AP14A - Pyrethroidal composition comprising more than one active ingredients.

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Abstract

Description

Claims

AP14A

Publication number: AP14A
Application number: APAP/P/1986/000024A
Authority: AP
Inventors: Pap László Dr; Hidasi György Mr; Zoltán Sándor Mr; Székely István Dr; Bertók Béla Mr; Soós Rudolf Dr; Radvány Née Hegedüs Erzsébet Mrs; Nagy Lajos Mr; Gajáry Antal Dr; Somfai Éva Dr; Hegedüs Ágnes Mrs; Botár Sándor Dr; Szabolcsi Tamás Dr
Original assignee: Chinoin Gyogyszer Es Vegyeszeti Termekek Grara R T
Priority date: 1986-01-08
Filing date: 1986-02-26
Publication date: 1988-03-08
Also published as: AP8600023A0; CS254994B2; CN1031996C; PL151661B1; CN86101357A; AP8600024A0; HUT41962A; CN1050810A; CN1015709B; CS254993B2; HU198373B; CN1031972C; CS48086A2; EG18336A; TR22867A; PL153005B1; PL149799B1; PL257772A1; TR22871A; PL269466A1

An insectidal composition containing more than

This invention relates to insecticidal compositions comprising more than or.e pyrethroids active ingredients, the use thereof, the active ingredients and a process fcr the preparation of the same.

ickground Art

In. the present specification the spatial configuration of the substituents related tc the chiral carb or. atom denoted with dL. is characterized by S and R respectively. The designations cis and trans, respectively, mark the position of the substituents attached to carbon atom 3 of the cyclopropane ring related to the spatial configuration of the substituents of carbon atom 1. The absolute spatial configuration of the substituent attached to carbon atom 1 is denoted with the prefix 1 PM' and IS, respectively.

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	In the	present	specificaticr.
an	d enantiomer	-pairs	are designated
a b	breviati or.s :
la	mixture of	IReisS	and IScisR
lb	mixture of	IRtransS and IStransR
Ic	mixture of	IRc isR	and IScisS
Id	mixture of	IRtransR and IStransS
If	IReisS
Ig	IRtransS
lh	IScisR
Ii	IStransR

From the compounds of the general Formula I

A3669-77 KY

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the following are - Cypermethrin commercially available of the Formula II

comprising all isomers;

AIphametrin of the Formula II comprising only the » —

IReisS and IScisR isomers;

Deltametrin of the Formula III

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00024 comprising c r. 1 y the 12 c i s S i 3 o r e r.

Selection of the possible isomers on the basis ci insecticidal effect is based on the experimental fact that - particularly according tc tests carried out or.

Musca domestica species - certain isomers proved to be highly and outstandingly toxical on certain insects and it was the obvicus trend to put the most active isomers to the market or to synthetise the same _/~Pest. Sci.

/7, 273- /1976/_7.

It is known that the pyrethroids of the Formula

II /known under the generic name cypermethrin ”/ belong to the valuable family of synthetic pyrethroids and is useful as insecticide /Hungarian patent Mo. 170,866/. This compound may be prepared by reacting m-phencxy15 -benzaldehyde cyar.chydr ir.e with eye 1 oprcpane carboxylic acid chloride in the presence of a base ^/Pestic. 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 trans and cis cyclopropane carboxylic acid chlorides is used, the mixture ccr.tains 18-19 % of enantiomer-pair la, 21-22 % of enact i cmer-pa i r Ic, 26-27 % of enantiomer-pair lb and 33-34 % of enantiomer-pair Id.

According to prior art the stereoisomers of cypermethrin - show different biological activity. It is generally accepted that the activity of molecules comprising cis cyclopropane carboxylic acids is superior to that cf the corresponding trans derivatives /Pest. Sci.

7, 273 /1976/-7.

In the comparative biological tests of various pyrethroids /^_2^sst· Sci. 9, 112-116 /l-978/_7 the cis and trans stereoisomers - including the cypermethrin sterecisoner-pairs - were evaluated together.

The comparative tests were carried out in Musca domestica L. and Phaedon cochleariae Fab species.

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30021$- 4 Concerning the 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 bioresmetrin /100/ amounts to 1400 and 81, respectively, on Musca domestica and to 2200 and 110, respectively, on Phaedon cochleariae_7. It was disclosed furtheron that the activity of a mixture of both 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 led to the development of alphametrin /isomer mixture of IReisS and IScisR /la/ of the chloro derivatives_7 and decametrine /comprising the only IReisS isomer /If/ of the bromo derivatives_7.

For this reason several procedures are known for the preparation of mixtures enriched in the cis isomers from known cypermethrine isomer mixtures.

Disclosure of Invention

According to an aspect of the present invention there is provided an insecticidal composition containing mere than one active ingredients which comprises as active ingredient in an amount of 0.001-99 % by weight a synthetic pyret'nroids of the general Formula I /wherein X stands for chlorine or bromine/ - namely out cf the eight possible isomers at least 95 % of a 55 : 45 25 : 75 mixture of the enantiomer-pairs Ia : lb, wherein

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Is is IRoisS + IScisR and lb is IRtnar.sS + IStransP if desired in admixture with an activator and/or with an amount of up to ICO % of an auxiliary agent, preferably an antioxidant, stabilizer, wetting agent, emulsify5 ir.g agent, dispersing agent, antifoam agent, diluent, carrier, and/or filler.

The present invention is based on the recognition that the isomeric mixture la + lb possesses valuable and advantageous biological properties. The said properties

1C are surprising and unaforeseen, although extended research work has already been performed in the field of pyrethroids of the general Formula I and a number of publications and patents have been published.

