SI8811075A - CONVERSION OF PYRETHROID ISOMERS TO PESTICIDELY MORE ACTIVE ISOMERS - Google Patents

Abstract

Pyrethroid crystalline isomers or enantiomeric pairs are converted to pesticidally more active isomers by contacting a hydrocarbon suspension of the starting isomers with a base and a catalyst, the catalyst being soluble in the suspension and selected from quaternary ammonium compounds, quaternary phosphonium compounds and crown ethers, stirring the suspension while maintaining a temperature effective for the conversion and isolating the resulting isomers. The tendency to form benzoin ester by-products is reduced by introducing into the suspension a weak base, an aldehyde scavenger such as metabisulfide and/or a tetraalkyl (C1-C5) ammonium halide catalyst dissolved in an aprotic solvent such as an organic nitrile. The process is typically effective for enriching cypermethrin, cyfluthrin and (cyano) (3-phenoxyphenyl) methyl 3-(2,2-dibromoethenyl)-2,2-dimethylcyclopropanecarboxylate into the more active species.

Description

CONVERSION OF PYRETHROID ISOMERS D TO MORE ACTIVE SPECIES

This invention relates to the transformation of pyrethroid isomers into isomers that are more pesticidally active than the starting isomers

Pyrethroids to which. to which this invention relates are esters that crystallize and have at least one asymmetric carbon atom to which a proton is attached that epimerizes. The more pesticidally active pyrethroids also contain at least one, but usually two or more, other asymmetric carbon atoms and therefore imply isomeric mixtures in which one or more isomers are more pesticidally active than the others.

Examples of such pyrethroids are alpha-cyano-benzyl esters of formula (A):

wherein R ¹ is halogen, haloalkyl, alkenyl or haloalkenyl; every 2

R is independently halogen, alkyl, haloalkyl, alkoxy, phenyl, phenoxy, phenylalkyl, substituted phenyl and substituted phenyl*alkyl where the substituents include one or more alkyl, halogen, haloalkyl, nitro, hydroxy and cyano; and n is 0-5, preferably 1-3.

In the formula above, asymmetric carbon atoms are marked with 1, i alpha. All substituents on the native group can be the same, or the substituents can be different. Alkyl and alkoxy may contain

1-8 carbon atoms, preferably 1-4 carbon atoms. Alkenyl may contain 2-8 carbon atoms, preferably 2-4 carbon atoms.

Halogen includes fluorine, chlorine or bromine. A typical phenylalkyl group is benzyl. Substituted phenyl includes tolyl, xylyl, trichlorophenyl and trifluoromethylphenyl. Substituted phenylalkyl includes methylbenzyl, trichlorobenzyl and trifluoromethylbenzyl.

The above and other pyrethroids are known and described, for example, in Kirk-Othmer, Encyclopedia of Chemical Technology,

Second Edition, Vol.13, pp.456-458, in the following US Patents:

4,024,163 - Elliot et al. (NRDC)

4,133,826 - Warnant et al (Roussel Uclaf)

4,136,195 - Warnant et al (Roussel Uclaf)

4,213,916 - Davies. et al (Shell)

4,287,208 - Fuchs et al (Bayer)

4,308,279 - Smeltz (FMC)

4,427,598 - Mason et al (Shell)

4,512,931 - Robson (ICI)

4,544,508 - Fuchs et al (Bayer)

4,560,515 - Stoutamire et al (Shell)

4,582,646 - Stoutamire et al (Shell)

4,670,464 - Doyle et al (ICI)

4,681,969 - Williams et al (ICI) and in the following PCT patent publications:

WO 86/04215 - Hidasi et al (Chinoin)

WO 86/04216 - Hidasi et al (Chinoin)

Preferred pyrethroids that are converted into more active isomers according to the present invention are those of the formula A in which R is dihalonyl 2 or tetrahalopropyl, R is phenoxy, and n is 1. More preferred pyrethroids, 1 are those in which n is 1, R is dihalonyl or tetrahalo

1 is propenyl and R is phenoxy; and those where n equals 2, R is dihalovinyl or tetrahalopropenyl and one ^R is fluorine while 2 the other R is phenoxy. The last preferred compounds are isomeric mixtures which have the common name cyfluthrin (cyfuthrin) tuba

2 1 R is dichlorovinyl, n is 2 and one of R is fluorine. When R is dichlorovinyl, n is 1 and R is phenoxy, the mixtures are known as cypermethrin.

Cypermethrin contains four cis and four trans isomers designated I-VIII as follows:

cis isomers

I. (S) (alpha-cyano) (3-phenoxyphenyl)methyl 1R,cis-3-(2,2dichloroethenyl)-2,2-dimethylcyclopropane-carboxylate (abbreviated 1R, cis S)

II. (R) (alpha-cyano) (3-phenoxyphenyl)methyl 1S,cis-3-(2,2dichloroethyl)-2,2-dimethylcyclopropane carboxylate (abbreviated 1S, cis R)

III. (S)(alpha-cyano)(3-phenoxyphenyl)methyl IS, cis-3-(2,2dichloroethenyl)-2,2-dimethylcyclopropane-carboxylate (abbreviated 1S, cis S)

IV. (R) (alpha-cyano) (3-phenoxyphenyl)methyl 1R.,cis-3-(2,2dichloroethenyl)-2,2-dimethylcyclopropane-carboxylate (abbreviated 1R, cis R) trans isomers

V. Trans isomer I (abbreviated 1R, trans S) VI. Transgender isomer II (abbreviated 1S, trans R) VII. Transgender isomer III (abbreviated 1S, trans S) VIII. Transgender isomer IV (abbreviated 1R, trans R).

Cyfluthrin and other pyrethroids to which the invention may apply include similar isomeric mixtures.

It is known that the most insecticidally active isomers are the isomers I and V listed above, but that enantiomeric pairs I/II (abbreviated cis-2) and V/VI (abbreviated trans-2) are more insecticidally active9 than enantiomeric pairs III/IV (abbreviated cis-1) and VII/VIII (abbreviated trans-1). It is very difficult and commercially impractical to separate the more active isomers such as I and V from the complex of isomeric mixtures in the usual pyrethroid synthesis. Accordingly, efforts have been made to produce more pesticidally active pyrethroids by techniques of conversion of less active isomers during the synthesis of the product mixture into more active isomers, i.e. that the isomeric mixtures are enriched in terms of their more active isomers, thus avoiding the complex decomposition procedures and losses in the rejection of less active isomers.

