WO1997046530A1

WO1997046530A1 - Herbicidal pyridinyl and pyrazolylphenyl ketones

Info

Publication number: WO1997046530A1
Application number: PCT/US1997/009569
Authority: WO
Inventors: Kanu Maganbhai Patel; Morris Padgett Rorer; Chi-Ping Tseng
Original assignee: E.I. Du Pont De Nemours And Company
Priority date: 1996-06-06
Filing date: 1997-06-02
Publication date: 1997-12-11
Also published as: CA2257196A1; EP0922032A1; AU3297397A

Abstract

Compounds of Formula (I), and their N-oxides and agriculturally suitable salts, are disclosed which are useful for controlling undesired vegetation wherein Q is Q-1, Q-2, Q-3 or Q-4; and A, W, R?1, R3-R11¿, and m 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 PYRIDINYL, AND PYRAZOLYLPHENYL KETONES

BACKGROUND OF THE INVENTION

This invention relates to certain phenyl ketones, their JV-oxides, agriculturally suitable salts 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, corn (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 96/26200 discloses pyrazoles of Formula i as herbicides:

wherein, inter alia

Q represents a cyclohexane- 1,3-dione ring;

L and M are hydrogen, C₁-C₆ alkyl, C₁-C₄ alkoxy, halogen or nitro; and

Z represents a five to six-membered heterocyclic saturated or unsaturated group.

The phenyl ketones of the present invention are not disclosed in this publication.

SUMMARY OF THE INVENTION

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

A is a five- to ten-membered monocyclic or fused bicyclic ring system, which may be fully aromatic or partially saturated, containing 1 to 4 heteroatoms independently selected from the group nitrogen, oxygen, and sulfur, provided that each heterocyclic ring system contains no more than 2 oxygens and no more than 2 sulfurs, and each ring system is optionally substituted with one to three R², provided that when a nitrogen atom of a heterocyclic ring is substituted with R², then R² is other than halogen;

each R¹ is independently H, C₁-C₆ alkyl, C₁-C₆ haloalkyl, C₁-C₆ alkoxy, C₁-C₆ haloalkoxy, halogen, cyano, nitro, -(Y)_tS(O)_nR¹⁵ or -(Y)_t-C(O)R¹⁵;

W is N or CH;

Y is O or NR¹²;

R² is C₁-C₆ alkyl, C₁-C₆ haloalkyl, C₃-C₆ alkenyl, C₃-C₆ haloalkenyl, C₃-C₆ alkynyl, C₃-C₆ haloalkynyl, C₁-C₆ alkoxy, C₁-C₆ haloalkoxy, C₃-C₆ alkenyloxy, C₃-C₆ alkynyloxy, mercapto, C₁-C₆ alkylthio, C₁-C₃ haloalkylthio, C₃-C₆ alkenylthio, C₃-C₆ haloalkenylthio, C₃-C₆ alkynylthio, C₂-C₅ alkoxyalkylthio, C₃-C₅ acetylalkylthio, C₃-C₆

alkoxycarbonylalkylthio, C₂-C₄ cyanoalkylthio, C₁-C₆ alkylsulfinyl, C₁-C₆ haloalkylsulfinyl, C₁-C₆ alkylsulfonyl, C₁-C₆ haloalkylsulfonyl,

aminosulfonyl, C₁-C₂ alkylaminosulfonyl, C₂-C₄ dialkylaminosulfonyl,

(CH₂)_rR¹⁶, NR¹²R¹³, halogen, cyano or nitro; or R² is phenyl or benzylthio, each optionally substituted on the phenyl ring with C₁-C₃ alkyl, C₁-C₃ haloalkyl, C₁-C₃ alkoxy, C₁-C₃ haloalkoxy, 1-2 halogen, cyano or nitro;

R³ is OR¹⁴, SH, C₁-C₆ alkylthio, C₁-C₆ haloalkylthio, C₁-C₆ alkylsulfinyl, C₁-C₆ haloalkylsulfinyl, C₁-C₆ alkylsulfonyl, C₁-C₆ haloalkylsulfonyl, halogen or

NR¹²R¹³; or R³ is phenylthio, phenylsulfonyl or -SCH₂C(O)Ph, each optionally substituted with C₁-C₃ alkyl, halogen, cyano or nitro;

each R⁴ is independently C₁-C₃ alkyl, C₁-C₃ alkoxy, C₁-C₃ alkylthio or halogen; or when two R⁴ are attached to the same carbon atom, then said R⁴ pair can be taken together to form -OCH₂CH₂O-, -OCH₂CH₂CH₂O-, -SCH₂CH₂S- or -SCH₂CH₂CH₂S-, each group optionally substituted with 1-4 CH₃;

R⁵ is OR¹⁴, SH, C₁-C₆ alkylthio, C₁-C₆ haloalkylthio, C₁-C₆ alkylsulfinyl, C₁-C₆ haloalkylsulfinyl, C₁-C₆ alkylsulfonyl, C₁-C₆ haloalkylsulfonyl, halogen or NR¹²R¹³; or R⁵ is phenylthio, phenylsulfonyl or -SCH₂C(O)Ph, each optionally substituted with C₁-C₃ alkyl, halogen, cyano or nitro;

R⁶ is H, C₁-C₆ alkyl, C₁-C₆ haloalkyl, C₃-C₆ alkenyl, C₃-C₆ alkynyl or

-CH₂CH₂OR¹²; or R⁶ is phenyl or benzyl, each optionally substituted on the phenyl ring with C₁-C₃ alkyl, halogen, cyano or nitro;

R⁷ is H, C₁-C₆ alkyl, C₁-C₆ haloalkyl, C₁-C₆ alkoxy, C₁-C₆ haloalkoxy, halogen, cyano or nitro;

R⁸ is H, C₁-C₆ alkyl, C₁-C₆ haloalkyl, C₃-C₆ cycloalkyl or C₃-C₆ halocycloalkyl;

R⁹ is H, C₂-C₆ alkoxycarbonyl, C₂-C₆ haloalkoxy carbonyl, CO₂H or cyano;

R¹⁰ is C₁-C₆ alkyl, C₁-C₆ haloalkyl, C₃-C₆ cycloalkyl optionally substituted with 1-4 C₁-C₃ alkyl or C₃-C₆ halocycloalkyl;

R^{1 1} is cyano, C₂-C₆ alkoxycarbonyl, C₂-C₆ alkylcarbonyl, S(O)_nR¹³ or

C(O)NR¹²R¹³;

each R¹² is independently H or C₁-C₆ alkyl;

R¹³ is C₁-C₆ alkyl or C₁-C₆ alkoxy; or

R¹² and R¹³ can be taken together as -CH₂CH₂-, -CH₂CH₂CH₂-,

-CH₂CH₂CH₂CH₂-, -CH₂CH₂CH₂CH₂CH₂- or -CH₂CH₂OCH₂CH₂-;

R¹⁴ is H, C₁-C₆ alkyl, C₁-C₆ haloalkyl, C₂-C₆ alkoxyalkyl, formyl, C₂-C₆

alkylcarbonyl, C₂-C₆ alkoxycarbonyl, C(O)NR¹²R¹³, C₁-C₆ alkylsulfonyl or C₁-C₆ haloalkylsulfonyl; or R¹⁴ is phenyl, benzyl, benzoyl, -CH₂C(O)phenyl or phenylsulfonyl, each optionally substituted on the phenyl ring with C₁-C₃ alkyl, halogen, cyano or nitro;

R¹⁵ is NR¹²R¹³, C₁-C₆ alkoxy, C,-C₆ haloalkoxy, C₁-C₆ alkyl, C₁-C₆ haloalkyl, C₃-C₆ alkenyl, C₃-C₆ haloalkenyl, C₃-C₆ alkynyl, C₃-C₆ haloalkynyl or C₃-C ₆ cycloalkyl; or R¹⁵ is phenyl optionally substituted with C₁-C₃ alkyl, C₁-C₃ haloalkyl, C₁-C₃ alkoxy, C₁-C₃ haloalkoxy, 1-2 halogen, cyano or nitro;

R¹⁶ is C₁-C₃ alkoxy, C₂-C₄ alkoxycarbonyl, C₁-C₃ alkylthio, C₁-C₃ alkylsulfinyl or C₁-C₃ alkylsulfonyl; or R¹⁶ is phenyl optionally substituted with C₁-C₃ alkyl, C₁-C₃ haloalkyl, C₁-C₃ alkoxy, C₁-C₃ haloalkoxy, 1-2 halogen, cyano or nitro;

m is 0, 1, 2 or 3;

n is 0, 1 or 2;

p is 0, 1, 2, 3 or 4;

r is 1, 2 or 3; and

t is 0 or 1 ;

provided that when W is CH and A is in the meta position with respect to the group Q-C(O)- of Formula I, then m is 3 and R¹ is other than H. 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, H-propyl, i-propyl, or the different butyl, pentyl or hexyl isomers. The term "1-2 alkyl" indicates that one or two of the available positions for that substituent may be alkyl. "Alkenyl" includes straight-chain or branched alkenes such as

1-propenyl, 2-proρenyl, and the different butenyl, pentenyl and hexenyl isomers.

"Alkenyl" also includes polyenes such as 1,2-propadienyl and 2,4-hexadienyl.

"Alkynyl" includes straight-chain or branched alkynes such as 1-propynyl, 2-propynyl and the different butynyl, pentynyl and hexynyl isomers. "Alkynyl" can also include moieties comprised of multiple triple bonds such as 2,5-hexadiynyl. "Alkoxy" includes, for example, methoxy, ethoxy, n-propyloxy, isopropyloxy and the different butoxy, pentoxy and hexyloxy isomers. "Alkoxyalkyl" denotes alkoxy substitution on alkyl. Examples of "alkoxyalkyl" include CH₃OCH₂, CH₃OCH₂CH₂, CH₃CH₂OCH₂, CH₃CH₂CH₂CH₂OCH₂ and CH₃CH₂OCH₂CH₂. "Alkylthio" includes branched or straight-chain alkylthio moieties such as methylthio, ethylthio, and the different propylthio, butylthio, pentylthio and hexylthio isomers. "Alkylsulfinyl" includes both enantiomers of an alkylsulfinyl group. Examples of "alkylsulfinyl" include CH₃S(O), CH₃CH₂S(O), CH₃CH₂CH₂S(O), (CH₃)₂CHS(O) and the different butylsulfinyl, pentylsulfinyl and hexylsulfinyl isomers. Examples of "alkylsulfonyl" include

CH₃S(O)₂, CH₃CH₂S(O)₂, CH₃CH₂CH₂S(O)₂, (CH₃)₂CHS(O)₂ and the different butylsulfonyl, pentylsulfonyl and hexylsulfonyl isomers. "Alkylamino",

"dialkylamino", and the like, are defined analogously to the above examples.

