LT3464B - Stable arthropodical composition - Google Patents

Abstract

1. Technical Result Increase in stability of the composition. 2. Essence A stable arthropodicidal composition containing stabilizer and as active ingredient cypermethrine of the formula (I) CH O Cl CO2 CH Cl  wherein carbon atoms indicated by 1,3 and  stand a chiral carbon atom and the wavy line indicates cis or trans configuration related to the cyclopropane ring – which contains at least 95% of 1R trans S and 1S trans R (Ib) isomer pair, or mixture of 1R cis S and 1S cis R (Ia) and the isomer pair (Ib) of the ratio (Ia):(Ib) = 55:45-25:75, or the isomer pair Ia or Ib and as a stabilizer non-volatile carboxylic acids of pK1=1-5 such as phtalic acid, succinic acid, tetraric acid, maleic acid, fumaric acid, malonic acid or once or several times substituted alkylated derivatives thereof and/or oxalic acid. 3. Field of Application Organic chemistry. 5 Tables.

Description

The present invention is directed to a stable composition comprising as active compounds mixtures of cypermethrin with the following formula:

the arthropodical component is structurally

(I)

The spatial configuration of substituents having a bond to a chiral carbon atom (represented by the letter ω in the formula) is designated by the symbols S and R. The terms go and trans are used to denote the position of the third carbon atom of the cyclopropane ring. IR and 1S. The following abbreviations are used to designate different enantiomers and pairs of enantiomers:

la the mixture IR will go S and 1S will go R; alphamethrin (Fastac) lb mixture of IR trans S and 1S trans R {trans mix) lc the mixture IR will go R and 1S will go S see mixture of IR trans R and 1S trans S lf AND will go to S ig IR trans S. lh 1S will go R II 1S trans R la + lb asymmetries (Chimix)

This description of the invention relates to such cypermethrin having the structure represented by formula (I):

(I) Goes (la) mixtures of isomers which, out of the theoretically possible 8 isomers of cypermethrin, contain at least 95% of the isomeric pair IR trans S and 1S trans R (lb) or only the isomeric pair IR and 1S will go R (la) and (lb) mixture wherein lb) = 55: 45-25: 75. These mixtures of cypermethrin isomers are prepared from a mixture of cypermethrin isomers having the following isomeric pair (lb) eis and other trans isomers or isomeric pair (la) + (lb) in an undesirable ratio in the presence of an amino base and a solvent. The process of preparing the mixtures takes place:

(a) reacting at 0-25 ° C with vigorous stirring a mixture of the oil or crystalline isomers of the formula (I) having a purity of at least 90% by weight, containing at least 60% of the trans isomers or eis to trans isomers in the ratio 65: 35-15: 85, in a system with a moisture content of up to 0.5%, containing 0.1-0.5 parts by weight of triethylamine or 0.0005-0.01 parts by weight of 1,5-diazobicyclo [4.3.0] non-5-ene (DBN) ) or

1,5-diazobicyclo [5.4.0] undecene (DBU), calculated from the initial weight of the mixture of isomers; in the presence of propanol, which is optionally added to the mixture at the saturation point of the mixture of isomers, in an epimerization reaction such that the ratio of propanol to cypermethrin is between 0.5 and 2 parts by weight, and the crystalline material precipitates out ;

b) after asymmetric conversion, the crystalline mass released is treated with an aqueous acid solution and / or dissolved at 0-70 ° C in the presence of a water-immiscible organic solvent or melted at 60-70 ° C without the addition of any solvent and washed with aqueous acid solution; the organic layer is washed with water, which may contain salts and acids, and / or the crude product is recrystallized from a solvent containing the organic acid;

(c) aldehyde is added to the solution to bind the cyanide but is not necessary;

(d) successive operations are carried out in several refrigeration and heating reactors as well as in a mixing reactor comprising a chain of 2 to 10 reactors.

The temperature of the reactors is controlled in the range of (+) 30 - (-) 25 ° C, with a maximum difference of 10 ° C between adjacent reactors. Initially, 1 part by weight of the final crystalline product is added to each reactor and up to 0.4 parts by weight of the base can also be added. The mixture of each reactor can be diluted by adding 0.4 parts by weight of a protic solvent.

The first reactor is then charged with 1 part by weight of a crude mixture of isomers of the formula (I) having a purity of at least 90%. An additional amount of base (0.4 parts by weight) may be added, up to 0.4 parts by weight of protic solvent may be added, the mixture stirred, and the reaction mixture or part transferred to a second and subsequent reactor, where the protic solvent and the base addition and mixing process can be repeated several times. At this time, green cypermethrin is added to the first reactor continuously or in portions, together with (up to 0.4 parts by weight) protic solvent and / or base. The reaction mixture treated in the above manner passes through the whole reactor chain. At the end of the reactor chain, a suspension of crystalline material is obtained from which crystalline material can be isolated.

The above are useful cypermethrin secticides (EP 205010 and EP 208758).

isomers have inbiological properties

In a known process, the desired mixture of isomers is isolated by crystallization of a mixture of cypermethrin isomers.

Crystallization occurs in the presence of a base that can cause epimerization at the α-carbon atom and, in theory, useless isomers can be converted into the desired product. In organic chemistry this process is known as the Second order asymmetric transformation.

Exclusively in the same manner as used to prepare the isomers, the (la) isomer was obtained from a mixture of ciscipermethrins. The starting material was suspended in excess triethylamine (1.5-3.0) or hot dissolved. To form the crystallization centers in solution, (Ia) having a 1: 1 IR ratio of S and 1 S of R isomers was added to this solution. Upon gradual freezing of the solution or suspension, the material slowly crystallizes. The purity of (la) is 90-95% and the yield is about 80% (EP Nos. 67461 and 109113).

Similar methods for the preparation of (lb) cypermethrin from lb + ld trans isomers were prepared by epimerizing at 30-60 ° C using an organic or inorganic base, or epimerizing, optionally in the presence of organic solvent GB 3464, such as light petroleum, and antioxidant:

To 2,6-ditretbutyl-4-methylphenol.

