GB2142632A - Process for the preparation of the pheromone 3,11-dimethyl-2-nonacosanone - Google Patents

Abstract

<IMAGE> The compound of the formula /I/ is prepared by a./reacting a 2,10-dimethyloctacosanoic acid ester of the general formula /II/, <IMAGE> wherein R is a C1-5 alkyl group, with a trialkylsilylmethyl lithium in an ether-type solvent, reacting the intermediate of the general formula /III/ thus obtained, <IMAGE> wherein R<1>, R<2> and R<3> may be the same or different and represent a C1-5 alkyl group with an aliphatic alcohol; or b./reacting a 2,10-dimethyloctacosanoic acid ester of the general formula /II/with a solution of methylsulfinylmethyde in dimethylsulfoxide in an ether-type solvent, reacting the compound thus obtained with a reducing agent, e.g. aluminium amalgam, and separating the compound of the formula /I/thus obtained from the reaction mixture. The 3,11-dimethyl-2-nonacosanone of the formula /I/ produces a strong stimulating reaction on male German cockroach /Blattella Germanica/. Compounds of formula (II) are novel.

Description

SPECIFICATION Process for the preparation of 3,11 -dimethyl-2-nonacosanone The invention relates to a new process for the preparation of 3,11 -dimethyl-2-nonacosanone.

It is known that the 3,1 1 -dimethyl-2-nonacosanone of the formula 111

produces a significantly strong stimulating reaction on male German cockroach /Blattella Germanica/.

The German cockroach is an unpleasant pest of residential and commercial buildings. Old, neglected edifices supplied with public utilities serve as ideal hiding-places for various species of crawling insects, especially the hard-to-kill cockroach. Its breeding season is short, so it becomes quickly widespread and appears also in the new housing estates.

In addition to the aesthetic view-points giving reason to the eradication of this pest, the direct harm caused by it is also considerable. Besides, it may spread viral infections.

The German cockroach has been a target for eradication by men for centuries. Lately, pesticides have been developed which have high toxicity for cockroaches, but such pesticides frequently present environmentai hazards when used in effective concentrations. On the other hand, an efficient eradication can be expected only in case of repeated application of chemical toxicants, because the quick breeding of a few surviving pests can reinfect the area in a short time.

Because of the above-mentioned difficulties it is advantageous to use pheromone-containing traps to combat this pest. Traps baited with the sex pheromone of it are not toxic to higher animals and human beings. By means of them the pests that have survived the eradications with chemical toxicants can be trapped, so the pollution of the pest can be hindered.

Nishida et al. [R. Nishida, H. Fukami and S. Ishii: Experientia 30, 978 /1974/; Appl. Ent. Zool. 10, 10/1975/. R.

Nishida, T. Sato, Y. Kuwahara, H. Fukami and S. Ishii: J. Chem. Ecol. 2,449/1976/; Agr. Biol. Chem. 40, 1407 /1976/] reported on the extraction of the pheromone of German cockroach. From cuticular wax of sexually mature females they isolated two components identified as 3,1 1-dimethyl-2-nonacosanone of the formula 111 and 29-hydroxy-3,1 1-dimethyl-2-nonacosanone of the formula /XI/.

Both compounds elicit wing-raising and direction-turning response from the male adults.

Later Mori et al. [K. Mori, T. Suguro and S. Mashda: Tetrahedron 37,1329/1981/] synthetized all of the possible stereoisomers of both pheromone components. The natural pheromones were shown to be of /35, 11S/configuration.

The compound of the formula /1/was synthetized first by Nishida et al. [R. Nishida, H. Fukami and S. Ishii: Appl. Entomol. Zool., 10, 10 /1975/]. They started with ethyl acetoacetate. The condensation reaction thereof with 1,6-dibromohexane was achieved in an alkaline solution to yield the corresponding bromoketoester, which when hydrolyzed and followed by spontaneous decarboxylation in concentrated hydrobromic acid gave 1 -bromo-8-oxononane. The latter was reacted with octadecylene-triphenylphosphorane to yield l-bromo-8-methyl-8-hexacosene, which was then reacted with an excess of ethyl methylacetoacetate in the presence of potassium t.butoxide.The ethyl /2,1 0-dimethyl-2-acetyl-1 1 -octacosenoate/ thus obtained was hydrolyzed and subsequently decarboxylated, and the 3,11 -dimethyl-2-oxo-i 1 -nonacosene thus obtained was converted into the compound of the formula 111 by catalytic hydrogenation.

