Synergistic insecticidal compositions

Abstract: The present invention provides insecticidal compositions, comprising a cytochrome P450 enzyme inhibitor compound and a substituted or unsubstituted N,N'-dibenzoyl-N'-tert-alkyl-hydrazine, which exhibit enhanced efficacy over compositions with an N,N'-dibenzoyl-N'-tert-alkylhydrazine alone.

Description: The present invention is concerned with insecticidal compositions, comprising a cytochrome P450 enzyme inhibitor compound and a substituted N,N'-dibenzoyl-N'-tert-alkyl-hydrazine, which exhibit enhanced efficacy over compositions with an N,N'-dibenzoyl-N'-tert-alkylhydrazine alone. Insecticidal compositions are known which contain N,N'-dibenzoyl-N'-tert-alkylhydrazines, such as those described in US-A- 4,985,461. Although such compositions may be effective against some insects, there is a need for compositions which are more efficacious against a broader spectrum of insects and require lower amounts of N,N'-dibenzoyl-N'-tert-alkyl-hydrazine as a matter of conservation, environmental concern and cost. We have now found that compositions, comprising a cytochrome P450 enzyme inhibitor compound and a substituted N,N'-dibenzoyl-N'-tert-alkyl-hydrazine, exhibit synergistic activity against insects. Accordingly, the present invention provides a composition which comprises a substituted N,N'-dibenzoyl-N'-tert-alkyl-hydrazine and a cytochrome P450 enzyme inhibitor, wherein the N,N'-dibenzoyl-N'-tert-alkyl-hydrazine is of the formula N-(2-A-3-B-benzoyl)-N'-(3-D-5-E-benzoyl)-N'-tert-alkyl-hydrazine, wherein A and B are substituent groups independently selected from (C 1 -C 4 )alkyl, preferably methyl or ethyl and (C 1 -C 4 )alkoxy, preferably methoxy or ethoxy; and D and E are substituent groups independently selected from (C 1 -C 2 )alkyl, preferably methyl. More preferably, the substituents groups A and B are selected independently from methoxy, ethoxy, methyl or ethyl. The tert-alkyl group of the N'-tert-alkyl substituent is preferably a tert-(C 4 -C 6 )alkyl, more preferably tert-butyl. Preferred N,N'-dibenzoyl-N'-tert-butyl-hydrazines are N-(2,3-dimethylbenzoyl)-N'-(3,5-dimethylbenzoyl)-N'-tert-butyl-hydrazine or N'-(3,5-dimethylbenzoyl)-N-(2-methyl-3-methoxybenzoyl)-N'-tert-butyl-hydrazine. The cytochrome P450 enzyme inhibitor usable in the present invention is prefereably selected from methylenedioxyphenyl compounds (such as sesamin, myristicin, apiol, sesamolin, tropital, piperonyl butoxide, sulfoxide, and propyl isome), sesamex, dillapiol, sesamine, N-decylimidazole and WARF-antiresistant as well as imidazoles, morpholines, pyrimidines and triazoles. The cytochrome inhibitor is preferably selected from imidazoles, morpholines, pyrimidines and triazoles. Preferred imidazoles are 1-[(1,1'-biphenyl)-4-ylphenylmethyl]-1H-imidazole (e.g. bifonazole); 1-[(2-chlorophenyl)diphenylmethyl]-1H-imidazole (e.g. clotrimazole); 1-[2-(2,4-dichlorophenyl)-2-propenyloxy) ethyl]-1H-imidazole (e.g. imazalil); cis-1-acetyl-4-[4-[[2-(2,4-dichlorophenyl)-2-(1H-imidazole-1-ylmethyl)-1,3-dioxolan-4-yl]-methoxyphenyl]piperazine (e.g. ketoconazole); 1-[2-(2,4-dichlorophenyl)-2-[(2-(2,4-dichlorophenyl)methoxy]ethyl]-1H-imidazole (e.g. micronazole); 1-(N-propyl-N-(2-(2,4,6-trichlorophenoxy) ethyl) carbamoyl) imidazole (e.g. prochloraz). The more preferred imidazole is prochloraz. A preferred morpholine is (+,-)-cis-4-[3-(4-tert-butylphenyl)-2-methylpropyl]-2,6-dimethylmorpholine (e.g. fenpropimorph). A preferred pyrimidine is 3-(2-chlorophenyl)-3-(4-chlorophenyl)-5-pyrimidinemethanol (e.g. fenarimol, also described as (+,-)-2,4'-dichloro-alpha-(pyrimidin-5-yl)benzhydryl alcohol). Preferred triazoles are 1-[[2-(2,4-dichlorophenyl)-1,3-dioxolan-2-yl]methyl]-1H-1,2,4-triazole (e.g. azaconazole); (E)-(RS)-1-(2,4-dichlorophenyl)-4,4-dimethyl-2-(1H-1,2,4-triazole-1-yl)-pent-1-en-3-ol (e.g. diniconazole); (+,-)-alpha-[2-(4-chlorophenyl)-ethyl]-alpha-phenyl-(1H-1,2,4-triazole)-1-propanitrile (e.g. fenbuconazole); alpha-(2,4-difluorophenyl)-alpha-(1H-1,2,4-triazol-1-ylmethyl)-1H-1,2,4-triazol-1-ethanol (e.g. fluconazole); (RS)-2-(2,4-dichlorophenyl)-1-(1H-1,2,4-triazol-1-yl)-hexan-2-ol (e.g. hexaconazole); 4-[4-[4-[4-[2-(2,4-dichlorophenyl)-2-(1H-1,2,4-triazol-1-ylmethyl)-1,3-dioxolan-4-yl]-methoxyphenyl]-1-piperazinyl]phenyl]-2,4-dihyro-2-(1-methylpropyl)-3H-1,2,4-triazol-3-one (e.g. itraconazole); alpha-butyl-alpha-(4-chlorophenyl)-1H-1,2,4-triazole-1-propanitrile (e.g. myclobutanil); 1-(2,4-dichloro-beta-propylphenethyl)-1H-1,2,4-triazole (e.g. penconazole); and (+,-)-1-[[2-(2,4-dichlorophenyl)-4-propyl-1,3-dioxolan-2-yl]methyl]-1H-1,2,4-triazole (e.g. propiconazole). The more preferred triazoles are diniconazole, fenbuconanzoles, hexaconazole, myclobutanil, and propiconazole. In one embodiment of the present invention the inhibitor is selected from bifonazole, clotrimazole, imazalil, ketoconazole, miconazole, myclobutanil, prochloraz, fenpropimorph, fenamoril, azaconazole, diniconazaole, fenbuconazole, fluconazole, hexaconazole, itraconazole, myclobutanil, penconazole, and propiconazole. The relative proportion of cytochrome P450 enzyme inhibitor compound to N,N'-dibenzoyl-N'-tert-alkyl-hydrazine compound in the embodied composition is that proportion which exhibits unexpected synergistic efficacy as an insecticide. In some embodied compositions, the presence of a combination of one or more cytochrome P450 enzyme inhibitor compounds and one or more N,N'-dibenzoyl N'-tert-alkyl-hydrazines is associated with an enhanced efficacy such that insecticidal activity is unexpectedly present as compared to the efficacy of the composition without any cytochrome P450 enzyme inhibitor compound, such composition without any cytochrome P450 enzyme inhibitor compound exhibiting little or substantially no efficacy as an insecticide. In other embodied compositions, the composition with N,N'- dibenzoyl-N'-tert-alkyl-hydrazine exhibits significant insecticidal activity without any cytochrome P450 enzyme inhibitor compound but combining the cytochrome P450 enzyme inhibitor compound with the N,N'-diberzoyl-N'-tert-alkyl-hydrazine composition exhibits a significantly enhanced insecticidal activity or efficacy. For such compositions the synergistic relative proportions by weight of the cytochrome P450 enzyme inhibitor compounds to N,N'-dibenzoyl-N'-tert-alkyl-hydrazine compounds preferably range from 0.1:1 to about 1000:1. Conveniently the range is at least about equal (i.e., 1:1), preferably at least 5 times as much (5:1), more preferably at least one hundred times as much. The ranges of proportions have practical upper limitations depending upon the particular application involved and would normally be expected to be at that particular proportion for complete kill for the amount of N,N'-dibenzoyl-N'-tert-alkyl-hydrazine compound used, but the maximum proportion of cytochrome P450 enzyme inhibitor compounds to hydrazine is not critical otherwise. Preferred compositions comprise one or more N,N'-dibenzoyl-N'-tert-alkyl-hydrazine compounds, preferably N-(2,3-dimethylbenzoyl)-N'-(3,5-dimethylbenzoyl)-N'-tert-butyl-hydrazine or N'-(3,5-dimethylbenzoyl)-N-(2-methyl-3-methoxybenzoyl)-N'-tert-butyl-hydrazine, and one or more cytochrome P450 enzyme inhibitor compound selected from diniconazole, fenarimol, fenbuconazole, fenpropimorph, myclobutanil, prochloraz and propiconazole, in synergistic ratios wherein the amount of inhibitor is effective to significantly enhance the insecticidal activity of the composition relative to the composition without the inhibitor. The embodied compositions of the present invention can be used in the form of agronomically acceptable compositions or formulations. Such agronomically acceptable compositions can be formed by dissolving, dispersing or diffusing the embodied compositions in an agronomically acceptable carrier or diluent without impairing the active ingredients effectiveness and which by itself has no significant detrimental effect on the soil, equipment, desirable plants, or agronomic environment. If desired, adjuvants such as surfactants, stabilizers, antifoam agents and antidrift agents may also be combined, as well as herbicides, fungicides and other agrichemically active materials used for their expected utility. Accordingly, the embodied compositions of the present invention may be employed alone or in the form of mixtures with one another and/or with such solid and/or liquid dispersible carrier vehicles and/or with other known compatible active agents, especially plant protection agents, such as other insecticides, arthropodicides, nematicides, fungicides, bactericides, rodenticides, herbicides, fertilizers, growth regulating agents, or other synergists. The active compounds can be applied as insecticide sprays by methods commonly employed, such as conventional high volume hydraulic sprays (high-gallonage hydraulic sprays), low -volume sprays (e.g. ultra-low volume sprays), airblast sprays, aerial sprays, and dusts. In addition to the aforementioned ingredients the preparations according to the invention may also contain