CS254993B2 - Insecticide and its efficient component production - Google Patents

Description

The present invention relates to an insecticidal composition comprising more than one pyrethroid as an active ingredient, and to a process for the preparation of such active ingredients.

In the description of the present invention, the spatial configuration of the substituents relative to the chiral carbon atom indicated by the letter is characterized by the letters "S" and "R". The terms "cis" and "trans" refer to the position of the substituents that are attached to the carbon atom "3" of the cyclopropane ring in relation to the spatial configuration of the carbon atom substituents "1" of the cyclopropane ring. The absolute spatial configuration of the substituent that is bonded to the carbon atom of the .1 "cyclopropane ring is designated by the prefix" 1 (R) "and" 1 (SJ ").

In this specification, various enantiomers and pairs of enantiomers are designated by the following abbreviations:

1a mixture of l (R) -cis (S) and l (S) -cis (R)

Ib mixture of 1 (R) -trans (S) and 1 (S) -trans (R) 1c mixture of 1 (R) -cis (R) and 1 (S) -cis (S)

Id mixture of 1 (Rj-trans (R) and 1 (S) -trans- (S)

If l (R) - cis (S)

Ig L (R) -trans (S)

Ih l (S) -cis (R) and l (S) -trans (R)

Of the compounds of formula 1

(I) in which:

X is> chlorine or bromine, the following compounds are commercially useful:

- 'Cypermethrin' of formula II

Ct

(II) which includes all isomers; only isomeric 1 (R) -cis (S) and 1 [S] -cis (R);

- "Deltamethrin" of formula III - "Alphamethrin" of formula II, which includes

house flies (Musea domestica) - certain isomers exhibit high and extraordinary toxicity to certain insects, with the most potent isomers being routinely applied to which includes only the 1 (R) -cis (S) isomer.

The choice of possible isomers for insecticidal activity is based on the experimentally established fact that - particularly according to experiments carried out on the market or synthetically prepared [cf. Fist. Sci. 7, 273 et seq. (1976)].

It is known that the pyrethroid of formula II (known under the generic name, Cypermethrin ') belongs to a valuable group of synthetic pyrethroids and is useful as an insecticide (cf. Hungarian patent specification 170 866). This compound can be prepared by reacting m-phenoxybenzaldehyde cyanohydrin with cyclopropanecarboxylic acid chloride in the presence of a base [cf. Pestic. Sci. 6, 537 et seq. (1975)]. The product thus obtained contains eight stereoisomers, i.e. a mixture of four pairs of enantiomers. When mixtures of cyclopropanecarboxylic acid chlorides with a ratio of 60: 40 trans and cis isomers are used, the mixture contains 18 to 19% enantiomer pair 1a, 21 to 22% enantiomer pair 1c, 26 to 27% enantiomer pair 1b and 33 to 34% pair enantiomers Id.

It is already known that stereoisomers of Cypermethrin have different biological activity. In general, the activity of molecules containing the cis-isomers of cyclopropanecarboxylic acid has been shown to be higher than that of the corresponding trans-derivatives [cf. Fist. Sci. 7, 273. (1976)].

In comparative biological tests of various pyrethroids [cf. Fist. Sci. 9, 112-116 (1978)], cis- and trans-stereoisomers - including the stereoisomeric pairs of Cy.permethrin - were evaluated together.

Comparative tests were carried out on house fly (Musea domestica L.) and leaf beetle (Phaedon cochleariae FabJ). As regards the chloro derivatives, data on the effect of the l (R) -trans (S) ( Ig) and 1 (R) -trans (R) The data shown shows that while the 1 (R) -irans (S) -isomer has strong potency, the 1 (R) -trans (R) -isomer is significantly less potent [ in the efficacy test using Bioresmetrin as a standard (100), the efficacy values are 1,400 and 81 (in the housefly test) and 2,200 and 110 (in the leaf beetle test)]. It is clear that the isomers exhibit antagonism rather than the expected synergism and the degree of antagonism is 1.42 for housefly or 1.43 for blueberry.

Based on the results of these tests and literature data, trans-isomers and mixtures thereof have become of biological interest and research has focused on active cis-derivatives and mixtures thereof. This led to the development of Alphametrin (an isomeric mixture of the 1 (R) -cis (S) and (S) -cis (R) (Ia) chloro derivatives) and Decametrin which consists of only the 1 (R) -cis (S) -isomer (If (bromo derivative).

For this reason, several methods for preparing mixtures enriched in cis isomers are also known from known mixtures of Cypermethrin isomers.

The present invention relates to an insecticidal composition comprising more than one active ingredient, characterized in that it contains from 0.001 to 99% by weight of the synthetic pyrethroids of the formula I as active ingredient.

in which

X is chlorine or bromine, of which at least 95% of the isomers are at least 95% of the mixture of enantiomeric pairs 1a: 1b-55: 45 to 25: 75, wherein la represents a mixture of 1 (R) -cis (S) and (S) 1-cis (R) and 1b represent a mixture of 1 (R) -trans (S) and (S) -trans (R), optionally in admixture with an activator and / or adjuvants, preferably an antioxidant, stabilizer, wetting agent, emulsifier a dispersant, anti-foaming agent, diluent, carrier and / or filler, the auxiliary components being present in an amount of up to 100% by weight.

The invention is based on the recognition that the isomeric mixture 1a + 1b has valuable and advantageous biological properties. These properties are surprising and unexpected, although research has already been carried out in the field of pyrethroids of the general formula I and a number of publications and patent publications have been published.

It is further known that mixtures enriched in cis-isomers can be prepared by crystallization from solutions containing other isomers [cf. C.A. 95, 1981, Kokai No. 57,755/81]. A substantially pure 1: 1 mixture of 1 (R) -cis (S) and (S) -cis (R) isomers can be separated from the mixture containing other cis-isomers using suitable solvents (cf. British Pat. (2,064,528). The isomeric mixture 1a is described to be very effective. For the preparation of intermediate cis-cyclopropanecarboxylic acids containing cis-isomers above a certain level (about 50%), special so-called "high cis" syntheses have been developed. However, these methods are somewhat expensive (cf. Angew. Chem. Ie, 24, (11), 996 (1985)).

The invention is based on the discovery that when using the combination of the l (Rptrans (S) -isomer Ig (which is the most potent trans-isomer of compounds of formula II)) and the (S) -trans (R) -isomer (II) active isomers from the remaining seven isomers), no antagonistic properties observed for the previously disclosed isomeric pairs were observed.

