Untitled record

(54) Title: SYNERGIC INSECTICIDE COMPOSITION, AND, PROCESSES FOR INSECT CONTROL, AND TO PROTECT PLANTS AGAINST INFESTATION AND INSECT ATTACK (30) Unionist Priority: 12/03/1999 us 6O / 124306, 10/07/1999 US 60 / 158201,07 / 10/1999 US 60/158201, 12/03/1999 US 60/124306 (73) Title (s): Basf Aktiengesellschaft (72) Inventor (s): Hassan Oloumi-Sadeghi, Kurt Allen Schwinghammer, Michael FrankTreacy, Paul Erich Rensner, Raymond Frank Borysewicz (74) Attorney (s): Momsen, Leonardos & CIA.

(86) International Order: pct usooo5879 of 07/03/2000 (87) International Publication: wo 00/54591 of 21/09/2000 (57) Abstract: synergistic insecticidal composition, and, PROCESSES FOR SYNERGIC INSECT CONTROL, AND FOR PROTECT PLANTS AGAINST INFESTATION AND INSECT ATTACK. The present invention provides a synergistic insecticidal composition comprising as essential active ingredients a neuronal sodium channel antagonist in combination with one or more compounds selected from the group consisting of recombinant pyrethroids, pyrethroid compounds, nucleopoliedrovirus capable of expressing an insect toxin, organophosphates, carbamates, formamidines, macrocyclic lactones, amidinohydrazones, GABA antagonists and acetylcholine receptor ligands. Processes are also provided for synergistic insect control and plantation protection.

ΡΙ0017618—4

SYNERGIC INSECTICIDE COMPOSITION AND PROCESSES FOR

INSECT CONTROL, AND TO PROTECT PLANTS AGAINST

INFESTATION AND ATTACK OF INSECTS.

Divided from PI 0008930-3, deposited on 03/07/2000

BACKGROUND OF THE INVENTION

Insecticidal agents and compositions have been developed for the control of insect pests such as agro-horticultural pests, hygiene pests or pests that feed on wood and which in practice have been used as a single agent or a mixed agent. However, the 10 economically efficient and ecologically safe insect control compositions are still in demand. Insecticidal compositions that allow for a reduced effective dosage ratio, increased safety from the environment and a lower incidence of insect resistance are highly desirable. Although the application 15 in rotation of agents for insect control having different modes of action can be adopted for a good practice of handling pests, this routing does not necessarily provide a satisfactory control of insects. Moreover, although combinations of agents for insect control have been studied, a high synergistic action has not always been found. Obtaining an insecticidal composition that does not demonstrate cross-resistance to existing insecticidal agents, no toxicity problems and low negative impact on the environment, is extremely difficult. <,

Therefore, it is an object of this invention to provide a synergistic insecticidal composition that demonstrates a high control effect with concomitant reduced production costs in the field and reduced environmental burden.

Another object of this invention is to provide processes for synergistic control of insects and enhanced protection of plantations.

SUMMARY OF THE INVENTION

The present invention provides a synergistic insecticidal composition comprising as essential active ingredients a synergistically effective amount of a neuronal sodium channel antagonist in combination with one or more compounds selected from the group consisting of pyrethroids, compounds of the pyrethroid type, recombinant nucleopoliedrovirus capable of express an insect toxin, organophosphates, carbamates, formamidines, macrocyclic lactones, amidinohydrazones, GABA (gamma-aminobutyric acid) antagonists, and acetylcholine receptor ligands.

The present invention also provides a process for synergistic insect control which comprises bringing said insect into contact with a synergistically effective amount of a neuronal sodium channel antagonist in combination with one or more compounds selected from the group consisting of pyrethroids, compounds of the pyrethrum type, 15 recombinant nucleopoliedrovirus capable of expressing an insect toxin, organophosphates, carbamates, formamidines, macrocyclic lactones, amidinohydrazones, GABA antagonists, and acetylcholine receptor ligands.

The present invention further provides a process for the marked protection of plants from infestations and attacks by insects.

DETAILED DESCRIPTION OF THE INVENTION

Definitions "Acetylcholine receptor binding compound" as used in this application means a compound that is capable of binding to the acetylcholine receptor site.

“Group A” as used in this application means insecticide

1) pyrethroid compounds;

2) pyrethroid type compounds;

3) recombinant nucleopoliedrovirus capable of expressing an insect toxin;

4) organophosphate compounds;

5) carbamate compounds;

6) formamidine compounds;

7) macrocyclic lactone compounds;

8) amidinohydrazone compounds;

9) antagonistic GABA compounds; and

10) acetylcholine receptor binding compounds.

"Haloalkyl" as used in this application means a C alkyl group_xH_2x+ i having from 1 to 2x + 1 halogen atoms that can be the same or different. Similarly, the terms "haloalkenyl", "haloalkynyl", "haloalkoxy", "halophenyl" and the like mean substitution of mono- to perhalogen where the halogens can be the same or different.

“Halogen” as used in this application means Cl, Br, I or F.

"Neuronal sodium channel antagonist" as used in this application means a compound that is capable of preventing the ability of a neuron cell to transfer sodium ions across the cell membrane.

"Pyrethroid type compound" as used in this application means those compounds characterized by a non-ester bonded aryl-phenoxybenzyl moiety.

"Synergism" as used in this application means a cooperative action found in a combination of two or more biologically active components in which the combined activity of the two or more components exceeds the sum of the activity of each component alone.

Surprisingly, it has now been found that a composition comprising a combination of a neuronal sodium channel antagonist and a second insecticidal ingredient provides superior insect control at lower levels of the combined active agents than that which can be obtained when the antagonist of the neuronal sodium channel or the second insecticidal ingredient are applied alone.

As previously established, the term neuronal sodium channel antagonist designates a compound that is capable of preventing the ability of a neuron cell to transfer sodium ions across the cell membrane.

A neuron cell so affected is unable to fire, resulting in paralysis and ultimately mortality, in the target host. Descriptions of neuronal sodium channel antagonists and their modes of action can be found in “Pesticide Biochemistry and Physiology”, 60: 177185 or “Archives of Insect Biochemistry and Physiology”, 37: 91-103.

