AP13A - Insecticidal compositions comprising more than one active ingredients. - Google Patents

Abstract

A synergic insecticidal composition

Description

INSECTICIDAL COMPOSITION COMPRISING MORE THAN ONE ACTIVE INGREDIENTS

Technical field 5

This invention relates to insecticidal compositions comprising more than one pyrethroid active ingredients of the Formula (I)

(I) £ I 0 0 0 0 dV the use thereof, the active ingredients and a process 20 for the preparation of the same.

Background Art

In the present specification the spatial 25 configuration of the substituents related to the chiral carbon atom denoted with cc is characterized by ”S and R , respectively. The designations cis’* and trans, respectively, mark the position of the

BAD ORIGINAL A substituents attached to carbon atom 3 of the cyclopropane ring related to the spatial configuration of the substituents of carbon atom I. The absolute spatial configuration of the substituent attached to carbon atom 1 is denoted with the prefix 1R and IS, respectively.

In the present specification the various enantiomers and enantiomer-pairs are designated with the following abbreviations:

la	mixture of IReisS and IScisR
lb	mixture of IRtransS and IStransR
Ic	mixture of IReisR and IScisS
Id	mixture of IStransR and IStransS
If	IReisS
Ig	IRtransS ;
In	t IRtransR
Ii	IS transzR
	It is known that pyrethroids of

AP 0 0 0 0 1 3 mula (I) (known under the generic name cypermethrin ) ( “·

I “ belong to the valuable family of synthetic pyrethroids and are useful as insecticide (Hungarian patent No. 170,866). These compounds may be prepared by reacting m-phenoxy-benzaldehyde cyanohydrine with the corresponding cyclopropane carboxylic acid chloride in the presence of a base CPestic. Sci. 6, 537-... (1975)) . The product thus obtained consists of eight stereoisomers i.e. of a mixture of four enantiomer-pairs. If a 60:40 mixture of the corresponding trans

BAD ORIGINAL and cis cyclopropane carboxylic acid chlorides is used, the mixture contains 18-19 % of enantiomer-pair la, 21-22 % of enantiomer-pair Ic, 26-27 % of enantiomer-pair lb and 33-34 % of enantiomer-pair

Id.

According to prior art the stereoisomers of cypermetrin show different biological activity. It is generally accepted that the activity of molecules comprising cis cyclopropane 'carboxylic acids is superior to that of the corresponding trans derivatives [Pest. Sci. 7» 273 (1976)].

In the comparative biological tests of . various pyrethroids [Pest, Sci. 9, 112-116 (1978)] the cis and trans stereoisomers - including the 15 cypermetrin stereoisomer-pairs - were evaluated together.

The comparative tests were carried out on Musca domestica L. and Phaedon. cochleariae Fab species. Concerning tbe chloro derivatives from the trans isomers activity data of IRtransS (Ig ) and IRtransR were disclosed. The said data show that while the IRtransS isomer possesses a strong activity - the IRtransR isomer is considerably less active [according to the test the activity related to bioresmetrine (100) amounts to 1400 and 81, respectively, on Musca domestica and to 2200 and 110, respectively, on Phaedon cochleariae]. It was disclosed furtheron that the activity of a mixture of both

BAD ORIGINAL Λ

- 4 tested, isomers was lower than the calculated value. Thus the isomers showed an antagonism rather than the expected synergism and the rate of antagonism amounted to 1.42 and 1.46 on house fly and mustard beetle, respectively.

As a result of the said tests and publications the trans isomers and mixtures thereof were pushed to the background of biological interest and research was focused to active cis derivatives and mixtures thereof. This lead to the development of alphametrine (isomer mixture of IRcisS and IScisR (la) of the chloro derivatives) and decametrine [comprising the IRcisS isomer (If) of the bromo derivatives] .

Similar data were set forth for the bromo derivative; on mustard beetle the rate of antagonism amounts to 1.48.

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Disclosure of Invention

According to an aspect of the present invention there is provided a synergistic insecticidal composition containing more than one active ingredients and being harmless to environment characterized by comprising in an amount of from 0.001 to 99 % by weight a synthetic pyrethroid of the Formula (I)

- namely substantially only the IRtransS and IStransR enantiomer-pairs (lb) out from the possible eight

BAD ORIGINAL &

c:

isomers - optionally in admixture with an amount of up to 100 % by weight of one or more activator(s) and. auxiliary agent(s), particularly antioxidants stabilising agents, wetting agents, emulsifying agents, dispersing agents, antifoam agents, diluents and/or fillers .

According to a preferred, embodiment of this aspect of the present invention there are provided insecticidal compositions comprising an isomer mixture having a purity of at least 95 %·

The said isomer mixture is a new crystalline substance, the physicochemical data thereof being disclosed in the Examples.

The present invention is based on the re15 cognition that isomer-mixture lb possesses useful and advantageous biological properties. This is surprising even if it is taken into consideration that in the field of pyrethroids of the Formula (I) extended experimental work was accomplished and a num20 ber of publications and patents were published.

Thus the present invention is based on the recognition that when using a combination of the IRtransS isomer Ig (being the most active trans isomer of the compounds of the Formula (I)) and the

IStransR isomer Ii (being ranged among the less active isomers from the remaining seven isomers) no antagonism characteristic of the earlier published isomer-pairs is observed.

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Moreover a synergistic effect occurs over the additive effect of the pure Ig and Ii isomers when used per se.

The above recognition enables a new type of selection from the isomers of synthetic pyrethroids in order to develop a new active ingredient type having outstanding properties. The said new active ingredient shows various advantages over hitherto known isomer selections:

- lower toxicity on warm-blooded species and humans;

- more economical manufacturing process;

- smaller damages caused to useful parasites and bees.

A significant and decisive advantage of the isomer-mixture lb of'the present invention is that it causes no allergy and skin diseases which were generally observed on the use of the corresponding ’cis cypermethrine isomers of similar activity.