In addition, there is a synergistic effect compared to Ig meres.

The above method for selecting isomers of synthetic pyrethroids in order to obtain a new active ingredient with superior properties.

This new active ingredient, as opposed to the previously known, is:

with the sum effect of pure isolates, when the self-reported finding is used, the new isomers have a number of advantages, such as ka;

lower toxicity to warm-blooded and more man-made processes;

- minor damage to useful parasites and bees.

Novel compositions containing an isomeric mixture of Ib are described in U.S. Pat. No. 254,994.

The invention is based on the further discovery that the order of biological activities previously observed for the individual isomers and the already known rules described for isomeric pairs do not absolutely apply to other isomeric pairs.

We have therefore attempted to compare and simultaneously test a pair of Ib enantiomers [i. 1 (R) -trans- (S) + 1 (S) -trans (R)], which in our experiments proved to be effective with other isomers. This comparison showed that the synergism observed between members of the pair of enantiomers of Ib (ie, between Ig and Ii) does not occur between members of the corresponding pair of cis-enantiomers (Ia, (ie, If and Ih).

Further, the invention is based on the finding that while of the isomers I (R) -cis (S) (i.e. I (E) and the isomers I (R) -trans (S) ie Ig), it is generally the isomer If more effectively, this is the case with respect to the enantiomeric pair Ia and Ib, on the contrary for certain types of biological activity.

As a result of the above investigations, we have surprisingly realized that a simultaneous use of the enantiomeric pairs Ia and Ib produces a synergistic effect, i.e., the effect of the combination is greater than the combined effect of both enantiomeric pairs when used alone.

It has been found that the synergistic biological effect of mixtures I and Ib is not limited to such mixtures in which Ib is more effective than

Ia. Thus, by using these two enantiomeric pairs on the Colorado potato beetle (Leptinotarsa decemlineata), there is considerable synergism. These results are discussed in more detail in the examples.

Based on the above findings, we have made a new selection of the known isomer mixtures which have led to the novel composition of the invention.

In addition to the synergistic effect, the composition according to the invention also has a number of other advantages and thus represents an excellent enrichment of the prior art. It is important that the compositions of the invention are less toxic to mammals than previously known compositions of similar efficacy. This is exemplified by any so-called selectivity index (517 and 747, respectively), which is the ratio of the approximate LD 50 values measured in rats when administered orally (280 and 355 mg / kg) and in domestic flies when administered topically (0.54 and 7, respectively). 0.48 mg / kg). This selectivity index for mixture Ia 50 / 0.45 ~ 111.

This synergistic effect can also be observed on mites (cf. example of biological activity # 19), so that the compositions of the invention are also useful as acaricidal agents. The compositions of the invention have low toxicity to bees and do not harm useful entophages and parasites (cf. biological examples 25 and 26). The above-mentioned advantageous properties are due to the repellent effect, the preferred persistence and the inherent activity of the active ingredient.

The above properties allow the use of the mixture of enantiomeric pairs of the present invention in Integrated Plant Protection (IPM).

The economic benefits of the compositions of the present invention are at least as important as their biological activity. The preparation of the pure cis-enantiomeric pair I and requires very expensive synthesis methods or is associated with the loss of the transcompounds that arise in the reaction mixture. In contrast, the invention allows the use of virtually all of the components Ia and Ib of the reaction mixture resulting from the most economical syntheses. (The degree of efficiency naturally depends on the synthetic methods used and the ratio of the components Ia and Ib in the resulting mixture).

The insecticidal compositions according to the invention comprising the isomeric pairs Ia and Ib in admixture with known additives can be formulated for ready-to-use forms.

The compositions according to the invention may be represented by the so-called ULV compositions (utra-low-volume), sprays, dispersible powders, granules, wettable or other powders, emulsions, etc. These compositions are suitable for pesticide treatment of vegetable, vineyard, garden, cereal and other cultures grown on large areas. Due to their low toxicity, the compositions according to the invention are particularly suitable for combating flying insects and pests with hidden ways of life, the walls of stables, and for treating pastures and ald.

As mentioned above, the present invention also relates to the use of the above-defined insecticidal compositions. It is preferred to use the formulations under field conditions with application of 2 to 25 g of active ingredient per ha.

The insecticide compositions of the present invention may contain, in addition to isomertuch pairs la p lb, activators and other cheeses. active ingredients, for example piperoyl. Said additives increase the efficacy of the active ingredient without increasing the warm-blooded toxicity.

According to a preferred embodiment of the present invention, the insecticidal compositions are used in the form of a dispersible granulate comprising 1 to 99% by weight of active ingredient in admixture with 99 to 1% by weight of a suitable additive. For example, 0.1 to 1% by weight of anionic and / or non-ionic surfactants, such as alkali metal alkylarylsulfonic acid salts, alkali metal formaldehyde alkylarylsulfonic acid condensation salts, alkyl aryl polyglycol ethers, sulfated alcohols with long chain, polyethylene oxide sulfated fatty alcohols, polyols of fatty acid polyesters and various other commercially available surfactants.

The insecticidal compositions of the present invention may also be prepared in the form of concentrates containing preferably 5 to 50% by weight of the active ingredient in admixture with 50 already 95% by weight of the ingredients which allow the preparation of a stable emulsion. water.

Furthermore, 1 to 20% by weight of surfactant and / or 0.1 to 5% by weight of stabilizer can be used as additives and the mixture is preferably made up to 100% by weight with an organic solvent.

Mixtures of anionic and non-ionic surfactants are preferably used as surfactants. Preferred surfactants are: calcium salts of alkylarylsuhonic acids, mono- and diesters of phosphoric acid, nonyl- and tributylphenol polyglycol ethers, fatty alcohol adducts with ethylene oxide, polyglycol esters of fatty acids, ethylene oxide block polymers with propylene oxide, etc.

The solvent used is preferably a mixture of aromatic hydrocarbons (e.g. xylenes), cyclohexanol, butanol, methyl ethyl ketone, isopropyl alcohol, etc.

The compositions of the present invention may also contain other synergistically active ingredients that allow the amount of active ingredient to be reduced. For this purpose, piperonyl butoxide may be advantageously used.

