IL33425A - Chrysanthemic acid esters,their preparation and insecticidal compositions containing them - Google Patents

Description

Chrysanthemic acid estere their preparation and insectlcidal compositions containing them SPARAMEDICA Αδ Cs 31658 33425/3 - 2 - The present invention is concerned with novel chrysanthemio acid esters and the manufacture thereof.

The chrysanthemio acid esters provided by the invention oan be generioally formulated thus: wherein the symbol R represents a grouping of the formula •CH2-Ci3C-CH2-CeCH (b) in which the symbol R represents a lower alkyl group and the symbols R and R^ individually represent a hydrogen atom or a lower alkyl group or the symbol R1 represents a hydrogen atom and the symbols R 2 and R3 each represent a lower alkyl group.

They are useful as insecticides.

Whereas the ester derived from 3-methyl-l-penten-4-% yn-3-ol, which is disclosed on page 1, column 1 of the U.S.

Specification No. 3» 285, 950, has been found to be inactive against houseflies at a concentration of 10 , the 5-hexen-2- ynyl and 2,5-hexadiynyl esters of the present invention are active against the same insects at a concentration of 10~^ -5 -6 to 10 or in some cases 10 . . / ;» ·:.. 33425/2, •¾¾oy are usef l as- l.nacrotleidoo.— It will be appreciated that the term "lower alkyl" is used to mean both straight-chain and branched-chain alkyl groups containing a relatively low number of oarbon atoms (e.g. methyl, ethyl and lsopropyl). The methyl group is the preferred lower alkyl group.

One interesting class of chrysanthemic a id esters of formula I comprises those in which the symbol R represents a grouping of formula (a) hereinbefore; that is to say those of the formula (la) wherein the symbols R , R and R have the significance given earlier.

Examples of such esters are 5-methyl-5-hexen-2-ynyl (i)-ois/ ' trans-2,2-dimethy1-3- (2-methyl-propenyl)-cyolopropane oarboxy' late; 6-methyl-5-hepten-2-ynyl (ΐ )-cis/trans-2,2-dimethy1- 3- (2-methyl-propenyl )-oyclopropane carboxylate and 5»6-di- methyl-5-hepten-2-ynyl (-)-cis/trans-2,2-dimethyl-3-(2-methyl propenyl)-cyclopropane carboxylate.

Another interesting class of chrysanitemic acid esters 33425/2 4 represents a grouping of formula (b) hereinbefore; that is to \ * say, those of the formula An example of such an ester is 2,5-nexadiynyl (-)-ois/trans-2,2-dimethyl-3- (2-methyl-propenyl)-cyolopropane carboxylate .

The chrysanthemic acid esters of formula I oan be manufactured in accordance with the invention by reacting an aoid halide of the formula wherein Hal represents a halogen atom, particularly a chlorine atom, with an alcohol of the general formula H0-CH2-C≡C-CH2-C≡CH (IV) 33425/2 - 5 The acid hallde starting materials of formula II are known and can be prepared, for example, by halogenating, e.g. chlorinating, the corresponding oarbox lic aoid, e.g. using thionyl chloride or the like.

The alcohol starting materials of formula III can be prepared by a variety of methods. One such method comprises reacting propargyl alcohol with an alkyl-magnesium halide (e.g. ethyl-magnesium bromide), treating the resulting Orignard complex with cuprous chloride or cuprous cyanide, treating the mixture with a halide of the formula 1 2 "5 wherein the symbols R. , R and R have the significance given earlier and wherein X represents a ohlorine or bromine atom, and decomposing the product by conventional techniques such as by treatment with aqueous ammonium chloride. Another method comprises treating a mixture of propargyl alcohol, cuprous chloride and sodium chloride in water with aqueous sodium hydroxide and a halide of formula VI simultaneously (see Ann., 1962 , 658, 6-20 ) . Yet another method comprises treating a mixture of propargyl alcohol, cuprous chloride and sodium carbonate in acetone with a- halide of formula ϊ 33425/2 6 The alcohol starting material of formulaIV can be prepared, for example, by reacting propargyl alcohol with an alkyl-magnesium halide (e.g. ethyl-magnesium bromide), treating the resulting Grignard complex with cuprous ohloride or cuprous cyanide, treating the resulting mixture with propargyl chloride or propargyl bromide and decomposing the product by conventional techniques such as by treatment with aqueous ammonium chloride.

The reaction of an acid halide starting material of formula II with an alcohol starting material of formula Ill-or iv 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. The preferred acid-binding agent is pyridine. The reaotion can conveniently be carried out in an inert organic solvent such as, for example, a hydrocarbon, e.g. benzene, toluene or xylene, an ether, e.g. diethyl ether or dioxan, a halogenated hydrocarbon, e.g. methylene chloride, chloroform or chloro-benzene and the like. It is preferred to carry out the reaction at a temperature within the approximate range of from 0°C to 30°C, preferably at about 20°C and to work under the atmosphere of an, inert 33425/2 - 7 \ gas such as nitrogen or argon.