It is known furtheron that mixtures enriched in cis isomers can be prepared by means of crystallization from solutions comprising other isomers /C.A. 95 , 1981;

KCKAI No. 57755/31_/. A substantially pure 1 : 1 mixture of the IPeisS and IScisR isomers may be separated by using suitable solvents from a mixture comprising the ether cis isemers too /British patent specification No. 2,064,528/. The isomeric mixture la is described to be very active. Special, so-called high cis syntheses are elaborated for the preparation of cis-cyclopropane carboxylic acid intermediates comprising cis isomers above a certain limit /about 50 %/, but these methods were rather expensive _/~Angew. Chem. Ie, 24, /11/, 596 /1985/7.

The present invention is based on the recognition that when using a combination of the IPtransS isomer Ig /being the most active trans isomer of the compounds of the Formula II/ and the IStransP isomer Ii /being ranged among the less active isemers from the remaining seven isomers/ no antagonism characteristic fcr the earlier published isomer-pairs is observed.

Moreover a synergistic effect occurs over the additive effect of the pure Ig and Ii isemers when used

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00024 perse.

The above recognition enables a new type cf selection from the is oners of synthetic pyre thro ids in order to develop a new active ingredient type having outstanding properties. The said new active ingredient shews various advantages over hitherto known iscr.er selections :

- lower toxicity on a warm-blooded species and humans;

- mere economical manufacturing process;

- smaller damages caused to useful parasites and bees.

The new compositions comprising the isomer-mixture lb are described and claimed in our co-pending patent application Ser. 'io. ·.·

The present invention is based or. the further recognictior. that the biological order of succession of biological activity previously observed for the individual isomers and the already known rules described for the isomer-pairs are not absolutely relevant for other is omer-pa irs .

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Thus we have tried to compare and simultaneously test the IRtransS + IStransR enantiomer-pair' lb - which was found to be active by our experiments - with other isomers. The comparison has shown that synergism observed between the members of enantiomer-pair lb /i.e. Ig and Ii/ does not take place between the members of the corresponding cis enantiomer-pair la /i.e. If and Ih/.

The present invention is based on the further recognition that while from the IReisS /If/ and IRtransS /Ig/ isomers it is generally the If isomer which is the more active, on certain specii the biological activity of the enantiomer-pairs la and lb proves to be opposite.

As a result cf the aforesaid we have come to the surprising recognition that when using simultaneously the enantiomer-pairs la and lb a synergistic effect is observed, i.e. the effect of the combination is superior

BAD ORIGINAL fi ΰύ024 £i to that of the additional effect of both enantiomer-pairs when used per se.

It has been found that the synergistic biological effect of mixtures la + lb is not limited to such mixtures in which lb is more active than la. Thus on Colorado potato beetle /Leptinotersa decemlineata/ the use of the two enantiomer-pairs results in a significant synergism. The said results are disclosed in details in the examples.

Based on the above recognitions we have performed a new selection from the already known isomer mixtures and this led to the new composition of the present invention.

In addition to the synergistic effect the composi15 tion of the present invention has a number of further advantages too and for this reason it is an outstanding product. It is very important that the compositions of the present invention are less toxical towards mammals than the hitherto known compositions of similar efficiency.

This is unambiguously proved by the so-called selectivity index /517 and 747, respectively/ which is the quotient of the approximative LD^q values measured on rats p.o.

/280 and 355 mg/kg, respectively/ and on house fly topically /0.54 and 0.48 mg/kg, respectively/. The said selectivity index of la amounts to 50/0.45=111.

The synergistic effect may be observed on mites too /see biological Example No. 19/, thus the compositions are also useful as acaricidal agents. The compositions of the present invention show a low toxicity towards bees and do not damage useful entomophages and parasites /biological Examples 25 and 26/. The said advantageous properties are due to the repellant effect, preferable persistence and suitable inherent activity of the active ingredient.

The above properties enable the use of the mixture of the enantiomer-pairs of the present invention

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- a in integrated plant protecting technology /IPM = Integrated Pest Management/.

The economical advantages of the compositions cf the present invention are at least as important as the biological efficiency. The preparation of a pure cis enantiomer-pair 'la requires very expensive synthetic methods or involves the loss of the trans components formed in the reaction mixture. On the other hand the present invention enables the use of practically all the components la and lb from the reaction mixture formed by the most economical syntheses. /The rate of efficiency depends naturally on the particular syntheses used and the ratio of the components la and lb of the mixture/.

The insecticidal compositions of the present ir.ven15 tion comprising the isomer-pairs la and 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

J powders, granules, wettable and other powders, stable emulsions etc. The said compositions are suitable for the pesticidal treatment of vegetables, grape fields, orchards, fields of cereals and other large scale cultures. Due to the low toxicity the compositions of the present inven-tion are particularly suitable for combating flying insects and pests having a hidden mode of life in households, walls of stables for the treatment of pasture etc.

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 present invention may comprise in addition to the isomer-pairs la

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00024 + lb activators and further synergists, e.g. piperonyl butoxide. The said additives increase 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 alkali salts of alkyl-aryl sulfonic acids, alkali salts of condensation products of alkyl aryl sulfonic acids and formaldehyde, alkyl-aryl-polyglycol ether, sulfatated long chained alcohols, polyethylene oxides, sulfated 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 tenside and/or 0.1-5 ’% by weight of a stabiliting agent may be. used and the mixture may be preferably filledup to 100 % with an organic solvent.

