Insecticidal compounds

Abstract

The present invention provides compounds of formula (I): ##STR00001##
wherein
A.sup.1, A.sup.2, A.sup.3 and A.sup.4 are independently of one another CH, CR.sup.5, or nitrogen;
B.sup.1-B.sup.2-B.sup.3-B.sup.4 is CH.sub.2CNCH.sub.2, CH.sub.2NCH.sub.2CH.sub.2, CH.sub.2CCHO or CHCCH.sub.2O;
G.sup.1 is oxygen or sulfur;
L is a single bond or C.sub.1-C.sub.8alkylene;
R.sup.1 is hydrogen, C.sub.1-C.sub.8alkyl, C.sub.1-C.sub.8alkylcarbonyl-, C.sub.1-C.sub.8alkoxy, C.sub.2-C.sub.8alkenyl, C.sub.2-C.sub.8alkynyl, C.sub.1-C.sub.8alkoxy-C.sub.1-C.sub.8alkyl, aryl or aryl substituted by one to three R.sup.6, or R.sup.1 is heterocyclyl or heterocyclyl substituted by one to three R.sup.6 or C.sub.1-C.sub.8alkoxycarbonyl-;
R.sup.2 is hydrogen, C.sub.1-C.sub.8haloalkyl or C.sub.1-C.sub.8alkyl;
R.sup.3 is C.sub.1-C.sub.8haloalkyl;
R.sup.4 is aryl or aryl substituted by one to three R.sup.6, or R.sup.4 is heterocyclyl or heterocyclyl substituted by one to three R.sup.6;
Y.sup.1 is CR.sup.7R.sup.8, CO or CS;
Y.sup.2, Y.sup.3 and Y.sup.4 are independently CR.sup.7R.sup.8, CO, CS, NR.sup.9, O, S, SO or SO.sub.2;
wherein at least two adjacent ring atoms in the ring formed by Y.sup.1, Y.sup.2, Y.sup.3 and Y.sup.4 are heteroatoms;
each R.sup.7 and R.sup.8 is independently hydrogen, halogen, C.sub.1-C.sub.8alkyl, or C.sub.1-C.sub.8haloalkyl;
and R.sup.5, R.sup.6, R.sup.7, R.sup.8 and R.sup.9 are as defined in the claims. The invention also relates to processes and intermediates for preparing these compounds, to insecticidal, acaricidal, nematicidal and molluscicidal compositions comprising these compounds and to methods of using these compounds to control insect, acarine, nematode and mollusc pests.

Claims

1. A compound of formula (I) ##STR00184## wherein A.sup.2, A.sup.3, and A.sup.4 are independently CH or N, wherein no more than one of A.sup.2, A.sup.3, and A.sup.4 is N; B.sup.1-B.sup.2-B.sup.3-B.sup.4 is CH.sub.2CNCH.sub.2 or CH.sub.2NCH.sub.2CH.sub.2; R.sup.5 is hydrogen, halogen, C.sub.1-C.sub.4alkyl, C.sub.3-C.sub.4cycloalkyl, C.sub.2-C.sub.4alkenyl or C.sub.1-C.sub.4haloalkyl; each R.sup.6 is independently hydrogen, halogen, C.sub.1-C.sub.4alkyl, C.sub.1-C.sub.4haloalkyl, C.sub.1-C.sub.4alkoxy, or C.sub.1-C.sub.4haloalkoxy; Y.sup.1 is CO, Y.sup.2 is NR.sup.9, Y.sup.3 is O, and Y.sup.4 is CH.sub.2; or Y.sup.1 is CH.sub.2, Y.sup.2 is SO, Y.sup.3 is O, and Y.sup.4 is CH.sub.2; and each R.sup.9 is independently hydrogen, cyano, cyano-C.sub.1-C.sub.4alkyl, C.sub.1-C.sub.4alkyl, C.sub.1-C.sub.4haloalkyl, C.sub.3-C.sub.8cycloalkyl, C.sub.3-C.sub.8cycloalkyl where one carbon atom is replaced by O, S, S(O) or SO.sub.2, or C.sub.3-C.sub.8cycloalkyl-C.sub.1-C.sub.4alkyl, C.sub.3-C.sub.8cycloalkyl-C.sub.1-C.sub.4alkyl where one carbon atom in the cycloalkyl group is replaced by O, S, S(O) or SO.sub.2, or C.sub.3-C.sub.8cycloalkyl-C.sub.1-C.sub.4haloalkyl, C.sub.1-C.sub.4hydroxyalkyl, C.sub.1-C.sub.4alkoxy-C.sub.1-C.sub.4alkyl, C.sub.2-C.sub.6alkenyl, C.sub.2-C.sub.4haloalkenyl, C.sub.2-C.sub.4alkynyl, C.sub.2-C.sub.4haloalkynyl, phenyl, phenyl substituted by one to three R.sup.10, heteroaryl, heteroaryl substituted by one to three R.sup.10, phenyl-C.sub.1-C.sub.4alkyl, phenyl-C.sub.1-C.sub.4alkyl wherein the phenyl moiety is substituted by one to three R.sup.10, heteroaryl-C.sub.1-C.sub.4alkyl or heteroaryl-C.sub.1-C.sub.4alkyl wherein the heteroaryl moiety is substituted by one to three R.sup.10, or C.sub.1-C.sub.4alkyl-(C.sub.1-C.sub.4alkyl-ON)CCH.sub.2; each R.sup.10 is independently halogen, cyano, nitro, C.sub.1-C.sub.4alkyl, C.sub.1-C.sub.4haloalkyl, C.sub.1-C.sub.4alkoxy, or C.sub.1-C.sub.4haloalkoxy, or a salt or N-oxide thereof.

2. The compound according to claim 1, wherein B.sup.1-B.sup.2-B.sup.3-B.sup.4 is CH.sub.2CNCH.sub.2.

3. The compound according to claim 1, wherein B.sup.1-B.sup.2-B.sup.3-B.sup.4 is CH.sub.2NCH.sub.2CH.sub.2.

4. The compound according to claim 1, wherein each R.sup.5 independently is bromo, chloro, fluoro, cyclopropyl, trifluoromethyl, vinyl, or methyl.

5. The compound according to claim 1, wherein each R.sup.9 is independently hydrogen, cyano-C.sub.1-C.sub.4alkyl, C.sub.1-C.sub.4alkyl, C.sub.3-C.sub.8cycloalkyl, C.sub.3-C.sub.8cycloalkyl where one carbon atom in the cycloalkyl group is replaced by O, S, S(O) or SO.sub.2, or C.sub.1-C.sub.4haloalkyl, C.sub.1-C.sub.4hydroxyalkyl, C.sub.2-C.sub.4alkenyl, C.sub.2-C.sub.4alkynyl, phenyl-C.sub.1-C.sub.4alkyl or phenyl-C.sub.1-C.sub.4alkyl wherein the phenyl moiety is substituted by one to three R.sup.10, 5-6 membered heteroaryl-C.sub.1-C.sub.4alkyl or 5-6 membered heteroaryl-C.sub.1-C.sub.4alkyl wherein the heteroaryl moiety is substituted by one to three R.sup.10, and wherein the heteroaryl is pyridyl, pyridazinyl, pyrimidinyl, pyrazinyl, pyrazolyl, furanyl, thiophenyl, oxazolyl, isoxazolyl or thiazolyl.