Neuronal sodium channel antagonist compounds include compounds such as those described in US 5543573; US 5708170; US 5324837 and US 5462938, among other publications. Examples of neuronal sodium channel antagonist compounds useful in the composition of this invention are those compounds having the structural formula γ

<img file="BRPI0017618B1_D0001.tif" />

(D

<img file="BRPI0017618B1_D0002.tif" />

(II) (III) where A is CR4R5 or NR₆;

W is O or S;

X, Υ, Ζ, X ', Υ' and Ζ 'are each independently Η;

halogen; OH; CN; AT THE₂; C1 -C6 alkyl groups optionally substituted with one or more halogens, C1-C3 alkoxy, C1-C3 haloalkoxy, C3Cé cycloalkyl, C alkenyloxy₂-Cô or sulfonyloxy;

C 1 -C 6 alkoxy groups optionally substituted with one or more halogens, C 1 -C 3 alkoxy or C 3 -C 6 cycloalkyl;

C1-6 alkoxycarbonyl, C3-C6 cycloalkylcarbonyloxy groups, phenyl optionally substituted with one or more halogens, C1-C4 alkyl or C1-C4 alkoxy;

aminocarbonyloxy groups optionally substituted with one or more C1-C3 alkyl;

alkoxycarbonyloxy Ci-Ce; Cj-C alkylsulfonyloxy₆; alkenyl C₂C ^; or NR_i₂Ri3;

m, p and q are each independently an integer of 1, 2, 3 4 or 5;

n is an integer of 0, 1 or 2;

r is an integer of 1 or 2;

t is an integer of 1,2, 3 or 4;

R, Ri, R₂, R3, R4 and R₅ are each independently H or C 1 -C alkyl₄;

R4 is H, C1 -Cô alkyl, Cj-Cô haloalkyl, C-Cé alkoxyalkyl, C-Cô alkoxy, Cj-Cô haloalkoxy, C alkenyl₂-Cé, alkynyl C₂-Cô, C-alkylcarbonyl] -Cé, C-Cô alkoxycarbonyl, C-C alkylthio₆ or C 1 -C haloalkylthio₆;

R₇ and Rg are each independently H; halogen; Cj-Có alkyl groups; alkylcarbonyloxy Cj-Cô or phenyl optionally substituted with one or more halogen, CN, NO₂, Cj-Cô alkyl, C haloalkyl₂-C6, C1-Cô alkoxy or C1-Cô haloalkoxy;

R₉ and Rio are each independently H or C 1 -C alkyl₄;

Rn is H, C [-Cg alkyl, C haloalkyl] -C₆, C1-C4 alkylcarbonyl, Cj-Cô alkoxycarbonyl ^or haloalkoxycarbonyl C] -Cg;

R12 and R13 are each independently H or C1-6 alkyl;

G is H; C 1 -C alkyl groups optionally substituted with one or more halogen, C 1-C 4 alkoxy, C 1 -C haloalkoxy₆, CN, NO₂ONLY)_uLaugh₄, COR15,

CO₂Ri6, phenyl or C3-C cycloalkyl₆;

C1-C6 alkoxy groups; haloalkoxy Ci-C₆; CN; AT THE₂; ONLY)_uLaugh₇; CORjg; CO₂Rj9; phenyl optionally substituted with one or more halogen, CN, C1-C3 haloalkyl or C1-C3 haloalkoxy;

C3-C6 cycloalkyl; or phenylthio;

Q is phenyl optionally substituted with one or more halogen, CN, SCN, NO₂, S (O)_uR₂₀, C1-C4 alkyl, C1-C4 haloalkyl groups, C1-C4 alkoxyalkyl, C-C alkoxy₆, haloalkoxy Ci-Cô or NR₂go₂₂;

u is an integer of 0, 1 or 2;

R14, R15, Riô, Ris, R19, R21 and R22 Each are independently H or C1-C alkyl₆;

Rn and R₂₀ are each independently C 1 -C alkyl₆ or halo C] -Cé;

R33 is CO₂R3₄;

R34 is H, Cj-Cô alkyl, Cj-Cô haloalkyl, phenyl or halophenyl; and the dotted line configuration C — N represents a double bond or a single bond (ie, CN or C = N); or a stereoisomer thereof.

Preferred neuronal sodium channel antagonists suitable for use in the composition of the invention are those compounds of formulas I, II or III where the dotted line configuration C — N represents a double bond.

The most preferred neuronal sodium channel antagonists suitable for use in the composition of the invention are those compounds of formula I or formula III where the dotted line configuration represents a double bond.

Particularly preferred neuronal sodium channel antagonists useful in the composition of the invention are those compounds of formula I or formula III where W is Ο; X is trifluormethoxy and is in position 4; Y is trifluormethyl and is in position 3; Z is CN and is in position 4; A is CH₂; huh

0; m, p and q are each 1; R and Ri are each Η; Z is Cú R33 and G are each CO₂CH₃; Q is p- (trifluormethoxy) phenyl; and the configuration with the dotted line C — N represents a double bond; or a stereoisomer thereof.

Other neuronal sodium channel antagonist compounds include those described in US 5116850 and US 5304573, among other publications. Examples of other neuronal sodium channel antagonist compounds suitable for use in the composition of the invention are those compounds having the structural formula

<img file="BRPI0017618B1_D0003.tif" />

<td>m</td><td>-X l^2€ll</td><td>R „ I²’</td>

<td></td><td>y — n — c-</td><td>-Ό ”ΝΝ — Q</td>

<td></td><td></td><td>G¹</td>

where W is O or S;