It is preferred to use as tenside a mixture of anionic and non-ionic tensides. 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, ethylen oxide - propylene oxide block polymers etc.

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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 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 an insecticidal active ingredient comprising out of the ’eight possible isomers of synthetic pyrethroids of the general Formula I /wherein X stands for chlorine or bromine/ substantially only a 55 : 45 - 25 : 75 mixture of enantiomer-pa irs la : lb - wherein la is IRcisS and IScisR and lb is IRtransS and IStransR which comprises a/ preparing from a mixture comprising in additon to the isomer-pairs la + lb other possible isomers too and/or comprising the isomer-pairs la + lb in a ratio other than the desired values a saturated solution with a protic or apolar aprotic inert organic solvent, seeding the solution with a seeding crystal consisting of a 55 : 45 - 25 : 75 mixture of enantiomer-pairs la and lb, and.isolating the crystals precipitating at a temperature between 30 °C and -30 °C; or b/ seeding a melt of a mixture comprising in addition to the isomer-pairs la + lb other isomers too and/or comprising the isomer-pairs la + lb in a ratio other than the desired value at a temperature between 10 °C and 60 °C with a seeding crystal comprising a 55 : 45 - 25 : 75 mixture of enantiomer-pairs la and lb, allowing the solution to crystallize at a temperature between 30 °C and -10 °C and if desired suspending the mixture thus obtained at a temperature between -10 °C

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- 11 and -20 °C in a erotic or apolar aprctic inert organic solvent and isolating the precipitated crystals; or c/ adding to a solution or a melt of a mixture comprising in addition to the isomer-pairs la'+ lb other isomers too and/or comprising the isomer-pairs la + lb in a rat.io other than the desired value an enantioner-pair la or lb in such an amount that the solution orthe melt should contain the isomers in a ratio of 55 : 45 - 25 : 75 and if desired performing crystalliza10 tion according to variant a/ or b/; or d/ admixing enantiomer-pairs la and lb in the desired ratio - if desired in the presence of a protic or apolar aprotic organic solvent - homogenizing the mixture and performing crystallization - if desired after the seeding step according to variant a/.

According to variants a/ of the process of the present invention one may preferably proceed by using a hydrocarbon, < chlorinated hydrocarbon, dialkyl ether or 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 a seeding crystal in the presence of an antioxidant -particularly tertiary butyl hydroxy toluene or 2,2,425 -trimethyl-quinoline - and to use ethanol, isopropanol petrolether or hexane as solvent.

One may proceed preferably by accomplishing crystallization under slow cooling.

According to a preferred form of realization 30 of the process of the present invention a mixture of % of trans and 40 % of cis cypermethrin enantiomer-pairs /18.2 % of la, 26.8 % of lb, 21.8 % of Ic and

33.2 % of Id; referred to furtheron as Ie/ is used as starting material. The said mixture is dissolved in isopropanol and the solution is seeded with seeding

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00024 crystals consisting of a mixture of la and It? in the presence of 0.01 % of 2,2 ,4-trimethyl-quinoline or tertiary butyl hydroxy toluene. A crystalline product is obtained with an absolute yield of 35-40 %, which melts at 63.5-65 °C, comprises the enantiomer-pairs la and lb in a ratio of AO : 60 and contains enantiomer-pairs Ic and Id as contamination in an amount of 5 %. The products thus obtained may be recrystallized as described above. Thus the mixture of enantiomer-pairs la and lb can be prepared with a purity above 99 %.

Similar results are obtained when recrystallizing mixtures of other cis/trans ratio.

The cypermethrin*s used as starting material may be prepared by esterifying the mixture of cyclopropane 15 carboxylic acids of suitable cis/trans ratio.

In the following Table the melting points of mixtures of various cis/trans ratio are disclosed.

Ia/Ib 25:75 30:70 40:60 50:50 55:45

m.p. :°C 67-71.5 65-68 63.5-65 60.5-62 61.5-64

The practical feasibility in the desired direction of the crystallization step strongly depends on the purity of the starting cypermethrin mixture. If the active ingredient content is lower than 95 %, the yields decrease. Tarry contaminations may even inhibit crystallization.

The crystallization of the mixture of enantiomer-pairs la and lb according to the present invention may be carried out in the absence of a solvent too. Thus cypermethrin of the composition Ie may be seeded with crystals consisting of la and lb. In a refrigerator the mixture of la and lb precipitates within a week. The crystals are isolated by adding ethanol cooled to -20 °C to the mixture and filtering the crystals.

The mixture of enantiomer-pairs la + lb according

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- 13 10 to the present invention may also be prepared byadmixing and/or crystallizing la and lb or various amounts thereof or by admixing and/or crystallizing a mixture of la and lb , or calculated amount of lb, respect ively.

The biological activity of the products according to the present invention is tested on various insect specii. In the test methods the effect of stereoisomers used as reference. standard and prepared by known method’s - e.g. by chromatographical separation or by chromatographical separation of cypermethrin* s prepared from chiral acids - is disclosed as well.

Vb

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 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 . 25 the said Examples.

