PESTICIDALLY ACTIVE THIOSEMICARBAZONE COMPOUNDS

Abstract

The present invention relates to the compounds of formula (I), and the N-oxides, stereoisomers, tautomers and agriculturally or veterinarily acceptable salts thereof wherein the variables are defined according to the description, The compounds of formula (I), as well as the N-oxides, stereoisomers, tautomers and The compounds of formula (I), as well as the N-oxides, stereoisomers, tautomers and agriculturally or veterinarily acceptable salts thereof, are useful for combating or controlling invertebrate pests, in particular arthropod pests and nematodes. The invention also relates to a method for controlling invertebrate pests by using these compounds and to plant propagation material and to an agricultural and a veterinary composition comprising said compounds.

##STR00001##

Claims

1. A compound of formula I ##STR00223## wherein A is N or CR.sup.A; B.sup.1 is N or CR.sup.B1; B.sup.2 is N or CR.sup.B2; R.sup.A is H, halogen, CN, C.sub.1-C.sub.6-alkyl, C.sub.1-C.sub.6-alkoxy, C.sub.2-C.sub.6-alkynyl, C.sub.3-C.sub.6-cycloalkyl, wherein the alkyl, alkoxy, alkynyl, and cycloalkyl moieties are unsubstituted or substituted with halogen; R.sup.B1 and R.sup.B2 independently of each other are H, halogen, OH, CN, SCN, SF.sub.5, C.sub.1-C.sub.6-alkyl, C.sub.1-C.sub.6-alkoxy, C.sub.2-C.sub.6-alkynyl, C.sub.1-C.sub.6-alkoxy-C.sub.1-C.sub.4-alkyl, C.sub.3-C.sub.6-cycloalkyl, C.sub.3-C.sub.6-cycloalkoxy, wherein the alkyl, alkoxy, alkynyl, cycloalkyl, and cycloalkoxy moieties are unsubstituted or substituted with halogen, C(O)OR.sup.a, NR.sup.bR.sup.c; Q is N(R.sup.2)C(O), N(R.sup.2)C(S), NC(X), or N(R.sup.2)C(NR), wherein Ar is bound to either side of Q; X is N(R.sup.3).sub.2; R is H, C.sub.1-C.sub.6-alkyl, C.sub.2-C.sub.6-alkynyl, or C.sub.3-C.sub.6-cycloalkyl, wherein the alkyl, and cycloalkyl moieties are unsubstituted or substituted with halogen, R.sup.3 is H, C.sub.1-C.sub.6-alkyl, C.sub.1-C.sub.6-alkoxy-C.sub.1-C.sub.4-alkyl; C.sub.3-C.sub.6-cycloalkyl; R.sup.2 is H, C.sub.1-C.sub.6-alkyl, C.sub.2-C.sub.6-alkynyl, C.sub.1-C.sub.6-alkoxy-C.sub.1-C.sub.4-alkyl, C.sub.3-C.sub.6-cycloalkyl, C.sub.3-C.sub.6-cycloalkyl-C.sub.1-C.sub.4-alkyl, wherein the alkyl, alkoxy, alkynyl, cycloalkyl, and cycloalkoxy moieties are unsubstituted or substituted with halogen, C(O)OR.sup.a; m is 0, 1, or 2; R.sup.6 is H, C.sub.1-C.sub.6-alkyl, C.sub.2-C.sub.6-alkynyl, C.sub.3-C.sub.6-cycloalkyl, wherein the alkyl, alkynyl, and cycloalkyl moieties are unsubstituted or substituted with halogen, Ar is phenyl or 5- or 6-membered heteroaryl or 1,3-benzodioxole, which are unsubstituted or substituted with R.sup.Ar, wherein R.sup.Ar is halogen, OH, CN, SCN, SF.sub.5, C.sub.1-C.sub.6-alkyl, C.sub.1-C.sub.6-alkoxy, C.sub.2-C.sub.6-alkenyl, C.sub.2-C.sub.6-alkynyl, C.sub.1-C.sub.6-alkoxy-C.sub.1-C.sub.4-alkyl, C.sub.1-C.sub.6-alkoxy-C.sub.1-C.sub.4-alkoxy, C.sub.3-C.sub.6-cycloalkyl, C.sub.3-C.sub.6-cycloalkoxy, C.sub.3-C.sub.6-cycloalkyl-C.sub.1-C.sub.4-alkyl, C.sub.3-C.sub.6-cycloalkoxy-C.sub.1-C.sub.4-alkyl, wherein the alkyl, alkoxy, alkenyl, alkynyl, cycloalkyl, and cycloalkoxy moieties are unsubstituted or substituted with halogen, C(O)OR.sup.a, NR.sup.bR.sup.c, C.sub.1-C.sub.6-alkylene-NR.sup.bR.sup.c, OC.sub.1-C.sub.6-alkylene-NR.sup.bR.sup.c, C.sub.1-C.sub.6-alkylene-CN, NHC.sub.1-C.sub.6-alkylene-NR.sup.bR.sup.c, C(O)NR.sup.bR.sup.c, SO.sub.2NR.sup.bR.sup.c, or S(O).sub.mR.sup.e; R.sup.s is selected from (CR.sup.xR.sup.y).sub.nOCO(OC.sub.1-C.sub.6-alkyl).sub.p-Y, (CR.sup.xR.sup.y).sub.nOCO(C.sub.2-C.sub.6-alkenyl).sub.q-Y, (CR.sup.xR.sup.y).sub.nOCONR.sub.jR.sup.k, n is 1, or 2; p is 0, 1, 2, 3, 4, or 5; q is 0, 1, or 2; Y is C.sub.1-C.sub.6-alkyl, C.sub.1-C.sub.6-alkoxy, C.sub.3-C.sub.6-cycloalkyl, 5- to 6-membered heterocyclic group, or phenyl, wherein the