The method of obtaining a mixture of isomers of cypermethrin in the form of a stable crystalline product


C07B57C07M9 -

 

(57) Abstract:

Usage: as insecticides in agriculture. The inventive method of obtaining a mixture of isomers of cypermethrin in the form of a stable crystalline product f - ly 1, given in the text descriptions, where the carbon atoms in position 1,3 and are chiral carbon atoms and the wavy line indicates the CIS - or TRANS - configuration with respect to cyclopropylamino ring, and the final mixture of isomers of theoretically possible 8 isomers of cypermethrin contains at least 95% or pairs of isomers: 1r TRANS s and 1r TRANS r(1B) pairs of isomers or mixture of 1r CIS r and 1s or r(1A) and a pair of isomers (1B) equation (1A):(1B) 55:45-25:75 obtained by asymmetric transformation of the initial mixture of isomers from the reaction of the second order in the presence of an amine base and a solvent, where the initial mixture is an oil or a crystalline mixture with a purity of at least 90%, and contains at least 60% TRANS - Izmerov cypermethrin or CIS - TRANS isomers of cypermethrin in the ratio of 65:35 to 15:65 in the system with content of less than 0.5% moisture. 7 C. p. F. - ly, 5 PL.

In the description of the invention it comes to obtaining mixtures Anant is maintained below cypermethrine) with the formula I

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with this ratio of isomers obtained by asymmetric transformation.

In the description of the invention the spatial configuration of the replacement atoms related to the chiral carbon atom (indicated in the formula as ) is characterized by the symbols S and R. the Terms "CIS" and "TRANS" are used to indicate the position of atoms that replaces the third carbon atom cyclopropanol rings, and the absolute spatial configuration of atoms that replaces the first carbon atom, conventionally denoted by 1R and 1S. To identify different enantiomers and their pairs use the following abbreviations:

1A mixture of 1R cisS and 1Scis R;

alphamethrin (Fastac)

1b is a mixture of 1R trans S and 1Strans R

(Semi-trailer)

1c mixture of 1R cisR and 1Scis S

1d mixture 1Rtrans R and 1Strans S

1f 1R cisS

1g 1Rtrans S

1h 1ScisR

1i 1S transR

1a+1b asymmetry (chinmix)

In the description of the invention it comes to such mixtures of isomers of cypermethrin formula I

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which contain, in contrast to theoretically possible 8 isomers of cypermethrin, at least 95% of pairs of isomers 1Rtrans S and 1Strans R(1b) or a mixture of pairs of isomers 1RcisS and 1ScisR(1a) and (1b) equation (1A):(1b)= 55: 45-25: 75 obtained by asymmetric transformation of 11-th order in the presence of amine base is transitory or a pair of isomers (1A)+(1b) in an undesirable ratio, and the way is due to:

a) a chemical reaction of a mixture of oil or crystalline isomers having the formula (I), purity at least 90 wt. containing at least 60% TRANS-isomers or CIS - and TRANS-isomers in the ratio of 65:35 to 15:85 at 0-25aboutWith the system, containing less than 0.5% water and 0.1-0.5 wt.h. (triethylamine or of 0.0005-0.01 wt. including 1,5-diazabicyclo-[4.3.0] Non-5-ene (DBN) or 1,5-diazabicyclo [5.4.0] undecene (DBU), depending on the mass of the original mixture of isomers, under intensive stirring; in the presence of propanol in the saturation point of the mixture of isomers with the desired ratio of concentration when added to the mixture simultaneously with the passage of the epimerization reaction of propanol and at the request of triethylamine to achieve at the end of the reaction the ratio of wt.h. propanol and cypermethrin 0.5 and 2, respectively, and when hitting a crystalline precipitate after optional gradual cooling;

C) after completion of asymmetric transformations, selected crystalline mass is treated with an aqueous acid solution and/or dissolve in the presence of immiscible with water, an organic solvent at 0-70aboutWith or melt without the addition of any solvent at 60-70aboutC and washed vadnere substance will recrystallised of the solvent, containing organic acid;

(C) as canvasses substances in solution add aldehyde;

d) the sequence of operations are continuously carried out in several reactors, forming a chain of 2-10 reactors, which can be cooled or heated and contain a mixer.

The temperature of the reactor regulating range(+) 30- (-) 25aboutWhen the maximum temperature difference in sequential reactors 10aboutC. First in each reactor was added 1 wt.h. target crystalline substance and optionally more than 0.4 wt.h. founding. The mixture in each reactor is diluted by adding 0.4 wt.h. proton solvent.

After the first reactor will add 1 wt.h. the crude mixture of isomers with the formula (I) and a purity of at least 90%, and optionally an additional amount of the base, the mixture is stirred and the reaction mixture or part thereof, is administered in the second and subsequent reactors, where the process of adding a proton to the solvent and base and mixing optionally repeated several times. Raw cypermethrin continuously or in part instead of from more than 0.4 wt.h. proton solvent and/or base re-added to the first reactor. After the toga reactor chain crystalline suspensions optionally produce crystals.

These isomers of cypermethrin insecticides are with favorable biological properties (EP 215.010 and EP 208.758).

In the course of a known process, the desired mixture of isomers produce by crystallization of the mixture of isomers of cypermethrin.

Crystallization takes place in the presence of a base, which causes the epimerization at the carbon atom and theoretically undesirable isomers can be converted into the desired substance. This method of organic chemistry known as "asymmetric conversion of 11-th order".