According to another method [M. Schwarz, J.E. Oliver and P.E. Sonnet: J. Org. Chem. 40,2410/1975/] 1,6-hexanediol was used as starting substance. It was converted into 6-chlorohexyl tetrahydro-2-pyranyl ether, which was reacted with sodium iodide and sodium cyanide in dimethylsulfoxide. Reduction of the thus-obtained 7-tetrahydropyranyloxyheptane nitrile with lithium diethoxyaluminium hydride yielded the corresponding aldehyde. The Wittig reaction between the latter compound and /1 -methylnonadecylidenel triphenylphosphorane afforded presumably a cis and trans mixture of 8-methyl-7-hexacosenyl tetrahydropyranyl ethers, which was hydrogenated to obtain 8-methylhexacosanyl tetrahydropyranyl ether.The latter was reacted with triphenylphosphine bromide, the 1-bromo-8-methylhexacosane thus obtained was reacted with an anion formed from /2-oxobutylidene/triphenylphosphorane and butyl lithium. The 3,11 -dimethyl-2-oxononacosylidene triphenylphosphorane thus obtained was hydrolyzed to obtain the aimed compound of the formula 111.

In a further method Burgstahler et al. [A.W. Burgstahler, L.O. Weigel, W.J. Bell and M.K. Rust: J. Org.

Chem. 40, 3456 /1975/] started with e-caprolactone. Treatment thereof with hydrogen bromide and concentrated sulfuric acid gave 6-bromohexanoic acid. Esterification of this acid afforded ethyl 6bromohexanoate, which was reacted with the sodium enolate of acetoacetate to obtain ethyl /7ethoxycarbonyl-8-oxononanoate/. The latter compound was hydrolyzed and decarboxylated into 8oxononanoic acid. Treatment of the methyl ester thereof in polar solvent with the Wittig reagent derived from octadecyltriphenylphosphonium bromide gave methyl-8-methyl-8-hexacosenoate. This was hydrogenated into the corresponding saturated ester which, after reduction with lithium aluminium hydride into 8-methyl-1-hexacosanol and conversion into the corresponding bromide, was used to alkylate diethyl methylmalonate.Hydrolysis of the resulting diester and decarboxylation of the thus-obtained acid gave 2,1 0-dimethyloctacosanoic acid, which was treated with methyl lithium to obtain the aimed compound of the formula 111.

According to a further method published by Rosenblum et al. [L.D. Rosenblum, R.J. Anderson, C.A.

Henrick: Tetrahedron Letters 419/1976/] the 3,11 -dimethyl-2-nonacosanone was synthetized from S-phenyl nonadecanethioate. Lithium di-6-[/1 -ethoxy/ethoxy]hexylcuprate reagent was prepared from the ethoxyethyl ether of 6-chiorohexanol, and this was reacted with 5-phenyl nonadecanethioate to obtain 7-oxopentacosan1-ol. Reaction of this ketoacetale with triphenylphosphonium methylide in tetrahydrofuran produced the corresponding methylene acetale, which was subjected to catalytic hydrogenation followed by hydrolysis with a catalytic amount of p-toluenesulfonic acid. The 7-methylpentacosan-1-ol thus obtained was reacted with mesyl chloride and triethylamine, and the mesylate was treated with lithium bromide to obtain 7-methylpentacosanyl bromide.The latter compound was coupled with 3-[/1 -ethoxy/ethoxy]-2methylbutyllithium obtained from 1-hydroxy-2-methyl-3-butanone in 2 reaction steps. Coupling reaction was carried out in the presence of dilithium-copper tetrachloride. Conversion of the 2-[/1 -ethoxy/ -ethoxyi-3,1 1 -dimethylnonacosane thus obtained was treated with trichloroacetic acid. Oxidation of the thus-obtained 2-hydroxy-3,1 l-dimethylnonacosane with Jones reagent gave the pheromone component of the formula 111.

According to the method of Place et al. [P. Place, M.L. Ronmestant, J. Gore: Tetrahedron, 34, 1931 /1978/] vinylallenes were used for the synthesis of the compound of the formula /I/.3-Hydroxy-3-methyl-1 -penten-4- yne obtained from methyl vinyl ketone and acetylene was treated with hydrogen chloride to obtain l-chloro-3-methyl-2-penten-4-yne, which was converted with magnesium into the corresponding magnesium vinylmethylallene.The latter was reacted with acrolein, the alcoholic hydroxy group of the thus-obtained 4-ethynyl-4-methyl-3-hydroxy-1,5-hexadiene was protected, and the compound was alkylated with hexadecanyl bromide at -30 C. Boiling of the 4-allyl-3-hydroxy-4-methyl-1 -docosen-5-yne thus obtained in diglyme resulted via oxy-Cope rearrangement in 6-methyl-5-ene-7-yn tetracosanal. The latter aldehyde was alkylated with an alkyllithium obtained from /4-ethylenedioxo/-3-methyl-1 -chloropentane with butyl lithium. The hydroxy group of the 3,11 -dimethyl-2-ethylenedioxo-6-hydroxy -1 0-nonacosene-i 2-yne thus obtained was removed by reducing the mesyl derivate with zinc in dimethoxyethane, in the presence of sodium iodide.The /2-ethylenedioxo/-3,i 1 -dimethyl-i 0-nonacosene-i 2-yne thus obtained was hydrogenated ahd the aimed compound of the formula/I/was obtained by removing the acetal protecting group.

According to a still further method elaborated by Seidel and Schafer [W. Seidel, H.J. Schäfer: Chem. Ber.