However, even when the isomeric mixtures were converted before interpretation, the conversion procedures were not commercially practical due to poor yields, usually due to the production of unwanted byproducts that often contained as much of the isomer as the desired product, and due to the lengthy process at high degrees, high temperatures, and/or the need for expensive reagents. In the case of cypermethrin, the major byproduct is (R,S)-2-oxo-1,2bis(3-phenoxyphenyl)ethyl cis- and trans-3-(2,2-dichloroethenyl)-2,2dimethylcyclopropanecarboxylate, a mixture of six isomers commonly referred to as the benzoin byproduct. Similar byproducts have been reported in the synthesis of other pyrethroids such as cyfluthrin. Examples of earlier efforts to convert isomeric mixtures into more active species are the procedures described in U.S. Patents 4,213,916, 4,308,279, 4,544,51( 4,544,508, 4,512,931, 4,427,598, 4,670,646 and 4,681,969 and two PCT patent applications listed above.

It has now been established, according to one aspect of this invention, that the crystallization pyrethroid isomers can be converted into the desired, more pesticidally active, isomers by contacting a suspension of the starting isomer mixture in a hydrocarbon solvent with a base and a catalyst, mixing the resulting mixture at a temperature which gives conversion, and isolating the obtained, crystallized, more active isomers.

In another aspect of the invention, the less active isomers themselves are converted into more active isomers by treatment, or the less active diastereoisomer mixtures are converted into the more active isomers themselves, or the starting mixture of more active and less active enantiomeric pairs is converted into an enriched mixture of the enantiomeric pair, i.e. where the more active enantiomeric pairs predominate.

In another aspect of the invention, the starting isomeric mixture is a mixture of four enantiomeric pairs of cypermethrin or cyfluthrin, its own pairs, or has some combination of pairs such as cis-1 and cis-2 pairs and trans-1 and trans-2 pairs, and a product mixture containing greater proportions of more active enantiomeric pairs.

By the method according to the invention, pesticidally inactive or less active isomers or enantiomers are converted into more active or active isomers or enantiomers, and mixtures of either more active or less active isomers or enantiomers are enriched into more active isomers or enantiomers. The procedure can be performed at room temperature and with solvents used in esterification reactions in which pyrethroids are formed, which avoids changing the solvent. In addition, the reagents for conversion are not expensive and the by-products are reduced to a minimum with a simultaneous increase in the yield of active substances! T*/'' t

of the product. The process is therefore extremely suitable for commercial production.

The by-product is significantly reduced by using as base a weakly basic compound such as an alkali metal salt of a weak acid, but is more effectively reduced by adding an aldehyde additive to the base-containing reaction suspension. The aldehyde additive is believed to prevent the formation of the benzoin ester by-product by reaction with the aldehydes believed to occur as benzoin ester intermediates.

While the following description describes the application of the invention to the isomers of cypermethrin and cyfluthrin, it is understood that the invention applies to any crystallization pyrethroid isomer or mixture of isomers, ie. pyrethroid compounds having at least one asymmetric proton-bearing carbon atom capable of epimerization. However, the invention is particularly adapted to the treatment of crystallising pyrethroids with an epimerizing proton on an asymmetric carbon atom and having multiple asymmetric carbon atoms. Such pyrethroids normally include mixtures of multiple isomers including enantiomeric pairs, such as the eight isomers (four enantiomeric pairs) of cypermethrin and cyfluthrin described above. As mentioned earlier, the more isomers a pyrethroid contains, the more difficult and expensive it is to produce more active isomers or mixtures enriched with them.

In this description, isomers refers to and includes enantiomeric pairs as well as individual isomers and mixtures of isomers.

Accordingly, the starting material of the present invention can be either a crude material, such as an unpurified reaction mixture containing crystallization pyrethroid isomers, or the starting material can be purified so that it contains known isomers and their proportions. While the starting material may initially be in a liquid state, for the success of the invention it is necessary that the crystallization is initiated in a liquid environment so that the material is in the form of a suspension when it is brought into contact and mixed with the base and the catalyst. Thus, the material can either be completely solid or it can be a liquid mixture in which crystallization is initiated by pelleting with one or more crystals of the active isomers that we want to produce. Preferably, the starting material is completely solid.

The liquid medium in which the suspension is formed consists mainly of an inert, non-polar hydrocarbon solvent in which the desired isomers are dissolved. Such inert hydrocarbons include aliphatic or cycloaliphatic hydrocarbons which are liquid at the room temperature used in the processes, eg, about 5-35°C, preferably 1-25°C. Hydrocarbons typically contain about 5-16 carbon atoms, preferably 6-8 carbon atoms, and thus include straight and branched pentanes, hexanes, heptanes, octanes, their cyclic analogs, and mixtures thereof.

With hydrocarbons, other solvents can also be used in the liquid medium, provided that they are not present in quantities that would reduce or destroy the efficiency of the treatment. For example, while some water or polar organic liquids such as acetonitrile may be present in the liquid medium, it has been found that polar liquids tend to inhibit the conversion process of pyrethroids to soluble forms and thus reduce yields of the desired active isomers. Water in large quantities is also undesirable because it reduces yields due to an increase in by-product yields. A similarly abrasive, hydrocarbon solvent may contain minor amounts of aromatic hydrocarbon components; again, these components lower the yield of useful product, mainly by increasing solubility by preventing crystallization. The liquid medium of the suspension must therefore mainly comprise an inert hydrocarbon solvent selected so that it does not dissolve the desired isomer in any way.

The solvent is used in an amount that provides a fluid medium for the conversion process and so that the medium can be easily mixed. About 1-10 parts by weight of solvent per part by weight of pyrethroid coating material is usually sufficient, or the amount may vary depending on the coating material. The preferred ratio is about 2-4 parts by weight of solvent to part by weight of pyrethroid.