alkyl, heterocyclic, and phenyl groups are unsubstituted or substituted with R.sup.f; R.sup.xR.sup.y independently are selected from H or C.sub.1-C.sub.6-alkyl, wherein the alkyl group is unsubstituted or substituted with R.sup.f; R.sup.j and R.sup.k independently are selected from H or C.sub.1-C.sub.6-alkyl, wherein the alkyl group is unsubstituted or substituted with R.sup.f; R.sup.n H, C.sub.1-C.sub.6-alkyl, wherein the alkyl moiety is unsubstituted or substituted with halogen, C.sub.1-C.sub.6-alkylene-CN; R.sup.11 is C.sub.1-C.sub.6-alkyl, C.sub.2-C.sub.6-alkenyl, C.sub.2-C.sub.6-alkynyl, C.sub.1-C.sub.6-alkoxy-C.sub.1-C.sub.4-alkyl, C.sub.3-C.sub.6-cycloalkyl, C.sub.3-C.sub.6-cycloalkyl-C.sub.1-C.sub.4-alkyl, C.sub.1-C.sub.4-alkyl-C.sub.3-C.sub.6-cycloalkoxy, wherein the alkyl, alkoxy, alkenyl, alkynyl, cycloalkyl, and cycloalkoxy moieties are unsubstituted or substituted with halogen, C.sub.1-C.sub.6-alkylene-NR.sup.bR.sup.c, C.sub.1-C.sub.6-alkylene-CN, C(O)NR.sup.bR.sup.c, aryl, aryl-carbonyl, aryl-C.sub.1-C.sub.4-alkyl, aryloxy-C.sub.1-C.sub.4-alkyl, heteroaryl, carbonyl-heteroaryl, heteroaryl-C.sub.1-C.sub.4-alkyl, or heteroaryloxy-C.sub.1-C.sub.4-alkyl, wherein the phenyl rings are unsubstituted or substituted with R.sup.g and wherein the heteroaryl is a 5- or 6-membered monocyclic heteroaryl or a 8-, 9- or 10-membered bicyclic heteroaryl; R.sup.a, R.sup.b, and R.sup.c are, identical or different, H, C.sub.1-C.sub.6-alkyl, C.sub.2-C.sub.6-alkenyl, C.sub.2-C.sub.6-alkynyl, C.sub.1-C.sub.6-alkoxy-C.sub.1-C.sub.4-alkyl, C.sub.3-C.sub.6-cycloalkyl, C.sub.3-C.sub.6-cycloalkyl-C.sub.1-C.sub.4-alkyl, C.sub.3-C.sub.6-cycloalkoxy-C.sub.1-C.sub.4-alkyl, wherein the alkyl, alkoxy, alkenyl, alkynyl, cycloalkyl, and cycloalkoxy moieties are unsubstituted or substituted with halogen, C.sub.1-C.sub.6-alkylene-CN, phenyl, or CH.sub.2 phenyl, wherein the phenyl rings are unsubstituted or substituted with R.sup.f; R.sup.e is C.sub.1-C.sub.6-alkyl, C.sub.3-C.sub.6-cycloalkyl, C.sub.3-C.sub.6-cycloalkyl-C.sub.1-C.sub.4-alkyl, wherein the alkyl, cycloalkyl moieties are unsubstituted or substituted with halogen; R.sup.f is halogen, N.sub.3, OH, CN, NO.sub.2, SCN, SF.sub.5, C.sub.1-C.sub.6-alkyl, C.sub.1-C.sub.6-alkoxy, C.sub.2-C.sub.6-alkenyl, tri-C.sub.1-C.sub.6-alkylsilyl, C.sub.2-C.sub.6-alkynyl, C.sub.1-C.sub.6-alkoxy-C.sub.1-C.sub.4-alkyl, C.sub.1-C.sub.6-alkoxy-C.sub.1-C.sub.4-alkoxy, C.sub.3-C.sub.6-cycloalkyl, C.sub.3-C.sub.6-cycloalkoxy, C.sub.3-C.sub.6-cycloalkyl-C.sub.1-C.sub.4-alkyl, C.sub.3-C.sub.6-cycloalkoxyx-C.sub.1-C.sub.4-alkyl, wherein the alkyl, alkoxy, alkenyl, alkynyl, cycloalkyl, and cycloalkoxy moieties are unsubstituted or substituted with halogen, C(O)OR.sup.a, NR.sup.bR.sup.c, C.sub.1-C.sub.6-alkylene-NR.sup.bR.sup.c, OC.sub.1-C.sub.6-alkylene-NR.sup.bR.sup.c, C.sub.1-C.sub.6-alkylene-CN, NHC.sub.1-C.sub.6-alkylene-NR.sup.bR.sup.c, C(O)NR.sup.bR.sup.c, SO.sub.2NR.sup.bR.sup.c, or S(O).sub.mR.sup.e; R.sup.g is halogen, OH, CN, SCN, SF.sub.5, C.sub.1-C.sub.6-alkyl, C.sub.1-C.sub.6-alkoxy, C.sub.2-C.sub.6-alkenyl, tri-C.sub.1-C.sub.6-alkylsilyl, C.sub.2-C.sub.6-alkynyl, C.sub.1-C.sub.6-alkoxy-C.sub.1-C.sub.4-alkyl, C.sub.1-C.sub.6-alkoxy-C.sub.1-C.sub.4-alkoxy, C.sub.3-C.sub.6-cycloalkyl, C.sub.3-C.sub.6-cycloalkoxy, C.sub.3-C.sub.6-cycloalkyl-C.sub.1-C.sub.4-alkyl, C.sub.3-C.sub.6-cycloalkoxy-C.sub.1-C.sub.4-alkyl, wherein the alkyl, alkoxy, alkenyl, alkynyl, cycloalkyl, and cycloalkoxy moieties are unsubstituted or substituted with halogen, C(O)OR.sup.a, NR.sup.bR.sup.c, C.sub.1-C.sub.6-alkylene-NR.sup.bR.sup.c, OC.sub.1-C.sub.6-alkylene-NR.sup.bR.sup.c, C.sub.1-C.sub.6-alkylene-CN, NHC.sub.1-C.sub.6-alkylene-NR.sup.bR.sup.c, C(O)NR.sup.bR.sup.c, SO.sub.2NR.sup.bR.sup.c, or S(O).sub.mR.sup.e; and N-oxides, stereoisomers, tautomers, and agriculturally or veterinarily acceptable salts thereof.