Subsequent publication states that la, lb and la + lb were obtained by interaction of a suspension of the initial isomers hydrocarbons with a base and a catalyst soluble in this suspension selected from quaternary ammonium compounds, quaternary phosphorus compounds and also crown ether. The suspension was shaken at the temperature needed to effect the conversion and the final isomers were obtained. The propensity to form benzoate ester byproducts has been reduced by adding to the suspension an aldehyde acceptor such as metabisulfite and / or a catalyst, ammonium tetraalkyl halide, dissolved in an aprotic solvent such as organic nitrile. The inorganic base was consumed in solid form or dissolved in water. Sodium cyanide is useful as the base. (PCT Publication WO No. 88/10249).

The disadvantage of this process is the significant degradation of cypermethrin under the proposed reaction conditions. This cleavage is accompanied by the formation of benzoin derivatives represented by the formula (II)

(II)

The proposed molecule-acceptor merely prevents the associated unstable cycle from being a by-product of benzoin derivatives, but permethrin degradation. Another disadvantage mentioned is the release of cyanide, a product of the decomposition of metrine. A further disadvantage is that the treatment of the reaction mixture consisting of several layers complicates the reliable operation of this reaction under industrial conditions. Perhaps this is why the large number of examples covered in this publication do not provide substantive results. The increasing difficulty with the use of mixtures containing the la and lb isomers together can be illustrated in EP-A-040418. 67461 according to which the pair of isomers la was obtained by the conversion of a mixture of isomers (la + lc) to triethylamine. The publication states that the presence of 6 or 10% of the trans isomeric impurities in the starting material reduces the yield of la to 63 or 36%. At higher trans isomers, crystallization does not occur.

According to the known method, a pure mixture (la + lb) can be obtained by selective crystallization of sufficiently pure cypermethrin, under suitable conditions: solvent, temperature and pure crystalline material to form the crystallization centers. The process continues for several weeks. In this way, the la + lb mixture can be obtained in 80% yield, which is calculated as the amount of la + lb from the initial amount of cypermethrin. The disadvantage of this method of production is that other, less bioavailable, isomers of cypermethrin remain available (EP 208 758).

The industrial availability of pure isomeric products (more than 97% active ingredient) is still a problem. When taken in liquorice, formulations containing la cause allergy to human skin, which makes the skin very itchy. Therefore, operation must be simplified.

According to the invention, the epimerization must be carried out in a system having a moisture content of up to 0.5%. According to our results, the catalytic amount of water can influence the formation of benzoin derivatives, the structure of which is expressed by formula (II). In contrast to the methods suggested above, we do not bind degradation products, but do not allow cypermethrin to undergo hydrolytic degradation.

In accordance with the process of the present invention, the industrial production process may be carried out by combining steps a), b) and c) and optionally step d). The result of this production method is the production (with good yield) of stable clean materials as well as a simple, safe process from a technical and human health point of view.

The stages of the proposed technique are further specified as follows:

Step (a) of this process is based on the fact that not only the appropriate base but also the amount of propanol to be added at the appropriate temperature is critical for the success of the second-order asymmetric conversion to maintain the rates of epimerization and crystallization. It has been observed that the addition of a solvent for crystallization, such as isopropanol, to the isomeric mixture of cypermethrin in oil results in a certain degree of decomposition of the solvent under the action of cypermethrin and the mixture is suddenly converted into an emulsion. As the solvent is further added, the resulting emulsion is gradually transferred to the actual solution. The same phenomenon can be observed when the solvent suitable for crystallization has a base. Once the state of saturation or equilibrium is reached, the asymmetric rearrangement can be accomplished more quickly. This phenomenon has not yet been associated with the asymmetric transition process in publications. As the amount of substance formed increases, the conversion slows down but can be accelerated by the addition of propanol (propanol selectively accelerates the crystallization of la and lb). This process is further activated by freezing the mixture.

Equilibrium or saturation is within a narrow range of parameters that influence them, so even small deviations of these parameters affect the composition of the resulting product. For example, raising the temperature from 14-15 ° C to 20 ° C to produce a mixture in which the isomer ratio la: lb = 4: 6 will greatly reduce the yield and instead of the thermodynamically available and expected pair of enantiomers la having a higher melting point (86 ° C), the lb content of the pair of enantiomers will increase. A significant increase in solvent yields the same result. The method of manufacture of the present invention allows the preparation of a material that is up to 30% different from the original composition of cypermethrin going to: trans. This method makes it possible to obtain a product having the desired ratio of isomer concentrations. Mixtures of oily or crystalline cypermethrin isomers may be used as starting material.

By using a crystalline starting material, the epimerization reaction can be accomplished more rapidly, even if the process is not continuous.

The preparation of some of the isomeric pairs of la: lb, which are of importance, is described below.

For mixtures wherein the isomer ratio la: lb = 40: 60 is used as starting material, a mixture based on cypermethrin, wherein the isomer ratio is as follows: (la + lc) = 35-45, (lb + ld) = 50-60% by weight. The reaction proceeds at a temperature of 3-16 ° C depending on the amount of the material, 4-10 days thereafter at a ratio of 1: 0.2-0.3: 1-1.5 for 1: 0.2-0.3: 1-1.5 at a temperature of 1 ° C. days. It is better to start with propanol on the second day and continue until the fifth day.

Then, a mixture of isomers (la + lc) = 40-55, (lb + ld) = 45-55% by weight is used as the starting material for the mixture la: lb = 50: 50% by weight. Isomerization lasts for 1-10 days.

Then, when a mixture of la: lb = 25-30: 75-70% by weight is required, the mixture of isomers used as starting material: (la + lc) = 35-45, (lb + ld) = 50-60% by weight. The asymmetric conversion and dissolution at 25 ° C takes 1-5 days.

In the case where oily cypermethrin is used as starting material, it is preferable to cool the reaction mixture below 0 ° C and to crystallize it from the precursor.

