GB1583600A - Allethrolone esters - Google Patents

Abstract

An optically active (R)- or (S)-allethrolone X-sulphonate is reacted with a salt of 2,2-dimethyl-3-(2'-R1-2'-R2-vinyl)cyclopropanecarboxylic acid, in an organic solvent. X above represents a C1-C3 alkyl or a phenyl optionally substituted at the para position by a methyl or a fluorine, chlorine or bromine atom and R1 and R2 are defined in Claim 1. Esters of formula: <IMAGE> are obtained in which the allethrolone has the antipode configuration, (S) or (R), of that of the sulfonate used. The process makes it possible to reuse (R)-allethrolone produced by resolution of racemic allethrolone. The esters (I) have an insecticidal action; they can be used, especially, in the form of an insecticidal composition.

Description

1(54) ALLETHROLONE ESTERS (71) We, ROUSSEL UCLAF, a French Body Corporate of 35 Boulevard des Invalides, Paris 7emu, France, do hereby declare the invention, for which we pray that a patent may be granted to us, and the method by which it is to be performed, to be particularly described in and by the following statement: This invention relates to a process for preparing optically active allethrolone esters of cyclopropane carboxylic acids.

It has previously been shown that in general the esterification of cyclopropane carboxylic acids with (S)-allethrolone leads to compounds having a much higher insecticidal activity than compounds formed using (R)-allethrolone or racemic allethrolone. However, the methods for obtaining such (S)-allethrolone esters described hitherto, all involve esterifying the cyclopropane carboxylic acid or a functional derivative thereof with (S)-allethrolone. In order to obtain the desired (S)-allethrolone, a resolution process such as that described in French Patent Specification No. 2,166,503 has been used. However, such processes lead to the obtention not only of the desired (S) isomer but also of the (R) isomer and therefore the yield of the desired (S) isomer is low.

We have recently found methods for converting the (R) isomer into the more preferred (S) isomer thereby obtaining increased yields of the (S) isomer.

One such method is described in our British Patent Application No. 20296/77 (Specification No. 1,528,115). However, the method described therein involves racemisation of the (R)-allethrolone followed by a further resolution step and thus is relatively complex to carry out whilst still leading intermediately to a mixture of the (R) and (S) isomers which inevitably leads to low yields unless the procedure is repeated several times.

Further methods of converting the (R) isomer into the (S) isomer are described in our British Patent Applications Nos. 26159/77 and 35744/77 (Specifications Nos.

1,535,157 and -1,548,474), which methods allow the direct conversion of (R)allethrolone into (S)-allethrolone by formation of an (R)-allethrolone sulphonate, in the latter case followed by conversion to a carboxylate, and subsequent hydrolysis thereof.

We have now found, however, that it is possible to convert (R)-allethrolone or indeed (S)-allethrolone sulphonates directly into an allethrolone cyclopropane carboxylic acid ester wherein the allethrolone has the configuration antipodal to that of the sulphonate, in a single reaction step and in high yields.

Thus according to one feature of the present invention there is provided a process for the preparation of compounds of general formula I,

(wherein the allethrolone ring is optically active and either (I) Rl and R2, which may be the same or different, each represents an alkyl radical containing from I to 3 carbon atoms; (2) Rl and R2, being the same, each represents a fluorine, chlorine, or bromine atom; (3) Rl represents an alkyl radical containing 1 or 2 carbon atoms and R2 represents an acetyl or methoxymethyl radical; or (4) R1 and R2, together with the carbon atom to which they are attached, form a carbocyclic ring containing from 3 to 6 carbon atoms or a group of formula

in which X represents an oxygen or sulphur atom) which comprises reacting an optically active compound of formula II,

(wherein R represents an alkyl radical containing from 1 to 3 carbon atoms or a phenyl radical optionally substituted in the para position by a methyl radical or a fluorine, chlorine or bromine atom) of appropriate configuration with a salt of a compound of formula III,

(wherein R1 and R2 are as defined above), in the presence of an organic solvent, the reaction proceeding with inversion of configuration in the allethrolone ring.

The compound of formula II may be in the form of a single isomer, e.g. the (R) isomer or in the form of a mixture of isomers in which one isomer, e.g. the (R) isomer, predominates. Similarly the salt of the compound of formula III may be in the form of a single optically active isomer or of a mixture thereof, e.g. a race mate, depending on the product which it is desired to obtain.

The salt of the compound of formula III is preferably an alkali metal, alkaline earth metal or an ammonium salt or a salt formed with a tertiary base, particularly preferred being an alkali metal salt especially the sodium and potassium salts.

The compound of formula III may, for example, be a 2,2 - dimethyl - 3 - (2' methylprop - I' - enyl) - cyclopropane - 1 - carboxylic acid; a 2,2 - dimethyl - 3 (2',2' - dichlorovinyl) - cyclopropane - l - carboxylic acid; a 2,2 - dimethyl - 3 2',2' - dibromovinyl) - cyclopropane - I - carboxylic acid ; a 2,2 - dimethyl - 3 (2',2' - difluorovinyl) - cyclopropane - I - carboxylic acid; a 2,2 - dimethyl - 3 - (2' methyl - 3' - methoxy - (E) - prop - 1' - enyl) - cyclopropane - I - carboxylic acid; a 2,2 - dimethyl - 3 - (2' - ethyl - 3' - oxo - but - 1' - enyl) - cyclopropane - I carboxylic acid; a 2,2 - dimethyl - 3 - (cyclopentylidene - methyl) - cyclopropane 1 - carboxylic acid; a 2,2 - dimethyl - 3 - (2' - oxo - 3' - oxa - cyclopentylidene - methyl) - cyclopropane - I - carboxylic acid; or a 2,2 - dimethyl - 3 - (2' - oxo - 3' thia - cyclopentylidene - methyl) - cyclopropane - 1 - carboxylic acid.

Particularly preferred compounds of general formula III are 2,2 - dimethyl 3R - (2' - methylprop - 1' - enyl) - cyclopropane - 1R - carboxylic acid; 2,2 - di methyl - 3S - (2' - methylprop - 1' - enyl) - cyclopropane - IR - carboxylic acid; 2,2 dimethyl - 3R - (cyclopentylidene - methyl) - cyclopropane - IR- carboxylic acid; 2,2 - dimethyl - 3S - (2',2' - dichlorovinyl) - cyclopropane - 1 R - carboxylic acid; 2,2 - dimethyl - 3S - (2',2' - difluorovinyl) - cyclopropane - IR - carboxylic acid; and 2,2 - dimethyl - 3R - (2',2' - difluorovinyl) - cyclopropane - IR - carboxylic acid.

The organic silvent used in the reaction between the compound of formula II and the salt of the compound of formula III preferably comprises dimethylformamide, hexamethylphosphorotriamide, dimethylsulphoxide, dimethoxyethane, acetonitrile, an- aliphatic ketone containing from 3 to 6 carbon atoms, an alkanol, a monocyclic aromatic hydrocarbon or a mixture thereof. Particularly preferred solvents are hexamethylphophorotriamide, dimethylsulphoxide, dimethylformamide, a mixture of toluene and dimethylsulDhoxide and a mixture of toluene and a secondary or tertiary alkanol containing from 4 to 6 carbon atoms, especially tertiary butanol.

The compounds of general formula II are described and claimed in British Patent Application No. 26159/77 (Specification No. 1,535,157) as well as processes for their preparation. Thus, for example, they may be obtained by reaction of optically active allethrolone of appropriate configuration with a compound of formula IV, R SO2 Cl (IV) (wherein R is as hereinbefore defined) in the presence of an organic solvent and of a basic agent, the reaction proceeding with retention of configuration in the allethrolone ring. The basic agent is preferably a tertiary base, particularly triethylamine and preferred organic solvents comprise an aliphatic ketone containing from 3 to 6 carbon atoms, a monocyclic aromatic hydrocarbon, an ether oxide, a chlorinated solvent or a mixture thereof. Particularly preferred solvents comprise acetone and toluene.

