CS214852B2 - Insecticidal agent - Google Patents

Abstract

The invention relates to a new insecticidal composition. The essence of this composition is that it contains as an active substance a compound from the group including (S)-or-cyano-3-phenoxybenzyl-[2,2-dimethyl-3R-(2,2-dichlorovinyl)cyclopropane-1R]carboxylate and (R)-a-cyano-3-phenoxybenzyl-[2,2-dimethyl- - ' -3R-(2,2-dichlorovinyl)cyclopropane-1R]carboxylate.

Description

The invention relates to a new insecticidal composition.

For several years, insecticidally active compounds with extraordinary biological activity have been prepared by esterification of chiral acids with α-cyano-3-phenoxybenzyl alcohol.

It has now been newly discovered that also esters of chiral 2,2-dimethyl-3R-(2,2-dichlorovinyl)cyclopropane-1R-carboxylic acid and optically active α-cyano-3-phenoxybenzyl alcohol of the formula

structures (Rj or (Sj) have useful insecticidal activity, which activity is significantly higher than the insecticidal activity of the above chiral acid in the form of an ester with optically inactive racemic a-cyano-3-phenoxybenzyl alcohol of the structure [R, S].

The subject of the invention is a new insecticidal composition, the essence of which lies in the fact that it contains as an active substance a compound from the group including (S)-α-cyano-3-phenoxybenzyl-[2,2-dimethyl-3R-(2,2-dichlorovinyl)cyclopropane-1R]carboxylate and (R]-α-cyano-phenoxybenzyl-[2,2-dimethyl-3R-(2,2-dichlorovinyl)cyclopropane-1R]carboxylate.

However, the aforementioned α ^, -cyano-3-phenoxybenzyl alcohol has so far only been prepared in the form of a racemic compound. Due to the relative instability of the molecule of the aforementioned alcohol, it has not been possible to prepare its enantiomers stereoselectively; for the same reason, it has also not been possible to resolve the aforementioned racemic alcohol into its optically active antipodes.

The only known method to date for obtaining esters of chiral acids with alcohols consists in separating the ester of a chiral acid and an alcohol of structure (RJ) from the ester of a chiral acid and an alcohol of structure (S) by selective desolubilization of the second of the said esters in a suitable solvent, which, however, leads to a relatively low yield lying well below 50%, based on the weight of the racemic ester used.

However, a method has now been found for the economical production of chiral acid esters of the formula

in which Hal represents a chlorine atom or a bromine atom, and an optically active alcohol of the structure (SJ) or/and (Rj) of the formula

This new method, by which the active ingredients of the insecticidal composition according to the invention can also be prepared (Hal means in the above-mentioned formula of the chiral acid a chlorine atom and which is the subject of Czechoslovak patent number 214 851, consists in treating the ester of a chiral acid and a racemic alcohol of the said structural formula (R, S) or the ester of a chiral acid and an optically active alcohol of the said structural formula (R) or a non-equimolar mixture of an ester of a chiral acid and an optically active alcohol of the said structural formula (R) and an ester of a chiral acid and an optically active alcohol of the said structural formula (S) with a basic agent selected from the group comprising ammonia, primary amines, secondary amines, tertiary amines, quaternary ammonium salts, basic ion exchange resins, high molecular weight liquid amines and strong bases, which strong bases are used in a catalytic amount, in a solvent or in a mixture of solvents, in which or in which the ester of a chiral acid and an optically active alcohol of the said structural formula is (R) soluble, after which the thus insoluble ester of the chiral acid of the active alcohol of the stated structural formula (SJ.

In this process, the basic agent is preferably selected from the group consisting of ammonia, triethylamine, diethylamine, morpholine, piperidine and a strong base from the group consisting of sodium carbonate, potassium carbonate, alkali metal alcoholates and alkali metal hydrides, said strong bases being used in a catalytic amount.

The basic agent may also be preferably selected from the group consisting of diisopropylamine, ephedrine, triethylenediamine, potassium tert-butylate and sodium isopropoxide, the latter two bases being used in catalytic amounts.

The above-mentioned solvent or solvent mixture is preferably selected from the group comprising acetonitrile, alkanols and mixtures of alkanol and petroleum ether.