6. The compound according to claim 1, wherein each R.sup.9 is independently hydrogen, C.sub.1-C.sub.4alkyl, C.sub.3-C.sub.6cycloalkyl, C.sub.1-C.sub.4haloalkyl, C.sub.1-C.sub.4hydroxyalkyl, C.sub.1-C.sub.4alkoxy-C.sub.1-C.sub.4alkyl, phenyl- or phenyl-CH.sub.2 wherein the phenyl moiety is substituted by one to three R.sup.10, furanyl or furanyl substituted by one to three R.sup.10, thietanyl, oxetanyl, oxo-thietanyl, or dioxo-thietanyl.

7. A method of combating and/or controlling an invertebrate animal pest which comprises applying to the pest, to a locus of the pest, or to a plant susceptible to attack by the pest a pesticidally effective amount of a compound of formula (I) as defined in claim 1.

8. A composition comprising a pesticidally effective amount of a compound of formula (I) as defined in claim 1 optionally comprising an additional pesticidally active ingredient.

9. A combination product comprising a pesticidally effective amount of a component A and a pesticidally effective amount of component B, wherein component A is a compound of formula (I) as defined in claim 1, and component B is imidacloprid, enrofloxacin, praziquantel, pyrantel embonate, febantel, penethamate, moloxicam, cefalexin, kanamycin, pimobendan, clenbuterol, fipronil, ivermectin, omeprazole, tiamulin, benazepril, milbemycin, cyromazine, thiamethoxam, pyriprole, deltamethrin, cefquinome, florfenicol, buserelin, cefovecin, tulathromycin, ceftiour, selamectin, carprofen, metaflumizone, moxidectin, methoprene (including S-methoprene), clorsulon, pyrantel, amitraz, triclabendazole, avermectin, abamectin, emamectin, eprinomectin, doramectin, selamectin, nemadectin, albendazole, cambendazole, fenbendazole, flubendazole, mebendazole, oxfendazole, oxibendazole, parbendazole, tetramisole, levamisole, pyrantel pamoate, oxantel, morantel, triclabendazole, epsiprantel, fipronil, lufenuron, ecdysone or tebufenozide.

10. The compound of claim 1, wherein the compound of formula (I) is selected from: ##STR00185## ##STR00186##

11. The compound of claim 1, wherein the compound of formula (I) is selected from: ##STR00187## ##STR00188## ##STR00189## ##STR00190##

12. A compound of formula (I) ##STR00191## wherein A.sup.2, A.sup.3, and A.sup.4 are independently CH or N, wherein no more than one of A.sup.2, A.sup.3, and A.sup.4 is N; B.sup.1-B.sup.2-B.sup.3-B.sup.4 is CH.sub.2CCHO or CHCCH.sub.2O; R.sup.5 is hydrogen, halogen, nitro, C.sub.1-C.sub.4alkyl, C.sub.3-C.sub.4cycloalkyl, C.sub.2-C.sub.4alkenyl or C.sub.1-C.sub.4haloalkyl; each R.sup.6 is independently hydrogen, halogen, cyano, nitro, C.sub.1-C.sub.4alkyl, C.sub.1-C.sub.4haloalkyl, C.sub.1-C.sub.4alkoxy, or C.sub.1-C.sub.4haloalkoxy; Y.sup.1 is CO, Y.sup.2 is NR.sup.9, Y.sup.3 is O, and Y.sup.4 is CH.sub.2; or Y.sup.1 is CH.sub.2, Y.sup.2 is SO, Y.sup.3 is O, and Y.sup.4 is CH.sub.2; and each R.sup.9 is independently hydrogen, cyano, cyano-C.sub.1-C.sub.4alkyl, C.sub.1-C.sub.4alkyl, C.sub.1-C.sub.4haloalkyl, C.sub.3-C.sub.8cycloalkyl, C.sub.3-C.sub.8cycloalkyl where one carbon atom is replaced by O, S, S(O) or SO.sub.2, or C.sub.3-C.sub.8cycloalkyl-C.sub.1-C.sub.4alkyl, C.sub.3-C.sub.8cycloalkyl-C.sub.1-C.sub.4alkyl where one carbon atom in the cycloalkyl group is replaced by O, S, S(O) or SO.sub.2, or C.sub.3-C.sub.8cycloalkyl-C.sub.1-C.sub.4haloalkyl, C.sub.1-C.sub.4hydroxyalkyl, C.sub.1-C.sub.4alkoxy-C.sub.1-C.sub.4alkyl, C.sub.2-C.sub.4alkenyl, C.sub.2-C.sub.4haloalkenyl, C.sub.2-C.sub.4alkynyl, C.sub.2-C.sub.4haloalkynyl, phenyl, phenyl substituted by one to three R.sup.10, heteroaryl, heteroaryl substituted by one to three R.sup.10, phenyl-C.sub.1-C.sub.4alkyl, phenyl-C.sub.1-C.sub.4alkyl wherein the phenyl moiety is substituted by one to three R.sup.10, heteroaryl-C.sub.1-C.sub.4alkyl or heteroaryl-C.sub.1-C.sub.4alkyl wherein the heteroaryl moiety is substituted by one to three R.sup.10, or C.sub.1-C.sub.4alkyl-(C.sub.1-C.sub.4alkyl-ON)CCH.sub.2; each R.sup.10 is independently halogen, cyano, nitro, C.sub.1-C.sub.4alkyl, C.sub.1-C.sub.4haloalkyl, C.sub.1-C.sub.4alkoxy, or C.sub.1-C.sub.4haloalkoxy, or a salt or N-oxide thereof providing that Y.sup.1-Y.sup.2-Y.sup.3-Y.sup.4 is not CH.sub.2ON(R.sup.a)C(O), wherein R.sup.a is hydrogen, methyl, ethyl, propyl, isopropyl, butyl, cyclopropyl, cyclopropyl-methyl, cyclobutyl, cyclobutyl-methyl, oxetanyl, thietanyl, trifluoroethyl, difluoroethyl, allyl, propargyl, cyanomethyl, benzyl, benzyl substituted by one to three R.sup.b, or R.sup.a is pyridyl-methyl- or pyridyl-methyl-substituted by one to three R.sup.b; and each R.sup.b is independently fluoro, chloro, bromo, trifluoromethyl, trifluoromethoxy, cyano or methoxy.

13. The compound according to claim 12, wherein B.sup.1-B.sup.2-B.sup.3-B.sup.4 is CH.sub.2CCHO.

14. The compound according to claim 13, wherein B.sup.1-B.sup.2-B.sup.3-B.sup.4 is CHCCH.sub.2O.

15. The compound according to claim 12, wherein each R.sup.5 independently is bromo, chloro, fluoro, cyclopropyl, trifluoromethyl, vinyl, or methyl.

16. The compound according to claim 12, wherein each R.sup.9 is independently hydrogen, cyano-C.sub.1-C.sub.4alkyl, C.sub.1-C.sub.4alkyl, C.sub.3-C.sub.8cycloalkyl, C.sub.3-C.sub.8cycloalkyl where one carbon atom in the cycloalkyl group is replaced by O, S, S(O) or SO.sub.2, or C.sub.1-C.sub.4haloalkyl, C.sub.1-C.sub.4hydroxyalkyl, C.sub.2-C.sub.4alkenyl, C.sub.2-C.sub.4alkynyl, phenyl-C.sub.1-C.sub.4alkyl or phenyl-C.sub.1-C.sub.4alkyl wherein the phenyl moiety is substituted by one to three R.sup.10, 5-6 membered heteroaryl-C.sub.1-C.sub.4alkyl or 5-6 membered heteroaryl-C.sub.1-C.sub.4alkyl wherein the heteroaryl moiety is substituted by one to three R.sup.10, and wherein the heteroaryl is pyridyl, pyridazinyl, pyrimidinyl, pyrazinyl, pyrazolyl, furanyl, thiophenyl, oxazolyl, isoxazolyl or thiazolyl.