Of the compounds of general formula II, especially preferred are those wherein R represents a methyl or p-tolyl radical. Preferably the compound of formula II is used in the reaction with the salt of the compound of formula III without isolation from the reaction mixture in which it was formed, in which case the solvent used in its preparation preferably comprises a monocyclic aromatic hydrocarbon.

The salt of the compound of Formula III is also desirably used in the reaction with the compound of formula II without isolation from the reaction mixture in which it was formed. Formation of the salt of the compound of formula III may, for example, be effected by reaction of a compound of formula III as hereinbefore defined with an appropriate base in the presence of an organic solvent, which solvent preferably comprises dimethylformamide, dimethylsulphoxide, hexamethylphosphorotriamide, dimethoxyethane, acetonitrile, an aliphatic ketone containing from 3 to 6 carbon atoms, an alkanol, a monocyclic aromatic hydrocarbon or a mixture thereof.

Thus, as mentioned above, the process according to the present invention enables an(R)-allethrolone sulphonate to be converted directly, in one stage, into an (S)-allethrolone cyclopropane carboxylic acid ester hence avoiding the necessity of isolating (S)-allethrolone and subsequently using this to esterify an appropriate cyclopropane carboxylic acid chloride. The process of the present invention is also of advantage in that it may be used not only on a single allethrolone sulphonate isomer but also on a mixture of isomers in which one isomer predominates since, such mixtures are almost invariably obtained after a particular isomer has been isolated during a resolution process.

Tie process accorEg to the present invention is surprising and could not have been predicted from the literature. Thus, although a few examples of the inversion of optically active alcohols by the action of an acetate on their tosylates have previously been described, this method has not hitherto been applied to allethrolone. The preparation of allethrolone sulphonates is known to give rise to difficulties and indeed the treatment of allethrolone with methanesulphonyl chloride in the presence of a weak base such as pyridine to give a chlorinated derivative rather than the sulphonate has previously been described.

The allethrolone sulphonates such as are used in the present invention are also unstable, being sensitive to heat and to the presence of mineral and organic bases which cause them to lose their sulphonyl group and thus lead to dimerisation by a Diels Alder reaction as follows.

base ẏ I 0 RS02 0 base < t + 0 jo I These sulphonates are also sensitive to the presence of hydrochlorides of bases such as e.g. triethylamine which induce the formation of chlorinated derivatives.

We have found, as described in our British Patent Application No. 26159/77 (Specification No. 1,535,157), that using certain conditions described therein as mentioned above, these sulphonates may be prepared in good yields, thus enabling their preparation for use in the present invention to be effected.

The reaction of these sulphonates with a cyclopropane carboxylic acid salt might also be expected to give rise to difficulties not only due to the alkaline nature of these salts which it might be expected would tend to lead to dimerisation of the sulphonates but also due to incomplete epimerization in the allethrolone ring leading to at least partial racemization.

However we have found that the process according to the present invention leads, with very high yields, to a remarkably pure product both from the chemical and optical point of view, undesirable side reactions being substantially avoided or reduced.

Of the compounds of general formula I which may, for example, be prepared according to the present invention, the following are novel compounds constituting a further feature of the present invention.

(S) - allethrolone 2,2 - dimethyl - 3R - (cyclopentylidenemethyl) - cyclo propane - I R - carboxylate (compound A), (S) - allethrolone 2,2 - dimethyl - 3S - (2',2' - dichlorovinyl) - cyclopropane I R - carboxylate (compound B), (S) - allethrolone 2,2 - dimethyl - 3S - (2',2' - difluorovinyl) - cyclopropane IR - carboxylate (compound C) and (S) - allethrolone 2,2 - dimethyl - 3R - (2',2' - difluorovinyl) - cyclopropane I R - carboxylate (compound D).

We have found that the above four compounds A, B, C and D possess good insecticidal activity including an extremely high knock-down power (i.e. power to paralyse insects) as illustrated hereinafter.

They are of particular use in the domestic field but are also applicable in agriculture in which case, in particular, they may optionally be combined with other pyrethrin compounds.

Thus, for example, the knock-down activity and lethal activity of the compounds A, B, C and D was tested on houseflies and on Aedes Aegypti: A) Study of the knock-down effect on the housefly The test insects are female houseflies, aged 3 days. Spraying is direct in a Kearns and March chamber, using, as solvent for the test compound, a mixture, in equal volumes, of acetone and kerosene (quantity of solution used: 500 mg).

About 50 insects are used per treatment. Checks are made every minute up to 15 minutes.

The result is expressed as the K.T. 50 which is the time necessary to paralyse 50% of the insects. Thus this time decreases as the activity of the test compound increases.

The experimental results obtained are summarized in the following Table:

Dose in PERCENTAGE K.D. (KNOCK-DOWN) KT 50 mg/l of in test compound 2 mins 4 mins 6 mins 8 mins 10 mins 15 mins minutes Compound A 1000 30.0 83.3 93.3 93.3 96.7 100 2.6 500 13.8 58.5 79.3 79.3 82.8 96.6 3.7 250 0 46.6 83.3 90.0 90.0 90.0 4.3 Compound B 500 32 70 89 100 - - 2.9 250 12.7 46.5 68.7 84.8 96.9 100 4.3 125 5 14 35 51 68 89 7.5 Compound C* 1000 92 98 100 100 100 100 < 1 500 94 98 100 100 100 100 1.16 250 52 96 98 100 100 100 1.7 Compound D* 1000 62 84 100 100 100 100 1.7 500 60 80 100 100 100 100 1.7 250 30 74 100 100 100 100 2.5 Conclusion: Compounds A, B, C and D are endowed with a good "knock-down" activity with respect to the housefly.

* For compounds C and D, the KT 50 were determined by graphic estimation.

B) Study of the lethal effect on the housefly The test insects are houseflies of both sexes. 1 l of an acetonic solution of the test compound is topically applied on the dorsal thorax of the insects. 50 individual flies are used per dosage. A check on mortality is made twenty four hours after treatment.

The compound to be tested is synergized by piperonyl butoxide (10 parts by weight of piperonyl butoxide for 1 part of the compound to be tested).

Dose in ng of test compound per % mortality LD 50 in ng fly after 24 hours per insect Compound A 50 90.9 25 72.5 17.5 12.5 28.2 Compound B 250 100 100 86.7 38.0 50 65.6 Compound C 25 100 12.5 53.3 10.1 6.25 16.7 Compound D 175 100 50 90 25.4 25 46.6 Conclusion: The compounds are endowed with a good lethal activity on the housefly.

C) Study of the insecticidal activity of compounds C and D in the form of fumigant compositions on Aedes Aegypti The knock-down effect and the lethal effect of the compound to be tested are studied on females of the species Aedes Aegypti.

The method of the Dainippon closed cylinder is used. A fumigenic coil containing the compound to be tested is burnt for one minute at one end of a closed cylinder of 20 cm diameter and 43 cm height containing 20 female Aedes Aegypti.

The knock-down effect is observed every thirty seconds for five minutes. The results are expressed in KT 50 (i.e. the time necessary to paralyse 50 percent of the insects) for each dose. This time decreases as the activity of the test compound increases.

The individual dead Aedes Aegypti are also counted after 24 hours and the results of lethal activity are expressed in percentage mortality.

3 series of successive tests were made and the averages of these tests were determined.