In accordance with the specified method exclusively for the CIS-isomers, (1A) isomer prepared from a mixture of acipenserinus. The original substance was suspended in excess of 1.5-3.0 triethylamine or it was dissolved in the hot way and the solution placed the germ of the crystal (1A), containing 1RcisS and 1ScisR isomers in the ratio of V:I. Slow crystallization of a solution or suspension occurred as a result of gradual cooling. Compound 1A 0-95% purity was obtained with a yield of about 80% (EP 67461 and 109113).

It was published a similar description of the methods of obtaining 1B of cypermethrin containing 1B+1d TRANS, by epimerization with the use of the orites, as petroleum ether and 2,6-di-tert-butyl-4-METHYLPHENOL as an antioxidant in 30-60about(EPA 215.010).

In accordance with a further publication, 1A, 1b, and 1A+1b were obtained by interaction of a suspension of hydrocarbon source isomers with a base and a catalyst, which was dissolved in the suspension and selected from Quaternary ammonium compounds and phosphorus, as well as crownether. The suspension was which at a temperature effective to convert and received final isomers. The tendency to form side benzoin ether were reduced by adding to the suspension of the acceptor aldehyde in the form of metabisulfite and/or catalyst in the form of a halide ammonitella, soluble in an aprotic solvent in the form of organic nitride. Inorganic bases were used in the solid state and in aqueous solutions. It is advisable as a reason to use sodium cyanide (PCT Publication WO 88/10249).

The disadvantage of this method is the significant degradation of cypermethrin in terms of the proposed reactions involving equally the formation of benzoin derivatives with formula (II)

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The proposed molecule acceptor" prevrashatesa creates a selection of CYANOGEN, as a by-product of decomposition. Processing of the reaction mixture, consisting of several layers, further complicates reliable industrial implementation of this critical response. Maybe that's why, in many examples, this publication contains significant results. The increasing difficulties associated with the use of mixtures containing isomers 1A and 1b, shown by example EP 67461, whereby obtaining a pair of isomers 1A revealed the transformation of a mixture of isomers (1A+1C) in triethylamine. In accordance with these publications, the presence of 6 or 10% impurities of TRANS fats in the original substance reduces exit 1A to 63 or 36% In the case of high content of TRANS fats, crystallization 1A will not occur.

In accordance with the known method, the pure compound (1A+1b) can be obtained by selective crystallization cypermethrin sufficient purity in the selection of appropriate conditions, a suitable solvent, temperature and clean the seed crystal. The process takes several weeks. Thus, a mixture of 1A+1b can be obtained with the yield of 80% calculated on the contents of the pair isomer 1A+1B source cypermethrin. The disadvantage of this method lies in the fact that is 2">

Industrial production of pure products of isomers (content of active components above 97% ) is still problematic. In particular, mixtures containing 1A, irritate human skin, caused by a severe allergic reaction. There is therefore a need to simplify research.

In accordance with the invention, the epimerization should be carried out in a system containing more than 0.5% moisture. According to our results, the catalytic amount of water can influence the formation of benzoin derivatives with structural formula (II). Unlike previous methods according to the invention are not intended to bind the products of decomposition, but prevent hydrolytic degradation of cypermethrin.

In accordance with the invention of the industrial process may be carried out by combining parts a), b) and C) and optionally d). The result of this method is obtaining a stable pure substances with a good yield, and ease of implementation and environmental cleanliness.

An integral part of further elaborates as follows:

part (a) of the method of the invention is based on the fact that from the point of view of a successful asymmetric is tallization is not only the choice of an appropriate base, but this amount of propanol, which must be added simultaneously to the reaction of epimerization at the corresponding temperature. It was observed that if the oil mixture of isomers of cypermethrin to add a solvent in the form of isopropanol for crystallization, under the action of cypermethrin solvent to some extent diluted and upon reaching the so-called indicator saturation or equilibrium mixture suddenly turns into the emulsion. Upon further addition of the solvent the resulting emulsion is gradually transformed into a true solution. The same phenomenon can be observed if the solvent for crystallization also contains a base. Asymmetric transformation can be carried out more quickly when you reach a state of saturation or equilibrium. This observation has not yet been related publications process of asymmetric transformations. The rate of conversion decreases with increasing number of the resulting material, but may be increased by further adding propanol (propyl alcohol selectively activates the crystallization 1A and 1b). This process is activated further by cooling the mixture.

This state ravnovesie the influence of small deviations. If in the preparation of the mixture with the ratio of the isomers 1A: 1b=4:6 to raise the temperature from 14-15 to 20aboutC, the output will be significantly reduced and instead of the expected pair of enantiomers of 1A with higher melting point (86aboutC) will be observed enrichment of a pair of enantiomers 1b. The same thing can happen if you consciously increase the amount of the solvent. This method according to the invention makes it possible to obtain the substance, different from CIS-Transmediale source cypermethrin even 30 wt. The product can be selected with the desired ratio of concentrations of the isomers. As starting substances can be used a mixture of isomers of oil and crystalline cypermethrin.

When using crystal initial matter, the epimerization reaction can be carried out faster, even if the process of its implementation will not be continuous.

Getting some pairs of isomers 1A:1b, of importance, are described below.

In order to obtain a mixture with a ratio of isomers 1A:1b+40:60, as the starting material a mixture on the basis of cypermethrin with the ratio of the isomers (1A+1C)=35-45, (1b+1d)=50-60 wt. The reaction lasts 4-10 days depending on quantity is ropanol, equal 1:0,2-0,3:1-1,5. Propanol is advisable to add, starting from the second day and continue until the fifth day.