Chemical Examples

Example 1

100 g of cypermethrin* /consisting according to gas chromatography of a mixture of 18.2 % of la, 21.8 % of Ic, 26.8 % of lb and 33.2 % of Id/, 0.2 g of potassium hydroxide and 0.2 g of 2,6-di-tertiary butyl-4-methyl-phenol are dissolved in 2000 ml of isopropanol under constant stirring at 45.0 °C. The solution is

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00024 slcwly ceded to 30 °C, clarified with activated charcoal ar.d filtered at 30 ^cC. The colourless solution is seeded with a crystal consisting of 60 % of lb and 40 % cf la and the mixture is stirred at -10 C for

24 hours. The precipitated product is filtered, washed with isopropanol and dried in vacuo. Thus 36.02 g of a snow-white crystalline product are obtained. M.p.:

62-65 °C /non-corrected value/. According to GC and TLC analysis the product contains 37 % of la an· 58 % of I’d isomers. Yield: 76 % /related to the la + lb isomer content of the cypermethrine starting material/.

Ia isomer R^. = 0.25; lb isomer R^. = 0.20.

After recrystallization from iscpropanol 32 g of the product are obtained as first crops. M.p.: 63.5-65.0 °C;

the product consists cf 39·5 % of Ia and 59-5 % cf lb.

IR /X3r/ : 1730, 1735 cm^-1

C — o

N/R /CDC1₃/ <T /ppm/: 1.05-2.45 m /3H/; 5.6, d,J =3Hz /=CH trans 0.6H/; 6.14, c, J=3Kz /=CH cis 0.4H/; 6.35, d, /1H/;

6.85-7.60 m, /9H/

Example 2

100 g of cypermethrin /27.8 % of Ia, 21.8 % of lb, 32.1 % of Ie and 18.2 % of Id/, 0.2 g of potassium hydroxide and 0.2 g of 2,6-di-tertiary buty1-4-methyl-phenol are dissolved in 2000 ml of iscpropanol under stirring at 45 °C. The solution is clarified with activated charcoal and filtered at 30 °C. The colourless solution is seeded with a seeding crystal cons is ting of

20 % of lb and 80 % of Ia and stirred at -10 °C for 36 hours. The precipitated product is filtered, washed with isopropanol and dried in vacuo. Thus 30 g of sr.cw-white crystalline product are obtained, m.p.: 66-73 °C.

According to gas chromatography the product contains

77 % of Ia + 19 % of lb, purity 96 % /TLC, see Example 1/.

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After recrysta 11ization from isoprcpanol az first generation 26.5 g of a snow-white crystalline product are obtained, m.p.: 70-73 °C, containing SI.5 of la + IS % of lb /GC analysis/.

IS /'Or/ V : 1730 cm^-1c = o

N>!R /CDC1₃/ eT'/ppm/: 1.05 - 2.45 m /SH/; 5.60 d J= 8HZ /=CH trans 0.2n/; 6.14 d J= 8Hz / = CH cis 0.8 H/; 6.35 d /ArCH 1H/ 6.85 - 7.60m/9H/.

Example 3

100 g of colourless clearly transparent oily cyperrr.ethrin /18.2 % of la, 21.8 % of Ic, 26.8 % of lb and 33.2 % of Id/ are seeded with a seeding crystal consisting of 60 % of lb and 40 % of la and the solution is allowed to crystallize at 7 ^CC for a week. The mixture is suspended in 100 ml of a 1:1 mixture of isopropanol and diisopropyl ether and filtered at -15 °C. The crystals are washed with isoproparol and dried in vacuo. Thus 40.1 g of a white crystalline product are obtained, containing 37.5 % of la and 59 % of I’d, m.p.:

62.5 - 65 °C. Yield 86 %. After recrystallization from isoprcpanol as first generation 36 g of a snow-white crystalline product are obtained, m.p.: 63.5 - 65 °C, consisting of 40 % of la and 60 % of lb /GC/. The IR and NHR are identical with those disclosed in Example 1.

Example 4

100 g of cypermethrin- /18.2 % of la, 21.8 % of Ic, 26.8 % of lb, 33.2 % of Id/ and 0.05 g of 2,6-di- tertiary butyl-4-methyl-phenol are dissolved in 100 ml of diisopropyl ether under constant stirring at 0 °C and the solution is clarified with 2 g of activated charcoal. The solution is filtered and seeded at -15 °C with a seeding crystal consisting of 60 % of lb and 40 % of la. The mixture is allowed tc crystallize for fiAD original $ ύύ024 hours, the crystals are filtered, .-.'ashed with diisccrccyl ether ar.d iscpropancl ar.d dried. Thus 3o g cf a snow-white crystalline product are obtained, yield 62-65 °C, comprising 37.5 % of la ar.d 53 % of lb. Yield 80.6 %. After recrystallication from isopropanol as first generation 35 g of a snow-white crystalline product are obtained, m.p.: 63,5-65 °C, the ratio of the la : lb isomers = 40 : 60. The physical constants are identical with those disclosed in Example 1.

Example 5 g of samples of the product obtained according . to Example 2 /the ratio of the la : lb isomers = 4:1/ are admixed with 4.60 g, 6 g, 10 g, 16.67 g and 22.0 g of pure seeding crystals of lb, respectively, and the mixtures thus obtained are recrystallized as described in Example 1 from a 10-fold amount of iscpropar.ol, each. The composition and melting point of the products thus obtained are shown in the following Table.

V 1· 0 0 0 0 dV la lb

M.d.: / C/

55:45 5:5 4:6 . 3:7 25:75

61.5- 64

60.5- 62

63.5-65 65-68 67-71.5

Example 6 g samples of pure crystalline isomer-pair la are admixed with 8.20 g, 10.00 g and 15.00 g of pure crystalline isomer-pair lb, respectively, and the mixtures are homogenized. The crystal mixtures thus obtained comprise the substances la + lb in a ratio

BAD ORIGINAL ύύΟ24 of 05:45, 50:50 and 40:60, respectively. . p. : 61. o-64 °C, 60.5-62 °C and 63.5-65 °C, respectively.