' ^; The synergistic activity of the components of the isomer-mixture lb is so much 'the' more surprising as'no similar synergism takes place between the components of the isomer mixture’ Ia.^V · - .

According to aspects of the present invention there' is provided the selected isomer pair, at in.. ·. - - -. · - -, - . _r 1 secticidal composition comrising the same and a process for the preparation and the use thereof.'.......

According to a still further aspect of the

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BAD ORIGINAL present invention there is provided a process for the. preparation of the said new isomer pair. According to a particularly important aspect of the present invention there is provided a process for the preparation of the cypermethrin isomer-pair lb which enables the highly economical preparation of an active ingredient having the same order of activity as the active ingredient which was hitherto available only be means of the very expensive isolation procedure of a pure and single cis isomer.

According to a further aspect of the present invention there is provided a synergistic insec ticidal composition containing more than one active ingredients and being harmless to environment cha15 racterized by comprising in an amount of from 0.001 to

X % by weight a synthetic pyrethroide of the Formula (I) - namely substantially only the IRtransS and IStransR enantiomer-pair (lb) out from the possible eight isomers - optionally in admixture with an amount of up to 100 % by weight of one or more activator(s) and auxiliary agent(s), particularly antioxidants, stabilising agents, wetting agents, emulsifying agents, dispersing agents, antifoam agents, diluents and/or fillers .

According to a further aspect of the present invention there is provided an isomer mixture lb having a purity of at least 95 % and comprising the IRtransS and IStransR enantiomer-pair of the Formula

BAD ORIGINAL (I).

The physical constants of the said enantiomer-pair are as follows:

IR(KBr) \?_c=0 = 1735 cm¹

NMR (CDCip (ppm) = 1.22, 1.27 CMe₂; 1.69d 1H Cl}

2.32 m 1H C3}' 5.6,d. 1H Cl} 6.39 s 1H alfaproton.

The said pure enantiomer-pair is a white crystalline material, never described in prior art according to our best knowledge. The melting point of the 1:1 mixture of the isomers amounts to 81.0-81.5 °C. It is to be noted that the components Ig and Ii of the isomer-pair are not crystalline per se.

Accordingly in addition to biological and economical advantages the combination of the present invention ) lb facilitates the process of manufacture, the formulation procedure, storing and method of treatment as well.

The isomer-pair lb of the present invention is superior to the known combinations from the » ** -20 point of view of side effects, too. The new isomer-pair of the present invention has a very low toxicity on bees and does not damage; useful entomophages and parasites (see biological Examples 4 and 5). This is due to the repellent effect, preferable persistence and suitable inherent activity_of the active ingredient . As a result of the above advantageous properties the insecticidal composition of the present invention may be useful in integrated plant protecting technoloBAD ORIGINAL $

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I gy (IFM = Integrated Pest Management).

The present invention is based, on the further recognition that the enantiomer-pair of the present invention has substantially the same insec5 ticidal activity as the enantiomer-pair la but is significantly' less toxical on warm-blooded species. This is clearly substantiated by the selectivity index ( 7800) being the quotient of approximative toxicity values on rats ( 5000 mg/kg) .and house fly (0.64 mg/kg). The said selectivity index of the enantiomer-pair la amounts to 50/0.45 = 111.

The isomer-pair lb is less toxical on parasites than the isomer-pair la and this is of particular importance. For this reason the insecticidal composition of the present invention may be used more J, safely, because on the edge of the sprayed area and after treatment (i.e. in area treated with a small concentration of the active ingredient) the parasites and bees are not killed. The repellant effect of the isomer-pair lb is outstandingly good, too.

The insecticidal compositions of the present invention comprising the isomer-pair lb in admixture with known additives may be formulated in forms suitable for direct use.

The composition of the present invention may be ULV (ultra-low-volume) compositions, spray, dispersible powders, granules, wettable and other powders, stable emulsions etc. The said compositions

BAD ORIGINAL £ are suitable for the pesticidal treatment of vegetables, orchards, fields of cereals and other large scale cultures. Due to the low toxicity the compositions of the present invention are particularly suitable for combating .flying insects and pests having a hidden mode of life in households, stables and also for use in bathing of domestic animals and for the treatment of pasture .

According to a further aspect of the present invention there is provided the use of the said insecticidal compositions. It is preferred to use the said compositions under field conditions at a rate of

2-25 g of active ingredient per hectare.

The insecticidal compositions of the preI ’ sent invention may comprise in addition to the isomer-pair lb activators and further synergists, e.g. piperonyl butoxide. The said additives strengthen the efficiency of the active ingredient without increasing the toxicity on warm-blooded species.

According to a preferred embodiment of the present invention there are provided dispersible granules comprising 1-99 % by weight of the active ingredient in admixture with 99-1 % by weight of suitable additives. As auxiliary agent e.g. 0.1-1 % by weight of anionic and/or non-ionic surfactants may be used, such as alkalisalts of alkyl-aryl sulfonic acids, alkali salts of condensation products of alkyl aryl sulfonic acids and formaldehyde, alkyl-aryl-polyglyccl

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BAD ORIGINAL ether, sulfatated long-chained, alcohols, polyethylene oxides, sulfatated fatty alcohols, fatty acid polyglycol esters and various other commercially available surfactants.

The insecticidal compositions of the present invention may also be formulated in the form of concentrates comprising preferably 5-50 % by weight of the active ingredient in admixture with 50-95 % by weight of additives which enable the formation of a stable emulsion when emulsifying the emulsion concentrate in or in the presence of water.

As additive 1-20 % by weight of a tensid and/or 0.1-5 % by weight of a stabiliting agent may be used and the mixture may be preferably filled up to 100 % with an organic solvent.

It is preferred to use as tenside a mixture of anionic and non-ionic tensides having a HLB-value of 8-14. The following tensides may be preferably applied: calcium salts of alkyl aryl sulfonic acids, mono and diesters of phosphoric acid, nonyl and tributyl phenol polyglycol ethers, adducts of fatty alcohols and ethylene oxide, fatty acid polyglycol esters, ethylene oxide-propylene oxide block polymers etc.