X'and Y 'are each

SCN; alkyl Cj-Cg optionally halogen, NO₂, CN, C alkoxy_r (V) independently H; halogen; CN; replaced with one or more Z groups₄, C1-C4 alkylthio, phenyl, halophenyl, C] -C alkylsulfonyl₄, C 1 -C haloalkylsulfonyl₄ or alkoxycarbonyl C] -C₄;

alkenyl groups C₂-Ç₄; haloalkenyl C₂-Ç₄; alkynyl C₂-Ç₄;

haloalkynyl C₂-Ç₄; cycloalkyl C₃-Cg; halocycloalkyl C₃-Cg; phenyl optionally substituted with one or more halogen groups, CN, NO₂, C1-C4 alkyl, C1-C4 haloalkyl, C1-C4 alkoxy, C] -C haloalkoxy₄, C1-C4 alkylthio, C1-C4 alkylsulfonyl or C] -C haloalkylsulfonyl₄;

C-C alkylcarbonyl₄; haloalkylcarbonyl C_rÇ₄ ouNR₂₈R₂₉;

m is an integer of 1, 2, 3, 4 or 5;

G 'is phenyl optionally substituted with one or more groups that can be the same or different selected from X';

a 5-membered heteroaromatic ring containing one or two heteroatoms selected from 0 or 1 oxygen, 0 or 1 sulfur and 0, 1 or 2 nitrogen atoms to said 5-membered heteroaromatic ring being fixed via carbon and optionally replaced with one or more groups that can be the same or different selected from X '; or a 6-membered heteroaromatic ring containing one or two heteroatoms selected from 0 or 1 oxygen, 0 or 1 sulfur and 0, 1 or 2 nitrogen atoms to said 6-membered heteroaromatic ring being fixed via carbon and optionally replaced with one or more groups that can be the same or different selected from X ';

Q 'is H; C 1 -C alkyl₆ optionally substituted with one or more halogen groups, CN, C1-C3 alkoxy, C] -C alkoxycarbonyl₆, or phenyl optionally substituted with one or more halogen, CN, NO₂, C] -C alkyl₄, haloalkyl Cj-C₄, C1-C alkylsulfonyl₄ or C 1 -C 6 alkylsulfinyl₄;

alkenyl C₂-Cô; alkynyl C₂-Cô; or phenyl optionally substituted with one to three groups, which can be the same or different, selected from X ';

R23? R-24, R25, &amp; 26, R27, R28 and R₂₉ are each independently H or C 1 -C alkyl₄; and the dotted line configuration CN represents a double bond or a single bond (ie, CN or C = N); or a stereoisomer thereof.

Other preferred neuronal sodium channel antagonist compounds of the invention are those compounds of formula IV or V where the dotted line configuration C - N represents a double bond.

Other neuronal sodium channel antagonist compounds suitable for use in the composition of the invention are those compounds of formulas IV or V where W is ο; X 'and Y' are each independently H or C 1 -C 6 haloalkyl; m is 1; R₂₅, R₂6 and R₂₇ are each H; G is phenyl optionally substituted with one or more halogen atoms; Q 'is halophenyl or C1-C4 alkyl optionally substituted with a phenyl or halophenyl group; and the dotted line configuration C — N represents a double bond; or a stereoisomer thereof.

the second active ingredient of the insecticidal composition of the invention includes one or more compounds selected from Group A:

1) pyrethroid compounds that are known to be insecticidally active such as cypermethrin, cyhalothrin, cyfluthrin, permethrin or the like;

2) pyrethroid-like compounds that are known to be insecticidally active such as etofenprox, silafluofen, or the like;

3) recombinant nucleopoliedrovirus capable of expressing an insect toxin, preferably an insect neurotoxin such as the insect toxin Androctonus australis (AaIT), for example HzNPV-AaIT;

4) organophosphate compounds that are known to be insecticidally active such as profenophos, acephate, sulprofos, malathion, diazinon, methyl paration, terbufos and the like;

5) carbamate compounds that are known to be insecticidally active such as methomyl, thiodicarb, phenotiodicarb, or the like;

6) formamidine compounds that are known to be insecticidally active such as amitraz, chlordimeform, hydramethylnone, chlorphenamidine, or the like;

7) macrocyclic lactone compounds that are known to be insecticidally active such as spinosad, avermecithin, emamectin, milbemectin, nemadectin, moxidectin or the like;

8) amidinohydrazone compounds that are known to be insecticidally active such as hydramethylnone;

9) GABA antagonist compounds that are known to be insecticidally effective such as fipronil, endosufan or the like;

10) acetylcholine receptor binding compounds that are known to be insecticidally effective such as imidacloprid, acetamiprid, nitenpiran, thiamethoxam or the like.

Descriptions of the commercially available compounds listed above can be found in “The Pesticide Manual”, 1 I^The Edition, “British Crop Protection Council” (1997) among other publications. Descriptions of the recombinant nucleopoliedrovirus capable of expressing an insect toxin include Tracy et al, “Proceedings Beltwide Cotton Conference” (1999), pgs. 1076-1083.

Preferred compositions of the invention are those compositions that have a neuronal sodium channel antagonist compound of formula I or formula III in combination with one or more compounds selected from Group A.

The most preferred compositions of the invention are those compositions that have a compound of formula I or formula III where W is Ο; X is trifluormethoxy and is in position 4; Y is trifluormethyl and is in position 3; Z is CN and is in position 4; A is CH₃; n is 0; m, p and q are each independently 1; R and Ri are each independently Η; Z 'is Cl; R₃₃ and G are each independently CO2CH₃; Q is p (trifluormethoxy) phenyl; and the dotted line configuration C — N represents a double bond, in combination with one or more compounds selected from Group A.

Each of the compounds of formula I, II, III, IV and V include asymmetric centers that can be represented in the R-form and the S-form of the stereoisomer. The present invention also includes the R-form and the S-form or mixtures comprising the R-form and the S-form in an arbitrary relationship. For compounds of formula III, the S-form is preferred.

Advantageously, the neuronal sodium channel antagonist compound of formulas I, II, III, IV or V or a mixture thereof, can be formulated with a second insecticide-effective ingredient and optionally other usual formulation adjuvants. Said formulation can be dispersed in a solid or liquid diluent for its application to the insect, its food supply, mating place or habitat, in the form of a diluted spray or as a solid powder or powder concentrate.

The active ingredients of the composition of the invention can also be formulated separately as a wettable powder, an emulsifiable concentrate, an aqueous suspension concentrate or flowable liquid or any of the conventional formulations used for insect control agents, and further mixed in the field tank. with water or other inexpensive liquid for application as a liquid spray mixture. Compositions formulated separately can also be applied sequentially.