If a mixture of 1A:1b=50:50 weight obtained, the mixture of isomers (1A+1C)=40-55, (1b+1d)= 45-55 wt.h. used as educt. Isomerization lasts for 1-10 days.

If a mixture of isomers 1A:1b=25-30:75--70 wt. you need to cook, the mixture of isomers 1A+1C=35-45,(1b+1d)=50-60 wt. used as educt. Asymmetric transformation and selection carried out within 1-5 days at 25aboutC.

If as the initial substance use oil cypermethrin, the reaction mixture is better to cool below 0aboutAnd to pre-crystallize.

A small number of pairs of isomers (1C+1d) in the selected substance can be recovered through the washing of the filtered crystal of finite substances. As solvents for washing can be used hexane, heptane, petroleum ether, ethanol and/or isopropanol or mixtures of these solvents with acids such as acetic, phthalic, maleic, fumaric, malonic or alkilirovanny malonic acid.

Asymmetric transformation can be made is that in the last third period of the reaction, the reaction mixture is gradually cooled below 0aboutFrom appropriate below 10-(-25)aboutC.

It was found that a small amount of Foundation in the form of admixtures containing nitrogen, participates in the epimerization of the final product. The same epimerization may be caused by the presence of impurities in the added solvent or any residual reagents involved in the preparation process, or the presence of impurities in substances that are added when obtaining drugs. In tables illustrating examples shows how you can prevent unwanted epimerization by the timely addition of acids (the addition of small amounts of triethylamine) and how substances can be stabilized. Research lead to part b) describe the way in which.

According to part b) of the description of the invention, the reaction mixture may be acidified or crystalline slurry may be boiled with the use of 0.1-5 wt. an aqueous solution of acid, preferably hydrochloric, formic, phthalic, malonic, fumaric or alkilirovanny malonic or maleic acids, optionally containing canvasses substance.

For extraction of crystalline suspensions can be used water-insoluble organic will dissolve the tetrachloride of carbon, ethyl acetate, benzene, toluene or xylene. It is advisable that the extract was washed with clean water or water saturated with sodium chloride and/or 0.1 wt. an aqueous solution of a mineral or organic acids, preferably solutions of hydrochloric, acetic, phthalic, malonic, alkilirovanny malonic, fumaric or maleic acids.

For recrystallization substances can be used nonpolar and proton solvent, preferably hexane, heptane, petroleum ether, methanol, ethanol, isopropanol or mixture of solvents such acids as acetic, maleic, fumaric, malonic or alkilirovanny malonic acid.

At the end of a consecutive series of operations substance get in the form of a crystal, the melt or solution. The substance contains isomers in a stable relationship and later of 12 months after receipt.

If the reaction takes place in anhydrous conditions should be prevented decomposition cypermethrin, as described above. The suppression of the decomposition process also causes a reduction in the content of cyanide in the reaction mixture.

However, during long-term treatment in an industrial environment may be minor Riana will not cause problems, security-related. Every time there is a formation of small amounts of free cyanide in the acidification of the environment, the reaction mixture was added the aldehyde as a stable canvasses substances to prevent the ingress of cyanide in the air. It is preferable to use formaldehyde. The thus obtained nitrile cyanoglucosides acid in the residual mixture can be hydrolyzed to glycolic acid by simple heating. Processing the mixture obtained is not dangerous.

Asymmetric transformation of the II-th order is heterogeneous equilibrium reaction, consisting of two stages. Determination of the kinetics of this reaction is possible only by experiment. In this case, the process is complicated due to the fact that the concentration changing in the crystallization process, then subjected to change as a result of the dilution process, and the temperature of the epimerization reaction can be increased, and then decreased during the process. To ascertain whether the kinetics of the reaction using a chain reactors in theory, was determined reaction order. The reaction can be described as a reaction to the apparent kinetics of II-th order that isn polovinu continuous chain reactors what can be achieved, respectively, per unit of time.

Part (d) of the invention is based on the fact that on the basis of reaction kinetics asymmetric transformations cypermethrin II-th order, the process can be carried out more favorably when using continuous or semi-continuous chain reactors. The reaction can be a continuous or quasi-continuous. In the first case of a substance added or removed continuously, while in the second case, the material is fed in parts so that the chain reactors worked without a break. Several chains of reactors can be formed parallel to each other. In the reactor circuit, it is preferable to use Transmediale, as it promotes recycling and renewal process. The advantage of this method is that the performance may be increased due to the several reactors of periodic action, and can also be improved degree of transformation. The resulting substance may be subjected to a continuous process that will allow you to avoid decomposition or aggregation that is associated with the stop. The desired conversion can be achieved in a short period of time depending on the units of matter that energii.

The present invention provides for obtaining a stable arthropodicides substances containing as active ingredient a mixture of isomers of cypermethrin with formula (I), which contains at least 95 wt. a pair of enantiomers 1RcisS and 1ScisR (1a) and enantiomer 1RtransS and 1StransR (1b) in a ratio of 1A:1b=55:45-25:75, or a couple of isomers 1A or 1b, and as a stabilizer compound containing 0.001 to 0.1 wt. depending on the active component, the acid or mixture of acids, preferably non-volatile carboxilic acids with pK1= 1-5, such as phthalic, succinic, tartaric, maleic, fumaric, malonic, or one or more times alkyl substituted derivatives of these acids and/or oxalic acid.

