IL33426A - Chrysanthemic acid esters,their preparation and insecticidal compositions containing them - Google Patents

Description

pna:>n»n»Dnat* 3 naoin >s> o»ieo» Cnryeantheiaie aoid esters, their preparation and InBeotlcidal compositions containing them t 31659 4 RAN 6101/27 The present invention is concerned with novel chrysanthemic acid esters and the manufacture thereof.

The chrysanthemic acid esters provided by the invention can be generically formulated thus: wherein R represents a hydrogen atom or a lower alkyl group and the broken line denotes an optional bond.

They are useful as insecticides.

It will be appreciated that the term 'lower alkyl' is used in this specification to mean both straight-chain and branched-chain alkyl groups containing a relatively low number of carbon atoms, e.g. methyl, ethyl and isopropyl. The methyl group is the preferred lower alkyl group.

One interesting class of esters provided by the invention comprises those in which R represents a hydrogen atom; for example, 4-phenyl-2-butynyl (+)-cis/trans-2 , 2-dimethyl-3-( 2-methyl-propenyl) -cyclopropane carboxylate and trans- -phenyl-2-butenyl ( +)-cis/trans-2 , 2-dimethyl-3 ( 2-methyl-propenyl)- provided by the invention comprises those in which R represents the methyl group; for example, 4- (2-methyl-phenyl) -2-butynyl ( +) -cis/trans-2 , 2-H imethyl-3-( 2-methyl-propenyl ) -cyclopropane carboxylate .

The chrysanthemic acid esters aforesaid can be manufactured according to the invention by reacting an acid halide of the general formula wherein Hal represents a halogen atom, particularly a a chlorine atom, with an alcohol of the general formula wherein R and the broken line have the significance given earlier .

The acid halide starting materials of formula II are known substances and can be prepared by halogenating , e.g. chlorinating, the corresponding carboxylic acids, e.g. using thionyl chloride or the like.

The acetylenic alcohol starting materials of formula III can be prepared, for example, by reacting propargyl alcohol with an alkyl-magneslum halide, e.g.. ethyl-magnesium bromide, treating the resulting Grignard. complex, with cuprous ..chloride or. cuprous cyanide, treating the resulting mixture with a halide of the general . formula wherein R has the .significance given earlier and.

X represents a chlorine or bromine atom, and decomposing the product b conventional techniques such as by treatment with aqueous ammonium chloride. They may also be prepared, for example, by reacting the appropriate ar.yl-magnesium halide, e.g. phen l-magnesium bromide , ' with 4-chloro-2-butyn-l-ol and decomposing the product by conventional techniques such as by treatment with aqueous ammonium chloride .

The olefinic alcohol startin materials of formula III can be prepared, for example, by reducing a corresponding acetvlenic alcohol starting material. either with an alkali-metal aluminum hydride or with hydrogen in the presence of ■ a partially deactivated palladium catalyst. The reduction of an acet lenic alcohol with an alkali-metal aluminum hydride, e.g. lithium aluminum hydride, yields an olefinic alcohol starting material of formula III having a trans ^configuration at the 2,3-position and is conveniently carried out in an inert organic solven , e.g. an ether such as diethyl ether, at an elevated temperature, e.g. the reflux temperature of the reduction mixture. On the ■a partially deactivated palladium catalyst yields an olefinic alcohol starting material of formula III having a cis configuration at the 2 ,3-position. This reduction is suitably carried' out in the presence of a palladium catalyst which has been partially deactivated with lea'd with the addition of quinoline and in the presence of an inert organic solvent such as petroleum ether at room temperature and atmospheric pressure.

. The reaction of an acid halide starting material of formula II with an alcohol starting material of formula III is conveniently carried out in the presence of an acid-binding agent. Suitable acid-binding agents include alkali-metal carbonates, e.g. sodium carbonate, alkali-metal bicarbonates , e.g. sodium bicarbonate, and tertiary organic amines, e.g. triethyl amine, pyridine and the like. Pyridine is the preferred acid binding-agent. The reaction may suitably be carried out in the presence of an inert solvent such as a hydrocarbon, e.g. benzene, toluene or xylene, an ether, e.g. diethyl ether or dioxan, a halogenated hydrocarbon, e.g. methylene chloride, chloroform, chlorobenzene , or the like. Suitably, the reaction is carried out at a temperature within the approximate range of from.0° C to 30° C, preferably at about 20° 0, under the atmosphere of an inert gas such as nitrogen or argon.