Advantageously, the composition of the invention can be formulated as a bait composition comprising a synergistically effective amount of a combination of a neuronal sodium channel antagonist plus one or more selected compounds from Group A and an edible solid or liquid nutritional substance. A preferred bait composition may contain by weight approximately 0.01% to 20% of active ingredients, preferably a neuronal sodium channel antagonist in combination with hydramethylnon.

In the present practice, the composition of the invention may be applied to the foliage of the plant or stem of the plant, or to the insect's habitat or to the location of the hygienic plague in the form of a diluted spray prepared from any of the above mentioned formulations. The ratio of the essential active ingredients of the composition of the invention is approximately 1 part by weight of a neuronal sodium channel antagonist to approximately 0.01 - 100 parts by weight of the one or more compounds selected from Group A.

The compositions of the invention are superior insecticidal compositions and are especially useful for the control of pests in agrohorticulture, hygienic pests or pests that feed on wood. Said compositions are highly effective for the protection of growing or harvested plants including: legume plantations such as soybeans, peas and wax beans and the like, as well as cotton, fodder plantations, cabbage plantations, leafy vegetables, tobacco, tomatoes, potatoes, ornamental flowers such as chrysanthemums, wine plantations such as grapes, for juices fruit, pumpkins or melons and fruit trees such as cherry, peach, apple or citrus, from insect attack.

The synergistic insecticidal composition of the invention is found to be highly active against a wide variety of lepidopteran and coleopteran insects such as Helicorvea zea (cotton caterpillar), Heliotis virescens (smoke bud caterpillar), Leptinotarsa ​​decemlineata (Colorado potato beetle) , Diabrotica spp. (corn rootworm) and the like.

Beneficially, the composition of the invention may be useful for the prevention and control of hygienic or public health pests such as: Diptera, eg, house flies, mosquitoes or the like; Hymenoptera, eg, ants, parasitic wasps, wasps or the like; Blattaria, eg, cockroaches; or similar.

In addition, the compositions of the invention may be particularly useful for the prevention and control of insects that feed on wood such as termites (Isoptera), carpenter ants (Hymenoptera), wood-destroying beetles (Coleoptera) or the like.

These and other advantages of the invention should be evident from the examples set out here below. These examples are provided merely as an illustration of the invention and are not intended to be considered as a limitation thereof.

EXAMPLE 1

Evaluation of the Synergistic Insecticidal Effect of a Combination of a Neuronal Sodium Channel Antagonist Plus a Second Insecticide

In this evaluation the Heliothis zea (cotton caterpillar), Heliothis virescens (smoke bud caterpillar) and the used pyrethroid resistant Heliothis virescens caterpillar are obtained from laboratory colonies. Pyrethroid-resistant H. virescens are derived from the PEG strain [Campannola &amp; Plapp, “Proceedings of Beltwide Cotton Conference” (1988)].

The cotton leaves are immersed in 1: 1 v / v, acetone / water solutions of the test compound, or solutions of a combination of test compounds, for a period of around 3 seconds. Following immersion, the leaves are left to air dry for 2-3 hours. Plastic trays for biotests containing multiple open-face wells (4.0 x 4.0 x 2.5 cm) are used as test arenas. Cut portions of a treated sheet, a moistened cotton floss and a single larva in the third stage are placed inside each well, covered with a transparent ventilated plastic sheet, with adhesive, and kept under constant fluorescent light at approximately 27 ° C for a predetermined period of time. Larval mortality / morbidity is assessed at 5 days after treatment. All treatments are replicated 4-5 times in a randomized block design with 16-32 larvae per treatment. Using conventional logprobit analysis, the LC50 for each treatment is determined.

Using the above protocol, a neuronal sodium channel antagonist (Compound A) can be evaluated alone with dosage ratios of

0.1 ppm, 1.0 ppm and 10.0 ppm in combination with 1.0 ppm of a second insecticidal compound. The treatments that can be used are shown in Table I.

Table I ratio according to ______________composite A¹

<td rowspan="2">active compound</td><td rowspan="2">dosage (ppm)</td><td rowspan="2">(ppm)</td><td colspan="3">dosage ratio</td>

<td>(ppm)</td><td>(ppm)</td><td>(ppm:</td>

<td>cypermethrin</td><td> 0</td><td> 0</td><td> 0,1</td><td> 1,0</td><td> 10,0</td>

<td></td><td> 1,0</td><td> 0</td><td> 0,1</td><td> 1,0</td><td> 10,0</td>

<td>amitraz</td><td> 0</td><td> 0</td><td> 0,1</td><td> 1,0</td><td> 10,0</td>

<td></td><td> 1,0</td><td> 0</td><td> 0,1</td><td> 1,0</td><td> 10,0</td>

<td>fipronil</td><td> 0</td><td> 0</td><td> 0,1</td><td> 1,0</td><td> 10,0</td>

<td></td><td> 1,0</td><td> 0</td><td> 0,1</td><td> 1,0</td><td> 10,0</td>

<td>acetamiprid</td><td> 0</td><td> 0</td><td> 0,1</td><td> 1,0</td><td> 10,0</td>

<td></td><td> 1,0</td><td> 0</td><td> 0,1</td><td> 1,0</td><td> 10,0</td>

<td>spinosad</td><td> 0</td><td> 0</td><td> 0,1</td><td> 1,0</td><td> 10,0</td>

<td></td><td> 1,0</td><td> 0</td><td> 0,1</td><td> 1,0</td><td> 10,0</td>

<td>tiodocarb</td><td> 0</td><td> 0</td><td> 0,1</td><td> 1,0</td><td> 10,0</td>

<td></td><td> 1,0</td><td> 0</td><td> 0,1</td><td> 1,0</td><td> 10,0</td>

¹ Compound A = neuronal sodium channel antagonist with formula (Ia).