The bases used in the process can include both strong and weak inorganic bases, of which the following can be listed: alkali metal or alkaline earth metal oxides, hydroxides, carbonates, bicarbonates, cyanides, cyanates, acetates and borates, and alkali metal fluorides such as KF. Other bases include organic amino compounds such as trialkylamine where the alkyl group contains 1 to about 8 carbon atoms, including both straight and branched alkyl groups such as triethylamine, and N-heterocycles such as pyridine, and

quinoline, pyrrole, pyrazole, pyrrolidine, and the like. Bases are preferably base salts of organic or inorganic acids such as sodium or potassium carbonate, bicarbonate, acetate and cyanide, and potassium salts are 3-(2,2-dichloroethenyl)-2,2-dimethylcyclopropanecarboxylic acid. The base can be used alone or in any mixture of two or more of them.

Bases are preferably added to the hydrocarbon solvent medium as solids. Aqueous solutions of one or more of the bases mentioned above can be used, or the amount of water which, if introduced into the liquid medium with these solutions, must not be such that it can influence the process or reduce the yield of the crystallization product, as mentioned above. The amount of base may vary depending on its strength and the economy of treatment, e.g. retention times. Weaker bases may require longer treatment than strong bases, but smaller amounts of strong bases may allow treatment times equivalent to those when a weaker base is used. Usually, for a base that has a pKa of about 9-11, about 1 mass part of the base per 10 mass. parts of pyrethroid coating material to be effective, but for a base with a pKa over 11, less than 1 part by mass of base per 10 parts by mass of pyrethroid should be sufficient.

In order to further reduce the content of benzoin by-products, it is preferable to add an aldehyde scavenger to the reaction suspension, either directly or indirectly by mixing with a base, in order to react with aldehydes which are considered to be present as intermediates of unwanted benzoin ester by-products. Suitable aldehyde scavengers include alkali metal metabisulfites, hydrogen sulfites, and hydrosulfites such as sodium metabisulfite, sodium hydrosulfite, and sodium hydrogen sulfite. Aldehyde scavengers are used in relative mass ratios to the base of about 2:1 to 1:2, preferably from 1:1. Preferred base/aldehyde scavenger pairs for optimal prevention of benzoin byproduct formation are potassium cyanide/sodium metabisulfite, sodium cyanide/sodium hydrogen sulfite, sodium cyanide/sodium hydrosulfite, and potassium cyanide/potassium metabisulfite.

Useful cabalizers include quaternary ammonium or phosphonium compounds and crown ethers other than the base. Suitable quaternary compounds are compounds that can be found on the market, and include the following, either alone or in some mixture:

-,8Methyl(Cg-C^θ-trialkyl)ammonium chloride

Benzyltributylammonium chloride

Benzyltriethylammonium chloride

Benzyltrimethylammonium chloride

Benzyltriphenylphosphonium chloride n-Butyltriphenylphosphonium bromide Cetyltrimethylammonium bromide Dodecyltriphenylphosphonium bromide Ethyltriphenylphosphonium bromide Methyltributylammonium iodide Methyltriphenylphosphonium bromide Myristyltrimethylammonium bromide Phenyltrimethylammonium bromide Phenyltrimethylammonium tribromide n-Propyltriphenylphosphonium bromide Tetrabutylammonium bromide Tetrabutylammonium chloride Tetrabutylammonium hydrogen sulfate Tetrabutylammonium hydroxide Tetraethylammonium bromide Tetramethylammonium chloride Tetramethylammonium fluoride pentahydrate Tetramethylammonium hexafluorophosphate Tetramethylammonium hydroxide Tetramethylammonium tetrafluoroborate Tetraethylammonium chloride Tricaprylmethylammonium chloride Tris(3,6-dioxaheptyl)amine.

Other halides than those mentioned above can be used, such as bromides, chlorides and some iodides. The catalyst can also react with the base to produce a compound suitable for treatment. Typical examples of such compounds are tricaprylmethylammonium phenolate, tricaprylmethylammonium methylate, benzyltrimethylammonium hydroxide, benzyltrimethylammonium methoxide, tetraethylammonium hydroxide, and tetrabutylammonium cyanide.

Since the catalysts of the shorter quaternary series (C^_Cg) are less soluble in the hydrocarbon solvent in the process than the quaternary compounds of the longer series, it is preferable to dissolve the quaternary catalyst of the shorter series in an aprotic organic solvent such as an organic nitrile (acetonitrile, propionitrile, or similar) before adding the catalyst to the reaction medium. The amount of aprotic solvent should be approximately equivalent to the weight of the catalyst.

Too much solvent can dissolve the starting pyrethroid isomers and thus prevent the formation of the reaction suspension necessary for the desired conversion to more active isomers.

Crown ethers include 18-crown-6 and variations thereof such as benzo-15-crown-5, 12-crown-4, 15-crown-5, dibenzo-18-crown-6, dibenzo-24-crown-8, dicyclohexane-18-crown-6, and the like. The above and other crown ethers are commercially available and are shown in literature such as Gokel and Durst, Crown Ether Chemistry: Principles and Applications, Aldrichimica Acta, 9(1), 3-12(1976), which is incorporated herein by reference.

Crown ethers and quaternary compounds of a shorter series (including their base adducts) tend to lose their effectiveness in an aqueous environment. Therefore, these catalysts are preferably used when the liquid medium of the hydrocarbon solvent is anhydrous. Preferred catalysts are tricaprylmethylammonium chloride, tetrabutylammonium chloride or tetraethylammonium chloride in acetonitrile, tris(3,6dioxa-heptyl)amine and 18-crown-6. The preferred liquid medium is anhydrous heptane. The preferred base is sodium cyanide.

Suitable amounts of catalyst are around 0.1-1.0 parts by weight of catalyst per 10 parts by weight. pyrethroid coating material, preferably around 0.2-0.5 parts by mass of catalyst per 10 parts by mass of pyrethroid. The catalyst can be added to the pyrethroid suspension in one addition or gradually, such as the first half and the rest in a stream for several hours, e.g. 3-8 hours later.

The order in which the reagent is added to the liquid medium is usually not critical; any reagent, including the pyrethroid starting material, may be added first or may be added later. In addition, the base and adduct may be added as a preformed adduct or the components may be added separately. In the case of a base-catalyst adduct, sequential addition is preferred, such as the first about half and the second half about 3-8 hours later. The order of addition, amount and proportion of reagents can be adjusted so as to minimize the production of unwanted by-products such as benzoin esters. The preferred order of addition is that the pyrethroid starting material is mixed with the aldehyde scavenger in a solvent for about two hours, and then the base and catalyst are added to the mixture.