The present invention further provides a process for the preparation of an insecticidally active ingredient comprising, out of the eight possible isomers of the synthetic pyrethroids of formula I wherein X is chlorine or bromine, only a mixture of enantiomeric pairs 1a: 1b in a ratio of 55: 45 to 25: 75; 1a represents a mixture of isomers 1 (R) -cis (S) and (S) -cis (R) and 1b represents a mixture of isomers 1 (R) -trans (S) and (S) -trans (R) consisting in that

a) prepare a saturated solution in a protic or apolar aprotic inert organic solvent from a mixture containing pairs of isomers 1a + 1b and other possible isomers and / / and containing isomeric pairs 1a + 1b in a ratio other than that desired, inoculated with this solution a crystal consisting of a mixture of enantiomeric pairs 1a and 1b in a ratio of 55: 45 to 25: 75, and the precipitated crystals are isolated at a temperature between 30 ° C and -30 ° C; or be

b) seeding a mixture containing, in addition to the isomeric pairs 1a-J-1b, further isomers and / and containing the isomeric pairs 1a-J-1b in a ratio other than that desired, at a temperature between 10 ^° C and 60 ° C with a seed crystal consisting of a mixture of enantiomeric pairs 1a and 1b in a ratio of 55: 45 to 25: 75, the solution is allowed to crystallize at a temperature between 30 ° C and 1010 ° C and optionally the suspension thus obtained is suspended at a temperature between -10 ° C and -20 ° C in a protic or apolar aprotic inert organic solvent and the precipitated crystals are isolated; or be

(c) add to the solution or melt a mixture containing, in addition to the isomeric pairs la + 1b, other isomers and / and containing isomeric pairs la1b in a ratio other than that required, add an enantiomeric pair la or lb in an amount such that the solution or melt contains isomers in a ratio of 55: 45 to 25: 75, followed by optional crystallization according to variant a) or variant b); or be

d) mixing the enantiomeric pairs 1a and 1b in the desired ratio, optionally in the presence of a protic or apolar aprotic organic solvent, homogenizing and crystallizing, optionally after seeding according to variant a).

According to variant a) of the process according to the invention, it is advantageous to work with hydrocarbons having 1 to 12 carbon atoms, chlorinated hydrocarbons having 1 to 6 carbon atoms, dialkyl ethers having 1 to 5 carbon atoms in alkyl radicals or alcohols having 1 to 10 carbon atoms as organic solvents . Said solvents may be straight or branched chain and cyclic or alicyclic.

It is advantageous to carry out the seeding with a seed crystal in the presence of an antioxidant, in particular tert-butylhydroxytoluene or 2,2,4-trimethylquinoline, and using ethanol, isopropyl alcohol, petroleum ether or hexane as solvent.

In the crystallization, the process is preferably carried out with slow cooling.

According to a preferred embodiment of the process of the invention, a mixture of 60% trans and 40% cis enantiomeric pairs of Cypermethrin (18.2% Ia, 26.8% 1b, 21.8% Ic and 33.2% Id) is used as the starting material; hereinafter referred to as Ie). Said mixture is dissolved in isopropyl alcohol and the solution is seeded with seed crystals consisting of a mixture of Ia and 1b in the presence of 0.01% 2,2,4-trimethylquinoline or tert-butylhydroxytoluene. The crystalline product is obtained in an absolute yield of 35 to 40%. Melting point 63.5-65 ° C. This product contains 40: 60 enantiomeric pairs Ia and 1b and contains 5% enantiomeric pairs Ic and Id as impurities. The product thus obtained may be recrystallized as described above. Thus, a mixture of enantiomeric pairs Ia and 1b can be prepared with a purity above 99%.

Similar results are obtained when mixtures with a different cis / trans ratio are recrystallized.

Cypermethrin, which is used as starting material, can be prepared by esterifying a mixture of cyclopropanecarboxylic acids with a suitable cis / trans ratio.

The following table shows the melting points of mixtures with different cis / trans ratio.

Table

Isomer ratio Melting point cis / trans Ia / Ib (° C): 75 67.0 to 71.5: 70 65.0 to 68.0: 60 63.5 to 65.0: 50 60.5 to 62.0: 45 61.5 to 64.0

The practical feasibility of crystallization in the desired direction greatly depends on the purity of the starting Cypermethrin mixture. If the active ingredient content is less than 95%, the yields decrease. Tar-like impurities may even inhibit crystallization.

Crystallization of the mixture of enantiomeric pairs Ia and 1b of the present invention can also be carried out in the absence of a solvent. Thus, Cypermethrin composition Ia can be seeded with crystals composed of Ia and 1b. In the refrigerator, a mixture of Ia and 1b crystallizes within 1 week. The crystals are isolated by adding ethanol, which is cooled to -20 ° C, to the mixture and filtering off the crystals.

The mixture of enantiomeric pairs Ia + 1b of the present invention can also be prepared by mixing and / or crystallizing Ia and 1b or various amounts thereof, or by mixing and / or crystallizing mixture Ia and 1b, or calculated amount 1b.

The biological activity of the products of the present invention is tested on various insect species. In the test methods, the effect of stereoisomers which are used as a standard and which are prepared by known methods - for example, by chromatographic separation or by chromatographic separation of Cypermethrines prepared from chiral acids - is well known.

The insecticidal compositions of the present invention are environmentally friendly and can be used in particular in homes and stables to combat flying insects and pests with a hidden way of life, as well as to treat forage.

Further details of the invention are contained in the following examples which illustrate the method of manufacture of the active ingredient and in the examples illustrating the biological effects. However, these examples do not limit the scope of the invention in any way.

Examples illustrating the method of manufacture of the active ingredient:

Example 1

100 g of Cypermethrin (consisting of 18,2% Ia according to gas chromatography),

21.8% of Ic, 26.8% of 1b and 33.2% of Id), 0.2 g of potassium hydroxide and 0.2 g of 2,6-di-tert-butyl-4-methylphenol are dissolved in 2000 ml of isopropyl alcohol with stirring at 45 ° C. The resulting solution was slowly cooled to 30 ° C, clarified with activated carbon and filtered at 30 ° C. The colorless solution is seeded with a crystal consisting of 60% of Ib and 40% of la and stirred at -10 ^Q C for 24 hours. The precipitated product is filtered off, washed with isopropyl alcohol and dried in vacuo. 36.02 g of a snow-white crystalline product are thus obtained. 62 DEG-65 DEG C. (uncorrected). According to gas chromatography and thin layer chromatography, the product contains 37% Ia and 58% 1b. Yield 76% (based on the content of the isomers Ia-4b in Cypermethrin used as starting material).

Isomer Ia: R _f = 0.25; Isomer b: R _f = 0.20.