<img file="BRPI0017618B1_D0004.tif" />

EXAMPLE 2

Evaluation of the Synergistic Insecticidal Effect of a Combination of a

Neuronal Sodium Channel Antagonist Plus Amidinohydrazone

In this evaluation adult male cockroaches (Blatela germanico) are used. For each test, a 4.0 g serving of ground Purina (Hi-Pro Glo®) dog food is treated with a 5-acetone solution of the test compound alone or in combination with a second test compound. After the treatment, the acetone is evaporated and the food is placed in a 22.2 ml plastic cup which is placed in a shelter made of folded sheets of blotting paper placed in a plastic box (40 cm L x 28 cm L x 15 cm H). The plastic box (test arena) is also equipped with a narrow mouth bottle of 29.5 ml with two dental threads inserted in the mouth. A control box is prepared in the same way using ground dog food that has been treated with reagent grade acetone. Each treatment is replicated three times. Within each test arena are placed 20 healthy adult male cockroaches that were bred in 15 an insectarium. The test arenas are then stored at 24.4 ° C and mortality is determined daily by visual examination. The data obtained are shown in Table II.

Table II% Mortality

<td>Test compound</td><td>% Active ingredient</td><td> 3</td><td colspan="4">Days after treatment 4 5 6 7</td><td> 8</td>

<td>THE¹</td><td> 0,05</td><td> 0</td><td> 0</td><td> 0</td><td> 0</td><td> 0</td><td> 0</td>

<td>THE</td><td> 0,10</td><td> 1,7</td><td> 11,7</td><td> 11,7</td><td> 11,7</td><td> 18,3</td><td> 18,3</td>

<td>THE</td><td> 0,50</td><td> 5,0</td><td> 5,0</td><td> 5,0</td><td> 5,0</td><td> 5,0</td><td> 5,0</td>

<td>B²</td><td> 1,00</td><td> 0</td><td> 5,0</td><td> 28,3</td><td> 71,7</td><td> 90,0</td><td> 93,3</td>

<td>A + B</td><td> 0,05 + 1,0</td><td> 0</td><td> 20,0</td><td> 41,7</td><td> 81,7</td><td> 95,0</td><td> 98,3</td>

<td>A + B</td><td> 0,10+1,0</td><td> 0</td><td> 21,7</td><td> 51,7</td><td> 88,3</td><td> 95,0</td><td> 95,0</td>

<td>A + B</td><td> 0,50 + 1,0</td><td> 16,7</td><td> 58,3</td><td> 80,0</td><td> 95,0</td><td> 98,3</td><td> 100,0</td>

<td>Control</td><td> 0</td><td> 0</td><td> 1,7</td><td> 3,3</td><td> 3,3</td><td> 3,3</td><td> 5,0</td>

¹ Compound A = neuronal sodium channel antagonist with formula Ia

Compound B = hydramethylnon

<img file="BRPI0017618B1_D0005.tif" />

As can be seen from the data shown in Table II, combinations of a neuronal sodium channel antagonist plus an amidinohydrazone insecticide demonstrate synergistic insect control.

EXAMPLE 3

Evaluation of the Synergistic Insecticidal Effect of a Combination of a Neuronal Sodium Channel Antagonist Plus a Nucleopoliedrovirus

Recombinant Able to Express an Insect Toxin

In this evaluation, Helicoverpa zea (cotton caterpillar) larvae are obtained from a laboratory colony. The test compounds are dissolved and acetone / water 1: 1 v / v. Plastic trays (CD Intemational, Pitman, NJ) are used as test arenas. Each tray contains 32 4.0 x 4.0 x 2.5 cm open-face pits. A portion (5 ml) of an artificial diet based on soybean wheat flour (Southland Products, Lake Village, AR) is poured into each well. After the diet hardens, 0.4 ml of the test solution is pipetted over the surface of the diet in each well. The test solutions are evenly distributed over the surfaces of the diet by lifting the tray and gently tilting it from side to side. The trays are then kept in a ventilated area for approximately 2 hours, until the water no longer forms puddles on the diet surfaces. A single H larva. zea at 4 days of age is then placed on the surface of each well's diet. After larval infestation, each well is covered with an adhesive, ventilated plastic sheet.

All test arenas are kept under constant fluorescent light and a temperature of approximately 27 ° C for the duration of the test. Larval mortality is determined at 2, 3, 4 and 7 days after treatment. The larva was considered dead if it presented little or no

I no movement after being shaken on the diet tray. A total of 32 insects were tested for each treatment.

The data obtained are shown in Table III.

Table III

Compound% Active test ingredient% Mortality

Days after treatment

7 8

<td>THE¹</td><td>0.1 ppm</td><td> 43,8</td><td> 46,9</td><td> 53,1</td><td> 53,1</td>

<td>B²</td><td>1000 OB³/ ml</td><td> 3,1</td><td> 34,4</td><td> 50,0</td><td> 62,5</td>

<td>B</td><td>500 OB / ml</td><td> 0,0</td><td> 9,4</td><td> 18,8</td><td> 40,6</td>

<td>B</td><td>100 OB / ml</td><td> 3,1</td><td> 3,1</td><td> 3,1</td><td> 15,6</td>

<td>A + B</td><td> 0,1 + 1000</td><td> 87,5</td><td> 90,6</td><td> 93,8</td><td> 96,9</td>

<td>A + B</td><td> 0,1 +500</td><td> 75,0</td><td> 78,1</td><td> 84,4</td><td> 87,5</td>

<td>A + B</td><td> 0,1 + 100</td><td> 62,5</td><td> 75,0</td><td> 75,0</td><td> 78,1</td>

<td>Control</td><td> 0</td><td> 3,1</td><td> 3,1</td><td> 3,1</td><td> 3,1</td>

¹ Compound A = neuronal sodium channel antagonist with formula Ia Compound B = HzNPV-AaIT, Nucleopoliedrovirus Helicoverpa zea that expresses the insect toxin Androctonus australis ³ OB = viral occlusion bodies

<img file="BRPI0017618B1_D0006.tif" />

As can be seen from the data shown in Table III, combinations of a neuronal sodium channel antagonist plus a recombinant nucleopoliedrovirus that is capable of expressing an insect toxin, demonstrate synergistic insect control.