2. The compound of formula I according to claim 1, wherein A is CR.sup.A, B.sup.1 is CR.sup.B1, and B.sup.2 is CR.sup.B2.

3. The compound of formula I according to claim 1, wherein A is N, B.sup.1 is CR.sup.B1, and B.sup.2 is CR.sup.B2.

4. The compound of formula I according to claim 1, wherein Q is N(R.sup.2)C(O) or NC(X).

5. The compound of formula I according to claim 1, wherein Q is N(R.sup.2)C(O) or NC(X).

6. The compound of formula I according to claim 1, wherein Ar is phenyl which is unsubstituted or substituted with R.sup.Ar.

7. A composition comprising a compound of formula I according to claim 1, an N-oxide or an agriculturally acceptable salt thereof, and at least one liquid and/or solid carrier.

8. A method for combating or controlling invertebrate pests, comprising contacting said invertebrate pests or their food supply, habitat or breeding grounds with a pesticidally effective amount of at least one compound according to claim 1.

9. A method for protecting growing plants from attack or infestation by invertebrate pests, comprising contacting a plant, or soil or water wherein the plant is growing, with a pesticidally effective amount of at least one compound according to claim 1.

10. A seed comprising a compound according to claim 1, or enantiomers, diastereomers, or salts thereof, in an amount of from 0.1 g to 10 kg per 100 kg of seed.

11. (canceled)

12. A non-therapeutical method for treating or protecting an animal from infestation or infection by invertebrate pests comprising bringing the animal in contact with a pesticidally effective amount of at least one compound of the formula I according to claim 1, a stereoisomer thereof and/or at least one veterinarily acceptable salt thereof.

Description

PREPARATION EXAMPLES

[0597] With appropriate modification of the starting materials, the procedures as described in the preparation examples below were used to obtain further compounds of formula I. The compounds obtained in this manner are listed in the table C that follows, together with physical data.

[0598] Compounds can be characterized e.g. by coupled High Performance Liquid Chromatography/mass spectrometry (HPLC/MS), by .sup.1H-NMR and/or by their melting points.

[0599] Analytical HPLCMethod 1: Agilent Eclipse Plus C18, 504.6 mm, ID 5 m; Elution: A=10 mM Amm. Formate (0.1% Formic Acid), B=Acetonitrile (0.1% Formic Acid), Flow=1.2 ml/min. at 30 C.; Gradient: 10% B to 100% B3 min, hold for 1 min, 1 min10% B. Run Time=5.01 min.

[0600] Analytical HPLCMethod 2: Kinetex XB C18 1.7 502.1 mm; A=Water+0.1% TFA, B=Acetonitrile, Flow=0.8 ml/min-1.0 ml/min in 1.5 min. at 60 C.; Gradient: 5% B to 100% B1.5 min.

[0601] .sup.1H-NMR: The signals are characterized by chemical shift (ppm, [delta]) vs. tetramethylsilane respectively, CDCl.sub.3 for .sup.13C-NMR, by their multiplicity and by their integral (relative number of hydrogen atoms given). The following abbreviations are used to characterize the multiplicity of the signals: m=multiplet, q=quartet, t=triplet, d=doublet and s=singlet.

[0602] Abbreviations used are: d for day(s), h for hour(s), min for minute(s), r.t./room temperature for 20-25 C., Rt for retention time; DMSO for dimethyl sulfoxide, OAc for acetate, EtOAc for ethyl acetate, THF for tetrahydrofuran, DMF for N,N-dimethylformamide, ACN for acetonitrile, DCM for dichloromethane, TEA for triethylamine and t-BuOH for tert-butanol.

Compound: C-1: Synthesis of N-[1-[4-[(E)-[(2-isopropyl-5-methyl-phenyl)carbamothioylhydrazono]methyl]phenyl]-3-methyl-pyrazol-4-yl]-4-(trifluoromethoxy)benzamide

Step 1: Synthesis of N-[1-(2-fluoro-4-formyl-phenyl)-3-methyl-pyrazol-4-yl]-4-(trifluoromethoxy)benzamide

[0603] To a stirred solution of N-(3-methyl-1H-pyrazol-4-yl)-4-(trifluoromethoxy)benzamide (25.0 g) in dry DMF (200 mL) were added cesium carbonate (32.8 g) and 4-fluoro benzaldehyde (11.4 g) at RT. The reaction mixture was heated at 106 C. for 22 h. The progress of the reaction was monitored by LCMS analysis. The reaction mixture was diluted with water (500 mL) then extracted with ethyl acetate (250 mL2). The combined organic layers were dried over sodium sulphate and concentrated under reduced pressure to get the crude product. The crude product was purified by washing with ethyl acetate (25 mL) to offer the desired product as white solid (18.0 g). HPLC/MS (Method 1): Rt: 1.909 min; m/z=390 (M+1).sup.+; .sup.1H NMR (500 MHz, DMSO-d.sub.6) 10.14 (s, 1H), 9.99 (s, 1H), 8.85 (s, 1H), 7.99-8.13 (m, 6H), 7.54-7.57 (m, 2H), 2.34 (s, 3H).

