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Title:
PESTICIDE COMPOUNDS, COMPOSITIONS AND PROCESS FOR THE PREPARATION THEREOF
Document Type and Number:
WIPO Patent Application WO/1998/051652
Kind Code:
A1
Abstract:
The subject of the invention is the (+) optically active isomer of the compound of formula (I) (VERBUTIN) or isomeric mixtures rich on the (+) optically active isomer of the compound of formula (I), compositions containing the (+) optically active isomer of the compound of formula (I), and the process for the preparation thereof. The (+) optically active isomer of the compound of formula (I) according to the invention can be used as active ingredient in arthropodicide compositions or as synergist for other arthropodicide active ingredients.

Inventors:
�RVAI, G�za (R�bert K??roly krt. 20, Budapest, H-1138, HU)
Bakonyv�ri, Ildik� (Per�nyi Zsigmond u. 55, Budapest, H-1047, HU)
Bert�k, B�la (Rizling u. 16, Budapest, H-1223, HU)
Kuruczn�, Ribai Zsuzsanna (Emo^"ke u. 1/b, �rd, H-2030, HU)
Pap, L�szl� (Gy�ngyvir�g u. 23, �rd, H-2030, HU)
Sz�kely, Istv�n (Krajc�r u. 6, Dunakeszi, H-2120, HU)
Application Number:
PCT/HU1998/000049
Publication Date:
November 19, 1998
Filing Date:
May 11, 1998
Export Citation:
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Assignee:
Chinoin, Gy�gyszer �S Vegy�szeti (Term�kek Gy�ra Rt, T� u. 1-5, Budapest, H-1045, HU)
�RVAI, G�za (R�bert K??roly krt. 20, Budapest, H-1138, HU)
Bakonyv�ri, Ildik� (Per�nyi Zsigmond u. 55, Budapest, H-1047, HU)
Bert�k, B�la (Rizling u. 16, Budapest, H-1223, HU)
Kuruczn�, Ribai Zsuzsanna (Emo^"ke u. 1/b, �rd, H-2030, HU)
Pap, L�szl� (Gy�ngyvir�g u. 23, �rd, H-2030, HU)
Sz�kely, Istv�n (Krajc�r u. 6, Dunakeszi, H-2120, HU)
International Classes:
A01N31/16; C07C43/215; (IPC1-7): C07C43/215; A01N31/16
Attorney, Agent or Firm:
Chinoin, Gy�gyszer �S Vegy�szeti (Term�kek Gy�ra Rt, Iparjog T� u. 1-5, Budapest, H-1045, HU)
Chinoin, Gy�gyszer �S Vegy�szeti (Term�kek Gy�ra Rt, Iparjog T� u. 1-5, Budapest, H-1045, HU)
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Claims:
Claims
1. (+) Optical isomer, isomeric mixture rich on the (+) optical isomer of the alkynyl ingredient compound of formula I.
2. Process for the preparation of the (+) optical isomer, or the isomeric mixture rich on the (+) optical isomer of the compound of formula I by reacting the (+) optical isomer, or the isomeric mixture rich in the (+) optical isomer of the compound of general formula II. with the compound of general formula III, wherein X and Y stand for groups suitable for the formation of ether bond.
3. Pesticide composition, comprising as active ingredient 0.000199.9 % by mass of the (+) optical isomer, or the isomeric mixture rich in the (+) optical isomer of the compound of formula I and, optionally, other known pesticide active ingredients, beside carriers and auxiliary materials.
4. Arthropodicide composition comprising as active ingredient 0.000199.9 % by mass of the (+) optical isomer, or the isomeric mixture rich on the (+) optical isomer of the compound of the formula I and, optionally, other arthropodicide active ingredients, beside carriers and auxiliary materials.