"Cycloalkyl" includes, for example, cyclopropyl, cyclobutyl, cyclopentyl, and cyclohexyl.

The term "halogen", either alone or in compound words such as "haloalkyl", includes fluorine, chlorine, bromine or iodine. 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", "haloalkynyl", "haloalkoxy", and the like, are defined analogously to the term "haloalkyl". Examples of "haloalkenyl" include (Cl)₂C=CHCH₂ and CF₃CH₂CH=CHCH₂. Examples of "haloalkynyl" include HC≡CCHCl, CF₃G≡C, CCl₃C=C and FCH₂C≡CCH₂. 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 6. For example, C₁-C₃ alkylsulfonyl designates methylsulfonyl through propylsulfonyl; C₂ alkoxyalkyl designates

CH₃OCH₂; C₃ alkoxyalkyl designates, for example, CH₃CH(OCH₃), CH₃OCH₂CH₂ or CH₃CH₂OCH₂; and C₄ alkoxyalkyl designates the various isomers of an alkyl group substituted with an alkoxy group containing a total of four carbon atoms, examples including CH₃CH₂CH₂OCH₂ and CH₃CH₂OCH₂CH₂. Examples of "alkylcarbonyl" include C(O)CH₃, C(O)CH₂CH₂CH₃ and C(O)CH(CH₃)₂. Examples of

"alkoxycarbonyl" include CH₃OC(=O), CH₃CH₂OC(=O), CH₃CH₂CH₂OC(=O), (CH₃)₂CHOC(=O) and the different butoxy- or pentoxycarbonyl isomers. In the above recitations, when a compound of Formula I is comprised of one or more heterocyclic rings, all substituents are attached to these rings through any available carbon or nitrogen by replacement of a hydrogen on said carbon or nitrogen.

When a group contains a substituent which can be hydrogen, for example R¹ or R¹⁴, 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.

Some compounds of this invention can exist as one or more tautomers. One skilled in the art will recognize, for example, that compounds of Formula la (Formula I where Q is Q-1, R³ is OR¹⁴, and R¹⁴ is H) can also exist as the tautomers of Formulae lb and Ic as shown below. One skilled in the art will recognize that said tautomers often exist in equilibrium with each other. As these tautomers interconvert under

environmental and physiological conditions, they provide the same useful biological effects. The present invention includes mixtures of such tautomers as well as the individual tautomers of compounds of Formula I.

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 such as a carboxylic acid or enol. Preferred salts include the lithium, sodium, potassium, triethylammonium, and quaternary ammonium salts of the compounds of the invention.

Preferred compounds for reasons of better activity and/or ease of synthesis are: Preferred 1. Compounds of Formula I, and N-oxides and agriculturally-suitable salts thereof, wherein:

A is selected from the group 1H-pyrrolyl; furanyl; thienyl; 1H-pyrazolyl;

1H-imidazolyl; isoxazolyl; oxazolyl; isothiazolyl; thiazolyl;

1H-1,2,3-triazolyl; 2H-1,2,3-triazolyl; 1H-1,2,4-triazolyl; 4H-1,2,4-triazolyl;

1,2,3-oxadiazolyl; 1,2,4-oxadiazolyl; 1,2,5-oxadiazolyl; 1,3,4-oxadiazolyl; 1,2,3-thiadiazolyl; 1,2,4-thiadiazolyl; 1,2,5-thiadiazolyl; 1,3,4-thiadiazolyl; 1H-tetrazolyl; 2H-tetrazolyl; pyridinyl; pyridazinyl; pyrimidinyl; pyrazinyl; 1,3,5-triazinyl; 1,2,4-triazinyl; and A may optionally be substituted by one to three R², provided that when a nitrogen atom of a heterocyclic ring is substituted with R², then R² is other than halogen;

Preferred 2. Compounds of Preferred 1 wherein:

Q is Q-1.

Preferred 3. Compounds of Preferred 2 wherein:

each R¹ is independently C₁-C₃ alkyl, C₁-C₃ alkoxy, halogen or nitro;

R³ is OR¹⁴; and

R¹⁴ is Η or C₁-C₄ alkylsulfonyl; or R¹⁴ is benzoyl or phenylsulfonyl, each optionally substituted with C₁-C₃ alkyl, halogen, cyano or nitro.

Preferred 4. Compounds of Preferred 3 wherein:

A is pyridinyl, pyridazinyl, pyrimidinyl or 1H-pyrazolyl;

R² is -(Y)_t-S(O)_nR¹⁵, CF₃, OCF₃, OCF₂Η or cyano;

R¹⁵ is C₁-C₆ alkyl;

t is 0; and

n is 2.

Preferred 5. Compounds of Preferred 1 wherein:

Q is Q-2;

Preferred 6. Compounds of Preferred 5 wherein:

each R¹ is independently C₁-C₃ alkyl, C₁-C₃ alkoxy, halogen or nitro; R⁵ is OR¹⁴;

R¹⁴ is H or C₁-C₄ alkylsulfonyl; or R¹⁴ is benzoyl or phenylsulfonyl, each optionally substituted with C₁-C₃ alkyl, halogen, cyano or nitro.

R⁶ is H, C₁-C₆ alkyl, or C₃-C₆ alkenyl; and

R⁷ is H;

Preferred 7. Compounds of Preferred 6 wherein:

A is pyridinyl, pyridazinyl, pyrimidinyl or 1H-pyrazolyl;

R² is -(Y)_t-S(O)_nR¹⁵, CF₃, OCF₃, OCF₂Η or cyano; R¹⁵ is C₁-C₆ alkyl;

t is 0; and

n is 2.

Preferred 8. Compounds of Preferred 1 wherein:

Q is Q-3.

Preferred 9. Compounds of Preferred 8 wherein:

each R¹ is independently C₁-C₃ alkyl, C₁-C₃ alkoxy, halogen or nitro; R⁸ is H, C₁-C₃ alkyl, or cyclopropyl; and

R⁹ is H or C₂-C₃ alkoxycarbonyl.

Preferred 10. Compounds of Preferred 9 wherein:

A is pyridinyl, pyridazinyl, pyrimidinyl or 1H-pyrazolyl;

R² is -(Y)_t-S(O)_nR¹⁵, CF₃, OCF₃, OCF₂Η or cyano;

R¹⁵ is C₁-C₆ alkyl;

t is 0; and

n is 2.

Preferred 11. Compounds of Preferred 1 wherein:

Q is Q-4.

Preferred 12. Compounds of Preferred 11 wherein:

each R¹ is independently C₁-C₃ alkyl, C₁-C₃ alkoxy, halogen or nitro; R¹⁰ is C₃-C₆ cycloalkyl or C₃-C₆ halocycloalkyl, each optionally

substituted with 1-4 C₁-C₃ alkyl; and

R¹¹ is cyano or C₂-C₆ alkoxycarbonyl.

Preferred 13. Compounds of Preferred 12 wherein:

A is pyridinyl, pyridazinyl, pyrimidinyl or 1H-pyrazolyl;

R² is -(Y)_rS(O)_nR¹⁵, CF₃, OCF₃, OCF₂Η or cyano;

R¹⁵ is C₁-C₆ alkyl;

t is 0; and

n is 2.

Most preferred are compounds of Formula la above, and sodium, potassium, and quaternary ammonium salts thereof, selected from the group:

a) 3-hydroxy-2-[[6-(trifluoromethyl)[2,4'-bipyridin]-3-yl]carbonyl]-2- cyclohexen-1-one;

b) 2-[2-chloro-4-(4-pyridinyl)benzoyl]-3-hydroxy-2-cyclohexen-1-one; and c) 2-[2,5-dimethyl-3-(1-methyl-1H-pyrazol-3-yl)-4-(methylsulfonyl)benzoyl]- 3-hydroxy-2-cyclohexen-1-one.

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 1-22. The definitions of W, Y, A, R¹-R¹⁶, m, n, p, r, and t in the compounds of Formulae 1-22 below are as defined above in the Summary of the Invention. Compounds of Formulae Ia-Ig are various subsets of the compounds of Formula I, and all substituents for Formulae Ia-Ig are as defined above for Formula I.

Compounds of General Formula Id can be readily prepared by one skilled in the art by using the reactions and techniques described in Schemes 1-14 of this section as well as by following the specific procedures given in Example 1.