The tests are made in parallel with a test using a comparison compound known for its high knock-down activity ((S)-allethrolone d-trans-chrysanthemate [or compound E]).

The experimental results obtained are summarized in the following table:

Average TEST I TEST II TEST III weight of average % average coil mortality KT 50 KT 50 mortality KT 50 mortality KT 50 mortality burnt in in Dose (1) in mins after 24 H in mins after 24 H in mins after 24 H in mg 24 H mins Compound C 0.15 0.60 100 0.75 100 0.75 100 44.5 100 0.70 0.075 1.40 93.8 1.25 100 1.25 100 49.9 97.8 1.30 0.037 1.90 62.5 2.0 80 2.40 52.1 48.5 64.9 2.10 Compound D 0.15 0.75 100 0.75 100 0.75 100 43.0 100 0.75 0.075 1.45 100 1.70 73.6 1.40 100 47.8 91.2 1.55 0.037 1.60 58.8 2.30 75 1.70 78.9 50.6 70.9 1.85 Compound E 0.60 1.40 100 1.15 100 1.65 100 48.2 100 1.40 0.30 2.25 100 2.40 95.7 2.25 100 43.7 98.9 2.30 0.15 2.70 100 3.10 100 2.70 81 47.5 93.4 2.80 Conclusion: The K.D. activity of compounds C and D is about 4 times greater than that of compound E. Compounds C and D also possess an interesting lethal activity.

(1) percentage by weight of test compound in the fumigenic coil.

According to a yet further feature of the present invention there are provided insecticidal compositions comprising, as active ingredient, at least one of the four compounds A, B, C and D mentioned above in association with an insecticidal carrier or excipient.

The insecticidal compositions may be in the form of any conventional insecticidal preparation and may optionally include one or more further pesticidal agents and/or synergistic agents such as, for example piperonyl butoxide or N (ethyl-2-heptyl)-bicyclo(2,2, I )-5-hepten-2,3-dicarboximide. Preferred forms include powders, pellets, suspensions, emulsions, solutions, aerosols, combustible strips and baits.

The active ingredient may be incorporated in carriers and excipient customarily employed in insecticidal compositions such as, for example, water, alcohols, hydrocarbons and other organic solvents, animal, vegetable and mineral oils, powders e.g. talc, clay, silicates and kieselguhr, and combustible solids e.g.

Tabu powder or Pyrethrum marc. Advantageously the compositions may contain surface-active agents, preferably non-ionic surface-active agents, to aid uniform dispersion of the constituents of the composition.

Preferably the compositions will contain from 0.01 to 95% by weight of active ingredient.

A particularly preferred form of the insecticidal compositions according to the invention are insecticidal coils, especially those containing from 0.01 to 10% by weight of active ingredient, in association with a combustible inert support composed, for example, of Pyrethrum marc, Tabu powder, powdered Machilus Thumbergii leaves, cedar leaf powder, wood dust (e.g. pine sawdust), starch, coconut shell powder or Pyrethrum stem powder.

The active ingredient may alternatively be incorporated, preferably in a concentration of 0.01 to 95% by weight, in an incombustible fibrous substrate and the fumigent thus obtained may then be placed on a heating apparatus e.g. of the type known as "electro mosquito destroyer" whereby the active ingredient may be vapourized at a controlled rate. Further forms include incorporating the active ingredient in a pulverizable oil, preferably in a concentration of 0.01 to 95% by weight, which oil may then be used to impregnate the wick of a lamp whereby combustion of the oil and thus vapourization of the active ingredient takes place.

(S) - allethrolone 2,2 - dimethyl - 3S - (2',2' - difluorovinyl) - cyclopropane IR - carboxylate and (S) - allethrolone 2,2 - dimethyl - 3R - (2',2' - difluorovinyl) cyclopropane - 1 R - carboxylate show a particularly advantageous activity when used in the form of a fumigent composition.

The following Examples illustrate the invention.

Example 1.

(4R)-2-Allyl-3- methyl -cyclopent-2-en-l- one -4- yl 2,2- dimethyl -3R-(2' methylprop - 1' enyl) - cyclopropane - IR - carboxylate for (R) - allethrolone d trans - chrysanthematel starting from (S) - allethrolone - methane sulphonate.

Into 33 cm3 of hexamethylphosphorotriamide are introduced 12.5 g of (S)allethrolone-methane sulphonate and 9.6t g of sodium d-trans-chrysanthemate are added thereto. The mixture obtained is stirred for ten minutes, then a mixture of 1N sodium hydroxide, water and n-heptane is added thereto. The resultant mixture is stirred and the organic phase is separated off by decantation. The aqueous phase is extracted with heptane and the organic phases are combined, washed and dried.

12.94 g of (R)-allethrolone d-trans-chrysanthemate are obtained.

Circular dichroism (dioxan) Infl. 345 nm AE=- 1.18 Max. 332 nm AE--- 2.41 Max. 321 nm AE=- 2.73 Infl. 310 nm AE--- 2.08 Max. 230 nm AE = + 1 5.9 The (S)-allethrolone-methane sulphonate used may be prepared in the following way: 7.35 g of (S)-allethrolone are dissolved in 7.5 cm3 of acetone. The solution obtained is cooled to -150C and then 8.4 cm3 of triethylamine, followed slowly by 4.3 cm3 of methanesulphonyl chloride in a solution in 11 cm3 of acetone are added thereto. The resultant mixture is stirred for fifteen minutes and then poured into a mixture of 23 cm3 of IN hydrochloric acid, 56 cm3 of water and 23 cm3 of methylene chloride. The mixture thus obtained is stirred for fifteen minutes and then the organic phase is separated off by decantation. The aqueous phase is extracted with methylene chloride and the organic phase are combined, washed, dried and concentrated to dryness. 12.5 g of crude (S)-allethrolone-methane sulphonate are obtained which are used in the above condensation without further purification.

The sodium chrysanthemate used above may be prepared in the following manner: Into a solution of 16.8 of 2,2-dimethyl-3R-(2'-methyl-prop-1'-enyl)cyclopropane-lR-carboxylic acid in 50 cm3 of acetone, is introduced the quantity of a 10N aqueous solution of sodium hydroxide necessary to obtain the turning of phenolphthalein. The precipitate thus formed is isolated by centrifugation and is washed and dried. 18.6 g of sodium 2,2-dimethyl-3R(2'-methylprop-1'-enyl)-cyclo- propane I R-carboxylate are obtained and are used for the condensation without further purification.

Example 2.

(S) - Allethrolone 2,2 - dimethyl - 3R - (2' - methylprop - I ' - enyl) - cyclopropane - IR carboxylate starting from (R) - allethrolone - methane sulphonate.

Operating in a manner analagous to that of Example 1, starting with (R)allethrolone-methane sulphonate, (S)-allethrolone 2,2-dimethyl-3R-(2' methylprop-l'-enyl)-cyclopropane-lR-carboxylate [a]20 - 50O (c = 5%, toluene) is obtained with the same yield.

Example 3.

(R) - allethrolone 2,2 - dimethyl - 3R - (2' - methylprop - I ' - enyl) - cyclopropane - IR carboxylate starting from (S) - allethrolone - methane sulphonate.

To a solution of potassium d-trans-chrysanthemate (obtained as described hereinafter starting with 110 g of d-trans chrysanthemic acid) is rapidly added, at +15"C, a solution of 165 g of (S)-allethrolone-methane sulphonate in 350 cm3 of dimethylsulphoxide. The mixture obtained is stirred at 200C for 24 hours and then 100 cm3 of heptane and 500 cm3 of water are added thereto. The resultant mixture is stirred and the organic phase is separated off by decantation. The aqueous phase is extracted with heptane and the heptane phases are combined, washed in an aqueous IN solution of sodium hydroxide and then in water. The aqueous washings are extracted with heptane and the heptane fractions are combined, dried and concentrated to dryness by distillation. 169 gof(R)-allethrolone2,2-dimethyl-3R- (2'-methylprop-1'-enyl)-cyclopropane-lR-carboxylate are obtained [a]20= - 11" (c = 1%, ethanol).