5. Composition according to claims 3 and 4, c ha r a c t e r i z e d by, that as for other active ingredient it contains one or more of the following active ingredients: Acetamide derivatives: e.g. oxamyl; Acetamidine derivatives: e.g. acetamiprid; Benzoylurea compounds: e.g. flucycloxuron, hexaflumuron, teflubenzuron, triflumuron, novaluron, lufenuron, chlorofluazuron; Bicycloheptadien compounds: e.g. heptenophos; Crossbridged diphenyl compounds: e.g. etofenprox, bromopropylate, methoxycholor, temephos, tetradifon; Carbamates: e.g. aminocarb, aldicarb, aldoxycarb, asulam, bendiocarb, benfuracarb, carbaryl, carbetamide, carbofuran, carbosulfan, diethofencarb, dioxacarb, ethiofencarb, fenobucarb, fenoxycarb, furathiocarb, isoprocarb, methomyl, oxamyl, pirimicarb (pirimor), propoxur, thiodicarb, thiofanox, xylylcarb; Carbamoyloxime derivatives: e.g. alanycarb, butocarboxim; Cyclodienes: e.g. aldrin, chlordane, endosulfan, heptachlor; Diazoles: e.g. fipronil; Diphenyl ethers: e.g. diophenolan; Hydrazides: RH 5992, RH 5849, CGA 215'944; Nereistoxin analogues: e.g. bensultap, cartap; Chloronicotinyl analogues: e.g. imidacloprid; Nitroethylen and nitromethylen analogues: e.g. nitenpiram; Organophosphor compounds e.g. quinalphos, diazinon, phosalone, dimethoate, azinphosmethyl, Organotin compounds: e.g. azocyclotin, cyhexatin, fenbutatin oxide; Oxadiazin carboxylates: e.g. DPXMP062, DPXJW062; Phenoxy compounds: e.g. diafenthiuron, diophenolan; Pyrazoles: e.g. pyrazophos; Pyrethroides: e.g. allethrin, bioallethrin (esbiol), acrinathrin, deltametrin, halphenprox, flumetrin, fenvalerate, empenthrin, prallethrin, resmethrin, MTI800, flufenprox, permethrin, tetramethrin, ZX8901, cypermethrin, and their isomers and isomercombinations, such as cypermethrin, theta cypermethrin; Pyridazinones: e.g. pyridaben, NC196; Pyridine derivatives: e.g. chlorpyriphos; Pyrimidine derivatives: e.g. pyrimiphosethyl, pyrimiphosmethyl; Pyrroles: e.g. AC 303, 630 (chlorphenapyr); Quinazolines: e.g. fenazaquin; Terpenoid derivatives: e.g. methoprene; Tetrazines: e.g. clofentezine, SzI121 (flufenzin); Thiadiazines: e.g. buprofezin; Thiazolidin: e.g. hexythiazox, ethoxazol; Triazoles: e.g. isazophos, RH 7988; Chlorinated hydrocarbons: e.g. lindane; Macrocyclic lactones: e.g. ivermecrin/avermectin, doramectin, noxidectin, emamectin, milbemicin; Tebuphenpyrade; Phenyproxymate; Triazamate; Insecticides of plant origine: e.g. azadiractin, naphthoquinones, pyretrides and their derivatives, plantextracts.
6. Composition according to claims 45, c h a r a c t e r i z e d b y, that as for active ingredient it comprises 0.0001.99.9 % by mass of the (+) optical isomer, or the isomeric mixture rich in the (+) optical isomer of the compound of formula I and an anthropodicide carbamate, pyretroide, pyretrine, chloronicotinyl analogue, diazole, macrocyclic lactone, preferably carbofurane, carbosulfan, pirimicarb, alanicarb, fipronil, imidaclopride and ivermectin/avermectin.
7. Process for extermination of pests, preferably arthropoda, comprising treating insects, preferably arthropoda with a suitable amount of the composition of claims 5 or 6, if desired in such a way that the compositions containing the (+) optical isomer, or the isomeric mixture rich on the (+) optical isomer of the compound of formula I, and the composition or compositions containing the known active ingredient(s) are used in a tank mixture or subsequently.
Description:
Pesticide compounds, compositions and process for the preparation thereof This invention relates to the (+) optically active isomer of the active ingredient of formula (I), to isomeric mixtures rich on the (+) optically active isomer, to pesticide compositions containing the (+) optically active isomer of the active ingredient of formula (I), to pesticide compositions containing the (+) optically active isomer of the active ingredient of formula (I) beside known pesticide synergists, to synergized pesticide compositions containing the (+) isomer of the pesticide synergist of formula (I) beside known pesticide active ingredients, furthermore to compositions containing the (+) isomer of the pesticide synergist of formula (I) beside known pesticide active ingredient and synergist, and to the process for the preparation thereof.