The suspension containing the pyrethroid isomers, the base and the catalyst is mixed for such a long time and at such a temperature that the conversion to the desired isomers is induced. One of the advantages of the invention is that the conversion can conveniently be carried out in ambient temperature conditions such as around 5-35°C, preferably around 10-25°C. Usually, the reaction mixture is stirred for about 2 to about 10 hours, preferably about 3 to 8 hours, after which the crystallization product can be isolated by conventional means such as filtration, evaporation, decantation, centrifugation, or some combination of these methods. Although the reaction mixture can be cooled before filtration, it is preferable that the temperature is maintained during the procedure in order to reduce the possibility of trapping unwanted impurities in the crystallization structure of the product. If desired, the product can be recrystallized one or more times to increase the degree of purity.

It is considered that the hydrocarbon solvent is critical for the success of the process because it has been established that the more active isomers, the less active isomers are poorly soluble, compared to the solubility in the base itself, such as triethylamine, or another solvent. In the equilibrium state, therefore, the formation of active isomers is favored and is further accelerated by the removal of the solid, more active species as soon as they are rewarded. Conversely, by using a hydrocarbon as the dominant solvent in the process, the reaction leads to the production of a more active cis-2 pair at the expense of a less active cis-1 pair. It is believed that similar principles can be applied to other isomeric mixtures, for example, the conversion of the less active trans-1 pair to the more active trans-2 pair.

According to the process according to the invention, starting isomeric mixtures containing two enantiomeric pairs of cypermethrin or cyfluthrin, e.g. about 15-25 wt.% of the cis-2 pair, and about 15-25 wt.% of the trans-2 pair, whereby the rest is up to 100% distributed between the cis-1 and trans-1 pairs, can be translated into mixtures where cis-2 and trans-2 pairs predominate, e.g. bar about 30 wt.% of each pair, preferably up to about 40 wt.% of each of this pair. In addition, starting mixtures of cis-1 and cis-2 enantiomeric pairs, e.g. about 20-80 wt.% cis-1 and 80-20 wt.% cis-2, can be translated into mixtures that have increased amounts of active cis-2 pairs, e.g. 30-90 wt.% or more. Similarly, starting mixtures of trans-1 and trans-2 enantiomeric pairs, e.g. about 20-80 wt.% trans-1 and 80-20 wt.% trans-2, turn into mixtures that have increased amounts of active trans-2 pairs, e.g. about 30-90 wt.% or more.

The following examples further illustrate the invention. In the examples, the terms cis, trans, cis-1, cis-2, trans-1, and trans-2 refer to the isomers and enantiomeric pairs of cypermethrin or cyfluthrin as defined above, as appropriate. In any case, the name of the compound is followed by liquid chromatographic analysis (% power) and is further abbreviated as follows: C^cis-1 enantiomeric pair; C2=cis-2 enantiomeric pair; T^=trans-1 enantiomeric pair; T2=trans-2 enantiomeric pair; B^=cis-1 benzoin by-product-enantiomeric pair; B2=cis-2 benzoin by-product-enantiomeric pair; B ₃ =trans-1 by-product benzoin enantiomeric pair; i B ₄ =trans-2 by-product benzoin enantiomeric pair.

EXAMPLE 1

Obtaining a mixture enriched in the cis-2 enantiomeric pair of cypermethrin with aqueous _Na2CO3

To a stirred mixture of 10.0 grams (0.024 mol) of (R,S)-(cyano)(3phenoxyphenyl)methyl cis-3-(2,2-dichloroethenyl)-2,2-dimethylcyclopropanecarboxylate (C^=53.8, C2=42.0, 1^=2.8 and T ₂ =1-2), in 20 g of n-heptane, 0.1 gram (0.00025 mol) was added. tricaprylmethylammonium chloride (Aliquat ^R 336, Aldrich Chemical Co.) and 10 ml of an aqueous, 10% sodium carbonate solution. The mixture is stirred at room temperature for five hours. Another 0.1 gram of tricaprylmethylammonium chloride was added, and the mixture was stirred at room temperature for about 13 hours. The reaction mixture was processed to give 8.37 grams of the cis-2 enantiomeric pair (R,S)-(cyano)(3-phenoxyphenyl)methyl cis-3-(2,2-dichloroethenyl) 2,2-dimethylcyclopropanecarboxylate in the form of a solid substance (0.,=4.0, C ₂ =94.0, B ₁ =1.1, B ₂ =0.6).

EXAMPLE 2

Obtaining a mixture enriched in the cis-2 enantiomeric pair of cypermethrin with solid ^200^

The crude solution of the reaction mixture was analyzed by liquid chromatography and found to contain 30.88% of (R,S)-(cyano)-(3-phenoxyphenyl)methyl cis-3-(2,2-dichloroethenyl,-2,2-dimethylcyclopropanecarboxylate) in a mixture of heptane. by chromatography i contains the following isomers:

0^=52.56, C ₂ =41.55, 1^=2.6, and T ₂ =2.7. The second sample of 32.4 grams of the solution was pelleted with cypermethrin crystals that have a high content of the cis isomer (at least 50%) and was mixed at room temperature for about 18 hours for crystallization. This mixture is treated with 0.1 gram (0.00025 mole) of tricaprylmethylammonium chloride and 0*5. , grams of solid sodium carbonate. The mixture is stirred at room temperature for four hours, during which time another 0.1 gram of tricaprylmethylammonium chloride is added. The reaction mixture is stirred for another 3.0 hours at room temperature. The reaction suspension was diluted with 15 ml of an aqueous solution containing 2.0 grams of concentrated hydrochloric acid to neutralize Na ₂ CO ₃ and stirred for 10 minutes. This mixture was processed to give 7.06 grams of the cis-2 enantiomeric pair (R,S)-(cyano)(3-phenoxyphenyl)-methyl cis-3-(2,2-dichloroethenyl)-2,2-dimethylcyclopropanecarboxylate as a solid (C^=4.0, C ₂ =95.0, T ₂ =0.6, B ₂ =0.3).