As solvent preferably mixtures of aromatic hydrocarbons (e.g. xylenes), cyclohexanol, butanol, methyl ethyl ketone, isopropanol etc. may be used.

The compositions of the present invention

BAD ORIGINAL may also comprise further synergists which enable the reduction of the amount of the active ingredient.

For this purpose preferably piperonyl butoxide may be applied.

According to a further aspect of the present invention there is provided a process for the preparation of a product comprising substantially only the enantiomer-pair IRtransS + IStransR (lb) out of the eight possible isomers of the compounds of the

Formula (I) from mixtures comprising other isomers of further components, too.

The enrichment of cypermethrine mixtures in isomers having presumably a higher activity is described in several patent specifications. Accord15 ingjto a patent publication |c.A. Vol. 95, (1981), Japanese Pat. KOKAI No. 57755/81] a crystalline cypermethrine isomeric mixture comprising 86.9 % of Ic, 9.5 % of la and 5·θ % of Ib+Id is prepared by seeding a.mixture comprising 53-5 % of Ic, 38.7 % of la and 7.8 % of Ib+Id. In this case it was expected that the biological activity of the compounds remaining in the mother-lye would be higher.

It is the object of the other known procedures, too, to prepare cis isomer-pairs or sub25 stances enriched in cis isomer-pairs. According to a known process a mixture of enantiomer-pairs la and Ic is subjected to epimerisation to convert the Ic enantiomer-pair into la enantiomer-pair and to produce

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AP 0 0 0 0 1 3

I

- 13 the known alphametrine and decametrine, respectively, by assymmetrical transformation CChem. and Ind., March 19, 1985, 199-204; British patent application ho.

13308; EP No. 0 067461; Dutch patent No. 883431, see Derwent 79766D].

Prior art is silent in teaching any methods directed to the preparation of trans isomers.

According to a further aspect of the present invention there is provided a process for the preparation of an isomer mixture lb consisting substantially of only the enantiomer-pair IRtransS and IStransR - i.e. substantially only two out of the eight possible isomers of the compounds of the Formula (I) - from mixtures comprising also other isomers of the Formula (I) which comprises

a) preparing a saturated solution from a mixture comprising the desired isomers in admixture with further possible isomers with a protic or , apolar aprotic inert organic solvent, seeding the solution with a seeding crystal consisting of the enantiomer-pair IRtransS + IStransR and isolating the precipitated crystals at a temperature between +30 °C and -30 °C; or

b) seeding a melt of a mixture comprising the desired isomers in admixture with further possible isomers at a temperature between 10 °C and 60 °C with a seeding crystal consisting of the lRtransS+ +lStransR enantiomer-pair, crystallizing at a

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J 14 .

temperature between 30 °C and -10 °C, and if desired suspending the mixture thus obtained in a protic or apolar aprotic organic solvent at a temperature between -10 °C and -20 °C and isolat5 ing the separated crystals; or

c) subjecting a mixture comprising the desired isomer-pair lb in admixture with further possible isomers to chromatography in an organic solvent preferably on a silica gel or Kieselguhr adsor10 bent; or

d) dissolving a mixture comprising trans isomers of the compounds of the Formula CD in a protic or apolar aprotic solvent, seeding the solution with a seeding crystal consisting of the enan15 tiomer-pair IRtransS + IStransR (lb), isolating the precipitated crystalline product' lb, and thereafter if desired epimerising the mixture ✓

comprising lb '+ Id being present in the mother' '-lye with an organic or inorganic base and if desired repeating the said step and/or the

.. \ .

crystallizing step; or

e) dissolving the mixture'comprising the trans isomer3 in'a secondary or tertiary organic

- · amine base comprising 4-9 carbon atoms - op25 tionally by adding an organic solvent - and seeding the solution. thus obtained with a seeding crystal consisting of IRtransS +' IStransR isomers and thereafter isolating the precipiAPOOOO 1 3

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- 15 tated crystals.

According to variants a) and e) of the process of the present invention one may preferably proceed by using a ^cp_]_2 hydrocarbon, chlorinat5 ed hydrocarbon, dialkyl ether or Ο-^^θ alcohol as organic solvent. The said solvents may be straight or branched chained, and cyclic and alicyclic, respectively.

It is preferred to carry out seeding with 10 a seeding crystal in the presence of an antioxidant

- particularly tertiary butyl hydroxy toluene or

2,2,4-trimethyl-quinoline - and to use ethanol, isopropanol petrolether or hexane as solvent.

According to variant d) of the process 15 of the present invention it is preferred to use a ^4-10 ^alh^ane> θ5_ιο cycloalkane, 0^_θ alkanol and/or ^5-8 ^cy^cl°^alhanol or a mixture thereof as solvent.

One may particularly advantageously use hexane, petrolether, cyclohexane, methanol, ethanol or iso20 propanol.

In the epimerisation step ammonia, secondary or tertiary alkyl amines or cyclic amines may be used as basic substance. Thus one may preferably use triethyl amine, diethyl amine, morpholine, pyrrolidine, piperidine, diisopropyl amine, ephedrine, triethylene diamine, benzyl amine, M-butyl amine, secondary butyl amine, tetrabutyl ammonium hydroxide, sodium hydroxide, potassium tertiary butylate, sodium isopropylate or an

BAD ORIGINAL ion-exchanging resin comprising a quaternary ammonium compound or a catalytic amount of an amine having a large molecular weight.

As solvent it is preferred to use methanol, 5 ethanol, isopropanol, petrolether or hexane.

The said reaction variants may be particularly economically used if the total manufacturing line comprises the use and preparation of isomers of the Formula (I) other than lb, too.