The racemic compound of formula I (MB-599) is described in WO 97/19040.

The compound of formula I has one center of asymmetry, thus it has two optical isomers. The two isomers can be distinguished -among others, most easily, by their direction of optical rotation. The above (+) optical isomer is the compound which, in its acetonic solution, rotates the plane of the linearly polarized light towards direction (+), i.e. to the right. The two optical isomers are mirror-image pairs, their general physical characteristics (boiling point, refractivity, solidification temperature) are the same, but in optically active systems, thus in biological medium too, they behave differently. Consequently, their synergistic activities may differe, too.

Compounds which are non-toxic, or only slightly toxic alone, but given together with a pesticide, in most cases with an arthropodicide agent, they enhance markedly the potency of the latter, are called synergists. The synergistic potency is characterized by the so-called SR synergist ratio, which is given, for example in the case of insecticides, as follows: LD50 insecticide SR50 -- = ------------- LD50 insecticide + synergist

The more the SR50 value differs from 1, the higher is the synergistic potency.

The use of synergists in arthropodicidal preparations is very attractive, since they afford a possibility to come out with new preparations with practically all representatives of the area. These new preparations, compared to the previous ones, promise to be less expensive, less toxic, more selective, encountering less environmental hazard, suppressing the evolution of resistance, and being active also on strains which already evolved resistance.

At present the number of the registered insecticide synergists is less than 10, but there are only 2-3 molecules listed as products in the Pesticide Manual, and only two materials (PBO, MGK264) are actually on the market. The reason for that: it is hard to find a chemical tool which can be used selectively and safely, and the cost/effectiveness ratio of which is competitive with that of the active ingredient.

To apply a synergist economically, it must be highly potent, it must act at small doses (around the original dose of the active ingredient).

Both selectivity and specific activity can be enhanced by use of pure material, containing only one isomer. PBO does not contain, but MGK264 has several centers of asymmetry. Thus, with this compound the possibility has been given to utilize the advantages of the optically pure preparation. Nevertheless, the material has not been used in that form. This may be explained by two non-contraversal reasons: there are only small differences between the activities of the isomers, and the cost of the preparation of the optically pure material is not covered by the savings due to the higher activities.

In case of some of compounds described in WO 97/19040, having asymmetric center -as for instance the a-methyl substituted benzyl derivative - it has been found that the R (+) derivatives are more potent than the S (-) enantiomers. As described in publications, the difference between the potencies of the isomers is increasing with the increasing activity of the racemic compound, but it never surpasses the 3-fold value. This means that the more potent isomer is at a maximum 1.5-times more potent than the racemic compound. This increase in potency does not cover the extra costs of the preparation of an optically pure compound.

The racemic compound of formula (I), known as MB-599, is an outstanding pesticide synergist, its optical isomers have not been previously prepared.

According to our invention we succeeded to prepare both the (+) isomer (MB- 755), and the (-) isomer (MB-754) and we subjected the compounds to a wide- range biological investigation. As expected, here again, the (+) optical isomer was biologically more active. However, the difference between the activities of the isomers, as obtained for resistent species, was much higher than expected and it showed one order of magnitude higher value (results are demonstrated in Table 1).

Table 1.

Treatment CHXSEL strain IX strain CARBSEL strain RR=234 RR=393 RR=381 SR SR SR Carbofuran + MB-755 (+) 2083 1000 2500 Carbofuran + MB-754 (-) 161 39 80 Ratio of activities (+)/(-) 13 26 31 RR: resistency factor SR: synergistic factor A similar trend for the differences has been found when the synergist-active ingredient ratio was lowered

Table 2.

