Insecticidal compounds

Abstract

The present invention relates to novel triazole derivatives of formula (I) having insecticidal activity, to processes and intermediates for preparing them, to insecticidal, acaricidal, nematicidal or molluscicidal compositions comprising them and to methods of using them to combat and control insect, acarine, nematode or mollusc pests ##STR00001## wherein R.sup.1, R.sup.2, G.sup.1, G.sup.2, Q.sup.1 and Q.sup.2 are as defined in claim 1; or salts thereof.

Claims

1. A compound according to the formula (IV) ##STR00059## wherein X is hydrogen or F and R.sup.1 is selected from ethyl, n-propyl and n-butyl R is selected from halogen, C.sub.1-C.sub.6-alkyl-C(O)O, phenyl-C(O)O, C.sub.1-C.sub.6-alkoxy-C(O)O, phenoxy-C(O)O, benzyloxy-C(O)O and imidazol-1-yl, or a salt thereof.

2. A method of use of compounds according to the formula (IV) ##STR00060## for the production of compounds according to formula (V) ##STR00061## wherein X is hydrogen or F and R.sup.1 is selected from methyl, ethyl, n-propyl and n-butyl, R is selected from halogen, C.sub.1-C.sub.6-alkyl-C(O)O, phenyl-C(O)O, C.sub.1-C.sub.6-alkoxy-C(O)O, phenoxy-C(O)O, benzyloxy-C(O)O and imidazol-1-yl, and Q.sup.1 is 4-pyridyl or 1-oxidopyridin-1-ium-4-yl; or a salt thereof; provided that when R.sub.1 is methyl, than R is not Cl.

3. A compound according to the formula (IV) ##STR00062## wherein X is hydrogen or F and R.sup.1 is selected from methyl, ethyl, n-propyl and n-butyl R is selected from F, Br, C.sub.1-C.sub.6-alkyl-C(O)O, phenyl-C(O)O, C.sub.1-C.sub.6-alkoxy-C(O)O, phenoxy-C(O)O, benzyloxy-C(O)O and imidazol-1-yl, or a salt thereof.

Description

PREPARATION EXAMPLES

Examples

(1) The following abbreviations were used throughout 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.

Example I 1.1: N-[2-bromo-6-chloro-4-(1,1,1,2,3,3,3-heptafluoro-prop-2-yl)phenyl]-2-fluoro-3-nitro-benzamide

(2) ##STR00034##

(3) To a suspension of 2-fluoro-3-nitrobenzoic acid (309 g, 1.67 mol) in dichloroethane (2090 ml) was added N,N-dimethylformamide (1.3 ml, 16.7 mmol) followed by slow addition of oxalyl chloride (150 ml, 1.69 mol) at ambient temperature. The reaction mixture was stirred and heated at 50 C. until a solution was formed. The reaction mixture was allowed to cool to ambient temperature and then added to a solution of 2-bromo-6-chloro-4-[1,1,1,2,3,3,3-heptafluoro-prop-2-yl]aniline (described in WO/10127926) (125 g, 334 mmol) in dichloroethane (477 ml) followed by addition of triethylamine (564 ml, 4.01 mol). The reaction mixture was stirred at reflux for 4 hours. The reaction was quenched by addition of saturated aqueous sodium hydrogen carbonate (500 ml). The layers were separated and the organic layer was washed with water (500 ml). The combined aqueous layers were extracted twice with dichloroethane (2500 ml). The combined organic extracts were dried over sodium sulfate and concentrated. The crude residue was dissolved in THF and a 1N solution of sodium hydroxide (2 eq) was added. The mixture was stirred at room temperature until the diacylated product disappeared. Then ethyl acetate (1 L) and saturated aqueous sodium hydrogen carbonate (1 L) were added. The layers were separated and the aqueous layer was extracted with ethyl acetate (4250 ml). The organic layer was concentrated, filtered through silica gel, and concentrated again. The residue (181 g) was used directly for the next step.

(4) .sup.1H NMR (CDCl.sub.3, 400 MHz): 8.39 (m, 1H), 8.21 (m, 1H), 8.09 (d, 1H), 7.78 (s, 1H), 7.67 (s, 1H), 7.43 (t, 1H).

Preparation Examples

Examples

(5) The following abbreviations were used throughout 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.