The chrysanthemic acid esters of formula I can also be manufactured in accordance with the invention by reacting an alkali-metal salt, silver salt or tri(lower alkyl) amine salt formula wherein R and the broken line have the significance given earlier and Hal stands for a halogen atom.

The alkali-metal salts and tri(lower alkyl) amine salts referred to earlier can be prepared, for example, by treating a chrysanthemum carboxylic acid in an inert solvent such as a lower-alkanol, e.g. ethanol, with the calculated amount of an alkali-metal hydroxide solution or a tri(lower alkyl) amine. The preferred alkali-metal salts are the sodium and potassium salts and the preferred tri(lower alkyl) amine salts are tiie triethyl amine salts. The silver salt can be prepared by treating an alkali-metal salt, such as the sodium salt, with silver nitrate.

The halide starting materials of formula V can be prepared, for example, by treating an alcohol of formula III with a suitable halogenating agent, e.g. thionyl chloride, phosphorus tribromide in pyridine or sodium iodide in acetone. The preferred halide starting materials of formula V are the chlorides and bromides.

The reaction of an alkali-metal salt, the silver salt or a tri lower alk l amine salt of a chr santhemum carbox lic acid with a halide of formula V is suitably carried out in an inert organic solvent . Any suitable inert organic solvent can be used, but it is preferred to use a ketone such as acetone or methyl ethyl ketone or diglyme. The reaction is preferably carried out at an elevated temperature, suitably at the reflux temperature of the reaction mixture. It is also advantageous to carry out the reaction under the atmosphere of an inert gas such as nitrogen Or argon.

It will be appreciated that the chrysanthemic acid moiety of formula I can show both geometric isomerism and optical isomerism. The alcohol moiety can also 3how geometric isomerism when a double-bond is present in the 2 , 3-posit ion. It will accordingly be understood that the esters provided by this invention include all of the various geometrical and optical isomers as well as mixtures thereof. One type of mixture is obtained by using an acid chloride starting material mixture, an alkali-metal salt starting material mixture, a silver salt starting mixture or a tri(lower alkyl) amine salt starting material mixture obtained from a commercial carboxylic acid which is a racemic cis/trans-mixture containing a cis/trans ratio of about 30:70 %.

As mentioned earlier, the esters provided by the invention are useful as insecticides. They are active against a variety of insects (particularly against Musca domestica) and have been found to be particularly effective when they are synergised with well-known pyrethrin synergists such as -propyl ]-benzene and the like. Furthermore, they have been found to have a very low mammalian toxicity. For example, 4-phenyl-2-butynyl ( +) -cis/trans-2 , 2-dimethyl-3-(2-methyl-propenyl) -cyclopropane carboxylate has an of 1600 mg/kg p.o. in mice and has been shown to have an activity against Musea domestica in the order of pyrethrin extract and DDT.

It also shows an activity against bean aphids, codlin moth and Colorado beetle.

The esters of the invention can be used, in the form of conventional insecticidal compositions which contain them in association with a compatible carrier material. The compositions can be made up, for example, as concentrates or with carriers as premixes or as sprays, aerosols or dusts.

In certain cases it may be desirable that the carrier materials include emulsions, solutions or organic solvents. Solid carriers which may be used include, for example, talc, silica and similar powders which do not bring about decomposition of the esters. The insecticidal compositions may, if desired, contain conventional additives such as emulsifying agents, wetting agents or the like and may also contain other compatible insecticides and/or synergists.

The following Examples illustrate the invention. The chrysanthemum monocarboxylic acid chloride mentioned therein was obtained from the commercial (+) carboxylic acid consisting of a cis/trans mixture in the ratio of about 30:70.