U.V. spectrum (ethanol) Maximum at 225 nm, E11 = 600; Maximum at 295 nm, E11 = 3.

Circular dichroism (dioxan) Max. 230nm AE=+l5 Infl. 310nm A=- 2.15 Max. 320nm AE=- 2.70 Infl. 330 nm AE= 2.43 Infl. 345 nm AE=- 1.14 The (S)-allethrolone-methane sulphonate used at the beginning of Example 3 may be prepared in the following manner: In 200 cm3 of acetone are dissolved 100 g of (S)-allethrolone lB.P.Q6 mmlHg = 115 C [a]20 = + 140 (c = 1.3%, chloroform), U.V. absorption (ethanol): maximum at 229 nm, E' = 180] and 114.5 cm3 of triethylamine are added thereto at -15"C. The mixture obtained is stirred and a solution of 86.5 g of methanesulphonyl chloride in 180 cm3 of anhydrous acetone is introduced therein at a temperature of between 0 and +5"C over a period of 20 minutes. Stirring of the mixture is effected for 20 minutes at --100C and then 200 cm3 of methylene chloride are introduced therein at --150C, followed by a mixture of 50 cm3 of an 11.8N aqueous solution of hydrochloric acid. The resultant mixture is stirred and the organic phase is separated off by decantation. The aqueous phase is extracted with methylene chloride and the organic phases are combined and washed with water.

The aqueous washings are extracted with methylene chloride and the chloromethylenic phases are combined, washed, dried and concentrated to dryness under reduced pressure. 165 g of crude (S)-allethrolone-methane sulphonate are obtained which are used in the condensation with the ptoassium d-trans chrysanthemate without further purification.

The solution of potassium d-trans-chrysanthemate used above may be prepared in the following manner: Into a mixture of 100 cm3 of dimethylsulphoxide and 30 cm3 of water, are introduced 110 g of 2,2-dimethyl-3R-(2'-methylprop-1'-enyl)-cyclopropane-1Rcarboxylic acid [[&alpha;]D20 = + 36.7 (dimethylformamide)] and 2 drops of an alcoholic solution of phenolphthalein are added thereto. The quantity of an aqueous solution of potash (50 Be) necessary to turn the phenolphthalein pink (about 49.5 cm3) is then added at + 1 50C. 0.7 cm3 of water are then added to the resultant mixture and a solution is obtained which contains potassium 2,2-dimethyl-3R-(2'-methylprop1 '-enyl)-cyclopropane- I R-carboxylate.

Example 4.

(4S) Allyl -J- methyl - cyclopent -2- en -1- one -4- yl 2,2- dimethyl -(2'- methylprop - 1' - enyl) - cyclopropane - IR - carboxylate [or (S) - allethrolone d - trans chrysanthemate] starting from (R) - allethrolone - methane sulphonate.

To a solution of potassium d-trans-chrysanthemate (obt 90 &num; &num; 95.8% 90+4 The rate of stereoconversion of (R)-allethrolone < the (S)-allethrolone ester is therefore quantitative (95.8) 95.5 The (R)-allethrolone-methane sulphonate used at the beginning of Example 4, may be prepared in the following manner: (R)-allethrolone of []DO = - 15 if , (c = 1%, chloroform) is used which, according to its circular dichroism, contains 95.5% of isomer (R) and 4.5% isomer (S).

10 g of (R)-allethrolone are dissolved in 20 cm3 acetone. The solution obtained is cooled to -150C and 11.4 cm3 of triethylamine are added thereto, followed, maintaining the temperature below 0 C, by a mixture of 18 cm3 of acetone and 5.8 cm3 of methanesulphonyl chloride. The resultant mixture is stirred for twenty minutes at -100C and methylene chloride is introduced therein. The mixture thus obtained is acidified by the addition of an aqueous IN solution of hydrochloric acid and the mixture obtained is stirred. The organic phase is separated off by decantation and the aqueous phase is again extracted with methylene chloride. The chloromethylenic phases are combined, washed with water, dried and concentrated under reduced pressure. 16 g of crude (R)-allethrolone-methane sulphonate are obtained which are used without further purification.

The solution of potassium d-trans-chrysanthemate used above may be prepared in the following manner: II g of d-trans-chrysanthemic acid (IR, 3R) are dissolved in 10 cm3 of dimethylsulphoxide and 3 cm3 of water are added thereto followed by a drop of an alcoholic solution of phenolphthalein. Potash lye is then introduced until the phenolphthalein turns colour.

Example 5.

(S) - Allethrolone 2,2 - dimethyl - 3R - (2' - methylprop - I ' - enyl) - cyclopropane - IR carboxylate starting from (R) - allethrolone - methane sulphonate (without isolation of the intermediate methane sulphonate).

At 20"C, a solution of (R)-allethrolone-methane sulphonate (obtained as described hereinafter from 250 g of (R)-allethrolone) is introduced rapidly into a solution of potassium d-trans-chrysanthemate (obtained also as described hereinafter starting from 293 g of d-trans-chrysanthemic acid). The mixture obtained is stirred at 200C for 24 hours and then 750 cm3 of water are added thereto over a period of about 10 minutes at 200 C. The resultant mixture is stirred and the organic phase is separated off by decantation. The aqueous phase is extracted with toluene and the combined organic phases are washed in water with a IN aqueous solution of sodium hydroxide, dried over magnesium sulphate and filtered. 250 g of alumina are added to the filtrate and the mixture obtained is stirred, filtered and concentrated to dryness under reduced pressure. 400.7 g of (S)-allethrolone 2,2dimethyl-3R-(2'-methylprop- 1 '-enyl)-cyclopropane I R-carboxylate are obtained.

[a]20 = -490 (c = 5%, toluene).

The solution of (R)-allethrolone-methane-sulphonate used above is prepared in the following manner: 250 g of (R)-allethrolone, [al30 = - 10.5" (e = 10%, chloroform) are dissolved in 750 cm3 toluene and 225 g of methanesulphonyl chloride are introduced therein over 10 minutes at -130C, followed, over about two hours at -80C, by a solution of 217.5 g of triethylamine in 200 cm3 of toluene. The mixture obtained is stirred for 15 minutes and then 1000 cm3 of water are added thereto at -50C over about 30 minutes. The resultant mixture is stirred and the organic phase is separated off by decantation. The aqueous phase is extracted with toluene and the toluenic phases are combined and washed with water. The aqueous washings are extracted with toluene and the toluenic phases are combined and dried to give the toluenic solution of (R)-allethrolone-methane sulphonate used above.

The solution of potassium d-trans-chrysanthemate used above may be prepared in the following manner: In 500 cm3 of dimethylsulphoxide are dissolved 293 g of 2,2-dimethyl-3R-(2'methylprop-1'-enyl)-cyclopropane-1R-carboxylic acid and 184.2 g of an aqueous solution of potash (500 Be) are introduced therein at 400C over about 30 minutes.

The mixture obtained is stirred for 30 minutes at 400C and a solution of potassium 2,2 - dimethyl - 3R - (2' - methylprop - 1' - enyl) - cyclppropane - 1R - carboxylate is obtained.

Example 6.

(R) - Allethrolone 2,2 - dimethyl - 3R - (2' - methylprop - I ' - enyl) - cyclopropane - IR carboxylate starting from (S) - allethrolone - methane sulphonate (without isolation of the intermediate methane sulphonate).