If synthetic cypermethrine manufacturing process makes it possible and if it is the aimed object of the invention to manufacture only a mixture of trans cypermethrines by means of one of the esterifying procedures, variant e) of the process of the present invention is particularly suitable for the economical manufacture of isomer-pair lb.. According to the said variant e) namely the complete amount of . h the trans mixture is converted into the desired en. antiotjier-pair lb.

According to variant e) it is preferred to :- use triethyl amine, morpholine, pyrrolidine, piperi'idine, diisopropyl amine, ephedrine or secondary butyl < amine as organic amine base.

^r It was a pre-condition of the feasibility of variant e) to provide and prepared highly pure -seeding crystals having a purity over 95 % and melting above 80 °C from the non-cry3tallizing pure isomers Ii and Id. This enables the aimed directed

AP 0 0 0 0 1 3

BAD ORIGINAL A asymmetrical transformation.

One may proceed furtheron preferably by dissolving the mixture in the amine in the presence of an organic solvent. For this purpose the solvents enumerated by variant a) may be used.

According to variant a) one may proceed by dissolving the isomer mixture of trans cypermethrines - comprising the IRtransS, IStransR, IRtransR and IStransS isomers - in triethyl amine. Crystalline start ing materials are dissolved at a temperature between 40 °C and 70 °C and the solution obtained may be filtered. An oily cypermethrine mixture may be dissolved at room temperature as well.

Crystallization of the IRtransS + IStransR

I isomer-pair may be carried out by seeding the solution at room temperature with crystals of a 1:1 mixture of the IRtransS and IStransR isomers (recommended purity 99·8 %) and thereafter subjecting the mixture thus obtained to crystallization at a temperature between

0 °C and 20 ' °C with or without stirring. The precipitated crystals are separated by filtration or centrifuging and the mother-lye adhered to the surface of the crystals is washed off with an alkane (preferably a solvent of the cycloalkane type particularly petrolether). The united mother-lyes are completely concentrated. The said crystallization procedure may be repeated. The asymmetrical transformation may be preferably accomplished in a dry inert gas (preferBAD ORIGINAL $ ably nitrogen) atmosphere.

According to the above process a

IRtransS + IStransR isomer-mixture having a purity of about 95 % may be prepared with a yield of 80 % per step. The purity may be increased to 99-99.5 % by means of further recrystallization from an alcohol, particularly isopropanol.

If the base serves as solvent, too, it is preferred to use an amine base having a water content not higher than 0.2-0.4 %. Cis isomer contaminations of the trans cypermethrine mixture used as starting material may decrease the yield.

Industrial applicability

The insecticidal compositions. of the present invention are harmless to environment and can be used particularly in household and stables for combating-flying insects and pests having a hidden mode of life and also for bathing domestic animals and for the treatment of pasture.

Modes of Carrying out the Invention

Further details of the present invention are to be found in the following chemical and biological examples without limiting the scope of protection to the said Examples.

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- 19 Chemical Examples

Example 1 g of a cypermethrine mixture consisting 5 of 18.2 % of la, 21.8 % of Ic, 26.8 % of lb and 33.2 % of Id are dissolved in 50 ml of a 95:5 mixture of n-hexane and tetrahydrofurane. The solution is subjected to chromatography on a column comprising 500 g __ « of silica gel G. 25 ml fractions are collected by 10 using a 95:5 mixture of n-hexane and tetrahydrofurane as eluting agent. Tractions corresponding to an value of 0,2 are collected (as TIC running mixture a 95:5 mixture of n-hexane and tetrahydrofurane is ·*used). The said fractions are evaporated in vacuo.

) 15 The residue thus obtained (2.9 g) is dissolved in 29

XI ml of ethanol at 45 °C and crystallized at 0 °C. The precipitated product is filtered off, washed twice with 10 ml of icecold ethanol each and dried in vacuo. Thus 2.6 g of a white crystalline product are obtained, mp: 80.2 °C.

Analytical characteristic data:

Rf = 0.2 (Kieselguhr G plate, 95:5 mixture of n-hexane and tetrahydrofurane)

IR (KBr) 9_c=o = 1735 cm¹

NMR (CDCl^) <5* (ppm) = 1.22, 1.27, CMe₂; 1.69, d, 1H

Cl; 2.32, m, 1H C3i 5.6, d, 1H Cl’} 6.39, s, 1H, C bad original &

.. - - » alfaproton.

Example 2

To 10 g of a crystalline trans cypermethrine mixture (comprising 53.9 % of lRtransR and IStransS isomers and 43-3 % of Ig isomers according to gas chromatography) 15 ml of anhydrous triethyl amine are added. The mixture is heated under nitrogen and under constant stirring to 60 °C, whereupon the solution is quickly filtered and cooled to 30 °C. The clear colourless solution thus obtained is seeded with a seeding crystal of a 1:1 mixture of lb isomers, cooled to room temperature and allowed to crystallize for a day. The mixture is fil. tered cold. The product is dried at room temperature. Thus 8.4 g of a snow-white crystalline product' are obtained. Mp.: 79.5-80.5 °C. According to gas chromatography enalysis the product comprises 95 % of a 1:1 mixture of the desired lb isomers. The mother-lye is evaporated. On repeating the above steps 1.05 g of white crystalline product are obtained as second crops, mp.:'79-80 °C. ·..·?·····£ :.. 1 ·? - The united product is'recrystallized from 50 ml of isopropanol. 8.5 g'of a snow-white crystalline product are obtained as first crops, mp.: 80.5 °C, active ingredient content 9θ %.~0n further 'recrystallization 7-5 g of a crystalline product are obtained, mp.: 81.5 °C, active ingredient content above 99.5 %.

AP 0 0 0 0 1 3

IR (KBr) 9 = 1735 cm

C—o

NMR (CDCl^) <T (ppm) = 1.22, 1.27 CMe₂; 1.69, d, 1H Clj

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2.32, m, 1H C3; 5.6, d, 1H Cl’j 6.39, s,'lH, C alphaproton.

