EP0804423A1 - Insecticidal and acaricidal oxazolines and thiazolines - Google Patents

Abstract

Compounds of formula (I), and their N-oxides and agriculturally-suitable salts, are disclosed which are useful as arthropodicides, wherein A is selected from the group a direct bond and C1-C3alkylene; each E is independently selected from the group C1-C4alkyl and C1-C4haloalkyl; Z is selected from the group O and S; R?1 and R2¿ are independently selected from the group H, 1-2 halogen, C¿1?-C6alkyl, C1-C6haloalkyl, C1-C6alkoxy, C1-C6haloalkoxy, C1-C6alkylthio, CN and NO2; q is 0, 1, 2 or 3; and R?3, R4 and R5¿ are as defined in the disclosure. Also disclosed are compositions containing the compounds of formula (I) and a method for controlling arthropods which involves contacting the arthropods or their environment with an effective amount of a compound of formula (I).

Description

TITLE INSECTICIDAL AND ACARICEDAL OXAZOLINES AND THIAZOLINES

BACKGROUND OF THE INVENTION This invention relates to certain oxazolines and thiazolines, their N-oxides, agriculturally-suitable salts and compositions, and methods of their use as arthropodicides in both agronomic and nonagronomic environments.

US 5,141,948 discloses insecticidal oxa- and thia-zolines of the formula:

wherein:

A is a direct bond or a lower alkylene group;

R_l and R₂ are independently H, lower alkyl, lower alkoxy, halogen, ΝO₂, lower haloalkyl or lower haloalkoxy;

R3 is H, lower alkyl, lower alkoxy or halogen; R₄ is broadly defined and includes a group of the formula

B is a direct bond, O or a variety of carbon chains; Q is CH or N;

R5 is H, alkyl, alkoxy, halogen, haloalkyl, haloalkoxy or a tri(lower alkyl)silyl group; Z is O or S; and n is 0-5. US 4,977,171 discloses insecticidal and acancidal oxa- or thia-zoline derivatives of the formula:

wherein:

X¹ and X² are independently H, lower alkyl, lower alkoxy, halogen, CF3 or OCF3 Y¹ and Y² are independently H, lower alkyl, lower alkoxy, lower alkylthio, CN, NO₂, halogen or CF₃; Z is O or S; and n is 0 or 1.

The oxazolines and thiazolines of the present invention are not disclosed in any of these publications.

SUMMARY OF THE INVENTION This invention is directed to compounds of Formula I including all geometric an stereoisomers, N-oxides, and agriculturally suitable salts thereof, agricultural compositions containing them and their use as arthropodicides in both agronomic and nonagronomic environments:

I wherein:

A is selected from the group a direct bond and C1-C3 alkylene; each E is independently selected from the group CJ-C4 alkyl and C-_j-C₄ haloalkyl; Z is selected from the group O and S; R¹ and R² are independently selected from the group H, 1-2 halogen, C-_j-Cg alkyl,

C_rC₆ haloalkyl, C_rC₆ alkoxy, C_rC₆ haloalkoxy, C_rC₆ alkylthio, CΝ and ΝO₂; R³ is selected from the group phenyl and pyridyl, each ring substituted with R⁶ an optionally substituted with W; or R³ is selected from the group -C(R⁷)=N-XR⁸; -CH₂-X-N=C(R7)(R°-); and C_rC₁₀ alkyl substituted with

C(O)R¹⁰ or C(O)OR^**0; R⁴ and R⁵ are independently selected from the group H; halogen; CN; NO ;

SiCR¹1)(R¹ )(R¹³); C_rC₁₆ alkyl; C_rC₁₆ alkoxy; C_rC₁₆ haloalkyl; C_rC₁₆ haloalkoxy; C3-C7 cycloalkyl; C -C₁₆ cycloalkylalkyl; C₂-C₁₆ alkenyl; C₂-C 1₆ haloalkenyl; C₂-C 1₆ alkynyl; C₂-C _{{ 6} haloalkynyl; C₂-C _{l 6} alkoxyalkoxy; and phenyl optionally substituted with up to three W; R⁶ is selected from the group -C(R⁷)=N-XR⁸; -CH₂-X-N=C(R⁷)(R⁸); OR¹⁵; S(O)_mR¹⁵; C]-C₅ alkylsulfonyloxy; C_rC₅ haloalkylsulfonyloxy; C_rC₅ alkyldithio; C₁-C₅ haloalkyldithio; and C-₂-C₅ alkenyl and C₂-C alkynyl, each group optionally substituted with up to three R⁹; X is selected from the group O and NR⁷; each R⁷ is independently selected from the group H, C-j-Cg alkyl, C Cg haloalkyl, C3-C₆ cycloalkyl, C2-C4 alkenyl, C₂-C₄ alkynyl, phenyl optionally substituted with W and benzyl optionally substituted with W; R⁸ is selected from the group H, Ci-Cg alkyl, Cj-C₆ haloalkyl, C3-C₆ cycloalkyl, C -C₄ alkenyl, C₂-C₄ alkynyl, phenyl optionally substituted with W and benzyl optionally substituted with W; each R⁹ is independently selected from the group halogen, CN and C₁-C₃ haloalkyl; R¹⁰ is selected from the group phenyl and pyridyl, each optionally substituted with up to three W; each W is independently selected from the group halogen, CN, CHO, NO₂, SF₅, S(O)_nR¹⁴, C1-C3 alkyl, C_rC₃ haloalkyl, C_rC₃ alkoxy, C_rC₃ haloalkoxy, C₂-C alkylcarbonyl and C₂-C alkoxycarbonyl; each R^{1 •}*, R¹² and R¹³ is independently selected from the group Cj-Cg alkyl; each R¹⁴ is independently selected from the group C₁-C3 alkyl and C₁-C₃ haloalkyl; R¹⁵ is selected from the group C₂-C₅ alkenyl, C₂-C₄ alkynyl, C3-C6 cycloalkyl, C₄-C7 cycloalkylalkyl, C₂-C5 alkoxyalkyl, and C₂-C₄ cyanoalkyl, each group optionally substituted with up to three R⁹; m is 0, 1 or 2; each n is independently 0, 1 or 2; and q is O, 1, 2 or 3.

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, pentyl or hexyl isomers. "Alkenyl" includes straight-chain or branched alkenes such as vinyl, 1-propenyl, 2-propenyl, 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 ethynyl, 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. "Alkylene" denotes a straight-chain or branched alkanediyl. Examples of "alkylene" include CH₂, CH₂CH₂, CH(CH₃), CH₂CH₂CH2, and CH₂CH(CH₃). "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. Examples of "alkylsulfonyl" include CH₃S(O)₂, CH₃CH₂S(O)₂, CH₃CH₂CH₂S(O)₂, (CH₃)₂CHS(O)₂ and the different butylsulfonyl and pentylsulfonyl isomers. "Alkyldithio" denotes branched or straight-chain alkyldithio moieties. Examples of "alkyldithio" include CH₃SS, CH₃CH₂SS, CH₃CH₂CH₂SS, (CH₃)₂CHSS and the different butyldithio and pentyldithio isomers. "Cyanoalkyl" denotes an alkyl group substituted with one cyano group. Examples of "cyanoalkyl" include NCCH₂, NCCH₂CH₂ and CH₃CH(CN)CH₂. "Cycloalkyl" includes, for example, cyclopropyl, cyclobutyl, cyclopentyl, and cyclohexyl. Examples of "cycloalkylalkyl" include cyclopropylmethyl, cyclohexylethyl, and other cycloalkyl moieties bonded to straight-chain or branched alkyl groups.

The term "halogen", either alone or in compound words such as "haloalkyl", includes fluorine, chlorine, bromine or iodine. The term "1-2 halogen" indicates that one or two of the available positions for that substituent may be halogen which are independently selected. Further, when used in compound words such as "haloalkyl", sai alkyl may be partially or fully substituted with halogen atoms which may be the same or different. Examples of "haloalkyl" include F₃C, C1CH₂, CF₃CH₂ and CF₃CC1₂. The terms "haloalkenyl", "haloalkynyl", "haloalkoxy", and the like, are defined analogously t the term "haloalkyl". Examples of "haloalkenyl" include (C1)₂C=CHCH₂ and CF₃CH₂CH=CHCH₂. Examples of "haloalkynyl" include HC-≡CCHCl, CF₃G≡C, CC1₃C≡C and FCH₂C≡CCH₂. Examples of "haloalkoxy" include CF₃O, CCl₃CH₂O, HCF₂CH₂CH₂O and CF₃CH₂O. 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 "Cj-Cj" prefix where i and j are numbers from 1 to 16. 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) and (CH3)₂CHOC(=O). In the above recitations, when a compound of Formula I includes a pyridinyl ring, all substituents are attached to this pyridinyl ring through the carbon atom(s) of said ring.

When a compound is substituted with a substituent bearing a subscript that indicates the number of said substituents can exceed 1, said substituents (when they exceed 1) are independently selected from the group of defined substituents.