Example I 1.1: N-[2-bromo-6-chloro-4-(1,1,1,2,3,3,3-heptafluoro-prop-2-yl)phenyl]-2-fluoro-3-nitro-benzamide

(6) ##STR00035##

(7) To a suspension of 2-fluoro-3-nitrobenzoic acid (309 g, 1.67 mol) in dichloroethane (2090 ml) was added N,N-dimethylformamide (1.3 ml, 16.7 mmol) followed by slow addition of oxalyl chloride (150 ml, 1.69 mol) at ambient temperature. The reaction mixture was stirred and heated at 50 C. until a solution was formed. The reaction mixture was allowed to cool to ambient temperature and then added to a solution of 2-bromo-6-chloro-4-[1,1,1,2,3,3,3-heptafluoro-prop-2-yl]aniline (described in WO/10127926) (125 g, 334 mmol) in dichloroethane (477 ml) followed by addition of triethylamine (564 ml, 4.01 mol). The reaction mixture was stirred at reflux for 4 hours. The reaction was quenched by addition of saturated aqueous sodium hydrogen carbonate (500 ml). The layers were separated and the organic layer was washed with water (500 ml). The combined aqueous layers were extracted twice with dichloroethane (2500 ml). The combined organic extracts were dried over sodium sulfate and concentrated. The crude residue was dissolved in THF and a 1N solution of sodium hydroxide (2 eq) was added. The mixture was stirred at room temperature until the diacylated product disappeared. Then ethyl acetate (1 L) and saturated aqueous sodium hydrogen carbonate (1 L) were added. The layers were separated and the aqueous layer was extracted with ethyl acetate (4250 ml). The organic layer was concentrated, filtered through silica gel, and concentrated again. The residue (181 g) was used directly for the next step.

(8) .sup.1H NMR (CDCl.sub.3, 400 MHz): 8.39 (m, 1H), 8.21 (m, 1H), 8.09 (d, 1H), 7.78 (s, 1H), 7.67 (s, 1H), 7.43 (t, 1H).

Example I 2.1: 3-Amino-N-[2-bromo-6-chloro-4-(1,2,2,2,3,3,3-heptafluoro-prop-2-yl)-phenyl]-2-fluoro-benzamide

(9) ##STR00036##

(10) N-[2-bromo-6-chloro-4-(1,2,2,2,3,3,3-heptafluoro-prop-2-yl)phenyl]-2-fluoro-3-nitro-benzamide (Example I 1.1) (2 g, 3.69 mmol) was dissolved in THF (16.6 ml). Then NaOH (9.2 ml), tetrabutylammonium bromide (0.121 g, 0.369 mmol) and sodium dithionite (2.27 g, 11.1 mmol) were added. The mixture was heated under reflux for 1.5 hours and then cooled down to room temperature. The reaction mixture was diluted with ethyl acetate, water was added and the phases were separated. The aqueous phase was extracted twice with ethyl acetate. The combined organic phases were washed with 1N aqueous HCl and then with a aqueous solution of sodium hydrogen carbonate, dried over sodium sulfate, filtered and concentrated. Flashchromatography (eluent: cyclohexane/ethyl acetate from 100:0 to 0:100) gave 3-amino-N-[2-bromo-6-chloro-4-(1,2,2,2,3,3,3-heptafluoro-prop-2-yl)-phenyl]-2-fluoro-benzamide (1.13 g, 59.6% yield).

(11) .sup.1H NMR (400 MHz, CDCl.sub.3): 8.25 (d, 1H), 7.85 (s, 1H), 7.74 (s, 1H) 7.52 (td, 1H), 7.12 (t, 1H), 7.03 (td, 1H), 3.80 (bs, 2H) ppm.

Example I 3.1: N-[2-bromo-6-chloro-4-(1,1,1,2,3,3,3-heptafluoro-prop-2-yl)-phenyl]-3-ethylamino-2-fluoro-benzamide

(12) ##STR00037##

(13) 3-amino-N-[2-bromo-6-chloro-4-(1,2,2,2,3,3,3-heptafluoro-prop-2-yl)-phenyl]-2-fluoro-benzamide (Example I 2.1) (0.585 g, 1.14 mmol) was dissolved in methanol (8.2 ml) and acetaldehyde (0.065 ml, 1.14 mmol) and acetic acid (0.07 ml, 1.26 mmol) were added. Then cyanoborohydride (0.083 g, 1.26 mmol) was added. The reaction mixture was stirred for 1 hour at room temperature. After evaporation of the solvent ethyl acetate and an aqueous solution of sodium hydroxide (0.1M) were added. The layers were separated and the aqueous layer was extracted twice with ethyl acetate. The combined organic layers were washed with water, dried over magnesium sulfate, filtered and concentrated. The residue was purified by flash chromatography (eluent: cyclohexane/ethyl acetate 100:0=>50:50) to give N-[2-bromo-6-chloro-4-(1,1,1,2,3,3,3-heptafluoro-prop-2-yl)-phenyl]-3-ethylamino-2-fluoro-benzamide (0.418 g, 68%).