17. The compound according to claim 12, wherein each R.sup.9 is independently hydrogen, C.sub.1-C.sub.4alkyl, C.sub.3-C.sub.6cycloalkyl, C.sub.1-C.sub.4haloalkyl, C.sub.1-C.sub.4hydroxyalkyl, C.sub.1-C.sub.4alkoxy-C.sub.1-C.sub.4alkyl, phenyl- or phenyl-CH.sub.2 wherein the phenyl moiety is substituted by one to three R.sup.10, furanyl or furanyl substituted by one to three R.sup.10, thietanyl, oxetanyl, oxo-thietanyl, or dioxo-thietanyl.

18. A method of combating and/or controlling an invertebrate animal pest which comprises applying to the pest, to a locus of the pest, or to a plant susceptible to attack by the pest a pesticidally effective amount of a compound of formula (I) as defined in claim 12.

19. A composition comprising a pesticidally effective amount of a compound of formula (I) as defined in claim 12 optionally comprising an additional pesticidally active ingredient.

20. A combination product comprising a pesticidally effective amount of a component A and a pesticidally effective amount of component B, wherein component A is a compound of formula (I) as defined in claim 12, and component B is imidacloprid, enrofloxacin, praziquantel, pyrantel embonate, febantel, penethamate, moloxicam, cefalexin, kanamycin, pimobendan, clenbuterol, fipronil, ivermectin, omeprazole, tiamulin, benazepril, milbemycin, cyromazine, thiamethoxam, pyriprole, deltamethrin, cefquinome, florfenicol, buserelin, cefovecin, tulathromycin, ceftiour, selamectin, carprofen, metaflumizone, moxidectin, methoprene (including S-methoprene), clorsulon, pyrantel, amitraz, triclabendazole, avermectin, abamectin, emamectin, eprinomectin, doramectin, selamectin, nemadectin, albendazole, cambendazole, fenbendazole, flubendazole, mebendazole, oxfendazole, oxibendazole, parbendazole, tetramisole, levamisole, pyrantel pamoate, oxantel, morantel, triclabendazole, epsiprantel, fipronil, lufenuron, ecdysone or tebufenozide.

21. The compound of claim 12, wherein the compound of formula (I) is selected from: ##STR00192##

Description

(1) The following Examples illustrate, but do not limit, the invention.

(2) The following abbreviations were used in this section: s=singlet; bs=broad singlet; d=doublet; dd=double doublet; dt=double triplet; t=triplet, tt=triple triplet, q=quartet, sept=septet; m=multiplet; Me=methyl; Et=ethyl; Pr=propyl; Bu=butyl; M.p.=melting point; RT=retention time, [M+H].sup.+=molecular mass of the molecular cation, [MH].sup.=molecular mass of the molecular anion.

Example P1: 4-(3,5-Dichloro-phenyl)-5,5,5-trifluoro-pent-2-yne-1,4-diol

(3) ##STR00164##

(4) To a stirring solution of magnesium (520 mg) in anhydrous tetrahydrofuran (50 mL) under argon at room temperature, was added ethyl bromide (1.7 mL). After stirring for 2 hours at room temperature, the solution was cooled to 0 C. and Trimethyl-prop-2-ynyloxy-silane (3.1 mL) was added. The solution was allowed to warm to room temperature and then after 40 minutes, it was cooled again to 0 C. To this cooled solution, 1-(3,5-Dichloro-phenyl)-2,2,2-trifluoro-ethanone (5 g) (Journal of Physical Organic Chemistry (1989), 2(4), 363-6) were added. The solution was stirred at 0 C. for 1 hour. The mixture was quenched with saturated ammonium chloride and then extracted with diethyl ether. The combined organic extracts were dried over magnesium sulfate and concentrated. The residue was then dissolved in ethyl acetate (60 mL) and the solution was stirred at room temperature under argon. A solution of tetrabutylammonium fluoride (21 mL of a 1 M solution in tetrahydrofuran) was added. The solution was stirred for one hour then was allowed to stand at room temperature for 21 hours. The mixture was quenched with saturated ammonium chloride and then extracted with diethyl ether. The combined organic extracts were dried over magnesium sulfate and concentrated. The residue was purified by chromatography on silica gel (eluent: heptane/ethyl acetate 1:0 to 7:3) to give 4-(3,5-Dichloro-phenyl)-5,5,5-trifluoro-pent-2-yne-1,4-diol (3.798 g) as a colorless oil.

(5) .sup.1H-NMR (CDCl.sub.3, 400 MHz): 7.61 (m, 2H), 7.43 (t, J=1.83 Hz, 1H), 4.44 (m, 2H), 3.45 (s, 1H) ppm.

Example P2: Tributyl-[5-(3,5-dichloro-phenyl-5-trifluoromethyl-2,5-dihydro-furan-3-yl]-stannane

(6) ##STR00165##

(7) To a solution of 4-(3,5-Dichloro-phenyl)-5,5,5-trifluoro-pent-2-yne-1,4-diol (2.5 g) in toluene under argon, was added tetrakis(triphenylphosphine) palladium (190 mg) and tributyltinhydride (2.25 mL). The reaction mixture was stirred for 45 minutes then the solvent was evaporated under vacuo. The residue was then dissolved in anhydrous tetrahydrofuran (50 mL) with triphenylphosphine (2.19 g) and the solution was stirred at 0 C. under argon. To this solution was slowly added diethyl azodicarboxylate (1.31 mL). The mixture was stirred at 0 C. for 90 minutes then the solvent was evaporated under vacuo. The residue was partitioned between acetonitrile and heptane and the acetonitrile part was washed twice with heptane. The combined heptane extracts were combined and evaporated to give a residue that was purified by chromatography on silica gel (eluent: heptane) to give

(8) Tributyl-[5-(3,5-dichloro-phenyl)-5-trifluoromethyl-2,5-dihydro-furan-3-yl]-stannane (1.587 g) as a colorless oil.

(9) .sup.1H-NMR (CDCl.sub.3, 400 MHz): 7.43 (m, 2H), 7.34 (d, J=1.83 Hz, 1H), 5.93 (t, J=2.57 Hz, 1H), 5.02-4.89 (2 dd, J=2.6 and 13.6 and 1.8 Hz, 2H), 1.52-1.46 (m, 6H), 1.34-1.28 (m, 6H), 1.03-0.99 (t, J=8.1 Hz, 6H), 0.89 (t, J=7.3 Hz, 9H) ppm.

Example P3: Preparation of 4-bromo-2-methyl-benzoic acid tert-butyl ester

(10) ##STR00166##

(11) 4-Bromo-2-methyl-benzoic acid (commercially available) (50 g) was suspended in dichloromethane (500 mL). A catalytic amount of N,N-dimethylformamide (DMF) and oxalyl chloride (23 mL) were added to the suspension. The reaction mixture was stirred at ambient temperature for 3 hours. The reaction mixture was concentrated and the residue dissolved in dry tetrahydrofuran (800 mL). The solution was cooled to 2 C. and added to a solution of potassium tert-butoxide (39.2 g) in dry tetrahydrofuran (300 mL) dropwise at 5-10 C. The reaction mixture was stirred at ambient temperature for 30 minutes and then poured onto a mixture of ice and water. The mixture was extracted with ethyl acetate. The organic extract was washed with water, dried over sodium sulfate and concentrated to give 4-bromo-2-methyl-benzoic acid ten-butyl ester (65.3 g) as yellow oil.