After recrystallization from isopropyl alcohol, 32 g of product are obtained as the first crop. Melting point 63.5-65.0 ° C. The product consists of

39.5% of the isomers Ia and 59.5% of the isomers 1b.

IR (KBr) v _c => a

730, 1735 cm ¹ .

NMR Spectrum (CDCl3): δ (ppm)

1.05 to 2.45 (m, 8H),

5.6 (d, J = HHz, = CH trans 0.6 H),

6.14 (d, J = 8 Hz, = CH cis 0.4H),

6.35 (d, IH);

6.85 to 7.60 (m, 9H).

Example 2

100 g Cypermethrin (27,8% isomer 1a,

21.8% of isomer 1b, 32.1% of isomer 1e and 18.2% of isomer 1d), 0.2 g of potassium hydroxide and 0.2 g of 2,6-di-tert-butyl-4-methylphenol are dissolved in 2000 ml isopropanol with stirring at 45 ° C. The solution obtained is clarified with activated carbon and the mixture is filtered at 30 ° C. The colorless solution was seeded with a seed crystal consisting of 20% of isomers 1b and 80% of isomers 1a and the mixture was stirred at -10 ^° C for 3-6 hours. The precipitated product is filtered off, washed with isopropanol and dried in vacuo. 30 g of a snow-white product are thus obtained. Mp 66-73 ° C.

According to gas chromatography, the product contained 77% of isomers 1 and 19% of isomers 1b. The purity of the product is 96% [by thin layer chromatography, cf. Example 1). After recrystallization from isopropyl alcohol, 26.5 g of a snow-white crystalline product having a melting point of 70 DEG-73 ^DEG C. are obtained first. This product contains 81.5% of isomers 1a and 18% of isomers 1b according to gas chromatography.

IC spectrum (KBr technique): » _e ... _o

730 cm ^-1 .

NMR (Deuterochloroform, Ti in ppm):

1.05 to 2.45 (m, 8H),

5.60 (d, J = 8Hz, --CH trans 0.2H),

6.14 (d, J = 8Hz, = CH cis 0.8H),

6.35 (d, ArCH, 1 H),

6.85 to 7.60 (m, 9H).

Example 3

100 g of a colorless clear transparent oily Cypermethrin (18.2% of the isomers 1a, 21.8% of the isomers Ic, 26.8% of the isomers I-b and

The 33.2% (isomer 1d) is seeded with a seed crystal consisting of 60% isomer 1b and 40% isomer 1a and the solution is then left to crystallize at 7 ° C for 1 week. The resulting mixture was suspended in 100 ml of a 1: 1 mixture of isopropyl alcohol and diisopropyl ether and filtered at -15 degrees Celsius.

The crystals were washed with isopropyl alcohol and dried under vacuum. This gives 40.1 g of a white crystalline product which contains 37.5% of isomers 1a and 59% of isomers 1b. 62.5 - 65 ° C. Yield 85%. After recrystallization from isopropyl alcohol, 36 g of a snow-white crystalline product having a melting point of 63.5 to 65 ° C is obtained as a first crop. IC spectra and NMR spectra are identical to those given in Example 1.

Example 4

100 g of Cypermethrin (18,2% of isomers 1a,

21.8% of the isomers Ic, 26.8% of the isomers 1b, 33.2% of the isomers 1d) and 0.05 g of 2,6-di-tert-butyl-4-methylphenol are dissolved in 100 ml of diisopropyl ether with stirring at temperature Low: 14 ° C. The solution is then clarified by the addition of 2 g of activated carbon. The mixture is filtered and the filtrate is seeded at -15 ° C with a seed crystal of 60% isomer 1b and 40% isomer 1a. The mixture is then allowed to crystallize for 72 hours, the precipitated crystals are filtered off, washed with diisopropyl ether and isopropyl alcohol and dried. 38 g of a snow-white crystalline product are thus obtained. Yield 80.6%. 62 ^DEG- 65 ^DEG C. The product contains

37.5% isomer 1a and 58% isomer 1b.

After recrystallization from isopropyl alcohol, 35 g of a snow-white crystalline product with a melting point of 63.5 DEG-65 DEG C. are obtained first. The ratio of isomers 1a: 1b is 40:60. The physical constants are identical to the physical constants given in Example 1.

Example 5 g of a sample of the product obtained according to Example 2 (ratio of isomers La: 1b = 4: 1) are mixed with 4.60 g, 6 g, 10 g, 16.67 g and 22.0 g of pure 1b seeding crystals. and the mixtures thus obtained are recrystallized as described in Example 1 each time from 10 times the amount of isopropyl alcohol. The following table shows the composition of the mixture and the melting points of the products thus obtained.

Table

la: lb Melting point (° C) 55: 45 <61.5 to 64.0 5: 5 60.5 to 62.0 4: 6 63.5 to 65.0 3: 7 <65.0 to 68.0 25: 75 67.0 to 71.5

Example 6 g of a sample of pure crystalline pair of isomers 1a is mixed with 8.20 g, 10.00 g and 15.00 grams of pure crystalline pair of isomers 1b, and the mixtures thus obtained are homogenized. The crystalline mixtures thus obtained contain isomers 1a + 1b in a ratio of 55: 45, 50: 50 and 40: 60 respectively. The melting points are as follows: 61.5 to 64 ° C, 60.5 to 62 ° C and 63.5 to 65

Example 7 g of a sample of pure crystalline pair of isomers 1a is dissolved in a 10-fold amount of 2334993 isopropyl alcohol and 23.34 g and 23.34 g respectively are added to each sample. 30.0 g of pure crystalline pair of Ib isomers. The resulting solutions are then allowed to crystallize. The precipitated white crystalline products (melting points: 65-68 ° C and 67-71.5 ° C) contain the la: Ib isomers in a ratio of 30:70, respectively. 25: 75. The product thus obtained can be used in the preparation of plant protection products and is suitable as an insecticidally active ingredient.

Example 7 a

The same procedure as described in Example 1 except that 100 g (α-cyano-m-phenoxybenzyl) of 3- ^(2,2! -Dibromvinyl) -2,2-dimethylcyclopropane acid (containing 20% of couples isomers 1a, 20% (pairs of isomers 1c) and 30% of pairs of isomers (1d) are dissolved in 2000 ml of isopropyl alcohol. 30 g of white crystalline product are obtained. 69 ^DEG- 73 ^DEG C. The substance contains 38% of the pairs of isomers 1a and 58% of the pairs of isomers Ib.