Step 2: Synthesis of N-[1-[4-[(E)-[(2-isopropyl-5-methyl-phenyl)carbamothioylhydrazono]methyl]phenyl]-3-methyl-pyrazol-4-yl]-4-(trifluoromethoxy)benzamide

[0604] To a stirred solution of N-[1-(4-formylphenyl)-3-methyl-pyrazol-4-yl]-4-(trifluoromethoxy)benzamide (1.5 g) in EtOH (30 mL) was added 1-amino-3-(2-isopropyl-5-methyl-phenyl)thiourea (0.86 g) at RT. To the reaction mixture was added acetic acid (1 mL). The reaction mixture was heated at 50 C. for 1 h. The progress of the reaction was monitored by LCMS analysis. The reaction mixture was diluted with water (100 mL) and neutralized with solid sodium bicarbonate then extracted with ethyl acetate (100 mL2). The combined organic layers were dried over sodium sulfate and concentrated under reduced pressure to get the desired product. The crude product was purified by washing with n-pentane to afford the desired product as yellow solid (2.3 g). HPLC/MS (Method 1): Rt: 1.86 min; m/z=595.8 (M+1).sup.+. .sup.1H NMR (500 MHz, DMSO-d.sub.6) 11.75 (s, 1H), 10.09 (s, 1H), 9.99 (s, 1H), 8.76 (s, 1H), 8.16 (s, 1H), 8.08-8.11 (d, J=8.67 Hz, 2H), 7.98-8.01 (d, J=8.73 Hz, 2H), 7.83-7.86 (d, J=8.61 Hz, 2H), 7.53-7.56 (d, J=8.35 Hz, 2H), 7.23-7.25 (d, J=7.98 Hz, 1H), 7.10-7.13 (d, J=8.53 Hz, 1H), 7.02 (s, 1H), 3.06-3.11 (m, 1H), 2.31 (s, 3H), 2.29 (s, 3H), 1.16-1.18 (d, J=6.82 Hz, 6H).

Step 3: Synthesis of N-[1-[4-[(E)-[(2-isopropyl-5-methyl-phenyl)carbamothioylhydrazono]methyl]phenyl]-3-methyl-pyrazol-4-yl]-4-(trifluoromethoxy)benzamide

[0605] To a stirred solution of N-[1-[4-[(E)-[(2-isopropyl-5-methyl-phenyl)carbamothioylhydrazono]methyl]phenyl]-3-methyl-pyrazol-4-yl]-4-(trifluoromethoxy)benzamide (0.3 g) in acetone (10 mL) was added N,N-diisopropylethyl amine (0.176 mL) and sodium iodide (0.008 g) at RT. To the reaction mixture was added chloromethyl ethyl carbonate (0.105 g) and reaction mixture was heated at 70 C. for 4 h. The progress of the reaction was monitored by LCMS analysis. After completion of the reaction, the reaction mixture was diluted with water (20 mL) and the crude product was extracted with ethyl acetate (20 mL2). The combined organic layers were dried over sodium sulphate and concentrated under reduced pressure to obtain the crude product. The crude product was then purified by using ethyl acetate and heptane as eluent to afford the desired product as yellow solid (0.34 g).

Compound: C-5: Synthesis of Synthesis of [(Z)N-(2-isopropyl-5-methyl-phenyl)-N-[(E)-[4-[3-methyl-4-[[4-(trifluoromethoxy)benzoyl]amino]pyrazol-1-yl]phenyl]methyleneamino]carbamimidoyl]sulfanylmethyl 2-[2-(2-methoxyethoxy)ethoxy]ethyl carbonate

Step 1: Synthesis of chloromethyl 2-[2-(2-methoxyethoxy)ethoxy]ethyl carbonate

[0606] To a stirred solution of 2-[2-(2-methoxyethoxy)ethoxy]ethanol (0.8 g) in dichloromethane (20 mL) was added pyridine (0.786 mL) and reaction mixture was cooled to 0 C. followed by dropwise addition of chloromethyl chloroformate (0.52 mL) and reaction mixture was then allowed to stir at RT for 12 h. The progress of the reaction was monitored by TLC. After completion of the reaction, the reaction mixture was diluted with water (30 mL) and the crude product was extracted with ethyl acetate (20 mL2). The combined organic layers were dried over sodium sulphate and concentrated under reduced pressure to obtain the crude product. The crude product was then purified by using ethyl acetate and heptane as eluent to afford the desired product as pale-yellow oil (0.95 g). .sup.1H NMR (500 MHz, CDCl.sub.3) 5.71 (s, 2H), 4.30-4.332 (m, 2H), 3.67-3.70 (m, 2H), 3.5-3.62 (s, 6H), 3.47-3.50 (m, 2H), 3.32 (s, 3H).