Scheme 1 illustrates the preparation of compounds of Formula Id (R³ is OR¹⁷ and R¹⁷ is the same as R¹⁴ as described in the Summary of the Invention excluding H) whereby a compound of Formula Id (R³ is OH) is reacted with a reagent of Formula 1 in the presence of a base wherein X¹ is chlorine, bromine, fluorine, trifluorosulfonyloxy (OTf) or acetyloxy (OAc) and R¹⁷ is as previously defined. The coupling is carried out by methods known in the art (or by slight modification of these methods): for example, see K. Nakamura, et al., WO 95/04054. Scheme 1

Id (R³ is OH) + R¹⁷χ¹ → Id (R³ is OR ¹⁷)

1

wherein R¹⁷ is the same as R¹⁴ as described

in the Summary of the Invention excluding H;

X¹ is chlorine, bromine, fluorine, trifluorosulfonyloxy

(OTf) or acetyloxy (OAc)

Scheme 2 illustrates the preparation of compounds of Formula Id (R³ is SO_nR¹⁸; n is 1 or 2; and R¹⁸ is C₁-C₆ alkyl or C₁-C₆ haloalkyl) whereby a compound of Formula Id (R³ is SR¹⁸) is reacted with an oxidizing reagent such as peroxyacetic acid, m-chloroperoxybenzoic acid, potassium peroxymonosulfate (e.g., Oxone®, available from Aldrich Chemical Company), or hydrogen peroxide (the reaction may be buffered with a base such as sodium acetate or sodium carbonate). The oxidation is carried out by methods known in the art (or by slight modification of these methods): for example, see B. M. Trost, et al., J. Org. Chem. (1988), 53, 532; B. M. Trost, et al., Tetrahedron Lett. (1981), 21, 1287; S. Patai, et al., The Chemistry of Sulphones and Sulphoxides, John Wiley & Sons, Protecting and deprotecting functional groups not compatible with the reaction condition may be necessary for compounds with such a functional group (for procedures, see T. W. Greene, et al., Protective Groups in Organic Synthesis, Second Edition, John Wiley & Sons, Inc.).

Scheme 2

Id (R³ is SR^{1 8}) Id (R³ is S(O)_nR^{1 8}; n is 1 or 2)

wherein R¹⁸ is C₁-C₆ alkyl or C₁-C₆ haloalkyl

Compounds of Formula Id (R³ is Nu; Nu is SR¹⁸or OR¹⁹; R¹⁸ is as defined previously ; R¹⁹ is C₁-C₆ alkyl, C₁-C₆ haloalkyl or C₂-C₆ alkoxyalkyl) can be prepared by one skilled in the art from a compound of Formula Id (R³ is halogen) by treatment with a nucleophile of Formula 2 (Nu is SR¹⁸or OR¹⁹; M is Na, K or Li) as shown in Scheme 3 using methods well documented in the literature (or slight modification of these methods): for example, see S. Miyano, et al., J. Chem. Soc., Perkin Trans. 1 (1976), 1 146. Scheme 3

Id (R³ is halogen) + MNu

Id (R³ is SR¹⁸ or OR¹⁹)

2

wherein Nu is SR¹⁸ or OR¹⁹; M is Na, K or Li;

and R¹⁹ is C₁-C₆ alkyl, C₁-C₆ haloalkyl or C₂-C₆

alkoxyalkyl

Compounds of Formula Id (R³ is halogen) can be prepared by reacting a compound of Formula Id (R³ is OH) with a halogenating reagent such as oxalyl bromide or oxalyl chloride (Scheme 4). This conversion is carried out by methods known in the art (or by slight modification of these methods): for example see S. Muller, et al., WO 94/13619; S. Muller, et al., DE 4,241,999.

Scheme 4

Id (R³ is OH)

Id (R³ is halogen)

Halogenating

reagent (e.g., oxalyl

bromide, oxalyl chloride)

Scheme 5 illustrates the preparation of compounds of Formula Id (R³ is OH), whereby an enol ester of Formula 3 is reacted with a base such as triethylamine in the presence of a catalytic amount of cyanide source (e.g., acetone cyanohydrin or potassium cyanide). This rearrangement is carried out by methods known in the art (or by slight modification of these methods): for example see W. J. Michaely,

EP 369,803.

3

Enol esters of Formula 3 can be prepared by reacting a dione of Formula 4 with an acid chloride of Formula 5 in the presence of a slight mole excess of a base such as triethylamine in an inert organic solvent such as acetonitrile, methylene chloride or toluene at temperatures between 0 °C and 110 °C (Scheme 6). This type of coupling is known in the art: for example, see W. J. Michaely, EP 369,803.

The acid chlorides of Formula 5 can be prepared by one skilled in the art by reacting an acid of Formula 6 with oxalyl chloride (or thionyl chloride) and a catalytic amount of dimethylformamide (Scheme 7). This chlorination is well known in the art: for example, see W. J. Michaely, EP 369,803.

Enol esters of Formula 3a can also be prepared by directly reacting the acid of Formula 6a with N-methyl-2-chloropyridinium iodide, followed by treatment of the formed intermediate with the dione of Formula 4 in the presence of a base such as triethylamine (Scheme 8). This coupling is carried out be methods known in the art (or by slight modification of these methods): for example, see E. Haslam Tetrahedron (1980), 36, 2409-2433.

Scheme 9 illustrates the preparation of acids of Formula 6 (R¹ is S(O)_nR¹⁵ and n is 1 or 2) whereby an acid of Formula 6 (R¹ is SR¹⁵) is reacted with an oxidizing reagent such as peroxyacetic acid, w-chloroperoxybenzoic acid, Oxone®, or hydrogen peroxide (the reaction may be buffered with a base such as sodium acetate or sodium carbonate). The oxidation is carried out by methods known in the art (or by slight modification of these methods): for example, see B. M. Trost, et al., J. Org. Chem.

(1988), 53, 532; B. M. Trost, et al., Tetrahedron Lett. (1981), 21, 1287; S. Patai, et al.,

The Chemistry of Sulphones and Sulphoxides, John Wiley & Sons. For some acids of

Formula 6 (R¹ is SR¹⁵) with a functional group not compatible with the reaction conditions, the functional group may be protected before the oxidation and then be deprotected after the oxidation. The protecting and deprotecting procedures are well known in the literature: for example see T. W. Greene, et al., Protective Groups in

Organic Synthesis (Second Edition), John Wiley & Sons, Inc.

wherein R¹ is S(O)_nR¹⁵ and n is 0 wherein R ¹ is S(O)_nR¹⁵ and n is 1 or 2 Scheme 10 illustrates the preparation of acids of Formula 6 (n is 0 if R¹ is S(O)_nR¹⁵) whereby a phenyl bromide of Formula 7 (n is 0 if R¹ is S(O)_n R¹⁵) is treated with n-butyllithium (or magnesium) and the lithium salt (or the Grignard reagent) generated in situ is then reacted with carbon dioxide followed by acidification with an acid such as hydrochloric acid. This conversion is carried out by methods known in the art (or by slight modification of these methods): for example, see M. A. Ogliaruso, et al., Synthesis of Carboxylic Acids, Esters and Their Derivatives, pp 27-28, John Wiley & Sons; A. J. Bridges, et al., J. Org. Chem. (1990), 55, 113; C. Franke, et al., Angew. Chem. Int. Ed. (1969), 8, 68. Protecting and deprotecting functional groups not compatible with the reaction conditions may be necessary for compounds with such a functional group.

Many acids of Formula 6 can also be prepared, as shown in Scheme 1 1 , whereby an ester of Formula 8 is saponified (for example, potassium hydroxide in methanol, then acidification with an acid such as hydrochloric acid), or, alternatively, hydrolyzed in acid (for example, 5N hydrochloric acid in acetic acid) by methods known in the art (or slight modification of these methods); see for example, M. A. Ogliaruso, et al., Synthesis of Carboxylic Acids, Esters and Their Derivatives, John Wiley & Sons,

(1991), pages 5-7.

2

Esters of Formula 8 can be prepared using methods known in the art (or by slight modification of these methods): for example, see A. R. Katritzky, et al., Comprehensive Heterocyclic Chemistry, volumes 2-6, Pergamon Press.

Esters of Formula 8a or 8b can also be prepared as shown in Scheme 12, whereby an ester of Formula 9a or 9b is contacted with an appropriate nucleophilic heterocycle Nu¹ and a suitable base in an inert solvent. This reaction can be carried out by a variety of well-known methods, preferably with potassium carbonate or potassium tert-butoxide as the base with N,N-dimethylfoimamide as the solvent and at a reaction temperature range of from approximately 0 to 100 °C.

2 /

//

Esters of Formula 9a and 9b are commercially available or can be prepared using methods known in the art (or by slight modification of these methods).

Scheme 13 illustrates the preparation of acids of Formula 6a whereby an aryl bromide of Formula 9c is treated with an aryl tin reagent in the presence of a palladium catalyst. This conversion is carried out by methods known in the art (or by slight modification of these methods): for example, see M. Fujta, et al., Tetrahedron Letters, (1995), 29, 5247-5250; Y. Yamamoto, et al., Heterocycles, (1996), 42, 189-194.

Saponification of the ester with a base such as sodium hydroxide provides the acids of Formula 6a.

Bromides of Formula 9c are either commercially available or can easily be prepared by methods known in the art (or by slight modification of these methods): for example, see T. Bryson, et al., J. Org. Chem., (1976), 41, 2066; Andrea, T. A. and

Liang, P. H., U.S. 5,393,734. Aryl and heteroaryl organotin compounds can be prepared by methods known in the art (or by slight modification of these methods): for example, see D. Peters, et al., J. Heterocyclic Chem., (1990), 27, 2165.

Bromides of Formula 7 (n is 0 if Rl is S(O)_n R¹⁵) can be prepared by one skilled in the art by using methods known in the art (or by slight modification of these methods): for example, see A. R. Katritzky, et al., Comprehensive Heterocyclic Chemistry, Volume 2-6, Pergamon Press; B. M. Lynch, et al., Tel. Lett. (1964), p. 617; M. A. Kahn, et al., Rev. Latinoam. Quim. (1972), 3, p. 1 19; M. Kosugi, et al., Bull. Chem. Soc. Jpn. (1986), 59 (2), p. 677.

Alternatively some of the bromides of Formula 7 (n is 0 if R¹ is S(O)_nR¹⁵) can also be prepared by bromination of the corresponding substituted benzenes of Formula 8 (n is 0 if R¹ is S(O)_nR¹⁵) with the bromine or other equivalent reagent in an inert organic solvent as shown in Scheme 14. This bromination is carried out by general methods known in the art; see, for example, E. Campaigne, et al., J. Heterocycl. Chem. (1969), 6, p. 517; H. Gilman, J. Am. Chem. Soc. (1955), 77, p. 6059;

The compounds of Formula 8 (n is 0 if R¹ is S(O)_nR¹⁵) can be prepared by one skilled in the art by using methods known in the art (or by slight modification of these methods): for example, see A. R. Katritzky, et. al., Comprehensive Heterocyclic Chemistry, Volume 2-6, Pergamon Press; B. M. Lynch, et al., Tet. Lett. (1964), p. 617; M. A. Kahn, et al., Rev. Latinoam. Quim. (1972), 3, p. 119; M. Kosugi, et al., Bull. Chem. Soc. Jpn. (1986), 59, (2), p. 677.