Isomer Ia: R _R ~ 0.4;

Ib isomer R _f = 0.37 (on silica gel plates using a mixture of hexane and diethyl ether 6: 1).

NMR spectrum (deuterochloroform, δ values in ppm):

1.20-2.25 (m, 8H),

6.17 (d, CH = trans, 0.6H),

6.70 (d, CH = cis, 0.4H),

6.38 (d, IH);

6.85 to 7.60 (m, 9H).

Recrystallization from a ten-fold amount of isopropyl alcohol according to the same method yielded 26 g of a white crystalline product. Mp 70-75 ° C. The substance contains 39% of the pairs of isomers 1a and 60% of the pairs of isomers Ib.

Example 7 b

The procedure is the same as described in Example 2 except that 100 g of 3- (2 ', 2'-dibromvinyl) -2,2-dimethylcyclopropanecarboxylic acid (N-cyano-m-phenoxybenzyl) ester (containing 20%) pairs of isomers 1a, 20% of the pairs of isomers 1c, 30% of the pairs of isomers Ib and 30% of the pairs of isomers 1d) are dissolved in 2000 ml of isopropyl alcohol. 18 g of a white crystalline product are thus obtained. Melting point 80-85 ° C. It contains 78% of the pairs of isomers 1a and 19% of the pairs of isomers Ib.

The material thus obtained is recrystallized from a ten-fold amount of isopropyl alcohol by the same method. 16 g of white crystalline product are thus obtained, m.p. 82-85.5 ° C. The substance contains 81.5% pairs of isomers 1a and 18% pairs of isomers Ib,

Examples of composition and formulation:

Example 8

К 166,2 g of perlite (d _max = 120 μΐη), 0,8 g of synthetic silicic acid (Aerosil 300) in a high-speed fluidisation stirrer add 20 g of Cypermethrin, ie a mixture of enantiomeric la: Ib pairs of 4: 6 and 2 g of a fatty alcohol polyglycol ether and the mixture is homogenized. The powder mixture obtained is first ground in a mechanical mill and then ground in an air jet mill, then 5 g of octylphenol polyglycol ether (20 units of ethylene oxide) and 2 g of sulfosuccinate are added to the mixture in a high speed stirrer. A wettable powder is obtained, which is then tested for suspension stability. The wetting time was 23 seconds, the buoyancy = 89% (WHO standard).

Example 9 g of a mixture of Cypermethrin, i.e. enantiomeric pairs 1a: Ib = 3: 7 and 0.3 g of polyglycol ether of fatty alcohol, is applied to a talc homogenizer (d _inax = = 15 μηι) by adjusting the pH to 6.5 using buffer -a with the addition of synthetic silicic acid (Aerosil 200) and 193.9 g of potassium phosphate and sodium phosphate. While stirring, 1 g of dioctylsulfosuccinate and 1 g of polyglycol ether of fatty alcohol in the sulphonated state are added to the mixture, and the mixture is then milled until a mean particle size of 20 μπι is obtained. An easily wettable powder is thus obtained.

Example 10 g of a mixture of Cypermethrin, i.e. a mixture of enantiomeric pairs 1a: Ib - 55: 45, is dissolved in a mixture of 21.25 g of xylene and 42.5 g of n-propanol with gentle stirring. To this solution is added a mixture of 4 g of ethoxylated alkylphenol and a linear salt of a linear alkylarylsulfonate and a mixture of 6 g of ethoxylated amine and an alkali salt of a linear alkylarylsulfonate and stirred until complete dissolution, followed by 21.25 g of water. A transparent solution is obtained which is stable for a long time at temperatures between 0 ° C and 50 ° C. This solution may optionally be diluted with water to any concentration to form an emulsion with 0.8 to 1.5 μΐη particles.

Example 11 g of a mixture of Cypermethrin, i.e. a mixture of enantiomeric pairs Ia: Ib = 25: 75, is dissolved in a mixture of 75 g of xylene and 10 g of aliphatic oil, followed by the addition of 7.5 g of ethoxylated alkylphenol and linear alkylarylsulfonate calcium. and 2.5 g of a mixture of ethoxylated fatty acid 254993 liner and a linear alkylarylsulfonate salt. According to the CIPAC method, the emulsion concentrate is stable for 170 hours.

Example 12

In the mechanical granulate, a mixture of enantiomeric pairs of Cypermethrin, i.e. a 50:50 mixture of isomers Ia and 1b, is mixed with 1500 g of alkali metal polycarboxylate, 500 g of sodium dodecylbenzenesulfonic acid, 500 g of sucrose and 7200 g of kaolin. The powder mixture is then mixed with 8,300 ml of water using a high shear strength stirrer (speed 10 m / s) and then the spray is dried. The particle size distribution is as follows 0.1 to 0.4 mm = 95%. The buoyancy is 98 ° / o (WHO method).

Example 13

Emulsifiable concentrates are prepared by mixing the following ingredients:

Emulsion Concentrate (10)

Component Amount kg / kg of isomeric pair la: lb = = 40: 600,105

Cyclohexanol0,290

Atlox 3,386 В0.020

Atlox 3,400 В0,045 mineral oil (odorless) 0,540

Emulsion Concentrate (5)

Component

Amount kg / kg of isomeric pair Ia: 1b = = 40: 600.050

Cyclohexanol0,290

Atlox 3,386 В0.020

Atlox 3,400 В0,045 mineral oil (odorless) 0,595

Examples illustrating biological activity:

Example 14

Table 1 shows the activity of various stereoisomers of Cypermethrin on housefly (Musea domestica).

The test is performed as follows:

The active ingredient is dissolved in a 1: 2 mixture of oil and acetone. The solutions of the corresponding stereoisomers or enantiomeric pairs are then impregnated with a filter paper roll (Whatman No. 1, 9 cm diameter). The acetone is then evaporated and then the test insects are placed on filter paper rolls in petri dishes. Three parallel experiments are performed at each concentration and 15 insect samples are placed in a Petri dish. Percent mortality is determined after 24 hours. The corrected mortality percentage is calculated using the Abbot formula.

Table 1

Dose (mg / bowl)

Stereoisomer

Cypermethrin 0.04 0.11 mortality 0.33 in% after 24 hours 1.00 3.00 If 68 93 100 ALIGN! 100 ALIGN! 100 ALIGN! Ia 44 84 100 ALIGN! 100 ALIGN! 100 ALIGN! Ig 48 68 83 100 ALIGN! 100 ALIGN! lb 32 62 95 100 ALIGN! 100 ALIGN! Ia: lb = = 40:60 41 81 100 ALIGN! 100 ALIGN! 100 ALIGN!