(12) .sup.1H-NMR (CDCl.sub.3, 400 MHz): 7.70 (d, 1H), 7.40 (s, 1H), 7.35 (d, 1H), 2.58 (s, 3H), 1.60 (s, 9H).

Example P4: 4-[5-(3,5-Dichloro-phenyl)-5-trifluoromethyl-2,5-dihydro-furan-3-yl]-2-methyl-benzoic acid tert-butyl ester

(13) ##STR00167##

(14) To a solution of Tributyl-[5-(3,5-dichloro-phenyl)-5-trifluoromethyl-2,5-dihydro-furan-3-yl]-stannane (1.587 g) in toluene (15 mL) under argon was successively added 4-Bromo-2-methyl-benzoic acid tert-butyl ester (630 mg), lithium chloride (600 mg) and then tetrakis(triphenylphosphine) palladium (110 mg). The reaction was refluxed at 100 C. under argon for 3 hours 30 minutes. The reaction was allowed to cool down to room temperature then after 3 hours, more tetrakis(triphenylphosphine) palladium (45 mg) was added. The solution was refluxed for a further 1 h45 and then the reaction was stopped. The mixture was cooled to room temperature and then the solvent was evaporated in vacuo to give a residue which was purified by chromatography on silica gel (eluent: heptanes\diethyl ether, from 1:0 to 9:1) to give 4-[5-(3,5-Dichloro-phenyl)-5-trifluoromethyl-2,5-dihydro-furan-3-yl]-2-methyl-benzoic acid tert-butyl ester (704 mg) as a white solid. Recrystallisation in heptane/ethyl acetate provided white crystals, m.p=160-162 C.

(15) .sup.1H-NMR (CDCl.sub.3, 400 MHz): 7.83 (d, J=8.4 Hz, 1H), 7.50 (m, 2H), 7.38 (t, J=1.4 Hz, 1H), 7.22 (m, 2H), 6.39 (m, 1H), 5.32 (dd, J=2.2 and 12.5 Hz, 1H), 5.20 (m, 1H), 2.59 (s, 3H), 1.61 (s, 9H) ppm.

Example P5: 4-[5-(3,5-Dichloro-phenyl)-5-trifluoromethyl-2,5-dihydro-furan-3-yl]-2-methyl-benzoic acid

(16) ##STR00168##

(17) To a solution of 4-[5-(3,5-Dichloro-phenyl)-5-trifluoromethyl-2,5-dihydro-furan-3-yl]-2-methyl-benzoic acid tert-butyl ester (322 mg) in dichloromethane (8 mL) was added trifluoroacetic acid (0.5 mL). The reaction mixture was stirred at room temperature for 3 h30 then the solution was concentrated under vacuo to give 4-[5-(3,5-Dichloro-phenyl)-5-trifluoromethyl-2,5-dihydro-furan-3-yl]-2-methyl-benzoic acid (200 mg) as a white foam.

(18) .sup.1H-NMR (CDCl.sub.3, 400 MHz): 8.07 (d, J=8.8 Hz, 1H), 7.49 (m, 2H), 7.39 (t, J=1.4 Hz, 1H), 7.3-7.26 (m, 2H), 6.46 (m, 1H), 5.34 (dd, J=2.2 and 12.5 Hz, 1H), 5.22 (m, 1H), 2.67 (s, 3H) ppm.

Example P6: Preparation of 4-[(R)-3-(3,5-Dichloro-phenyl)-4,4,4-trifluoro-3-nitromethyl-butyryl]-2-methyl-benzoic acid tert-butyl ester

(19) ##STR00169##

(20) 4-[(E)-3-(3,5-Dichloro-phenyl)-4,4,4-trifluoro-but-2-enoyl]-2-methyl-benzoic acid tert-butyl ester (0.0928 g, 0.198 mmol) and 1-[3,5-bis(trifluoromethyl)phenyl)-3-{(S)[(2S,4S,5R)-5-ethyl-1-aza-bicyclo[2.2.2]oct-2-yl]-(6-methoxy-4-quinolinyl)methyl}thiourea (0.0121 g, 0.020 mmol) were dissolved in nitromethane (0.6 ml) and the resulting solution was stirred at 50 C. for 2.5 days. The reaction mixture was cooled to room temperature and aqueous saturated ammonium chloride was added. The resulting mixture was extracted with dichloromethane (3) and the combined organic fractions were dried over sodium sulfate. The crude product was purified by flash chromatography (0% to 5% ethyl acetate in cyclohexane) to afford 4-[(R)-3-(3,5-dichloro-phenyl)-4,4,4-trifluoro-3-nitromethyl-butyryl]-2-methyl-benzoic acid tert-butyl ester (0.080 g, 77%) as a beige solid. Chiral HPLC analysis (Chiralpack AS-RH, MeCN:MeOH:H.sub.2O=75:5:20, 1 ml/min, retention time 3.26 minutes (major enantiomer), 2.86 minutes (minor enantiomer) indicated that the reaction proceeded with 97.4% enantioselectivity.

(21) .sup.1H NMR (400 MHz, CDCl.sub.3) 7.91 (d, 1H), 7.82-7.78 (m, 2H), 7.42 (t, 1H), 7.20 (s, 2H), 5.61 (d, 1H), 5.47 (d, 1H), 4.16 (d, 1H), 3.99 (d, 1H), 2.64 (s, 3H), 1.63 (s, 9H)

(22) The absolute configuration of the major enantiomer was unambiguously assigned as being (R) by X ray diffraction on crystals of the compound (recrystallization from EtOH).

Example P7: Preparation of 4-[(R)-4-(3,5-Dichloro-phenyl)-4-trifluoromethyl-4,5-dihydro-3H-pyrrol-2-yl]-2-methyl-benzoic acid tert-butyl ester

(23) ##STR00170##

(24) To a vigorously stirred suspension of zinc (0.060 g, 0.913 mmol) in dimethylformamide (2.0 ml) was added a solution of 4-[(R)-3-(3,5-dichloro-phenyl)-4,4,4-trifluoro-3-nitromethyl-butyryl]-2-methyl-benzoic acid tert-butyl ester (0.190 g, 0.365 mmol) in dimethylformamide (2.0 ml). The resulting mixture was warmed to 80 C. and 37% aqueous hydrochloric acid (3.0 ml) was added very slowly to minimize the foaming. After stirring for 2 hours the reaction was cooled to room temperature and quenched by adding a pH 7 buffer solution. The mixture was extracted with dichloromethane; the organic layer was washed with water (3) and brine. The crude product was purified by flash chromatography (6% ethyl acetate in cyclohexane) to afford 4-[(R)-4-(3,5-dichloro-phenyl)-4-trifluoromethyl-4,5-dihydro-3H-pyrrol-2-yl]-2-methyl-benzoic acid tert-butyl ester as a pale yellow oil (0.050 g, 29%).