Compounds of General Formula le can be readily prepared by one skilled in the art by using the reactions and techniques described in Schemes 15-17 of this section.

Scheme 15 illustrates the preparation of compounds of Formula le (R¹⁴ is R^14a and R^14a is the same as R¹⁴ as described in the Summary of the Invention excluding H) whereby a compound of Formula le ( R'⁴ is H) is reacted with a reagent of Formula 9 in the presence of a base wherein X² is chlorine, bromine, fluorine, OTf or OAc and R^{, 4a} is as previously defined. This coupling is carried out by methods known in the art (or by slight modification of these methods): for example, see K. Nakamura, et al.,

WO 95/04054.

Scheme 15 le (R¹⁴ is H) + R^14aX²→

le (R ¹⁴ is R^14a)

9

Scheme 16 illustrates the preparation of compounds of Formula le (R¹⁴ is H). whereby an ester of Formula 10 is reacted with a base such as triethylamine in the presence of a catalytic amount of cyanide source (e.g., acetone cyanohydrin or potassium cyanide). This rearrangement is carried out by methods known in the art (or by slight modification of these methods): for example, see W. J. Michaely, EP 369,803.

10 Esters of Formula 10 can be prepared by reacting a hydroxypyrazole of

Formula 11 with an acid chloride of Formula 5 in the presence of a slight mole excess of a base such as triethylamine in an inert organic solvent such as acetonitrile, methylene chloride or toluene at temperatures between 0 °C and 110 °C (Scheme 17). This type of coupling is carried out by methods known in the art (or by slight modification of these methods): for example, see W. J. Michaely, EP 369,803.

Compounds of General Formula If can be readily prepared by one skilled in the art by using the reactions and techniques described in Schemes 18-21 of this section.

Scheme 18 illustrates the preparation of compounds of Formula If whereby a compound of Formula 12 is reacted with a salt of hydroxylamine such as hydroxylamine hydrochloride in the presence of a base or acid acceptor such as triethylamine or sodium acetate. The substituents of the immediate products may be further modified if appropriate. This cyclization is carried out by methods known in the art (or by slight modification of these methods): for example, see P. A. Cain, et al., EP 560,483; C. J. Pearson, et al., EP 636,622.

12

wherein

L is a leaving group such as C ₁-C₄alkoxy (e.g. OC₂H₅)

or MN-dialkylamino (e.g. dimethyl amino)

R⁹a is R⁹ or CONH₂

Scheme 19 illustrates the preparation of compounds of Formula 12 whereby a compound of Formula 13 is reacted with a reagent of Formula 14 or Formula 15. This conversion is carried out by methods known in the art (or by slight modification of these methods): for example, see P. A. Cain, et al., EP 560,483; C. J. Pearson, et al.,

EP 636,622.

Scheme 20 illustrates the preparation of compounds of Formula 13 whereby a ester of Formula 16 is decarboxylated in the presence of a catalyst, such as

p-toluenesulfonic acid, in an inert solvent such as toluene. This conversion is carried out by methods known in the art (or by slight modification of these methods): for example, see P. A. Cain, et al., EP 560,483; C. J. Pearson, et al., EP 636,622.

Esters of Formula 16 can be prepared by reacting the metal salt of a compound of

Formula 17 with an acid chloride of Formula 5 (Scheme 21). This type of coupling is known in the art: for example see P. A. Cain, et al., EP 560,483; C. J. Pearson, et al.,

EP 636,622.

Scheme 22 illustrates the preparation of compounds of Formula Ig whereby a compound of Formula 5 is reacted with a compound of Formula 18 in the presence of a base such as triethylamine, potassium carbonate, sodium hydride or Mg(OEt)₂ in an inert organic solvent such as diethyl ether, tetrahydrofuran, NN-dimethylformamide, dichloromethane or acetonitrile.

This conversion is carried out by methods known in the art (or slight modification of these methods); for example, see J. W. Ashmore, EP 213,892 and P. A. Cain, EP 496,631 Al.

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 intercon versions 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.

•H NMR spectra are reported in ppm downfield from tetramethylsilane; s = singlet, d = doublet, t = triplet, q = quartet, m = multiplet, dd = doublet of doublets, dt = doublet of triplets, br s = broad singlet.

EXAMPLE 1

Step A: Preparation of 3-[(2,5-dimethylphenyl)thiolpropanoic acid

43.4 g (1.086 mol) of sodium hydroxide was added to 230 mL of water, 75.0 g (0.543 mol) of 2,5-dimethylthiophenol (purchased from Aldrich Chemical Company) was then added and the mixture was cooled to about 10 C. 91.30 g (0.597 mol) of 3- bromopropionic acid (purchased from Aldrich Chemical Company) was added in portions keeping the temperature below 25 °C. The mixture was warmed to room temperature, stirred for 2 hr under nitrogen, and was then washed with diethyl ether (3 x 500 mL). The aqueous layer was acidified with 1N HCl and filtered to yield 112.79 g of the title compound of step A as a solid, m.p. 97-98 °C.

¹H NMR (CDCI₃): 52.3 (s, 3H), 2.34 (s, 3H), 2.68 (t, 2H), 3.1 (t, 2H), 6.9 (d, 1H), 7.06-7.14 (2H).

Step B: Preparation of 2,3-dihydro-5,8-dimethyl-4H-1-benzopyran-4-one

530 mL of concentrated sulfuric acid was added to 24.91 g (0.1 19 mol) of the title compound of step A while being cooled with an acetone/ice bath. The ice bath was removed, the mixture was stirred for 1 hr and was then poured over crushed ice. The aqueous phase was extracted with a mixture of diethyl ether : hexane (1:9, 6 x 500 mL), dried (MgSO₄), filtered, and evaporated to dryness to yield 11.75 g of the title compound of step B as an oil.

1H NMR (CDCI₃): δ 2.3 (s, 3H), 2.6 (s, 3H), 2.97 (m, 2H), 3.2 (m, 2H), 6.9-7.1

(2H).

Step C: Preparation of 6-bromo-2,3-dihydro-5,8-dimethyl-4H-1-benzothiopyran-

4-one

A solution of 4.07 g (0.021 mol) of the title compound of step B in 25 mL of methylene chloride was added dropwise to a mixture of 7.07 g (0.053 mol) of aluminum chloride (purchased from Aldrich Chemical Company) in 25 mL of methylene chloride. The suspension was stirred for approximately 15 minutes, 1.14 mL (0.022 mol) of bromine (purchased from Janssen) was added dropwise, and the mixture was then refluxed for 10 minutes. The warm mixture was poured into 10 mL of concentrated hydrochloric acid containing 75 g of ice, stirred for 10 minutes, diluted with 50 mL of water, and extracted with diethyl ether (2 x 200 mL). The combined organic layers were washed with water (2 x 200 mL), dried (Na₂SO₄), filtered, and evaporated to dryness. The crude product was chromatographed over silica gel eluting with a mixture of ethyl acetate : hexane (5:95) to yield 2.62 g of the title compound of step C as a solid, m.p. 87-88 °C.

¹Η NMR (CDCI₃): δ 2.3 (s, 3Η), 2.6 (s, 3H), 3.0 (m, 2H), 3.2 (m, 2H), 7.45 (s, 1H).

Step D: Preparation of 6-bromo-5,8-dimethyl-4H-1 -benzothiopyran-4-one

30 g (0.11 mol) of the title compound of step C and 8.95 mL (0.1 1 mol) of pyridine were added to 250 mL of methylene chloride. The solution was cooled to about 0 °C and 14.76 g (0.11 mol) of N-chlorosuccinimide was added. The mixture was stirred overnight under nitrogen while warming to room temperature and then refluxed for 12 h. The reaction was evaporated to dryness, the residue was stirred in diethyl ether, and filtered. The filtrate was dried (MgSO₄), filtered, and evaporated to dryness to yield 13.25 g of the title compound of step D as a solid, m.p. 123-124 °C.

1H NMR (CDCI₃): δ 2.5 (s, 3Η), 2.9 (s, 3H), 7.0 (d, 1H), 7.7 (m, 2H).

Step E: Preparation of 3-[3-bromo-2,5-dimethyl-6-(methylthio)phenyl]-1-methyl- 1H-pyrazole

13.25 g (0.049 mol) of the title compound of step D and 2.88 mL (0.054 mol) of methylhydrazine (purchased from Aldrich Chemical Company) was added to 150 mL of absolute ethanol. After stirring at reflux under nitrogen for 5 hr the mixture was allowed to warm to room temperature and stir for 2.5 days. The mixture was refluxed for 3 hr after which time 0.5 mL of acetic acid was added and the reaction was refluxed overnight. After cooling to room temperature, 12.35 mL (0.054 mol) of sodium methoxide (25% in methanol) and 3.66 mL (0.059 mol) of iodomethane were added and the reaction stirred for 2 hr. The mixture was evaporated to dryness. The residue was stirred in water, extracted with methylene chloride (250 mL), dried (MgSO₄), filtered, and evaporated to dryness. The crude product was chromatographed over silica gel eluting with methylene chloride to yield 5.97 g of the title compound of step E as an oil.

¹H NMR (CDCI₃): δ 2.0 (s, 3H), 2.1 (s, 3H), 2.5 (s, 3H), 3.6 (s, 3H), 6.2 (s, 1H), 7.6 (m, 2H).