113, 451/1980/] the key step for the preparation of the pheromone component of the formula 111 is the coelectrolysis of 6-methyltetracosanoic acid with 5-methyl-6-oxoheptanoic acid. They started with sec.butyl-/ 2-butenoate/, which was reacted with octadecylmagnesium bromide in the presence of cupric chloride. The sec.butyl-/3-methylheneicosanoate/thus obtained was subjected to hydrolysis to obtain the corresponding acid, which was then coelectrolized with 5,5-dimethoxyvaleric acid. The methyl-/6-methyltetracosanoate/ thus obtained was subjected to alkaline hydrolysis to give the corresponding acid.This compound was coelectrolized with 5-methyl-6-oxoheptanoic acid derived from methyl acetoacetate via alkylation with ethyl 4-bromobutyrate and subsequent decarboxylation to obtain the compound of the formula /I/.

Mori et al. [K. Mori, S. Mosuda, T. Sugara: Tetrahedron Letters, 3444/1978/; Tetrahedron, 37, 1329 /1981/] have published a method for the stereocontrolled synthesis of all of the possible stereoisomers of 3,1 i-dimethyl-2-nonacosanone of the formula 111 and 29-hydroxy-3,1 1-dimethyl-2-nonacosanone of the formula lXII. The key step of their synthesis is the coupling of a chiral tosylate - in case of the pheromone of the formula/I/the 5R- and 5S-methyltricosanyl tosylate, respectively - with a chiral Grignard reagent derived from 4R- and 4S-methyl-5-hexenyl bromide, respectively, in the presence of dilithium copper tetrachloride. To prepare 5R-methyltricosanyl tosylate R-/+/-citronellic acid was reduced with lithium aluminium hydride into R-/+/-citronellol.The tosylate thereof was converted into R-/+/-citronellyl iodide with sodium iodide. By the standard malonic ester synthesis it was converted to 5R,i0-dimethyl-9-decenoic acid via the malonate. This was reduced with lithium aluminium hydride to the corresponding alcohol whose acetylation gave 5S,1 0-dimethyl-9-decenyl acetate. The latter was oxidized with m-chloroperbenzoic acid, oxidation of the epoxide thus obtained with periodic acid yielded 7-formyl-5S-methylheptyl acetate. The Wittig reaction between the latter compound and triphenylpentadecenyl phosphorane gave an olefinic alcohol. This was hydrogenated over palladium to give 5R-methyltricosanol. The corresponding tosylate was prepared in the conventional manner.

To produce the antipode tosylate 1-hexadecyne was alkylated with R-/-/-citronellyl iodide. The acetylene compound thus obtained was first epoxidized, then oxidized with periodic acid to give 4S-methyl-7 docosynal. This was reduced with lithium aluminium hydride, the alcohol thus obtained was converted into the corresponding tosylate whose reaction with potassium cyanide yielded the corresponding nitrile.

Alkaline hydrolysis, reduction of the thus-obtained acid and subsequent catalytic hydrogenation afforded the aimed 55-methyltricosanol. The corresponding tosylate was prepared in the conventional manner.

4-R-Methyl-5-hexenyl bromide, the other component of the synthesis, was prepared from 3R,7-dimethyl 6,7-epoxy-1 -heptene. Oxidation thereof with periodic acid gave the corresponding aldehyde, which was reduced with lithium aluminium hydride to give 4R-methyl-5-hexanol. The corresponding tosylate was treated with lithium bromide in acetone. To prepare the antipode of the compound thus obtained 7-phenyl-4R-methylhexanoic ester was reacted with chrome /VI/ oxide to a half ester. Its silver salt was submitted to the Hunsdiecker reaction to give methyl /4S-methyl-6-bromohexanoate/.This was reacted with o-nitroselenophenol, the selenyl group of the compound thus obtained was removed by oxidative elimination, the olefinic acid thus obtained was reduced with lithium aluminium hydride to give the corresponding alcohol, whose tosylate was converted to 4S-methyl-5-hexenyl bromide in the conventional manner.

To produce the stereoisomers of the compound of the formula 111, the Grignard reagent derived from 4Rand 4S-methyl-5-hexenyl bromide, respectively, was coupled with 5R- and 5S-methyltricosanole tosylate, respectively. The reaction was carried out in the presence of dilithiumcuprous tetrachloride. The Markownikoff hydration of the resulting 3,1 1-dimethylnonacosene stereoisomers by oxymercurationdemercuration with mercuric acetate and sodium borohydride gave an alcohol. This alcohol was oxidized with chrome Nix oxide to give the aimed pheromone component of the formula 111.

In case of both pheromone components [formulae/I/and /XI/] the compounds of /3S,1 1S/ configuration proved to be identical with the natural sex lure of the pest. The authors did not find a significant difference between the biological activities of the different stereoisomers.

The known processes for the preparation of the pheromone component of the formu la 111 are unfavourable and uneconomical because of the high number of the cumbersome reaction steps and the expensive reactants.

The aim of the present invention was to provide a more economical process for the preparation of the pheromone component of the formula /1/, which can be more readily carried out also on an industrial scale.