During implementation d) in accordance with the invention, when continuous or periodic supply is advisable to use the original reaction mixture following concentrations: 50-80 wt. cypermethrin, 1-50 wt. propanol, 10-20 wt. triethylamine or is 0.0002-0.01 wt. DBN or DBU.

It is also advisable to ensure that the concentration in the final reaction mixture after completion of the asymmetric transformation will be as follows: 25-45 wt. cypermethrin, 45-75 wt. propanol, 4-14 wt. triethylamine or is 0.0002 wt. 0.004 wt. DBN or DBU.

Stable solutions or compounds containing isomers of cypermethrin with stable acids, which was defined above, can be used in a mixture with additives used in the manufacture of pesticides for agriculture, veterinary science, in order to protect human health and/or hygiene (EP 208, 758). Use supplements that can counteract the stabilizing action of acids, especially the use of reason, should be avoided or taken into account in determining the amount of acid used. Also should BWT appropriately selected solvents.

Further details of the invention are illustrated in the following examples.

The analysis used and the selected substances was made by high performance liquid chromatography. Cm. "Analytical methods of Plant Growth Regulators and Pesticides": XIII, ed. Zweig and far exceed Sharm, demic Press, 1984.

Where this is not special links, the water content of the substance is less than 0.1 wt.

P R I m e R 1. Preparation of a mixture of 40:60 pairs of enantiomers 1RcisS and 1ScisR (1a) and a pair of enantiomers 1RtransS and 1StransR (1b) of cypermethrin.

In the device with magnetic somerow: 1A at 18.1 wt. 1b of 23.1 wt. 1c 23.5 wt. 1d=34,3 wt. suspendered in mixture of 21.7 g of triethylamine and 23.5 g of isopropanol. The mixture is stirred for 24 h at 16aboutC. Gradually swell, the suspension is diluted 4 times by adding to 31.5 g of isopropanol every 24 hours the mixture is stirred for 24 h at 0aboutC. the Suspension is filtered, washed with 39,3 g of isopropanol, to 31.5 g of isopropanol, containing by weight 0.25. acetic acid and then with the help of 23.5 g of isopropanol. Then dried in vacuum at room temperature and obtain 87 g of snow-white crystalline substance.

The melting point of 62-63aboutC.

The ratio of the isomers: 1A 38,0 wt. 1b 59,3 wt. S,2 wt. 1d=0.4.

The purity of the 98.9 wt.

The original liquor is evaporated and the above process is repeated using 13.5 g of the obtained substance, a mixture of 13.0 g of isopropanol and 2.8 g of triethylamine. In the second stage of the process get 7 g of snow-white crystalline substance.

The melting temperature of 62-65aboutC.

The composition of isomers: 1a=48 wt. 1B= 48,2 wt. 1E=1 wt. 1d=0.4.

The purity of 97.6 wt.

P R I m m e R 2. Preparation of a mixture of 40:60 1RcisS and 1ScisR(1A) and 1RtransS and 1StransR (1b) of cypermethrin you can take Spa (purity, 95.6 wt. the composition of the isomers 1A:17.6 wt. 1b: 22,6, wt. 1C: 22,9 wt. 1d:32,4 wt.).

The reaction takes place at the 11aboutC. When combining results of I and II stages of the process obtain 91 g (91%) of snow-white crystalline substance.

Melting point: 62-64aboutC.

The composition of isomers: 1A: 38,1 wt. 1b: 58,1 wt. 1C: 1.1 wt. 1d=0.7 wt.

Purity of 98 wt.

P R I m e R 3. The mixture 50:50 1RcisS and 1ScisR (1a) and 1RtransS and 1StransR (1b) of cypermethrin can be made by the method described in example 1. But as an initial matter you need to take 100 g of crystalline cypermethrin (purity: 98 wt. 1A: 22.3 wt. 1b: 20.4 wt. 1C: to 26.6 wt. 1d: 28.7 wt.).

When combining the results of I and II stages of the process obtain 95 g of snow-white crystalline substance.

Melting point: 64,5-65,5aboutC.

The composition of isomers: 1A: 48,2 wt. 1B: 48.4 wt. 1C: 1.1 wt, 1d: 0.6

The purity of 98.3 wt.

P R I m e R 4. Getting 1RcisS and 1ScisR(1a) and 1StransR 1RtransS and (1b) of cypermethrin at 25aboutC.

As an initial matter take cypermethrin, as described in example 1, but the epimerization is carried out at 25aboutWith and get to 52.1 g of snow-white crystalline substance.

Melting point 65-6"ptx2">

P R I m e R 5. Getting 1RcisS and 1ScisR (1a) and 1RtransS and 1StransR (1b) of cypermethrin using DBN.

As an initial matter take cypermethrin as described in example 1, but the triethylamine is replaced by 0.1 g DBN and, when combining the results of I and II stages of the process, obtain 95 g of a white crystalline substance.

Melting point 62-64aboutC.

The composition of isomers: 1a: X9,4 wt. 1b: 57,4 wt. 1C: 1,2 wt. 1d: 0.8 wt.

Purity 98,8 Mac

P R I m e R 6. Getting 1RcisS and 1ScisR(1a) and 1RtransS and 1Strans (1b) with a ratio of 40:60 of cypermethrin using n-propanol.