The small amount of isomeric pairs (lc + ld) present in the isolated material can be further reduced by washing the filtered crystalline material. Solvents used for washing: hexane, heptane, petroleum ether, ethanol and / or isopropanol or mixtures of these solvents with the following acids: acetic, phthalic, maleic, fumaric, malonic or alkylated malonic.

The asymmetric conversion can be accomplished in the presence of isopropanol or n-propanol.

An important feature of the production process of the present invention is that during the third reaction period the reaction mixture is gradually cooled below 0 ° C, preferably cooled below -10 - (-25) ° C.

Low levels of basic impurities, such as nitrogen, have been found to influence the epimerization of the final product. The same epimerization can be caused by impurities present in the solvent used, or by the residue of any reagent used in the manufacturing process, or by impurities in the materials added during the preparation of the apparatus. The illustrative tables illustrate how undesirable epimerization can be avoided by the addition of a suitable acid (illustrated by the addition of a small amount of triethylamine) and the stabilization of the resulting materials. The investigations started the process step b).

In step b), the reaction mixture may be acidified or the crystalline suspension may be boiled using a 0.1-0.5 wt% acid solution in water. Aqueous solutions of acids such as hydrochloric, formic or alkylated malonic acid or maleic acid are preferred. These solutions may contain a cyanide-binding agent.

Water-insoluble organic solvents may be used to extract the crystalline suspension. Hexane, cyclohexane, petroleum ether, dichloromethane, dichloroethane, chloroform, carbon tetrachloride, ethyl acetate, benzene, toluene or xylene are the most suitable. The extract is preferably washed with water or water saturated with sodium chloride and / or 0.1% by weight aqueous solution of mineral or organic acid, preferably salt, vinegar, phthalate, pleasant, alkylated pleasant, fumar.

Non-polar and protic solvents, preferably hexane, heptane, petroleum ether, methanol, ethanol, isopropanol or mixtures of solvents with acetic, maleic, fumaric, malonic or alkylated malonic acids, may be used to recrystallize the material.

Crystalline molten or dissolved material is obtained at the end of the sequence of operations. The ratio of isomers in the material remains stable 12 months after production.

In the absence of water, the reaction may be carried out in:. as above, to prevent cypermethrin from degradation. Inhibition of the decomposition process also reduces the amount of cyanide in the reaction mixture.

However, under processing conditions, the reaction mixture may undergo minor degradation due to the long duration of the treatment. Therefore, in step c) of the process of the present invention, it is ensured that the released free cyanide does not endanger safety. Each time a small amount of cyanide is released due to acidification of the medium, aldehyde, a stable cyanogen-binding agent, is added to the reaction mixture to prevent the release of cyanide into ambient air. Formaldehyde is best suited for this purpose. Cyanogen glycolic acid nitrile formed by cyanide bonding may be hydrolysed to glycolic acid in the waste mixture by heating. The treatment of the resulting mixture is non-hazardous.

Second order asymmetric conversion is a heterogeneous equilibrium reaction consisting of two steps. The kinetics of this reaction can only be determined experimentally. In the case described, the process becomes even more complicated as the concentration changes not only during the crystallization but also during subsequent dilution and during the epimerization process the reaction temperature can be increased and then lowered. To determine whether the kinetics of the reaction theoretically allow the reactor chain to be used, we determined the degree of the reaction. The reaction can be described as a second-order reaction with apparent kinetics, which means that the continuous reactor circuit can increase the production efficiency and the degree of conversion, respectively, per unit time.

Step (d) of this process is based on the fact that the kinetics of second order asymmetric conversion of cypermethrin are such that it is more profitable to run the process using a continuous or semi-continuous chain of reactors. The reaction may be continuous or semi-continuous. In the first case, the materials are added or removed continuously, in the second case, the materials are added in portions such that the reactor circuit operates continuously. Several reactor circuits may be arranged in parallel. It is better to make transitions in the reactor circuit. Such connections can be recirculated or bypassed. The advantage of the method is that the efficiency can be increased by the fact that several batch reactors can be used and the degree of asymmetric conversion can be increased. The resulting material can be treated continuously, thereby preventing degradation or aggregation that occurs when the process is stopped. Conversion of a unit quantity of a substance can take place in a shorter time, reducing the risk of degradation. Individual units can be kept at a constant temperature, which saves energy.

The present invention provides stable arthropodic compositions comprising as active ingredient a mixture of isomers of cypermethrin of the formula (I) containing at least 95% by weight of the enantiomeric pair IR eis S and 1S eis R (la) and the enantiomeric pair IR trans S and 1S trans R (lb) in the ratio: la: lb = 55: 45-25: 75 or the la or lb isomeric pair. In these compositions, the stabilizer is an acid or a mixture of acids. Preferred are the volatile carboxylic acids having a pKi of 1-5, such as phthalic, succinic, tartaric, maleic, fumaric, malonic acids, or alkylation derivatives of the said acids and / or oxalic acid containing one or more alkyl radicals. The stabilizer content is 0.001 to 0.1% by weight of the active component.

In step (d) of the proposed process, in the case of continuous or batch feeds, it is expedient to use the following concentrations in the initial reaction mixture: 50-80% by weight of cypermethrin, 1-50% by weight of propanol. 10-20 wt% thyrethylamine or 0.00020.01 wt% DBN or DBU.

It is also important to ensure that at the end of the asymmetric conversion the final reaction mixture contains the following concentrations: 25-45% by weight of cypermethrin, 45-75% by weight of propanol, 4-14% by weight of triethylamine or 0.0002% by weight of DBN or DBU.

During the continuous process, the reaction mixture flow rate should be 50-150 kg / h / liter reactor working volume.

Stabilized solutions or substances containing, as above, cypermethrin isomers in combination with stabilizing acids may be used in admixture with additives used in agricultural pesticide manufacturing, veterinary, human health and / or hygiene purposes (EP 208 758).

Additives, especially bases, which may inhibit the stabilizing effect of acids, should be avoided. If such additives are used, their amount should be estimated by calculating the amount of stabilizing acid needed. Solvents must be selected appropriately.