When a group contains a substituent which can be hydrogen, for example R¹ or R⁸, 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 agriculturally-suitable salts thereof, wherein: A is a direct bond;

R¹ is selected from the group F and Cl in the 2-position; R² is selected from the group H, F and Cl in the 6-position; and

R³ is selected from the group phenyl and pyridyl, each ring substituted with R⁶ and optionally substituted with W. Preferred 2. Compounds of Formula I above, and agriculturally-suitable salts thereof, wherein: A is a direct bond;

R¹ is selected from the group F and Cl in the 2-position; R² is selected from the group H, F and Cl in the 6-position; R³ is selected from the group -C(R⁷)=N-XR⁸ and -CH₂-X-N=C(R )(R⁸); and X is O. Preferred 3. Compounds of Preferred 1 wherein: R³ is phenyl substituted with R⁶ and optionally substituted with W;

R⁵ is H; R⁶ is selected from the group -C(R⁷)=N-XR⁸ and -CH₂-X-N=C(R⁷)(R⁸); and X is O. Preferred 4. Compounds of Preferred 1 wherein:

R³ is phenyl substituted with R⁶ and optionally substituted with W; R⁵ is H;

R⁶ is selected from the group OR¹⁵; S(O)_mR¹⁵; C_rC₅ alkylsulfonyloxy; and C₂-C5 alkenyl and C₂-C alkynyl, each group optionally substituted with up to three R⁹; and

R¹⁵ is C₂-C₄ cyanoalkyl optionally substituted with up to three R⁹. Preferred 5. Compounds of Preferred 2 wherein:

R⁸ is selected from the group phenyl optionally substituted with W and benzyl optionally substituted with W. Most preferred are compounds of Preferred 1 selected from the group:

4'-[2-(2,6-difluorophenyl)-4,5-dihydro-4-oxazolyl] [1,1 -biphenyl]-4- carboxaldehyde O-methyloxime;

4-[4'-(2,2-dichloroethenyl)[ 1 , 1 '-biphenyl]-4-yl]-2-(2,6-difluorophenyl)-4,5- dihydrooxazole; 4-[4'-(2-chloroethenyl)[ 1 , 1 '-biphenyl]-4-yl]-2-(2,6-difluorophenyl)-4,5- dihydrooxazole; and

4-[4'-(2,2-difluoroethenyl)[ 1 , 1 '-biphenyl]-4-yl]-2-(2,6-difluorophenyl)-4,5- dihydrooxazole. This invention also relates to arthropodicidal compositions comprising arthropodicidally effective amounts of the compounds of Formula I and at least one of a surfactant, a solid diluent or a Uquid 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 arthropods comprising contacting the arthropods or their environment with an arthropodicidally effective amount of the compounds of Formula I (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 1-21. The definitions of A, E, Z, R---R¹⁵, X, W, m, n and q in the compounds of Formulae I-XXXVI below are as defined above in the Summary of the Invention.

Compounds of Formula I can be made from amino alcohols (or thiols) of Formula II and benzoic acid derivatives as shown in Scheme 1. The transformation generally consists of two steps. First, the compound of Formula II is condensed with the benzoic acid derivative to form an amide of Formula HI. A generally useful way to do this is to treat the compound of Formula II with an aroyl chloride in the presence of an acid acceptor (usually a tertiary amine base such as triethylamine) at room temperature or below. This reaction can be carried out in an inert solvent such as dichloromethane, tetrahydrofuran, toluene, and other solvents that will not react with acid chlorides or bases. There are other useful ways to form amides, many examples of which are found in Larock, "Comprehensive Organic Transformations," VCH New York, pp 972-981. The second step carried out is the ring closure. This can be accomplished by treating the intermediate amide of Formula m with a dehydrating agent. Some useful reagent systems for this transformation include but are not limited to triphenylphosphine carbon tetrachloride, diethyl azodicarboxylate/triphenylphosphine, and thionyl chloride. An especially useful method for ring closure involves treatment of the amide with thionyl chloride in benzene or another inert solvent at reflux until the starting material is consumed (usually 30 min to 3 h). The residue of this reaction is treated with an inorganic base such as sodium or potassium hydroxide in an alcoholic or aqueous medium (usually heating to reflux for 30 min to 2 h is required). Many methods for ring closure to oxazolines have been compiled by Frump (Chemical Rev. (1911) 71, 483-505).

Scheme 1

Alternatively, compounds of Formula III (where A is a direct bond) can be prepared in two steps as shown in Scheme 2. First, compounds of Formula IV are amidoalkylated with a compound of Formula V to form Formula VI compounds. A typical reaction involves the combination of compounds of Formulae IV and V in an aci such as sulfuric acid, methanesulfonic acid, trifluoroacetic acid, polyphosphoric acid or perchloric acid. The reaction can be run in a cosolvent such as acetic acid. The reaction temperature can range from -10° to 200 °C with 0° -100 °C being preferred. Alternatively, the reaction can be carried out in an inert solvent such as chloroform, methylene chloride, benzene, toluene or ether in the presence of a Lewis acid such as aluminum chloride or boron trifluoride. The acid, temperature, and time of the reaction vary according to the relative reactivity of the Q group towards electrophilic substitution reactions. Amidoalkylation reactions have been extensively reviewed in the literature (see Zaugg, Synthesis (1984) 85-110). The second step is the reduction of a Formula V compound to form a Formula m compound. Reductions of this type are well-known in the art (see Hudlicky, Reductions in Organic Chemistry (1984) 136-163). Typical reducing agents include the alkali metal borohydrides and diborane. When V is a lower alkyl group, the use of lithium borohydride as reducing agent, tetrahydrofuran as solvent and performing the reactions at 65 °C for 1-6 h is preferred.

Scheme 2

m

A = direct bond

The preparation of Formula V compounds can be accomplished by refluxing glyoxylic acid derivatives (Formula VII) and commercially available benzamides (Formula VIII) in an inert solvent such as acetone, benzene or chloroform (Scheme 3). This procedure is known in the art (see Ben-Ishai, Tetrahedron (1975) 31, 863-866 and Tetrahedron (1977) 33, 881-883). Scheme 3

vπ vπi

V = H, lower alkyl

As shown in Scheme 4, amino alcohols of Formula II can be produced by the treatment of an amino acid derivative of Formula DC with a reducing agent. In the reduction process, aminoesters are preferred, but amino acids themselves can also be used. There are many reagents known to reduce acids and esters to alcohols. (See Larock, loc. cit., pp 548-553). Particularly useful are alkali metal hydrides and boranes. For example, treatment of a compound of Formula DC with lithium aluminum hydride at 0-50 °C in ethereal solvents such as tetrahydrofuran, ether, or dimethoxyethane gives an alcohol of Formula π.

Scheme 4

Reducing

Agent -». π

K V = H, lower alkyl

As shown in Scheme 5, amino alcohols of Formula π can be produced by the direct reduction of oximino acids and esters of Formula X with boranes or alkali metal hydrides. The reaction conditions with lithium aluminum hydride are as described for Scheme 4.

V = H, lower alkyl

Aryl-substituted amino acids and esters of Formula DC are known in the art as are methods for their preparation. Useful compendia of methods for their synthesis are contained in Kukolja (J. Med. Chem. (1985) 28, 1886-1896), Bohme (J. Med. Chem. (1980) 23, 405-412), and O'Donnell (Tetrahedron Lett. (1989) 30, 3909-3912) and references cited within.

Oxime esters of Formula X are especially suitable intermediates for the synthesis of compounds of Formula I. They can be made from aryl acetic esters of Formula XI by reaction, in the presence of base, with nitrosating agents such as inorganic and organic nitrites as shown in Scheme 6. Typically, the compound of Formula XI is treated with an alkyl nitrite such as butyl nitrite in an alcoholic solvent such as ethanol in the presence of a strong base such as sodium ethoxide at the reflux temperature of the solvent.

Scheme 6

V = H, lower alkyl R = alkyl, H

Alternatively, as shown in Scheme 7, compounds of Formula X can be produced from aryl glyoxalates of Formula XII by treatment with a derivative of hydroxylamine.

Scheme 7

V = H, lower alkyl A method for the synthesis of compounds of Formula XII, shown in Scheme 8, is by use of the Friedel-Crafts reaction. Monoesters of oxalyl chloride react with electron- rich aromatics in the presence of Lewis acids to give compounds of Formula XII. See Olah Ed., "Friedel-Crqfts and Related Reactions," Vol. 3, Part 1, pp 1-16. Treatment of optionally substituted benzenes with aluminum chloride and ethyl or methyloxalyl chloride in an inert solvent such as dichloromethane, nitrobenzene, carbon disulfide, or dichloroethane will produce compounds of Formula XII. Aryl glyoxalates can also be made by the reaction of an organometallic species with a derivative of oxalic acid. For instance, diethyl oxalate can be treated with an aryl Grignard or lithium reagent at low temperature in ether/tetrahydrofuran mixtures (Rambaud, et al., Synthesis (1988) 564-567). The Grignard or lithium reagent can be generated from an optionally substituted haloaromatic compound by conventional methods.