Step F: Preparation of 2,5-dimethyl-3-(1-methyl-1H-pyrazol-3-yl)-4- (methylthio)benzoic acid

5.9 g (0.019 mol) of the title compound of step E was added to 100 mL of tetrahydrofuran and cooled to -70 °C. 9.1 mL (0.023 mol) of 2.5M n-butyllithium (purchased from Aldrich Chemical Company) was added dropwise keeping the temperature below -65ºC. Solid carbon dioxide was added in one portion and the mixture warmed to room temperature. 200 mL of hexane was added and the mixture was filtered. The solid collected was added to water and acidified to about pΗ 1 with concentrated hydrochloric acid. The aqueous was extracted with methylene chloride (3 x 100 mL), dried (MgSO4), filtered, and evaporated to dryness to yield 3.13 g of the title compound of step F as a semi-solid.

1 Η NMR (CDCI₃): δ 2.1 (s, 3Η), 2.3 (s, 3H), 2.6 (s, 3H), 3.6 (s, 3H), 6.2 (m,

1H), 7.6 (d, 1H), 7.97 (s, 1H).

Step G: Preparation of 2,5-dimethyl-3-(1-methyl-1H-pyrazol-3-yl)-4-

(methylsulfonyl)benzoic acid

4.5 mL (0.046 mol) of hydrogen peroxide (35%) was added to 25 mL of trifluoroacetic acid. The mixture was allowed to stir for 30 min under nitrogen and was then cooled to 0 C. A solution of 3.1 g (0.011 mol) of the title compound of step F in 25 mL of trifluoroacetic acid was added dropwise keeping the temperature below 10 °C. The mixture was warmed to room temperature and stirred for 3 days. 2 mL of dimethylsulfide was added and the reaction stirred for 30 min. The mixture was then evaporated to dryness, and the residue was triturated with water and filtered. The collected solid was dissolved in methylene chloride, dried (MgSO4), filtered, and evaporated to dryness to yield 1.41 g of the title compound of step G as a solid, m.p. 60

°C (dec).

¹Η NMR (CDCI₃): δ 2.2 (s, 3Η), 2.8 (s, 3H), 3.0 (s, 3H), 3.7 (s, 3H), 6.2 (m, 1H), 7.7 (m, 1H), 8.0 (s, 1H). Step H: Preparation of 3-oxo-1-cylcohexen-1-yl 2,5-dimethyl-3-(1-methyl-1H- pyrazol-3-yl)-4-(methylsulfonyl)benzoate

1.39 g (0.0045 mol) of the title compound of step G, 1.18 mL (0.0135 mol) of oxalyl chloride (purchased from Janssen), and 2 drops of N,N-dimethylformamide were added to 50 mL of methylene chloride. The mixture was refluxed under nitrogen for 2.5 hr and was then evaporated to dryness. 50 mL of methylene chloride was added to the residue and the solution was again evaporated to dryness. Another 50 mL of methylene chloride was added to the residue, and the solution was cooled to about 0 °C. 0.56 g (0.0049 mol) of 1,3-cyclohexanedione (purchased from Aldrich Chemical Company) was added followed by 1.94 mL (0.0139 mol) of triethylamine, and the mixture was stirred overnight while warming to room temperature. The mixture was evaporated to dryness and the crude product was chromatographed over silica gel eluting with a mixture of ethyl acetate:hexane (6:4, then 7:3) to yield 0.47 g of the title compound of step Η as a solid, m.p. 165 - 167 ºC.

1Η NMR (CDCI₃): 6 2.1 - 2.2 (m, 5Η), 2.5 (m, 2H), 2.7 (m, 2H), 2.8 (s, 3H),

2.98 (s, 3H), 3.6 (s, 3H), 6.0 (s, 1H), 6.1 (m, 1H), 7.6 (m, 1H), 7.9 (s, 1H).

Step I: Preparation of 2-[2,5-dimethyl-3-(1-methyl-1H-pyrazol-3-yl)-4-

(methylsulfonyl)benzoyl]-1,3-cycIohexanedione

0.47 g (0.0012 mol) of the title compound of step Η, 1 drop of acetone cyanohydrin (purchased from Aldrich Chemical Company), and 0.29 mL (0.0020 mol) of triethylamine were added to 25 mL of acetonitrile and allowed to stir overnight at room temperature under nitrogen. The mixture was evaporated to dryness, water was added to the residue, and the solution was acidified to pΗ 1 with concentrated hydrochloric acid. The aqueous was extracted with methylene chloride, dried (MgSO₄), filtered, and evaporated to dryness to yield 0.27 g of the title compound of example 1 , a compound of the invention, as a solid, m.p. 93 C (decomposed).

¹Η NMR (CDCI₃): δ 1.8 (s, 3Η), 2.1 (m, 2H), 2.4 (m, 2H), 2.7 (s, 3H), 2.8 (m, 2H), 2.98 (s, 3H), 3.7 (s, 3H), 6.2 (s, 1H), 7.1 (s, 1H), 7.6 (s, 1H).

EXAMPLE 2

Step A: Preparation of 2-[3-(trifluoromethyl)-1H-pyrazol-1-yl]benzoic acid

To 100 mL of dimethylformamide was added sequentially 19.3 g (0.125 mol) of methyl 2-fluorobenzoate, 18.7 g (0.138 mol) of 3-(trifluoromethyl)pyrazole (purchased from Maybridge Chemical Company), and 19.0 g (0.138 mol) of potassium carbonate. The suspension was stirred and heated at about 100 °C for 16 hours, then cooled to 25 °C and poured into excess water. The aqueous suspension was extracted three times with 75 mL of diethyl ether and the combined ether layers were dried over magnesium sulfate and concentrated under reduced pressure. The residual oil was chromatographed over silica gel eluting with hexane:ethyl acetate (9.6:0.4, then 100% ethyl acetate) to yield 15.3 g of crude methyl 2-[3-(trifluoromethyl)-1H-pyrazol-1-yl]benzoate as an oil. 14 g (0.052 mol) of this oil was added to a solution of 3.8 g (0.057 mol) of potassium hydroxide (85%) dissolved in 60 mL of methanol. The solution was stirred at 25 °C for one hour, refluxed for 5 hours, stirred at 25 °C for 48 hours, and finally concentrated under reduced pressure. 100 mL of water was added to the residue and the cloudy solution was extracted twice with 40 mL of diethyl ether. The clear aqueous layer was acidified with concentrated ΗCl and filtered. The collected solid was dissolved in dichloromethane, dried over magnesium sulfate, and the solvent was removed under reduced pressure to yield 5.0 g of the title compound of Step A as a solid melting at 138-144 °C.

¹Η NMR (CDCl₃): δ 6.95 (d, 1Η), 7.65 (m, 2Η), 7.7 (m, 1H), 7.85 (m, 1H), 8.35 (d, 1H), 13.15 (s, 1H).

Step B: Preparation of 3-oxo-1-cyclohexen-1-yl 2-[3-(trifluoromethyl)-1H- pyrazol-1-yl]benzoate

To 20 mL of oxalyl chloride was added portionwise 4.0 g of the title compound of Step A. The suspension was refluxed for about 3 hours and then concentrated under reduced pressure. The residue was azeotroped with dichloromethane (two times with 20 mL at 60 °C) to yield an oil which solidified upon cooling and melted at 64-68 °C. 2.0 g (0.0073 mol) of this acid chloride was added to 20 mL of dichloromethane, followed by the addition of 0.99 g (0.0088 mol) of 1,3-cyclohexanedione, and 2.2 g (0.022 mol) of triethylamine. The suspension was stirred overnight and then concentrated under reduced pressure. The residue was dissolved in diethyl ether and the solution was then extracted with water, dried over magnesium sulfate, and concentrated under reduced pressure to yield 2.0 g of the title compound of Step B as an oil.

1Η NMR (CDCI₃): δ 2.0 (m, 2H), 2.35 (m, 2H), 2.5 (m, 2H), 5.85 (s, 1H), 6.75

(d, 1H), 7.5 (m, 1H), 7.6 (m, 1H), 7.7 (m, 1H), 7.8 (d, 1H), 8.0 (m, 1H).

Step C: Preparation of 3-hydroxy-2-[2-[3-(trifluoromethyl)-1H-pyrazol- 1- yl]benzoyl]-2-cyclohexen-1-one

To 20 mL of acetonitrile was added sequentially 1.8 g (0.005 mol) of the title compound of Step B, 1.0 g (0.01 mol) of triethylamine, and 8 drops of acetone cyanohydrin. The solution was stirred under a nitrogen atmosphere at 25 °C overnight, and then diluted with 40 mL of water and acidified by the addition of concentrated hydrochloric acid (red to litmus paper). The suspension was filtered, and the collected solid was washed three times with 20 mL of water, suction dried, and then recrystallized from 2-propanol to yield 0.97 g of the title compound of Step C, a compound of this invention, as a solid melting at 141-143 °C.

¹Η NMR (CDCI₃): δ 1.8 (m, 2Η), 2.1 (m, 2H), 2.6 (m, 2H), 6.6 (d, 1H), 7.4-7.6 (m, 4H), 7.75 (d, 1H), 16.6 (s, 1H). EXAMPLE 3

Step A: Preparation of methyl 6-(trifluoromethyl)[2,4'-bipyridinel-3-carboxylate

To a stirred solution of 8.49 g (0.03 mol) of methyl 2-bromo-6-(trifluoromethyl)- 3-ρyridine carboxylate (prepared as described by Andrea T. A. and Liang P. H., U.S. Patent 5,393,734) in 25 mL of N,N-dimethylformamide under a nitrogen atmosphere was added 0.5 g of tetrakis(triphenylphosphine)palladium(0) and the mixture was heated at 100 °C for 30 minutes. 11 g (0.03 mol) of 4-tributylstannylpyridine (prepared by a modification of the procedure described by A. Lee and W. Dai, Tetrahedron Letters (1996), 37, 495-498) was added and heating was continued at 100 °C for 24 hours. The reaction mixture was cooled to room temperature and N,N-dimethylformamide was removed by distillation under high vacuum. The residue was purified by flash chromatography over silica gel utilizing dichloromethane:ethyl acetate (8:2) to provide 4.0 g of the title compound of Step A as a red oil.

¹H NMR (CDCI₃): δ 8.76 (d, 2H), 8.4 (d, 1H), 7.8 (d, 1H), 7.47 (m, 2H), 3.76 (s, 3H).