EXAMPLE 3

Obtaining a mixture enriched in cis-2 and trans-2 enantiomeric pairs of cypermethrin

The mixed mixture of 10.0 grams of n-heptane and 10.0 grams of aqueous 1.0% sodium carbonate solution was cooled to 10°C. Pelleted crystals of (R,S)-(cyano)(3-phenoxyphenyl)methyl cis-3-(2,2-dichloroethenyl)-2,2-dimethylcyclopropanecarboxylate (C^=54, C ₂ =42, T^=3, T ₂ =1) were added. With continuous maintenance of the temperature at 10°C, a solution consisting of 10.0 grams (0.024 mol) of (R,S)(cyano)(3-phenoxyphenyl)methyl cis,trans-3-(2,2-dichloroethenyl)-2,2dimethylcyclopropanecarboxylate (C^=26.7, C ₂ =18.9, T^=23.0, T ₂ ) was added dropwise over a period of 12 hours to form a suspension. = 15 and B ₂ =0.2 grams (0.005 mol) of tricaprylmethylammonium chloride in 10.0 grams of n-heptane. After the addition is complete, the suspension is stirred at 10 C for about 18 hours. This mixture is processed to give 7.5 grams of cis-2 and trans-2 enantiomeric pairs (R,S)-(3phenoxyphenyl)methyl. cis,trans-3-(2,2-dichloroethenyl)-2,2-dimethylcyclopropanecarboxylate as solids (C^=7, C ₂ =41, T^=7, T ₂ =32, B.,=4.6, B ₂ =2.5 and B ₃ =3.8).

EXAMPLE 4

Obtaining a mixture enriched in the trans-2 enantiomeric pair of cypermethrin

A suspension of 10.0 grams (0.024 mol) (R,S)(cyano)(3phenoxyphenyl)methyl trans-3-(2,2-dichloroethenyl)-2,2-dimethylcyclopropanecarboxylate (C^ + C ₂ =1.1, T^=55.4, i T2=43.5), 0.1 gram (0.00025 mol) tricaprylmethylammonium chloride, and 1.0 gram sodium carbonate 20 grams of n-heptane is mixed at room temperature for three hours. Another 0.1 gram of tricaprylmethylammonium chloride was added and the mixture was stirred for another three hours. The reaction mixture is diluted with 10 ml of water and stirred under current for 15 minutes. The resulting mixture is filtered. The filter cake was washed with n-heptane to give 9.17 grams of the trans-2 enantiomeric pair (R,S)-(3-phenoxyphenyl)methyl trans-3-(2,2-dichloroethenyl)-2,2-dimethylcyclopropanecarboxylate (T ₁ =1.7 and T ₂ =97.5).

EXAMPLE 5

Obtaining a mixture enriched in the cis-2 enantiomeric pair of cypermethrin with solid I^CO^

A suspension of 10.0 grams (0.024 moles) of solid (R,S)(cyano)(3-phenoxyphenyl)methyl cis-3-(2,2-dichloroethenyl)-2,-dimethylcyclopropanecarboxylate (C^=51.7, C2=46.8, i T^+ T ₂ =1.5), 0.25 grams (0.00095 moles) of 18-crown-6, i 1.0 grams (0.0072 moles) of potassium carbonate in 20.0 grams of n-heptane was mixed at room temperature for about 18 hours. Dilute hydrochloric acid is added to the reaction mixture to neutralize the potassium carbonate. This mixture is stirred at room temperature for two days. The mixture was filtered and the filter cake dried to give 8.72 grams of the cis-2 enantiomeric pair (R,S)(cyano)(3-phenoxyphenyl)methyl cis-3-(2,2-dichloroethenyl)2,2-dimethylcyclopropanecarboxylate (C^=3.8, i 02=94.9).

*

EXAMPLE 6

Obtaining a mixture enriched in the cis-2 enantiomeric pair of cyfluthrin

A suspension of 5.0 grams (0.012 moles) of solid (R,S) (cyano)(4fluoro-3-phenoxyphenyl)methyl cis-3-(2,2-dichloroethenyl)-2,2-dimethylcyclopropanecarboxylate (0^=49.2 and C ₂ =50.8), 0.5 grams (0.0047 moles) of sodium carbonate, and 0.05 grams (0.00012 moles) 10.0 grams of tricaprylammonium chloride was mixed at room temperature for four hours. Another 0.05 grams of tricaprylmethylammonium chloride was added and the suspension was stirred at room temperature for about 13 hours. The reaction mixture was neutralized with dilute hydrochloric acid and stirred for about 30 minutes 4.45 grams of the cis-2 enantiomeric pair (R,S) (cyano) (4-fluoro-3phenoxyphenyl)methyl cis-3-(2,2-dichloroethenyl)-2,2-dimethylcyclopropanecarboxylate (C^=0.1 and O2=99.8).

EXAMPLE 7

Obtaining a mixture enriched in the cis-2 enantiomeric pair of cypermethrin with triethylamine "

A suspension of 10.0 grams (0.024 mol of (R,S)-(cyano)(3phenoxyphenyl)methyl cis-3-(2,2-dichloroethenyl)-2,2-dimethylcyclopropanecarboxylate (0^=53.8, C ₂ =42.0, 1^=2.8, T ₂ =1.2), 0.1 gram (0.00025 mol) tricaprylmethylammonium chloride, i 8.0 grams (0.079 mole) of triethylamine was stirred at room temperature for 5.5 hours. Another 0.1 gram of tricaprylammonium chloride was added and the mixture was stirred for another 17 hours. The filter cake was washed with n-heptane to give 7.78 grams of the cis-2 enantiomeric pair (R,S)(cyano)(3-phenoxyphenyl)methyl-cis-3-(2,2dichloroethenyl)-2,2-dimethylcyclopropanecarboxylate (C^=3.6, C ₂ =

91.0, _T2 =0.9).