In a device with a magnetic stirrer, thermometer and two holes add 100 g oil cypermethrin (purity, with 91.4 wt. 1A: 16.6 wt. 1b: a 21.5 wt. 1C: 21.8 wt. 1d: 31.5 wt.). The substance is stirred with a mixture of 14.5 g of triethylamine and 24.1 g of n-propanol for 4 days at 10-12aboutC. for 24 h, the suspension is diluted with a mixture of 14.5 g of triethylamine and 16 g of n-propanol. Dilution of the suspension with the help and 24.1 g of n-propanol is repeated every 24 h for three times. After adding the last portion of the solvent the temperature of the reaction mixture is reduced to 5aboutAnd the following 24 h the mixture is stirred.

The precipitated crystals tfilter the Tapa process is to obtain 82 g of snow-white crystalline substance.

The melting point of 62-63aboutC.

The composition of the isomers 1A; 38,0 wt. 1b: 60,0 wt. 1C: 1,0 wt. 1d: 0.5

Purity of 99.5 wt.

After evaporation of the mother liquor is recrystallized as described in example 1.

P R I m e R 7. In a device with a capacity of 3000 l with controlled cooling and steam heat with two-screw mixer add 600 kg oil cypermethrin (purity, 92 wt, composition: (1a+1c)=42 wt. (1b+1d)=50 wt. 180 kg of anhydrous isopropanol (water content: max 0.2 wt.), 180 kg of anhydrous triethylamine (water content: max 0.2 wt.). The mixture was dissolved under stirring. If desired, 1 kg of crystalline cypermethrin (1A= 38 wt. 1b=58 wt.) can be added to the seed crystals at the 25aboutC. To implement the asymmetric transformation solution stirred at 3-7aboutC for 18 h and added to a crystalline mixture of 228 kg of anhydrous isopropanol. The mixture is again stirred for 24 h at 3-7aboutTo add 96 kg of anhydrous isopropanol, stirred for 24 h at 3-7aboutAnd finally, add 96 kg of anhydrous isopropanol. The mixture is then stirred for 168 h at 3-7aboutC.

Next, the reaction mixture is cooled to 0-1-5aboutC and p is Asti using a pressure filter using nitrogen. 120 kg crystalline mass is washed with anhydrous isopropanol, filtered off, otmuchivajut using 4 wt. solution of acetic acid and isopropanol and filtered under nitrogen pressure.

The obtained crystals are dried for 12 h at 40-45aboutAnd stirred in a vacuum dryer using a blade mixer. Receive 500 kg asymmetria. Its composition according to chromatographic analysis: (1a)-38,2 wt. (1b)= 58,3 wt. (1C)=0.6. (1d)=0,8 wt.

Purity is 97.9 wt.

P R I m e R 8. The process is performed as described in example 1, but using a disk stirrer, and after the third dilution spend the fourth dilution of the suspension after 48 hours the Mixture is stirred for 48 h at 0aboutC and the substance is further diluted with 40 ml (31.5 g) isopropanol. The mixture is then cooled and stirred at -5aboutC for 48 h at -10aboutC for 72 hours In accordance with the description given in example 1, to obtain 90 g of snow-white crystalline substance.

The melting temperature of 62.5aboutC.

The composition of isomers: 1A: 39,0 wt. 1b: 59,5 wt. 1C: 0.6. 1d: 0.2 wt.

P R I m e R 9. The process takes place as described in example 1, except that instead of triethylamine, ispolzuya melting point: 62,5-64oC.

The composition of isomers: 1a: X9,6 wt. 1b: 57,2 wt. 1C: 1,2 wt. 1d: 0.9 wt.

Purity 98,8 wt.

P R I m e R 10. In the chain link 7 reactors with a capacity of 750 ml, equipped with a refrigerator and a stirrer. The first reactor is cooled to 0aboutFrom the second to the 8aboutWith progressing to 14, 15, 10, 0 and -10aboutC. To the reactor was added 100 g of isomers 1RcisS and 1ScisR(1a) and 1RtransS and 1StransR(1b) equation (1A): (1b)=40:60 and 95% crystalline-cyan-(m-phenoxybenzyl)-ether 22-dimethyl-3-(2:dichlorovinyl)-cyclopropane-carboxylato acid (cypermethrin). In the first and second reactors also add 30 ml isopropanol and 30 ml of triethylamine, and optionally in a third reactor 40, 80 fourth, fifth, 120, 160 in the sixth and seventh 20 ml of isopropanol. The mixture thermostatic with vigorous stirring. In the first reactor was added 100 g oil cypermethrin containing all CIS - and TRANS-isomers in a ratio of 41:59, average purity of 94% and 30 ml of isopropanol. The mixture is continuously stirred and after 12 hours in the first reactor was loaded with 30 ml of triethylamine. Half diluted mixture enters the next reactor, and the process of adding cypermethrin and isopropanol in the first reactor is repeated again. After 12 h the mixture in the first reactor is diluted with 30 ml three is ergodic in the second reactor. Then 100 g of cypermethrin and 30 ml of isopropyl alcohol again added to the first reactor and after 12 h of stirring the contents of the first reactor is diluted with 30 ml of triethylamine, in the third reactor add 40 ml of isopropanol, and half mixture passes from the third to the fourth reactor, from the second to the third, and from the first to the second reactor.

Repeating the process for submitting cypermethrin and isopropanol after a 12-hour mixing and passage of substances in the first reactor, add 30 ml of triethylamine, and 3, 4, 5, 6 and 7 reactors add 40 ml of isopropanol. Half of the mixture from one reactor passes into the next, and the substance is obtained at the end of the reactor circuit, passes through the filter. The complete sequence of operations is repeated every 12 hours, Filtered substance containing 01 wt. formaldehyde is washed with isopropanol containing 0.5% acetic acid, and dried at room temperature. Every time you get 85 g of snow-white crystalline substance.