Step 2: Synthesis of [(Z)N-(2-isopropyl-5-methyl-phenyl)-N-[(E)-[4-[3-methyl-4-[[4-(trifluoromethoxy)benzoyl]amino]pyrazol-1-yl]phenyl]methyleneamino]carbamimidoyl]sulfanylmethyl 2-[2-(2-methoxyethoxy)ethoxy]ethyl carbonate was achieved following Step-3 of compound C-1 as mentioned previously

Compound: C-6: Synthesis of [(Z)N-(2-isopropyl-5-methyl-phenyl)-N-[(E)-[4-[3-methyl-4-[[4 (trifluoromethoxy)benzoyl]amino]pyrazol-1-yl]phenyl]methyleneamino]carbamimidoyl]sulfanylmethyl 2-methylpropanoate

[0607] To a stirred solution of N-[1-[4-[(E)-[(2-isopropyl-5-methyl-phenyl)carbamothioylhydrazono]methyl]phenyl]-3-methyl-pyrazol-4-yl]-4-(trifluoromethoxy)benzamide (0.2 g) in acetone (5 mL) was added N,N-diisopropylethyl amine (0.117 mL) and sodium iodide (0.005 g) at RT. To the reaction mixture was added chloromethyl isobutyrate (0.069 g) and reaction mixture was heated at 70 C. for 4 h. The progress of the reaction was monitored by LCMS analysis. After completion of the reaction, the reaction mixture was diluted with water (20 mL) and the crude product was extracted with ethyl acetate (20 mL2). The combined organic layers were dried over sodium sulphate and concentrated under reduced pressure to obtain the crude product. The crude product was then purified by using ethyl acetate and heptane as eluent to afford the desired product as white solid (0.24 g).

Compound: C-10: Synthesis of [(Z)N-(2-isopropyl-5-methyl-phenyl)-N-[(E)-[4-[3-methyl-4-[[4-(trifluoromethoxy)benzoyl]amino]pyrazol-1-yl]phenyl]methyleneamino]carbamimidoyl]sulfanylmethyl morpholine-4-carboxylate

[0608] To a stirred solution of N-[1-[4-[(E)-[(2-isopropyl-5-methyl-phenyl)carbamothioylhydrazono]methyl]phenyl]-3-methyl-pyrazol-4-yl]-4-(trifluoromethoxy)benzamide (0.2 g) in acetone (5 mL) was added N,N-diisopropylethyl amine (0.117 mL) and sodium iodide (0.005 g) at RT. To the reaction mixture was added chloromethyl morpholine-4-carboxylate (0.082 mL) and reaction mixture was heated at 70 C. for 4 h. The progress of the reaction was monitored by LCMS analysis. After completion of the reaction, the reaction mixture was diluted with water (20 mL) and the crude product was extracted with ethyl acetate (20 mL2). The combined organic layers were dried over sodium sulphate and concentrated under reduced pressure to obtain the crude product. The crude product was then purified by using ethyl acetate and heptane as eluent to afford the desired product as white solid (0.24 g).

Compound: C-15: Synthesis of [(Z)N-(2-isopropyl-5-methyl-phenyl)-N-[(E)-[2-methyl-4-[3-methyl-4-[[4-(trifluoromethoxy)benzoyl]amino]pyrazol-1-yl]phenyl]methyleneamino]carbamimidoyl]sulfanylmethyl 2-[2-[2-(2-methoxyethoxy)ethoxy]ethoxy]ethyl carbonate

Step 1: Synthesis of chloromethyl 2-[2-[2-(2-methoxyethoxy)ethoxy]ethoxy]ethyl carbonate

[0609] To a stirred solution of 2-[2-[2-(2-methoxyethoxy)ethoxy]ethoxy]ethanol (1.0 g) in dichloromethane (20 mL) was added pyridine (0.775 mL) and reaction mixture was cooled to 0 C. followed by dropwise addition of chloromethyl chloroformate (0.512 mL) and reaction mixture was then allowed to stir at RT for 12 h. The progress of the reaction was monitored by TLC. After completion of the reaction, the reaction mixture was diluted with water (30 mL) and the crude product was extracted with ethyl acetate (20 mL2). The combined organic layers were dried over sodium sulphate and concentrated under reduced pressure to obtain the crude product. The crude product was then purified by using ethyl acetate and heptane as eluent to afford the desired product as pale-yellow oil (1.4 g). .sup.1H NMR (500 MHz, CDCl.sub.3) 5.663 (s, 2H), 4.295-4.307 (m, 2H), 3.675-3.687 (m, 2H), 3.589 (s, 9H), 3.481-3.487 (m, 2H), 3.312 (s, 3H).

Step 2: Synthesis of [(Z)N-(2-isopropyl-5-methyl-phenyl)-N-[(E)-[2-methyl-4-[3-methyl-4-[[4-(trifluoromethoxy)benzoyl]amino]pyrazol-1-yl]phenyl]methyleneamino]carbamimidoyl]sulfanylmethyl 2-[2-[2-(2-methoxyethoxy)ethoxy]ethoxy]ethyl carbonate was achieved following Step-3 of compound C-1 as mentioned previously

Compound: C-21: Synthesis of [(Z)N-(2-isopropyl-5-methyl-phenyl)-N-[(E)-[2-methyl-4-[3-methyl-4-[[4-(trifluoromethoxy)benzoyl]amino]pyrazol-1-yl]phenyl]methyleneamino]carbamimidoyl]sulfanylmethyl cyclohexanecarboxylate

Step 1: Synthesis of Chloromethyl Cyclohexane Carboxylate

[0610] To a stirred solution of cyclohexanecarboxylic acid (1.0 g) in mixture of DCM:H.sub.2O (15 mL:15 mL) was added sodium bicarbonate (2.62 g) and tetrabutylammonium hydrogen sulphate (0.265 g) at RT. Reaction mixture was cooled to 0 C. and a solution of chloro(chlorosulfonyloxy)methane (0.948 mL) in DCM (5 mL) was added dropwise over 5 mins. After the addition was completed reaction mixture was allowed to stir at RT was 12 h. The progress of the reaction was monitored by TLC. After completion of the reaction, the reaction mixture was diluted with water (40 mL) and the crude product was extracted with ethyl acetate (40 mL2). The combined organic layers were dried over sodium sulphate and concentrated under reduced pressure to obtain the crude product. The crude product was then purified by using ethyl acetate and heptane as eluent to afford the desired product as colourless liquid (1.0 g). .sup.1H NMR (300 MHz, CDCl.sub.3): 5.64 (s, 2H), 2.25-2.35 (m, 1H), 1.83-1.87 (m, 2H), 1.55-1.73 (m, 3H), 1.35-1.46 (m, 2H), 1.13-1.30 (m, 3H).