EXAMPLE 4

Synergism of Ia plus Acephate

Serial dilutions of compound Ia and acephate were performed at 1: 1 acetone / water as a diluent. Bean leaves were dipped in the treatment solutions and left to dry dry. A single treated sheet was segmented and placed with the upper surface facing upwards in filter paper soaked in water inside plastic Petri dishes; Southern caterpillars of the third instar of Spodoptera eridania, 7 larvae / Petri dish were placed on each leaf and each area was sealed with the Petri dish caps. Each treatment was repeated 4 times. After the application of the treatment, the infested Petri dishes were kept in the laboratory under fluorescent light and constant temperature of 26 ° C. Larval mortality / morbidity and damage to food were evaluated after 5 days of post-treatment.

The expected effect was calculated using the Cleanse formula E = X + Y - XY / 100.

If the observed effect is greater than the expected effect then synergism is displayed. If the observed effect is less than the expected effect, then the antagonistic effect is demonstrated.

The results for compound Ia and acephate alone are shown in Tables IV and V. The results of the treatments for the combinations of compound Ia and acephate are shown in Table VI.

Table IV - Compound Ia according to the present invention at 1.0; 0.6 and 0.3 ppm and mortality observed at 5 D AT (days after treatment)

<td>Table IV</td><td colspan="2">% of southern larvae controlled</td>

<td>Compound Ia</td><td>ppm</td><td>Observed Mortality</td>

<td></td><td> 1,0</td><td> 14,3</td>

<td></td><td> 0,6</td><td> 3,6</td>

<td></td><td> 0,3</td><td> 3,6</td>

Table V - 10ppm Acephate and mortality observed at 5 DAT (days after treatment)

<td>Table V</td><td colspan="2">% of southern larvae controlled</td>

<td>Acephate</td><td>ppm</td><td>Observed Mortality</td>

<td></td><td> 10</td><td> 7,1</td>

Table VI - Compound Ia according to the present invention at 1.0, 0.6 and 0.3 ppm combined with 10 ppm asphate and observed and expected mortality:

<td>Table 4</td><td colspan="3">% of southern larvae controlled</td>

<td>Compound Ia + Acephate</td><td>ppm</td><td>Mortality Observed</td><td>Mortality Expected</td>

<td></td><td> 1,0+10</td><td> 82,1</td><td> 20,3847</td>

<td></td><td> 0,6 + 10</td><td> 50,0</td><td> 10,4444</td>

<td></td><td> 0,3 + 10</td><td> 35,7</td><td> 10,4444</td>

The expected mortality was calculated using the Cleanse formula (E = X + Y - XY / 100).

EXAMPLE 5 Synergy of BAS 3201 (compound Ia) plus acetamipride

Serial dilutions with technical grade acetamipride and BAS 3201 were made with 1: 1 acetone: water as a diluent. Segmented bean leaves were dipped in the treatment solutions and left to dry dry. Two treated sheets were placed with the upper surface facing upwards on filter paper soaked in water inside plastic Petri dishes; Southern caterpillars of the third instar of Spodoptera eridania, 7 larvae / Petri dish were placed on each leaf and each area was sealed with the Petri dish caps. The treatments were repeated 4 times. Larval mortality / morbidity and food damage was assessed after 4 days post-treatment.

The expected effect was calculated using the formula of

I cleaned and_and = X + Y - XY / 100. When using the Cleaned formula, the current control percentage (E_The) exceeds the expected control percentage (E_and) under the additive effects. Synergism was apparent with the combination of acetamiprid at 10 ppm in combination with BAS 3201 at 0.2 ppm. The control percentage of S. eridania was 92.90% when the plants were treated with the mixture of acetamipride and BAS 3201 compared to 35.7% and 60.7% when the plants were treated respectively with acetamipride and BAS 3201, respectively .

AND_and = 35,7% + 60,7% - (35,7%)(60,7%)/100

AND_and = 96,4 % - 21,7%

AND_and = 74,7 %

AND_The = 92,9%

EXAMPLE 6

Synergy of compound Ia plus pyrethroid

Insect control percentage

The potential synergism of BAS 3201 with alpha-cypermethrin was tested by evaluating the control percentage of the crucifer moth, Plutella xylostella.

Cabbage infested with larvae of different ages from P. xylostella was treated with one of the following treatments:

• Control (without treatment) • 436 ppm BAS 3201 • 30 ppm alpha-cypermethrin • 436 ppm BAS 3201 + 30 ppm alpha-cyprometrine

The number of P. xylostella larvae was counted 8 days after the application of the treatment.

Based on the number of insects in the control plants, the percentage of control was calculated for each treatment. The Cleanse Formula¹ was used to assess synergistic effects.

Damage to insect feeding

The potential synergy of BAS 3201 with alpha-cypermethrin was tested, evaluating the damage to insects' food incurred by caterpillars, Spodoptera liturga, in cabbage.

Cabbage infested with larvae of varying ages from the 3rd *. liturga was treated with one of the following treatments:

• Control (without treatment) • 436 ppm BAS 3201 • 30 ppm alpha-cypermethrin • 436 ppm BAS 3201 + 30 ppm alpha-cyprometrine

Damage to food was assessed by assigning scores to damage to food from 0-10 (0 - no damage, 10 = complete defoliation) 8 days after treatment application.

Results - Percentage of insect control

The percentage of control of Plutella xylostella was higher when the cabbages were treated with a mixture of BAS 3201 and alpha -ipermethrin compared to the isolated treatments. The percentage of P. xylostella control was 79.8% when the plants were treated with a mixture of BAS 3201 and alpha-cypermethrin, compared with 65.7% and 17.6% when the plants were treated with BAS 3201 and alpha -cipermethrin, respectively.

When applying the Limpei formula (Limpei, LE; Schuldt, PH; Lamont, D. Proc. Ν. E. Weed Control Conf. 1962. 16: 48-53), the current control center (E_The) exceeds the expected control percentage (E_and) under the additive effects:

AND_and = X + Y - XY / 100

Where is_and = expected effect, X = effect caused by treatment with BAS 3201 alone and Y = effect caused by the treatment of alphaprometrine alone.