Starting with 250 g of (S)-allethrolone, [a]O = + 14" (c = 1.3%, chloroform), a toluenic solution of (S)-allethrolone-methane sulphonate is prepared operating in a manner analagous to that of Example 5 and, after condensation with potassium dtrans-chrysanthemate, used in solution, according to a modus operandi similar to that of Example 5, 397 g of (R)-allethrolone 2,2-dimethyl-3R-(2'-methylprop-1'- enyl)-cyclopropane-lR-carboxylate are obtained [CE]20 = - 4 (c = 5%, toluene).

Example 7.

(S) - Allethrolone 2,2 - dimethyl - 3R - (2' - methylprop - 1' - enyl) - cyclopropane - IR carboxylate starting from (R) - allethrolone - methane sulphonate (without isolation of the intermediate methane sulphonate).

Into a solution of potassium d-trans-chrysanthemate (obtained as described hereinafter starting from 82.8 g of d-trans-chrysanthemic acid) is introduced at 18--20"C, over a few minutes, a solution of (R)-allethrolone-methane sulphonate (obtained as described hereinafter starting with 50 g of (R)-allethrolone). The obtained mixture is stirred vigorously for 35 hours at 18-200C and then 150 cm3 of water are added thereto. The toluenic phase thus obtained is separated off by decantation and the aqueous phase is extracted with toluene. The toluenic phases are combined, washed with water, washed free ot chrysanthemic acid using an aqueous solution containing 5U/O sodium bicarbonate and 5% sodium carbonate, then again with water until neutral, dried and finally filtered. 0.1 g of hydroquinone are added to the filtrate and the mixture obtained is concentrated to dryness by distillation under reduced pressure. 92.9 g of (S)-allethrolone 2,2-dimethyl-3R-(2' methylprop- I '-enyl)-cyclopropane- 1 R-carboxylate are obtained. [a] 20 = - 50.50 (c = 5%, toluene).

The solution of (R)-allethrolone-methane sulphonate used above is prepared in the following manner: Into 150 cm3 of toluene are introduced 50 g of (R)-allethrolone followed, over about 10 minutes at 00 C, by 45 g of methanesulphonyl chloride. A solution of 43.5 g of triethylamine in 40 cm3 of toluene is then added to the mixture obtained, over about one hour at 0 C. The resultant mixture is stirred for 30 minutes at 0 C and then 200 cm3 of water are introduced therein at 0 C over about 30 minutes. The mixture thus obtained is stirred and the toluenic phase is separated off by decantation. The toluene phase is washed with water until free of chloride, operating at a temperature lower than +5"C and is then dried and filtered. A solution of (R)-allethrolone-methane sulphonate is obtained which is used in the condensation with the potassium chrysanthemate without further purification.

The solution of potassium d-trans-chrysanthemate used above may be prepared in the following manner: Into a mixture of 100 cm3 of tertiary butanol and 100 cm3 of toluene, are introduced, at 200 C, 24.9 g of potash (titrating 90.8%) followed by 82.8 g of 2,2dimethyl-3 R-(2'-methylprop- 1 '-enyl)-cyclopropane- I R-carboxylic acid over about 30 minutes at 25-300C. The mixture obtained is stirred for 2+ hours at 25-300C and then cooled to 20 C. A solution of potassium 2,2-dimethyl-3R-(2'-methylprop 1'-enyl)-cyclopropane-1R-carboxylate is obtained which is used without further purification.

Example 8.

(S) - Allethrolone 2,2 - dimethyl - 3S - (2' - methylprop - I ' - enyl) - cyclopropane - IR carboxylate starting from (R) - allethrolone - methane sulphonate (without isolation of the intermediate methane sulphonate).

Into a mixture of 20 cm3 of toluene and 20 cm3 of tertiary butanol are introduced 10 g of sodium 2,2-dimethyl-3S-(2'-methylprop-1'-enyl)-cyclopropane- lR-carboxylate [sodium cis-chrysanthemate] followed, rapidly, by 31.8 cm3 of a toluenic solution containing 1.1 mole/l of (R)-allethrolone-methane sulphonate.

The mixture obtained is stirred for 2 hours and then 30 cm3 of toluene and 20 cm3 of tertiary butanol are added thereto. The resultant mixture is stirred for 65 hours and then water is added thereto. The mixture thus formed is extracted with ether and the ethereal extracts are washed with water and with a dilute aqueous solution of ammonia, dried and concentrated to dryness by distillation under reduced pressure. 9.94 g of the crude ester are obtained which are purified by chromatography on silica gel, eluting with a mixture of cyclohexane and ethyl acetate (9:1). 7.38 g of (S)-allethrolone 2,2-dimethyl-3S-(2'-methylprop-1'-enyl)cyclopropane-1R-carboxylate are obtained. [&alpha;]D20 = + 39.5 (c = 0.8%, chloroform).

Circular dichroism (dioxan) = - 9.85 at 231 nm AE = + 2.68 at 320 nm AE = + 2.38 at 332 nm The sodium cis-chrysanthemate used above is prepared in the following manner: Into 200 cm3 of ethanol are introduced 20 g of 2,2-dimethyl-3S-(2'-methylprop-1'-enyl)-cyclopropane-1R-carboxylic acid and a few crystals of phenolphthalein. To the mixture obtained is slowly added concentrated soda lye until the mixture turns pink. The solvents are then eliminated by distillation under reduced pressure. 22 g of sodium 2,2-dimethyl-3S-(2'-methylprop-1'-enyl)-cyclopropane- lR-carboxylic acid are obtained.

The toluenic solution of (R)-allethrolone-methane sulphonate used above is prepared in the following manner: Into 105 cm3 of toluene are introduced 35 g of freshly rectified (R)allethrolone (B.P. = 970C under 0.2 mm of mercury). The mixture obtained is stirred and then cooled to +20 C. 22 cm3 of methanesulphonyl chloride are added thereto over 15 minutes at +2"C, followed by a mixture of 28 cm3 of toluene and 42 cm3 of triethylamine over one hour at +2 C. The resultant mixture is stirred for 30 minutes at 0 C and then 35 cm3 of ice-water are added thereto over 10 minutes at 0 C, followed by a single addition of 100 cm of ice-water. The mixture thus formed is stirred and the aqueous phase is separated from the organic phase by decantation. The organic phase is washed in water at 0 C and the toluenic phase is dried and filtered. The solution obtained, which is maintained at 0 C, contains 1.13 mole of allethrolone-methane sulphonate per litre.

Example 9.

(S) - Allethrolone 2,2 - dimethyl - 3S - (2' - methylprop - I ' - enyl) - cyclopropane - IR carboxylate starting from (R) - allethrolone - p - toluene sulphonate.

Into a mixture of 20 cm3 of dimethylsulphoxide and 2 cm3 of water are introduced 2.28 g of sodium 2,2-dimethyl-3S-(2'-methylprop-1'-enyl)-cyclo- propane-lR-carboxylate [sodium cis-chrysanthemate] followed by 3.4 g of (R)allethrolone-p-toluene sulphonate. The mixture obtained is stirred for 2 hours at ambient temperature and then poured into an aqueous solution of hydrochloric acid. The resultant mixture is stirred and the aqueous phase is separated and extracted with petroleum ether (B.P. 35--75"C). The organic extracts are washed in water, dried and concentrated to dryness. 2.4 gof a residue are obtained which are chromatographed on silica gel, eluting with a mixture of benzene and ethyl acetate (9:1). 2.06 g of (S)-allethrolone 2,2-dimethyl-3S-(2'-methylprop-l'-enyl)- cyclopropane-l R-carboxylate are obtained.