Example 3

100 g of an oily crude (purity 95 %) trans cypermethrine mixture (comprising 48 % of IRtransR and IStransS isomers and 47 % of lb isomers according to gas chromatography) are dissolved in a solution of 150 ml of anhydrous triethyl amine and 0.2 g of tertier butyl hydroxy toluene under stirring. The solution is quickly filtered, seeded, twice crystallized and recrystallized in an analo. guous manner to Example 2. Thus 82 g of snow-white crystalline isomer pair lb are obtained, mp.: 80-80.5 °C, active ingredient content 97-5 %.

Example 4 g of oily trans cypermethrine mixture (comprising 85 % of IRtrnasR and IStransS isomers and 14 % of lb isomers) are dissolved in 15 ml of anhydrous triethyl amine under stirring at room temperature, whereupon the solution is filtered and crystallized as described in Example 2. Thus 8 g of snow-white crystalline isomer mixture lb are obtained, mp.: 79-80.5 °C.

Example 5 g of crystalline trans-cypermethrine bad original (comprising 52 % of IRtransR and IStransS isomers and 47 % of lb isomer-pair) are dissolved in 15 ml of tri-n-propyl amine at 50 °C. The solution is filtered, cooled to 30 °C and seeded with a seeding crystal consisting of a 1:1 mixture of the lb isomers. The mixture is allowed to crystallize for 48 hours. Thus 8.2 g of a snow-white crystalline product are obtained, mp.: 78-80 °C. Purity 95 % (according to gas chromatography analysis).

One proceeds according to Example 5 except that 15 ml of tributyl amine are used as base.

Thus 7-5 g of snow-white crystalline isomer-pair lb are obtained, mp.: 77-79 °C, purity 93 %.

Example 7

One proceeds according to Example 5 except that 15 mi of triisopropyl amine are used as base. Thus

7.5 g of snow-white crystalline isomer-pair lb are obtained, mp.: 78-80 °C, purity 95-5 %·

Example 8

One proceeds according to Example 5 except that 15 ml of diisopropyl amine are used as base.

Thus 8.0 g snow-white crystalline isomer-pair lb are obtained, mp.: 78-80 °C, purity 95-5 %·

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•1»'Example 9 g of trans cypermethrine (comprising 48 % of IRtransS and IStransR isomers and 49 % of lb isomer-pair) are dissolved in 50 ml of isopropanol under stirring and heating whereupon 2 ml of an aqueous ammonium hydroxide solution are added (specific weight 0.880 g/ml). The solution is seeded with seeding crystals of the isomer-mixture lb, stirred at 20 °C for 24 hours, cooled to 0 - 5 °C, and stirring is continued at this temperature. The suspension is filtered, the product is washed with isopropanol and petrolether and dried. Thus 6 g of

F . white crystalline isomer-pair lb (1:1) are obtained, mp.: 78-79 °C, purity 92 % (GC analysis). Prom the mother-lye 1.5 g of white crystalline product are obtained as second crops. Mp.: 78-79 °C. The composition of the second crops is identical with that of the crystals of the first generation.

Example 10 g of trans cypermethrine (comprising 54 % of IRtransS and IStransR- isomers and 45 % of isomers lb) are dissolved in 100 ml of petrolether (b.p.: 60-80 °C) whereupon 1 ml of a 0.5 molar sodium carbonate solution and a 1:1 vol. mixture of water and methanol comprising 10 w/v of tetrabutyl ammonium bromide are added. The solution is seeded with a seeding crystal according to Example 2, allowed to crystallize

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- 24 for 4 days, filtered, washed with petrolether and dried. Thus 6.8 g of white crystalline isomer-pair lb are obtained, mp.: 78-80 °C, purity 95 %, (GC analysis).

Example 11 g of crystalline trans cypermethrine (comprising 52 % of IRtransS and IStransR isomers and 47 % of IRtransR and IStransS isomers) are dis1θ solved in 100 ml of petrolether at 50-60 °C. To the solution 0.02 g 2,6-di-tertiary butyl-4-methyl-phenol is added. After filtration the filtrate is seeded at 30 °C with seeding crystals consisting of a 1:1 mixture of the lb isomers. Crystallization is accomplish15 ed as disclosed above. Thus 3>8 g of snow-white crystalline isomer-pair lb (1:1) are obtained, mp.: 77-79 °C, purity 93 %♦ On recrystallization from petrolether the melting point rises 80.5 °C. The crystallization mother-lye is epimerised in a separate step.

AP 0 0 0 0 1 3 g of crystalline trans cypermethrine (comprising 45 % of IRtransS and IStransR isomers and 53 % of IRtransR and IStransS,isomers) are dissolved in 75 ml of isopropanol at 50-60.°C. The solution is treated in an analoguous manner .to Example

11. Thus 3.6 g snow-white crystalline isomer-pair lb

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- 25 are obtained. According to gas chromatography analysis the purity of the 1:1 mixture amounts to 94- %. Mp.:

°C. Further recrystallization is accomplished as described in Example 2. Thus a product having an ac5 tive ingredient content above 99 % is obtained. The crystallization mother-lye is epimerised in a separate ' step. · ··- - - ’ - ⁽ Example 13 * · - · ^J

•. - ·. · «ί.

Into an apparatus equipped with a stirrer' *“ the mother-lye obtained according to Example 11 (a solution enriched in isomer Id) is introduced and ^v 1 g of Dowex Type 2x4 mesh (serva) basical ion-exchanging resin are added¹. The heterogenous suspension is stirred at 40 C foi* 12 hours, filtered, washed ^e twice with 2 ml of isopropanol each. According to

X gas chromatography the solution comprises 41 % cf lb isomer-pair and 46 % of Id isomer. The solution is evaporatedand crystallized as described in Example

11.

Example 14

One proceeds according to Example 13 except that petrolether is used as solvent. According to gas chromatography analysis the solution comprises % of lb isomer and 5θ % of the 1R transR and IStransS isomers.