(25) .sup.1H NMR (400 MHz, CDCl.sub.3) 7.87 (d, 1H), 7.71 (s, 1H), 7.67 (d, 1H), 7.38 (t, 1H), 7.27 (s, 2H), 4.90 (dd, 1H), 4.45 (d, 1H), 3.81 (dd, 1H), 3.46 (d, 1H), 2.62 (s, 3H), 1.61 (s, 9H)

Example P8: Preparation of 4-[(R)-4-(3,5-Dichloro-phenyl)-4-trifluoromethyl-4,5-dihydro-3H-pyrrol-2-yl]-2-methyl-benzoic acid

(26) ##STR00171##

(27) To a solution of 4-[(R)-4-(3,5-Dichloro-phenyl)-4-trifluoromethyl-4,5-dihydro-3H-pyrrol-2-yl]-2-methyl-benzoic acid tert-butyl ester (0.68 g) in dichloromethane (0.7 ml) was added trifluoromethyl acetic acid (TFA) (0.07 ml). The reaction mixture was stirred at ambient temperature for 4.5 hours. The dichloromethane was evaporated under reduced pressure and the residue was taken up in ethyl acetate and water. The organic phase was washed with water and brine and evaporated under reduced pressure to afford 4-[(R)-4-(3,5-Dichloro-phenyl)-4-trifluoromethyl-4,5-dihydro-3H-pyrrol-2-yl]-2-methyl-benzoic acid which was used as such in the next reaction). LCMS (Method F) RT=2.07 min, [MH].sup.=414/416.

Example A14: Preparation of 4-[(R)-4-(3,5-Dichloro-phenyl)-4-trifluoromethyl-4,5-dihydro-3H-pyrrol-2-yl]-N((R)-2-ethyl-3-oxo-isoxazolidin-4-yl)-2-methyl-benzamide

(28) ##STR00172##

(29) To a suspension of 4-[(R)-4-(3,5-Dichloro-phenyl)-4-trifluoromethyl-4,5-dihydro-3H-pyrrol-2-yl]-2-methyl-benzoic acid (22 mg) in dichloromethane (0.45 ml) was added thionyl chloride (0.005 ml) and then one drop of dimethylformamide. The reaction mixture stirred at room temperature for 1 hour, and the solvent was evaporated in vacuo. The acyl chloride thus obtained was dissolved in tetrahydrofuran (0.2 ml) and to the resulting solution was added dropwise to a solution of triethylamine (0.015 ml) and (R)-4-Amino-2-methyl-isoxazolidin-3-one (15 mg) in tetrahydrofuran (0.2 ml) at room temperature, under argon. The reaction was stirred overnight at room temperature. Then the solvent was evaporated in vacuo, the residue was diluted with water and a solution of sodium hydroxide (2N) and extracted with ethyl acetate. The organic phase was washed two times with water, dried over anhydrous sodium sulfate, filtered and concentrated in vacuo. Purification by column chromatography (eluent cyclohexane/ethyl acetate) afforded the title compound as a solid (6.5 mg). .sup.1H-NMR (CDCl.sub.3, 400 MHz): 7.75 (s, 1H), 7.69 (d, 1H), 7.53 (d, 1H), 7.39 (m, 1H), 7.28 (m, 2H), 6.47 (m, 1H), 5.03-4.84 (m, 3H), 4.46 (d, 1H), 4.06 (t, 1H), 3.83-3.60 (m, 3H), 3.47 (d, 1H), 2.52 (s, 3H), 1.28 (t, 3H).

Example P10: (R)-2-Oxo-2lambda*4*-[1,2]oxathiolan-4-ylamine trifluoroacetic acid salt

(30) ##STR00173##

(31) (2-Oxo-2lambda*4*-[1,2]oxathiolan-4-yl)-carbamic acid tert-butyl ester (prepared in 3 steps from L-cystine according to J. Org. Chem. 1981, 46, 5408-5413) (345 mg) was dissolved in dichloromethane (7.8 ml) and treated with trifluoroacetic acid (0.36 ml). The reaction mixture was stirred at room temperature overnight and the solvent removed in vacuo to afford (R)-2-Oxo-2lambda*4*-[1,2]oxathiolan-4-ylamine (trifluoroacetic acid salt), which was used directly in the next step. LCMS (Method E) 0.20 min, M+H 122.

Example P11: Method for Preparing the Compounds of the Invention from a Carboxylic Acid

(32) ##STR00174##

(33) To a solution of the appropriate carboxylic acid (30 mol), for example 4-[4-(3,5-dichloro-phenyl)-4-trifluoromethyl-4,5-dihydro-3H-pyrrol-2-yl]-2-methyl-benzoic acid (preparation see WO 2010/149506) in the case of compound No. A1 of Table A, in dimethylacetamide (0.4 ml) was added successively a solution of an amine of formula HNR.sup.1R.sup.2 (36 mol), for example 2-Oxo-[1,2]oxathiolan-4-ylamine (preparation example P10) in the case of Compound No. A1 of Table A, in dimethylacetamide (0.145 ml), diisopropylethylamine (Hunig's Base) (0.02 ml and a solution of bis(2-oxo-3-oxazolidinyl)phosphonic chloride (BOP-Cl) (15.3 mg) in dimethylacetamide (0.2 ml). The reaction mixture was stirred at 90 C. for 16 hours. Then the reaction mixture was diluted with acetonitrile (0.6 ml) and a sample was used for LC-MS analysis. The remaining mixture was further diluted with acetonitrile/dimethylformamide (4:1) (0.8 ml) and separated by HPLC. This method was used to prepare a number of compounds (Compound Nos. A1 to A4 and A7 to A11 of Table A) in parallel, A5 and A6 were obtained using a similar procedure.

Example P12: Method for Preparing the Compounds of the Invention from a Carboxylic Acid

(34) ##STR00175##

(35) To a solution of the appropriate carboxylic acid (25 mol), for example 6-[3-(3,5-Dichloro-phenyl)-3-trifluoromethyl-pyrrolidin-1-yl]-4-methyl-nicotinic acid (preparation described in JP 2008/110971) in dimethylacetamide (0.4 ml) was added an amine of formula HNR.sup.1R.sup.2 (37.5 mol), for example ethyl cacloserine (preparation described in, for example, WO 2008/033562) in the case of compound No. B1 of Table B, diisopropylethylamine (Hunig's Base) (0.020 ml), followed by 1-ethyl-3-(3-dimethylaminopropyl)carbodiimid (EDC) (14 mg) in dimethylacetamide (0.02 ml) and hydroxybenzotriazole (HOBt) (3.7 mg) in dimethylacetamide (0.01 ml). The reaction mixture was stirred at ambient temperature for 16 hours. The reaction mixture was diluted with acetonitrile/dimethylformamide (4:1) (0.8 ml) and purified by HPLC. This method was used to prepare a number of compounds (Compound Nos. B1 to B4 of Table B) in parallel.

