O, S, or ΝR⁵;

Y is O, S, ΝR⁶, -CH=CH-, or -CH=Ν-, where the -CH=N- can be attached in either possible orientation;

Z is CH or N;

W is CH or N;

V is CH, CCH₃ or N, provided that V is CH or CCH₃ when W is CH;

R¹ is C₁-C₅ alkyl optionally substituted with C₁-C₂ alkoxy, OH, 1-7 halogen, or C₁-C₂ alkylthio; CH₂(C₃-C₄ cycloalkyl); C₃-C₆ cycloalkyl optionally substituted with 1-3 halogen or 1-4 methyl groups; C₂-C₄ alkenyl; C₂-C₄ haloalkenyl; or phenyl optionally substituted with C₁-C₄ alkyl, C₁-C₄ haloalkyl, C₁-C₄ alkoxy, 1-2 halogen, nitro, or cyano; provided that when X is O, S, or NR⁵, then R¹ is other than C₂ alkenyl and C₂ haloalkenyl;

R² is H, halogen, C₁-C₂ alkyl, C₁-C₂ alkoxy, C₁-C₂ alkylthio, C₂-C₃ alkoxyalkyl, C₂-C₃ alkylthioalkyl, cyano, nitro, NH(C₁-C₂ alkyl), or N(C₁-C₂ alkyl)₂; R³ is H, halogen, C₁-C₂ alkyl, C₁-C₂ alkoxy, C₁-C₂ alkylthio, C₂-C₃ alkoxyalkyl,

C₂-C₃ alkylthioalkyl, cyano, nitro, NH(C₁-C₂ alkyl), or N(C₁-C₂ alkyl)₂; R⁴ is C₁-C₄ haloalkyl, C₁-C₄ haloalkoxy, C₁-C₄ haloalkylthio, C₁-C₄ alkylsulfonyl,

C₁-C₄ haloalkylsulfonyl, halogen, cyano, or nitro;

R⁵ is H, CH₃, or OCH₃;

R⁶ is H or CH₃; and

n is 0 or 1.

2. A compound of Claim 1 wherein:

R¹ is C₁-C₄ alkyl optionally substituted with methoxy or 1-3 halogen; C₃-C₄

cycloalkyl optionally substituted with one methyl group; C₂-C₄ alkenyl; or C₂-C₄ haloalkenyl;

R² is chlorine, bromine, C₁-C₂ alkyl, C₁-C₂ alkoxy, cyano, nitro, NH(C₁-C₂ alkyl), or N(C₁-C₂ alkyl)₂; and

R³ is H.

3. A compound of Claim 2 wherein:

X is a single bond; and

R⁴ is C₁-C₂ haloalkyl, C₁-C₂ haloalkoxy, C₁-C₂ haloalkylthio, chlorine, or

bromine.

4. A compound of Claim 3 wherein:

Q is Q-1.

5. A compound of Claim 3 wherein:

Q is Q-2.

6. A compound of Claim 3 wherein:

Q is Q-3.

7. The compound of Claim 3 which is selected from the group:

3-memyl-N-[4-methyl-2-[2-(trifluoromethyl)thiazolo[3,2-b][1,2,4]triazol-6- yl]phenyl]butanamide;

N-[4-memyl-2-[2-(trifluoromethyl)thiazolo[3,2-b][1,2,4]triazol-6- yl]phenyl]cyclopropanecarboxamide;

2-methyl-N-[4-methyl-2-[3-(trifluoromethyl)-1H-pyrazol-1- yl]phenyl]propanamide;

N-[4-methyl-2-[3-(trifluoromethyl)-1H-pyrazol-1- yl]phenyl]cyclopropanecarboxamide;

3-methyl-N-[4-methyl-2-[3-(trifluoromethyl)-1H-pyrazol-1- yl]phenyl]butanamide;

2-methyl-N-[4-methyl-2-[[3-(trifluoromethyl)-1H-pyrazol-1- yI]methyl]phenyl]propanamide; and

2,2-dimethyl-N-[4-methyl-2-[3-(trifluoromethyl)-1,2,4-triazolo[4,3-b]pyridazin-

6-yl]phenyl]propanamide.

8. A herbicidal composition comprising a herbicidally effective amount of a compound of Claim 1 and at least one of a surfactant, a solid diluent or a liquid diluent.

9. A method for controlling the growth of undesired vegetation comprising contacting the vegetation or its environment with a herbicidally effective amount of a compound of Claim 1.