AND_and = 65,7% + 17,6% - (65,7%)(17,6%)/100

AND_and = 83,3 %- 11,6%

AND_and = 71.7% E_The = 79,8%

Results - Damage to insect food

The rates of damage to insect feeding in cabbages infested with Spodoptera liturga were lower when the plants had been treated with a mixture of BAS 3201 and alpha-cyprometrine compared to plants treated with isolated treatments. The mean index of damage to food was 5.3 when the plants were treated with a mixture of BAS 3201 and alpha-cyprometrine, compared with 7 and 10 when plants 10 were treated with BAS 3201 and alpha-cyprometrine, respectively. Due to the fact that no control on feeding was observed when the plants were treated only with alpha-cyprometrine, the damage was not expected to be reduced to 5.3 when treated with the combination of index 7 products, when treated with BAS only. 3201.

EXAMPLE 7

Synergy of Metaflumizone (compound Ia) plus amitraz

To assess the control of the tobacco caterpillar (Heliothis virescens}, the test unit consisted of microtiter plates with 96 wells containing an insect diet and 15-25 eggs of H. virescens. 20 Metaflumizone (compound Ia, see structure in the report descriptive), amitraz or a mixture of both compounds were formulated using a solution containing 75% water and 25% DMSO. Different concentrations of the formulated compounds or mixtures were sprayed on the insect's 10μ1 diet, using a customized micro-atomizer, and two replications. For the 25 experimental mixtures, in this test identical volumes of both components of the mixture in the concentrations respectively desired were mixed. After application, the microtiter plates were incubated at 28 ± 1 ° C, 80 ± 5% relative humidity (RH) for 5 days. Mortality of eggs and larvae was then assessed visually.

The presence of a synergistic effect in terms of the percentage of control between the two substances in the mixture was determined using Colby's equation (Colby, SR, 1967, Calculating Synergistic and

Antagonistic Responses in Herbicide Combinations, ffleeds, 15, 20-22):

XY

E = --100 where X, Y: substances in the mixture

When the observed combined control effect is greater than the expected combined control effect (E), then the combined effect is synergistic.

The results of the tests performed are shown in Table VII.

Table VII

<td>Tobacco caterpillar</td><td>ppm</td><td>Mean (% control)</td>

<td>Control</td><td> 0 + 0</td><td> 0</td>

<td>Isolated metaflumizone</td><td> 0,3 + 0</td><td> 0</td>

<td>Amitraz isolated</td><td> 0 + 300</td><td> 0</td>

<td>Metaflumizona + amitraz</td><td> 0,3 + 300</td><td> 75 *</td>

synergistic control effect according to Colby equation

EXAMPLE 8

Synergy of BAS 3201 (compound Ia) plus phpronil

Serial dilutions with technical grade phypronyl and BAS 3201 were made with 1: 1 acetone: water as a diluent. Segmented bean leaves 15 were dipped in the treatment solutions and left to dry dry. Two treated sheets were placed with the upper surface facing upwards on filter paper soaked in water inside plastic Petri dishes; Southern caterpillars of the third instar, Spodoptera eridania, 7 larvae / Petri dish were placed on each leaf and each area was sealed with the Petri dish caps. The treatments were repeated 4 times. Larval mortality / morbidity and damage to food were assessed after days of post-treatment.

The expected effect was calculated using the Cleanse E formula_and = X + Y - XY / 100. When using the Cleaned formula, the current control percentage (E_The) exceeds the expected control percentage (E_and) under the additive effects. Synergism was apparent with fipronil at 3 ppm in combination with BAS 3201 at 0.1 ppm. The control percentage of S. eridania was 25.0% when the plants were treated with the mixture of fipronil and BAS 3201 compared to 17.9% and 3.6% when the plants were treated with fipronil and BAS 3201, respectively .

AND_and = 17,9% + 3,6% - (19,7%)(3,6%)/100

AND_and = 21,5 % - 0,6%

AND_and = 20,9 %

AND_The = 25,0%

EXAMPLE 9

Synergism of Metaflumizone (compound Ia) plus spinosad

The presence of a synergistic effect in terms of percentage of control between the two substances in the mixture was determined using the Colby equation (Colby, SR, 1967, Calculating Synergistic and

Antagonistic Responses in Herbicide Combinations, Weeds, 15, 20-22):

XY

E = --100

Where X, Y: substances in the mixture

When the observed combined control effect is greater than the expected combined control effect (E), then the combined effect is synergistic.

To evaluate the control of the Mediterranean drosophila (Ceratilis capitata), the test unit consisted of microtiter plates with 96 wells containing an insect diet and 50-80 eggs of C. capitata.

Metaflumizone (compound Ia, see structure in the specification), spinosad or a mixture of both compounds were formulated using a solution containing 75% water and 25% DMSO. Different concentrations of the formulated compounds or mixtures were sprayed on the insect's diet at 5μ1, using a customized micro-atomizer, and two replications. For the experimental mixtures, in this test identical volumes of both components of the mixture in the respectively desired concentration were mixed. After application, the microtiter plates were incubated at 28 ± 1 ° C, 80 ± 5% relative humidity (RH) for 5 days. Mortality of eggs and larvae was then assessed visually.

The results of the tests carried out with Mediterranean drosophilae are shown in Table VIII.

Table VIII

<td>Drosophilae</td><td rowspan="2">ppm</td><td>Average</td>

<td>Mediterranean</td><td>(% control)</td>

<td>Control</td><td> 0 + 0</td><td> 0</td>

<td>Metaflumizona alone</td><td> 1 +0</td><td> 0</td>

<td>Spinosad alone</td><td> 0+10</td><td> 0</td>

<td>Metaflumizona + spinosad</td><td> 0,3 + 1</td><td> 75 *</td>

* synergistic control effect according to Colby's equation

To assess the control of the tobacco caterpillar (Heliothis virescens), the test unit consisted of microtiter plates with 96 wells containing an insect diet and 15-25 eggs of H. virescens. Metaflumizone, spinosad or a mixture of both compounds were formulated using a solution containing 75% water and 25% DMSO. Different concentrations of the formulated compounds or mixtures were sprayed on the insect's 10μ1 diet, using a customized micro-atomizer, and two replications. For the experimental mixtures, in this test identical volumes of both components of the mixture at the respectively desired concentrations were mixed. After application, the microtiter plates were incubated at 28 ± 1 ° C, 80 ± 5% relative humidity (RH) for 5 days. Mortality of eggs and larvae was then assessed visually.