Step 2: Synthesis of [(Z)N-(2-isopropyl-5-methyl-phenyl)-N-[(E)-[2-methyl-4-[3-methyl-4-[[4-(trifluoromethoxy)benzoyl]amino]pyrazol-1-yl]phenyl]methyleneamino]carbamimidoyl]sulfanylmethyl cyclohexanecarboxylate was achieved following Step-3 of compound C-1 as mentioned previously

Compound: C-22: Synthesis of [(Z)N-(2-isopropyl-5-methyl-phenyl)-N-[(E)-[2-methyl-4-[3-methyl-4-[[4-(trifluoromethoxy)benzoyl]amino]pyrazol-1-yl]phenyl]methyleneamino]carbamimidoyl]sulfanylmethyl cyclopropanecarboxylate: Step 1: Synthesis of chloromethyl cyclopropyl carboxylate

[0611] To a stirred solution of cyclopropylcarboxylic acid (1.0 g) in mixture of DCM:H.sub.2O (15 mL:15 mL) was added sodium bicarbonate (3.903 g) and tetrabutylammonium hydrogen sulphate (0.394 g) at RT. Reaction mixture was cooled to 0 C. and a solution of chloro(chlorosulfonyloxy)methane (1.4 mL) in DCM (5 mL) was added dropwise over 5 mins. After the addition was completed reaction mixture was allowed to stir at RT was 12 h. The progress of the reaction was monitored by TLC. After completion of the reaction, the reaction mixture was diluted with water (40 mL) and the crude product was extracted with ethyl acetate (40 mL2). The combined organic layers were dried over sodium sulphate and concentrated under reduced pressure to obtain the crude product (0.9 g) as colourless liquid which was used as such for next step without purification. .sup.1H NMR (500 MHz, CDCl.sub.3): 5.38 (s, 2H), 1.62-1.67 (m, 1H), 1.06-1.07 (m, 2H), 0.91-0.93 (m, 2H).

Step 2: Synthesis of [(Z)N-(2-isopropyl-5-methyl-phenyl)-N-[(E)-[2-methyl-4-[3-methyl-4-[[4-(trifluoromethoxy)benzoyl]amino]pyrazol-1-yl]phenyl]methyleneamino]carbamimidoyl]sulfanylmethyl cyclopropanecarboxylate was achieved following Step-3 of compound C-1 as mentioned previously

Compound: C-23: Synthesis of [(Z)N-(2-isopropyl-5-methyl-phenyl)-N-[(E)-[2-methyl-4-[3-methyl-4-[[4-(trifluoromethoxy) benzoyl]amino]pyrazol-1-yl]phenyl]methyleneamino]carbamimidoyl]sulfanylmethyl (E)-3-(4-methoxyphenyl)prop-2-enoate

Step 1: Synthesis of chloromethyl (E)-3-(4-methoxyphenyl)prop-2-enoate

[0612] To a stirred solution of 4-methoxycinnamic acid (1.0 g) in mixture of DCM:H.sub.2O (15 mL:15 mL) was added sodium bicarbonate (1.88 g) and tetrabutylammonium hydrogen sulphate (0.191 g) at RT. Reaction mixture was cooled to 0 C. and a solution of chloro(chlorosulfonyloxy)methane (0.682 mL) in DCM (5 mL) was added dropwise over 5 mins. After the addition was completed reaction mixture was allowed to stir at RT was 12 h. The progress of the reaction was monitored by TLC. After completion of the reaction, the reaction mixture was diluted with water (40 mL) and the crude product was extracted with ethyl acetate (40 mL2). The combined organic layers were dried over sodium sulphate and concentrated under reduced pressure to obtain the crude product. The crude product was then purified by using ethyl acetate and heptane as eluent to afford the desired product as colourless liquid (0.9 g). HPLC/MS (Method 1): Rt: 2.03 min; m/z=227.3 (M+1).sup.+, .sup.1H NMR (500 MHz, DMSO-d.sub.6): 7.74-7.79 (m, 3H), 7.00-7.01 (d, J=7.75 Hz, 2H), 6.56-6.59 (d, J=15.96 Hz, 1H), 5.98 (s, 2H), 3.82 (s, 3H).