Purity of 97 wt. is 38.5% for the pair of isomers 1A and 58.5% for the pair of isomers 1b.

Melting point 63aboutC.

The output relative to the initial substance 85%

P R I m e R 11. In the chain link 7 reactors with a capacity of 750 m is th to the 25aboutFrom the fourth to the 20aboutWith the remaining reactors cooled to a temperature of 5aboutBelow the previous temperature of the reactor. To the reactor was added 100 g of a pair of isomers (1b), containing at least 95% crystalline finite substances. In the first and second reactors are placed 30 ml of triethylamine and 30 ml of isopropanol. Additionally, in the third reactor type 40, 80 fourth, fifth, 120, 180 in the sixth and seventh 200 ml of isopropanol. The mixture thermostatic with vigorous stirring and then in the first reactor was added 100 g oil cypermethrin containing all TRANS average purity of 94% or melt cypermethrin and 30 ml of isopropanol. 12 h after mixing in the first reactor, add 30 ml of triethylamine. Half diluted mixture enters the next reactor, and the process of adding cypermethrin and isopropanol repeat. After 12 h the mixture in the first reactor is diluted with 30 ml of triethylamine. Half of the mixture from the second reactor is transferred into a third and a half of the content of the third reactor passes in the fourth. Then in the first reactor again add 100 g of cypermethrin and 30 ml of isopropyl alcohol. 12 h after mixing in the first reactor, add 30 ml of triethylamine, and the third 40 ml isreli, then from the first reactor to the second. After repeating the process of adding cypermethrin and isopropanol, 12 h after mixing in the first reactor, add 30 ml of triethylamine, and 3, 4, 5, 6 and 7 reactors 40 ml of isopropanol. Half the contents of the reactor is transferred to the next reactor and substance, obtained at the end of the reactor circuit, passes through the filter. The complete sequence of operations is repeated every 12 hours, Filtered substance containing 0.05 wt. formaldehyde is washed with isopropanol containing 0.5 phthalic acid and dried at room temperature. Every time you get 85 g of snow-white crystalline substance, containing 98% of a pair of isomers 1A.

Melting point 80aboutC.

P R I m e R 12. The process takes place as described in example 1, except that as the initial substance use cypermethrin containing CIS - TRANS-isomers in the ratio 1:1, and as the seed crystal take crystal containing isomers 1A and 1b in the ratio of 1:1 concentration of at least 95% Obtain 85 g of snow-white crystalline substance.

Purity of 97 wt.

The ratio of the isomers: 1A:1b=48:49.

Temperature plvl is about, what substance is obtained at the end of the reactor circuit containing 0.2 wt. formaldehyde, are oxidized with 0.2 wt. an aqueous solution of hydrochloric acid, extracted by heating to 65aboutWith out using 500 ml of heptane and washed with hot the way with 50 ml of 1% hydrochloric acid, 100 ml water and 100 ml of saturated solution of sodium chloride. The mixture is crystallized at a constant cooling to -5aboutC. the Precipitated substance is filtered off and dried. Every time you get 87 g of white crystalline product.

The purity of 98.5 wt.

The ratio isomerase:1b=39,0:59,5.

Melting point 65,5aboutC.

P R I m e R 14. The process takes place as described in example 10, except that the substance obtained at the end of the reactor circuit containing 0.3 wt. formaldehyde, are oxidized with 0.2 wt. hydrochloric acid. The mixture is extracted with dichloromethane, the organic layer is washed with 50 ml of 1 wt. an aqueous solution of hydrochloric acid and twice with 100 ml of water is evaporated in double the amount of methanol. Crystallization occurs during the gradual cooling to -5aboutC. Every time you get 86 g of snow-white Chris is the atur melting 63aboutC.

P R I m e R 15. The process occurs as described in 10 of the example, except that the substance obtained at the end of the reactor circuit, neutralized with 2 wt. hydrochloric acid, extracted with ethyl acetate and washed the organic layer is 5 times with 50 ml of 0.5 wt. an aqueous solution of phthalic acid containing 0.1 wt. of formaldehyde. After evaporation is dissolved in double the amount of 2 wt. solution of phthalic acid and methanol. Crystallization occurs during the gradual cooling to -5aboutC. the Crystals are filtered and dried. Obtain 86 g of snow-white crystalline substance.

Purity 98%

The ratio of the isomers: 1a:1b=39:59.

The ratio of the isomers remains unchanged after a shelf life of 12 months.

Melting point 63aboutC.

P R I m e R 16. The process takes place as described in example 10, except that after the start of the process in the reactor circuit type crystalline cypermethrin of 99.5% purity containing CIS - and TRANS-isomers in the ratio of 4:6. Every 24 h the transfer of matter. At the end of the reactor circuit, the resulting suspension is oxidized with an aqueous solution containing 0.4 wt. formald the CSOs solution of phthalic acid and 100 ml (1%) solution of maleic acid. So get 535 g of the solution Chinmix containing 6.9% of the pairs of isomers 1A, 10.6% of the pairs of isomers 1B, 0,35 pair of isomers 1C and 0.28% pairs of isomers 1d.