EXAMPLE 8

Obtaining a mixture enriched in the trans-2 enantiomeric pair of cyfluthrin

A suspension of 5.0 grams (0.012 moles) of solid (R,S)(cyano)4fluoro-3-phenoxyphenylJ trans-3-(2,2-dichloroethenyl)-2,2-dimethylcyclopropanecarboxylate (T^=71.0, T ₂ =28.0), 0.5 grams (0.0036 moles) of potassium carbonate, and 0.05 grams (0.00012 moles) tricaprylmethylammonium chloride in 10.0 grams of n-heptane is mixed at room temperature for about 17 hours. The base mixture is neutralized with dilute hydrochloric acid and stirred under current for about 30 minutes. This mixture was filtered and the filter cake was dried to give 4.82 grams of the trans-2enantiomeric pair (R,S)(cyano)-(4-fluoro-3-phenoxyphenyl)methyl 15 trans-3-(2,2-dichloroethenyl)-2,2-dimethylcyclopropanecarboxylate (Τ ₁ =4 _ί 6, T ₂ =94.0).

EXAMPLE 9

Obtaining a mixture of enriched IR, cis S bromo analogue of isomer I of cypermethrin from a mixture of diastereoisomers

A solution of 9.4 grams (0.019 mol) of (R,S)(cyano)(3-phenoxyphenyl)methyl 1R,cis-3-(2,2-dibromoethenyl)-2,2-dimethylcyclopropanecarboxylate (IR,cis S = 46.0%, IR,cis R = 52.0%) in 18 grams of n-heptane was stirred at room temperature until a solid phase was formed. To this suspension was added 0.2 grams (0.00076 moles) of 18-crown-6 and 1.0 grams (0.0072 moles) of potassium carbonate. This mixture is stirred at room temperature for about 20 hours. A sample of the solid was analyzed by gas chromatography (area %) to determine that it contained 87.8% of the (S)-(cyano)(3-phenoxyphenyl)methyl IR,cis-3-(2,2-dibromoethenyl)-2,2-dimethylcyclopropanecarboxylate and 6.9% of the IR,cis R isomer.

EXAMPLE 10

Preparation of the cis-2 enantiomeric pair (R,S)-(cyano)(3-phenoxyphenyl)methyl cis-3-(2,2-dichloroethenyl)-2,2-dimethylcyclopropanecarboxylate using potassium fluoride and tricaprylmethylammonium chloride

A suspension of 10.0 grams (0.024 mol) (R,S)-(cyano)(3-phenoxy phenyl)methyl cis-3-(2,2-dichloroethenyl)-2,2-dimethylcyclopropanecarboxylate (0^53.9, C ₂ =44.4, i T ₂ = 1.7), 0.1 gram (0.00025 mol ^: ) tripropylammonium chloride and 1.0 gram (0.02 mol) of potassium fluoride in 20 grams of n-heptane is mixed at room temperature for two hours. The reaction mixture is neutralized with dilute hydrochloric acid and stirred under current for about 30 minutes. This mixture was filtered, but the filter cake was dried to give 8.84 grams of the cis-2 enantiomeric pair (R,S)-(cyano)(3-phenoxyphenyl)methyl cis-3-(2,2dichloroethenyl)-2,2-dimethylcyclopropanecarboxylate (C^ =7.0, C ₂ =90.0)

EXAMPLES 11-50

The attached plates illustrate other effective conditions for carrying out the invention. Table 1 gives the conditions and results for the procedure performed as described in Example 1 with indicated variations.

Tables 2 and 3 have a similar relationship with Examples 3 and 4, respectively

Benzoin in tablets means the benzoin by-product described earlier in this application. NR indicates no result.

TABLE 1

Preparation of Cypermethrin mixtures enriched with cis-2 enantiomeric pairs

Reactants Product analysis (area % HPLC)

Ex. No. Catal. Type ^{c r} .Base Type ^c weather (h) material Analysis ⁰ AHT (g) £i ^c 2 Trans Total Benzoin Total Type (?) 11 A 0.1 A A 2.0 A e 17.8 80.0 2.3 NR 4.0 e 9.8 87.6 2.6 NR 6.0 e 7.3 90.4 2.3 NR 8.0 8.9 6.7 92.3 NR NR 12 A 0.1 A B 18.0 B 8.7 6.2 92.6 0.5 NR 13 A 0.1 B C 18.0 B 8.9 5.8 92.2 0.5 NR 14 A 0.2 C D 17.5 C 7.7 3.9 86.0 1.2 1.2 15 A 0.2 A E 17.0 C 8.5 4.0 93.5 2.0 NR 16 see base * F 5.5 C - 26.0 71.0 NR NR 11.0 • 22.0 75.0 NR 1.3 23.0 8.4 5.0 92.0 NR 2.6 17 A 0.2 A G 18.0 C 9.1 7.1 89.2 NR 2.5 18 A 0.2 A H 17.5 C 8.1 5.0 92.0 0.8 NR 19 B 0.5 A C 18.0 D 8.4 6.0 93.7 NR 0.2 20 B 0.5 A A 18.0 D 8.9 6.6 92.4 NR 0.3 21 B 0.5 A I 18.0 0 8.4 19.0 80.5 NR NR 22 B 0.5 A J 18.0 D 8.9 5.8 93.6 NR NR 23 C 0.5 A C 18.0 D 8.1 22.0 77.0 NR NR 24 C 0.5 A A 18.0 D 8.5 18.0 80.0 NR NR 25 c 0.5 A K 29.0 D 8.0 7.0 89.0 NR 2.0 26 0 0.4 A L 8.0 D 9.9 19.8 71.8 0.6 NR 27 E 0.2 A L ' 24.0 C 7.8 5.0 92.6 1.4 NR 28 f 0.4 A L 19.0 C 8.3 4.0 79.0 NR . NR

TABLE 1 (continued)

D 0.2 D M 22.0 E NR 8.8 86.0 2.0 2.2 D 0.2 D N 4.0 E NR 11.6 82.0 2.2 3.1 D 0.2 D In 22.0 E NR 9.3 82.0 2.1 4.8 D 0.4 λ 0 21.0 F NR 8.6 88.0 2.1 0.1 D 0.1 D P 7.0 E NR 10.4 83.8 2.6 2.3 0 0.2 D 0 18.0 E NR 9.0 86.0 2.0 2.0 D 0.2 D R 18.0 E NR 10.0 84.0 2.0 2.3 ε 0.28 0 P 18.0 E NR 9.8 86.0 1.9 1.1 D 0.2 D With 17.0 E NR 17.0 80.0 2.0 NR G 0.2 D P 18.0 E NR 9.0 88.0 2.0 NR G 0.2 0 T 46.0 E NR 8.2 87.0 2.0 NR D 0.2 0 T 24.0 E NR 7.7 89.0 2.1 0.1 D 0.2 D in 26.0 E NR 9.0 85.0 2.1 3.0 0 0.2 0 in 18.0 E NR 10.8 86.0 2.4 0.5 D 0.2 D X 18.0 E NR 9.0 86.0 1.7 1.8

a. Catalyst

A = Tricaprylmethylammonium chloride B = 18-crown-6

C = Tris(3,6-diOxaheptyl)amine

D = Tetrabutylammonium chloride/acetonitrile (50/50 mixture) E = Tetrabutylammonium chloride