In the production of the ester of 2,2-dimethyl-3R-(2,2-dichlorovinyl)cyclopropane-1R-carboxylic acid and optically active α-cyano-3-phenoxybenzyl alcohol of structure (S) and structure (R), the above-mentioned process proceeds in such a way that the basic agent is preferably selected from the group comprising ammonia, triethylamine, diethylamine, morpholine, pyrrolidone, pi1

2ΪΟ52 pyridine and a strong base from the group consisting of sodium carbonate, potassium carbonate, alkali metal alcoholates, alkali metal amides and alkali metal hydrides, the latter strong bases being used in a catalytic amount and the solvent or solvent mixture used being selected from the group consisting of acetonitrile, alkanols and mixtures of alkanol and petroleum ether.

Preferably, the basic agent is selected from the group consisting of diisopropylamine, ephedrine, triethylenediamine, potassium tert-butylate and sodium isopropoxide, the latter two bases being used in catalytic amounts, and the solvent or solvent mixture used is selected from the group consisting of acetonitrile, alkanols and a mixture of alkoxides and petroleum ether.

The solution forming the essence of the invention is surprising, since until now there has been no method that would enable the transformation of an optically active alcohol into an ester of an optically active alcohol, which would represent its optically active antipode to the aforementioned optically active alcohol, in practically quantitative yield.

However, this method makes it possible, for example, to transform directly and in quantitative yield the ester of 2,2-dimethyl-3R-[2,2-dichlorovinyl]cyclopropanecarboxylic acid or 2,2-dimethyl-3R-(2,2-dichlorovinyl)cyclopropane-1R-carboxylic acid and optically active α-cyano-3-phenoxybenzyl alcohol of structure (R) or esters of the said chiral acids and racemic α-cyano-3-phenoxybenzyl alcohol of structure (R) or a mixture of the ester of the said chiral acid and optically active α-cyano-3-phenoxybenzyl alcohol of structure (S) and the ester of the said chiral acid and optically active α-cyano-3-phenoxybenzyl alcohol of structure (S) with a rich content of the ester of the said chiral acid and optically active α-cyano-3-phenoxybenzyl alcohol of structure (R) into the ester of the said chiral acid and optically active α-cyano-3-phenoxybenzyl alcohol of structure (S).

It goes without saying that the terms "insoluble" in the case of esters of a chiral acid and an optically active alcohol of structure (S) and "insoluble" in the case of esters of a chiral acid and an optically active alcohol of structure (S) are to be understood in their ordinary meaning. In the solvents used in the method, the esters of a chiral acid and an optically active alcohol of structure (S) are nevertheless soluble to a certain limited extent; given the volume of solvent used, the solubility must be sufficiently low to achieve a good yield of the desired product. In practice, such a volume of solvent or solvent mixture is used that allows the resulting ester of a chiral acid and an optically active alkyl-3-phenoxybenzyl alcohol of structure (S) to be obtained in at least 80% yield.

As for the esters of the above chiral acids and optically active o-cyano-3-phenoxybenzyl alcohol of structure (R), these esters are very soluble in the solvents used in the above-described method, so that even a limited volume of these solvents allows their complete dissolution.

The reaction temperature affects the reaction rate.

The reaction time depends on the temperature and also on the nature of the base used.

In the following description, the mechanism by which the above-described method takes place will be explained.

By the action of a base of suitable strength, which in the above-described method is selected from the group comprising:

Ammonia, primary amines, secondary amines, tertiary amines, quaternary ammonium salts, basic ion exchange resins, high molecular weight liquid amines and strong bases, used in catalytic amounts, react with the ester of a chiral acid and an optically active alcohol of structure (R) contained in the starting product to form an a-cyano-carbanion, which causes racemization of the corresponding carbon.