Step 2: Synthesis of [(Z)N-(2-isopropyl-5-methyl-phenyl)-N-[(E)-[2-methyl-4-[3-methyl-4-[[4-(trifluoromethoxy)benzoyl]amino]pyrazol-1-yl]phenyl]methyleneamino]carbamimidoyl]sulfanylmethyl (E)-3-(4-methoxyphenyl)prop-2-enoate was achieved following Step-3 of compound C-1 as mentioned previously

##STR00122##

TABLE-US-00005 TABLE C wherein i-Pr is isopropyl group. No ArQ [00123] R.sup.1 HPLC/MS Rt (min) C-1 [00124] [00125] [00126] 697 (Method 1) 2.357 C-2 [00127] [00128] [00129] 751 (Method 1) 2.319 C-3 [00130] [00131] [00132] 724 (Method 1) 2.464 C-4 [00133] [00134] [00135] 737 (Method 1) 2.804 C-5 [00136] [00137] [00138] 813 (Method 1) 2.369 C-6 [00139] [00140] [00141] 696 (Method 1) 2.481 1C-7 [00142] [00143] [00144] 707 (Method 1) 2.614 C-8 [00145] [00146] [00147] 723 (Method 1) 2.987 C-9 [00148] [00149] [00150] 667 (Method 1) 2.304 C-10 [00151] [00152] [00153] 738 (Method 1) 2.805 C-11 [00154] [00155] [00156] 713 (Method 1) 2.609 C-12 [00157] [00158] [00159] 707 (Method 1) 2.66 C-13 [00160] [00161] [00162] 709 (Method 1) 1.973 C-14 [00163] [00164] [00165] 723 (Method 1) 2.101 C-15 [00166] [00167] [00168] 872 (Method 1) 1.76 C-16 [00169] [00170] [00171] 721 (Method 1) 2.357 C-17 [00172] [00173] [00174] 733 (Method 1) 1.931 C-18 [00175] [00176] [00177] 724 (Method 1) 1.931 C-19 [00178] [00179] [00180] 733 (Method 1) 1.952 C-20 [00181] [00182] [00183] 741 (Method 1) 2.261 C-21 [00184] [00185] [00186] 750 (Method 1) 2.549 C-22 [00187] [00188] [00189] 705 (Method 1) 2.091 C-23 [00190] [00191] [00192] 797 (Method 1) 4.032 C-24 [00193] [00194] [00195] 723 (Method 1) 2.165 C-25 [00196] [00197] [00198] 724 (Method 1) 2.432 C-26 [00199] [00200] [00201] 731 (Method 1) 2.421 C-27 [00202] [00203] [00204] 740 (Method 1) 2.315 C-28 [00205] [00206] [00207] 726 (Method 1) 2.069 C-29 [00208] [00209] [00210] 712 (Method 2) 1.508 C-30 [00211] [00212] [00213] 740 (Method 2) 1.553 C-31 [00214] [00215] [00216] 726 (Method 2) 1.553 C-32 [00217] [00218] [00219] 610 (Method 2) 1.521 C-33 [00220] [00221] [00222] 677 (Method 1) 2.6

BIOLOGICAL EXAMPLES

Example B1: Action on Yellow Fever Mosquito (Aedes aegypti)

[0613] For evaluating control of yellow fever mosquito (Aedes aegypti) the test unit consisted of 96-well-microtiter plates containing 200 l of tap water per well and 5-15 freshly hatched A. aegypti larvae.

[0614] The active compounds or mixtures were formulated using a solution containing 75% (v/v) water and 25% (v/v) DMSO. Different concentrations of formulated compounds or mixtures were sprayed onto the insect diet at 2.5 l, using a custom built micro atomizer, at two replications. For experimental mixtures in these tests identical volumes of both mixing partners at the desired concentrations respectively, were mixed together.

[0615] After application, microtiter plates were incubated at 281 C., 805% RH for 2 days. Larval mortality was then visually assessed.

[0616] In this test, compounds C-1, C-3, C-4, C-5, C-6, C-7, C-9, C-14, C-15, C-20, C-22, C-26, C-29, C-30, C-32 at 800 ppm showed at least 50% mortality in comparison with untreated controls.

Example B2: Action on Orchid Thrips (Dichromothrips corbetti)

[0617] Dichromothrips corbetti adults used for bioassay were obtained from a colony maintained continuously under laboratory conditions. For testing purposes, the test compound is diluted in a 1:1 mixture of acetone:water (vol:vol), plus Kinetic HV at a rate of 0.01% v/v.

[0618] Thrips potency of each compound was evaluated by using a floral-immersion technique. All petals of individual, intact orchid flowers were dipped into treatment solution and allowed to dry in Petri dishes. Treated petals were placed into individual re-sealable plastic along with about 20 adult thrips. All test arenas were held under continuous light and a temperature of about 28 C. for duration of the assay. After 3 days, the numbers of live thrips were counted on each petal. The percent mortality was recorded 72 hours after treatment.

[0619] In this test, compounds C-1, C-2, C-3, C-4, C-5, C-6, C-7, C-8, C-9, C-10, C-12, C-13, C-14, C-15, C-16, C-17, C-18, C-19, C-20, C-21, C-22, C-23, C-24, C-25, C-26, C-27, C-28, C-29, C-30, C-31, C-32 at 500 ppm showed at least 75% mortality in comparison with untreated controls.

Example B3: Action on Boll Weevil (Anthonomus grandis)

[0620] For evaluating control of boll weevil (Anthonomus grandis) the test unit consisted of 96-well-microtiter plates containing an insect diet and 5-10 A. grandis eggs.

[0621] The compounds were formulated using a solution containing 75% (v/v) water and 25% (v/v) DMSO. Different concentrations of formulated compounds were sprayed onto the insect diet at 5 l, using a custom built micro atomizer, at two replications.

[0622] After application, microtiter plates were incubated at about 25+1 C. and about 75+5% relative humidity for 5 days. Egg and larval mortality were then visually assessed.

[0623] In this test, compounds C-1, C-2, C-3, C-4, C-5, C-6, C-7, C-8, C-9, C-10, C-11, C-12, C-13, C-14, C-15, C-16, C-17, C-18, C-19, C-20, C-21, C-22, C-23, C-24, C-25, C-26, C-27, C-28, C-29, C-30, C-31, C-32 at 800 ppm showed at least 75% mortality in comparison with untreated controls.