Circular dichroism (dioxan) As = - 7.8 at 233 nm AE = + 2.4 at 320 nm AE = + 2.1 at 332 nm The sodium cis-chrysanthemate used above is prepared in the same manner as in Example 8.

The (R)-allethrolone-p-toluene sulphonate used above is prepared in the following manner: Into 100 cm3 of tetrahydrofuran containing 11.6 g of (R)-allethrolone, are introduced 11.6 g of triethylamine, at -500C under an inert atmosphere, followed by 21.9 of p-toluenesulphonyl chloride. The mixture obtained is stirred for 48 hours at +5 C and then poured into an 0.1N aqueous solution of hydrochloric acid. The resultant mixture is stirred and the aqueous phase is separated and extracted with chloroform. The organic extracts are washed with water, dried and concentrated to dryness. The residue (29 g) is chromatographed on silica gel, eluting with a mixture of benzene and ethyl acetate (95:5). 6.8 g of (R)-allethrolone-p-toluene sulphonate are obtained.

Example 10.

(S) - Allethrolone 2,2 - dimethyl - 3S - (2' - methylprop - 1' - enyl) - cyclopropane - IR carboxylate starting from (R) - allethrolone - p - bromobenzene sulphonate.

Into a mixture of 38 cm3 of dimethylsulphoxide and 3.8 cm3 of water, are introduced 3.8 g of sodium 2,2-dimethyl-3S-(2'-methylprop- 1 '-enyl)-cyclopropane- I R-carboxylate [sodium cis-chrysanthemate] followed by 3.77 g of (R)allethrolone-bromobenzene sulphonate and 5 cm3 of dimethylsulphoxide. The mixture obtained is stirred for 30 minutes and then left for 15 hours. A IN aqueous solution of hydrochloric acid is then added thereto and the aqueous phase thus obtained is separated and extracted with petroleum ether (B.P. = 35--75"C). The organic phases are washed with IN sodium hydroxide and water, dried and concentrated to dryness. 1.02 g of a residue are obtained which are chromatographed on silica gel, eluting with a mixture of petroleum ether (B.P. = 35--75"C) and diethyl ether (7:3). 0.422 g of (S)-allethrolone 2,2-dimethyl3S-(2'-methylprop- 1 '-enyl)-cyclopropane- 1 R-carboxylate are obtained.

Circular dichroism (dioxan) AE = - 3.4 at 233 nm = = + 1.5 at 321 nm AE = + 1.7 at 332 nm The sodium cis-chrysanthemate used above is prepared in the same manner as that prepared in Example 8.

The (R)-allethrolone-p-bromobenzene sulphonate used is prepared in the following manner: Into 25 cm3 of tetrahydrofuran are introduced 2.5 g of (R)-allethrolone. The mixture obtained is cooled to OOC and 2.5 g of triethylamine are added thereto followed by 6.3 g of p-bromobenzenesulphonyl chloride. The resultant mixture is stirred for 6 hours at +50C and then a dilute aqueous solution of hydrochloric acid is added thereto. The mixture thus formed is stirred and extracted with methylene chloride. The combined phases are washed with water, dried and concentrated to dryness. 7.47 g of crude (R)-allethrolone-p-bromobenzene sulphonate are obtained, which are used without further purification.

Example 11.

(4S) - 2 - Allyl - 3 - methyl - cyclopent - 2 - en - I - one - 4 -yl[(S) - allethrolonel 2,2 - di methyl - 3R - (cyclopentylidene - methyl) - cyclopropane - IR - carboxylate starting from (R) - allethrolone - methane sulphonate.

0.530 g of (R)-allethrolone-methane sulphonate (obtained as described hereinafter from 0.362 g of (R)-allethrolone) are dissolved in 10 cm3 of dimethylformamide. The solution obtained is cooled to +50C and 0.576 g of potassium 2,2-dimethyl-3 R-(cyclopentylidene-methyl)- 1 R-carboxylate (obtained as described hereinafter) are added thereto. The mixture obtained is stirred at +50C for one hour and then poured into water. The resultant mixture is acidified to pH 4 by addition of dilute hydrochloric acid and then extracted with petroleum ether.

The organic phase is dried and concentrated. The residue is chromatographed on silica gel, eluting with a mixture of benzene and ethyl acetate (95:5). 0.443 g of (S)allethrolone 2,2-dimethyl-3 R-(cyclopentylidene-methyl)-cyclopropane- I R carboxylate are isolated having the following characteristics [a]O = - 38" I 2.5 (c = 0.6%, chloroform).

Circular dichroism (dioxan) Infl. at 345 nm AE = + 1.09 Max. at 332 nm AE = + 2.32 Max. at 320nm Aye= + 2.60 Infl. at 310 nm AE=- 1.97 Max. at 230 nm AE = - 26.7 The (R)-allethrolone-methane sulphonate used above may be prepared in the following manner: 0.362 g of (R)-allethrolone (which, according to its circular dichroism has an optical purity of 9798%) are dissolved in 4 cm3 of a mixture of benzene and ether (50:50). The solution obtained is cooled to -60C and 0.46 cm3 of triethylamine are added thereto followed slowly by 0.2 cm3 of methanesulphonyl chloride in solution in 2.7 cm3 of a mixture of benzene and ether (50:50). The resultant mixture is stirred for 2 hours at --100C then poured into a dilute solution of hydrochloric acid. The organic phase thus formed is separated off by decantation. The aqueous phase is extracted with ether and the organic phases are combined, washed with water, dried and concentrated to dryness by distillation under reduced pressure. 0.530 g of crude (R)-allethrolone-methane sulphonate are obtained and are used without further purification.

The potassium 2,2-dimethyl-3R-(cyclopentylidene-methyl)-cyclopropane-l Rcarboxylate used above may be prepared as follows: 0.576 g of potassium 2,2-dimethyl-3 R-(cyclopentylidenemethyl)-cyclo- propane-l R-carboxylate are prepared by neutralisation of a methanolic solution of 2,2-dimethyl-3 R-(cyclopentylidene-methyl)-cyclopropane- I R-carboxyylic acid with methanolic potash (turning of phenolphthalein), distillation of the resultant mixture to dryness under reduced pressure and rectification with benzene.

Example 12.

(S) - Allethrolone 2,2 - dimethyl - 3S - (2',2' - dichlorovinyl) - cyclopropane - IR carboxylate [or (S) - allethrolone (IR,trans) - 2,2 - dimethyl - 3 - (2',2' - dichloro vinyl) - cyclopropane - I - carboxylatel starting from (R) - allethrolone - methane sulphonate (without isolation of the intermediate methane sulphonate).

Into a mixture of 20 cm3 of toluene and 20 cm3 of tertiary butanol are introduced 10 g of sodium (lR,trans)-2,2-dimethyl-3-(2',2'-dichlorovinyl)-cyclo- propane-l-carboxylic acid, followed by 26.2 cm3 of a toluenic solution of (R)allethrolone-methane sulphonate (titrating 1.3 mole/litre). The mixture obtained is stirred for 2 hours and then 30 cm3 of toluene and 20 cm3 of tertiary butanol are added thereto. The resultant mixture is stirred for 65 hours and then treated analagously to Example 8. 9.26 g of crude ester are obtained which are chromatographed on silica gel, eluting with a mixture of cyclohexane and ethyl acetate (9:1). 7.91 g of (S)-allethrolone (lR,trans)-2,2-dimethyl-3-(2',2'-dichloro- vinyl)-cyclopropane-l-carboxylate are obtained. [a]20 = - 26 (c = 0.5%, chloroform).