According to the invention the 3,11 -dimethyl-2-nonacosanone of the formula /I/ is prepared from the new esters of the general formula /II/

wherein R is a C15 alkyl group, by a./ reacting a 2,10-dimethyloctacosanoic acid ester of the general formula /11/with a trialkylsilylmethyl lithium in an ether-type solvent, preferably under cooling, reacting the intermediate of the general formula /III/ thus obtained,

wherein R1, R2 and R3 may be the same or different and represent a C1-5 alkyl group, preferably without isolation, with an aliphatic alcohol; or b./ reacting a 2,10-dimethyloctacosanoic acid ester of the general formula /II/, wherein R has the above-defined meaning, with a solution of methylsulfinylmethyde in dimethylsulfoxide in an ether-type solvent, reacting the compound thus obtained, preferably without isolation, with a reducing agent, preferably aluminium amalgam; and separating the compound of the formula /1/thus obtained from the reaction mixture.

According to variant a./ of the process according to the invention a compound of the general formula/Il/is reacted with a trialkylsilylmethyl lithium in an ether-type solvent, preferably under cooling. It is not necessary to isolate the thus-obtained intermediate of the general formula /III/, it can be reacted in the reaction mixture where it has been formed with an aliphatic alcohol, preferably methanol.

According to variant b./ of the process according to the invention a compound of the general formula /II/ is reacted with a solution of methylsulfinylmethyde in dimethylsulfoxide. Methylsulfinylmethyde can be prepared from dimethylsulfoxide with a strong base, preferably sodium hydride, at a temperature below 70 "C. The intermediate obtained in the reaction of the compound of the formula /11/with methylsulfinylmethyde is not necessary to isolate, the reduction thereof can be performed in the reaction mixture where it has been formed. The reduction is carried out preferably with aluminium amalgam derived from aluminium and mercuric chloride in the conventional manner.

The compound of the formula 111 obtained in the reaction can be separated from the reaction mixture by known methods/e.g. distillation, chromatography/.

The esters of the general formula /II/ used as starting substances have not so far been described in the literature. For their preparation we have elaborated two methods. According to the first one 10-undecenic acid of the formula /IV/, CH2=CH-/CH2/8-COOH /lV/ a commercial product, is converted to an ester of the general formula N/,

wherein R is a C15 alkyl group. This reaction can be performed in two ways. Either the 10-undecenic acid is oxidized with hydrogen peroxide in the presence of catalytic amounts of a palladium salt, preferably palladium acetate, and the acid thus obtained is converted to the ester of the general formula Nl, or the lO-undecenic acid is first converted to a corresponding ester which is then oxidized to the compound of the general formula Nl.The latter is then reacted with a phosphorane derived from a compound of the general formula Nll, /C5H3P±CH2-/CH2/15-CH3 X- Nl/ wherein X represents halogen, with a strong base, preferably methylsulfinylmethyde. The ester of the general formula /VII/ thus obtained,

wherein R is as defined above, is hydrogenated catalytically over palladium on charcoal catalyst. The saturated ester of the general formula /VIII/thus obtained,

wherein R is as defined above, is hydrolized, the acid thus obtained is converted into the corresponding dianion with a strong base, preferably an alkyl lithium. The dianion is reacted with methyl iodide, and the acid thus obtained is converted to the esters of the general formula /II/.

According to our second method elaborated for the preparation of the esters of the general formula/ll/the 10-undecenic acid of the formula IIVI is reacted with an alkyl lithium, the dianion thus obtained is alkylated with methyl iodide, the 2-methyl-i 0-undecenic acid thus obtained is converted into the corresponding ester, which is oxidized with hydrogen peroxide, in the presence of a palladium salt catalyst - preferably palladium acetate - to a compound of the general formula /IX/,

wherein R is as defined above. The latter is reacted with a phosphorane derived from a phosphonium salt of the general formula Null. An ester of the formula /X/ is obtained,

wherein R is as defined above, which is subjected to catalytic reduction to obtain the esters of the general formula /il/.

According to another variant of the above method the compound of the formula /IX/ is prepared from 2-methyl-lO-undecenic acid so that it is first oxidized to the corresponding oxocarboxylic acid and the latter is converted to the ester of the general formula /IX/.

The trialkylsilylmethyl lithium used for variant a./ of our synthesis is prepared from a trialkylsilylmethyl halide with lithium metal.

The invention is elucidated in detail by the aid of the following non-limiting Examples: EXAMPLE 1 Preparation of 3,1 1-dimethyl-2-nonacosanone /1/ a.l Preparation of 10-oxoundecanoic acid; R=H/ 1.0 g of palladium chloride and 1.0 g of crystalline cupric chloride are dissolved in the mixture of 50 ml of purified dimethylformamide and 7.5 ml of water, and the solution is heated to 100 C in oxygen stream. The oxygen stream is maintained, a solution of 9.0 g /0.0049 mole/of 10-undecenoic acid /lV/ in 10 ml of purified dimethylformamide is dropped to it at the same temperature, and the mixture is stirred for further3 hours.