Example P13 (Reference): Preparation of 4-[2-(3,5-dichlorophenyl)-2-(trifluoromethyl)-3H-furan-4-yl]-2-methyl-N-[(4R)-3-oxo-2-(2,2,2-trifluoroethyl-isoxazolidin-4-yl]benzamide (C2)

(36) ##STR00176##

(37) To a suspension of 4-[2-(3,5-dichlorophenyl)-2-(trifluoromethyl)-3H-furan-4-yl]-2-methyl-benzoic acid (250 mg, prepared as described in WO2011101229) in dichloromethane (5 ml) was added thionyl chloride (0.06 ml) and then two drops of dimethylformamide. The reaction mixture was stirred at room temperature for 1 hour, and the solvent was evaporated in vacuo. The acyl chloride thus obtained was dissolved in dichloromethane (1 ml) and was added dropwise to a suspension of triethylamine (0.25 ml) and the hydrochloride salt of (4R)-4-amino-2-(2,2,2-trifluoroethyl)isoxazolidin-3-one (145 mg) in dichloromethane (5 ml) at room temperature, under argon. The reaction was stirred for 40 minutes at room temperature. Then the reaction was diluted with water and extracted with ethyl acetate. The organic phase was washed two times with water, dried over anhydrous magnesium sulfate, filtered and concentrated in vacuo. Purification by column chromatography (eluent cyclohexane/ethyl acetate, 1:0 to 0:1) afforded the title compound as a solid (215 mg). .sup.1H-NMR (CDCl.sub.3, 400 MHz): =7.47-7.55 (m, 2H), 7.37-7.45 (m, 2H), 7.06-7.14 (m, 2H), 7.01 (s, 1H), 6.33 (d, J=4.4 Hz, 1H), 4.98-5.09 (m, 1H), 4.93 (ddd, J=10.5, 8.3, 4.4 Hz, 1H), 4.03-4.31 (m, 3H), 3.74 (dd, J=15.0, 2.2 Hz, 1H), 3.30 (d, J=15.8 Hz, 1H), 2.47 ppm (s, 3H)

Example P14 (Reference) Preparation of 4-[2-(3,5-dichlorophenyl)-2-(trifluoromethyl-3H-furan-4-yl]-N-[(4R)-2-ethyl-3-oxo-isoxazolidin-4-yl]-2-methyl-benzamide (C1)

(38) ##STR00177##

(39) To a suspension of 4-[2-(3,5-dichlorophenyl)-2-(trifluoromethyl)-3H-furan-4-yl]-2-methyl-benzoic acid (250 mg, prepared as described in WO2011101229) in dichloromethane (4 ml) was added thionyl chloride (0.06 ml) and then two drops of dimethylformamide. The reaction mixture was stirred at room temperature for 1 hour, and the solvent was evaporated in vacuo. The acyl chloride thus obtained was dissolved in dichloromethane (1 ml) and was added dropwise to a suspension of triethylamine (0.25 ml) and the hydrochloride salt of (4R)-4-amino-2-ethylisoxazolidin-3-one (120 mg) in dichloromethane (5 ml) at room temperature, under argon. The reaction was stirred overnight at room temperature. Then the reaction was diluted with water and extracted with ethyl acetate. The organic phase was washed two times with water, dried over anhydrous magnesium sulfate, filtered and concentrated in vacuo. Purification by column chromatography (eluent cyclohexane/ethyl acetate, 1:0 to 0:1) afforded the title compound as a solid (182 mg). .sup.1H-NMR (CDCl.sub.3, 400 MHz): =7.49 (d, J=1.5 Hz, 2H), 7.42 (dt, J=3.9, 2.2 Hz, 2H), 7.05-7.14 (m, 2H), 7.00 (s, 1H), 6.38 (d, J=3.7 Hz, 1H), 4.94-5.05 (m, 1H), 4.04 (dd, J=11.0, 8.4 Hz, 1H), 3.56-3.80 (m, 3H), 3.32 (s, 1H), 2.47 ppm (s, 3H)

Example P15: Preparation of 4-[3-(3,5-dichlorophenyl)-3-(trifluoromethyl)-2,4-dihydropyrrol-5-yl]-2-methyl-N-[(4R)-3-oxoisoxazolidin-4-yl]benzamide (compound D1)

(40) ##STR00178##

(41) D-Cycloserine (0.58 g) was added to a solution of 4-[3-(3,5-dichlorophenyl)-3,4-dihydro-3-(trifluoromethyl)-2H-pyrrol-5-yl]-2-methyl-benzoic acid, (1 g) (prepared according to WO 2010/020522) in N,N-dimethylformamide (DMF) (20 ml), followed by the addition of Hnig's base (1.9 ml), hydroxybenzotriazole (HOBT) (0.28 g) and 1-(3-Dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (EDCl) (0.54 g). The reaction mixture was stirred at ambient temperature for 63 hours. Further N,N-dimethylformamide (DMF) (10 ml) was added and the reaction mixture was stirred at ambient temperature for another 24 hours.

(42) The reaction mixture was diluted with water and extracted 3 times with ethyl acetate. The organic phases were combined, washed twice with water, dried over sodium sulfate and concentrated. The residue was purified by chromatography on silica gel (eluent: dichloromethane/methanol) to give the title compound (135 mg) as a colorless solid.

Example II: General Method for Preparing the Compounds of the Invention in Parallel

(43) ##STR00179##

(44) To a solution of 4-[3-(3,5-dichlorophenyl)-3-(trifluoromethyl)-2,4-dihydropyrrol-5-yl]-2-methyl-N-[(4R)-3-oxoisoxazolidin-4-yl]benzamide (compound B1) (12.5 mol) in N,N-dimethylformamide (DMF) (0.2 ml) was added potassium carbonate (25 mol). The suspension was stirred for 3 hours at ambient temperature. A solution of an alkylhalogenide of formula RX (22 mol) in N,N-dimethylformamide (DMF) (0.2 ml) was added and reaction mixture was stirred at ambient temperature for 16 hours. Then the reaction mixture was separated by HPLC. This method was used to prepare a number of compounds (Compound Nos. D2 to D18 of Table D) in parallel

(45) Table A:

(46) Table A provides compounds of formula (I-a) where G.sup.1 is oxygen, R.sup.5 is methyl, R.sup.1 is hydrogen and R and R have the values listed in the table below.

(47) TABLE-US-00002 (I-a) 0 Compound RT LC-MS No. R R (min) [M + H].sup.+ method A1 2-Oxo- 4-(3,5-Dichloro-phenyl)-4- 1.68 519.2 B (isomer A) [1,2]oxathiolan-4- trifluoromethyl-4,5-dihydro- yl- 3H-pyrrol-2-yl A2 2-Oxo- 4-(3,5-Dichloro-phenyl)-4- 1.72 519.2 B (isomer B) [1,2]oxathiolan-4- trifluoromethyl-4,5-dihydro- yl- 3H-pyrrol-2-yl A3 2-Oxo- 4-(3,4,5-Trichloro-phenyl)-4- 1.78 553.2 B (isomer A) [1,2]oxathiolan-4- trifluoromethyl-4,5-dihydro- yl- 3H-pyrrol-2-yl A4 2-Oxo- 4-(3,4,5-Trichloro-phenyl)-4- 1.83 553.2 B (isomer B) [1,2]oxathiolan-4- trifluoromethyl-4,5-dihydro- yl- 3H-pyrrol-2-yl A5 2-Ethyl-3-oxo- 4-(3,5-Dichloro-phenyl)-4- 1.97 528.0 A isoxazolidin-4-yl trifluoromethyl-4,5-dihydro- 3H-pyrrol-2-yl A6 2-Ethyl-3-oxo- 4-(3,4,5-Trichloro-phenyl)-4- 2.07 564.0 A isoxazolidin-4-yl trifluoromethyl-4,5-dihydro- 3H-pyrrol-2-yl A7 (R)-2-Ethyl-3- 4-(3,4,5-Trichloro-phenyl)-4- 1.85 562.2 B oxo-isoxazolidin- trifluoromethyl-4,5-dihydro- 4-yl 3H-pyrrol-2-yl A8 (R)-2-Ethyl-3- 3-(3,5-Dichloro-phenyl)-3- 1.70 530.3 B oxo-isoxazolidin- trifluoromethyl-pyrrolidinyl 4-yl A9 (R)-3-Oxo-2- 4-(3,4,5-Trichloro-phenyl)-4- 1.96 616.2 B (2,2,2-trifluoro- trifluoromethyl-4,5-dihydro- ethyl)- 3H-pyrrol-2-yl isoxazolidin-4-yl A10 (R)-3-Oxo-2- 3-(3,5-Dichloro-phenyl)-3- 1.81 584.1 B (2,2,2-trifluoro- trifluoromethyl-pyrrolidinyl ethyl)- isoxazolidin-4-yl A11 (R)-3-Oxo-2- (R)-4-(3,5-Dichloro-phenyl)- 1.86 582.4 B (2,2,2-trifluoro- 4-trifluoromethyl-4,5-dihydro- ethyl)- 3H-pyrrol-2-yl isoxazolidin-4-yl A12 (R)-2-Ethyl-3- 5-(3,5-Dichloro-phenyl)-5- 1.94 529.3 B oxo-isoxazolidin- trifluoro 4-yl methyl-2,5-dihydro-furan-3-yl A13 (R)-3-Oxo-2- 5-(3,5-Dichloro-phenyl)-5- 2.03 583.3 B (2,2,2-trifluoro- trifluoro ethyl)- methyl-2,5-dihydro-furan-3-yl isoxazolidin-4-yl
Table B
Table B provides compounds of formula (I-b) where G.sup.1 is oxygen, R.sup.5 is methyl, R.sup.1 is hydrogen and X, Y, R and R have the values listed in the table below.