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Λ

Example 15 g of colourless oily cypermethrine (comprising 30 % of lb, 31 % of Id., 16 % cf la and 21 % of Ic) are seeded with seeding crystals of a

1:1 mixture of the lb isomers and allowed to crystallize at 7 °C for a week. The viscous crystalline oil obtained is cooled to -15 °C, suspended in 10 ml of a 1:1 mixture of isopropanol and diisopropyl ether cooled to -15 °C and filtered ccld. The crystals thus obtained are washed v-ith 5 ml of icecold isopropanol and dried at room temperature. Thus 2 g of white crystalline product lb are obtained, mp.: 78-80 °C, purity 96 % (GC). On recrystallizaticn from 13 ml of hexane 2.25 g of a snow-white crystalline product are obtained, mp.: 80-81 °C, active ingredient content 99 %.

Example 16 ' · ~ -10 g of cypermethrin (comprising 30 % of lb, 31 % of Id, 18 % of la and 21 % of Icpere dissolved in 100 ml of warm isopropanol whereupon 0.02 g of 2,5-di-tertiary butyl-4-methyl-phenol is / .added._The solution is clarified with 0.2 g of charcoal, filtered warm and the filtrate is seeded at

30 ’ °C with a seeding crystal consisting of β 1:1 mixture of the lb isomers. The mixture is allowed to crystallize at 10 °C for 24 hours, at 0 °C for 48 hours and finally at -5 °C for 24 hours (crysAP 0 0 0 0 1 3

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- 27 tallization is accomplished so that an oily separation of the product should be avoided). The crystals are filtered cold, washed with isopropanol and dried at room temperature. Thus 2.6 g of snow-white crystalline lb isomer-pair (1:1) are obtained, mp.:

78-80 °C, purity 95 %· On recrystallization from hexane 2.3 g of a snow-white crystalline product are obtained, mp.: 80-81 °C, active ingredient content 99 %.

Formulation examples Example 17 Emulsifiable concentrates (EC) are pre pared by admixing the following components:

EC

Component

Isomer-pair lb Cyclohexanol Atlox 3386 B Atlox 3400 B

Odourless mineral oil

Amount, kg/kg

0.105

0.290

0.020

0.045

0.540

5_EG

Component

Isomer-pair lb

Cyclohexanol

Atlox 3386 B

Atlox 3400 B

Colourless mineral oil

Amount, kg/kg

0.050

0.290

0.020

0.045

0.595

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- 28 In a dose of 20 g of active ingredient/ha the composition 5 EC gives the same protection against Colorado beetle as a preparation of identical composition but comprising isomer la (alphametrine composi5 tion).

Example 18

A solution of 1.5 g of isomer-pair lb and

1.5 g of fatty alcohol polyglycol ether is homogenized

1θ in a powder homogenizer with 30 g of synthetic silicic acid (Wessalon S), 60 g of talc (pH 7.1), 5 g of saccharose and 3.35 g of dodecyl benzene sulfonic acid. Thus a thin flowing powder is obtained.

Example 19 i g of isomer-pair lb are diluted with g of ethanol. The solution is admixed in a powder homogenizer with 5 g of calcium lignosulphonate, 5 g of nonyl-phenyl polyglycol ether (E0=20) and 70 g of calcium carbonate. The product thus obtained is ground in an Alpine 100 type mill. According to CIPAC the floatability amounts to 81 %; wetting time = 18 seconds.

APtttO 1 3 bad original &

Biological Examples

Example 20

The comparative activity tests of enan5 tiomer-pairs la and lb on bean weevil (Acanthoscelides obtectus), fleur-beetle (Tribolium confusum) and sheep maggot fly (Lucilia sericata) show that enantiomer-pair lb is more active than enantiomer-pair la.

«« *

T/ The results are summarized in Table 1.

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o

KO

Species . Enantiomer Dose (mg/disc) pair 0.02 0.07 0.22 0.67 2.0 , mortality %

o	o	o	o	n	o
o	o	o	o	MO	o
i—1	A	A	i—l		r-4

o	o	o	o	o	o
o	o	o	o	KO	o
A	r-t	i“4	f—1		A

o	o	o	O	t-	n
o	o	o	o	n	t-
A	rH	r—1	i—l

ΓΆ C— KO CO ο CM A ΟΛ σ\ O cm c—

CO cn A ίco £> ω a AH AH

O n m in

O CM CM

CO . £>

H A

ω	ε	co
3		3		-Ρ
-p		01		co
ο		2		ο
<u		A		Ή
-Ρ	ο	C4	ο		Ο
A	ao	Ο	fcO	ω	ω
ο	erf	ο	erf	01	erf
	ε		ε		ε
•	A	•	'Γ-ί	•	·γ4
		a		A

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AP 0 0 0 0 1 3 ^: -31.ϊ,/·

The test is carried out as follows:

The stereoisomers are dissolved in a 1:2 mixture of mineral oil and acetone and filter paper ' discs (Whatman No. 1., diameter 9 cm) are impregnated with the corresponding dosage of the solution of the active ingredient. The acetone is allowed to evaporate and the insects are examined on filter paper discs placed into Petri-dishes. Three parallels are used for , each dose and 15 animals are placed in each Petri-dish. Mortality rate is determined after 24 hours.

The corrected mortality % data are calculated by means ** of the Abbot formula. '

Example 21 • 15 In Table 2 the synergism between the &

stereoisomers of the enantiomer-pair lb is proved.

The test is carried out on T. confusom and the following results are obtained by the contact method for various active ingredient doses.

Table 2

Dose (mg/disc)	0.11	0.33	1.00	3.00
		mortality %
IStransR Ii	0	0	71	90
IRtransS Ig	80	94	100	100
lb enantiomer-pair	90	100	100	100

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The test is carried out according to the method described in Example 20

Example 22

In Table 3 the LD^q values of the Ig and

Ii isomers and those of the lb isomer-pair are disclosed. The data are topically measured.