Then it is cooled and poured onto water. The mixture is extracted 4 times with a total amount of 200 ml of ether, the ether solutions are combined, washed with water, dried and the solvent is distilled off. The residual yellow crystals are recrystallized from hexane.

Yield: 4.4 g /45%/ of yellow crystalline product.

M.p.: 57-59 C/in the literature: 58-60 C, R.E. Bowman: J. Chem. Soc. 1950,322/.

IR/KBr/: 1720, 1705, /CO/, 1460, 1440, 1420, 1360, 1280, 1240,1205, 1140 cm-1.

'H-NMR /CDCl3/: 3 1.35 /12H, m, 6 CH2/, 2.14/3H, s, CH3/, 2.35/4H, Br q, 2CH2/, 9.5/1H, br s, COOH/ Ms: M+ 200/1/, m/z 182/2/, 125/8/, 97/8/, 71/13/, 57/53/, 54/36/, 44/100/.

b./ Preparation of methyl 10-oxoundecanoate N; R =CH3/ 1./To an ether solution containing 3 g /0.07 mole/ of diazomethane 10.0 g/0.05 mole/ of 10-oxoundecanic acid are added at 0 C, under stirring, and the mixture is stirred at the same temperature for half an hour. The solvent is distilled off, and the residue is distilled in vacuo.

Yield: 9,3 g/87 %/ of colourless liquid.

B.p.: 158-160 C/10 mm/ in the literature: 133-135 C/2 mm, A. Citterio and E. Vismara: Synthesis 1980, 751/.

IR/film/: 1730, 1715,/CO/, 1460, 1430, 1360, 1230, 1150 cm-' H-NMR/CCl4/: # 1./12H, m, 6 CH2/, 2.05 /3H, s, CH3/, 2.25 /4H, br q, 2 CH2/, 3.58 /3H, s, OCH3/ Ms: M 214/11/, m/z 183/28/, 157/47/, 125/85/, 97/38/, 87/29/, 83/26/, 74/29/, 58/73/, 55 /100/, 41/91/.

2./To a solution of 13.5 g of 10-oxoundecanoic acid in 100 ml of anhydrous methanol 0.5 ml of sulfuric acid is added, and the solution is boiled for 4 hours. The solvent is distilled in vacuo, the residue is taken up in 100 ml of ether, the ether solution is washed with water and dried over magnesium sulfate. The solvent is distilled off and the residue is distilled in vacuo.

Yield: 12.0 g /83 /O/, the product is identical with the compound prepared according to variant 1./ c./ Preparation of octadecyltriphenylphosphonium bromide /VI; X= Br/ 10.0 g /0.03 mole/ of stearyl bromide and 8.0 g /0.03 mole/ of triphenylphosphine are dissolved in 20 ml of anhydrous benzene, and the solution is refluxed for 48 hours. The solvent is distilled off, the residue is taken up in 20 ml of anhydrous ether, the crystalline product is filtered and washed with anhydrous ether.

Yield: 14.06 g /79%/of white crystalline product.

1H - NMR /CDCl3/: 3 0.85 /3H, t, J =6 Hz, CH3/, 1.28 /32H, m, 16 CH2/ 3,6 /2H, m, CH2/, 7.75 /9H, m, aromatic pr./, 8.0 /6H, m, aromatic pr./.

d./Preparation of methyl/10-methyl-10-octacosenoate/VII; R=CH3/ 0.8 g /0.033 mole/of sodium hydride is added to 20 ml of anhydrous dimethylsulfoxide, and the mixture is stirred at 70 C under argon for one hour. The solution is then cooled to room temperature, and a solution of 16.0 g /0.027 mole/ of octadecyltriphenylphosphonium bromide NI; X=Br/ in 80 ml of anhydrous dimethylsulfoxide is dropped to it under vigorous stirring. The reaction mixture is stirred at a temperature between 40 C and 50 C for half an hour, cooled to room temperature, and a solution of 4.5 g /0.021 mole/ of methyl 1 0-oxou ndecanoate N; R=CH3/ in 10 ml of anhydrous dimethylsulfoxide is dropped to it under vigorous stirring.The reaction mixture is stirred at room temperature for 8 hours, 30 ml of distilled water are added to it, and the mixture is extracted three times with a total amount of 30 ml of hexane. The hexane solution is washed successively with water and saturated sodium chloride solution and dried over magnesium sulfate. The solvent is distilled off, the residual product is taken up in 20 ml of hexane, the separated precipitate is filtered off, the solvent is distilled off and the residue is purified by column chromatography /Kieselgel 60, benzene-methanol 10:0.2/.

Yield: 4.44 g /47 %/ of colourless oil /according to liquid chromatography it is a 3:2 mixture of E and Z isomers/.

IR /film/: 1740 /CO/, 1460, 1440, 1380, 1360, 1220, 1180, 1160,1090, 1020 cm-1.