Further protonation in a solvent or in a mixture of solvents leads to the formation of two diastereoisomers (an ester of a chiral acid and a steric alcohol (S) and an ester of a chiral acid and a steric alcohol (R)) in unequal amounts according to the following scheme:

In the solvent or solvent mixture which is or is not used in the above-described process, the ester of the chiral acid and the alcohol of the structure (SJ) is insoluble, while the ester of the chiral acid and the alcohol of the structure (RJ) is soluble in this medium; the equilibrium is therefore shifted in favor of the formation of the ester of the chiral acid and the alcohol of the structure (S), whereby in practice yields of the ester of the chiral acid and the optically active alcohol of the structure (SJ) of about 80 to 90% are achieved, based on the initial amount of the optically active ester that was taken into the reaction; the ester of the chiral acid and the optically active alcohol of the structure (SJ) is therefore excluded from the reaction mixture.

The formation of an intermediate non-equimolar mixture of an ester of a chiral acid and an alcohol of structure (SJ) and an ester of a chiral acid and an alcohol of structure (RJ) can be demonstrated by separating the soluble fraction. Racemization takes place practically in quantitative yield, since here, unlike the last phase of the method described above, a solvent or a mixture of solvents is used in which, or in which, the esters of the chiral acid and the alcohol of structure (S), the ester of the chiral acid and the alcohol of structure (R) and the ester of the chiral acid and the racemic alcohol of structure (R,SJ) are soluble.

(S)-α-cyano-3-phenoxybenzyl-[2,2-dimethyl-3R-(2,2-dichlorovinyl)cyclopropane-1R]carboxylate and (R)-α-cyano-3-phenoxybenzyl-[2,2-dimethyl-3R-(2,2-dichlorovinyl)cyclopropane-1R]carboxylate are new compounds, as they have not yet been described in the literature.

The first of these compounds, i.e. an ester of a chiral acid and an alcohol of the structure (SJ), is particularly suitable for controlling insects in agriculture.

This compound can be used, for example, to kill butterfly larvae. It can also be used as an insecticide against domestic insects, such as mosquitoes or flies.

The insecticidal efficacy tests given in the exemplary part of the description demonstrate the high insecticidal efficacy of the compounds according to the invention in controlling house flies and larvae of the species Spodoptera Littoralis and Epilachna Varivestris.

(R)-α-cyano-3-phenoxybenzyl-[2,2-dimethyl-3R-(2,2-dichlorovinyl cyclopropane-1R]carboxylate exhibits lower insecticidal activity than the corresponding ester of the alcohol of structure 1S).

(S)-α-cyano-3-phenoxybenzyl-[2,2-dimethyl-3R-(2,2-dichlorovinyl)cyclopropam-1R]carboxylate and (R)-α-cyano-3-phenoxybenzyl-[2,2-dimethyl-3R-(2,2-dichlorovinyl)cyclopropain-1R]carboxylate can therefore be used for the preparation of insecticidal compositions which contain one or the other of the compounds mentioned as an active ingredient.

In these compositions, the active ingredient may consist of one or more pesticidal agents. These compositions may be formulated as dusts, granules, suspensions, emulsions, solutions, aerosol solutions and other formulations known per se for applications of the type mentioned.

The insecticidal compositions may contain, in addition to the active ingredient, a carrier and/or a nonionic surfactant, which ensures, among other things, uniform dispersion of the components of the mixture. As a carrier, it is possible to use a liquid carrier, such as water, alcohol, hydrocarbons or other organic solvents, mineral oil, animal oil or vegetable oil, a powder carrier, such as talc, clays, silicates or silica gel, or a solid flammable carrier.

In order to increase the insecticidal activity of the above compounds, it is possible to add to these compounds conventional synergistic compounds, such as 1-(2,5,8-trixadodecyl-2-propyl-4,5-methylenedioxy)benzene, N-(2-ethylheptyl)bicyclo[2,2,1]-5-heptene-2,3-dicarboximide and piperonyl-bis-2-(2'-n-butoxy)ethyl acetal.

Said insecticidal compositions preferably contain 0.005 to 10 weight percent of active ingredient.

In order to further explain the invention, several exemplary embodiments are given in the following description.