Example 7

10 g samples of pure crystalline iscmer-pair la are dissolved in 10-fold amount of isoprcpanoi and to each sample 23.34 g and 30.0 g of pure crystalline isomer-pair lb are added, respectively. The solutions are crystallized. The precipitated white crystalline products /m.p.: 65-68 °C and 67-71.5 °C, respectively/ comprise the la : lb isomers in a ratio of 30:70 and 25:75, respectively. The product thus obtained car. be formulated as plant protecting agent and is a useful insecticidal active ingredient.

Formulating examples

Example 8

To 166.2 g of perlite /d_max = 120 ^urn/ 0.8 g of syntheti-c silicic acid /Aerosil 300/ are added in a fluidizing rapid stirrer. 20 g of a cypermethrine mixture of enantiomer-pairs Ia:Ib = 4:6 and 2 g of fatty alcohol polyglycol ether are added so that the mixture is uniformly homogenized. The powder mixture is grouhd first in a mechanical mill and afterwards in an air flow mill, whereupon 5 g of octyl phenol polyglycol ether /£0=20/ and 2 g of sulfcsucc ir.ate are added in a rapid stirrer. The wettable powder mixture /W?/ thus obtained is subjected to suspension stability test. Wetting time = 23 seconds; floatability = 89 % /standard WHO method/.

Example 9 g of a mixture of cypermethrin enantiomer35 -pairs la : lb = 3 : 7 and 0.3 g of fatty alcohol poly^BAD ORIGINAL $ ¹ ΰΰΰ24

- 13 glycol ether are applied in a homogenizing apparatus onto talc /d = 15 ,um/ adjusted to the pH value of 6.5 with a buffer of 0.8 of synthetic silicic acid /Aerosil 200/ and 193.9 g of potassium and sodium phosphate. To the mixture 1 g of dioctyl sulfosuccinate an 1 g of fatty alcohol polyglycol ether sulfonate are added under stirring and the mixture is ground to an average particle size of 20 ^um. Thus a thin flowable powder mixture is obtained.

Example 10 g of a mixture of cypermethrin enantiomer-pairs la : lb = 55 : 45 are dissolved in a mixture of 21.25 g of xylene and 42.5 g of n-propanol under slow stirring. To the solution a mixture of 4 g of ethoxylated alkyl phenol + calcium salt of linear alkyl aryl sulfonate and a mixture of 6 g of ethoxyla ted amine + alkali salt of linear alkyl aryl su lfona te is added under stirring until all the materials are completely dissolved, whereupon 21..25 g of water are added. Thus a transparent solution is obtained which maintains its properties at a temperature between 0 °C and 50 °C for long period of time. The solution can be optionally diluted with water at any rate under the formation of an emulsion having a droplet-size of 0.8-1.5 /Urn.

Example 11 g of a mixture of cypermethrin enantiomer-pairs la : lb = 25 : 75 are dissolved in a mixture of 75 g of xylene and 10 g of an aliphatic oil whereupon under slow stirring a mixture /7.5 g/ of ethoxylated alkyl phenol + calcium salt of linear alkyl aryl sulfonate and also a mixture /2.5 g/ of ethoxylated fatty acid + linear alkyl aryl sulfonate salt are added. When measured according to the method of CIPAC the

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- 19 emulsion concentrate proves to be stable after 170 hours .

Example 12

In a mechanical granulator a 50 : 50 mixture of the la and lb cypermethrin enantiomer-pairs is admixed with 1500 g of polycarboxylate alkali salt, 500 g of sodium dodecyl benzene sulfonate, 500 g of saccharose and 7200 g of China-clay. The powder ·mixture is admixed with 8300 ml of water by using a stirrer of large shearing strength /v=10 m/sec/ and subjected to spray drying. The distribution of'particle size is as follows:

0.1 - 0.4 mm = 95 %. The floatability amounts to 98 % /according to the WHO method/.

Example 13

Emulsifiable concentrates /EC/ are prepared by admixing the following components:

EC

Component

Isomer-pairs Ia:Ib=4O-6O Cyclohexanol “

Atlox 3386 B Atlox 3400 B Odourless mineral oil

EC

Component

Isomer-pairs Ia:Ib=40:60 Cyclohexanol Atlox 3386 B Atlox 3400 B Odourless mineral c-il

Amount, kg/kg

0.105

0.290

0.020

0.045

0.540

Amount, kg/kj

0.050

0.290

0.020

0.045

0.595 bad ORIGINAL g

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- 20 Biological Examples

Example 14

In Table 1 the activity of various stereoisomers 5 cf cypermethrin on house fly /Musca domestica/ is shown.

The test i.s carried out as follows:

The active ingredient is dissolved in a 1:2 mixture of oil and acetone; filter paper discs /Whatman No. 1, diameter 9 cm/ are impregnated with the solutions of the corresponding stereoisomers and enantiomer-pairs, respectively. The acetone is allowed to evaporate, whereupon the insects are exposed to filter paper discs placed in Petri-dishes . Three parallels are used or each dose* and 15 insects are placed into each Petri-dish.

The percental mortality is determined after 24 hours.

The corrected percental mortality is calculated by means of the Abbot Formula.

Table 1

Cypermethrin Dose /mg/disc/ s tereoisomer 0.04 0.11 0.33 1.00 3.00 hour^ mortality /%/

AP 0 0 0 0 1 4

If	68	93	100	100	100
la	44	84	100	100	100
I^σ ^x o	48	68	83	100	100
lb	32	62	95	100	100
Ia:Ib=40:60	41	81	100	100	100

-_:-=According to this test the activity of mixture la + lb corresponds to that of the pure isomer la.