F = Tetrabutylammonium chloride/Methanol (50/50 mixture)

G = Tetraethylammonium chloride/acetonitrile (50/50 mixture)

b. Solvent

A = n-heptane (20 grams)

B = n-octane (20 grams)

C = n-pentane (20 grams)

D = n-heptane (10 grams)

c. Base (1.0 gram unless otherwise indicated)

A = Solid potassium cyanide B = Solid potassium hydroxide C = Solid potassium carbonate

D = Aqueous, 10% sodium carbonate solution (10 ml)

E = Aqueous, 10% sodium carbonate/sodium bicarbonate - pH 9.5 (10 ml)

F = Catalyst/base compound: tricaprylmethylammonium phenolate (0.1 g)

G = Solid sodium cyanide H = Borate buffer solution - pH 10 (10 ml)

I = Potassium acetate

J = Potassium cyanide

K = Potassium phenoxide j

L = Solid sodium carbonate M = Solid sodium acetate (0.5 grams)

N = Solid potassium cyanide (0.5 grams)

O = Potassium Cyanide (2.2 grams)/Sodium Metabisulfite (1.0 grams) P = Solid Sodium Cyanide (0.5 grams)

Q = Sodium cyanide (0.5 grams)/sodium sulfite (0.5 grams)

R = Sodium cyanide (0.5 grams)/Sodium bicarbonate (0.5 grams)

S = Sodium cyanide (0.5 grams)/sodium hydrogen sulfide (0.5 grams)

T = Sodium cyanide (0.5 grams)/sodium metabisulfite (0.5 grams)

U = 3-(2,2-Dichloroethenyl)-2,2-dimethylcyclopropanecarboxylic acid, potassium salt (0.5 grams)

V = solid potassium acetate (0.5 grams)

W = Sodium Cyanide (0.5 grams)/Sodium Hydrosulfite (0.5 grams)

X = Sodium Cyanide (0.5 grams)/Sodium Sulfate (0.5 grams)

d. Analysis of laying material - % area. HPLC (10.0 g starting material in Pr.11-28, 5.0 g in Pr.29-43)

A. C _] = 54.1; C ₂ = 44.2; = 1.7

B. C ₁ = 52.9; C ₂ = 45.1; Ί^+Ί^ =2.0

C. C ₁ = 53.8; C ₂ = 42.0; = 4.0

D. C ₁ = 51.7; C ₂ = 46.8; T.,+T ₂ = 1.5

E. C _] = 51.9; C ₂ = 47.1; T^+T ₂ ^{= 2} *°

F. Same as E but use one 10 g of coating material

e. Analysis by gas chromatography (area %) before HPLC.

TABLE 2

Obtaining a mixture of Cypermethrin enriched with Cis-2 and Trans-2 Enantiomeric pairs

b c Pr. Catalyst Solvent Base Reaction time (h) No. (g) Type (g) 44 0.2 A 5 A 40 45 0.2 B 20 A 17 46 0.4 C 20 B 72 47 0.4 C 20 C 18

Analysis of the product Polazni (% area.HPLC

Material AMT normalized) Total

Analysis^ (g) C^ C ₂ Τ-] Z ₂

A NR 17.4 27.9 12.0 27.6 15.1

A NR 15.4 26.6 13.1 28.3 16.6

B 9.64 5.0 41.0 3.0 47.7 1.5

B NR 5.8 41.0 3.8 47.6 0.5

a. Catalyst: Tricaprylmethylammonium chloride (Ex. no. 44,45)

Tetrabutylammonium chloride/acetonitrile, 50/50 (Pr.br.46,47)

b. Shepherds

A = n-Pentane

B = 19.0 g n-pentane and 1.0 g methanol C = n-heptane

c. Base: A = Aqueous, 10% sodium carbonate solution (10 ml) - 1.0 g

B = Potassium cyanide (1.0 g)/sodium metabisulfite (1.0 g)

C = Potassium cyanide (1.0 g)/Potassium metabisulfite (1.2 g)

d. Analysis (% surface HPCL) 10.0 g of coating material used in

Pr.45, 12.6 g in Pr.44; 10.0 g in Ex. 46 and 47.

Ex. 44 and 45

A = C ₁ = 26.7;. C ₂ = 18.9; = 23.0; Ί* ₂ = 16.0; Total benzoin = 0.6

Ex. 46 and 47

B = C ₁ = 26.6; C ₂ = 22.7; = 27.6; T ₂ = 20.7.

TABLE 3

Obtaining a mixture of Cypermethrin enriched with trans-2 enantiomers

Ex. Catalyst Solvent ⁰ Base Type ^c (g) Reactionary Starting Point Product Analysis (Area % HPIC) Weather (h) Material Analysis^ . ΑΜΓ Total Total Benzoin No. (g) (g) (g) cis T-i _This 48 0.4 40 A 1.0 18 A 18.3 NR 7.1 90.1 1.4 49 1.0 200 B 10 13 B 89.2 NR 9.0 91.0 NR 50 1.0 200 B 10 13 B 94.5 NR 2.8 96.3 NR a. Catalyst : Tricaprylmethylammonium chloride

b. Solvent: n-heptane

c. Base:

A = Aqueous solution of sodium carbonate and sodium bicarbonate; pH 9.0-9.5; 10 ml

B = solid sodium carbonate

d. Analysis of the base material

A = 20.0 grams; total cis = NR; = 56.1; T ₂ = 41.0 B = 100.0 grams; Total cis = 1.1; = 55.4; T ₂ = 43.5

Claims (29)