(48) TABLE-US-00003 (I-b) Compound RT LC-MS No. A.sup.2 A.sup.3 R R (min) [M + H].sup.+ method B1 C N 2-Ethyl-3-oxo- 3-(3,5-Dichloro- 1.57 531.4 B isoxazolidin-4-yl phenyl)-3- trifluoromethyl- pyrrolidinyl B2 C N 3-Oxo-2-(2,2,2- 3-(3,5-Dichloro- 1.73 585.3 B trifluoro-ethyl)- phenyl)-3- isoxazolidin-4-yl trifluoromethyl- pyrrolidinyl B3 N C 2-Ethyl-3-oxo- 3-(3,5-Dichloro- 1.65 531.4 B isoxazolidin-4-yl phenyl)-3- trifluoromethyl- pyrrolidinyl B4 N C 3-Oxo-2-(2,2,2- 3-(3,5-Dichloro- 1.81 585.3 B trifluoro-ethyl)- phenyl)-3- isoxazolidin-4-yl trifluoromethyl- pyrrolidinyl
Table C (Reference):
Table C provides compounds of formula (I-a) where G.sup.1 is oxygen, R.sup.5 is methyl, R.sup.1 is hydrogen and R and R have the values listed in the table below.

(49) TABLE-US-00004 (I-a) Compound No. R R C1 (R)-2-Ethyl-3- 4-[5-(3,5-Dichloro-phenyl)-5- oxo-isoxazolidin- trifluoromethyl- 4-yl 4,5-dihydro-furan- 3-yl]- C2 (R)-3-Oxo-2- 4-[5-(3,5-Dichloro-phenyl)-5- (2,2,2-trifluoro- trifluoromethyl- ethyl)- 4,5-dihydro-furan- isoxazolidin-4-yl 3-yl]-
Table D: Compounds of Formula (I-c):

(50) TABLE-US-00005 (I-c) Comp LCMS RT (M + H)- No. R.sup.5 G.sup.1 R.sup.9 Method (min) (measured) D1 Me O H C 0.98 500 D2 Me O 3-methyl-but-2-enyl J 1.94 568.34 D3 Me O 4-nitro-benzyl J 1.91 635.09 D4 Me O 1,1,1-trifluoropropan-3- J 1.87 596.23 yl D5 Me O 4-fluoro-benzyl J 1.94 608.47 D6 Me O 1,1,1-trifluorobutan-4-yl J 1.92 610.22 D7 Me O 2,6-difluoro-benzyl J 1.93 626.28 D8 Me O cyclopropylmethyl J 1.87 554.30 D9 Me O 2-[1,3]dioxan-2-yl-ethyl J 1.77 613.64 D10 Me O 5-trifluoromethyl-furan- J 2.00 648.30 2-ylmethyl D11 Me O 2,5-dimethyl-2H- J 1.74 609.38 [1,2,3]triazol-4-yl- methyl D12 Me O cyclobutylmethyl J 1.96 568.20 D13 Me O (propan-2-one J 1.83 585.33 O-methyl-oxime)-1-yl D14 Me O allyl J 1.79 540.31 D15 Me O 3-cyanopropyl J 1.71 567.39 D16 Me O 3-phenyl-propyl J 2.05 618.37 D17 Me O cyclohexylmethyl J 2.10 596.43 D18 Me O 4-methoxybutyl J 1.81 586.02
The following LC-MS methods were used to characterize the compounds:
Method A

(51) TABLE-US-00006 MS ACQUITY SQD Mass Spectrometer from Waters (Single quadrupole mass spectrometer) Ionisation method: Electrospray Polarity: positive ions Capillary (kV) 3.00, Cone (V) 20.00, Extractor (V) 3.00, Source Temperature (150 C.) Desolvation Temperature ( C.) 400, Cone Gas Flow (L/Hr) 60, Desolvation Gas Flow (L/Hr) 700, Mass range: 100 to 800 Da LC Method Waters ACQUITY UPLC with the following HPLC gradient conditions (Solvent A: water/methanol 9:1, 0.1% formic acid and Solvent B: acetonitrile, 0.1% formic acid) DAD Wavelength range (nm): 210 to 400 Type of column: Waters ACQUITY UPLC HSS T3; Column length: 30 mm; Internal diameter of column: 2.1 mm; Particle Size: 1.8 micron; Temperature: 60 C. Time (min) A (%) B (%) Flow rate (ml/min) 0 100 0 0.75 2.5 0 100 0.75 2.8 0 100 0.75 3.0 100 0 0.75
Method B

(52) TABLE-US-00007 MS ZQ Mass Spectrometer from Waters (single quadrupole mass spectrometer), ionization method: electrospray, polarity: positive ionization, capillary (kV) 3.00, cone (V) 30.00, extractor (V) 3.00, source temperature ( C.) 100, desolvation temperature ( C.) 200, cone gas flow (L/Hr) 200, desolvation gas flow (L/Hr) 250, mass range: 150 to 800 Da. LC 1100er Series HPLC from Agilent: quaternary pump, heated column compartment and diode-array detector. Column: Waters Atlantis dc18; length: 20 mm; internal diameter: 3 mm; particle size: 3 m, temperature ( C.) 40, DAD wavelength range (nm): 200 to 500, solvent gradient: A = 0.1% of formic acid in water and B: 0.1% of formic acid in acetonitrile. Time (min) A (%) B (%) Flow rate (ml/min) 0.0 90 10 1.7 5.5 0.0 100 1.7 5.8 0.0 100 1.7 5.9 90 10 1.7
Method C