(14) .sup.1H NMR (400 MHz, CDCl.sub.3): 8.23 (d, 1H), 7.85 (s, 1H), 7.72 (s, 1H), 7.40 (td, 1H), 7.17 (t, 1H), 6.92 (td, 1H), 4.01 (bs, 1H), 3.28 (q, 2H), 1.36 (t, 3H) ppm.

Example P 1.1: N-[3-[[2-bromo-6-chloro-4-[1,1,1,2,3,3,3-heptafluoro-prop-2-yl]phenyl]carbamoyl]-2-fluoro-phenyl]-N-ethyl-pyridine-4-carboxamide (Compound No. 1 of Table A)

(15) ##STR00038##

(16) N-[2-bromo-6-chloro-4-(1,1,1,2,3,3,3-heptafluoro-prop-2-yl)-phenyl]-3-ethylamino-2-fluoro-benzamide (Example I 3.1) (418 mg, 0.775 mmol) was dissolved in tetrahydrofuran (4.3 ml). Pyridine (0.25 ml, 3.1 mmol) and isonicotinoyl chloride hydrochloride (290 mg, 1.55 mol) were added and the reaction mixture was stirred at ambient temperature for 16 hours. The reaction mixture was poured into aqueous sodium hydrogen carbonate. The aqueous phase was extracted twice with ethyl acetate. The combined organic phases were dried over sodium sulfate, filtered and concentrated. The residue was purified by column chromatography on silica gel (eluent: ethyl acetate/cyclohexane 20/80=>0:100). The fractions containing the desired product were combined and the solvents were evaporated to give pure compound No. 1 of Table A (500 mg, quantitative). M.p. 99-101 C.

(17) .sup.1H NMR (400 MHz, CDCl.sub.3): 8.51 (bs, 2H), 7.90-8.15 (m, 2H), 7.86 (s, 1H), 7.72 (s, 1H), 7.25-7.62 (m, 2H), 7.20 (bs, 2H), 3.60-4.18 (m, 2H), 1.20-1.40 (m, 3H) ppm.

Example P1.2: N-[3-[[2-bromo-6-chloro-4-[1,1,1,2,3,3,3-heptafluoro-prop-2-yl]phenyl]carbamoyl]-2-fluoro-phenyl]-N-ethyl-1-oxido-pyridin-1-ium-4-carboxamide (Compound No. 2 of Table A)

(18) ##STR00039##

(19) N-[3-[[2-bromo-6-chloro-4-[1,1,1,2,3,3,3-heptafluoro-prop-2-yl]phenyl]carbamoyl]-2-fluoro-phenyl]-N-ethyl-pyridine-4-carboxamide (Example P 1.1; compound No. 1 of Table A) (0.320 g, 0.496 mmol) was dissolved in dichloromethane (3 ml) 3-chloroperoxybenzoic acid (0.245 g, 0.993 mmol) was added. After stirring for 1 h at room temperature the mixture was diluted with water and an aqueous solution of sodium hydrogen carbonate. The phases were separated and the aqueous phase was extracted with dichloromethane. The combined organic phases were dried over magnesium sulfate, filtered and concentrated. The residue was purified by column chromatography on silica gel (eluent: DCM/MeOH from 100:0 to 85:15) to give pure compound No. 2 of Table A (304 mg, 93% yield). M.p. 115-117 C. .sup.1H NMR (400 MHz, CDCl.sub.3): 8.00-8.18 (m, 4H), 7.84 (s, 1H), 7.72 (s, 1H), 7.40-7.52 (m, 1H) 7.32-7.40 (m, 1H), 7.19-7.30 (m, 2H), 3.87-4.15 (m, 2H), 1.28 (t, 3H) ppm.

(20) LC-MS Methods: ZCQ12, ZCQ13 and OA STANDARD

(21) ZQ Mass Spectrometer from Waters (Single Quadrupole Mass Spectrometer)

(22) Instrument Parameter:

(23) Ionization method: Electrospray

(24) Polarity: positive and negative ions

(25) Capillary: 3.00 kV

(26) Cone: 30 V

(27) Extractor: 2.00 V

(28) Source Temperature: 150 C.,

(29) Desolvation Temperature: 350 C

(30) Cone Gas Flow: 50 L/Hr

(31) Desolvation Gas Flow: 400 L/Hr

(32) Mass range: 100 to 900 Da

(33) Acquity UPLC from Waters:

(34) Binary pump, heated column compartment and diode-array detector.