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

The alkali-metal salt and tri( lower alkyl) amine salt starting materials referred to earlier can be prepared, for example, by treating a chrysanthemum carboxylio acid in an inert solvent such as a lower-alkanol,, e.g. ethanol, with the calculated amount of an alkali-metal hydroxide solution or 33425/2 . a tri( lower alkyl)amine. The preferred alkali-metal salts are the sodium and potassium salts and the preferred tri( lower alkyDamine salts are the triethy1 amine salts. The silver salts can be prepared by treating an alkali-metal salt, such as the sodium salt, in an aqueous solution, with silver nitrate.

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

The reaction between an alkali-metal salt, a silver salt, or a tri( lower alkyl)amine salt of a chrysanthemum carboxylic acid and a halide of formula VI or VII 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 oarry out the 0 reaction under the atmosphere of an inert gas such as nitrogen or argon. J 33425/2 9 Optical isomerism. It will also be appreciated that, where the symbol R in formula I represents a grouping of formula (a), this grouping can show geometric isomerism in the case where 2 the symhols R and R are different. Accordingly, it will be understood that the novel esters provided by the invention include all of the various geomejtric and optical isomers as well as mixtures thereof. One type o mixture is obtained by using an acid halide starting material mixture, an alkali-metal salt starting material mixture, a silver salt starting material mixture or a tri( lower alkyl) mine salt starting material mixture prepared from the commercial carboxylio aold hich oonsists of a cis/trans mixture in a ratio of about 30x70$.

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 plperonyl butoxide; (l,2-methylenedioxy)- -[2-(octylsulfinyl)- propyl]-benzene and the like. Furthermore, they have been found to have a very low mammalian toxicity. For example, 5-methyl-5-hexen-2-ynyl (-)-cis/trans-2,2-dimethyl^3-(2-methyl- propenyl)-cyclopropane carboxylate; 6-methyl-5-hepten-2-ynyl (-)-ois/trans-2,2-dimethy1-3- (2-methyl-propenyl)-cyclopropane (2-.methyl-propenyl)-oyolopropane car oxylate all have an LD_-. of greater than l600 mg/kg p.o« In miee and have been shown to have an activity against Musoa domestioa in the order of pyrethrin extraot and DDT* The first named ester also shows an activity against codlln moth and the third named ester also shows an aotivity against codlln moth, Colorado beetle, red spider mite and bean aphids.

The esters of the invention can be used in the form of conventional inseotioldal 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 some instances it may be desirable that the carriers include emulsions, solutions or organio solvents. Solid carriers which may also be used in preparing the lnsectlcidal compositions include, for example, talc, silica and similar powders which do not bring about decomposition of the esters. The lnsectlcidal compositions may, if desired, contain conventional additives such as emulsifying agents, wetting agents or the like and may also contain other insecticides and/or synergists.

The following Examples illustrate the invention. The chrysanthemum monooarboxyllc acid ohloride mentioned therein was obtained from the commercial (-) oarboxylic acid consisting of a cis/trans~mixture in the ratio of ca.30*70.

Example 1 A solution of 14.0 g of chrysanthemum raonooarboxylic acid chloride in 50 ml of dry benzene is added dropwise at 20°C in a nitrogen atmosphere over a period of 0.5 hour to a stirred solution of 9.07 g of 5-meth l-5-hexen-2-yn-l-ol and 11.85 g of dry pyridine in 120 ml of dry benzene. The resulting mixture is stirred at 20°C in a nitrogen atmosphere for 48 hours, then the precipitated pyridine hydrochloride is filtered off and washed with benzene. The combined filtrate and washings are washed successively with 5-N aqueous hydrochloric acid, 2-N aqueous sodium hydroxide solution, 2-N aqueous hydrochloric acid, saturated aqueous sodium bicarbonate solution and brine, dried over anhydrous sodium sulfate, filtered and evaporated. The residue is distilled to yield 5-methyl-5-hexen-2-ynyl (- )-cis/trans-2,2-dimethyl-3-(2-methyl-propenyl)-cyclopropane carboxylate of boiling point 128-129°C/0.2 mm; n^1 - 1.4895· Example 2 In a similar manner to that described in Example 1, from 6-methyl-5-hepten-2-yn-l-ol and chrysanthemum monocarboxyllc acid chloride there is obtained 6-methyl-5-hepten-2-ynyl (-)-cis/trans-2,2-dimethy1-3-(2-methyl-propenyl)-cyclopropane carboxylate (boiling point « l62-l63°C/0.2 mm, n^° - I.4931) and from 5,6-dimethyl-5-hepten-2-yn-l-ol and chrysanthemum monocarboxyllc acid chloride there is obtained 53425/2 12 (2-methyl-propenyl)-cyclopropane carbox late (boiling point * 145 - 143°C/1.1 mm).