1H - NMR /CCl4/: 3 0.9 /3H, t, J =6Hz, CH3/, 1.26 /42H, m, 21 CH2/, 1.55 /3H, m, CH3/, 1.8-2.4 /6H, m, 3 CH2/, 3.55 /3H, s, OCH3/, 5.0/1 H, br t, J =6Hz, C=CH/.

Ms: M+ 450/31/, m/z 419/3/, 418/8/,300/3/,295/10/,294/40/,279/13/,213/16/,212/18/,197/27/,180/31/,165 /16/,157/51/,125/32/,111/30/,97/59/,85/22/,82/25/,81/35/,71/34/,69/83/,68/25/,58/80/,57/51/, 56/100/,43/66/.

e./Preparation of methyl/10-methyloctacosanoatel/VIII; R=CH3/ A solution of 4.0 g of methyl/10-methyl-10-octacosenoate/VII; R=CH3/ in 200 ml of methanol is hydrogenated in the presence of 1.0 g of palladium on charcoal catalyst. When the theoretic amount of hydrogen has been taken up /about 210 ml, 4 hours/, the catalyst is filtered off, washed with methanol, the organic solutions are combined and the solvent is distilled off. The residual oily product solidifies upon standing.

Yield: 3.85 9 /96.3 %/.

IR/KBr/9 1740,/CO/, 1460, 1440, 1380, 1360, 1240, 1150 cm-1.

H-NMR/CDCl3/: 3 0.88 /3H, t, J=7Hz, CH3/, 1.3 /52H, m, 24 CH2, CH3, CH/,2.2/2H,t,J=7 Hz, CH2/, 3.68 /3H, s, OCH3/.

Ms: M+ 452/100/, m/z421 /31,409/51,199/8/, 172/5/, 167/61,143/191,129/82, 111 /6/,87/41/,83/20/,75/33/, 74/55/,71/23/,69/27/,57/47/.

f/Preparation of 10-methyloctacosanoic acid/VIII; R=H/ 3.0 g of methyl/10-methyloctacosanoate/VIII; R=CH3/ are dissolved in the mixture of 30 ml of methanol and 15 ml of water, 3 g of potassium hydroxide are added to the solution and the mixture is stirred at 40 C for 4 hours. Then it is acidified with hydrogen chloride and extracted three times with a total amount of 150 ml of ether. The ether solution is washed with water, dried over magnesium sulfate and the solvent is distilled off. The residual product solidifies upon standing.

Yield: 2.7 g/93 /O/.

M.p.:31-32 C.

IR/KBr/: 1710/CO/, 1460, 1440, 1380, 1200, 1140 cm-1.

H-NMR/CDCl3/: # 0.87/3H, t, J=6Hz/, 1-17/5H,m,24CH2, CH3, CH/, 2.1/2H,m,CH2/.

Ms: M+ 438/92/, m/z320/12/, 185/231,167/24/, 158/251,149/11/, 129/19/, 97/23I,85/34/,71/53/, 57/100A g./Preparation of 2,10-dimethyloctacosanoic acid/II; R=H/ To a solution of 0.85 g/0.0083 mole/ of diisopropylamine in 20 ml of anhydrous tetrahydrofuran 8 ml of 2M hexane butyllithium solution/containing 0.72 g. 0.011 mole of butyllithium/ are added at 0 C, under argon, and the mixture is stirred at 0 C for 20 minutes. Then a solution of 1.86 9 /0.004 mole/of 10-methyloctacosanoic acid /VIII; R=H/ in 5 ml of anhydrous tetrahydrofuran and 5 ml of anhydrous hexamethylphosphoramide is dropped to it and the solution is stirred at 5 C for half an hour.Thereafter 0.58 g/0.255 ml, 0.004 mol/ of methyl iodide is added to the mixture in one portion /the temperature rises to 20 C/, and the mixture is stirred at room temperature for one hour. Then it is acidified with aqueous hydrogen chloride solution, extracted 4 times with a total amount of 200 ml of petroleum ether, the petroleum extract is washed successively with water and saturated sodium chloride solution, dried over magnesium sulfate and the solvent is distilled off.

Yield: 1,3 g/68%/.

IR/film/: 1750/CO/, 1460, 1380, 1230, 1140 cm-1.

H-NMR/CDCl3/: # 0.88/3H, t, J=7Hz/, 1-1.7/56H,m,24 CH2, 2Ch3, 2CH/.

Ms: M+ 452/69/, m/z 438/7/,320/5/,199/10/,143/9/, 130/11/,97/17/,57/32/,85/15/,83/24/,74/100/.

h./ Preparation of methyl /2, 10-dimethyloctacosanoatel Ill; R=CH3/ 1.0 9 of 2,1 0-dimethyloctacosanoic acid /II; R= H/ is treated with an ethereal diazomethane solution containing 0.2 g of diazomethane. The solvent is distilled off and 1 9 of colourless oily product is obtained.

IR/film/: 1735 /CO/, 1460, 1440, 1385, 1365, 1240, 1140 cm-1.

1H- NMR /CDCl3/: 3 0.89 /3H, t, J=6 Hz, CH3/, 1.1-1.8/56 H, m, 24 CH2, 2CH3/3,7/3H, s, OCH3/.