According to this test, the activity of the mixture Ia - 1 - 1b corresponds to that of the pure isomers Ia.

Example 15 The potency reported in Example 14 due to the synergistic effect of the trans isomers.

Table 2 shows the effect on darkling (Tribolum confusam).

As can be seen from Table 2, it is increasing

Table 2

Active ingredient Dose (mg / bowl)

0.11 0.33 1.00 3.00 Mortality in% after 24 hours

l (S) -cis (R) (lh) 0 38 80 100 ALIGN! l (R) - cis (S) (If) 80 100 ALIGN! 100 ALIGN! 100 ALIGN! la 2.2 65 94 100 ALIGN! l (S1-trans (R) (li) 0 0 71 90 l (R) -trans (S) (lg) 70 92 100 ALIGN! 100 ALIGN! lb 64 89 100 ALIGN! 100 ALIGN! la: lb == 40:60 61 89 100 ALIGN! 100 ALIGN!

In Example 18, the examples of another insect species show that the enantiomeric pair 1b of the present invention is more effective than the enantiomeric pair 1a. Increased efficacy is demonstrated not only by mortality within 24 hours, but also by the fact that the toxic effect manifests more rapidly.

Example. 16

Table 3 shows the insecticidal effect of a mixture of enantiomeric pairs 1a and 1b in varying proportions in a test for darkling (Tribolium confusum). The method of performing the assay is described in Example 14.

Table 3 la: lb Dose (mg / dish)

0.02 0,06 0,25 mortality in% after 24 hours 1.00 10: 0 0 14 54 100 ALIGN! 5: : 5 0 43 100 100 ALIGN! 4: 6 14 53 100 100 ALIGN! 3: : 7 20 May 81 100 100 ALIGN! 0: 10 8 46 100 100 ALIGN!

The above data clearly demonstrate the synergism between the enantiomeric pairs 1a and 1b.

Example 17

According to a further evaluation of the effects of the present invention, it has been found that when combining a mixture of enantiomeric pairs 1a and 1b with conventional pyrethroid synergists (e.g. with piperonyl butaxide, NIA 16 388 etc.), the efficacy increase is higher than conventional values (cf. Example 16). ).

Table 4 shows the efficacy on Colorado potato beetle (Leptinotarsa decemlineata).

Test samples are dissolved in 2-ethoxyethanol. 1 drop of solution (0.3 μΐ) is applied to the abdominal part of the imago. Each treatment was performed using two parallel experiments and 10 specimens of test insects for each dose. Mortality is determined after 48 hours.

Table 4

Active ingredient

Dose (^ g / Colorado beetle)

0.05 0.10 0.20 0 _; 40 mortality in percent after 24 h

la 50 55 75 80 lb 0 25 75 85 LA: IB - 4: 6 45 60 70 80 la: lb = 3: 7 45 65 75 85 Deltametrin 45 60 75 85 Cypermethrin 0 20 May 45 75

enantiomeric pair lb. Mixtures of enantiomeric pairs 1a and 1b exhibit the same activity as Deltametrin.

Synergism can be observed between the enantiomeric pairs 1a and 1b, although the enantiomeric pair 1a is more potent than the one (Tribolium confusum), the house fly (Musea domestica) and the buzzard (Lucillia sericata). The procedure described in Example 14 is used. The results of this test are summarized in Table 5 below.

Example 18

The comparative test between the enantiomeric pair la, Ib and the la: Ib mixture at a ratio of 40:60 is carried out on a bean beetle (Acanthoscelides obtectus), a storage beetle Table 5

Dr u h E n n i n o or n i n few 0.02 Acanthoscelila 10 des obtectus Ib 32 (imago) Ia: Ib = 4: 6 30 Tribolium conla 0 fusum (imago) Ib 14 la: Ib = 4: 6 16 Musea domesticla 36 (Imago) Ib 0 la: Ib = 4: 6 25 Lucillia sericatala 0 (Imago) Ib 22nd la: Ib = 4: 6 18 Example 19 Efficiency of stereoisomer pairs Cyperinethri- change as a function of time on the darkness of the warehouse (Trifolium confusum)

The specimens of the darkling beetle (Trifolium confusum) (imago) are placed in Pe-

0.07 Dose (mg / bowl) 2,0 6Ό 0.22 mortality 0.67 In percent 37 63 95 100 ALIGN! 100 ALIGN! 55 87 100 ALIGN! 100 ALIGN! 100 ALIGN! 55 90 100 ALIGN! 100 ALIGN! 100 ALIGN! 18 51 100 ALIGN! 100 ALIGN! 100 ALIGN! 73 100 ALIGN! 100 ALIGN! 100 ALIGN! 100 ALIGN! 80 100 ALIGN! 100 ALIGN! 100 ALIGN! 100 ALIGN! 63 88 100 ALIGN! 100 ALIGN! 100 ALIGN! 18 67 100 ALIGN! 100 ALIGN! 100 ALIGN! 45 85 100 ALIGN! 100 ALIGN! 100 ALIGN! 30 29 57 60 65 55 70 75 100 ALIGN! 100 ALIGN! 50 60 75 100 ALIGN! 100 ALIGN!

The plates were run as described in Example 14. Three parallel experiments were performed per dose, and 15 specimens were used per experiment. At the indicated time intervals, the number of insect specimens in the supine position is always calculated and the percentage results are shown in Table 6 below.

ХЗ

Table 6

Pairs of stereoisomers and pairs of enantiomers Time of observation (min) 0.11 Dose (mg / bowl) 0.33 1.00 the percentage of insects that show signs of toxicity 3.00 Ih 30 0 0 0 0 60 0 0 0 8 120 0 0 0 67 180 0 0 0 88 If 30 0 0 48 64 60 0 5 84 100 ALIGN! 120 0 40 100 ALIGN! 100 ALIGN! 180 39 . 61 100 ALIGN! 100 ALIGN! la 30 0 0 0 33 60 0 0 16 88 120 0 14 66 100 ALIGN! 180 10 49 100 ALIGN! 100 ALIGN! if 30 0 0 0 15 Dec 60 0 0 0 70 120 0 0 0 100 ALIGN! 180 0 0 0 100 ALIGN! Ig 30 0 0 15 Dec 68 60 18 34 98 100 ALIGN! 120 30 70 100 ALIGN! 100 ALIGN! 180 34 84 100 ALIGN! 100 ALIGN! [0057] Ib 30 0 0 47 61 60 0 21 82 100 ALIGN! 120 23 100 ALIGN! 10П 100 ALIGN! 180 56 100 ALIGN! 100 ALIGN! 100 ALIGN! LA: Ib - 4: 6 30 0 0 50 55 60 15 Dec 85 85 100 ALIGN! 120 30 100 ALIGN! 1.00 100 ALIGN! 180 55 100 ALIGN! 100 ALIGN! 100 ALIGN!