Further details of the present invention are given in the Examples.

The materials used in the production process and isolated during or at the end of the process were analyzed by high performance liquid chromatography. See. Plant growth regulators and pesticides analytical meLT 3464 B tod. (Analythical Methods for Pesticides and Plants Regulators: XIII, Ed by G. Zweig and J. Sherma,

Academic Press, 1984).

Unless specifically stated, the water content of the materials is less than 0.1% by weight.

example

Preparation of a 40:60 mixture of enantiomeric pairs IR eis S and 1S eis R (la) and an enantiomeric pair IR trans S and 1S trans R (lb) from cypermethrin.

In a device equipped with a magnetic stirrer, in a mixture of 21.7 g of triethylamine and 23.5 g of isopropanol, suspended in 100 g of 90% pure crystalline cypermethrin (melting point = 38-43 ° C, isomer ratio: la = 18.1% by weight) %, lb = 23.1 wt%, lc = 23.5 wt%, ld = 34.3 wt%). Ratio ciper20 metrin: isopropanol 1: 1.495. The mixture was stirred for 24 hours at 16 ° C. The gradually thickening suspension is diluted four times with 31.5 g of isopropanol added every 24 hours. The mixture was then stirred for 24 hours at 0 ° C. The suspension is filtered and the filtrate is washed with 39.3 g of isopropanol,

31.5 g of isopropanol containing 0.25% by weight of acetic acid, followed by 23.5 g of isopropanol. Dry under vacuum at room temperature. 87 g of snow-white crystals are obtained.

3Ό

Melting point: 62-63 ° C

Composition of isomers: la = 38.0 wt%, lb = 59.3 wt%, lc = l, 2 wt%, ld = 0.4 wt%.

Purity: 98.9% by weight

The starting layer is evaporated and the process described above is repeated using 13.5 g of the product obtained and a mixture of 13.0 g of isopropanol and 2.8 g of triethylamine. Ratio Cypermethrin: Isopropanol

1.35: 1.30. At the end of the second step of the process, 7 g of a snow-white crystalline material are obtained.

Melting point: 62-65 ° C

Composition of isomers: la = 48 wt%, lb = 48.2 wt%, lc = l wt%, ld = 0.4 wt%.

Purity: 97.6% by weight.

example

A mixture of IR going S and 1S going R (la) and IR trans S and 1S trans R (lb) at a ratio of 40:60 from cypermethrin can be prepared in the same manner as described in Example 1. Only crystalline cypermethrin should be replaced with 100 g of dense cypermethrin oil (purity: 95.6% by weight, isomer composition: la: 17.6% by weight, lb: 22.6% by weight, lc: 22.9% by weight, ld: 32 , 4% by weight) and the reaction should be carried out at 11 ° C.

Combining the results of the first and second process steps gives 91 g (91%) of a snow-white crystalline material.

Melting point: 62-64 ° C

Composition of isomers: la: 38, lwt%, lb: 58, lwt%, lc: l, lwt%, ld: 0.7wt

Purity: 98% by weight.

O

o ·

Ratios Cypermethrin: Isopropanol the same as in Example 1.

example

Mixture IR of S and 1S of R (la) and IR trans of S and 1S of trans R (lb) in a ratio of 50:50 of cypermethrin can be prepared in the same manner as described in Example 1. In this case only, the starting material is 100 g of crystalline cypermethrin (purity: 98% by weight, la: 22.3% by weight, lb: 20.4% by weight, lc: 26.6% by weight, ld: 28.7% by weight).

Combining the results of the first and second process steps yields 95 g of a snow-white crystalline material.

Melting point: 64.5-65.5 ° C.

Composition of isomers: la: 48.2 wt%, lb: 48.4 wt%, lc: l, l wt%, ld: 0.6 wt%.

Purity: 98.3% by weight.

Ratios Cypermethrin: Isopropanol the same as in Example 1.

example

Preparation of IR eis S and 1S eis R (la) and 1S trans R and IR trans S (lb) from cypermethrin at 25 ° C:

The same starting material, cypermethrin, as in Example 1, is used, only epimerization is carried out at 25 ° C to give 52.1 g of a snow-white crystalline material.

Melting point: 65-68 ° C.

Composition of isomers: la: 28.8% by weight, lb: 67.3% by weight.

lc: 0.8 wt%, ld: 0.3 wt%.

Purity: 97.2% by weight.

Ratios Cypermethrin: Isopropanol the same as in Example 1.

example

IR trans S and 1 S trans R (la) and IR trans S and 1S trans R (lb) are produced from cypermethrin using DBN.

The same starting material is taken, cypermethrin as in Example 1, except that triethylamine is replaced by 0.1 g DBN.

Combining the results of the first and second process steps yields 95 g of white crystalline material.

Melting point: 62-64 ° C.

Isomer composition: la: 39.4 wt%, lb: 57.4 wt%, lc: l, 2 wt%, ld: 0.8 wt%.

Purity: 98.8% by weight.

Ratios Cypermethrin: Isopropanol the same as in Example 1.

example

Preparation of IR eis S and 1S eis R (la) and 40:60 IR trans S and 1S trans R (lb) from cypermethrin using n-propanol.

In a device equipped with a magnetic stirrer, a thermometer and two openings, add 100 g of cypermethrin oil (purity 91.4% by weight, la: 16.6% by weight, lb: 21.5% by weight, lc: 21.8% by weight, ld: 31.5 wt%). The material is stirred for days at 10 to 12 ° C in a mixture of

14.5 g of triethylamine and 24.1 g of n-propanol. After 24 or so. from the start of mixing, the suspension is diluted with a mixture of 14.5 g of triethylamine and 16 g of n-propanol, and the dilution is repeated 3 times with 24.1 g of n-propanol every 24 hours. After the last portion of the solvent is added, the temperature of the reaction mixture is lowered to 5 ° C and stirred for an additional 24 hours. Ratio Cypermethrin: Isopropanol 1: 1.124.