XT! where A is a direct bond

ethyl

Compounds of Formula I in which R³ = phenyl substituted by OR¹⁵ or SR¹⁵ can be synthesized as shown in Scheme 9. A compound of Formula XHI may be alkylated by a halide (or the corresponding alkyl or aryl sulfonate) of Formula XTV in the presence of an acid acceptor. The reaction can be carried out in a variety of inert polar aprotic solvents such as acetonitrile, dimethylformamide, dimethylacetamide, dimethyl sulfoxide, or 2-butanone. Suitable acid acceptors include both organic and inorganic bases such as alkali hydrides, carbonates, and hydroxides. A preferred base and solvent combination is potassium carbonate in dimethylformamide. The process can be carried out from 0-150 °C, preferably at 25 °C. Scheme 9

OR¹⁵ or SR¹⁵)

R^m = alkynyl, alkenyl, haloalkenyl, haloalkynyl, cyanoalkyl, cycloalkyl, cycloalkylalkyl, each substituted by R⁹

As shown in Scheme 10 Compounds of Formula XVII may be made from ketones of Formula XV by the known reaction of hydroxylamines of Formula XVI. This reactio is best carried out in alcoholic solvents between 20-100 °C.

The ketones of Formula XV can be made in several ways from halides and sulfonates of Formula XVm via transition metal catalyzed reactions as shown in Scheme 11. Reaction of organometallic compounds of Formula XDC with carbon monoxide and the compounds of Formula XVHI leads to ketones in the presence of palladium catalysts. The reactions are best carried out under an atmosphere of carbon monoxide in the presence of a palladium catalyst. The optimal catalyst depends on the metal used. (For organoaluminum compounds see Wakita et al., J. Organometallic Chem., 288, 261-268 (1985); for organoboron compounds see Ishiyama et al., Bull. Chem. Soc. Jpn., 64, 1999-2001 (1991), for organozinc compounds see Tamaru et al., Tetrahedron Lett., 36, 3869-3872 (1983), for tin compounds see Stille, Angewandte Chem., Int. Ed., 25, 508-524 (1986)). Scheme 11

xvra

Lg = halogen or (halo)alkylsulfonate Met = B, Sn, Al, etc.

Scheme 12 shows that the ketones of Formula XV can also be made by the reaction of vinyl ethers of Formula XX with compounds of Formula XVL . Optimal reaction conditions for the arylation of vinyl ethers with aryl halides and sulfonates have been described by Cabri (J. Org. Chem., 57, 3558-3563 (1992)). The reaction proceeds best in dipolar aprotic solvents such as dimethylformamide when tethered phosphine ligands are employed. Bis(diphenylphosphino)propane is the preferred ligand. W ile organic bases may be employed as acid acceptors in this process, inorganic bases such as silver or thallium salts are preferred. Thallium acetate is most preferred. The reaction is best carried out at elevated temperature with temperatures from 60-150 °C being preferred. On conclusion of the reaction it must be worked up in the presence of protic acid to hydrolyze the vinyl ether intermediate. Dilute hydrochloric acid is preferred for this use.

Scheme 12

xvm XX

R^x = alkyl

R^v = one carbon less than R⁷

Lg = halogen or (halo)alkylsulfonate

Compounds of Formula XXLLI can be made by the reaction of the appropriate known oxime of Formula XXII with a halide of Formula XXI as shown in Scheme 13. The reaction is best carried out in dipolar aprotic solvents such as dimethylformamide using an inorganic base such as potassium carbonate, potassium hydroxide or sodium hydride as acid receptor. The reaction can be carried out at temperatures between 0-100 °C with temperatures around 25 °C being preferred.

Scheme 13

XXI xxπ Lg = halide

The halides of Formula XXI can be made by well known reactions of alcohols with halogenating agents as shown in Scheme 14. One preferred method for this reaction uses triphenylphosphine and carbon tetrabromide in dichloromethane at 25 °C. A compendium of methods for this process may be found in Larock, loc. cit. pp 353-363. The requisite alcohols of Formula XXV can be made by the reduction of esters of Formula XXIV with hydride agents such as lithium aluminum hydride. A useful compendium of reagents and conditions for this transformation can be found in Larock, loc. cit., pp 548-553. Esters of Formula XXTV can be made by carbonylation of halides of Formula XVLTI in the presence of a palladium catalyst and a lower alcohol. Tethered phosphines such as bis(diphenylphosphino)propane give optimal results in combination with palladium catalysis. The reaction is best carried out in dimethyl sulfoxide as solvent and the temperature is best maintained between 60-80 °C. Organic bases such as tertiary amines are preferred as acid acceptor with triethylamine being especially preferred. Reducing Agent

RX = alkyl

XXV

XXV + halogenating agent- XXI

As shown in Scheme 15 compounds of Formula XX VII can be prepared by the palladium catalyzed reaction of compounds of Formula XVLTI with unsaturated alcohols of Formula XXVI. Larock has studied the reaction of aryl halides with unsaturated alcohols and published a convement procedure for carrying out the process (Tetrahedron Lett., 30, 6629-6632 (1989)). The reaction is best carried out in a dipolar aprotic solvent such as dimethylformamide or acetonitrile in the presence of a phase transfer agent such as tetrabutylammonium chloride or the like. In addition, the presence of an inorganic base such as sodium bicarbonate, potassium carbonate, lithium acetate, or sodium acetate is required. The reaction may be carried out at 25 °C to 150 °C. In some cases the reaction is improved by the addition of a lithium salt such as lithium chloride.

Scheme \5

xvm

XXVI

Compounds of Formula XXDC can be made by reaction of substituted hydroxylamines of Formula XVI and an aldehyde or ketone of Formula XXVLLI in a lower alcoholic solvent as shown in Scheme 16. The reaction is best carried out at 25 to 100 °C.

Scheme 16

Compounds where R³ is aryl substituted alkenyl or alkynyl substituents (Formulae XXXiπ and XXXIV) can be made by reacting compounds of Formula XXX and an alkene or alkyne of Formula XXXI or XXXII in the presence of a palladium catalyst as shown in Scheme 17.

Scheme 17

Lg = halogen, sulfonate

R^x = H, halogen, haloalkyl, alkyl, CN

R? = H, halogen, haloalkyl, alkyl, CN

This sequence is known as the Heck reaction and has been discussed in great detail by Heck in "Palladium Reagents in Organic Synthesis"; Academic, London, 1985. Other more recent modifications of this reaction are summarized in Larock and Baker, Tetrahedron Lett. (1988) 29, 905-908 and in Cabri et. al. J. Org. Chem. (1992) 57, 3558-3563. Typically, the compound of Formula XXX and palladium acetate (1-5 mol %) and triphenylphosphine (2-10 mol %) are heated with the alkene (XXXI) (1 to 3 equivalents) in dimethylformamide or other aprotic solvents at 60-120 °C. The presence of a base such as triethylamine, sodium acetate, sodium carbonate or potassium carbonate is required. When an alkyne (XXXII) is used, the presence of a catalytic amount of Cul (1-5 mol %) accelerates the reaction. In this case it is often preferable to carry out the reaction using an organic base (i.e., triethylamine) as the solvent. Under these conditions the reaction with alkynes (XXXII) often proceeds without external heating.

Alternatively the compounds of Formula XXXiπ can be made by the means of the Wittig or Horner-Emmons reaction as shown in Scheme 18. Reaction between phosphonium salts or phosphonates of Formula XXXV with strong base followed by reaction with compounds of Formula XXVHI give the alkenes. A compendium of conditions and references for these reactions can be found in Larock, loc. cit. pp 173-185 and 295-296. A convenient version of the reaction for making dichloroalkenes of Formula XXXm from compounds of Formula XXVIII is carried out by reaction of phosphines with carbon tetrahalides. Salmond (Tetrahedron Lett. 14, 1239-1240 (1977) has described conditions for carrying out this reaction. Typically the reaction is carried out in dichloromethane as solvent at 25 °C.

Scheme 18

XXVIII ^StronK ^Bas< xxx-rjj

XXXV

XXVIII CX₄

R^l ₃P XXXπi where R^x = Ry = halogen

R^x = H, halogen, haloalkyl, alkyl, CN Ry = H, halogen, haloalkyl, alkyl, CN R^z = alkyl, aryl R^l = alkyl, dialkylamino, aryl

Compounds of Formula XXXVI can be made by reaction of compounds of Formula XXVIII with the anion of (trimethylsilyl)diazomethane as shown in Scheme 1 . The anion is formed in an ether or tetrahydrofuran solvent system by reaction of the diazomethane with a strong base such as lithium diisopropylamide and then is treated with the compound of Formula XXVIII at low temperature (-20 to -70 °C). The mixture is then heated to 65 °C to effect the Colvin rearrangement. The reaction has been described by Shioiri and coworkers in Syn. Lett. (1994), 107-108.