Step B: Preparation of 6-(trifluoromethyl)[2,4'-bipyridinel-3-carboxylic acid

To a solution of 1.7 g of the title compound of Step A in 20 mL of methanol was added 2 mL of 50% aqueous sodium hydroxide and the reaction was stirred at room temperature for 24 hours. The mixture was concentrated and acidified with 6N aqueous hydrochloric acid to pH 3 and extracted three times with 20 mL of ethyl acetate. The combined organic layers were dried over magnesium sulfate and concentrated under reduced pressure to provide 1.6 g of title compound of Step B as a crude solid.

¹H NMR (CD₃)₂SO): δ 9.02 (d, 2H), 8.26 (d, 1H), 8.22 (m, 1H), 8.14 (d, 2H). Step C: Preparation of 3-oxo-1-cyclohexen-1-yl 6-(trifluoromethyl)[2,4'- bipyridinel-3-carboxylate

To a suspension of 1.6 g (6 mmol) of the title compound of Step B in 100 mL of dichloromethane was added 0.78 g (7 mmol) of 1,3-cyclohexanedione followed by 2.4 mL (16 mmol) of triethylamine and 1.8 g (7 mmol) of 2-chloro-1-methylpyridinium iodide. The mixture was stirred at room temperature under nitrogen for 24 hours and then applied directly to a silica gel column and purified by flash chromatography using ethyl acetate/dichloromethane (2:8) to afford 1.34 g of the title compound of Step C as a tan solid melting at 49-56 °C.

¹H NMR (CDCI₃): δ 8.78 (d, 2H), 8.6 (d, 1H), 7.51 (d, 2H), 5.93 (s, 1H), 2.2 (m, 2H), 2.1 (m, 2H), 2.0 (m, 2H).

Step D: Preparation of 3-hydroxy-2-[[6-(trifluoromethyl)[2,4'-bipyridin]-3- yl]carbonyl]-2-cyclohexen-1-one

To a solution of 1.22 g (3.5 mmol) of the title compound of Step C in 25 mL of acetonitrile was added 1.16 mL (8.36 mmol) of triethylamine, followed by 2 drops of acetonecyanohydrin. The mixture was stirred under nitrogen for 18 hours. The mixture was then concentrated under reduced pressure, and the residual oil was acidified with aqueous 1N hydrochloric acid and extracted three times with 20 mL of dichloromethane. The combined organic layers were dried over magnesium sulfate and concentrated under reduced pressure to afford 0.4 g of the title compound of Step D, a compound of this invention, as a white solid melting at 137-145 °C.

¹H NMR (CDCl₃): δ 8.66 (m, 2H), 7.79 (m, 2H), 7.45 (m, 2H), 2.8 (m, 2H), 2.0 (m, 2H), 1.8 (m, 2H).

By the procedures described herein together with methods known in the art, the following compounds of Tables 1 to 20 can be prepared. The following abbreviations are used in the Tables which follow: NO₂ = nitro and Ph = phenyl.

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-mefhyl-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-C.

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 alfalfa, barley, cotton, wheat, rape, sugar beets, corn (maize), sorghum, soybeans, rice, oats, peanuts, vegetables, tomato, potato, perennial plantation crops including coffee, cocoa, oil palm, rubber, sugarcane, citrus, grapes, fruit trees, nut trees, banana, plantain, pineapple, hops, tea and 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 the art will appreciate that not all compounds are equally effective against all weeds. Alternatively, the subject compounds are useful to modify plant growth.

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.

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, azafenidin, azimsulfuron, benazolin, benazolin-ethyl, benfluralin, benfuresate,

bensulfuron-methyl, bensulide, bentazone, bifenox, bispyribac and its sodium salt, bromacil, bromoxynil, bromoxynil octanoate, butachlor, butralin, butroxydim (ICIA0500), butylate, caloxydim (BAS 620H), carfentrazone-ethyl, chlomethoxyfen, chloramben, chlorbromuron, chloridazon, chlorimuron-ethyl, chlornitrofen, chlorotoluron, chlorpropham, chlorsulfuron, chlorfhal-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-methyl-4-(1-methylethyl)-5-oxo-1H-imidazol-2-yl]-5-methyl-3- pyridinecarboxylic acid (AC 263,222), difenzoquat metilsulfate, diflufenican, dimepiperate, dimefhenamid, dimethylarsinic acid and its sodium salt, dinitramine, diphenamid, diquat dibromide, dithiopyr, diuron, DNOC, endothal, EPTC, esprocarb, ethalfluralin,

ethametsulfuron-methyl, ethofumesate, ethoxysulfuron, 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, flupoxam, flupyrsulfuron-methyl and its sodium salt, fluridone, flurochloridone, fluroxypyr,

fluthiacet-methyl, fomesafen, fosamine-ammonium, glufosinate, glufosinate-ammonium, glyphosate, glyphosate-isopropylammonium, glyphosate-sesquisodium,

glyphosate-trimesium, halosulfuron-methyl, haloxyfop-etotyl, haloxy fop-methyl,

hexazinone, imazamethabenz-methyl, imazamox, imazapyr, imazaquin,

imazaquin-ammonium, imazethapyr, imazethapyr-ammonium, imazosulfuron, ioxynil, ioxynil octanoate, ioxynil-sodium, isoproturon, isouron, isoxaben, isoxaflutole, lactofen, lenacil, linuron, maleic hydrazide, MCPA and its dimethylammonium, potassium and sodium salts, MCPA-isoctyl, mecoprop, mecoprop-P, mefenacet, mefluidide, metam-sodium, methabenzthiazuron, methylarsonic acid and its calcium, monoammonium, monosodium and disodium salts, methyl [[[1-[5-[2-chloro-4-(trifluoromethyl)phenoxy]-2-nitrophenyl]-2- methoxyethylidene]amino]oxy]acetate (AKH-7088), methyl 5-[[[[(4,6-dimethyl-2- pyrimidinyl)amino]carbonyl]amino]sulfonyl]-1-(2-pyridinyl)-1H-pyrazole-4-carboxylate (NC-330), metobenzuron, metolachlor, metosulam, metoxuron, metribuzin,

metsulfuron-methyl, molinate, monolinuron, napropamide, naptalam, neburon, nicosulfuron, norflurazon, oryzalin, oxadiazon, oxasulfuron, oxyfluorfen, paraquat dichloride, pebulate, pendimethalin, pentoxazone (KPP-314), perfluidone, phenmedipham, picloram,

picloram-potassium, pretilachlor, primisulfuron-methyl, prometon, prometryn, propachlor, propanil, propaquizafop, propazine, propham, propyzamide, prosulfuron, pyrazolynate, pyrazosulfuron-ethyl, pyridate, pyriminobac-methyl, 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, thiafluamidc (BAY 1 1390), thifensulfuron-methyl, thiobencarb, tralkoxydim, iri-allate, triasulfuron, triaziflam, 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 nicosulfuron, rimsulfuron, nicosulfuron in combination with rimsulfuron, imazethapyr, sethoxydim, glyphosate, and glufosinate.

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 abbreviation "dec." indicates that the compound appeared to decompose on melting. The abbreviation "Ex." stands for "Example" and is followed by a number indicating in which example the compound is prepared.

INDEX TABLE D

Cmpd No. ¹H NMR Data (CDCI₃ solution unless indicated otherwise)^a

1 δ 9.7 (m, 2H), 7.63 (m, 2H), 7.62 (m, 1H), 7.6 (s, 1H), 7.37 (m, 1H), 2.8 (m,

2H), 2.5 (m, 2H), 2.08 (m, 2H).

2 δ 8.65 (d, 2H), 7.6 (d, 1H), 7.5 (m, 3H), 7.27 (m, 1H), 3.13 (m, 6H), 2.32 (s,

4H), 1.3 (m, 9H), 1.04 (s, 6H).

3 δ 8.8 (m, 2H), 7.84 (m, 2H), 7.69 (m, 2H), 7.38 (d, 1H), 2.4 (m, 2H), 1.2 (m,

2H), 1.04 (d, 6H).

4 δ 8.62 (d, 2H), 7.6 (s, 1H), 7.5 (m, 3H), 7.28 (d, 1H), 3.17 (m, 6H), 2.5 (d,

2H), 2.2 (d, 1H), 1.7 (m, 1H), 1.31 (m, 9H), 1.03 (d, 3H).

5 δ 8.72 (m, 2H), 7.65 (m, 3H), 7.5 (d. 1H), 7.3 (d, 1H), 2.6-2.0 (m, 4H), 1.6

(m, 1H), 1.13 (d, 6H).

6 δ 7.9 (s, 1H), 7.7 (s, 1H), 7.5 (d, 1H), 7.28 (d, 1H), 6.8 (s, 1H), 3.18 (m,

6H), 2.42 (m, 4H), 1.98 (m, 2H), 1.29 (m, 9H).

8 δ 8.63 (d, 2H), 7.48 (s, 1H), 7.46 (m, 3H), 7.2 (d, 1H), 3.15 (m, 6H), 2.43

(m, 4H), 1.98 (m, 2H), 1.29 (m, 9H).

9 δ 8.7 (m, 1H), 8.0 (s, 1H), 7.8 (d, 1H), 7.72 (m, 1H), 7.70 (m, 1H), 7.26 (m,

1H), 3.14 (m, 6H), 2.45 (m, 4H), 1.99 (m, 2H), 1.26 (m, 9H).

10 δ 7.8 (d, 1H), 7.77 (s, 1H), 7.6 (d, 1H), 7.3 (m, 1H), 7.18 (d, 1H), 3.09 (m,

6H), 2.45 (m, 4H), 2.34 (s, 3H), 1.99 (m, 2H), 1.26 (m, 9H).

11 δ 7.88 (m, 2H), 7.85 (m, 1H), 7.33 (s, 1H), 7.16 (d, 1H), 2.71 (m, 2H), 2.4

(m, 2H), 2.33 (s, 3H), 2.0 (m, 2H).

