GB2142633A - Process for the preparation of the pheromone 29-hydroxy-3,11- dimethyl-2-nonacosanone - Google Patents

Process for the preparation of the pheromone 29-hydroxy-3,11- dimethyl-2-nonacosanone Download PDF

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GB2142633A
GB2142633A GB08416630A GB8416630A GB2142633A GB 2142633 A GB2142633 A GB 2142633A GB 08416630 A GB08416630 A GB 08416630A GB 8416630 A GB8416630 A GB 8416630A GB 2142633 A GB2142633 A GB 2142633A
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formula
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dimethyl
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acid
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Csaba Szantay
Lajos Novak
Gabor Baan
Andras Dancso
Attila Kis-Tamas
Ferenc Jurak
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Egyt Gyogyszervegyeszeti Gyar
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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
    • C07F9/00—Compounds containing elements of Groups 5 or 15 of the Periodic Table
    • C07F9/02—Phosphorus compounds
    • C07F9/547—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom
    • C07F9/655—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom having oxygen atoms, with or without sulfur, selenium, or tellurium atoms, as the only ring hetero atoms
    • C07F9/65515—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom having oxygen atoms, with or without sulfur, selenium, or tellurium atoms, as the only ring hetero atoms the oxygen atom being part of a five-membered ring
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C45/00—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds
    • C07C45/61—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds by reactions not involving the formation of >C = O groups
    • C07C45/67—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds by reactions not involving the formation of >C = O groups by isomerisation; by change of size of the carbon skeleton
    • C07C45/673—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds by reactions not involving the formation of >C = O groups by isomerisation; by change of size of the carbon skeleton by change of size of the carbon skeleton
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    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C49/00—Ketones; Ketenes; Dimeric ketenes; Ketonic chelates
    • C07C49/04—Saturated compounds containing keto groups bound to acyclic carbon atoms
    • C07C49/17—Saturated compounds containing keto groups bound to acyclic carbon atoms containing hydroxy groups
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D309/00—Heterocyclic compounds containing six-membered rings having one oxygen atom as the only ring hetero atom, not condensed with other rings
    • C07D309/02—Heterocyclic compounds containing six-membered rings having one oxygen atom as the only ring hetero atom, not condensed with other rings having no double bonds between ring members or between ring members and non-ring members
    • C07D309/08—Heterocyclic compounds containing six-membered rings having one oxygen atom as the only ring hetero atom, not condensed with other rings having no double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
    • C07D309/10—Oxygen atoms
    • C07D309/12—Oxygen atoms only hydrogen atoms and one oxygen atom directly attached to ring carbon atoms, e.g. tetrahydropyranyl ethers