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Example 15

It appears from Table 2 that the increased

5 10	activity shown effect of the Active ingredient	in Example 14 is due to the synergistic trans-isomers, to tribolium confusum.
Table 0.11 24	2
Dose 0.33 hours	/mg/disc/ 1.00 ’ mortality	3.00 0/ /0
	IScisR /Ih/	0 ·	3c	SO	100
♦	IReisS /If/	60 .	100	100	100
	la	22	65	94	100
15	IStrar.sR /Ii/	0	0	71	90
	IRtransS /Ig/	70	92	100	100
	lb	64	89	100	100
	la :13=40:60	61	89	100	100
20		-
	In Example 13 it is	shown	on further	insect species
	that the enantiomer-pair lb	of the present	invention
	is more active	than la. The	increased activity manifests
	itself not only in the 24 hours’	mortality	but also in
25	the fact that	the toxical effect	is exhibited mere
	rapidly.

Example 16

In Table 3 the insecticidal effect of .mixtures of enantiomer-pairs la and lb of various ratio is shewn on flour beetle /Tribolium confusum/. The test method is that disclosed in Example 1^,

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- 22 Table 3

la : lb	Dose /mg/disc/
0.02	0.06 24 hours’	0.25 mortality	o o
10:0	0	14	54	100
5:5	0	43	100	100
4:6	14	53	100	100
3:7	20	81	100	100
0:10	8	46	100	100

The above data clearly prove the synergism between enantiomer-pairs la and lb.

Example 17

According to a further recognition of the present invention when the mixtures of enantiomer-pairs la and lb are combined with conventional pyrethroids synergists /e.g. piperonyl butoxide, NIA 16388 etc./ the'increase of activity is larger than the usual value /see Example 16/.

In Table A the activity on Colorado potato beetle is shown.

The test method is as follows:

The test materials are dissolved in 2-ethoxyethanol /Cellosolve/. One 0.3 ^ul drop of the solution is applied to the abdominal stern'a of the imago. The treatment is carried out by using 2 parallels and 10 insects for each dose. Mortality is determined after 48 hours.

AP 0 0 0 0 1 A

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Table 4

Active ingredient	Dose / ’j^/beetle / °
	0.05	0.10 24 hours’	0.20 mortality	0.40 0/ ;o
la	50	55	75	80
lb	0	25	75	85
la:Ib=4:6	45	60	70	80
Ia:Ib=3:7	45	65	75	85
deltametrin	A5	60	75	85
cyperm.etr in	0	20	45	75

Synergism is observed between enan ticmer-pairs la and lb, although on imago of Colorado potato beetle Is is more active than lb. Mixtures of enantiomer-pairs la and lb exert the same activity a deltametrine.

Example 18

The comparative test of la, I'd and a 40:60 mixture of la : lb is carried out on bean weevil /Acanthoscelides obtectus/, flour-beetle /Tribolium confusum/, house fly /Musca domestica/ and sheep maggot fly /Lucillia sericata/. The test method described is Example 14 is used. The results are summarized in Table 5.

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Table 5

5	Species	Enantiomer pa ir	Dose /mg/disc/
0.02	0.07	0.22 mor ta1	0.67 ity %	2.0	6.
	A.obtectus	la	10	37	63	95	100	100
	/imago/	lb	32	55	87	100	100	100
		Ia:Ib=4:6	30	55	90	100	100	100
	T.confusum	la	0	18	51	100	100	100
10	/ imago/	lb	14	73	100	100	100	100
		Ia:Ib=4:6	16	80	100	100	100	100
	M.domestica	la	36	63	88	100	100	100
*	/imago/	I'd	0	18	67	100	100	100
		Ia:Ib=4:6	25	45	85	100	100	100
15	L.sericata	la	0	30	29	57	60	65
	/imago/	lb	22	55	70	75	100	100
		Ia:Ib=4:6	18	50	60	75	100	100

APO 0 0 0 1 4

Example 19

Activity of cypermethrin stereoisomer-pairs as function of time on flour beetle /T. Confusum/.

Flour beetle /T. confusum imagos are exposed in Petri-dishes according to the method described in Example 14.“For each dose 3 parallels are used and 15 animals are applied for each parallel test. In each point of time the insects lying on their backs are counted and the percental results are expressed in Table 6.

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ΟϋΙTable 6

Stereoisomer-pairs Exposition and enantiomer- time /minutes/ pairs

Case /mg/disc/

0.11 C.33 1.00 3/·.·' % cf insects shewing toxical symptoms

	Ih	30	0	0	0	0
				60	0	0	0	8
				120	0	0	0	67
				ISO	0	0	0	88
	10	If		30	0	0	48	64
				60	0	5	84	100
				120	0	40	100	100
				ISO	39	61	100	100
	*	la		30	0	0	0	33
	15			60	0	0	16	88
			120	0	14	66	100
				150	J.0	49	100	100
'4, J
				30	0	0	C	15
&				60	0	0	0	70
			120	0	0	0	100
				ISO	0	0	0	100
	20
		Tg		30 ‘	0	0	1 C	68
				60	13	34	98	100
				120	30	70	ICO	100
				180	34	84	ICO	100
		lb		30	0	0	47	61
	25			60	0	21	82	100
			120	28	ICO	100	100
				180	56	100	100	100
		Ia:Ib=4;6		30	0	0	50	55
				60	15	85	85	100
				120	30	100	100	100
				180	55 -	.ICO	100	100

Example 20

Imagos of flour-beetle /T. confusum/ are treated in an analogous manner to Example 14. As synergist piperonyl butexide is used in a dose cf 0.5 mg/disc.