Ms: M+ 466/100/, m/z 435/4/,l423/3/,409/7/,213/7/,186/3/,157/14/,143/10/,11178/,97/14/,88/98/,85/13/, 83/19/.

i./ Preparation of 1 1-dimethyl-2-nonacosanone Ill To a mixture of 0.05 9 /8 mmoles/ of lithium in 25 ml of anhydrous ether 2.0 9 /16 mmoles/ of trimethylsilylmethyl chloride are added, under argon, and the reaction mixture is boiled for 4 hours under stirring. Then it is cooled to 0 C and a solution of 1.5 g /3.2 mmoles/ of methyl/2,10-dimethylocatacosanoate/ /II; R=CH3/ in 5 ml of anhydrous ether is added dropwise to it. The mixture is stirred at 0 C for 4 hours, 5 ml of methanol are added to it under cooling, and it is stirred further for 2 hours. Then it is poured onto ice water, extracted with ether, the ether solution is washed successively with water and saturated sodium chloride solution and dried over magnesium sulfate. The solvent is distilled off and the residual product is purified by column chromatography.

Yield: 0.75 g/52 %/ of colourless oil.

IR/film/: 1715/CO/, 1460, 1450, 1380,1220, 1170 cm-1.

H-NMR/CDCl3/: 3 0.84/3H,t,J=7 Hz, CH3/, 1.03 /3H, d, J=6 Hz, CH3/, 1.15-1.9/49H, m, 24 CH2, CH/, 2.02/3H, s, CH3CO/, 2.3/1 H, m, CH/.

EXAMPLE 2 Preparation of 3,1 1-dimethyl-2-nonacosanone /1/ a.l Preparation of 2-methyl- 10-undecenic acid To a solution of 16.6 g /23 ml, 0.15 mole/of diisopropylamine in 80 ml of anhydrous tetrahydrofuran 100 ml of 15 % hexaneous butyllithium solution are added. Then a solution of 10 g /0.054 mole/ of 1 0-undecenic acid in 15 ml of anhydrous hexamethylphosphoramide is added to the mixture at 0 'C. The reaction mixture is stirred at a temperature between 0 C and 5 C for 20 minutes, then the cooling is ceased and 9.3 g /4.1 ml, 0.065 mole/of methyl iodide are added at such a rate that the temperature rises until 36 C.The reaction mixture is stirred for 2 hours, poured into 60 ml of 1:1 hydrogen chloride solution and extracted with ether.

The ether extract is washed successively with hydrogen chloride solution, water, 5 % sodium hydrogen sulfite solution, water again and saturated sodium chloride solution and dried over magnesium sulfate. The solvent is distilled off and the residue is distilled in vacuo.

Yield: 8.5 g /80 %/.

B.p.: 100-104 C/0.01 mm.

IR/film/: 1710/CO/, 1630, 1440, 1370, 1270, 970, 905, 880 cm-1.

H-NMR/CDCl3/: # 1.15/3H,d,J=7 Hz, Ch3/, 1.1-1.85/12H,m,CH2/, 1.4-2.15/2H,m,CH2/,2.34/1H,t,J=7 Hz.

CH/,4.85-5.15/2H, m, C=CH2/, 5.6-6.0/1H, m, -CH=C/.

13C- N MR /CDCl3/: 16.8 /CH3/, 27.2, 29.0 24.2, 29.4, 29.6,33.6 /CH2/, 33.9 lallyl CH2/, 39.5/CH/, 114.2, 139.0 /CH2-CH/, 183.7 /CO/.

Ms: M + 198/13/, m/z 180/13/, 153/16/, 125/85/, 97/20/, 83/40/,73/100/, 69/90/, 55/851,41/45/, 27/65/.

Analysis: C12H2202/198.31/ Calculated: C%=72.68 H% = 11.18 Found: C%=72.46 H%=11.32 b./ Preparation of methyl /2-methyl-10-oxoundecanoate/ /IX; R = CH3/ 1./28.5 g /0.025 mole/of 30 % hydrogen peroxide, 0.085 g /0.0001 mole/of palladium/II/acetate and 10.0 9 /0.05 mole/ of 2-methyl-1 0-undecenic acid are dissolved in 80 ml of acetic acid, and the solution is stirred at 80 C for 6 hours. Then it is cooled and 40 ml of water are added to it. The mixture is extracted with ether, the ethereal solution is washed successively with water and saturated sodium chloride solution, dried over sodium sulfate and the solvent is distilled off in vacuo. 10 g of crude, brown 2-methyl-10-oxoundecanoic acid are obtained.

IR/film/: 1710/CO/, 1460, 1230 cm-1 H-NMR/CDCl3/: 1.12/3H,d,J=7 Hz, Ch3/, 1.1-1.8/12H,m,6 CH2/,2.1/3H,s,CH3/,2.3/3H,m,CH2,CH/.