XXVm + Me5SiCHN₂

XXXVI As shown in Scheme 20 compounds of Formula XXXIV can be made from the compounds of Formula XXXIϋ substituted by 2 halogens. Treatment of compounds of Formula XXXIQ with a strong base such as lithium dialkylamides, potassium t-but oxide, or π-butyl lithium can cause the elimination of hydrogen halide to give the haloacetylene of Formula XXXTV where R^x = halogen. The reaction is best carried out at low temperature (-30 to -80 °C) in ethereal solvents. Conditions for this transformation can be found in Villieras et al., Synthesis, 458-461, (1975).

Scheme 20

xxxm Strong Base XXXIV wherein R^x= halogen where R = Ry - halogen

Organometallic coupling reactions may be used to synthesize compounds of Formula Xiπ, XXVIII and XXX as shown in Scheme 21. Known or commercially available organometallic reagents may be coupled with aryl halides or sulfonates of Formula XViπ in the presence of palladium or nickel catalysts. The wide range of catalysts and conditions for these transformations has been summarized by Tamao in Comprehensive Organic Synthesis, B. M. Trost, Ed., Pergamon, (1991), 3, 435-520. For the synthesis of arylzinc reagents (Met = Zn), see Knochel, Chem. Rev., (1993), 93, 2117-2188. For the synthesis of aryltin reagents (Met = S11R3), see Stille, Angewandte Chemie, Int. Ed., (1986), 25, 508-524. For the synthesis of arylboronic acids

(Met = B(OH)₂), see Lappert, Chem. Rev., (1956), 56, 959-1064. Generally, the organometallic reagents can be made from commercially available or known aryl halides by methods disclosed in the references above.

Scheme 21

Met = Zn, B(OH)₂, SnR3

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 synthesi 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 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 downfϊeld from tetramethylsilane; s = singlet, d = doublet, t = triplet, m = multiplet.

Intermediate 1 Step A: Methyl r(2.6-difluorobenzoyl)aminolhydroxyacetate

A solution of glyoxylic acid monohydrate (37.2 g) was stirred in methanol (125 mL) and after 72 h the solvent was evaporated. The residue was dissolved in benzene (150 mL) and heated to reflux with 2,6-difluorobenzamide (44 g). After 16 h the cooled reaction mixture was diluted with benzene (100 mL) and filtered. Air drying left 64 g of crude title compound of Step A which was used without further purification: *H NMR (CDC1₃, 200 MHz): δ 9.7(1H), 7.5(1H), 7.2(2H), 6.9(1H), 3.7(3H). Step B: 2-(2.6-DifluorophenyD* .5-dihydro* -(4-iodophenyl)oxazole

The title compound of Step A (31.0 g, 0.13 mol) and iodobenzene (40.2 g, 0.19 mol) were suspended in sulfuric acid (100 mL) and stirred for 3 days at 23 °C. The mixture was poured onto ice and extracted with dichloromethane (200 mL). The dichloromethane layer was dried over magnesium sulfate and evaporated under reduced pressure. Methanol (200 mL) and thionyl chloride (6 mL) were added and the mixture was heated at reflux for 30 min. The methanol was removed under reduced pressure and the residue was dissolved in tetrahydrofuran (200 mL). Lithium borohydride (55 mL, 2 in tetrahydrofuran, 0.11 mol) was added slowly and, after completion of he addition, the mixture was heated at reflux for 1 h. The mixture was cooled and quenched by slow addition of aqueous hydrochloric acid (200 mL, IN). The mixture was extracted with dichloromethane (200 mL), dried over magnesium sulfate and evaporated under reduced pressure. The residue was then treated with toluene (100 mL) and thionyl chloride (23 mL, 0.3 mol). The mixture was heated to reflux for 45 min and then evaporated under reduced pressure. The residue was dissolved in methanol (200 mL) and treated with aqueous sodium hydroxide (30 mL, 50% solution). The mixture was heated to reflux for 30 min and then evaporated under reduced pressure. The residue was partitioned between water (100 mL) and dichloromethane (200 mL). The dichloromethane solution was dried over magnesium sulfate and evaporated under reduced pressure. The residue was subjected to column chromatography on silica gel using hexanes/ethyl acetate (10: 1) as eluent to give the title compound of Step B, Intermediate 1, (23.1 g) as a white solid melting at 105-106 °C. ^JH NMR (CDC1₃, 200 MHz): δ 7.7(m,2H), 7. (m,lH), 7.1(m,lH), 7.0(m,2H), 5.4(m,lH), 4.8(m,lH), 4.3(m,lH).

Intermediate 2 4'-f2-(2.6-Difluorophenyl)-4-5-dihydro-4-oxazolyll l. -biphenyl1-4-carboxaldehyde

Intermediate 1 (8.5 g), 4-formylphenylboronic acid (4.6 g), and bis(triphenylphosphine)palladium dichloride (0.2 g) were suspended in a mixture of ethylene glycol dimethyl ether (100 mL) and water (100 mL) containing sodium carbonate (12.3 g). The mixture was heated at reflux for 5 h, cooled, and partitioned between dichloromethane (150 mL) and water. The organic phase was dried over magnesium sulfate and evaporated. The residue was subjected to chromatography on silica gel with hexanes ethyl acetate (4:1 to 2:1) to give Intermediate 2 (6.8 g) as a white solid melting at 148-149 °C. *H NMR (CDC1₃) δ 10.0(1H), 8.0-7.0(m,l 1H), 5.55(m,lH), 4.85(m,lH), 4.35(m,lH).

EXAMPLE 1 4'-r2-f2.6-Difluorophenyn-4.5-dihvdro-4-oxazolvnπ.l'-biphenvn-4- carboxaldehyde 0-methyloxime Intermediate 2 (0.5 g), methoxylamine hydrochloride (0.14 g), and sodium acetate

(0.30 g) were suspended in methanol (30 mL) and stirred for 4 h at 25 °C. The methanol was removed by evaporation at reduced pressure and the residue was partitioned between dichloromethane and water. The organic layer was dried and evaporated. The residue was subjected to silica gel chromatography with hexanes/ethyl acetate (4:1) to give the title compound of Example 1 (0.16 g), a compound of the invention, as a solid melting at 140-141 °C. ^JH NMR (CDC1₃): δ 8.1(s,lH), 7.6-7.0(m,l 1H), 5.55(m,lH), 4.9(m,lH), 4.3(m,lH), 3.99(s,3H). EXAMPLE 2 4-r4'-f2.2-Dichloroethenvnπ-l'-biphenvn-4-yll-2-(^'2.6-difluorophenvn-4.5- dihydrooxazole Intermediate 2 (1.5 g) was dissolved in dichloromethane (30 mL) and treated with bromotrichloromethane (0.8 g, 0.4 mL) and the solution was cooled to -20 °C.

Hexamethylphosphorous triamide (1.2 mL in dichloromethane (50 mL)) was added and the mixture was allowed to stir at 25 °C for 72 h. The reaction was charged with . bromotrichloromethane (0.8 g, 0.4 mL) and hexamethylphosphorous triamide (1.2 mL) and stirring was resumed for 18 h. The reaction mixture was treated with water ( 100 mL) and the organic layer was washed with water (100 mL). The organic layer was dried and evaporated under reduced pressure. The residue was subjected to silica gel chromatography with hexanes ethyl acetate (6:1) as eluent to give the title compound of Example 2 (0.11 g), a compound of the invention, as a white solid melting at 156-157 °C. !H NMR (CDC1₃): δ 7.6(m,6H), 7.4(m,3H), 7.0(m,2H), 6.9(m,lH), 5.5(m,lH), 4.9(m,lH), 4.3(m,lH).