The results of the tests carried out with the apple caterpillars are shown in Table IX.

Table IX

<td>Tobacco caterpillar</td><td>PPm</td><td>Mean (% control)</td>

<td>Control</td><td> 0 + 0</td><td> 0</td>

<td>Metaflumizona alone</td><td> 0,1 +0</td><td> 0</td>

<td>Spinosad alone</td><td> 0 + 0,3</td><td> 0</td>

<td>Metaflumizona + spinosad</td><td> 0,03 + 0,3</td><td> 100 *</td>

* synergistic control effect according to Colby's equation

EXAMPLE 10

Metaflumizone (Compound Ia) plus various insecticides (chlorodimeform, emamectin, etofemprox, thiametoxam and tiodicarb)

Synergism can be described as an interaction where the combined effect of two or more compounds is greater than the sum of the individual effects of each of the compounds. The presence of a synergistic effect in terms of the percentage of control between two components of the mixture (X and Y) can be calculated using the Colby equation (Colby, SR, 1967, Calculating Synergistic and Antagonistic Responses in Herbicide Combinations, Weeds, 15 , 20-22):

E = X + Y-100

When the observed combined control effect is greater than the expected combined control effect (E), then the combined effect is synergistic.

Tested

To evaluate the control of the cotton weevil (Anthonomus grandis), the test unit consisted of microtiter plates with 24 wells containing an insect diet and 20-30 eggs of A. grandis.

The compounds or mixtures were formulated using a solution containing 75% water and 25% DMSO. Different concentrations of the formulated compounds or mixtures were sprayed on the insect's diet at 20μ1, using a customized micro-atomizer, and two replications.

For the experimental mixtures, in this test identical volumes of both components of the mixture at the respectively desired concentrations were mixed.

After application, the microtiter plates were incubated at 23 ± 1 ° C, 50 ± 5% relative humidity (RH) for 5 days. Mortality of eggs and larvae was then assessed visually. For the tested mixtures, the results are shown in Table X.

Table X

<td>Cottonweed</td><td>ppm</td><td>Average (% of control)</td>

<td>Chlodimeform + compound Ia</td><td> 0 + 4</td><td> 25</td>

<td></td><td> 50 + 0</td><td> 0</td>

<td></td><td> 50 + 4</td><td> 75 *</td>

<td>Tiodicarb + compound Ia</td><td> 0 + 4</td><td> 50</td>

<td></td><td> 2 + 0</td><td> 0</td>

<td></td><td> 2 + 4</td><td> 75*</td>

* synergistic control effect according to Colby's equation

Test 2

To evaluate the control of the Mediterranean drosophila (Ceratilis capitata) the test unit consisted of microtiter plates with wells containing an insect diet and 50-80 eggs of C. capitata.

The compounds or mixtures were formulated using a solution containing 75% water and 25% DMSO. Different concentrations of the formulated compounds or mixtures were sprayed on the insect's diet at 5μ1, using a customized micro-atomizer, and two replications.

For the experimental mixtures, in this test identical volumes of both components of the mixture at the respectively desired concentrations were mixed.

After application, the microtiter plates were incubated at 28 ± 1 ° C, 80 ± 5% relative humidity (RH) for 5 days. Mortality of eggs and larvae was then assessed visually. For the mixtures tested, the results are shown in Table XI.

Table XI

<td>Mediterranean Drosophilae</td><td>ppm</td><td>Mean (% control)</td>

<td>Emamectin + compound Ia</td><td> 0 + 4</td><td> 0</td>

<td></td><td> 0,4 + 0</td><td> 0</td>

<td></td><td> 0,4 + 4</td><td> 50*</td>

<td>Etofemprox + compound Ia</td><td> 0 + 2</td><td> 25</td>

<td></td><td> 20 + 0</td><td> 0</td>

<td></td><td> 20 + 2</td><td> 75 *</td>

<td>Tiodicarb + compound Ia</td><td> 0 + 20</td><td> 0</td>

<td></td><td> 2 + 0</td><td> 0</td>

<td></td><td> 2 + 20</td><td> 75*</td>

* synergistic control effect according to Colby's equation

Test 3

To evaluate the control of the tobacco caterpillar (Heliothis virescens), the test unit consisted of microtiter plates with wells containing an insect diet and 15-25 H virescens eggs.

The compounds or mixtures were formulated using a solution containing 75% water and 25% DMSO. Different concentrations of the formulated compounds or mixtures were sprayed on the insect's 10μ1 diet, using a customized micro-atomizer, and two replications.

For the experimental mixtures, in this test identical volumes of both components of the mixture at the respectively desired concentrations were mixed.

After application, the microtiter plates were incubated at 28 ± 1 ° C, 80 ± 5% relative humidity (RH) for 5 days. The mortality of eggs and larvae was then assessed visually. For the tested mixtures, the results are shown in Table XII.

Table XII

<td>Tobacco caterpillar</td><td>PPm</td><td>Mean (% control)</td>

<td>Chlorodimeform + compound Ia</td><td> 0 + 0,16</td><td> 0</td>

<td></td><td> 50 + 0</td><td> 0</td>

<td></td><td> 50 + 0,16</td><td> 75*</td>

<td>Etofemprox + compound Ia</td><td> 0 + 0,016</td><td> 0</td>

<td></td><td> 50 + 0</td><td> 25</td>

<td></td><td> 50 + 0,016</td><td> 50 *</td>

<td>Thioamtoxam + compound Ia</td><td> 0 + 0,8</td><td> 0</td>

<td></td><td> 10 + 0</td><td> 0</td>

<td></td><td> 10 + 0,8</td><td> 75*</td>

* synergistic control effect according to Colby's equation