Circular dichroism (dioxan) AE = - 23.6 at 228 nm AE = + 2.62 at 321 nm AE = + 2.32 at 332 nm The sodium (I R,trans)-2,2-dimethyl-3-(2',2'-dichlorovinyl)-cyclopropane-l carboxylate used above is obtained in the following manner: Into 200 cm3 of ethanol are introduced 20 g of (1 R,trans)-2,2-dimethyl-3-(2',2' dichlorovinyl)-cyclopropane-l-carboxylic acid and a few crystals of phenol phthalein. To the mixture obtained is slowly added soda lye until the colour turns pink. The mixture thus formed is concentrated to dryness by distillation under reduced pressure. Benzene is added to the residue and the resultant mixture is concentrated to dryness. This operatiuon is then carried out a second time. 22.6 g sodium ( I R,trans)-2,2-dimethyl-3-(2',2'-dichlorovinyl)-cyclopropane I -carboxylate are obtained.

The toluenic solution of (R)-allethrolone-methane sulphonate used above is prepared in the same manner as that used in Example 8.

Example 13.

(S) - Allethrolone 2,2 - dimethyl - 3S - (2',2' - dichlorovinyl) - cyclopropane - IR carboxylate [or (S) - allethrolone (IR,trans) 2,2 - dimethyl - 3 - (2',2' - dichloro vinyl) - cyclopropane - I - carboxylate] starting from (R) - allethrolone - p toluene sulphonate.

Into a mixture of 20 cm3 of dimethylsulphoxide and 2 cm3 of water are introduced 2.78 g of sodium (1 R,trans)-2,2-dimethyl-3-(2',2'-dichlorovinyl)- cyclopropane-l-carboxylate followed by 3.4 g of (R)-allethrolone-p-toluene sulphonate. The mixture obtained is stirred for two hours at ambient temperature, then acidified and extracted with petroleum ether (B.P. = 35--75"C). The organic phases are washed with 1N sodium hydroxide, then with water, dried and concentrated to dryness. 3 g of residue are obtained which are chromatographed on silica gel, eluting with a mixture of benzene and ethyl acetate (9:1). 2.31 g of (S)allethrolone (1 R,trans)-2,2-dimethyl-3-(2',2'-dichlorovinyl)-cyclopropane- 1- carboxylate are obtained.

The sodium (1 R,trans)-2,2-dimethyl-3-(2' ,2'-dichlorovinyl)-cyclopropane- 1 - carboxylate is obtained in the same manner as in Example 12.

The (R)-allethrolone-p-toluene sulphonate used above is obtained in the same way as that of Example 9.

Example 14.

(S) - Allethrolone 2,2 - dimethyl - 3S - (2',2' - difluorovinyl) - cyclopropane - IR carboxylate [or (S) - allethrolone (IR,trans) - 2,2 - dimethyl - 3 - (2',2' - difluoro vinyl) - cyclopropane - I - carboxylatel starting from (R) - allethrolone - methane sulphonate (without isolation of the intermediate methane sulphonate).

Into a mixture of 36 cm3 of toluene and 36 cm3 of tertiary butanol are introduced 18.26 g of sodium (1 R,trans)-2,2-dimethyl-3-(2',2'-difluorovinyl)-cyclo- propane-l-carboxylate followed, over one minute by 54.5 cm3 ofatoluenic solution of (R)-allethrolone-methane sulphonate (titrating 1.13 mole/litre). The mixture obtained is stirred for 76 hours at 200C and then treated in the same manner as that of Example 8. 18.69 g of crude ester are obtained which are chromatographed on silica gel, eluting with a mixture of cyclohexane and ethyl acetate (9:1). 15.1 g of (S)-allethrolone (1 R,trans)-2,2-dimethyl-3-(2' ,2'-difluorovinyl)-cyclopropane 1 - carboxylate are obtained.

[CE]20 - - 24.50 (c = 1%, chloroform) Circular dichroism (dioxan) AE = - 22.6 at 225 nm AE = + 2.51 at 320 nm AE = + 2.23 at 332 nm U. V. spectrum (ethanol) Max. at 228 nm E = 15 300 The sodium salt used in Example 14 is prepared in an analagous manner to that used for preparing the sodium salt of Example 8. Starting with 17 g of (I R,trans)- 2,2-dimethyl-3-(2',2'-difluorovinyl)-cyclopropane- 1 -carboxylic acid, 18.27 g of the sodium salt are obtained.

The toluenic solution of (R)-allethrolone-methane sulphonate used in Example 14 is obtained in the same manner as that used in Example 8.

Example 15.

(S) - Allethrolone 2,2 - dimethyl - 3R - (2',2' - difluorovinyl) - cyclopropane - IR carboxylate [or (S) - allethrolone (IR,cis) - 2,2 - dimethyl - 3 - (2',2' - difluoro vinyl) - cyclopropane - I - carboxylatel starting from (R) - allethrolone - methane sulphonate (without isolation of the intermediate methane sulphonate).

Into a mixture of 23 cm3 of toluene and 23 cm3 of tertiary butanol, are introduced 11.5 g of sodium (lR,cis)-2,2-dimethyl-3-(2',2'-difluorovinyl)-cyclo- propane-l-carboxylate, followed, over one minute, by 35 cm ofatoluenic solution of allethrolone-methane sulphonate (titrating 1.13 mole/litre). The mixture obtained is stirred for 76 hours at 200C and then treated in the same manner as in Example 8. 12.25 g of crude ester are obtained which are purified by chromatography on silica gel, eluting with a mixture of cyclohexane and ethyl acetate (9:1). 9.61 g of (S)-allethrolone (I R,cis)-2,2-dimethyl-3-(2' ,2'-difluoro- vinyl)-cyclopropane-I-carboxylate are obtained. [a]O = + 5O (c = 0.8%, chloroform).

Circular dichroism (dioxan) AE = - 18.1 at 226 nm AE = + 2.6 at 321 nm AE = + 2.3 at 332 nm U. V. spectrum (ethanol) Max. at 228 nm E = 15 200 The sodium salt used above is prepared in the same way as that used for preparing the sodium salt of Example 8. Starting from 10.57 g of (1R,cis)-2,2- dimethyl-3-(2',2'-difluorovinyl)-cyclopropane-l-carboxylic acid, 11.65 g of the sodium salt are obtained The toluenic solution of (R)-allethrolone-methane sulphonate used above is identical to that prepared in Example 8.

Example 16.

Preparation of an emulsifable concentrate.

The following are intimately mixed: (S)-allethrolone (1 Rtrans)-2,2-dimethyl- 3-(2',2'-difluorovinyl)-cyclopropane- I -carboxylate 0.3 g piperonyl butoxide 3 g topanol A 0 l g xylene 96.6g Example 17.

Preparation of a fumigenic coil.

A solution of 0.1 g of (S)-allethrolone(lR, trans)-2,2-dimethyl-3-(2',2'-di fluorovinyl)-cyclopropane-l-carboxylate in 5 cm3 of methanol is carefully incorporated into a mixture constituted by 30 g of Pyrethrum marc, 12 g Pyrethrum stem powder, 51.1 g of coconut shell powder and 6 g of soluble starch. The powder obtained is mixed with about 100 g of water, dried and shaped as a coil with a thickness of about 0.4 cm and a diameter of about 12 cm.

Example 18.

Preparation of a fumigenic coil.

A solution of 0.15 g of(S)-allethrolone (IR, cis)-2,2-dimethyl-3-(2',2'-difluorovinyl)-cyclopropane-l-carboxylate in 5 cm3 of methanol is carefully incorporated into a mixture constituted by 43 g of Pyrethrum stem powder, 52 g of coconut shell powder and 4.4 g of soluble starch. The powder obtained is mixed with about 100 g of water, dried and shaped as a coil, with a thickness of about 0.4 cm and a diameter of about 12 cm.