SI 1 10 100-200 SR SR SR Carbofuran + 755 (+) >20 >25 > 25 Carbofuran + 754 (-) <5 <10 <12 Ratio of activities (+/-) 24 >2.5 SR: synergistic factor SI: synergist index; synergist/active ingredient ratio Using synergists in the practice the main criterium is that the amount of the synergists must be comparable with that of the active ingredient, the total amount of the synergists and the active ingredient must be as little as possible. The significance of our invention lays in this point. It not only allows savings, which can cover the extra costs of the preparation of the optical isomers, but it is very important from the view of the environmental biology. The material can be applied in much smaller quantities, it is more selective and it is safer. The high difference in the activities of the isomers was observed for various types of active ingredients.

With the compound according to our invention the effect of the following known arthropodicide active ingredients can favourably be synergized: Acetamide derivatives: e.g. oxamyl; Acetamidine derivatives: e.g. acetamiprid; Benzoylurea compounds: e.g. flucycloxuron, hexaflumuron, teflubenzuron, triflumuron, novaluron, lufenuron, chlorofluazuron; Bicycloheptadien compounds: e.g. heptenophos; Cross-bridged diphenyl compounds: e.g. etofenprox, bromopropylate, methoxycholor, temephos, tetradifon; Carbamates: e.g. aminocarb, aldicarb, aldoxycarb, asulam, bendiocarb, benfiracarb, carbaryl, carbetamide, carbofuran, carbosulfan, diethofencarb,

dioxacarb, ethiofencarb, fenobucarb, fenoxycarb, furathiocarb, isoprocarb, methomyl, oxamyl, pirimicarb (pirimor), propoxur, thiodicarb, thiofanox, xylylcarb; Carbamoyloxime derivatives: e.g. alanycarb, butocarboxim; Cyclodienes: e.g. aldrin, chlordane, endosulfan, heptachlor; Diazoles: e.g. fipronil; Diphenyl ethers: e.g. diophenolan; Hydrazides: RH 5992, RH 5849, COA 215'944; Nereistoxin analogues: e.g. bensultap, cartap; Chloronicotinyl analogues: e.g. imidacloprid; Nitroethylen and nitromethylen analogues: e.g. nitenpiram; Organophosphor compounds e.g. quinalphos, diazinon, phosalone, dimethoate, azinphos-methyl, Organotin compounds: e.g. azocyclotin, cyhexatin, fenbutatin oxide; Oxadiazin carboxylates: e.g. DPX-MP062, DPX-JW062; Phenoxy compounds: e.g. diafenthiuron, diophenolan; Pyrazoles: e.g. pyrazophos; Pyrethroides: e.g. allethrin, bioallethrin (esbiol), acrinathrin, deltametrin, halphenprox, flumetrin, fenvalerate, empenthrin, prallethrin, resmethrin, MTI-800, flufenprox, permethrin, tetramethrin, ZX-8901, cypermethrin, and their isomers and isomer-combinations, such as -cypermethrin, theta- cypermethrin; Pyridazinones: e.g. pyridaben, NC-196; Pyridine derivatives: e.g. chlorpyriphos; Pyrimidine derivatives: e.g. pyrimiphos-ethyl, pyrimiphos-methyl; Pyrroles: e.g. AC 303, 630 (chlorphenapyr); Quinazolines: e.g. fenazaquin; Terpenoid derivatives: e.g. methoprene; Tetrazines: e.g. clofentezine, SzI-12 1 (flufenzin); Thiadiazines: e.g. buprofezin; Thiazolidin: e.g. hexythiazox, ethoxazol;

Triazoles: e.g. isazophos, RH 7988; Chlorinated hydrocarbons: e.g. lindane; Macrocyclic lactones: e.g. ivermecrin/avermectin, doramectin, noxidectin, emamectin, milbemicin; Tebuphenpyrade; Phenyproxymate; Triazamate; Insecticides of plant origine: e.g. azadiractin, naphthoquinones, pyretrides and their derivatives, plant-extracts.

(the above known active ingredients are described in the 8th and 10th Edition of the Pesticide Manual, A.G.Chem.New Compound Review Vol. 11(1993) and ACS Symposium Series 504 p. 272., and the European Patent Application No. 0635499 (SZI-121), respectively.

The effect was demonstrated by us on various arthropode species The compounds of our invention proved to be active on insects, plant-louses and also on acari. A significant advantage of the compound of formula (I) is that it shows practically the same activity on species which already evolved resistance, as on the sensitive strains.