2./The crude 2-methyl-1 0-oxoundecanoic acid prepared as described above is dissolved in 70 ml of anhydrous methanol, 0.2 ml of sulfuric acid is added, and the solution is boiled for 8 hours. Then it is cooled, neutralized with solid sodium hydrogen carbonate, the solvent is distilled off in vacuo, the residue is taken up in ether, the ethereal solution is washed successively with 5 % sodium hydrogen carbonate solution, water and saturated sodium chloride solution and dried over magnesium sulfate. The solvent is distilled off and the residue is distilled in vacuo.

Yield: 6.0 g /53 %/of yellowish oil.

B.p.: 146 C/0.8 mm.

IR/film/: 1740, 1710/CO/, 1460, 1440, 1360, 1185, 1155 cm-1.

H-NMR/CDCl3/: # 1.0-1.9/12H,m,6 CH2/, 1.1/3H,d,J=7 Hz, CH3/,2.05/3H,s,CH3CO/,2.3-2.45/3H,m,CH2.

CH/, 3.65 /3H, s, OCH3/.

Analysis: C13H2403/228.34/ Calculated: C% = 68.38 H% = 10.59 Found: C%=68.21 H%=10.45 c./ Preparation of methyl /2, 10-dimethyl- 10-octacosenoatel IX; R =CH3/ 2.2 g of sodium hydride /80 % oily suspension, 0.073 mole/ are added to 50 ml of anhydrous dimethylsulfoxide, and the mixture is stirred at 70 C under argon until the hydrogen gas evolution ceases /about 40 minutes/. The solution is cooled to room temperature and a solution of 40.0 g/0.067 mole/of octadecyltriphenylphosphonium bromide/VI; X=Br/ in 250 ml of anhydrous dimethylsulfoxide is added to it.

The mixture is stirred at 40 C for half an hour, cooled to 20 C and a solution of 12.0 g/0.056 mole/ of methyl /2-methyl-1 O-oxoundecanoate/ lIX; R=CH3/ in 20 ml of an hydrous dimethylsulfoxide is added to it. The reaction mixture is stirred at room temperature for 6 hours, poured onto ice and extracted three times with a total amount of 600 ml of pentane. The pentane solution is washed with water, dried over magnesium sulfate, and the solvent is distilled off in vacuo. The residual crude ester is purified by column chromatography.

Yield: 6.7 g /47.9 /O/, according to liquid chromatography it is a 3:2 mixture of E and Z isomers.

IR/film/: 1735/CO/, 1460, 1640, 1380, 1360, 1230, 1180, 1060, 990 cm-1.

H-NMR/CDCl3/ # 0.9/3H,t,J=7 Hz, CH3/, 1.15/3H,d,J=6 Hz/, 1.2-1.8/42H,m,21 CH2/, 1.4-2.3/5H,m,2CH2.

CH/, 3.55/3H, s, OCH3/, 5.0/1 H, m, CH=C/.

d./ Preparation of methyl /2, 10-dimethyloctacosanoatel Ill; R =CH3/ A solution of 4.0 g of methyl /2,10-dimethyl-l O-octacosenoate//X; R=CH3/ in 200 ml of anhydrous methanol is hydrogenated over 0.5 g of palladium on bone coal catalyst. When the theoretical amount of hydrogen has been taken up /about 200 ml, 6 hours, the catalyst is filtered off, the solution is washed several times with methanol, the methanol solutions are combined and the solvent is distilled off. 3.8 g /95.0%/of methyl /2,10-dimethyloctacosanoate/, identical with the product prepared according to Example 1/h, are obtained. It can be converted into the pheromone component of the formula 111 as described in Example 1/i.

Claims (6)

1. A process for the preparation of 3,11 -dimethyl-2-nonacosanone of the formula/Il,

characterized by a./ reacting a 2,10-dimethyloctacosanoic acid ester of the general formula /II/,

wherein R is a C1-5 alkyl group, with a trialkylsilylmethyl lithium in an ether-type solvent, preferably under cooling, reacting the intermediate of the general formula /111/thus obtained,

wherein R1, R2 and R3 may be the same or different and represent a C1 5 alkyl group, preferably without isolation, with an aliphatic alcohol; or b./ reacting a 2,1 0-dimethyloctacosanoic acid ester of the general formula/Ill, wherein R has the above-defined meaning, with a solution of methylsulfinylmethyde in dimethylsulfoxide in an ether-type solvent, reacting the compound thus obtained, preferably without isolation, with a reducing agent, preferably aluminium amalgam; and separating the compound of the formula Ill thus obtained from the reaction mixture.

2. A process according to variant a./ of claim 1, characterized by using trimethylsilylmethyl lithium as trialkylsilylmethyl lithium.

3. A process according to variant a./ of claim 1, characterized by using methanol as aliphatic alcohol.

4. 2,1 0-Dimethyloctacosanoic acid esters of the general formula/Ill, wherein R is as defined in claim 1.

5. A process as claimed in claim 1, substantially as hereinbefore described in Example 1 or 2.

6. 3,1 1-dimethyl-2-nonacosanone of the formula (I) when prepared by a process as claimed in any of claims 1 to 3 or 5.