Example 1 A solution of 14.0 g of chrysanthemum monocarboxylic acid chloride in 50 ml of dry benzene is added dropwise over a period of 0.25 hour at 20° C under a nitrogen atmosphere to a stirred solution of 12.0 g of 4-phenyl-2-butyn-l-ol and 11.85 g of dry pyridine in 120 ml of dry benzene. The resulting mixture is stirred' at 20° C for a further 16 hours, then the precipitated pyridine hydrochloride is filtered off and washed with benzene. The combined filtrate and. washings are washed successively with dilute aqueous hydrochloric acid, 2-N aqueous sodium hydroxide solution, dilute aqueous hydrochloric acid, saturated aqueous sodium bicarbonate solution and brine, dried over anhydrous sodium sulfate, filtered and evaporated. The residue is distilled to yield 1 .5 g of 4-phenyl-2-butynyl (+) cis/trans-2,2-dimetlryl-3- (2-methyl-propenyl) -cyclopropane carboxylate of boiling point 172° - 174° C/0.65 mm; ^° = 1.5277. 4-Phenyl-2-butyn-l-ol used as one of the starting materials in the above process can be obtained as follows: Ethyl magnesium bromide is prepared from 97.2 g of magnesium and 436 g of ethyl bromide in 300 ml of dry ether and 500 ml of dry tetrahydrofuran and the resulting solution is decanted free of unreacted magnesium. All subsequent operations are performed under an atmosphere of nitrogen. 112.8 g of redistilled propargyl alcohol are added over a for 2 hours and partially cooled. 12.0 g of cuprous cyanide are added followed, over a period of 0.5 hour by 275 g of benzyl bromide. The mixture is then heated under reflux for 92 hours, treated with excess saturated aqueous ammonium chloride solution and extracted with ether. The ether extract is dried over anhydrous sodium sulfate, filtered and evaporated. The residue is distilled and subsequently refractionated (to remove any traces of benzyl bromide) to yield 95· 5 g of 4-phenyl-2-butyn-l-ol of boiling point 116° 0/0.2 mm.

Another method of preparing 4-phenyl-2-butyn-l-ol is as follows: A suspension of 12.2 g of dry magnesium in 120 ml of dry ether is treated with a crystal of iodine and 78.5 g of bromo-benzene are added dropwise thereto over a period of 0.75 hour with stirring and cooling. The resulting mixture is stirred for a further 0.25 hour at 0 - 10 C. The resulting Grignard solution is decanted from unreacted magnesium, 20 ml of dry ether being used to assist transfer. A solution of 26.3 g of 4-chloro-2-butyn-l-ol in 20 ml of dry ether is added to the stirred Grignard solution over a period of 20 minutes at 20° 0. The resulting mixture is stirred at 20° C for a further 0.75 hour, then heated under gentle reflux for 80 minutes, cooled, poured into a mixture of saturated aqueous ammonium chloride solution and ice, and extracted three times with ether. The ether extracts are filtered and evaporated. The residue is destilled to yield 24.7 g of 4-phenyl-2-butyn-l-ol of boiling point 143°-150° 0/ Example 2 By a procedure analogous to that described in Example 1, from 8.8 g of 4-(2-methyl-phenyl)-2-butyn-l-ol and 9.33 g of chrysanthemum monocarboxylic acid chloride there are obtained 12.9 g of 4-(2-methyl-phenyl)-2-butynyl (+)-cis/trans-2 , 2-d imethyl-3-( 2-methyl-propenyl) -cyclopropane carboxylate of boiling point 190° - 200° C/0.9 mm.

Example 3 By a procedure analogous to that described in Example 1,' from 10.5 g of trans-4-phenyl-2-bute'n-l-ol (containing a trace, of hydroq inone ) and 12.5 g of. chrysanthemum monocarboxylic acid, chloride there are obtained 15.5 g of trans-4-p enyl-2-butenyl ( +) -ci s/trans-2 , -d imethyl-3 ( 2-methyl-propenyl ) -cyclopropane carboxylate in the form of a colourless sjTup of boiling point 168° - 170° C/1.4 mm; n^° = 1.5200.

Example 4 7.2 g of the sodium salt of chrysanthemum monocarboxylic acid are finely' powdered and suspended in 400 ml of diglyme. A solution of 6.3 g of l-chloro-4-phenyl-2-butyne in 50 ml of diglyme is added and the mixture is stirred and heated in an oil bath at 140° C under a nitrogen atmosphere for 100 hours. The precipitated sodium chloride is filtered off and the diglyme is removed under reduced pressure. The residue is treated with water and extracted three times with 150 ml of ether each time. The ether extracts are combined, washed successively with 2-N sodium hydroxide solution, water and sodium chloride solution and then dried over sodium sulfate. The solution is then filtered, evaporated and the residue distilled. 5-1 g of a product of boiling range 112° - 150° C/ 1.0 - 0.8 mm (bath temperature 185° C) are obtained.