1. A process for converting a starting mixture of crystallizable pyrethroid isomers to the desired pesticidally more active isomers, characterized in that: a) form a suspension of the starting mixture in a liquid medium consisting of an inert hydrocarbon solvent in which the desired isomers are insoluble, b) the suspension is contacted with the base and the catalyst, the catalyst being soluble in the liquid medium and selected from quaternary ammonium compound, quaternary phosphonium compound and crown ethers, c) the resulting mixture is stirred while maintaining a temperature that is effective for conversion; and d) isolate the crystallized isomers obtained. The process according to claim 1, characterized in that the starting mixture comprises the more active and less active enantiomers of cypermethrin and that the crystallized product obtained predominantly contains the more active enantiomers. Process according to claim 2, characterized in that the starting mixture comprises four enantiomers of cypermethrin vapor and that the crystalline product obtained mainly comprises cis2 and trans-2 enantiomers of vapor. The process according to claim 2, characterized in that the starting mixture comprises cis-1 and cis-2 enantiomers of cypermethrin vapor and that the crystalline product obtained predominantly comprises a cis-2 enantiomeric pair. Process according to claim 2, characterized in that the starting mixture comprises trans-1 and trans-2 enantiomers of cypermethrin vapor and that the crystalline product obtained contains predominantly a trans-2 enantiomeric pair. Process according to claim 1, characterized in that the starting mixture contains more active and less active cyfluthrin enantiomers and that the crystalline product obtained mainly contains more active enantiomers. AL Ί. The process according to claim 6, characterized in that the starting mixture contains four enantiomeric pairs of cyfluthrin and that the crystalline product obtained predominantly contains cis-2 and trans-2 enantiomeric vapors. Process according to claim 6, characterized in that the starting mixture comprises cis-1 and cis-2 enantiomeric pairs of cyfluthrin and that the crystalline product obtained contains predominantly a cis-2 enantiomeric pair. Process according to claim 6, characterized in that the starting mixture contains trans-1 and trans-2 enantiomers of cyfluthrin vapor and that the crystalline product obtained predominantly contains a trans-2 enantiomers pair. A process according to claim 1, characterized in that the starting mixture contains more active and less active enantiomers (cyano) (3-phenoxyphenyl) methyl-3- (2,2-dibromoethenyl) 2,2-dimethylcyclopropanecarboxylate and the crystalline product obtained predominantly contains more active enantiomers. Process according to claim 10, characterized in that the starting mixture contains IR, cis S and IR, cis R isomers of (cyano) (3-phenoxyphenyl) methyl 3- (2,2, -dibromoethenyl) -2,2 dimethylcyclopropane carboxylate) and that the product obtained predominantly contains the IR, cis S isomer. A process according to claim 1, characterized in that the base is a basic salt of organic or inorganic acid. Process according to claim 12, characterized in that the base is an aqueous solution of a basic salt of organic or inorganic acid. Process according to claim 12, characterized in that the base is a solid. A process according to claim 1, characterized in that the suspension is anhydrous. 16. The process according to claim 1, wherein the base is a solid alkali metal or alkaline earth metal oxide, hydroxide, carbonate, bicarbonate, cyanide, cyanate, acetate or borate, an aqueous solution of one or more thereof, or trialkylamine. Zb Yl. The process according to claim 1, characterized in that in step (b), the base and catalyst adducts are formed before contacting the suspension. 18. The process according to claim 1, characterized in that the starting mixture comprises cis-1 and cis-2 enantiomeric vapor cypermethrin, the solvent is at least one aliphatic or cycloaliphatic hydrocarbon having 5-16 carbon atoms, the base is a basic salt of organic or inorganic acid and is a catalyst for tricaprylmethylammonium chloride. 19. The process according to claim 18, wherein the solvent is heptane and the basic salt is an alkali metal carbonate. Process according to claim 1, characterized in that the suspension is formed by splitting a solution of the starting mixture with at least one crystal of the desired isomers. 21. The process according to claim 1, characterized in that the starting mixture comprises four enantiomeric cypermethrin vapors, the solvent is at least one aliphatic or cycloaliphatic hydrocarbon having 5-16 carbon atoms, the base is a basic salt of organic or inorganic acid and the catalyst is tricaprylmethylammonium chloride. Process according to claim 21, characterized in that the solvent is heptane and the basic salt is an alkali metal carbonate. A process according to claim 1, characterized in that the starting mixture comprises trans-1 and trans-2 enantiomeric vapors of cypermethrin, the solvent is at least one aliphatic or cycloaliphatic hydrocarbon having 5-16 carbon atoms, the base is a basic salt of organic or inorganic acid and is a catalyst for tricaprylmethylammonium chloride. • Process according to claim 23, characterized in that the solvent is heptane and the basic salt is an alkali metal carbonate. Process according to claim 1, characterized in that the starting mixture comprises four enantiomeric pairs of cypermethrin or cyfluthrin, the amounts of cis-2 and trans-2 enantiomeric pairs being in the range from 15 to 25% by weight and the crystalline product comprises at least 30 % by weight of each of the cis-2 and trans-2 enantiomeric pairs. 26. A process according to claim 1, characterized in that the starting mixture comprises 20-80% by weight of cis-1 and 80-20% by weight of the cis-2 enantiomeric pairs of cypermethrin or cyfluthrin and that the crystalline product comprises at least 30-90% by weight. % cis-2 pairs. Process according to claim 1, characterized in that the starting mixture comprises 20-80 wt% trans-1 and 80-20 wt% trans-2 enantiomers of cypermethrin or cyfluthrin and that the crystalline product comprises at least 30-90 wt% trans-2 pairs. Process according to claim 1, characterized in that in step (b), the suspension containing the base and the catalyst is contacted with an aldehyde stripper. A process according to claim 28, characterized in that the aldehyde removal agent is metabisulphite, hydrogen sulphite or alkali metal hydrogen sulphite. Process according to claim 28, characterized in that the base is an alkali metal cyanide and the tetraalkyl (C _x -C ₅ ) ammonium halide catalyst is dissolved in an aprotic organic solvent. 31. The process of claim 28, wherein the base is potassium cyanide, the tetraalkyl (C _x -C ₅ ) ammonium halide catalyst is dissolved in organic nitrile and the aldehyde removal agent is alkali metal metabisulfide.