Compounds of formula I can be prepared by stereoselective substitution, by reacting the compounds of general formula II and III, where X and Y mean groups suitable for ether formation. Favourably we can react the alkali- or alkali earth metal salt of the resolved benzylalcohol of general formula II, under SN2 conditions, with a 2-butynyl derivative of general formula III, which contains a suitable leaving group.

The compound according to the present invention is not known from the literature.

When identifying the compound, after checking the purity by GC and TLC investigations, the structure was unequivocally supported by IR, 1 H and C13 NMR investigations. Optical purity was characterized by optical rotation values and by

the optical purity of the starting material, determined with the help of NMR measurements.

The compound of formula I can be formulated as independent composition or in admixture with other known pesticide (s), preferably arthropodicide active ingredients, and according to the application goal known carriers and other auxiliary materials may be used. Thus, by methods known per se, emulsion concentrates, microemulsions, ULVs, microsuspensions, suspensions, dusters, aerosols, vaporators and smokers may be prepared. [Rhone Poulenc-Geronazzo: Surfactant and Specialities for Plant Protection, Application Manual (1994), ICI: Surfactants, Application Manual (1992)].

In the course of the application the compositions containing the compound of the present invention and the compositions containing the known active ingredient(s) can be used consecutively, or by making a tank-mixture of them.

To demonstrate the scope of our invention we present the following examples, without limiting the scope to the examples.

Examples for preparation: Example 1.

(+)-4-(But-2-ynyloxyerhyl)-1,2-dimethoxyhenzene, MB- 755, (+) VERBUTIN Into a 25 ml round-bottom flask, equipped with thermometer, magnetic stirrer and connected to an inert gas system 8 ml of abs. THF are added and 0.44 g (0.0165 mol, approx. 90%) of NaH is suspended in it. To this suspension is added slowly, dropwise, at room temperature, the solution made of 5 ml abs. THF and 1.0 g (0.0055 mol) (+)-a-methylveratrylalcohol (rotation values: [a]2D = +33,1°, c=l methanol ands [a]20 =+35,5o, c=1 acetone, . Mp: 43.2-44.9 OC), and the mixture is heated under reflux conditions for 1 hour. The mixture is cooled then to room temperature, 0,77 g (0.082 mol) of 1-bromo-2-butyn are added and heating under reflux is continued. The reaction is followed by TLC (eluent: hexane-Etac 7:3).

Expected reaction time: 3-4 hours.

To the cooled thick suspension 50 ml of water and 50 ml of ethyl acetate are added, the mixture is filtered on celite, the filtrate is washed with distilled water, dried over magnesium sulfate and evaporated. The residue is purified by column chromatography. (eluent: hexane-Etac 7:3, Rf=0.536).

Yield: 0.926 g (3.95 mmol), 72.34%.

Purity was checked by GC analysis: (CP 9000, CP-SIL-SCB, 60 m x 0.53 pm, 5 ml/min N2, FID, 250"C) tR = 3,87 min, >97.4%.

The material proved to be homogeneouse and well defined. On the basis of its behavior in TLC, GC and NMR investigation it is identical with the racemic compound, MB-599.

Elucidation of structure: 1H-NMR (200 MHz, CDCl3) 6: 1.45 (3H, d, J=6.47 Hz, ArCH-CH3), 1.85 (3H, t, J=2.35 Hz, =-C-CH3), 3.87 and 3.89 (6H, s, aryl- OCH3), 3.79 and 3.98 (2H, ABX3, JAB=14.97 Hz, JAX--JBX=2 3 Hz, =C-CH2O), 4.54 (2H, q,

J=5.83 Hz, Ar-CHO), 6.83-6.89 (3H, m, aromatic).

13C-NMR (50 MHz, CDC13) b: 3.66 (#C-CH3), 23.86 (ArCH-CH3), 55.88 (OCH3), 56.02 (=-C-al2O), 75.38 (#C-CH2), 81.97 (#C-CH3), 109.08 (C-3), 110.87 (C-6), 118.98 (C-5), 135.33 (C-4), 148.55 (C-1), 149.22 (C-2).