Purification of this product by chromatography on aluminum oxide using petroleum ether (boiling range 40° - 60° C) as the eluant yielded 3.3 g of 4-phenyl-2-butynyl ( +).-cis/trans-2 , 2-d imethyl-3-( 2-methyl-propenyl ) -cyclopropane carboxylate ; n^° = 1.5285.

Claims (21)

Having now particularly described and ascertained the nature of our said invention and in what manner the same is to be performed, we declare that what we claim is:

1. Process for the manufacture of chrysanthemic acid esters of the general formula wherein. R represents a hydrogen atom or a lower alkyl group and the broken line denotes an optional bond, characterized in that an acid halide of the general formula wherein Hal represents a halogen atom, is reacted with an alcohol of the general formula H0-CH2 wherein R and the broken line have the above meaning, or that an alkali-metal salt a silver salt or a tri lower alk l) amine salt of a chrysanthemum carboxylic acid is reacted with a halide of the formula wherein R, the "broken line and Hal have the above meaning .

2. Process as claimed in Claim 1, characterized in that a starting material of formula III or V s used, wherein R represents hydrogen.

3. 5. Process as claimed in Claim 1 or 2, characterized in that 4-phen l-2-butyn-l-ol is used as the starting material of formula III.

4. Process as claimed in Claim 1 or 2, characterized in that trans- 4-phenyl-2-buten-l-ol is used as starting material of formula III.

5. Process as claimed in Claim 1, characterized in that a starting material of formula III or V is used, wherein R represents the methyl group.

6. Process as claimed in Claim 1 or 5 >■ characterized in that 4-(2-methyl-phenyl)-2-butyn-l-ol is used as starting material of formula III.

7. Process for the manufacture of chrysanthemic acid esters substantially as hereinbefore d escribed , particularly with reference to the foregoing examples.

8. Process for the manufacture of insecticidal compositions, characterized in that a chrysanthemic acid ester of the formula I set forth hereinbefore is mixed with a compatible carrier.

9. Insecticidal composition containing as an essential active ingredient a chrysanthemic acid ester of the formula I set forth hereinbefore, in association with a compatible carrier .

10. Chrysanthemic acid esters of the general formula wherein R represents a hydrogen atom or a lower alkyl group and the broken line denotes an optional bond, whenever prepared by the process claimed in Claim 1, or by an obvious chemical equivalent thereof.

11. Chrysanthemic acid esters, according to Claim 10., wherein R represents a hydrogen atom, whenever prepared by the process claimed in Claim 1 or 2 , or by an obvious chemical equivalent thereof.

12. 4-Phenyl-2-butynyl ( +) -cis/trans-2 , 2-d imethyl-3-(2-methyl-propenyl)-cyclopropane carboxylate, whenever ■· prepared by the process claimed in Claim 1, 2 or 3 , or by an obvious chemica.l equivalent thereof.

13. · Trans-4-piienyl-2-butenyl (+) -cis/trans-2 , 2-d.imethyl- 3-( 2-methyl-propen l) -cyclopropane carboxylate , whenever prepared by the process claimed in Claim 1, 2 or by an obvious chemical equivalent thereof.

14. Chrysanthemic acid esters according to Claim 10, wherein R represents a methyl group, whenever prepared by th process claimed in Claim 1 or 5, or by an obvious chemical equivalent thereof.

15. 4-(2- ethyl-phenyl)-2-butynyl (+) -cis/trans-2 , 2-dimethyl-propenyl)-cyclopropane carboxylate, whenever prepared, by the process claimed in Claim 1, 5 or 6, or by an obvious chemical equivalent thereof.

16. Chrysanthemic acid esters of the general formula wherein R represents a hydrogen atom or a lower alkyl group and the broken line denotes an optional bond.

17. Chrysanthemic acid esters, according to Claim 16, wherein R represents a hydrogen atom.

18. 4-Phenyl-2-butynyl ( +)-cis/trans-2 , 2-dimethyl-3-(2-methyl-propen l) -cyclopropane carboxylate .

19. · Trans-4-phenyl-2-butenyl (+)-cis/trans-2,2-dimethyl-3- ( 2-methyl-propenyl) -cyclopropane carboxylate .

20. Chrysanthemic acid esters according to Claim l6, wherein R represents a methyl group.

21. 4-(2-Methyl-phenyl)-2-butynyl ( +) -cis/trans-2 , 2-d imeth l- ro en l -c clo ro ane carbox late .