The precipitated crystals are filtered off, washed until no impurities are present, as in Example 1, and the material is dried. The first step of the process yields 82 g of snow-white crystalline material.

Melting point: 62-63 ° C.

Composition of isomers: la: 38.0 wt%, lb: 60.0 wt%, lc: l, 0 wt%, ld: 0.5 wt%.

Purity: 99.5% by weight.

After evaporation of the crystalline crude solution, recrystallize as described in Example 1.

example

Add 300 kg of cypermethrin oil (purity: 92% by weight, composition: (la + lc) = 42% by weight, (lb + ld) +) to a 300 l unit equipped with a controlled refrigeration and steam heating system and a propeller mixer. 50% by weight), 180 kg anhydrous isopropanol (water content max 0.2% by weight), 180 kg anhydrous triethylamine (water content max 0.2% by weight). The mixture is dissolved by stirring. 4 kg of crystalline cypermethrin (la = 38% by weight, lb = 58% by weight) can be added to initiate crystallization at 25 ° C. For asymmetric conversion, the solution is stirred for 18 hours at 3-7 ° C and 228 kg of anhydrous isopropanol are added to the crystallization mixture. The mixture was then stirred at 3-7 ° C for 168 hours. Ratio Cypermethrin: Isopropanol 1.184: 1.

The reaction mixture is then cooled to 0 - (- 5) ° C and stirred for 96 hours. The resulting suspension of crystalline material is divided into four equal portions and filtered under nitrogen pressure. The crystalline mass (120 kg) is washed with anhydrous isopropanol, filtered, filtered through a 4% w / w acetic acid / isopropanol solution and filtered under nitrogen pressure.

The obtained crystals were dried in a vacuum dryer. Dry by heating (40-45 ° C) and stirring with a blender. Drying time 12 hours in the specified conditions. 500 kg of asymmetryin are obtained. Its composition as determined by chromatographic analysis is as follows: (la) = 38.2% by weight, (lb) = 58.3% by weight, (lc) = 0.6% by weight, (ld) = 0.8% by weight .

Purity: 97.9% by weight.

example

The process proceeds as described in Example 1, except that a disk mixer is used and, after a third dilution, 48 hours later, the suspension is diluted a fourth time. The mixture is stirred for 48 hours at 0 ° C and the material is further diluted with 40 ml (31.5 g) of isopropanol. The mixture was then cooled to -5 C ^U is stirred 48 hours at -10 ° C 3464 B temLT Incubation was stirred for 72 hours. According to the description given in Example 1, 90 g of a snow-white crystalline material are obtained. Ratio Cypermethrin: Isopropanol 1: 1.895.

Melting point: 62.5 ^U C.

Composition of isomers: la: 39.0 wt%, lb: 59.5 wt%, lc: 0.6 wt%, ld: 0.2 wt%.

example

The process proceeds as described in Example 1, using only 0.1 g of DBU instead of triethylamine. Combining the first and second process steps yields 94 g of white crystalline material.

Ratios Cypermethrin: Isopropanol the same as in Example 1.

Melting point: 62.5-64 ' ^J C.

Composition of isomers: la: 39.6 wt%, lb: 57.2 wt%, lc: l, 2 wt%, ld: 0.9 wt%.

Purity: 98.9% by weight.

example

The seven 750 ml reactors, equipped with refrigeration and mixing units, are connected in a single circuit. The first reactor is cooled to 0 ° C, the second reactor to 8 ° C, and successive reactors are cooled to 14, 15, 10, 0 and -10 ° C. Add 100 g of the isomers IR eis S and 1S eis R (la) and IR trans S and 1S trans R (lb) to the reactors in the ratio (la): (lb) = 40:60 and at least 95% of crystalline L-cyan-3 -phenoxybenzyl 3- (2,2-dichloro 3434 B vinyl) - 2,2-dimethyl-cyclopropanecarboxylate (cypermethrin). The first and second reactors are also charged with 30 ml of isopropanol and 30 ml of triethylamine, and an additional 40 ml of the third reactor, 80 of the fourth reactor, 160 of the fifth reactor and 200 ml of the seventh reactor. The mixtures are thermostated and stirred vigorously: to the first reactor are added 100 g of 94% pure cypermethrin with a purity of 41:59 in all the isomers and trans isomers, and continuously mixed with 1 ml of isopropanol. The mixtures and after 12 hours 30 ml of triethylamine were added to the first reactor. Half of the diluted mixture goes to the next reactor and the addition of cypermethrin and isopropanol to the first reactor is repeated again. After 12 hours, the reaction mixture is diluted with 30 ml of triethylamine in the first reactor and half of the mixture of the second reactor goes to the third reactor and half of the mixture of the first reactor goes to the second reactor. Then, 100 g of cypermethrin and 30 ml of isopropyl alcohol are again added to the first reactor and, after stirring for 12 hours, the contents of the first reactor are diluted with 30 ml of laminate, 40 ml isopropanol is added to the third reactor and the mixture goes to the third reactor, and half of the mixture of the first reactor goes to the second reactor.

After repeating the feeding of cypermethrin and isopropanol after 12 hours of mixing and material transfer, the contents of the first reactor are diluted with 30 ml of triethylamine and the contents of reactors 3, 4, 5, 6 and 7 (individually) are diluted with 40 ml of isopropanol. , and the material obtained at the end of the reactor chain is filtered. The complete sequence of operations is repeated every 12 hours. The filtered material containing 0.1% w / w formaldehyde was washed with isopropanol containing 0.5% acetic acid and dried at room temperature. Each time 85 g of snow-white crystals are obtained.

Isopropanol: Cypermethrin in individual reactors:

Reactor 1 2 3 4 5 6th 7th Isopropanol 3 3 7 11th 15th 21 23 Cypermethrin 10th 10 10 10th 10th 10th 10th Purity: 97 weight %; 38.5% by weight la ir 58.5 lbs

rio% lb.

Melting point: 63 ° C.