P R I m e R 17. The process occurs as described in 10 example except that obtained at the end of the reactor mixture the substance is oxidized with an aqueous solution containing 0.2 wt. hydrochloric acid and 0.4 wt. of formaldehyde. The mixture is extracted using 400 ml of petroleum ether (100-120) when heated to 60aboutWith, the organic layer was washed with an aqueous solution containing 0.1 wt. formaldehyde and 0.1 wt. hydrochloric acid and then 50 ml of a solution containing 1 wt. hydrochloric acid and 0.1 wt. formalin, 50 ml of water and 50 ml of an aqueous solution containing 5 wt. diethylmalonate acid. The organic layer is separated, and the solution is crystallized upon slow cooling. After filtration and drying obtain 88 g of snow-white crystalline mixture of isomers 1A:1b=39,0: 59,5.

Purity 98%

Melting point 65aboutC.

P R I m e R 18. The process takes place as described in example 17, except that after washing with a solution of malonic acid in the last step, use 50 ml of water and the Department is result during slow cooling. After filtration and drying obtain 87 g of a white crystalline substance which is a mixture of isomers 1A:1b=39,0:59,5.

The purity of 98.5%

Melting point 64-66aboutC.

The ratio of the isomers remains unchanged in the expired after 12 months.

P R I m e R 19. Test for stability. A mixture of crystalline isomers of cypermethrin 99.9% purity, containing 40 wt. 1 g of the pair of isomers 1A and 60 wt. 1 g of the pair of isomers 1B dissolved in 2 ml of toluene. The solution was diluted with 8 ml of anhydrous ethanol. Similar solutions are respectively pairs of isomers 1A and 1b. In the solutions for analysis add various acids listed in table.1, then dissolved in about 10.anhydrous ethanol and about 10. of triethylamine in anhydrous ethanol. The solution was kept at room temperature and in a week exploring the isomeric composition of the material.

The results are summarized in table.1-3.

P R I m e R 20. The test is not sustainable. 1 g of the substance obtained by the method described in example 18, was dissolved in 2 ml of toluene and the solution was diluted with 8 ml of anhydrous ethanol, add about 10. solution of triethylamine. The solutions are incubated for one week at room temperature and then studies the m e R 21. 200 g of the reaction mixture containing crystalline substance, obtained as described in example 10, is placed in the device, equipped with heater, stirrer and discharged through the bottom. The mixture is oxidized with constant stirring with an aqueous solution containing 2 wt. hydrochloric acid and 0.2 wt. formaldehyde to pH=2. After stirring for 15 minutes the pH of the solution is checked and melt the crystal suspension to the emulsion by heating to 60aboutC. After 15 min stirring the oil cypermethrin precipitated and separated. Heat a substance added to 150 ml of isopropanol containing 1 wt. maleic acid, crystallized after slow cooling and viewauth. Fallen snow-white crystals are filtered, washed with 50 ml of ice-cold isopropanol containing 1 wt. maleic acid, and dried. Thus obtain 56 g of snow-white crystalline substance.

The melting temperature of 62.5-63aboutC.

Purity 97%

The ratio of the isomers: 1a:1b=38,5:58,5.

The output relative to the amount of the original substance is 88%

P R I m e R 22. The process is carried out in accordance with the description given in example 10, but 1000 times more volume. Download.

The average daily gain of 171 kg of substance by the method described in example 10.

P R I m e R 23. The process is carried out in accordance with the description of example 22, but as the source of matter take an oil transcobalamin and in each reactor load crystalline substance containing 93% of the isomers 1b. The mixture is maintained at a temperature in correlation with the data of example 11. Then triethylamine with a flow rate of 1.83 kg/h is transferred to the second reactor, which increases kristalloobrazuyushchikh the ability of a substance in the first reactor. So get 173,2 kg of snow-white crystalline substance containing a pair of isomers 1b in to 98.1% with a melting point 80,5aboutC.

P R I m e R 24. In the mixing apparatus to to 166.2 g of perlite (dmax=120 μm) add 0.8 g of synthetic silicic acid (Airosil 300). 20 g of a mixture of cypermethrin with a ratio of pairs of enantiomers of 1A:1b=4:6, 0.04% of fumaric acid and 2 g polyglycolic ether fatty alcohol is added to the mixture for uniform homogenization. The powder mixture is first ground in a mechanical mill, and then in vostokstrojj mill. Then in high-speed mixing apparatus add 5 g polyglycolide ester op (EO=20) and 2 g of sulfosuccinate. T is time wetting 23, flotation activity of 89% (standard BUT the method).

P R I m e R 25. 5 g of a mixture of pairs of enantiomers cypermethrin 1A:1b=55:45, and 0.1% malonic acid dissolved in a mixture each holding 21.25 g of xylene and 42.5 g of n-propanol under slow stirring. A mixture of 4 g of ethoxylated alkylphenol + n-alkylarylsulfonate calcium and a mixture of 6 g of ethoxylated amine + n-alkylarylsulfonate alkali metal added under stirring until then, until the substance will not dissolve completely, then pour each holding 21.25 g of water. Thus obtained transparent solution that retains its properties at temperatures between 0 and 50aboutWith a long period of time. The solution can be diluted with water in any ratio, which is accompanied by the formation of emulsions with droplet size of 0.8-1.5 μm.