Example 20

Trifolium confusum is treated in an analogous manner to that described in Example 14. As a synergist, piperonylbutoxide is used at a dose of 0.5 mg / dish.

The results are summarized in Table 7 below.

Table 7

Stereoisomer Dose (mg / bowl)

Cypermethrin 0.4 0.2 0.1 0.05 0.025 Percent mortality after 24 hours

la 96 53 12 0 0 la + PBO 100 ALIGN! 58 16 0 0 la + Ib 100 ALIGN! 90 57 18 0 la 'p Ib + PBO 100 ALIGN! 95 75 43 7

PBO = piperonyl butoxide

Example 21

The active ingredients are dissolved in 2-ethoxyethanol and the solutions obtained are applied in

From these values, it can be seen that the mixture of enantiomers Ia and Ib can be synergized to a greater extent than enantiomer Ia.

(Ia: Ib = 4: 6).

in the form of 0.2 µl droplets on the back of Hyphantria cunea in the 7th to 8th larval stages. Treated insect specimens are placed on strawberry leaves in Petrlho dishes. For each dose, the test is repeated in two parallel experiments using 10 test insects per dose. After 24 hours, the number of killed insects is counted and the percent mortality is calculated. The results of this test are summarized in Table 8 below.

Table 8

Active ingredient 0,023 0,047 Dose (^ g / larva) 0,094 0.188 0.375 Ia 40 60 65 80 90 [0057] Ib 10 15 Dec 30 70 80 Ia: Ib = 4: 6 40 50 55 65 75 Cypermethrin 0 10 25 50 75

Example 22

Example 23

Leaves that are contaminated by the spider mite (Tetranychus urtlcae) are sprayed with the active ingredient using a sprayer. After 24 hours, mortality was determined and compared to mortality on untreated leaves.

Table 9

Active ingredient

Approximate values of LDsu (PPm)

Ia 0,056 [0057] Ib 0.340 Ia: Ib = 4: 6 0,060 Cypermethrin 0.120 Deltamethrin 0,1'85

The emulsion concentrates (5) prepared according to Example 12 were diluted with 50X, 100X, 200X, 400X, 800X and 1600X with water and 0.5 ml each sprayed onto a glass plate. After the spray layer has dried, 10 images of Leptinotarsa decemlineata are placed on each glass plate and the insects are covered with a Petri dish. All assays are performed using 6 doses and 3 parallel experiments for each dose. The killed insects are counted after 48 hours. The results are summarized in Table 10.

Table 10

Emulsion Concentrate (5) Diluted

1 600 X 800 X 400 X mortality 200 X In percent 100 X Ia 0 27 Mar: 53 63 87 Ia: Ib = 4: 6 0 33 53 73 80 Deltamethrin 7 35 53 67 83 Cypermethrin 0 17 33 50 67

100 ALIGN!

Example 24

The glass plates are sprayed with emulsion concentrates (5) prepared according to Example 13 in an analogous manner to that described in Example 23. After the spray layer has dried, 10 specimens of Acanthoscelides obtectus (imago) are placed on each plate and the test insects are placed. to Petri dishes. The test is performed using 6 doses, with 3 parallel experiments performed for each dose. The test results are summarized in Table 11.

Table 11

Emulsion Concentrate (5)

Diluted

1600X 800 X 400 X mortality v 200 X percent 100 X 50 X Ia 0 13 27 Mar: 33 50 70 Ia: Ib = 4: 6 10 17 30 37 53 70 Deltamethrin 7 13 20 May 37 57 75 Cypermethrin 0 3 10 20 May 45 ' 60

234993

Example 25 Bean plants infected with peach aphid (Myzus persicae) are grown in one pot at 6 days of age. At 12 days of age, the strongly and uniformly infected plants are selected and sprayed with freshly prepared emulsions prepared from the emulsion concentrates of Example 13, until the dripping stage. Each treatment is performed for 3 doses (active ingredient concentrations 2.5, 5 and 10 ppm) and 4 parallel experiments (1 pot per 1 parallel experiment) are used for each dose. On the second, fourth and eighth days after treatment, the aphids are swept off with a fine plant brush on white paper and the number of live insects is counted. The results are summarized in Table 12 below.

Table 12

Emulsion Concentrate (5) Concentration Average number of specimens (PPm) aphids for 1 flower pot days after treatment 2 4 8

Ia 2.5 44 83 245 5.0 22nd 29 90 10.0 8 ^{17 30} Ia: Ib = 4: 6 2.5 38 71 251 5.0 21 32 82 10.0 10- 11 21 Deltamethrin 2.5 26 47 137 5,0 ' 13 19 Dec 29 10.0 6 11 23 control 1 850 2 780 4120

Example 26

Tomato plants previously grown in pots are sprayed with a suspension of the active ingredient consisting of a mixture of acetone and water. The treated plants are placed in a chamber and infected with the larvae of Colorado potato beetle (Leptinotarsa decemlineata) in

Larval stage. After 6 hours, the percentage of paralleled larvae falling from the plants was determined as a percentage. The results are summarized in Table 13 below.

Table 13

Concentration (ppm)

Ia Ia: Ib = 4: 6 percent of the larvae paralleled

1000

200

100 ALIGN!

100 ALIGN!

100 ALIGN!

100 ALIGN!

Example 2 7

The treatment is carried out on a plot of 25 m ² which is heavily infested with Colorado potato beetle (Leptinotarsa decemlineata). The 10 plants per plot are specifically labeled; the number of specimens of Colorado potato beetle is predetermined on these plants. (Only second-generation adults are considered during the pest assessment, as the larval stage 3 and 4 larval stage ratios are negligible at the time of the test.) Treatment is performed on plots of 25 m ² using 10 g of active ingredient per hectare with aqueous suspensions of the formulations described in Example 10. Three parallel experiments were carried out for each dose. The test is evaluated by counting live insect specimens on the labeled plants. The mean values of the three parallel tests are shown in Table 14.