12 δ 8.8 (s, 1H), 8.6 (d, 1H), 7.8 (dd, 1H), 7.5 (s, 1H), 7.4 (d, 1H), 7.35 (m,

1H), 7.24 (d, 1H), 3.21 (m, 6H), 2.45 (m, 4H), 1.99 (m, 2H), 1.28 (m, 9H).

14 δ 8.6 (d, 1H), 8.55 (d, 1H), 7.8 (d, 1H), 7.5 (m, 3H), 3.0 (m, 6H), 2.33 (m,

4H), 1.8 (m, 2H), 1.16 (m, 9H).

19 δ 8.6 (m, 2H), 7.7 (m, 1H), 7.65 (m, 1H), 7.5 (m, 1H), 7.2 (m, 1H), 2.95 (m,

6H), 2.9 (m, 1H), 2.3 (m, 2H), 1.6 (m, 2H), 1.13 (m, 9H), 0.95 (m, 6H).

21 δ 8.47 (m, 1H), 8.44 (m, 1H), 7.8 (m, 1H), 7.73 (m, 1H), 7.7 (m, 1H), 7.25

(m, 1H), 2.6 (m, 1H), 2.02 (m, 2H), 0.92 (m, 6H).

22 δ 8.6 (m, 2H), 8.0 (m, 1H), 7.77 (m, 1H), 7.6 (m, 1H), 7.4 (m, 1H), 3.2-1.8

(m, 6H).

26 67.57 (d. 1H), 7.1 (s, 1H), 6.1 (d, 1H), 3.67 (s, 3H), 3.2-2.1 (m, 10H), 1.73

(s, 3H), 1.29 (t, 3H), 1.13 (d. 3H).

27 67.56 (d, 1H), 7.1 (s, 1H), 6.11 (d, 1H), 3.67 (s, 3H), 3.2-3.0 (m, 2H), 2.82

(t, 2H), 2.74 (s, 3H), 2.42 (t, 2H), 2.14-2.0 (m, 2H), 1.74 (s, 3H), 1.29 (t, 3H). 29 δ 8.7 (m, 2H), 7.7-7.4 (m, 5H), 7.09 (s, 1H), 3.9 (q, 2H), 3.24 (m, 6H), 1.35

(m, 12H). ^{a 1}H NMR data are in ppm downfield from tetramethylsilane. Couplings are designated by (s)-singlet, (d)-doublet, (dd)-doublet of doublets, (t)-triplet, (q)-quartet, (m)-multiplet. BIOLOGICAL EXAMPLES OF THE INVENTION

TEST A

Seeds of barley (Hordeum vulgare), barnyardgrass (Echinochloa crus-gallϊ), 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), morningglory (ϊpomoea hederacea), rape (Brassica napus), rice (Oryza sativa), sorghum (Sorghum bicolor), soybean (Glycine max), sugar beet (Beta vulgaris), velvetleaf (Abutilon theophrasti), wheat (Triticum aestivum), wild buckwheat (Polygonum convolvulus), wild oat (Avenafatua) 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 A, 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 B

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 (Alopecurus myosuroides), chickweed (Stellaria media), cocklebur (Xanthium strumarium), corn (Zea mays v. Pioneer 3394), cotton (Gossypium hirsutum), crabgrass (Digitaria sanguinalis), downy brome (Bromus tectorum), giant foxtail (Setaria faberii), johnsongrass (Sorghum halpense), lambsquarters (Chenopodium album), morningglory (Ipomoea hederacea), pigweed (Amaranthus retroflexus), rape (Brassica napus), ryegrass (Lolium multiflorum), soybean (Glycine max), speedwell (Veronica persica), sugar beet (Beta vulgaris), velvetleaf (Abutilon theophrasti), wheat (Triticum aestivum), wild buckwheat (Polygonum convolvulus), and wild oat (Avenafatua). Additionally, two 10.3 cm pots each containing two plant of corn (Zea mays) of the varieties M17 and B73 were treated in addition to the normal compliment of crop species.

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), barnyardgrass2 (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 ratings, summarized in Table B, 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 C

Plastic pots were partially filled with silt loam soil. The soil was then saturated with water. Indica Rice (Oryza saliva) seed or seedlings at the 2.0 to 3.5 leaf stage; seeds, tubers or plant parts selected from arrowhead (Sagittaria rigida), barnyardgrass (Echinochloa crus- galli), ducksalad (Heteranthera limosa), early watergrass (Echinochloa oryzoides), junglerice (Echinochloa colonum), late watergrass (Echinochloa oryzicola), redstem

(Ammonia species), rice flatsedge (Cyperus iria), 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 C, 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.

Seeds, tubers, or plant parts of alexandergrass (Brachiaria plantaginea), bermudagrass (Cynodon dactylon), 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 exaltatά), Johnson grass (Sorghum halepense), large crabgrass (Digitaria sanguinalis), peanuts (Arachis hypogaea), pitted morningglory (Ipomoea lacunosa), purple nutsedge (Cyperus rotundus), sandbur (Cenchrus echinatus), sourgrass (Trichachne insularis), and Surinam grass (Brachiaria decumbens) were planted into greenhouse pots of flats containing greenhouse planting medium. Plant species were grown in separate pots or individual compartments. 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).

Test chemicals were formulated in a non-phytotoxic solvent mixture which included a surfactant and applied preemergence and postemergence to the plants. 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 D, 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 E

Seeds of barnyardgrass (Echinochloa crus-galli), bindweed (Concolculus arvensis), black nightshade (Solanum ptycanthum dunal), cassia (Cassia obtusifolia), cocklebur (Xanthium strumarium), common ragweed (Ambrosia artemisiifoliά), corn (Zea mays v. Pioneer 3394), corn2 (Zea mays v. IMR Ciba 4393), cotton (Gossypium hirsutam), crabgrass (Digitaria spp.), fall panicum (Panicum dichotomiflorum), giant foxtail (Setaria faberii), green foxtail (Setaria viridis), jimsonweed (Datura stramonium), johnsongrass (Sorghum halepense), lambsquarter (Chenopodium album), morningglory (Ipomoea spp.), pigweed (Amaranthus retroflexus), prickly sida (Sida spinosa), shattercane (Sorghum vulgare), signalgrass (Brachiaria platyphylla), smartweed (Polygonum pensylvanicum), soybean (Glycine max v. Williams 95) and soybean2 (Glycine max v. Asgrow 3304), sunflower (Helianthus annuus), velvetleaf (Abutilon theophrasti), wild proso (Pancium 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 included a surfactant. 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 E, are reported on a 0 to 100 scale where 0 is no effect and 100 is complete control.

TEST F

Compounds evaluated in this test were formulated in a non-phytotoxic solvent mixture which included a surfactant and applied to plants that were grown for various periods of time before treatment (postemergence application). A mixture of sandy loam soil and greenhouse potting mix in a 60:40 ratio was used for the postemergence 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 arrowleaf sida (Sida rhombifoliά), barnyardgrass (Echinochloa crus-galli), cocklebur (Xanthium strumarium), common lambsquarters (Chenopodium album), 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 faberii), hairy beggarticks (Bidens pilosa), ivyleaf morningglory (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 theophrasti) 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 F, were based upon a 0 to 100 scale where 0 was no effect and 100 was complete control. A dash response (-) means no test result.

TEST G

Compounds evaluated in this test were formulated in a non-phytotoxic solvent mixture which includes a surfactant and applied to plants that were grown for various periods of time before treatment (postemergence application). 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 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 bristly starbur (Acanthospermun hispidum) alexandergrass (Brachiaria plantaginea), american black nightshade (Solanum americanum), apple-of-Peru (Nicandra physaloides), arrowleaf sida (Sida rhombifolia), Brazilian sicklepod (Cassia tora Brazilian), Surinam grass (Brachiaria decumbens), capim- colchao (Digitaria horizontalis), Crist, soybean (Glycine max v. Cristalina), florida beggarweed (Desmodium purpureum), hairy beggarticks (Bidens pilosa), slender amaranth (Amaranthus viridis), southern sandbur (Cenchrus echinatus), tall morningglory (Ipomoea purpurea), tropical spiderwort (Commelina benghalensis), W20 Soybean (Glycine max v. W20), W4-4 Soybean (Glycine max v. W4-4), corn (Zea mays v. Pioneer 3394) and wild pointsettia (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 G, are based upon a 0 to 100 scale where 0 is no effect and 100 is complete control.

TEST H

Compounds evaluated in this test were formulated in a non-phytotoxic solvent mixture which includes a surfactant and applied to plants that were in the one-to four leaf stage (postemergence application). A mixture of sandy loam soil and greenhouse potting mix in a 60:40 ratio was used for the postemergence 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 annuά), blackgrass (Alopecurus myosuroides), black nightshade (Solanum nigra), chickweed

(Stellaria media), common poppy (Papaver rhoeas), 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 retroflexus), Russian thistle (Salsola kali), ryegrass (Lolium multiflorum), scentless chamomile (Matricaria inodora), spring barley (Hordeum vulgare), sugar beet (Beta vulgaris), sunflower (Helianthus annuus), ivyleaf speedwell (Veronica hederaefolia), spring wheat (Triticum aestivum), winter wheat (Triticum aestivum), wild buckwheat (Polygonum convolvulus), wild mustard (Sinapis arvensis), wild oat (Avenafatua), windgrass (Apera spica-venti) and winter barley (Hordeum vulgare).

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.