EXAMPLE 3 2-(2.6-Difluorophenyl)-4-r4'-ethynyl^rl.r-biphenyl1-4-yl)-4.5-dihydrooxazole (Trimethylsilyl)diazomethane (0.8 mL of a 2M solution in hexanes) was dissolved in a mixture of ether (5 mL) and tetrahydrofuran (3 mL) and treated with lithium diisopropylamide (1.1 mL of 1.5 M solution in hexanes) at a temperature of -70 °C. The mixture was stirred at this temperature for 30 min and treated with Intermediate 2 (0.3 g in 5 mL of tetrahydrofuran). The temperature was allowed to rise to 25 °C and then the mixture was heated at reflux for 3 h. After stirring for 18 h at 25 °C, the reaction was partitioned between ether and water. The organic layer was dried over magnesium sulfate and evaporated under reduced pressure. The residue was subjected to silica gel chromatography with hexanes/ethyl acetate (5:1) to give the title compound of Example 3, a compound of the invention, as a white solid (0.06 g) melting at 125- 126 °C. *H NMR (CDC1₃): δ 7.6-7.0(m,l 1H), 5.5(m,lH), 4,9(m,lH), 4.3(m,lH), 3.1(s,lH). EXAMPLE 4

4-r4'-(2-Chloroethynyl)r 1.1 '-biphenyll-4-yll-2-(2.6-difluorophenyl)-4.5-dihvdrooxazole

The title compound of Example 2 (0.25 g) was dissolved in tetrahydrofuran (8 mL) and treated with lithium diisopropylamide (0.6 mL, 1.5M in hexanes). The cooling bath was removed and the reaction was allowed to come to 25 °C. The reaction mixture was treated with saturated aqueous ammonium chloride solution (5 mL) and water (20 mL). The ether phase was dried over magnesium sulfate and evaporated to give 0.2 g of the tide compound of Example 4, a compound of the invention, as a solid melting at 120-123 °C. ^lH NMR (CDC1₃): δ 7.6-7.0(m,l 1H), 5.5(m,lH), 4.9(m,lH), 4.3(m,lH). EXAMPLE 5 4-[4-^r2-( 2.6-Difluorophenyl)-4.5-dihydro-4-oxazolynphenyll- 1 -(4- fluorophenyl 1 -butanone Intermediate 1 (1.35 g), 4-(4-fluorophenyl)but-l-en-4-ol (1.05 g), lithium acetate (1.35 g), lithium chloride (0.56 g), tetrabutylammonium chloride (2.05 g), and palladium acetate (0.07 g) were suspended in DMF (7 mL) and heated to 80-100 °C for 1.5 h and allowed to stir at 25 °C for 18 h. The mixture was partitioned between ether and water. The ether layer was washed with water and dried over magnesium sulfate. Evaporation of the solvent left a solid which was crystallized from hexanes/butyl chloride. The solid was then subjected to silica gel chromatography with hexanes/ethyl acetate (4: 1) to give the title compound of Example 5, a compound of the invention, as a white solid (0.8 g) melting at 120-121 °C. ^lH NMR (CDC1₃): δ 7.9-7.0(m,l 1H), 5.45(m,lH), 4.8(m,lH), 4.3(m,lH), 2.9(m,2H), 2.7(m,2H), 2.1(m,2H).

EXAMPLE 6 Step A: l-f4-r2-(2.6-Difluorophenyl)-4.5-dihydro-4-oxazolynphenyllethanone

Intermediate 1 (6.5 g) was dissolved in dimethylformamide (20 mL) and treated with butyl vinyl ether (8.5 g), thallium acetate (4.9 g), palladium acetate (0.11 g), and bis(diphenylphosphino)propane (0.2 g). The mixture was heated to 130 °C for 1 h. The cooled mixture was filtered through Celite^® and treated with hydrochloric acid (IN, 30 mL) and water (100 mL). After stirring for 15 min, the mixture was extracted with ether. The ether layer was washed with water and then dried over magnesium sulfate. After evaporation of the solvent, the residue was subjected to silica gel chromatography with hexanes/ethyl acetate (5: 1 to 2: 1) to give the title compound of Step A as a white solid (1.6 g) melting at 83-84 °C. ¹H NMR (CDC1₃): δ 8.0(m,2H), 7.4(m,3H), 7.0(m,2H), 5.55(m,lH), 4.85(m,lH), 4.3(m,lH), 2.6(s,3H).

Step B: 1 - 4-[2-(2.6-Difluorophenyπ-4.5-dihydro-4-oxazolynphenyllethanone O- fphenylmethvnoxime The title compound of Step A (0.5 g) and 0-benzylhydroxylamine hydrochloride (0.36 g) were suspended in methanol (15 mL) and treated with sodium acetate (0.23 g). The mixture was stirred at 25 °C for 2.5 h. More O-benzylhydroxylamine hydrochloride (0.1 g) was added and the mixture was heated to reflux for 10 min and allowed to stir at 25 °C for 1 h. The reaction mixture was partitioned between ether and water. The organic layer was dried over magnesium sulfate. The residue after evaporation of the solvent was subjected to chromatography on silica gel using hexanes/ethyl acetate (5: 1 to 4: 1) as eluent to give the title compound of Step B, a compound of the invention, as a clear oil (0.5 g). ^lH NMR (CDC1₃): δ 7.7-7.0(m,12H), 5.5(m,lH), 5.2(s,2H), 4.8(m,lH), 4.3(m,lH), 2.26(s,3H). EXAMPLE 7 2-(2.6-Difluorophenyπ-4.5-dihvdro-4-r4'-(^'2-propynyloxy^,)[l. -biphenyn-4-ylloxazole Intermediate 1 (1.5 g) was suspended in ethylene glycol dimethyl ether (15 mL) and treated with an aqueous solution of sodium carbonate (1.8 g in 12 mL of water) and 4-hydroxyphenylboronic acid (0.75 g, J. Am. Chem. Soc, (1934), 56, 1865)., followed by bis(triphenylphosphine)palladium dichloride (0.06 g). The mixture was heated at reflux for 2.5 h and stirred at 23 °C for 18 h. The mixture was partitioned between diethyl ether and water. The aqueous layer was extracted twice with dichloromethane (50 mL). The organic layers were combined, dried over magnesium sulfate, and evaporated under reduced pressure. The residue was chromatographed on silica gel with hexanes/ethyl acetate (4:1 to 2:1 as eluent) to provide 0.7 g of residue which was dissolved in dimethylformamide (30 mL). Half of this solution (15 mL) was treated with potassium carbonate (0.36 g) and propargyl bromide (0.24 mL) and stirred for 18 h at 23 °C. The reaction mixture was partitioned between diethyl ether and water. The aqueous layer was washed with diethyl ether and the organic layers were combined and dried over magnesium sulfate. The residue was subjected to chromatography on silica gel with hexanes/ethyl acetate 4: 1 as eluent to give the title compound of Example 7, a compound of the invention, as a solid (0.2 g) melting at 108-109 °C. ^JH NMR (CDC1₃): δ 7.6-7.0(m,l lH), 5.5(m,lH), 4,.9(m,lH), 4.75(s, 2H), 4.3(m,lH), 2.6(s, 1H). EXAMPLE 8

Step A: Ethyl 4-r2-(2.6-difluorophenyD-4.5-dihydro-4-oxazolyllbenzoate

Intermediate 1 (10 g) and ethanol (5 mL) were dissolved in dimethyl sulfoxide (35 mL) and treated with triethylamine (5 mL) and bis(diphenylphosphino)propane (0.3 g). Carbon monoxide was bubbled through the mixture for 5 min and palladium acetate (0.15 g) was added. The mixture was evacuated and carbon monoxide was released into d e reaction by means of a balloon. The evacuation and carbon monoxide release was repeated and the reaction was heated to 65 °C. under a carbon monoxide atmosphere for 6 h. After stirring at 23 °C for 18 h, more bis(diphenylphosphino)propane (0.08 g) and palladium acetate (0.04 g) were added and heating was continued for 5 h. The mixture was stirred at 23 °C for 18 h and was then added to water (100 mL) and extracted with diethyl ether. The organic layer was dried over magnesium sulfate. The residue after evaporation under reduced pressure was chromatographed on silica gel with hexanes/ethyl acetate (9: 1 to 4: 1) to give the title compound of Step A as an oil (2.7 g). ^lH NMR (CDC1₃): δ 8. l(d,lH), 7.4(m,3H), 7.0(t,2H), 5.6(m,lH), 4.85(m,lH), 4.4(m,2H), 4.3(m,lH), 1.4(t,3H).

Step B: 4-f2-(2.6-Difluorophenyl)-4.5-dihydro-4-oxazolynbenzenemethanol

The title compound of Step A (3 g) was dissolved in tetrahydrofuran (50 mL) and treated with lithium aluminum hydride (1M in tetrahydrofuran, 10 mL). After stirring for 3 h, ethyl acetate (1 mL) was added followed by saturated aqueous sodium sulfate (3 mL) and diethyl ether (50 mL). Magnesium sulfate was added and the mixture was filtered and the solvent was evaporated under reduced pressure to give the title compound of Step B as an oil (1.7 g). ^JH NMR (CDC1₃): δ 7.5-7.2(m,5H), 7.0(m,2H), 5.5(m,lH), 4.8(m,lH), 4.7(m,2H), 4.3(m,lH).