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	-2d -
•	Table 7
cypermetrin		Dose	/mg/d	isc/
stereoisomer	0.4	0.2	0.1	0.05	0.025
	24	hours’	mortality %
la	96	53	12	0	0
la + P30	100	58	16	0	0
Ia+Ib	100	90	57	18	0
Ia+Ib+PSO	100	95	75	' 43	7

It may be seen that the mixture of enantiomers la and lb can be synengized to a larger extent than enantiomer Ie . /la :16 = 4:6/.

Example 21

The active ingredients are dissolved in 2-ethoxyethanol and the solutions are applied in the form of 0.2 /Ul droplets onto the back of fall webwonm /Hyphantria cunea/ of L^-Lg larvae soage. The treated worms are placed on strawberry leaves in Petri-disches. The test is carried out by using a doses, 2 parallels and 10 insects for for each dose. The killed worms are counted aft_er 24 hours and the percental mortality rate is calculated. The results are summarized in Table 8.

Table 8

Active ingredient Dose / ,ug/larvae/

0.023 0.047 ^Z0.0?4 0.188 0.375 hours’ mortality % ·

la	40	60	65	80	90
lb	10	15	30	70 ’	80
la :Ib = 4:6	40	50	55	65	75
cypermetrin	0	10	25	50	75

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0ύ024

Example 22

Leaves already infested with mites /Tetranychus urticae/ were sprayed under Potter Tower. Mortality after 24 hours on the treated leaves was compared with the control.

Table 9

Active ingredient approx LD^q /ppm/

Ia	0.056
lb	0.340
Ia:Ib=4:6	0.060
cypermetrir.	0.120
deltametrin	0.185

Example 23

The 5 EC formulations prepared according to Example 13 are diluted 50x, lOOx, 200x, 400x, 800x and 16C0x with water and 0.5 ml doses are sprayed onto glass plates. After drying 10 L. decemlineata imagos are placed on each glass plate and the insects are covered with Petri-dishes. The tests are carried out by using 6 doses and 3 parallels for each dose. The killed insects are counted after 48 hours. The result are disclosed in Table 10.

Table 10

EC dilution

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Example 24

Glass plates are sprayed with 5 EC formulations prepared according to Example 13 in an analogous manner to Example 23. After drying 10 bean weevil /Acanthoscelides obtectus/ imagos are placed on each plate and the insects are covered with Petri-dishes . The killed insects are counted after 24 hours. The test is carried out with 6 doses by using 3 parallels for each dose.

The results are summarized in Table 11.

Table 11

EC dilution

f ormulation	1600	x 800x 400x mortali	200x ty %	lOOx	50x
la	0	13	27	33	50	70
Ia:Ib=4:6	10	17	30	37	53	⁷⁰
deltametrin	7	13	20	37	57	75
cypermetrin	0	3	10	20	45	60

Example 25 bean plants infected with green peach aphids/Myzus persicae/ at 6 days’ age are cultivated in each pot.

At 12 days’ age the strongly and uniformly infected plants are selected and sprayed to run-off with emulsions freshly prepared from the formulation according to Example 13. Treatments are carried out with three doses /active ingredient 2.5, 5 and 10 ppm/ and four parallels are used /one pot per parallel/. The second, fourth a-nd eighth day after treatment the aphids are swept down from the plants to a white paper with a fine brush and the live insects are counted. The results are disclosed in Table 12.

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5	5 EC formulations	Concentrat ion '/ cpm/	Average number of aphids per pot Days after treatment
2	4	8
	la	2.5	44	83	245
		5.0	22	29	90
10		10.0	8	17	30
	la:Ib = 4:6	2.5	38	71	251
		5.0	21	32	82
		10.0	10	11	21
15	de1 tame tr in	2.5	26	47	137
		5.0	13	19	29
		10.0	6	11	23
20	control	-	1850	2780	4120

J?

Example 26

Tomato plants pre-cultivated in pots are sprayed with·a suspension of the active ingredient formed with 25 a mixture of acetone and water. The treated plants are placed into isolators and infected with stage Leptinotarsa decemlineara larvae. The percental ratio of paralysed larvae which fall down from the plants is determined after 6 hours. The results are disclosed in Table 13.

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Concentration la la : lb : 4 : 6 /pern/ % ratio of paralysed larvae

10C0	• ICG	100
200	100	100
40	4c	75
8	13	60

Example 27

Toe treatments are performed on a 25 m plot strongly infected with Colorado potato beetle. 10 plants per plot are specially marked on which the

Colorado potato beetles were counted previously. /During assessment of the number of pests only adults of the second Summer generation are taken into consideration, because at the point cf time of the test the ratio of lavae cf stages and L, is negligible/. Treatment is accomplished on 25 m plots at a dose of 10 g of active 2r.gredient/ha with aqueous suspensions of the formulations according to Example 10 and three parallels are used. The test is evaluated by counting the live insects on the marked plants. The average values of three parallel tests are disclosed in Table 14.

Table 14

5 ME Average number of live insects/10 plants formulation Time elapsed after treatment /in days/

13 9

ΑΡ0 0 0 0 1 4

la	171	11	9'	25
la: Ib = 4:6	213	8	4	22
Deltametrin·	131	7	10	19
Control	211	206	179	183

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- 31 Example 28

Residual contact test on adults of Aphidinus matricariae. Adults of A matricariae are exposed to residues of the active ingredients freshly applied on glass plates forming cages, then the survivors are counted.