Claims

CLAIMS What is claimed is:

1. A compound selected from the formula

and N-oxides and agriculturally suitable salts thereof, wherein

Q is

each R¹ is independently H, C₁-C₆ alkyl, C₁-C₆ haloalkyl, C₁-C₆ alkoxy, C₁-C₆

haloalkoxy, halogen, cyano, nitro, -(Y)_t-S(O)_nR¹⁵ or -(Y)_t-C(O)R¹⁵;

W is N or CH; Y is O or NR¹²;

R² is C₁-C₆ alkyl, C₁-C₆ haloalkyl, C₃-C₆ alkenyl, C₃-C₆ haloalkenyl, C₃-C₆ alkynyl,

C₃-C₆ haloalkynyl, C₁-C₆ alkoxy, C₁-C₆ haloalkoxy, C₃-C₆ alkenyloxy, C₃-C₆ alkynyloxy, mercapto, C₁-C₆ alkylthio, C₁-C₃ haloalkylthio, C₃-C₆ alkenylthio, C₃-C₆ haloalkenylthio, C₃-C₆ alkynylthio, C₂-C₅ alkoxyalkylthio, C₃-C₅ acetylalkylthio, C₃-C₆ alkoxycarbonylalkylthio, C₂-C₄ cyanoalkylthio, C₁-C₆ alkylsulfinyl, C₁-C₆ haloalkylsulfinyl, C₁-C₆ alkylsulfonyl, C₁-C₆

haloalkylsulfonyl, aminosulfonyl, C₁-C₂ alkylaminosulfonyl, C₂-C₄

dialkylaminosulfonyl, (CH₂)_rR¹⁶, NR¹²R¹³, halogen, cyano or nitro; or R² is phenyl or benzylthio, each optionally substituted on the phenyl ring with C₁-C₃ alkyl, C₁-C₃ haloalkyl, C₁-C₃ alkoxy, C₁-C₃ haloalkoxy, 1-2 halogen, cyano or nitro;

R³ is OR¹⁴, SH, C₁-C₆ alkylthio, C₁-C₆ haloalkylthio, C₁-C₆ alkylsulfinyl, C₁-C₆ haloalkylsulfinyl, C₁-C₆ alkylsulfonyl, C₁-C₆ haloalkylsulfonyl, halogen or NR¹²R¹³; or R³ is phenylthio, phenylsulfonyl or -SCH₂C(O)Ph, each optionally substituted with C₁-C₃ alkyl, halogen, cyano or nitro;

each R⁴ is independently C₁-C₃ alkyl, C₁-C₃ alkoxy, C₁-C₃ alkylthio or halogen; or when two R⁴ are attached to the same carbon atom, then said R⁴ pair can be taken together to form -OCH₂CH₂O-, -OCH₂CH₂CH₂O-, -SCH₂CH₂S- or -SCH₂CH₂CH₂S-, each group optionally substituted with 1 -4 CH₃;

R⁵ is OR¹⁴, SH, C₁-C₆ alkylthio, C₁-C₆ haloalkylthio, C₁-C₆ alkylsulfinyl, C₁-C₆ haloalkylsulfinyl, C₁-C₆ alkylsulfonyl, C₁-C₆ haloalkylsulfonyl, halogen or

NR¹²R¹³; or R⁵ is phenylthio, phenylsulfonyl or -SCH₂C(O)Ph, each optionally substituted with C₁-C₃ alkyl, halogen, cyano or nitro;

R⁸ is H, C₁-C₆ alkyl, C₁-C₆ haloalkyl, C₃-C₆ cycloalkyl or C₁-C₆ halocycloalkyl;

R⁹ is H, C₂-C₆ alkoxycarbonyl, C₂-C₆ haloalkoxycarbonyl, CO₂H or cyano;

R¹⁰ is C₁-C₆ alkyl, C₁-C₆ haloalkyl, C₃-C₆ cycloalkyl optionally substituted with 1-4 C₁-C₃ alkyl or C₃-C6 halocycloalkyl;

R^{1 1} is cyano, C₂-C₆ alkoxycarbonyl, C₂-C₆ alkylcarbonyl, S(O)_nR¹³ or C(O)NR¹²R¹³; each R¹² is independently H or C₁-C₆ alkyl ;

R¹³ is C₁-C₆ alkyl or C₁-C₆ alkoxy; or

R¹² and R¹³ can be taken together as -CH₂CH₂-, -CH₂CH₂CH₂-,

-CH₂CH₂CH₂CH₂-, -CH₂CH₂CH₂CH₂CH₂- or -CH₂CH₂OCH₂CH₂-; R¹⁴ is H, C₁-C₆ alkyl, C₁-C₆ haloalkyl, C₂-C₆ alkoxyalkyl, formyl, C₂-C₆

R¹⁵ is NR¹²R¹³, C₁-C₆ alkoxy, C₁-C₆ haloalkoxy, C₁-C₆ alkyl, C₁-C₆ haloalkyl, C₃-C₆ alkenyl, C₃-C6 haloalkenyl, C₃-C₆ alkynyl, C₃-C₆ haloalkynyl or C₃-C₆ cycloalkyl; or R¹⁵ is phenyl optionally substituted with C₁-C₃ alkyl, C₁-C₃ haloalkyl, C₁-C₃ alkoxy, C₁-C₃ haloalkoxy, 1-2 halogen, cyano or nitro;

R¹⁶ is C₁-C₃ alkoxy, C₂-C₄ alkoxycarbonyl, C₁-C₃ alkylthio, C₁-C₃ alkylsulfinyl or

C₁-C₃ alkylsulfonyl; or R¹⁶ is phenyl optionally substituted with C₁-C₃ alkyl, C₁-C₃ haloalkyl, C₁-C₃ alkoxy, C₁-C₃ haloalkoxy, 1-2 halogen, cyano or nitro; m is 0, 1, 2 or 3;

n is 0, 1 or 2;

p is 0, 1, 2, 3 or 4;

r is 1, 2 or 3; and

t is 0 or 1 ;

provided that when W is CH and A is in the meta position with respect to the group Q- C(O)- of Formula I, then m is 3 and R¹ is other than H.

2. A compound of Claim 1 wherein

A is selected from the group 1H-pyrrolyl; furanyl; thienyl; 1H-pyrazolyl;

1H-imidazolyl; isoxazolyl; oxazolyl; isothiazolyl; thiazolyl; 1H-1,2,3-triazolyl;

2H-1,2,3-triazolyl; 1H-1,2,4-triazolyl; 4H-1,2,4-triazolyl; 1,2,3-oxadiazolyl; 1,2,4-oxadiazolyl; 1,2,5-oxadiazolyl; 1,3,4-oxadiazolyl; 1,2,3-thiadiazolyl;

1,2,4-thiadiazolyl; 1,2,5-thiadiazolyl; 1,3,4-thiadiazolyl; 1H-tetrazolyl;

2H-tetrazolyl; pyridinyl; pyridazinyl; pyrimidinyl; pyrazinyl; 1,3,5-triazinyl;

1,2,4-triazinyl; and A may optionally be substituted by one to three R², provided that when a nitrogen atom of a heterocyclic ring is substituted with R², then R² is other than halogen.

3. A compound of Claim 2 wherein

Q is Q-1.

4. A compound of Claim 3 wherein

each R¹ is independently C₁-C₃ alkyl, C₁-C₃ alkoxy, halogen or nitro;

R³ is OR¹⁴; and R¹⁴ is H or C₁-C₄ alkylsulfonyl; or R¹⁴ is benzoyl or phenylsulfonyl, each optionally substituted with C₁-C₃ alkyl, halogen, cyano or nitro.

5. A compound of Claim 4 wherein

A is pyridinyl, pyridazinyl, pyrimidinyl or 1H-pyrazolyl;

R² is -(Y)_t-S(O)_nR¹⁵, CF₃, OCF₃, OCF₂Η or cyano;

R¹⁵ is C₁-C₆ alkyl;

t is 0; and

n is 2.

6. A compound of Claim 2 wherein:

Q is Q-2.

7. A compound of Claim 6 wherein:

each R¹ is independently C₁-C₃ alkyl, C₁-C₃ alkoxy, halogen or nitro;

R⁵ is OR¹⁴;

R⁶ is H, C₁-C₆ alkyl, or C₃-C₆ alkenyl; and

R⁷ is H.

8. A compound of Claim 7 wherein

A is pyridinyl, pyridazinyl, pyrimidinyl or 1H-pyrazolyl;

R² is -(Y)_t-S(O)_nR¹⁵, CF₃, OCF₃, OCF₂Η or cyano;

R¹⁵ is C₁-C₆ alkyl;

t is 0; and

n is 2.

9. A compound of Claim 2 wherein

Q is Q-3.

10. A compound of Claim 9 wherein

each R¹ is independently C₁-C₃ alkyl, C₁-C₃ alkoxy, halogen or nitro;

R⁸ is H, C₁-C₃ alkyl, or cyclopropyl; and

R⁹ is H or C₂-C₃ alkoxycarbonyl.

11. A compound of Claim 10 wherein

A is pyridinyl, pyridazinyl, pyrimidinyl or 1H-pyrazolyl; R² is -(Y)_t-S(O)_nR¹⁵, CF₃, OCF₃, OCF₂H or cyano;

R¹⁵ is C₁-C₆ alkyl;

t is 0; and

n is 2.

12. A compound of Claim 2 wherein

Q is Q-4.

13. A compound of Claim 12 wherein

each R¹ is independently C₁-C₃ alkyl, C₁-C₃ alkoxy, halogen or nitro;

R¹⁰ is C₃-C₆ cycloalkyl or C₃-C₆ halocycloalkyl, each optionally substituted with 1-4 C₁-C₃ alkyl; and

R^{1 1} is cyano or C₂-C₆ alkoxycarbonyl.

14. A compound of Claim 13 wherein

A is pyridinyl, pyridazinyl, pyrimidinyl or 1H-pyrazolyl;

R² is -(Y)_t-S(O)_nR¹⁵, CF₃, OCF₃, OCF₂Η or cyano;

R¹⁵ is C₁-C₆ alkyl;

t is 0; and

n is 2.

15. The compound of Claim 5 which is selected from the group

a) 3-hydroxy-2-[[6-(trifluoromethyl)[2,4'-bipyridin]-3-yl]carbonyl]-2-cyclohexen- 1-one;

b) 2-[2-chloro-4-(4-pyridinyl)benzoyl]-3-hydroxy-2-cyclohexen-1-one; and c) 2-[2,5-dimethyl-3-(1-methyl-1H-pyrazol-3-yl)-4-(methylsulfonyl)benzoyl]-3- hydroxy-2-cyclohexen-1-one.

16. 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.

17. 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.