Step C: 1 -Phenylethanone Q-. f4-.2-(2.6-difluorophenyl ι-4.5-dihvdro-4- oxazolyl1phenyl]methynoxime The title compound of Step B was dissolved in toluene (50 mL), cooled in an ice bath and treated with thionyl chloride (1.5 mL) in toluene (20 mL). The mixture was stirred for 3 h and then evaporated to dryness under reduced pressure. The unstable oil (2.0 g) was immediately dissolved in dimethylformamide (10 mL). Half of the solution (5 mL, 1 g of material) was added to a stirred mixture of acetophenone oxime (0.5 g) and sodium hydride (0.2 g of 60% active in oil) in dimethylformamide (15 mL). After 3 h, the mixture was partitioned between diethyl ether (50 mL)and water. The water was reextracted with ethyl acetate and the combined organic layers were dried over magnesium sulfate. The solvents were evaporated under reduced pressure and the residue dried further by vacuum pump to remove residual dimethylformamide. The residue was subjected to silica gel chromatography with hexanes/ethyl acetate (5: 1) to provide the title compound of Step C, a compound of the invention, as an oil (0.6 g). *H NMR (CDC1₃): δ 7.7-7.6 (m,2H), 7.6-7.3 (m,8H), 7.0-6.9 (m,2H), 5.5 (m,lH), 5.3 (s,2H), 4.8 (m,lH), 4.3 (m,lH), 2.3 (s,3H).

EXAMPLE 9 Step A: f^Bromophenvnthioltrisfl-methvlethyllsilane

To a solution of 45 g of 4-bromothiophenol in 250 mL of THF was added 53 mL of trusopropylsilyl chloride and 38 mL of DBU ( 1 ,8-diazabicyclo[5.4.0]undec-7-ene) under a nitrogen atmosphere. The reaction mixture heated spontaneously to reflux. The reaction mixture was allowed to cool and was diluted with 500 mL of hexanes. The resultant white suspension was filtered through a pad of Celite^®, and the filter cake was washed with additional hexanes and 100 mL of ether. The filtrate was washed successively with ice-cold 0.1 N HCl, water, aqueous NaHCO3, and brine, and then dried over MgSO₄ and concentrated under vacuum to give 82 g of the title compound of

Step A as a clear oil. *H NMR (CDC1₃, 300 MHz): δ l.l(m,18H), 1.2(m,3H),

7.3-7.4(m,4H).

Step B: 2-(2.6-Difluorophenyn-4.5-dihvdro-4-r4'-rrtris(l-methylethvnsUyllthioiri.l'- biphenyll-4-ynoxazole

The title compound of Step A (4.3 g) was dissolved in 15 mL of THF under a nitrogen atmosphere and cooled below -65°C, and then n-BuLi in hexanes (4.7 mL of 2.5M solution) was added dropwise. After 15 minutes, 26 mL of a 0.5M solution of ZnCl₂ in THF was added dropwise. In a separate reaction flask, 67 mg of Pd(OAc)₂ was added to a solution of 201 mg of tri(o-tolyl)phosphine in 5 mL of THF, and this mixture was stirred for 5 min before its addition, via cannula, to the main reaction mixture. A solution of 3.85 g of Intermediate 1 in 10 mL of THF was added, and the reaction mixture was allowed to warm to room temperature and was stirred for 2 to 3 h. The reaction mixture was poured into ice-cold aqueous NH₄C1 and extracted with ethyl acetate. The organic phase was washed with brine, dried over MgSO₄, and concentrate under vacuum. The oily residue was adsorbed onto silica gel , applied to a column of silica gel and eluted witii hexane/ethyl acetate (6:1) to obtain 3.58 g of the title compound of Step B as a viscous oil. **H NMR (CDC1₃, 300 MHz): δ l.l(m,18H), 1.3(m,3H), 4.3(m,lH), 4.8(m,lH), 5.5(m,lH), 7.0(m,2H), 7.3-7.5(m,5H), 7.5-7.6(m,4H).

Step C: rr4'- .2-f 2.6-DifluorophenyD-4.5-dihydro-4-oxazolyll f 1.1 '-biphenyl -4- yllthiolacetonitrile To a solution of 0.54 g of the title compound of Step B in 10 mL of THF was added 1.0 mL of a 1.1 M THF solution of «-Bu₄NF at 15 to 20 °C (water bath cooling) under a nitrogen atmosphere. After 5 min, 0.9 mL of iodoacetonitrile was added and th reaction mixture was stirred overnight at room temperature. This mixture was then poured into ice-cold aqueous NaHCO3 and extracted with etiiyl acetate. The organic phase was washed with water and brine, dried over MgSO₄, and concentrated under vacuum. The residue was adsorbed onto silica gel, applied to a column of silica gel and eluted with hexanes/ethyl acetate (2:1 to 1:1) to obtain an oil. The oil crystallized upon trituration with ether to produce a white solid which was dried to obtain 0.23 g of the title compound of Step C, a compound of the invention, as a solid melting at 99-101 °C. ^JH NMR (CDCI3, 300 MHz): δ 3.6(s,2H), 4.3-4.4(m,lH), 4.8(m,lH), 5.5(m,lH), 7.0(m,2H), 7.4(m,3H), 7.6(m,6H).

By the procedures described herein together with methods known in the art, the following compounds of Tables 1 to 5 can be prepared. The following abbreviations are used in the Tables which follow: t = tertiary, i = iso, c = cyclo, Me = methyl, Et = ethyl, Pr = propyl, ι'-Pr = isopropyl, Bu = butyl, Ph = phenyl, OMe = methoxy, OEt = ethoxy, SMe = methylthio, CN = cyano, NO₂ = nitro, SiMβ3 = trimethylsilyl, Ac = acetyl, Py = pyridinyl, CO Me = methoxycarbonyl, and - = direct bond. Kev Structure for Table 1

Table 1

R⁷ R⁷ R⁸

Kev Structure for Table 2

Table 2

Rl R⁷ R⁸ Rl R⁷ R⁸

Me 4-F-Ph Cl Me 4-F-Ph

Kev Structure for Table 3

Table 4

F F F F F F F

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, Alms, 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.

High Strength Compositions 90-99 0-10 0-2

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, NN-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-B.

Example A Wettable Powder Compound 4 65.0% dodecylphenol polyethylene glycol ether 2.0% sodium ligninsulfonate 4.0% sodium silicoaluminate 6.0% montmorillonite (calcined) 23.0%. Example B

Granule

Compound 4 10.0% attapulgite granules (low volatile matter,

0.71/0.30 mm; U.S.S. No. 25-50 sieves) 90.0%. Example C

Extruded Pellet

Compound 4 25.0% anhydrous sodium sulfate 10.0% crude calcium ligninsulfonate 5.0% sodium alkylnaphthalenesulfonate 1.0% calcium/magnesium bentonite 59.0%. Example D Emulsifiable Concentrate

Compound 4 20.0% blend of oil soluble sulfonates and polyoxyethylene ethers 10.0% isophorone 70.0%.

The compounds of this invention exhibit activity against a wide spectrum of foliar-feeding, fruit-feeding, stem or root feeding, seed-feeding, aquatic and soil-inhabiting arthropods (term "arthropods" includes insects, mites and nematodes) which are pests of growing and stored agronomic crops, forestry, greenhouse crops, ornamentals, nursery crops, stored food and fiber products, livestock, household, and public and animal health. Those skilled in the art will appreciate that not all compounds are equally effective against all growth stages of all pests. Nevertheless, all of the compounds of this invention display activity against pests that include: eggs, larvae and adults of the Order Lepidoptera; eggs, foliar-feeding, fruit-feeding, root-feeding, seed-feeding larvae and adults of the Order Coleoptera; eggs, immatures and adults of the Orders Hemiptera and Homoptera; eggs, larvae, nymphs and adults of the Order Acari; eggs, immatures and adults of the Orders Thysanoptera, Orthoptera and Dermaptera; eggs, immatures and adults of the Order Diptera; and eggs, juveniles and adults of the Phylum Nematoda. The compounds of this invention are also active agains pests of the Orders Hymenoptera, Isoptera, Siphonaptera, Blattaria, Thysanura and Psocoptera; pests belonging to the Class Arachnida and Phylum Platyhelminthes. Specifically, the compounds are active against southern corn rootworm (Diabrotica undecimpunctata howardi), aster leafhopper (Mascrosteles fascifrons), boll weevil (Anthonomus grandis), two-spotted spider mite (Tetranychus urticae), fall armyworm (Spodoptera frugiperda), black bean aphid (Aphis fabae), green peach aphid (Myzus persica), cotton aphid (Aphis gossypii), Russian wheat aphid (Diuraphis noxia), English grain aphid (Sitobion avenae), tobacco budworm (Heliothis virescens), rice water weevi (Lissorhoptrus oryzophilus), rice leaf beetle (Oulema oryzae), whitebacked planthopper (Sogatellafurciferά), green leafhopper (Nephotettix cincticeps), brown planthopper

(Nilaparvata lugens), small brown planthopper (Laodelphax striatellus), rice stem borer (Chilo suppressalis), rice leafroller (Cnaphalocrocis medinalis), black rice stink bug (Scotinophara lurida), rice stink bug (Oebalus pugnax), rice bug (Leptocoήsa chinensis), slender rice bug (Cletus puntiger), and southern green stink bug (Nezara viridula). The compounds are active on mites, demonstrating ovicidal, larvicidal and chemosterilant activity against such families as Tetranychidae including Tetranychus urticae, Tetranychus cinnabarinus, Tetranychus mcdanieli, Tetranychus pacificus, Tetranychus turkestani, Byrobia rubrioculus, Panonychus ulmi, Panonychus citri, Eotetranychus carpini borealis, Eotetranychus, hicoriae, Eotetranychus sexmaculatus, Eotetranychus yumensis, Eotetranychus banksi and Oligonychus pratensis; Tenuipalpidae including Brevipalpus lewisi, Brevipalpus phoenicis, Brevipalpus californicus and Brevipalpus obovatus; Eriophyidae including Phyllocoptruta oleivora, Eriophyes sheldoni, Aculus cornutus, Epitrimerus pyri and Eriophyes mangiferae. See WO 90/10623 and WO 92/00673 for more detailed pest descriptions.