other substances commonly used in preparations of this kind. For example, a lubricant, such as calcium stearate or magnesium stearate, may be added to a wettable powder or to a mixture to be granulated. Furthermore there may, for example, be added adhesives such as polyvinylalcohol-cellulose derivatives or other colloidal materials, such as casein, to improve the adherence of the pesticide to the surface to be protected. According to the present invention there is also provided a method of killing, combating or controlling insects, which comprises contacting insects with a pesticidally effective amount of a composition according to the invention, the N,N'-dibenzoyl-N'-tert-alkyl-hydrazine and the cytochrome P450 enzyme inhibitor being present in amounts which exhibit synergistic insecticidal activity One embodiment of the method of the present invention comprises applying the embodied composition to the soil or foliage where it is absorbed by the plant, translocated to other plant parts and ultimately ingested by the pest or insects by means of ingestion of the plant part(s). This means of application is referred to as "systemic" application. Alternatively, the embodied composition may be applied to the soil and contacted therein with the insects and other pests to be controlled. This means of application is referred to as "soil" application. In another alternative, the embodied composition may be foliarly applied to the plants to be freed from insects and other pests which feed on the foliage. In this regard then the present invention also contemplates a method of killing, combating or controlling insects which comprises contacting insects with a combative or toxic amount (i.e. pesticidally effective amount) of at least one composition comprising a first amount of an N,N'-dibenzoyl-N'-tert-alkyl-hydrazine and a second amount of a cytochrome P450 enzyme inhibitor, wherein said second amount of inhibitor is effective to significantly enhance the insecticidal activity of said hydrazine. The embodied composition can be applied alone or together with a carrier vehicle as noted above. The term "contacting" as employed in the specification and claims means applying to at least one of (a) such insects and (b) the corresponding habitat thereof (i.e., the locus to be protected, for example, to a growing crop or to an area where a crop is to be grown) the embodied composition of this invention alone or as a constituent of a larger composition or formulation.

Claims: A synergistic composition which comprises a substituted N,N'-dibenzoyl-N'-tert-alkyl-hydrazine and a cytochrome P450 inhibitor wherein the N,N'-dibenzoyl-N'-tert-alkyl-hydrazine is of the formula N-(2-A-3-B-benzoyl)-N'-(3-D-5-E-benzoyl)-N'-tert-alkyl hydrazine, wherein A and B are substituent groups independently selected from (C 1 -C 4 ) alkyl and (C 1 -C 4 ) alkoxy and D and E are substituent groups independently selected from (C 1 -C 2 ) alkyl. A synergistic composition as claimed in claim 1, wherein the N,N'-dibenzoyl-N'-tert-alkyl-hydrazine is selected from N-(2,3-dimethylbenzoyl)-N'-(3,5-dimethylbenzoyl)-N'-tert-butylhydrazine and N'-(3,5-dimethylbenzoyl)-N-(2-methyl-3-methoxybenzoyl)-N'-tert-butylhydrazine. A synergistic composition as claimed in any preceding claim, wherein the cytochrome P450 inhibitor is selected from imidazoles, morpholines, pyrimidines, and triazoles. A synergistic composition as claimed in claim 3, wherein said inhibitor is selected from bifonazole, clotrimazole, imazalil, ketoconazole, miconazole, myclobutanil, prochloraz, fenpropimorph, fenamoril, azaconazole, diniconazole, fenbuconazole, fluconazole, hexaconazole, itraconazole, myclobutanil, penconazole, and propiconazole. A synergistic composition as claimed in any preceding claim, wherein the ratio of said cytochrome P450 enzyme inhibitor to said N,N'-dibenzoyl-N'-tert-alkyl-hydrazine is 0.1:1 to 1000:1. A method of killing, combating, or controlling insects, which comprises contacting insects with a pesticidally effective amount of a synergistic composition as claimed in any preceding claim, the N,N'-dibenzoyl-N'-tert-alkyl-hydrazine and the cytochrome P450 enzyme inhibitor being present in amounts which exhibit synergistic insecticidal activity. A method as claimed in claim 6, wherein said insects are one or more of Spodoptera eridania and Trichoplusis includens .

Inventors: MUTHUVELU THIRUGNANAM, MUTHUVELU, THIRUGNANAM
Applicants: ROHM & HAAS, ROHM AND HAAS COMPANY
Application year: 1995
Main classification: A01N37
IPC codes: A01N33, A01N37