Optical rotation: Of the (+)-verbutin a solution was made with accurate weight-in (54.7mg/ 5ml acetone in a 5ml volumetric flask, c=1.094 g/l ), then the optical rotation was determined at various wave-lengths in a cuvette of 1dm length and of 1cm3 volume. # α [α]D20 589 2.185 +199.7 578 2.276 +207.5 546 2.605 +237.5 436 4.574 +416.9 365 7.584 +691.1 Optical purity: Optical purity of the starting material was determined by HNMR measurement, by using optically active shift reagent. By this method 3% enantiomeric impurity was shown. According to the accuracy of the method the material MB-755 contains the (+) isomer in 94%.

Example 2.

(-)-4-(But-2-ynyloxyethyl)-1,2-dimethoJcybenzene, MB- 754, (-) VERBUTIN Into a 25 ml round-bottom flask, equipped with thermometer, magnetic stirrer and connected to an inert gas system 8 ml of abs. THF are added and 0.44 g (0.0165 mol, approx. 90%) of NaH is suspended in it. To this suspension is added slowly, dropwise, at room temperature, the solution made of 5 ml abs. THF and 1.0 g <BR> <BR> <BR> <BR> (0.0055 mol) (-)-a-methylveratrylalcohol (rotation values: [a]2DO = -3 -31.7°, c=l methanol ands [a]D20 =-34.3°, c=l acetone, . Mp: 44 °C), and the mixture is heated under reflux conditions for 1 hour. The mixture is cooled then to room temperature, 0,77 g (0.082 mol) of l-bromo-2-butyn are added and heating under reflux is continued. The reaction is followed by TLC (eluent: hexane-Etac 7:3).

Expected reaction time: 3-4 hours.

To the cooled thick suspension 50 ml of water and 50 ml of ethyl acetate are added, the mixture is filtered on celite, the filtrate is washed with distilled water, dried over magnesium sulfate and evaporated. The residue is purified by coloumn chromatography (eluent: hexane-Etac 7:3, Ref=0.536).

Yield: 0.79 g (3.37 mmol), 61.7%.

Purity was checked by GC analysis: (CP 9000, CP-SIL-5CB, 60 m x 0.53 plum, 5 ml/min N2, FID, 250"C) tR = 3,87 min, >93,5%.

The material proved to be homogeneous and well defined. On the basis of TLC, GC and NMR investigation it is identical with the racemic compound, MB-599.

Elucidation of structure: 1H-NMR (200 MHz, CDC13) 6: 1.46 3H, d, J=6.47 Hz, ArCH-CH3), 1.85 (3H, t, J=2.33 z, =-C-CH3), 3.90 and 3.88 (6H, s, aryl- OCH3), 3.82 and 4.01(2H ABX3, JAB=14.98 Hz, JAX=JBX=2.37 Hz, -C-CH20), 4.54 (2H, q, J=6.47 Hz, Ar-CHO), 6.83-6.89 (3H, m, aromatic).

13C-NMR (50 MHz, CDCl3) 6: 3.66 (C-CH3), 23.80 (ArCH-CH3), 55.88 (OCH3), 56.02 (-C-CH2O), 75.38 (-C-CH2), 81.97 (=-C-CH3), 109.08 (C-3), 110.87 (C-6), 118.98 (C-5), 135.33 (C-4), 148.55 (C-1), 149.22 (C-2).

Optical rotation: Of the (-)-verbutin a solution was made with accurate weight-in (52.8 mg/ 5ml acetone in a 5ml volumetric flask, c=1.056 g/l ), then the optical rotation was determined at various wave-lengths in a cuvette of ldm length and of lcm3 volume. # α [α]D20 589 -1.986 -186.0 578 -2.045 -193.6 546 -2.340 -221.6 436 -4.111 -389.3 365 -6.817 -645.5 Optical purity: Optical purity of the starting material was determined by HNMR measurement, by using optically active shift reagent. By this method 4% enantiomer impurity was shown. According to the accuracy of the method the material MB-754 contains the (-) isomer in 92%.

Activitv results: Example 3.