BXAHKKB 3 A solution of 14 g chrysanthemum monocarbox llc acid ehloride in 30 ml of dry benzene is added dropwise over a period of 0.5 hour at 20°C under a nitrogen atmosphere to a stirred solution of 7.8 g of 2,5-hexadiyn-l-ol and 11.85 β of dry pyridine in 120 ml of dry benzene. She resulting mixture is stirred under a nitrogen atmosphere for a further 64 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 sodium sulfate and, after the addition of a few crystals of hydroquinone, evaporated. The residue is distilled under nitrogen to yield 2,5-hexadiynyl (±)-cis/trans-2,2-dimethyl-3- (2-methyl-propenyl)-cyclopropane carboxylate as a yellow syrup which is stabilized with hydroquinone; boiling point = 157-158°J n ° = 1.4970. 2,5-Hexadiyn-l-ol used as one of the starting materials in the above process can be prepared as follows: Ethyl magnesium bromide is prepared from 24.2 g of magnesium and 109 g of ethyl bromide in 190 ml of tetrahydro-furan. The resulting solution is filtered and diluted with 300 ml of tetrahydrofuran. 28.2 g of redistilled propargyl alcohol are added dropwise over 0.5 hour and the resulting mixture is then heated under reflux for 1.5 hours and then allowed to cool. 1.5 g of cuprous chloride are added, followed by a solution of 60 g of redistilled propargyl bromide in ml of tetrahydrofuran. The mixture obtained is heated under reflux for l6 hours and then worked up in the manner described in Example 1. Rapid distillation of the crude of nitrogen and redistillation gives 20 g of 2,5-hexadiyn-l-ol of boiling point = 68-70°C/0.6 nun; n^° = I.5OI5. 9.5 g of the sodium salt of chrysanthemum monooarbox lic acid are ground to a fine powder and dissolved, with stirring, in 400 ml of diglyme at 100°C under an atmosphere of nitrogen. 8,65 g of l-bromo-5-meth l-hex-5-en-2-yne in 80 ml of diglyme are added dropwise over a period of 0.25 hour with stirring The mixture is heated at 150°C for 88 hours under an atmosphere of nitrogen. The precipitated solids are filtered off and the diglyme is removed under reduced pressure ( 5 mm Hg).

The residue is treated with water and extracted three times with ether. The ether extracts are combined and washed twice with water, twice with 2-N sodium hydroxide solution and twice with sodium chloride solution and then dried over anhydrous sodium sulfate. After filtration and evaporation of the ether, the residue is distilled to yield 5-methyl-5-hexen-2-ynyl (-)-cis/trans-2,2-dimethyl-3- (2-methyl-propenyl)-cyclopropane carboxylate of boiling point 145-151°C/ 1.0 mm (bath temperature 170 C); n = 1.4920. 33425/2

Claims (1)

1. CLAIMS Process for the manufacture of ohrysanthemic acid esters of the general formula wherein the symbol R represents a grouping of the formula in whioh the symbol represents a lower alkyl group and the symbols R and individually represent a hydrogen atom or a lower alkyl group or the symbol 1 2 R represents a hydrogen atom and the symbols R and each represent a lower alkyl oharacterlzed that an acid halide of the formula wherein Hal represents a halogen is reacted with an of the general formula in which the symbols R2 and R3 have the foregoing or that an a silver salt or a lower salt of a chrysanthemum oarboxylio acid with a halide of the formula 17 in which the symbols R and Hal have the above meaning Process as claimed in Claim characterized in that a starting material of formula III or VI is wherein 1 2 3 R is methyl and R and R are Process as claimed in Claim characterized in that 1 a starting material of formula VI is used wherein R 2 3 is hydrogen and R and are Process as claimed in Claim characterized in that a starting material of formula III or is used wherein 3 R R and R each represent a methyl 18 as claimed in Claim characterized in is used starting material of formula Process for the manufacture of chrysanthemic acid as hereinbefore particularly with reference to the foregoing Process the manufacture of an insecticidal characterized in that a chrysanthemic acid ester of the general formula I as set hereinbefore is mixed with a compatible An insecticidal composition containing as an essential active a chrysanthemic acid ester of the formula I V as set forth hereinbefore in association with a compatible Chrysanthemic acid esters of the general formula symbol R represents a grouping of the 19 in which the symbol R represents a lower group 2 3 and the symbols R and individually represent a hydrogen atom or a lower alkyl or the symbol represents a 2 3 hydrogen atom and the symbols R and R each represent a lower alkyl whenever prepared by the process as claimed in Claim 1 or by an obvious chemical equivalent h whenever propared by the process as claimed in Claim 1 or 2 or by an obvious ohemioal equivalent whenever prepared by the process as claimed in Claim 1 or 3 or by an obvious equivalent whenever prepared by the process as claimed in Claim 1 or or by an obvious chemical equivalent whenever prepared by the process as c laimed in Claim 1 or or by an obvious chemical equivalent Chr santhemic J 20 wherein the symbol R represents a grouping of the formula in which the symbol R represents a lower alkyl group 2 and the symbols R and individually represent a hydrogen atom or a lower alkyl group or the symbol 2 represents a hydrogen atom and the symbols R and each represent a lower alkyl 21 ep For the AMD PARTNERS insufficientOCRQuality