(35) Solvent degasser, binary pump, heated column compartment and diode-array detector.

(36) Column: Waters UPLC HSS T3, 1.8 m, 302.1 mm,

(37) Temp: 60 C.

(38) DAD Wavelength range (nm): 210 to 500

(39) Solvent Gradient: A=H2O+5% MeOH+0.05% HCOOH B=Acetonitril+0.05% HCOOH

(40) TABLE-US-00005 Time A % B % Flow (ml/min) 0.00 90 10 0.85 1.20 0 100.0 0.85 1.50 0 100.0 0.85
LC-MS Method: ZDQ11
ZQ Mass Spectrometer from Waters (Single Quadrupole Mass Spectrometer)
Instrument Parameter:

(41) Ionization method: Electrospray

(42) Polarity: positive and negative ions

(43) Capillary: 3.00 kV

(44) Cone: 30 V

(45) Extractor: 2.00 V

(46) Source Temperature: 150 C.,

(47) Desolvation Temperature: 350C

(48) Cone Gas Flow: 50 L/Hr

(49) Desolvation Gas Flow: 400 L/Hr

(50) Mass range: 100 to 900 Da

(51) Acquity UPLC from Waters:

(52) Binary pump, heated column compartment and diode-array detector.

(53) Solvent degasser, binary pump, heated column compartment and diode-array detector.

(54) Column: Waters UPLC HSS T3, 1.8 m, 302.1 mm,

(55) Temp: 60 C.

(56) DAD Wavelength range (nm): 210 to 500

(57) Solvent Gradient: A=H2O+5% MeOH+0.05% HCOOH B=Acetonitril+0.05% HCOOH

(58) TABLE-US-00006 Time A % B % Flow (ml/min) 0.00 90 10 0.85 2.70 0 100.0 0.85 3.00 0 100.0 0.85

(59) The compounds in tables A were prepared in the same or a similar way as described above:

(60) TABLE-US-00007 TABLE A RT [M + H] Entry STRUCTURE (min) (measured) Method MP C. 1 0 1.89 644, 646, 648 ZDQ11 99-101 2 1.80 660, 662, 664 ZDQ11 115-117 3 1.05 630, 632, 634 ZCQ12 99-160 4 1.11 588 ZCQ12 190-193 5 1.03 604 ZCQ12 105-111 6 1.07 688, 690, 692 ZCQ13 97-100 7 1.07 676, 678 ZCQ13 186-188 8 1.05 674, 676, 678 OA_STANDARD 112-250 9 0.97 690, 692, 694 OA_STANDARD 146-262 10 1.03 586, 588, 590 OA_STANDARD 85-90 11 0 1.07 600, 602, 604 OA_STANDARD 91-94 12 1.04 566, 568 OA_STANDARD 99-100 13 1.10 594, 596 OA_STANDARD 14 1.07 580, 582 OA_STANDARD 15 1.12 650, 652 OA_STANDARD 97-100 16 1.05 666, 668 OA_STANDARD 110-114 17 1.01 692, 694 OA_STANDARD 103-106 18 1.08 632, 634 OA_STANDARD 183-184 19 1.07 612 OA_STANDARD 186-188

Biological Examples

(61) These Examples illustrate the insecticidal and acaricidal properties of the compounds of formula (I). The tests were performed as follows:

(62) Spodoptera littoralis (Egyptian Cotton Leafworm):

(63) 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).

(64) The following compound gave at least 80% control of Spodoptera littoralis: 1, 2, 3, 4, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19.

(65) Heliothis virescens (Tobacco Budworm):

(66) 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.

(67) The following compound gave at least 80% control of Heliothis virescens: 1, 2, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17.

(68) Plutella xylostella (Diamond Back Moth):

(69) 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.

(70) The following compound gave at least 80% control of Plutella xylostella: 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19.

(71) Diabrotica balteata (Corn Root Worm):

(72) 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.

(73) The following compound gave at least 80% control of Diabrotica balteata: 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19.

(74) Thrips tabaci (Onion Thrips):

(75) 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 an aphid population of mixed ages. After an incubation period of 7 days, samples were checked for mortality.

(76) The following compounds gave at least 80% control of Thrips tabaci: 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19.

(77) Tetranychus urticae (Two-Spotted Spider Mite):

(78) 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.

(79) The following compounds gave at least 80% control of Tetranychus urticae: 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19.

(80) Myzus persicae (Green Peach Aphid):

(81) 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 an aphid population of mixed ages. After an incubation period of 6 DAT, samples were checked for mortality.

(82) The following compounds gave at least 80% control of Myzus persicae: 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19.