Compounds of this invention can also be mixed with one or more other insecticides, fungicides, nematocides, bactericides, acaricides, growth regulators, chemosterilants, semiochemicals, repellents, attractants, pheromones, feeding stimulants or other biologically active compounds to form a multi-component pesticide giving an even broader spectrum of agricultural protection. Examples of such agricultural protectants with which compounds of this invention can be formulated are: insecticides such as abamectin, acephate, azinphos-methyl, bifenthrin, buprofezin, carbofuran, chlorpyrifos, chlorpyrifos-methyl, cyfluthrin, beta-cyfluthrin, deltamethrin, diafenthiuron, diazinon, diflubenzuron, dimethoate, esfenvalerate, fenpropathrin, fenvalerate, fipronil, flucythrinate, tau-fluvalinate, fonophos, imidacloprid, isofenphos, malathion, metaldehyde, methamidophos, methidathion, methomyl, methoprene, methoxychlor, monocrotophos, oxamyl, parathion, parathion-methyl, permethrin, phorate, phosalone, phosmet, phosphamidon, pirimicarb, profenofos, rotenone, sulprofos, tebufenozide, tefluthrin, terbufos, tetrachlorvinphos, thiodicarb, tralomethrin, trichlorfon and triflumuron; fungicides such as azoxystrobin (ICIA5504), benomyl, blasticidin-S, Bordeaux mixture (tribasic copper sulfate), bromuconazole, captafol, captan, carbendazim, chloroneb, chlorothalonil, copper oxychloride, copper salts, cymoxanil, cyproconazole, cyprodinil (CGA 219417), diclomezine, dicloran, difenoconazole, dimethomorph, diniconazole, diniconazole-M, dodine, edifenphos, epoxyconazole (BAS 480F), fenarimol, fenbuconazole, fenpiclonil, fenpropidin, fenpropimorph, fluquinconazole, flusilazole, flutolanil, flutriafol, folpet, fosetyl-aluminum, furalaxyl, hexaconazole, ipconazole, iprobenfos, iprodione, isoprothiolane, kasugamycin, kresoxim-methyl (BAS 490F), mancozeb, maneb, mepronil, metalaxyl, metconazole, myclobutanil, neo-asozin (ferric methanearsonate), oxadixyl, penconazole, pencycuron, probenazole, prochloraz, propiconazole, pyrifenox, pyroquilon, sulfur, tebuconazole, tetraconazole, thiabendazole, thiophanate-methyl, thiram, triadimefon, triadimenol, tricyclazole, triticonazole, uniconazole, validamycin and vinclozolin; nematocides such as aldoxycarb and fenamiphos; bactericides such as streptomycin; acaricides such as amitraz, chinomethionat, chlorobenzilate, cyhexatin, dicofol, dienochlor, fenazaquin, fenbutatin oxide, fenpropathrin, fenpyroximate, hexythiazox, propargite, pyridaben and tebufenpyrad; and biological agents such as Bacillus thuringiensis, Bacillus thuringiensis delta endotoxin, baculovirus, and entomopathogenic bacteria, virus and fungi. In certain instances, combinations with other arthropodicides having a similar spectrum of control but a different mode of action will be particularly advantageous for resistance management.

Preferred for better control of pests (use rate or spectrum) or resistance management are mixtures of a compound of this invention with an arthropodicide selected from the group abamectin, fenpropathrin, fipronil, imidacloprid, methomyl, propargite, pyridaben, tebufenozide and tebufenpyrad. Specifically preferred mixtures (compound numbers refer to compounds in Index Tables A-B) are selected from the group: compound 3 and abamectin; compound 3 and fenpropathrin; compound 3 and fipronil; compound 3 and imidacloprid; compound 3 and metiiomyl; compound 3 and propargite; compound 3 and pyridaben; compound 3 and tebufenozide; compound 3 and tebufenpyrad; compound 4 and abamectin; compound 4 and fenpropathrin; compound 4 and fipronil; compound 4 and imidacloprid; compound 4 and methomyl; compound 4 an propargite; compound 4 and pyridaben; compound 4 and tebufenozide; compound 4 and tebufenpyrad; compound 15 and abamectin; compound 15 and fenpropathrin; compound 15 and fipronil; compound 15 and imidacloprid; compound 15 and methomyl; compound 15 and propargite; compound 15 and pyridaben; and compound 15 and tebufenozide; compound 15 and tebufenpyrad; compound 25 and abamectin; compound 25 and fenpropathrin; compound 25 and fipronil; compound 25 and imidacloprid; compound 25 and methomyl; compound 25 and propargite; compound 25 and pyridaben; and compound 25 and tebufenozide; and compound 25 and tebufenpyrad.

Arthropod pests are controlled and protection of agronomic, horticultural and specialty crops, animal and human health is achieved by applying one or more of the compounds of this invention, in an effective amount, to the environment of the pests including the agronomic and/or nonagronomic locus of infestation, to the area to be protected, or directly on the pests to be controlled. Thus, the present invention further comprises a method for the control of foliar and soil inhabiting arthropods and nematode pests and protection of agronomic and/or nonagronomic crops, comprising applying one or more of the compounds of the invention, or compositions containing at least one such compound, in an effective amount, to the environment of the pests including the agronomic and/or nonagronomic locus of infestation, to the area to be protected, or directly on the pests to be controlled. A preferred method of application is by spraying. Alternatively, granular formulations of these compounds can be applied to the plant foliage or the soil. Other methods of application include direct and residual sprays, aerial sprays, seed coats, microencapsulations, systemic uptake, baits, eartags, boluses, foggers, fumigants, aerosols, dusts and many others. The compounds can be incorporated into baits that are consumed by the arthropods or in devices such as traps and the like. The compounds of this invention can be applied in their pure state, but most often application will be of a formulation comprising one or more compounds with suitable carriers, diluents, and surfactants and possibly in combination with a food depending on the contemplated end use. A preferred method of application involves spraying a water dispersion or refined oil solution of the compounds. Combinations with spray oils, spray oil concentrations, spreader stickers, adjuvants, other solvents, and synergists such as piperonyl butoxide often enhance compound efficacy.

The rate of application required for effective control will depend on such factors as the species of arthropod to be controlled, the pest's life cycle, life stage, its size, location, time of year, host crop or animal, feeding behavior, mating behavior, ambient moisture, temperature, and the like. Under normal circumstances, application rates of about 0.01 to 2 kg of active ingredient per hectare are sufficient to control pests in agronomic ecosystems, but as little as 0.001 kg/hectare may be sufficient or as much as 8 kg hectare may be required. For nonagronomic applications, effective use rates will range from about 1.0 to 50 mg/square meter but as little as 0.1 mg/square meter may be sufficient or as much as 150 mg/square meter may be required.

The following TESTS demonstrate the control efficacy of compounds of this invention on specific pests. "Control efficacy" represents inhibition of arthropod development (including mortality) that causes significantly reduced feeding. The pest control protection afforded by the compounds is not limited, however, to these species. See Index Tables A-B for compound descriptions.

INDEX TABLE A

*See Index Table B for lH NMR data.

INDEX TABLE B

Cmpd No. H NMR Data (CDCI3 solution unless indicated otherwise)⁸ δ 7.7-7.0(m,12H), 5.5(m,lH), 5.2(s,2H), 4.8(m,lH), 4.3(m,lH),

2.26(s,3H).

5 δ 8.0-7.0(11H), 5.5(1H), 4.8(1H), 4.3(1H), 2.6(s,3H). 6 δ 8.0(m,2H), 7.6-7.0(m,9H), 5.4(m,lH), 4.8(m,lH), 4.3(m,lH),

3.3(m,2H), 3.1(m,2H).

12 δ 7.7-7.6(m,2H), 7.6-7.3(m,8H), 7.0-6.9(m,2H), 5.5(m,lH), 5.3(s,2H),

4.8(m,lH), 4.3(m,lH), 2.3(s,3H).

13 δ 7.8-7.3(m,9H), 7.0(m,2H), 5.5(m,lH), 5.2(s,2H), 4.8(m,lH), 4.3(m,lH),

2.2(m,lH), 0.9(m,2H), 0.6(m,2H).