2549

Table 14

Active ingredient Average number

Ia171

Ia: Ib = 4: 6213

Deltamethrln181 control211

Example 28

Aphidinus matricariae adults test - residual protective effect

The tests are carried out in glass containers onto the walls of which the active substance is applied. Adult residues of Aphidinus matricariae are exposed to the remnants of this active ingredient and the number of surviving insect specimens is determined.

The treatment is carried out with the active substances to be tested and with water (control experiment).

Each experiment is repeated at least three times.

live specimens on 10 plants time after treatment (days)

139

925

422

1019

206 179183

The size of the treated area is represented by the area of the interior of the glass container.

Parasites of known age (24 hours) are used.

The products to be tested are applied to the interior of the glass container at a concentration of 5 and 1 ppm.

Ten female Aphidinus matricariae specimens and honey as food are placed in each of the glass containers. After 1, 5 and 24 hours, the number of surviving specimens was determined in independent experiments. The total number of surviving specimens for each vessel was determined. The results are shown in Table 15.

Table 15

Concentration ppm 1 ppm h 1 h 5 h 24 h

Ia

Ia: Ib = 4: 6 Deltamethrin

100 ALIGN! 100 ALIGN! 100 ALIGN! 9'6 100 ALIGN! 50 90 '63 100 ALIGN! 20 May 100 ALIGN! 85

Example 29

Direct contact effect on Aphidinus matricariae pupae

Adult pupae of Aphidinus jnatricariae on pepper leaves are placed in petri dishes and sprayed with active ingredients. Pepper leaves are used that have pupae in the stage 2 to 3 days before hatching. The leaves are placed on a moistened filter paper in a plastic petri dish.

Table 16

Active substance ppm

The treatment is carried out in the same manner as in Example 28.

The leaf pieces are transferred after treatment to the bottom of transparent Petri dishes. The dishes are stored in an air-conditioned room at 70% relative humidity, 20 ° C and a 16-hour light and 8-hour dark cycle. Surviving pupae hatch after 2 to 3 days; The number of live and killed specimens of the test insects is determined.

The test results are shown in Table 16.

Concentration ppm 5 ppm 1 ppm mortality in%

Ia: Ib = 4: 6 Deltamethrin Ia control

14,3 00

75.0 33.00

77.0 12.50

ООО

Claims (9)

An insecticidal composition comprising more than one active ingredient, characterized in that it comprises as active ingredient from 0.001 to 99% by weight of a synthetic pyrethroid of the general formula I in which: X is chlorine or bromine, of which the eight possible isomers are at least 95% of a 55: 45 to 25: 75 mixture of enantiomeric pairs Ia: 1b, wherein: Ia represents a mixture of 1 (R) -cis (S) and 1 (SJ-cis (R)) and 1b represents a mixture of 1 (R) -trans (S) and 1 (SJ-trans (R), optionally mixed with an activator or and with auxiliary components, preferably an antioxidant, stabilizer, wetting agent, emulsifier, dispersant, anti-foaming agent, diluent, carrier or / and filler, which auxiliary components are present in an amount of up to 100% by weight. 2. A composition according to claim 1, comprising as an active mixture a 40: 60 enantiomeric pair Ia: 1b. 3. Composition according to claim 1, characterized in that it contains as active ingredient a mixture of enantiomeric pairs Ia: 1b in a ratio of 30: : 70. 4. A composition according to claim 1 comprising a 50: 50 mixture of the enantiomeric pairs Ia: 1b. A process for the preparation of an insecticidally active ingredient comprising, out of the 8 possible isomers of the synthetic pyrethroids of formula I, wherein X is chlorine or bromine, only a mixture of enantiomeric pairs Ia: 1b in a ratio of 55:45 to 25:75, wherein Ia is a mixture of isomers 1 (R) -cis (S) and (S) -cis (R) and 1b is a mixture of isomers of 1 (R) -trans (S) and (S) -trans (R), characterized in that a) prepare a saturated solution in a protic or apolar aprotic inert organic solvent from a mixture containing isomers of Ia + 1b and other possible isomers and / or containing isomeric pairs Ia + 1b in a ratio other than that required, inoculated with a crystal consisting of a mixture of enantiomeric pairs Ia and 1b in a ratio of 55: 45 to 25: 75. and the precipitated crystals are isolated at a temperature between 30 and -30 ° C, or b) inoculate the melt of a mixture containing more than the isomeric pairs Ia-j-1b in addition to the isomeric pairs Ia-j-1b and / or containing the isomeric pairs Ia-1b in a ratio other than that desired at a temperature between 10 and 60 ° C Ia and 1b in a ratio of 55: 45 to 25: 75, the solution is allowed to crystallize at a temperature of between 30 and -10 ° C and optionally the suspension thus obtained is suspended at a temperature of between -10 and -20 ° C in a protic or apolar aprotic inert organic the solvent and the precipitated crystals are isolated or collected (c) add to the solution or melt of a mixture containing, in addition to the isomeric pairs Ia + 1b, other isomers and / and containing isomeric pairs Ia "|" lb in a ratio other than that required, add enantiomeric pair Ia or lb in such quantity; if the solution or melt contains isomers in a ratio of 55: 45 to 25: 75, whereupon the crystallizers according to variant a) or variant b) are optionally carried out, or is crystallized. d) mixing the enantiomeric pairs Ia and 1b in the desired ratio, optionally in the presence of a protic or apolar aprotic organic solvent, homogenizing the mixture and carrying out the crystallization, optionally after seeding according to variant a). 6. The process of claim 5, wherein the organic solvent is a hydrocarbon of from 1 to 12 carbon atoms, a chlorinated hydrocarbon of from 1 to 6 carbon atoms, a dialkyl ether of 2 to 6 carbon atoms or an alkanol of 1 to 6 carbon atoms. up to 10 carbon atoms, wherein said solvents may be straight or branched chain and may be cyclic or alicyclic in nature. 7. The method of item 5, variants a), c) or d). characterized in that the inoculation with the crystal is carried out in the presence of an antioxidant. 8. The process of claim 7 wherein the antioxidant is tert-butylhydroxytoluene or 2,2,4-trimethylquinoline. 9. A process according to any one of claims 7 and 8, wherein the solvent is ethanol, petroleum ether or hexane.