The yield was calculated from the starting material content, 85%.

example

Seven 750 ml reactors with refrigeration units are connected in a circuit. The first reactor is cooled to 2O ^J C, the second - 25 ° C, and the third - to 25 ° C, the fourth to 20 ° C, and the remaining reactors are cooled to a temperature 5 ° C lower than the reactor temperature by standing. Add 100 g of a pair of isomers (lb) containing at least 95% of the final crystalline material to the reactors. Add 30 ml of triethylamine and 30 ml of isopropanol to the first and second reactors. An additional 40 ml isopropanol is added to the third reactor, 80 to the fourth reactor, 120 to the fifth reactor, 180 to the sixth reactor and 200 ml to the seventh reactor. The mixtures are thermostated, with vigorous stirring, and then 100 g of 94% pure cypermethrin oil or alloy of cypermethrin and 30 ml of isopropanol are added to the first reactor. Half of the diluted mixture is transferred to the next reactor and the addition of cypermethrin and isopropanol is repeated. After 12 hours, the mixture of the first reactor is diluted with 30 ml of triethylamine and half of the mixture of the second reactor passes to the third reactor and half of the mixture of the third reactor goes to the fourth reactor. Thereafter, 100 g of cypermethrin and 30 ml of isopropyl alcohol are again fed to the first reactor. After stirring for 12 hours, 30 ml of triethylamine is added to the first reactor and 40 ml of isopropanol to the third reactor. Half of the third reactor mixture goes to the fourth reactor and the second reactor mixture goes to the third reactor. After repeated addition of cypermethrin and isopropanol, after stirring for 12 hours, 30 ml of triethylamine are added to the first reactor, 40 ml of isopropanol are added to reactors 3, 4, 5, 6, and 7, and half of the reactor contents are . The complete sequence of operations is repeated every 12 hours. The filtered material containing 0.05% w / w formaldehyde was washed with isopropanol containing 0.5% phthalic acid and dried at room temperature. Each time 85 g of a snow-white crystalline material is obtained, containing 98% of the pair of isomers la.

Ratios isopropanol: cypermethrin in individual reactors

Reactor 1234567

IΞ 2 P ££ PA ⁿ _? Jj ^s Cypermethrin _3_____3_

10 _7_ _n_ _i5_

Oh

Melting point: 80 ^v C sample

The process proceeds as described in Example 1 except that the starting material used is ciLT 3464 B permethrin containing cis-trans isomers in a ratio of 1: 1 and the crystallization center used being a 1: 1 crystal of la and lb having concentration of at least 95%. 85 g of snow-white crystalline material are obtained. Ratios isopropanol: cypermethrin in individual reactors as in Example 1.

Purity: 97%

Isomer ratio: la: lb = 48: 49

Melting point: 65 ° C sample

The process proceeds as described in Examples 10-13, except that the material obtained at the end of the reactor circuit containing 0.2% by weight of formaldehyde is acidified with 2% by weight of hydrochloric acid in water and extracted with 500 ml of heptane. , rinse hot with 50 ml of 1% hydrochloric acid, 100 ml of water and 100 ml of saturated sodium chloride solution. The mixture is crystallized by gradual freezing to -5C. The precipitate is filtered off and dried. Each time 87 g of white crystalline product are obtained. Ratios isopropanol: cypermethrin the same as in Examples 10, 11.

Purity: 98.5%

Isomer ratio: la: lb = 39.0: 59.5

Melting point: Example 65.5 ° C

The process proceeds as described in Example 10, except that the material obtained at the end of the reactor chain containing 0, 3% by weight of formaldehyde is acidified with 2% by weight of hydrochloric acid. The mixture is extracted with dichloroethane, the organic layer is washed with 50 ml of a 1% hydrochloric acid solution and twice with 100 ml of water, evaporated and dissolved in two volumes of methanol, crystallized by gradual cooling to -5 ° C. Each time 86 g of snow-white crystalline material are obtained. Ratios isopropanol: cypermethrin the same as in Example 10.

Purity: 98% by weight

Isomer ratio: la: lb = 39: 59

Melting point: 63 ° C.

example

The process proceeds as described in Example 10 except that the material obtained at the end of the reactor chain is neutralized with 2% by weight hydrochloric acid, extracted with ethyl acetate and the organic layer is washed 5 times with 50 ml of 0.5% hydrogen phthalic acid in 0, 1% by weight of formaldehyde, after evaporation, is dissolved in two volumes of 2% by weight of phthalic acid and methanol and crystallized by gradual cooling to -5 ° C. The crystals are filtered off and dried. 86 g of snow-white crystals are obtained. Ratios isopropanol: cypermethrin the same as in Example 10.

Purity: 98%

Isomer ratio: la: lb = 39: 59

The ratio of isomers remains unchanged at the end of the 12-month administration period.

Melting point: 63 ° C sample

The process proceeds as described in Example 10 except that 95% pure crystalline cypermethrin having eis and trans isomers in a ratio of 4: 6 is added to the chain-linked reactors at the start of the process. Material is transferred every 24 hours. The suspension obtained at the end of the reactor chain is acidified with an aqueous solution containing 0.4% by weight of formaldehyde and 2% by weight of hydrochloric acid, extracted with 500 ml of 433 g of xylene, washed with 50 ml of 2% by weight aqueous phthalic acid and 100 ml (1%) acid solution. 535 g of a solution of quinmix containing 6.9% of a pair of isomers la, 10.6% of a pair of isomers lb, 0.35% of a pair of isomers lc and 0.28% of a pair of isomers ld are obtained. Ratios isopropanol: cypermethrin the same as in Example 10.

example

The process proceeds as described in Example 10, except that the material obtained at the end of the reactor chain is acidified with an aqueous solution containing 2% by weight of hydrochloric acid and 0.4% by weight of formaldehyde. The mixture was heated to 60 ° C and extracted with 400 ml of light petroleum (100-120). The organic layer is washed with an aqueous solution containing 0.1% by weight of formaldehyde and 0.1% by weight of hydrochloric acid, followed by 50 ml of a solution of 1% by weight of hydrochloric acid and 0.1% by weight of formalin, 50 ml of water and 50 ml of hydrogen containing by weight% diethylmalonic acid. The organic layer is separated and the material is crystallized by slow cooling. Filtration and drying gave 88 g of a snow-white crystalline mixture of isomers, with la: lb = 39.0: 59.5. Ratios isopropanol: cypermethrin are the same as in Example 10.