19 δ 1.2(t,3H), 3.7(q,2H), 4.3(m,lH), 4.8(m,lH), 5.0(s,2H), 5.5(m,lH),

7.0(m,2H), 7.4-7.5(m,3H), 7.5-7.6(m,6H).

21 δ 2.6(t,2H), 3.1(m,2H), 4.3(m,lH), 4.8(m,lH), 5.5(m,lH), 7.0(m,2H),

7.4-7.5(m,5H). 7.5-7.6(m,4H).

22 δ 4.1(s,2H), 4.3(m,lH), 4.9(m,lH), 5.5(m,lH), 7.0(m,2H), 7.4-7.5(m,3H),

7.6(m,2H), 7.8(m,2H), 8.1(m,2H). 23 δ4.3(m,lH), 4.8(s,2H), 4.8(m,lH), 5.5(m,lH), 7.0(m,4H), 7.4-7.5(m,3H),

7.5-7.6(m,4H). 25 δ 4.35(m,lH), 4.85(m,lH), 5.35(dd,lH), 5.50(m,lH), 6.90-7.70(m,l 1H).

- ^lH NMR data are in ppm downfield from tetramethylsilane. Couplings are designated by (s)-singlet, (d)-doublet, (t)-triplet, (q)-quartet, (m)-multiplet, (dd)-doublet of doublets.

TEST A Larval two-Spotted Spider Mites (Tetranychus urticae)

Solutions of the test compounds were prepared by dissolving in a minimum of acetone and then adding water containing a wetting agent until the concentration of the compound was 50 ppm. Two- week old red kidney bean plants infested with two-spotted spider mites eggs were sprayed to run-off (equivalent to 28 g/ha) with the test solution using a turntable sprayer. Plants were held in a chamber at 25 °C and 50% relative humidity. Of the compounds tested, the following gave mortality levels of 80% or higher seven days after spraying: 1, 2, 3, 4, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 23* and 24*.

* Compound was sprayed at a concentration of 5 ppm (equivalent to 2.8 g/ha).

TEST B

Fall Armyworm Whole Plant Test

Solutions of the test compounds were prepared by dissolving in a minimum of acetone and adding water containing a wetting agent until the concentration of the compounds was 10 ppm. Test compounds were then spray to run-off (equivalent to

5.5 g/ha) onto soybean plants utilizing a rotating platform and an atomizing sprayer.

Treated plants were dried, and fall armyworm (Spodopterafrugiperda) larvae were exposed to excised, treated leaves. Test units were held at 27°C and 50% relative humidity, and evaluated for larval mortality 120 h post-infestation. Of the compounds tested, the following gave mortality levels of 80% or higher: 2, 3, 4, 7*, 8**, 10*, 11*,

14*, 15*, 16, 17, 19, 20, 21 and 24.

* Compound was sprayed at a concentration of 3 ppm (equivalent to 1.4 g/ha). ** Compound was sprayed at a concentration of 1 ppm (equivalent to 0.55 g/ha).

Claims

CLAIMSWhat is claimed is:

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

I wherein:

A is selected from the group a direct bond and C1-C3 alkylene; each E is independently selected from the group C alkyl and C-,-C₄ haloalkyl; Z is selected from the group O and S;

R^l and R² are independently selected from the group H, 1-2 halogen, Cι-C₆ alkyl, C_rC₆ haloalkyl, C_rC₆ alkoxy, C_rC₆ haloalkoxy, C_rC₆ alkylthio, CΝ and ΝO₂; R³ is selected from the group phenyl and pyridyl, each ring substituted with R⁶ and optionally substituted with W; or R³ is selected from the group

-C(R⁷)=N-XR⁸; -CH₂-X-N=C(R⁷)(R⁸); and C_rC₁₀ alkyl substituted with C(O)R^l° or C(O)OR^l°; R⁴ and R⁵ are independently selected from the group H; halogen; CN; NO₂;

Si(R^{l l})(R¹²)(R¹³); C_rC₁₆ alkyl; C_rC₁₆ alkoxy; C_rC₁₆ haloalkyl; C_rC₁₆ haloalkoxy; C3-C7 cycloalkyl; C₄-C _{j 6} cycloalkylalkyl; C₂-C _{j 6} alkenyl;

C₂-Cι₆ haloalkenyl; C₂-Cι₆ alkynyl; C₂-Cιg haloalkynyl; C₂-C₁₆ alkoxyalkoxy; and phenyl optionally substituted with up to three W; R⁶ is selected from the group -C(R⁷)=N-XR⁸; -CH₂-X-N=C(R⁷)(R⁸); OR^I5; S(O)_mR^l5; C_rC₅ alkylsulfonyloxy; C_rC₅ haloalkylsulfonyloxy; C_rC₅ alkyldithio; C1-C5 haloalkyldithio; and C₂-C₅ alkenyl and C₂-C₄ alkynyl, each group optionally substituted with up to three R⁹; X is selected from the group O and NR⁷; each R⁷ is independently selected from the group H, Cj-Cg alkyl, C Cg haloalkyl, C3-C₆ cycloalkyl, C₂-C alkenyl, C₂-C alkynyl, phenyl optionally substituted with W and benzyl optionally substituted with W; R⁸ is selected from the group H, Ci-Cg alkyl, C-_j-Cg haloalkyl, yC^ cycloalkyl,

C₂-C₄ alkenyl, C -C₄ alkynyl, phenyl optionally substituted with W and benzyl optionally substituted with W; each R⁹ is independently selected from the group halogen, CN and C₁-C₃ haloalkyl;

R^l° is selected from the group phenyl and pyridyl, each optionally substituted with up to three W; each W is independently selected from the group halogen, CN, CHO, NO₂, SF₅,

S(O)_nR^l4, C1-C3 alkyl, C_rC₃ haloalkyl, C_rC₃ alkoxy, C_rC₃ haloalkoxy, C₂-C₄ alkylcarbonyl and C₂-C₄ alkoxycarbonyl; each R^l **, R¹² and R^ϊ3 is independently selected from the group Ci-Cg alkyl; each R^l4 is independently selected from the group C_j^ alkyl and C-1-C₃ haloalkyl; R^l-⁵ is selected from the group C₂-C5 alkenyl, C₂-C alkynyl, C₃-C₆ cycloalkyl, C -C7 cycloalkylalkyl, C₂-C5 alkoxyalkyl, and C₂-C cyanoalkyl, each group optionally substituted with up to three R⁹; m is 0, 1 or 2; each n is independently 0, 1 or 2; and q is O, 1, 2 or 3.

2. A compound of Claim 1 wherein:

A is a direct bond;

R^l is selected from the group F and Cl in the 2-position; R² is selected from the group H, F and Cl in the 6-position; and R³ is selected from the group phenyl and pyridyl, each ring substituted with R⁶ and optionally substituted with W.

3. A compound of Claim 1 wherein: A is a direct bond;

R^l is selected from the group F and Cl in the 2-position; R² is selected from the group H, F and Cl in the 6-position; R³ is selected from the group -C(R⁷)=N-XR⁸ and -CH₂-X-N=C(R⁷)(R⁸); and

X is O.

4. A compound of Claim 2 wherein:

R³ is phenyl substituted witii R⁶ and optionally substituted with W; R⁵ is H; R⁶ is selected from the group -C(R⁷)=N-XR⁸ and -CH₂-X-N=C(R⁷)(R⁸); and

X is O.

5. A compound of Claim 2 wherein:

R³ is phenyl substituted with R⁶ and optionally substituted with W; R⁵ is H;

R⁶ is selected from the group OR*⁵; S(O)_mR^l5; C C₅ alkylsulfonyloxy; and

C₂-C5 alkenyl and C₂-C₄ alkynyl, each group optionally substituted with up to three R⁹; and R^l5 is C -C₄ cyanoalkyl optionally substituted with up to three R⁹.

6. A compound of Claim 3 wherein:

R⁸ is selected from the group phenyl optionally substituted with W and benzyl optionally substituted with W.

7. The compound of Claim 2 which is selected from the group: 4- [2-(2,6-difluorophenyl)-4,5-dihydro-4-oxazolyl] [1,1 '-biphenyl]-4- carboxaldehyde O-methyloxime;

4-[4'-(2,2-dichloroethenyl)[ 1 , 1 '-biphenyl]-4-yl]-2-(2,6-difluorophenyl)-4,5- dihydrooxazole;

4-[4^,-(2-chloroethenyl)[l,l'-biphenyl]-4-yl]-2-(2,6-difluorophenyl)-4,5- dihydrooxazole; and

4-[4'-(2,2-difluoroethenyl)[ 1 , 1 '-biphenyl]-4-yl]-2-(2,6-difluorophenyl)-4,5- dihydrooxazole.

8. An arthropodicidal composition comprising an arthropodicidally effective amount of a compound of Claim 1 and at least one of a surfactant, a solid diluent or a Uquid diluent.

9. A method for controlhng arthropods comprising contacting the arthropods o their environment with an arthropodicidally effective amount of a compound of Claim 1.