Treatment: test product/s/ and control treated with water.

Replicates: at least 3. Plot size /net/: 1 cage.

Parasites of known age /24 hours/ are used.

The products are applied at 5.1 ppm concentration, to each of the glass plates.

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 shown in Table 15.

Table 15

Concentration ppm 1 pom

X lh lh 5h 24h mortality % ^: ~

la	100	100	100	96
la :Ib = 4: 6	100	50	90	63
deltametrin	100	20	100	85

³⁰

Example 29

Direct contact test on pupae of A. metricariae Mature pupae of A. matricariae on paprika leaves in Petri-dishes are exposed to a direct spray of the 35 active ingredients. Two or three days before emergence

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- 32 paprika leaves with parasitized pupae are used. The leaves are laid on moistened filter paper in a plastic Petri-d ish.

App1ica tion of treatment: see Example 28.

The pieces of leaf are transferred after treatment to clean Petri-dish bottoms. The trays are stored in a climatic chamber at 20 °C temperature, 70 % 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 are shown in Table 16.

Table 16

Active ingredient Concentration ppm 10 ppm 5 ppm 1 ppm mortality %

Ib:Ia=6:4	14.3	0
Deltametrin	75.0	33.0
la	77.0	12.5
control	0	0

APO 0 0 0 1 4

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f ormuLa t ion

800x 400x 200x mortality %

deltametrin

cypermetrir. .

What we claim is,

1/ Insecticidal composition containing more than one active ingredients, which comprises as active ingredient in an amount of 0.001-99 % by weight a synthetic pyrethroid of the general Formula I

20 /wherein X stands for chlorine or bromine/ - namely out of the eight possible isomers at least 95 %' of a 55:45 - 25:75 mixture of the enantiomer-pairs Ia:Ib, wherein la is IReisS + IScisR and lb is IRtransS + IStransR if desired in admixture with an activator and/or with

25 an amount of up to 100 % of an auxiliary agent, preferably an antioxidant, stabilizer, wetting agent, emulsifying agent, dispersing agent, antifoam agent, diluent, carrier, and/or filler.
2/ Insecticidal composition according to Claim 1,

30 which comprises as active ingredient a 40:60 mixture of Ia:Ib.
3/ Insecticidal composition according to Claim 1, which comprises as active ingredient a 30:70 mixture of la : lb .

35
4/ Insecticidal compcsiticr. according to Claim 1,

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ZD which c o m p r i s e s as active i n g r e d i n e t a 50:50 mixture cf Ia : Ib.
5/ Process for the prepara tier, of an insecticidal active ingredient comprising out of the eight possible isomers cf synthetic pyre thro ids of the general Formula I /wherein X stands for chlorine or bromine/ substantially only a 55:45 - 25:75 mixture of enantiomer-pairs Ia:Ib - wherein la is IReisS and IScisR and lb is IRtransS and IStransR - , which comprises a/ preparing from a mixture comprising in addition to the isomer-pairs la + lb other possible isemers too and/or comprising the isemer-pairs la + lb in a ratio ether than the desired value a saturated solution with a protic or apolar aprotic inert organic solvent, seeding the solution with a seeding ervsta1 consisting of a 55:45 - 25:75 mixture cf enantiomer-pairs la and lb, and isolating the crystals precipitating at a temperature between 30 °C and -30 °C; or b/ seeding a melt of a mixture comprising in addition to the isemer-pairs la + lb ether isemers tco and/or comprising the isemer-pairs la +'Ib in a ratio other than the desired value at a temperature between 10 °C and 60 °C with a seeding crystal comprising a 55:45 - 25:75 mixture cf enantiomer-pairs la and lb, allowing the solution to crystallize at a temperature between 30 °C and -10 °C and, if desired, suspending the mixture thus obtained at a temperature between -10 °C and -20 °C in a protic or apolar aprotic inert organic solvent and isolating the precipitated crystals; or c/ adding to a solution or a melt of a mixture comprising in addition to the isemer-pairs la + lb other isemers too and/or comprising the isemer-pairs la + lb in a. ratio other than the desired value an er.antiomer-cair la or lb in such ar. amour.·: that the solution or the melt should contain the isemers in a ratio cf 55:45 35

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- 25:75 and, if desired, performing crystallization according to variant a/ cr b/; or d/ admixing enantiomer-pairs la and Io in the desired ratio - if desired, in the presence of a protic

5 cr apolar aprotic organic solvent - homogenizing the mixture and performing crystallization - if desired, after the seeding step according to variant a/.
6/ Process according to Claim variant a/ of Claim 5, which compr ises using as organic

10 solvent a hydrocarbon, & chlorinated hydrocarbon, C2 θ dialkyl ether or alkanol, whereby the said solvents may be a straight cr branched chained and cyclic or alioyclic, respectively.
7/ Process according to variant a/, c/ or d/

15 of Claim 5, which comprises carrying cut seeding with a seeding crystal in the presence of an antioxidant.
8/ Process according to Claim 7, which comprises using as antioxidant tertiary butyl20 -hydroxy-toluene or 2,2,4-trimethyl quinoline.
9/ Process according to any of Claims.7 and 8, which comprises using as solvent ethanol, petrolethen or hexane.
10/ Use of an insecticidal composition accending

25 to CLaim 1 to combat insect pests at a dcse of 2.0-25 g of active ingredient/ha.