APO 0 0 0 1 3

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P	(ft	c+
		0	Ό
CO	P	4	Φ
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4	c+	O	3
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P	0	0	c+
ω	P	O	p-
	0	3	4
	co	0	P
		H	P
		0	0

kn	P r\o kO	--3
P	P	kJ
•	•	•
kO	CD	Ok

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P P r\o p kJ • · · kO ->

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The above data prove the synergism between the trans isomers on both species.

The tests are carried out as follows:

^a) Musea domestica

The active ingredients are dissolved in 2-ethoxyethanol (cellosolve) and 0.3 /Ul droplets of the'solutions are applied onto the dorsal cuticulum of 3-5 days’ old female house flies. 10 animals are used and 2 parallels are carried out for each dose. The tests are carried out for 5 dose levels between activity limits of 0 % and 100 %. After treatment . the files are placed into glass vials. Mortality is determined after 24 hours. Data are transformed to log^Q dosage and probit mortality. LD^q end confidence interval valuesare calculated by linear regression analysis of the log-probit data. The expected values required for the calculation of synergism .are obtained by means of harmonic average. The synergistic factor is the quotient of the expected and measured values .

AP 0 0 0 0 1 3

b) T. confusum

The active ingredients are dissolved in 2-ethoxyethanol and 0.3 /Ul droplets of the solutions are applied onto the abdominal side of 1-2 weeks’ old images. Treatment is carried out with 2 parallels and 20 animals for each dose by using 5 dose levels in

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the range between activity limits of 0 % and 100 %.

Evaluation and determination of LD_C„ values and 50 synergistic factors are carried out as described in Example 21.

Example 23

Residual contact test on adults of « 7

- Aphidinus matricanae _Λ «

Adults of A. matricariae are exposed to 10 residues of the active ingredients freshly applied on glass plates forming cages then the survivors are counted.

Treatments: test product(s) and control treated with water.

I ¹ Replicates: at least 3· Plot size (net):

cage.

Parasites of known age 24 hours are used.

The products are applied at 5-1 ppm concentration, to each of the glass plates.

2θ 10 females of A. matricariae are introduced into each cage and supplied with honey as food. The number of females surviving exposure is determined after 1.5 and 24 hours, in independent runs. Total number of survivors is calculated for each cage.

The results are summarized in Table 4·

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- 36 Table 4

Concentration 5 ppm 1 ppm lh lh 5h 24h hours

	m o	r t a	1 i t y	%
la '	100	100	100	96
lb	100	0	75	88
control	0	0	0	1.5

Example 24

Direct contact test on pupae of A.

matricariae

Mature pupae of A. matricariae on paprika leaves in Petri dishes are exposed to a direct spray of the active ingredients.

Two or three days before emergence paprika leaves with-parasitized pupae are used. The leaves are laid on filter paper in a plastic Petri dish.

The filter paper is moistened.

Application of treatment: see Example 23.

The pieces of leaf are transferred after treatment to clean Petri dish bottems. The trays are stored in a climatic chamber at 20 °C temperature, % relative humidity and a light-dark , cycle of 16-8 h. Surviving pupae hatch after 2-3 days. The numbers of hatched and dead pupae are counted. Results

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APO 0 0 0 1 3

- 37 are shown in Table 5.

Table 5 ____________

	concentration (ppm)	1
30	rwE)rtalit-y %
lb	61.0	0 0 __ «	0
deltametrin	75.0	33- 0 0	0
control	0	0 0	0

Example 25

The active ingredients are dissolved in

2-ethoxyethanol and 0.3 /Ul droplets of the solutions ^•5 are applied onto the abdominal sterna of potato beetle (Leptinotarsa decemlineata) imagos. The treatments are carried out by using two parallels and 10 insects for each dose. After treatment the insects » ** are placed, into Petri-dishes and mortality is deter20 mined after 48 hours. The results are set forth in Table 6.

Table 6
cyperme thrine		Dose	(yug/insect)
enantiomers	0.05	0.10	0.20	0.40
		24 hours	’ mortality %
lb	0	25	75	85
cypermethrine	0	20	45	75

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- 38 7'

Example 26

T. conf us urn (confused flour -beetle) imagos are treated according to Example 20 and percental mortality is determined after 24 hours. The dose of piperonyl butoxide (referred to furtheron as PBO) amounts to 0.5 mg/disc. The results are disclosed in Table 7. It c_aN be seen that enantiomer-pair lb can be synergized at a higher level than isomer pair la.

Table 7

Active Dose (mg/disc) ingredient 0.4 0-2 0.1 0.05 0.025 hours’ mortality %

15 la	96	53 ·	12	θ ,	0
la + BBO	100	58	16	0	0
lb	100	85	51	10	0
lb + BBO	100	91	68	39	9

APOOOO 13

Example 27

The active ingredients are dissolved in

2-ethoxyethanol and the solutions are applied in the form of 0.2 yul droplets onto the back of fall webworm (Hyphantria cunea) of Βγ-1θ larvae stage.

The treated worms are placed on strawberry leaves in Betri-dishes . The test is carried out by using 5 doses; 2 parallels and 10 insects for each dose. The killed worms are counted after 24 hours and the perBAD ORIGINAL

- 39 cental mortality rate is calculated. The results are summarized in Table 8.

Table 8

5________________

cypermethrine stereoisomers	0.023	Dose (/ug/larvae) 0.047 0.094 0.188 24 hours’ mortality	0.375
lb	10	15	30 - 70 ·	80
cypermethrine	0	0	25 50	75

Example 28

Prom a 5 EC formulation according to Example 17 50-, 100-, 200-, 4-00-, 800- and 160015 -fold diluted emulsions are prepared by diluting with ' water. 0.5 ml of the emulsions are sprayed onto glass £ plates whereupon after drying 10 Colorado beetles (L.

decemlineata) imagos are placed on each glass plate and,the insects are covered. The tests are carried _out with 6 doses by carrying out 3 parallels for

I each dose. The killed insects are counted after 48 hours and the percental mortality rate is calculated. The results are shown in Table 9·

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- 40 Table 9

Dilution

5 EC formulation	l600x	800x 400x 200x mortality %	lOOx	50x
cypermethrine	0	17	33 50	67	83
lb	0	13	37 57	87	100

Example 29

The insecticidal effect is tested on .Enan' Weavil (Acanthoscelides obtectus) imagos. The killed insects are counted after 24 hours and the percental mortality rate is calculated. The results are shown in Table 10.