(53) TABLE-US-00008 MS SQD Mass Spectrometer from Waters (Single quadrupole mass spectrometer) Instrument Parameter: Ionization method: Electrospray Polarity: positive and negative ions Capillary: 3.00 kV; Cone: 45.00 V Extractor: 2.00 V; Source Temperature: 150 C., Desolvation Temperature: 250 C.; Cone Gas Flow: 0 L/Hr Desolvation Gas Flow: 650 L/Hr; Mass range: 100 to 900 Da LC Acquity UPLC from Waters: Binary pump, heated column compartment and diode-array detector. Solvent degasser, binary pump, heated column compartment and diode-array detector. Column: Phenomenex Gemini C18, 3 m, 30 2 mm, Temp: 60 C. DAD Wavelength range (nm): 210 to 500 Solvent Gradient: A = H2O + 5% MeOH + 0.05% HCOOH; B = Acetonitril + 0.05% HCOOH Time A % B % Flow (ml/min) 0.00 100 0 0.850 1.2 0 100.0 0.850 1.50 0 100.0 0.850
Method E

(54) TABLE-US-00009 MS ZQ Mass Spectrometer from Waters (single quadrupole mass spectrometer), ionization method: electrospray, polarity: positive ionization, capillary (kV) 3.00, cone (V) 30.00, extractor (V) 3.00, source temperature ( C.) 100, desolvation temperature ( C.) 200, cone gas flow (L/Hr) 200, desolvation gas flow (L/Hr) 250, mass range: 150 to 800 Da. LC 1100er Series HPLC from Agilent: quaternary pump, heated column compartment and diode-array detector. Column: Waters Atlantis dc18, length (mm) 20, internal diameter (mm) 3, particle size (m) 3, temperature ( C.) 40, DAD wavelength range (nm): 200 to 500, solvent gradient: A = 0.1% v/v formic acid in water and B = 0.1% v/v formic acid in acetonitrile. Time (min) A % B % Flow (ml/min) 0.0 80 20 1.7 2.5 0.0 100 1.7 2.8 0.0 100 1.7 2.9 80 20 1.7
Method F

(55) TABLE-US-00010 MS ZQ Mass Spectrometer from Waters (single quadrupole mass spectrometer), ionization method: electrospray, polarity: negative ionization, capillary (kV) 3.00, cone (V) 45.00, source temperature ( C.) 100, desolvation temperature ( C.) 250, cone gas flow (L/Hr) 50, desolvation gas flow (L/Hr) 400, mass range: 150 to 1000 Da. LC HP 1100 HPLC from Agilent: solvent degasser, binary pump, heated column compartment and diode-array detector. Column: Phenomenex Gemini C18, length (mm) 30, internal diameter (mm) 3, particle size (m) 3, temperature ( C.) 60, DAD wavelength range (nm): 200 to 500, solvent gradient: A = 0.05% v/v formic acid in water and B = 0.04% v/v formic acid in acetonitrile/methanol (4:1). Time (min) A % B % Flow (ml/min) 0.0 95 5.0 1.7 2.0 0.0 100 1.7 2.8 0.0 100 1.7 2.9 95 5.0 1.7 3.1 95 5 1.7
Method J

(56) TABLE-US-00011 MS Waters ACQUITY SQD Mass Spectrometer from Waters (Single quadrupole mass spectrometer) Ionisation method: Electrospray Polarity: positive ions Capillary (kV) 3.00, Cone (V) 20.00, Extractor (V) 3.00, Source Temperature ( C.) 150, Desolvation Temperature ( C.) 400, Cone Gas Flow (L/Hr) 60, Desolvation Gas Flow (L/Hr) 700 Mass range: 100 to 800 Da DAD Wavelength range (nm): 210 to 400 LC Waters ACQUITY UPLC with the following HPLC gradient conditions (Solvent A: Water/Methanol 9:1, 0.1% formic acid and Solvent B: Acetonitrile, 0.1% formic acid) Time (minutes) A (%) B (%) Flow rate (ml/min) 0 100 0 0.75 2.5 0 100 0.75 2.8 0 100 0.75 3.0 100 0 0.75 Type of column: Waters ACQUITY UPLC HSS T3; Column length: 30 mm; Internal diameter of column: 2.1 mm; Particle Size: 1.8 micron; Temperature: 60 C.

BIOLOGICAL EXAMPLES

(57) This Example illustrates the insecticidal and acaricidal properties of compounds of formula (I). The tests were performed as follows:

(58) Spodoptera littoralis (Egyptian Cotton Leafworm):

(59) Cotton leaf discs were placed on agar in a 24-well microtiter plate and sprayed with test solutions at an application rate of 200 ppm. After drying, the leaf discs were infested with 5 L1 larvae. The samples were checked for mortality, feeding behavior, and growth regulation 3 days after treatment (DAT).

(60) The following compound gave at least 80% control of Spodoptera littoralis: A5, A6, A7, A8, A9, A10, B1, B2, B3, B4, A14, A11, A13, A12, D8, D15, D18, C1, C2.

(61) Heliothis virescens (Tobacco Budworm):

(62) Eggs (0-24 h old) were placed in 24-well microtiter plate on artificial diet and treated with test solutions at an application rate of 200 ppm (concentration in well 18 ppm) by pipetting. After an incubation period of 4 days, samples were checked for egg mortality, larval mortality, and growth regulation.

(63) The following compound gave at least 80% control of Heliothis virescens: A5, A6, A7, A8, A9, A10, B1, B2, B3, B4, A14, A11, A4, A13, A12, D4, D8, D1, D12, D13, D14, D15, D16, D18, C1, C2.

(64) Plutella xylostella (Diamond Back Moth):

(65) 24-well microtiter plate (MTP) with artificial diet was treated with test solutions at an application rate of 200 ppm (concentration in well 18 ppm) by pipetting. After drying, the MTP's were infested with L2 larvae (7-12 per well). After an incubation period of 6 days, samples were checked for larval mortality and growth regulation.

(66) The following compound gave at least 80% control of Plutella xylostella: A5, A6, A7, A8, A9, A10, B2, B3, B4, A14, A11, A13, A12, D2, D4, D5, D7, D8, D11, D12, D13, D14, D15, C1, C2.

(67) Diabrotica balteata (Corn Root Worm):

(68) A 24-well microtiter plate (MTP) with artificial diet was treated with test solutions at an application rate of 200 ppm (concentration in well 18 ppm) by pipetting. After drying, the MTP's were infested with L2 larvae (6-10 per well). After an incubation period of 5 days, samples were checked for larval mortality and growth regulation.

(69) The following compound gave at least 80% control of Diabrotica balteata: A5, A6, A7, A8, A9, A10, B2, B3, B4, A14, A11, A13, A12, D4, D5, D6, D7, D10, D13, D14, D16, C1, C2.

(70) Thrips tabaci (Onion Thrips):

(71) Sunflower leaf discs were placed on agar in a 24-well microtiter plate and sprayed with test solutions at an application rate of 200 ppm. After drying, the leaf discs were infested with a thrip population of mixed ages. After an incubation period of 7 days, samples were checked for mortality.

(72) The following compounds gave at least 80% control of Thrips tabaci: A5, A6, A7, A8, A9, A10, B3, B4, A14, A11, A13, A12, D4, D15, C1, C2.

(73) Terranychus urticae (Two-Spotted Spider Mite):

(74) Bean leaf discs on agar in 24-well microtiter plates were sprayed with test solutions at an application rate of 200 ppm. After drying, the leaf discs are infested with mite populations of mixed ages. 8 days later, discs are checked for egg mortality, larval mortality, and adult mortality.

(75) The following compound gave at least 80% control of Tetranychus urricae: A5, A6, A7, A8, A9, A10, B1, B2, B3, B4, A14, A11, A13, A12, D2, D3, D4, D5, D6, D7, D8, D9, D10, D11, D12, D13, D14, D15, D16, C1, C2.