P R I m e R 26. 5 g of a mixture of a pair of enantiomers of cypermethrin in the ratio of 1A:1b=25:75 and 0.002 g diethylmalonate acid dissolved in a mixture of 75 g of xylene and 10 g of aliphatic oil, then with slow stirring, the mixture (75 g) ethoxylated alkylphenol + n-alkylarylsulfonate calcium and a mixture (2.5 g) ethoxylated fatty acid+n-alkylarylsulfonate. Measurement method lPAC show that the emulsion concentrate saves us EBUSY components:

10EC Component Quantity kg/kg of a Pair of isomers 1A:1b=40:60 0,105 Diethylmalonate acid 0,00005 cyclohexanol 0,290 3386 In 0,020 3400 In 0,045 Mineral oil odourless 0,540

AS Component Quantity kg/kg of a Pair of isomers 1A:1b=40:60 0,050 Diethylmalonate acid 0,00005 cyclohexanol 0,290 3386 In 0,020 3400 In 0,045 Mineral oil odourless 0,595

P R I m e R 28. Emulsifiable concentrates (EC) prepared by mixing the following components:

10 EU Component Quantity kg/kg of Steam isomers 1b 0,105 Diethylmalonate acid 0,00005 cyclohexanol 0,290 3386 In 0,020 3400 In 0,045 Mineral oil odourless 0,540

AS Component Quantity kg/kg of Steam isomers 1b 0,050 Diethylmalonate acid 0,00005 cyclohexanol 0,290 3386 In 0,020 3400 In 0,045 Mineral oil no color 0,595

P R I m e R 29. 20 g of a pair of isomers 1 diluted with 2 g of ethanol. The solution is mixed in powder homogenizer with 0.02 g of maleic acid, 5 g of lignosulfonate, 5 g noninterpolating ether (EO=20) and 70 g of calcium carbonate. The thus obtained substance is ground in the mill type Alpine 10 C. In accordance with CIPAC flotation activity is 81% of the time wetting 18 C.

as well as a mixture (2.5 g) ethoxylated fatty acid + n-alkylarylsulfonate. Change

1. THE METHOD ACCORDING TO THE BR> where the carbon atoms in positions 1,3 and are chiral carbon atoms;

the wavy line indicates the CIS - or transconfiguration relatively cyclopropanol rings,

and the final mixture of isomers of theoretically possible 8 isomers of cypermethrin contains at least 95% or pairs of isomers: 1R TRANS S and 1S TRANS R (1b), or a mixture of a pair of isomers 1R CIS S-and 1S CIS R (1a) and a pair of isomers with a ratio of 1a : 1b = 55 : 45 - 25 : 75, based on a mixture of isomers of cypermethrin, which contains, along with a pair of isomers 1 B CIS - and other TRANS, or a couple of isomers 1a + 1b with spam ratio by asymmetric transformation of a P-order in the presence of an amine base and a solvent, wherein the first carry out asymmetric transformation of the initial mixture of isomers from the reaction of the second order, and the initial mixture is an oil or a crystalline purity of at least 90% and contains at least 60% TRANS-isomers of cypermethrin or CIS-TRANS-isomers of cypermethrin in the ratio of 65 : 35 to 15 : 85, in the system with content of less than 0.5% moisture at 0 - 25oWith from 0.1 to 0.5.h. triethylamine or of 0.0005 - 0.01 wt.h. 1,5-diazabicyclo-(1, 4, 3)nonene-5 or 1.5-diazabicyclo(5, 4, 0)undecene 1 wt.h.the source with ora saturated only target isomers of cypermethrin, then add propanol or isopropanol to maintain saturation of the target isomers, so that at the end of the reaction receive the crystal cypermethrin product, selectively containing a pair of cypermethrin isomers 1b or isomeric pairs 1a and 1b, which precipitates as a crystalline mass with respect to the product propanol or isopropanol to a crystalline mass of isomers of cypermethrin 0.5 to 2.0 wt.h. propanol or isopropanol at 1 wt.h. isomers of cypermethrin, then add the aldehyde as an agent that binds cyanide to prevent release of cyanide and then either a) produce crystalline mass from the reaction environment handle allocated crystalline mass of the acid solution containing 0.1 - 5% wt. organic or inorganic acid, and if necessary, dissolve the product in an organic solvent, extracted with a solution of the product aqueous acid solution containing 0.1 - 0.5 wt.% acid, and produce the product in the form of a stable crystalline cypermethrin or in the form of a stable solution of cypermethrin, or b) the reaction mass containing the crystalline suspension of the target product is treated with an acid solution containing 0.1 - 5 wt.% acid, extragear is as stable melt or solution of cypermethrin, and, if necessary, recrystallized product from a solvent containing 0.1 - 5.0 wt.% acid to obtain the desired stable crystalline cypermethrin.

2. The method according to p. 1, characterized in that during the last third of the reaction time, the reaction mixture is gradually cooled below 0oC.

3. The method according to p. 1 for the preparation of a mixture of isomers 1a : 1b = 50 - 50%, characterized in that used as the starting material a mixture of isomers 1a + 1c = 45 to 55 wt.% and 1b + 1d = 45 to 55 wt.%.

4. The method according to p. 1 for the preparation of a mixture of isomers 1a : 1b = 25 - 30 : 75 - 70, characterized in that used as the starting material a mixture of isomers 1a + 1c = 35 - 45 wt.% and 1b + 1d = 65 - 55 wt.% and conduct response and the allocation of the 25oC.

5. The method according to p. 1b, characterized in that is used for the extraction of the crystalline suspension is not miscible with water, an organic solvent.

6. The method according to p. 5, characterized in that washing the extract with water, saturated with sodium chloride and/or an aqueous solution of a mineral or organic acid (optional), containing canvasses substance concentration of 0.1 - 5.0 wt.%.

7. The method according to p. 1, characterized in that the binder is crystallizatio nonpolar substances or proton solvent, mixed with acid.

 

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