Table 10

AP 0 0 0 0 1 3

Dilution

5 EC	l600x	800x 4OOx 200x	lOOx	50x
formulation		mortality %
cypermethrine	0	3 10 20	43	60
lb	3	10 20 37	53	67

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Claims (10)

1. What we claim is,

   1. A synergistic insecticidal composition containing more than one active ingredients and being harmless to environment characterized by comprising in an amount of from 0.001 to 99 % by weight a synthetic pyrethroid of the Formula (I)

   - namely substantially only the IRtransS and IStransS enantiomer-pair (lb) out from the possible eight isomers - -optionally in admixture with an amount of up to 100 % by weight of one or more activator(s) and auxiliary agent(s), particularly antioxidants, stabilising agents, wetting agents, emulsifying agents, dispersing agents, antifom agents, diluents and/or fillers. (Priority: 16th January 1985)
2. 2. Isomer mixture of the Formula (I) consisting substantially of enantiomer-pair IRtransS and IStransR having a purity of at least 95 % and the following IR and NMR data:

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   - 42 ‘ IR (KBr) V_c=0 = 1735 cm¹ NMR (CDC1₃) (ppm) = 1.22, 1.27, CMe₂; 1.69, d,

   1H cl; 2.32 m, 1H C3; 5-6, d, 1H Cl’; 6.39, s, 1H,

   C alphaproton

   5 (Priority: 16th January 1985)·
3. 3· Isomer mixture of the Formula (I) consisting substantially of the IRtransS and IStransR enantiomer-pair having a melting point of 80.5-81.5 °C and the IR and NMR data according to Claim 2.

   1° (Priority: 8th January 1986).
4. 4. A process for the preparation of an isomer mixture lb consisting substantially of only the enantiomer-pair IRtransS and IStransR - i.e. substantially only two out of the eight possible

   15 isomers of the compounds of the Formula (I) - !

   CN

   APOOOO 1 3 (I)

   - from mixtures comprising also other isomers of the Formula (I) which comprises

   a) preparing a saturated solution from a mixture

   BAD ORIGINAL &

   b)

   c)

   d) comprising the desired isomers in admixture with further possible isomers with a protic or apolar aprotic inert organic solvent, seeding the solution with a seeding crystal consisting of the enantiomer-pair IRtransS + IStransR and isolating the precipitated crystals at a temperature between +30 °C and -30 °C} or seeding a melt of a mixture comprising the deI sired isomers in admixture with further possible isomers at a temperature between 10 °C and 60 °C with a seeding crystal consisting of the IRtransS + IStransR enantiomer-pair, crystallizing at a temperature between. 30 °C and -10 °C, and if desired suspending the mixture thus obtained in a protic or apolar aprotic organic solvent at a temperature between -10 °C and -20 °C and isolating the separated crystals; or subjecting a mixture comprising the desired isomer-pair lb in admixture with further possible isomers to chromatography in an organic solvent preferably on a silica gel or Kieselguhr adsorbent; or dissolving a mixture comprising trans isomers of the compounds of the Formula (I) in a protic or apolar aprotic solvent, seeding the solution with a seeding crystal consisting of the enantiomer-pair IRtransS + IStransR (lb), isolating the precipitated crystalline product lb, and there-

   BAD ORIGINAL after if desired epimerising the mixture comprising lb + Id being present in the mother-lye with an organic or inorganic base and if desired repeating the said step and/or the crystallizing step; or

   e) dissolving the mixture comprising the trans isomers in a secondary or tertiary organic amine base comprising 4-9 carbon atoms - optionally by adding an organic solvent - and seeding the solution thus obtained with a seeding crystal consisting of IRtransS + IStransR isomers and thereafter isolating the precipitated crystals.

   (Priority: 8th January 1986).
5. 5¼ Process according to variant a) or e)

   I of Claim 4 which comprises using as organic solvent a θ]__22 hydrocarbon, a (^-g chlorinated hydrocarbon, a dialkyl ether or a ^Cl-10 alcohol, wherein the said solvents may be straight or branched chained » and cyclic of alicyclic, respectively.

   (Priority: l6th January 1985)·
6. 6. Process according to variant a) of

   Claim 4 which comprises carrying out the seeding operation with the seeding crystal in the presence of an antioxidant - preferably tertiary butyl hydroxy toluene or 2,2,4-trimethylquiroline - and using' ethanol, isopropancl or hexane as solvent.

   (Priority: 16th January 1985).
7. 7· Process according to variant a) of

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   ΑΡ0 00 0 1 3

   Claim 4 which comprises using a O^-lO C_c ]__c cycloalkane, 0^_θ alkanol and/or C^_g cycloalkanol or a mixture thereof - preferably hexane, petrolether, cyclohexane, methanol, ethanol or isopropanol - as solvent.

   (Priority: 8th January 1986).
8. 8. Process according to variant c) of

   Claim 4 which comprises carrying out epimerisation by adding ammonia, a secondary or tertiary alkyl amine or a cyclic amine as basic substance. (Priority: 8th January 1986)
9. 9. Process according to variant a) of

   Claim 4 which comprises using methanol, ethanol or iso propanol as solvent. !

   (Priority: 8th January 1986)
10. 10. Process according to variant d) of

    Claim 4 which comprises using triethyl amine, morpholine, pyrrolidine, piperidine, diisopropyl amine, ephedrine or secondary butyl amine as organic amine base .