Purity: 98%

Melting point: 65'C.

example

The process proceeds as described in Example 17, except that after washing with a solution of malonic acid, 50 ml of water is used for the final step of washing and the organic layer is separated. To the solution is added 0.2 ml of isopropanol containing 0.04 g of maleic acid. The mixture is crystallized by slow cooling. Filtration and drying afforded 87 g of a white crystalline material which is a mixture of isomers la: lb = 39.0: 59.5. Ratios isopropanol: cypermethrin the same as in Example 10.

Purity: 98.5%

Melting point: 64-66 ° C

The ratio of isomers remains unchanged at the end of the 12-month administration period.

example

Stability test

A mixture of 99.9% pure crystalline cypermethrin isomers containing 40% by weight of lg isomeric pair of lg isomers and 60% by weight of 3464% by weight of lg isomeric pair of lg isomers are dissolved in 9 ml of toluene. Dilute the solution with 8 ml of anhydrous ethanol. Similar solutions are prepared from the isomeric pairs la and lb. Add the various acids specified in the solutions

5 in the tables below, triethylamine in anhydrous komi at room temperature isomeric composition of the substance. then dissolved in 10% by volume in ethanol. Solutions for costs- and after 1 weeks under investigation 10th The results are summarized below in the in the tables

Table I

Y = la + lb

X = lc + ld

Acid Acid solution ml Content and composition of triethylamine solution 01 0, lml 0.1 ml 11th X (%) Y (%) X (%) Y (%) X (%) Y {%) X (%) Y (%) - 0 0 99.9 50 49, 9 47 45 40 43 Phthalic 1 0 99, 9 0 99, 9 0 99, 9 50 49.9 Fta1io 2 0 99, 9 0 99, 9 0 99, 9 5 94, 9 Maleino 1 0 99, 9 0 99, 9 0 99, 9 3 96, 9 Maleino 2 0 99, 9 0 99, 9 0 99, 9 0 99, 9 Nice 0, 1 0 99, 9 0 99, 9 5 94, 9 50 49, 9 Nice 1 0 99, 9 0 99, 9 0 99, 9 0 99, 9 Fumaro 1 0 99, 9 0 99, 9 0 99, 9 3 96, 9 Fumaro 2 0 99, 9 0 99, 9 0 99, 9 0 99, 9 Oxal 1 0 99, 9 0 99, 9 0 99, 9 2 97, 9 Oxal 2 0 99, 9 0 99, 9 0 99, 9 0 99, 9 Paratoluene sulfo 1 0 99, 9 0 99, 9 0 99, 9 49.9 50 Paratoluene sulfo 2 0 99, 9 0 99, 9 0 99, 9 2 97.9

Table II

Y '= 1b

X '= ld

R Content of triethylamine solution, composition Acid T * 0 ml 0.0] L ml 0,] ml 1 ml ml X '(%) Y '(%) X '(%) Y '(%) X '(%) Y '(%) X '(%) Y '(%) - 0 0 99, 9 50, 1 49, 8 46th 45, 8 41 42 Phthalic 2 0 99, 9 0 99, 9 4.9 95, 1 Maleino 2 0 99, 9 0 99, 9 0 99, 9 0 99, 9 Nice 1 0 99, 9 0 99, 9 0 99, 9 0 99, 9 Fumaro 2 0 99, 9 0 99, 9 0 99, 9 0 99, 9

* - Acid solution

Table III

Y = la

X = lc

R

Content and composition of triethylamine solution

Acid T * 0 ml 0, 0] L ml 0, 1 ml 1 ml ml X (%) Y (%) X (%) Y (%) X (%) Y (%) X (%) Y (%) - 0 0 99, 9 50.4 49, 2 48 43 41 42 Phthalic 2 0 99, 9 0 99, 9 0 99, 9 6th 94.2 Maleino 2 0 99, 9 0 99, 9 0 99, 9 0 99, 9 Nice 1 0 99, 9 0 99, 9 0 99, 9 0 99, 9 Fumaro 2 0 99, 9 0 99, 9 0 99, 9 0 99, 9 Oxal 1 0 99, 9 0 99, 9 0 99, 9 2.2 97, 1 Oxal 2 0 99, 9 0 99, 9 0 99, 9 0 99, 9

An example of an acid solution

Stability test Dissolve g of the product of Example 18 in 2 ml of toluene, dilute with 8 ml of anhydrous ethanol and add 10% v / v triethylamine solution. The solutions are kept at room temperature for 1 week and the isomer composition is then examined.

Table IV

X = lc + ld

Y = la + lb

Isomers Content of triethylamine solution (ml) 0, 1 0, 01 0.02 0, 05 0, 1 0.2 X (%) 2 2 2 20th 48 47 Y (%) 96 96 96 78 49, 5 48

example

200 g of the reaction mixture, containing the crystalline material obtained in the manner described in Example 10, are placed in an apparatus containing a heater and a stirrer and having a discharge outlet at the bottom. The mixture is acidified to pH2 with aqueous solution containing 2% by weight of hydrochloric acid and 0.2% by weight of formaldehyde with stirring. After 15 minutes of stirring the pH is checked, and the solution heated to 60 ^u C, the crystalline suspension is melted to an emulsion. After stirring for 15 minutes, the oily cypermethrin is precipitated and separated. The warm material is added to 150 mL of isopropanol containing 1% by weight maleic acid and crystallized by slow cooling and addition of crystallization centers. The precipitated snow-white crystals are filtered off, washed with 50 ml of glacial isopropanol containing 1% by weight of malic acid and dried. This gives 56 g of snow-white crystalline material.