Example 1

Transformation of (R)-α-cyano-3-phenoxybenzyl-[2,2-diniethyl-3R-(2,2-dichlorovinyl)cyclopropane-1R] carboxylate to (S)-α-cyano-3-phenoxybenzyl-[2,2-dimethyl-3R-(2,2-dichlorovinyl)cyclopropane-1R] carboxylate a) Preparation of the alcohol ester of structure (R):

g of the racemic ester of the alcohol (R, S), having [α] _D ²⁰ = + 16.5° (10%, benzene) is chromatographed on silica gel, eluting with a mixture of petroleum ether (boiling point 40-70°C) and isopropyl] ether (85:15); 3 g of (R)-«-cyano-3-phenoxybenzyl[2,2-dimethyl-3R-(2,2-. -dichlorovinyl)cyclopropane-1R J carboxylate are obtained, having [α] _D ²⁰ = — 31° (1%, benzene) or [«] _D ²⁰ = — 21.5° (1%, chloroform).

b) Transformation into an ester of the alcohol of structure (S):

To 60 g of (R)-α-cyano-3-phenoxybenzyl-[2,2-dimethyl-3R-(2,2-dichlorovinyl)cyclopropane-1R]carboxylate, having [α] _D ²⁰ = — 31° (1%, benzene) or [α] _D ²⁰ = — 21.5° (1%, chloroform), obtained in paragraph a), are added 120 ml of isopropanol and then 9 ml of aqueous ammonia solution (22 °Bé); the mixture thus obtained is cooled to 0 °C and then stirred for forty-eight hours at 0 °C. The precipitate formed is then isolated by centrifugation, washed with 30 ml of isopropanol at -20°C and dried, yielding 48.5 g of (S)-α-cyano-3-phenoxybenzyl-[2,2-dimethyl-3R-(2,2-dichlorovinyl)cyclopropane-1R]carboxylate, having a melting point of 60°C;

[a]n ²⁰ = + 66° (1%, benzene) or [os]d ²⁰ = + 34° (1%, chloroform).

Example 1 and 2

Transformation of (R,S)-α-cyano-3-phenoxybenzyl-[2,2-dimethyl-3R-(2,2-dichlorovinyl)cyclopropane-1R]carboxylate to (SJ-α-cyano-3-phenoxybenzyl-[2,2-dimethyl-3R-(2,2-dichlorovinyl)cyclopropane-1R]carboxylate

To 600 g of the racemic alcohol ester (R,S), having [<1>]d ²⁰ = + 16.5° (10%, benzene), 1200 ml of isopropanol are added, after which 90 ml of aqueous ammonia solution (22°Bé) are added to the mixture thus obtained. The resulting mixture is cooled to 0°C and stirred at this temperature for forty-eight hours. The precipitate that forms is isolated by centrifugation, washed with 300 ml of isopropanol at -20°C, dried and weighed, yielding 485 g of (S)-a'-cyano-3-phenoxybenzyl-[2,2-dimethyl-3R-(2,2-dichlorovinyl)cyclopropane-1R]-carboxylate, having a melting point of 60°C;

[°C ²⁰ = -66° (1%, benzene) or [°C ²⁰ = +- 34° (1%, chloroform).

Analysis: C22H19O3NCI2 (416.28)

Calculated:

63.48% C, 4.60. % H, 3.36% N, 17.03% Cl,

Found:

63.7% C, 4.60% H, 3.4% N,

17.1% Cl.

14113 2

Example 3

Example 4

Preparation based on (Sj-řr-cyano-S-phenyloxybenzyl-[2,2-dimethyl-3R-(2,2-dichloro‘Vinyl)cyclopropane-3R]carboxylate

Mixes:

(S) -1-cyano-S-enoxybenzyl[22-dimethyl-3R-(2,2-dichlorovinyl jcyclopropane-1R]carboxylate 25 g/1

2,6-ditert.butylcresol 10 g/1 surfactant consisting of a mixture of calcium salts of alkylbenzenesulfonate (anionic part) and polyoxyethylene ethers (nonionic part) 70 g/1

Aromatic solvent mixture 785 g/1

Study of the insecticidal activity of (S)-«-cyano-3-phenoxy ^benzyl- {E,2-dimethyl-3R--C2,S-Uichlorovinyl) cyclic propane-IR carboxylate (compound A)

a) Study of insecticidal efficacy on houseflies

The test insects are mixed-sex domestic flies. The administration of the active substance is carried out by topical application of 1 µl of acetone solution to the dorsal thorax of the test insect. 50 insect individuals are tested. 24 hours after application of the active substance, the mortality of the insects is determined, whereby the lethal dose (LD50) of the test compound is determined. The results obtained are summarized in the following table:

Dose % mortality after 24 hours

ELSO

3.75

2.5

1.25

0.625

93.3

83.2

68.0

34.5

10.0 iisnograniu for individuals

From the previous table it is clear that compound A exhibits high insecticidal activity against houseflies,

b) Study of insecticidal efficacy against Spodoptera Littoralis larvae

The tests were carried out using a thermal application. 1 μΐ of an acetone solution of the test compound is placed on the dorsal thorax of each individual. 15 Spodoptera Littoralis caterpillars in the fourth larval stage are used for each dose applied. After application, the individuals used are placed in an artificial nutrient medium (Poltot), 24 hours and 48 hours after application, the effectiveness of the test product is checked (percentage of mortality relative to the control group of individuals), while the lethal dose (LD50) is determined in nanograms for the caterpillar.

The results obtained are summarized in the following table.

Dose % mortality LDso after 48 hours after 24 hours after 48 hours

125 85 6 97.8 0.625 80.0 82.2 0.3 nanograms per 0.3125 48.9 62.2 caterpillar 0.1562 20.5 27.3

Example 5

Comparison of the insecticidal efficacy of the active compounds according to the invention with the insecticidal efficacy of similar known compounds The compounds tested are:

- (S]-[3-cyano-3-phenoxybenzyl-[2,2-dimethyl-3R-(2,2-dichlorovinyl)cyclopropane-1R]-carboxylate (compound A; according to the invention);

- (R,S)-α-cyano-3-phenoxybenzyl-[2,2-dimethyl-3R-(2,2-dichlorovinyl)cyclopropane-1R)carboxylate (compound B; known art);

-(R)-4-[2,2-dimethyl-3R-(2,2-dichlorovinyl)cyclopropane-1R]-carboxylate (compound C; according to the invention);

1. Study of insecticidal efficacy against houseflies

The test insects are female house flies of a strain not resistant to pyrethrinoid compounds; the test insects were kept at a temperature of 22 to 23 °C at a relative humidity of 60 to 65%; the insects are 4 to 5 days old. Topical applications of 1 μl of acetone solution of the test compound are used on the dorsal thorax of the insects using an Ar214852 Nolda micromanipulator. 50 individuals are used for each dose of the test compound. 24 hours after application, the mortality of the insects is evaluated. The lethal dose LD50 is determined in nano grams per insect.

Compound LD50 without synergy

Compound A 2.07

Compound B 4.06

Compound C —

2. Study of the shocking effect on the housefly

The test insects are female houseflies aged 4 to 5 days. Direct spraying in a Kearns-March cylinder is used; a mixture of acetone (5%) and kerosene is used as solvent (amount of solvent used: 2 ml per second). 50 individuals are used for each dose. Every minute up to 10 minutes and then, after 15 minutes, the KT 50 is determined by the usual methods. The results obtained are shown in the following table:

Compound KT 50 Compound A 4.03 Compound B 4.6 Compound C 7.4

-.......

The test is performed both without the addition of a synergistic agent and in the presence of the synergistically active piperonyl butoxide.

The results obtained are summarized in the following table:

in nanograms per insect individual with synergy ...... —

1.22

35.3

3. Study of efficacy on Epilachna Varivestris larvae

The test is carried out using a similar topical application as that used in the housefly and Spodoptera LittoraPs tests. Penultimate instar larvae are used; after application, the larvae are fed on bean plants. Mortality is assessed 72 hours after application. The results are expressed as the lethal dose LD50 in nanograms per insect. The results obtained are shown in the following table:

Compound LD50 in nanograms per individual

Compound A 1.98

Compound B —

Compound C 49.1

Claims (1)

An insecticidal composition comprising, as active ingredient, a compound selected from the group consisting of (S-α-cyano-3-phenoxybenzyl- [2,2-dimethylmethyl-3R- (2,2-dichlorvinyl) -cyclopropane-1R] carboxylate, and (R 1 -α-Cyano-3-phenoxybenzyl- [2,2-dimethyl-3R- (2,2-dichlorvinyl) cyclopropane-1R] carboxylate.