Investigation of the synergistic activity on resistent house fly (Musca domestica) population In two parallel experiments 10 female, 2-3 day old house flies were treated on the vental side of their thorax with 0.2 ul of the test solution, with the help of Hamilton MicroLab P microdispenser. Beside fixed synergist dose of 1000 ng/fly the animals were treated with carbofuran at a dose of 20 ng/fly. For solvent cellosolve was used. Selection and counting of the flies were performed under the action of CO2. After treatment the flies were kept in plastic cups covered with tulle. Mortality after 24 hours was expressed in %. From the dose-mortality relationship the LD50 (ng/fly) values were calculated by probit analysis For the tests CHXEL, CARBSEL IX insecticide-resistent fly-strains were used The resistency factors (RR) are expressed as the quotient of the LD50 values obtained for the carbofuran resistent and sensitive (WHO/SRS) strains.

Results are demonstrated in the table below:

Table 3 Treatment CHXSEL strain IX strain CARBSEL strain RR=234 RR=393 RR=381 LD50 SR LD50 SR LD50 SR carbofuran >25000 - >25000 - >25000 - carbofuran + 754 (-) 155 161 646 39 314 80 carbofuran + 755 (+) 12 2083 25 1000 10 2500 carbofuran + 599 (+/-) - - 82 305 15 1667 carbofuran + PBO* 323 77 4687 5 2071 12 carbofuran+MGK264** 10176 3 23501 1 12494 2 * PBO: piperonyl butoxide * * MGK 264: N-(2-ethylhexyl)-8,9, 1 0-trinorborn-S -en-2,3 -dicarboxamide (ENT- 8184) Example 4.

Investigation of synergist spectrum on house fly (Musca domestica) and cotton bollworm (Helicoverpa armigera) Synergistic activities of compound MB-755 of the present invention and of reference compound MB-599 have been determined for various active ingredients on house fly (Musca domestica) and on L2 phase larvae of cotton bollworm (Helicoverpa armigera) using the method of treatments described in biological Example 3. For the active ingredients ISO common names are given (see: Pesticide Manual 1994). The obtained synergist ratios are shown below:

Table 4 Active Synergist factors for 755 Synergist factors for 599 ingredients Musca domestica Helicoverpa Musca domestica Helicoverpa arm igera armigera carbofuran > 40 > 40 >40 >20 bendiocarb > 20 > 20 >20 >20 isoprocarb > 40 >40 >20 fenobucarb > 40 >20 aminocarb > 20 >20 thiodicarb > 20 >10 methomyl > 15 >10 pirimicarb > 20 >20 dioxacarb > 40 > 20 >40 >20 propoxur > 20 > 40 >40 >20 imidacloprid > 10 >5 lindan >5 >5 zinphos-methyl > 5 >5 chiorpyriphos > 5 > 5 esbiol >5 >10 permethrin >5 > 10 >5 >10 tetramethrin >5 > 10 >5 >10 Example 5.

Effect of the active ingredient:synergist ratio on the synergistic activity Treatment was performed as described in Example 3, using Hamilton MicroLab P microdispenser. In two parallel experiments 10 female, 2-3 day old flies were treated on the ventral side of their thorax with 0.2 ,ul test solution. Beside 1000-400-200-80 ng/fly fixed doses of the synergist they were treated with constant 20 ng/fly carbofitran. Selection and counting of the flies were performed under the action of CO2. After treatment the flies were kept in plastic cups covered with tulle. After 24 hours mortality % was recorded. Depending on the results the experiments were performed in 2-4 replica. Results are demonstrated in the table below.

Table 5 Materials Dose of the synergist (ng/fly) 0 180 200 1 11000 Mortality after 24 hours (%) 599 0 - 65 90 95 100 754 0 0 25 75 90 755 0 95 100 100 100 PBO 0 0 0 10 70 MGK 0 0 0 0 0 Examples for formulation: (Names of the marketed auxiliary materials are given in quotation marks, followed by the makers name.) Example 6. Preparation of powders A) To 158g of fine-grained perlite 20g of carbofuran and 20g of compound 755, were mixed in a homogenizator, to this mixture 2g of fatty alcohol polyglycol ether ("G-3920" ICI) were added and the mixture was homogenized. The powder mixture was grained in an ejector mill and to it were added 5g of octyl-phenol-

polyglycol-ether (EO=20) ("Triton X-165" Rohm & Haas) and 2g of alkyl- sulfosuccinate ("Aerosol-13" Cyanamid). The resulting product is a wettable powder mixture (WP).