Example B4: Action on Silverleaf Whitefly (Bemisia argentifolii) (Adults)

[0624] The active compounds were formulated by a Tecan liquid handler in 100% cyclohexanone as a 10,000 ppm solution supplied in tubes. The 10,000 ppm solution was serially diluted in 100% cyclohexanone to make interim solutions. These served as stock solutions for which final dilutions were made by the Tecan in 50% acetone:50% water (v/v) into 5 or 10 ml glass vials. A non-ionic surfactant (Kinetic) was included in the solution at a volume of 0.01% (v/v). The vials were then inserted into an automated electrostatic sprayer equipped with an atomizing nozzle for application to plants/insects.

[0625] Cotton plants at the cotyledon stage (one plant per pot) were sprayed by an automated electrostatic plant sprayer equipped with an atomizing spray nozzle. The plants were dried in the sprayer fume hood and then removed from the sprayer. Each pot was placed into a plastic cup and about 10 to 12 whitefly adults (approximately 3-5 days old) were introduced. The insects were collected using an aspirator and a nontoxic Tygon tubing connected to a barrier pipette tip. The tip, containing the collected insects, was then gently inserted into the soil containing the treated plant, allowing insects to crawl out of the tip to reach the foliage for feeding. Cups were covered with a reusable screened lid. Test plants were maintained in a growth room at about 25 C. and about 20-40% relative humidity for 3 days, avoiding direct exposure to fluorescent light (24 hour photoperiod) to prevent trapping of heat inside the cup. Mortality was assessed 3 days after treatment, compared to untreated control plants.

[0626] In this test, compounds C-1, C-2, C-3, C-5, C-7, C-8, C-9, C-12, C-13, C-14, C-15, C-16, C-18, C-19, C-21, C-23, C-27 at 300 ppm showed at least 75% mortality in comparison with untreated controls.

Example B5: Action on Tobacco Budworm (Heliothis virescens)

[0627] For evaluating control of tobacco budworm (Heliothis virescens) the test unit consisted of 96-well-microtiter plates containing an insect diet and 15-25 H. virescens eggs.

[0628] The compounds were formulated using a solution containing 75% v/v water and 25% v/v DMSO. Different concentrations of formulated compounds were sprayed onto the insect diet at 10 l, using a custom-built micro atomizer, at two replications.

[0629] After application, microtiter plates were incubated at about 28+1 C. and about 80+5% relative humidity for 5 days. Egg and larval mortality were then visually assessed.

[0630] In this test, compounds C-1, C-2, C-3, C-4, C-5, C-6, C-7, C-8, C-9, C-10, C-11, C-12, C-13, C-14, C-15, C-16, C-17, C-18, C-19, C-20, C-21, C-22, C-23, C-24, C-25, C-26, C-27, C-28, C-29, C-30, C-31, C-32 at 800 ppm showed at least 75% mortality in comparison with untreated controls.

Example B6: Action on Diamond Back Moth (Plutella xylostella)

[0631] The active compound is dissolved at the desired concentration in a mixture of 1:1 (v/v) distilled water:acetone. Surfactant (Kinetic HV) is added at a rate of 0.01% (v/v). The test solution is prepared at the day of use.

[0632] Leaves of cabbage were dipped in test solution and air-dried. Treated leaves were placed in petri dishes lined with moist filter paper and inoculated with ten 3rd instar larvae. Mortality was recorded 72 hours after treatment. Feeding damages were also recorded using a scale of 0-100%.

[0633] In this test, compounds C-1, C-2, C-3, C-4, C-5, C-6, C-7, C-8, C-9, C-10, C-11, C-12, C-13, C-14, C-15, C-16, C-17, C-18, C-19, C-20, C-21, C-22, C-23, C-24, C-25, C-26, C-27, C-28, C-29, C-30, C-31, C-32 at 500 ppm showed at least 75% mortality in comparison with untreated controls.

Example B7: Action on Southern Armyworm (Spodoptera eridania), 2nd Instar Larvae

[0634] The active compounds were formulated by a Tecan liquid handler in 100% cyclohexanone as a 10,000 ppm solution supplied in tubes. The 10,000 ppm solution was serially diluted in 100% cyclohexanone to make interim solutions. These served as stock solutions for which final dilutions were made by the Tecan in 50% acetone:50% water (v/v) into 10 or 20 ml glass vials. A nonionic surfactant (Kinetic) was included in the solution at a volume of 0.01% (v/v). The vials were then inserted into an automated electrostatic sprayer equipped with an atomizing nozzle for application to plants/insects.

[0635] Lima bean plants (variety Sieva) were grown 2 plants to a pot and selected for treatment at the 1st true leaf stage. Test solutions were sprayed onto the foliage by an automated electrostatic plant sprayer equipped with an atomizing spray nozzle. The plants were dried in the sprayer fume hood and then removed from the sprayer. Each pot was placed into perforated plastic bags with a zip closure. About 10 to 11 armyworm larvae were placed into the bag and the bags zipped closed. Test plants were maintained in a growth room at about 25 C. and about 20-40% relative humidity for 4 days, avoiding direct exposure to fluorescent light (24 hour photoperiod) to prevent trapping of heat inside the bags. Mortality and reduced feeding were assessed 4 days after treatment, compared to untreated control plants.

[0636] In this test, compounds C-1, C-2, C-3, C-4, C-5, C-6, C-7, C-8, C-9, C-10, C-11, C-12, C-13, C-14, C-15, C-16, C-17, C-18, C-19, C-20, C-21, C-22, C-23, C-24, C-25, C-26, C-27, C-28, C-29, C-30, C-31, C-32 at 300 ppm showed at least 75% mortality in comparison with untreated controls.