Example 19.

Preparation of a composition intended to be electrically heated.

A solution of 0.2 g of (S)-allethrolone (1 R,trans)-2,2-dimethyl-3-(2',2'-di- fluorovinyl)-cyclopropane-l-carboxylate in 5 cm3 of toluene is adsorbed onto the surface of a parallelepipedic piece of asbestos measuring 2 x 2 x 0.8 cm. A second piece of asbestos having the same dimensions is fixed to the first. In this way, a fumigenic composition is obtained which is used by being heated on a plate provided with an electric resistance.

Claims (27)

WHAT WE CLAIM IS:

1. A process for the preparation of compounds of general formula I,

(wherein the allethrolone ring is optically active and either (I) R, and R2, which may be the same or different, each represents an alkyl radical containing from I to 3 carbon atoms; (2) R1 and R2, being the same, each represents a fluorine, chlorine or bromine atom; (3) R, represents an alkyl radical containing 1 or 2 carbon atoms and R2 represents an acetyl or methoxymethyl radical; or (4) R, and R2, together with the carbon atom to which they are attached, form a carbocyclic ring containing from 3 to 6 carbon atoms or a group of formula

in which X represents an oxygen or sulphur atom) which comprises reacting an optically active compound of formula II,

(wherein R represents an alkyl radical containing from I to 3 carbon atoms or a phenyl radical optionally substituted in the para position by a methyl radical or a fluorine, chlorine or bromine atom) of appropriate configuration with a salt of a compound of formula III,

(wherein R, and R2 are as defined above), in the presence of an organic solvent, the reaction proceeding with inversion of configuration in the allethrolone ring.

2. A process as claimed in claim 1 wherein the salt of the compound of formula III is an alkali metal, alkaline earth metal or ammonium salt or a salt formed with a tertiary base.

3. A process as claimed in claim 2 wherein the salt of the compound of formula III is a sodium or potassium salt.

4. A process as claimed in any of the preceding claims wherein the compound of formula III is a 2,2 - dimethyl - 3 - (2' - methylprop - I ' - enyl) - cyclopropane I - carboxylic acid; a 2,2 - dimethyl - 3 - (2',2' - dichlorovinyl) - cyclopropane - I carboxylic acid; a 2,2 - dimethyl - 3 - (2',2' - dibromovinyl) - cyclopropane - I carboxylic acid; a 2,2 - dimethyl - 3 - (2',2' - difluorovinyl) - cyclopropane - 1 carboxylic acid; a 2,2 - dimethyl - 3 - (2' - methyl - 3' - methoxy - (E) - prop - I' enyl) - cyclopropane - 1 - carboxylic acid; a 2,2 - dimethyl - 3 - (2' - ethyl - 3' - oxo but - I - enyl) - cyclopropane - I - carboxylic acid; a 2,2 - dimethyl - 3 - (cyclo pentylidene - methyl) - cyclopropane - I - carboxylic acid; a 2,2 - dimethyl - 3 - (2' oxo - 3' - oxacyclopentylidene - methyl) - cyclopropane - I - carboxylic acid; or a 2,2 - dimethyl - 3 - (2' - oxo - 3' - thia - cyclopentylidene - methyl) - cyclopropane I - carboxylic acid.

5. A process as claimed in claim 4 wherein the compound of formula III is 2,2 - dimethyl - 3R - (2' - methylprop - 1' - enyl) - cyclopropane - IR - carboxylic acid; 2,2 - dimethyl - 3S - (2' - methylprop - 1' - enyl) - cyclopropane - lR - carboxylic acid; 2,2 - dimethyl - 3R - (cyclopentylidene - methyl) - cyclopropane IR - carboxylic acid; 2,2 - dimethyl - 3S - (2',2' - dichlorovinyl) - cyclopropane 1R - carboxylic acid; 2,2 - dimethyl - 3S - (2',2' - difluorovinyl) - cyclopropane IR - carboxylic acid; or 2,2 - dimethyl - 3R - (2',2' - difluorovinyl) - cyclopropane IR - carboxylic acid.

6. A process as claimed in any of the preceding claims wherein the organic solvent comprises dimethylformamide, hexamethylphosphorotriamide, dimethylsulphoxide, dimethoxyethane, acetonitrile, an aliphatic ketone containing from 3 to 6 carbon atoms, an alkanol, a monocyclic aromatic hydrocarbon or a mixture thereof.

7. A process as claimed in claim 6 wherein the solvent is hexamethylphosphorotriamide, dimethylsulphoxide, dimethylformamide, a mixture of toluene and dimethylsulphoxide or a mixture of toluene and a secondary or tertiary alkanol containing from 4 to 6 carbon atoms.

8. A process as claimed in claim 7 wherein the solvent is a mixture of toluene and tertiary butanol.

9. A process as claimed in any of the preceding claims wherein, in the compound of formula II, R represents a methyl or p-tolyl radical.

10. A process as claimed in any of the preceding claims wherein, in the compound of formula II, the allethrolone ring has the (R) configuration.

11. A process as claimed in any of claims 1 to 8 wherein the compound of formula II is in the form of a mixture of (R) and (S) isomers in which the (R) isomer predominates.

12. A process as claimed in any of the preceding claims wherein the compound of formula II is obtained by reaction of optically active allethrolone of appropriate configuration with a compound of formula IV, RSO2 Cl (IV) (wherein R is as defined in claim 1) in the presence of an organic solvent and of a basic agent, the reaction proceeding with retention of configuration in the allethrolone ring.

13. A process as claimed in claim 12 wherein the compound of formula II is not isolated.

14. A process as claimed in claim 12 or claim 13 wherein, in the reaction of allethrolone with the compound of formula IV, the solvent comprises a monocyclic aromatic hydrocarbon.

15. A process as claimed in any of the preceding claims wherein the salt of the compound of formula III is obtained by reacting a compound of formula III with an appropriate base in the presence of an organic solvent.

16. A process as claimed in claim 15 wherein the salt of the compound of formula III is not isolated.

17. A process as claimed in claim 15 or claim 16 wherein, in the reaction of the compound of formula III with the base, the solvent comprises dimethylformamide, dimethylsulphoxide, hexamethylphosphorotriamide, dimethoxyethane, aceto nitrile, an aliphatic ketone containing from 3 to 6 carbon atoms, an alkanol, a monocyclic aromatic hydrocarbon or a mixture thereof.

18. A process for the preparation of compounds of general formula I as claimed in claim 1 substantially as herein described.

19. A process for the preparation of compounds of general formula I as defined in claim I substantially as herein described in any one of Examples 1 to 15.

20. Compounds of general formula I as defined in claim 1 whenever prepared by a process as claimed in any one of claims I to 19.

21. (S) - Allethrolone 2,2 - dimethyl - 3R - (cyclopentylidene - methyl) - cyclo propane - 1 R - carboxylate.

22. (S) - Allethrolone 2,2 - dimethyl - 3S - (2',2' - dichlorovinyl) - cyclopropane IR - carboxylate.

23. (S) - Allethrolone 2,2 - dimethyl - 3S - (2',2' - difluorovinyl) - cyclopropane I R - carboxylate.

24. (S) - Allethrolone 2,2 - dimethyl - 3R - (2',2' - difluorovinyl) - cyclo propane - IR - carboxylate.

25. Insecticidal compositions comprising, as active ingredient, at least one compound as claimed in any one of claims 21 to 24 in association with an insecticidal carrier or excipient.

26. Insecticidal compositions as claimed in claim 25 substantially as herein described.

27. Insecticidal compositions substantially as herein described in any one of Examples 16 to 19.