B) 10g of compound 755 and 10g of carbofuran were diluted with 2g of ethanol.

The solution was mixed in a powder homogenisator with 5g of calcium-lignin- sulfonate ("Borrespeseca" Borregard), 5g of nonyl-phenol-polyglycol-ether (EO=20) ("Arkopal N-200" Hoechst), and 70g of calcium carbonate. The resulting product was grained in an alpine-100 typ mill. Average particle size was 1-2 pm.

This composition may be used to prepare microsupensions.

C) The mixture of 3g of Diazinon, 3g of compound 755 and 0.3g of fatty alcohol-polyglycol-ether ("G-3920" ICI) was taken up in a homogenisator apparatus on the mixture of 1.0g synthetic silicic acid (Aerosil 200) and 191g talc (dmaX =15-30 um), the pH of the latter was previously adjusted to pH=7.0 with potassium- and sodium-phosphate buffer. Under further stirring 1 g of dioctyl-sulfo-succinate ("Aerosol OTB" Cyanamid) and 1g of fatty alcohol-polyglycol-ether-sulfonate ("Genapol LRD" Hoechst) were added and finally the mixture was grained to an average particle size of 20 clam. The resulting product is an easy flowing powder preparation.

Example 7. Preparation of emulsion concentrates A) The mixture of 5g of pirimicarb and 5g of compound 755 was dissolved in the mixture of 20g of xylene and 40g of propanol. To this solutoin was added the mixture of 4g of ethoxylated alkyl-phenol + lineare alkyl-aryl-sulfonate-calcium salt ("heron FF/U Geronazzo) and 6g of ethoxylated amine + fatty acid +

lineare alkyl-aryl-sulfonate alkali metal salt ("Geronol MS" Geronazzo). After complete dissolution 20g of water were added. Transparent solution was obtained, for which is characteristic, that on dilution with water it forms an emulsion of 0.8- 1.5 um drop-diameter.

B) The mixture of 5g of quinalphos and 10g of compound 755 and the mixture of 7g of ethoxylated-(EO=13)-propoxylated-(PO=21)-nonylphenol, 2g of lineare- dodecylbenzenesulfonic acid-calcium salt and 12g POE-(20)-sorbitan-monooleate were dissolved in the mixture of 28.6-28.6 ml of propyleneglycol and pine-fatty acid and 23.8m1 of sun-flower oil, 9.5ml of etanol and 95 ml of aliphatic hydrocarbone with 45% naphthene contant. The material thus obtained may be preferably used for the preparation of microemulsions.

C) The mixture of 0.02-0.02 parts by mass of the active ingredient and of the synergist is dissolved in 10 parts by mass of propanol, to the resulting solution 99.96 parts by mass of odourless petroleum are added and the mixture is stirred until a homogenous solution is obtained. The resulting oily dispersible preparation can directly be used in ULV applications.

Example 8 Preparation of granulates In a mechanical granulator 300g of carbofuran, 300g of compound 755, 1500g of polycarboxylate alkali salt ("Sorphol," Toho), 500g of dodecyl- benzenesulfonic acid sodium salt ("Marlon TP 370" Hills), 500g of beet sugar and 7200g of caolinite are mixed. The powder mixture thus obtained is mixed with 8300ml of water using a mixer of high shear force (v=lOm/s). The mixture is finally spray-dried. Particle-size distribution of the product is 0.1-0.4 mm.

Example 9. Preparation of aerosols In a 100 1 apparatus supplied with stirrer lkg of bioallethrin, 0.5kg of compound 755, 0.1kg of aerosil-air 972, 0.1 kg of ethyleneglycol-monosalicylate, 15kg of odourless petroleum and 50kg of propanol are mixed. After dissolution it is filled into cylinders with 33.3kg of liquid propane-butane (25-75) gas.

Example 10. Preparation of vaporators In 60 ml of ethanol 5g of S-bioallethrin, 5g of compound 755 and 1 g of lemon aroma are dissolved The solution is applied in vaporators, at a temperature of 50 OC.