Melting point: 62.5-63 ° C.

Purity: 97%

Isomer ratio: la: lb = 38.5: 58.5

Yield 88% based on starting material.

example

The process proceeds as described in Example 10, except that the volume is a thousand times greater and the materials are charged and discharged without interruption.

The material flows are as follows:

Reaction Material Flow to the reactor (kg / h) Materials flow reas Zipermet- Before it triethyl isopro- kg / h of no. rin existing reactor amine panol of the reactor 1 8, 33 0 1, 83 2, 0 12, 16 2 0 12, 16 0 0 12, 16 3 0 12, 16 0 2, 6 14.76 4 0 14, 76 0 2, 6 17.36 5 0 17, 76 0 2.6 19, 96 6th 0 19, 96 0 2, 6 22.56 7th 0 22, 56 0 2, 6 25, 16

An average of 171 kg of the substance described in Example 10 is obtained daily.

example

The process is carried out as described in Example 22, except that the starting material is transcipermethrin oil and that each reactor is loaded with a crystalline material containing 93% of the lb isomers. The mixture is maintained at the temperature indicated in Example 2. Subsequently, to increase the crystallization capacity of the material in the first reactor, triethylamine is fed to the second reactor at a rate of 1.83 kg / h. This gives 173.2 kg of snow-white crystalline material containing 98.1% of the lb. of isomer pair. This material has a melting point of 80.5 ° C.

example

To 166.2 g of perlite (d _max = 120 microns) was added to a rapidly stirring apparatus, 0.8 g of synthetic silicic acid (Aerosil 300) was added. To the homogeneous homogeneity of this mixture is added a mixture of 20 g of cypermethrin having a pore ratio of la: lb = 4: 6, 0.04% fumaric acid and 2 g of polyglycol ether of saturated alcohol. The powder mixture is milled first in a mechanical mill and later in an air jet mill. 5 g of octophenol polyglycol ether (EO = 20) and 2 g of sulfosuccinate are then added to this rapid mixing apparatus. The powdered wettable mixture (WP) thus obtained is tested for suspension stability. Wetting time = 23 seconds, flotation activity = 89% (WHO standard method).

Example 1 g of a mixture of pore enantiomers of cypermethrin la: lb = 55: 45 and 0.1% malonic acid are dissolved by slow stirring in a mixture of 21.25 g xylene and 42.5 g n-propanol. To the resulting solution is added a mixture of 4 g of ethoxylated alkylphenol + calcium n-alkylarylsulfonate and a mixture of 6 g of ethoxylated amino + alkali metal n-alkylarylsulfonate until complete dissolution, followed by addition of 21.25 g of water. . In this way, a clear solution is obtained which retains its properties at 0 ° -50 ° C for a long time. The solution can be diluted with water in any ratio. Dilution with water produces an emulsion with droplet sizes between 0.8 and 1.5 microns.

sample g of a mixture of cypermethrin enantiomers pair la: lb = 25: 75 and 0.002 g of diethylmalonic acid, dissolved in a mixture of 75 g of xylene and 10 g of aliphatic oil, followed by slow stirring

7.5 g mixture of ethoxylated alkylphenol + calcium n-alkylarylsulfonate and 2.5 g mixture of ethoxylated fatty acid and n-acrylic sulfonate. Measurements by CIPAC show that the emulsion concentrate is stable for 170 hours.

example

Emulsifiable concentrates (EC) are obtained by mixing the following components:

EC

Component amount in kg / kg

Pair of isomers la: lb = 40: 60 Diethylmalonic acid Cyclohexane Atlox 3386 B Atlox 3400 B

Odorless mineral oil

0, 105

0.00005

0, 290 0, 020 0, 045 0, 540

EC

The component amount in kg / kg Pair of isomers la: lb = 40: 60 0, 050 Diethylmalonic acid 0.00005 Cyclohexanol 0.290 Atlox 3386 B 0.020 Atlox 3400 B 0, 045 Odorless mineral oil 0.595 Example 28 Emulsifiable Concentrates (EC) the following components: are produced in m, 10 EC The component amount in kg / kg A pair of isomers lb 0, 105 Diethylmalonic acid 0.00005 Cyclohexanol 0.290 Atlox 3386 B 0.020 Atlox 3400 B 0, 045 Odorless mineral oil 0.540 5 EC The component amount in kg / kg A pair of isomers lb 0, 050 Diethylmalonic acid 0.00005 Cyclohexanol 0.290 Atlox 3386 B 0.020 Atlox 3400 B 0, 045 Colorless mineral oil 0.595

Example 1g of a pair of isomers lb is diluted with 2 g of ethanol. The solution in the powder homogenizer is mixed with 0.02 g maleic acid, 5 g calcium lignosulfonate, 5 g nonylphemyl glycol ether (EO = 20) and 70 g calcium carbonate. The material thus obtained is ground in an Alpine 10C type mill. Flotation activity as determined by CIPAC 81%, wetting time = 18 seconds.

Claims (1)

DEFINITION OF INVENTION Stable arthropodic composition, containing as active ingredient mixtures of isomeric cypermethrin of the structure Cl Cl - where the carbon atoms designated 1,3 and a are chiral carbon atoms and the wavy line represents the eis or trans configuration with respect to the cyclopropane ring having at least 95% of the isomeric pair IR trans S and 1S trans R (lb) or only a mixture of the isomeric pair IR will go to S and 1S will go to R (la) and the pairs of isomers (lb) in the ratio (la): (lb) = 55: 45-25: 75, or the pairs of isomers la and lb, characterized in that it has 0.001-0-0 as stabilizer. 1% by weight, calculated on the active ingredient, of an acid or mixture of acids, preferably of a non-volatile carboxylic acid having a pK ^ 1-5, such as phthalic acid, succinic acid, tartaric acid, maleic acid, fumaric acid, malonic acid or one or more substituents on the chain, such as alkylation derivatives, and / or oxalic acid.