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Abstract

<IMAGE> The compound of the formula /I/ is prepared by a./ reacting an alkyl /2,10-dimethyl-28-octacosanoate/ of the formula /II/, <IMAGE> wherein R represents a C1-5 alkyl group and Y stands for a tetrahydropyranyl or a 2-ethoxyethyl group, with a trialkylsilylmethyl lithium in an ether-type solvent, reacting the thus-obtained intermediate of the general formula /III/, <IMAGE> wherein R1, R2 and R3 each represent a C1-4 alkyl group with an aliphatic alcohol, treating the compound of the general formula /IV/ thus obtained, <IMAGE> wherein Y is as defined above, with an acid; or b./ reacting an alkyl /2,10-dimethyl-28-octacosanoate/ of the general formula /II/ with a solution of methylsulfinylmethyde in dimethylsulfoxide in an ether-type solvent, treating the compound thus obtained with a reducing agent, e.g. aluminium amalgam, treating the thus-obtained compound of the general formula /IV/ with an acid, and separating the compound of the formula /I/ thus obtained from the reaction mixture. The compound 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 29-hydroxy-3,1 1-dimethyl-2-nonacosanone The invention relates to a new process for the preparation of 29-hydroxy-3,1 1 -dimethyl-2-nonacosanone.
It is known that the 29-hydroxy-3,1 1 -dimethyl-2-nonacosanone of the formula/Il
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 environmental 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 may 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 pullulation 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. lshii: J. Chem. Ecol, 2, 449 /1976/; Agr. Biol. Chem. 40, 1407 /1976/] reported on the extraction of the pheromone of German cockroach. From cuticularwax of sexually mature females they isolated two components identified as 29-hydroxy-3,11 -dimethyl-2-nonacosanone of the formula /1/and 3,11 -dimethyl-2-nonacosanone of the formula IXII.
Both compounds elicit wing-raising and direction-turning response from the male adults. The compound of the formuía 111 proved to be more active.
Later Mori et al. [K. Mori, T. Suguro and S. Mashda: Tetrahedron 37, 1329/1981/] synthetized all ofthe possible stereoisomers of both pheromone components. The natural pheromones were shown to be of /3S, llS/ configuration.
The compound of the formula /1/was synthetized first by Nishida et al. [R. Nishida, T. Sato, Y. Kuwahara, H.
Fukami and S. Ishii: Agr. Biol. Chem. 40/7/, 1407/1976/]. They started with ethyl methylacetoacetate. The anion obtained in the reaction thereof with potassium tert.butylate was reacted with 1,6-dibromohexane.
The ethyl /8-bromo-2-acetyl-2-methyloctanoate/thus obtained was subjected to hydrolysis and subsequent decarboxylation to give 9-bromo-3-methyl-2-nonanone. This ketone was converted to its ethylene ketal, which was reacted with an anion obtained from ethyl acetoacetate. The ethyleneacetal of the ethyl /2-acetyl-9-methyl-1 0-oxoundecanoatel thus obtained was subjected to alkaline hydrolysis and subsequent decarboxylation. To the 3-methyl-2,1 1-dodecanedion-2-ethyleneacetal thus obtained 18tetrahydropyranyloxyoctadecyl magnesium bromide obtained from 1,1 8-dihydroxyoctadecane in 4 reaction steps was added.The ethyleneacetal of the 3,1 1-dimethyl-1 1-hydroxy-29-tetrahydropyranyloxy-2nonacosanone thus obtained was dehydrated and the resulting 3,1 1-dimethyl-29-hydroxy-1 1-nonacosen-2ol was subjected to catalytic hydrogenation to give the pheromone component of the formula 111.
According to the method of Burgstahler et al. [A. W. Burgstahler, L. O. Weigel, M. E. Sanders, C. G. Shaefer, W. J. Bell and S. B. Vuturo: J. Org. Chem. 42, 566/1977/] the benzyl ether of 4-bromo-1 -butanol was reacted with lithium acetylide in the presence of ethylenediamine. The lithium salt of the acetylene derivative thus obtained was alkylated with 1,1 2-dibromododecane. 1 -Bromo-1 8-benzyloxy-1 3-octadecyne was obtained, which was converted to the corresponding phosphorane. In the next step, a Wittig reaction was performed between the phosphorane and 9-bromo-2-nonanone. The bromo compound thus obtained was used to the alkylation of the anion obtained from 2-methylacetoacetate with sodium hydride.Subsequent catalytic hydrogenation gave 3,1 1-dimethyl-3-ethoxycarbonyl-29-hydroxy-2-nonacosanone which, when hydrolyzed and decarboxylated, afforded the desired compound of the formula 111.
Later Burgstahler et al. elaborated an improved method for the preparation of the compound of the formula /1/ [A.W. Burgstahler, M.E. Sanders, C.G. Shaefer and L.O. Weigel: Synthesis,405/1 977/]. They employed a phase-transfer methylation of benzyl acetoacetate using tetra-n-butylammonium hydrogen sulfate catalyst to give benzyl 2-methyl-3-oxobutanoate, followed by further alkylation with 26-benzyloxy-8 methyl-8-hexacosen-21 -ynyl bromide to produce benzyl /2-acetyl-2,1 0-dimethyl-28-benzyloxy-1 0-octacosen23-ynoate/. The latter compound was then subjected to catalytic reduction, and the 2-acetyl-2,1 0-dimethyl- 28-hydroxyoctacosanoic acid thus obtained was decarboxylated to produce the pheromone component of the formula 111.
Mori etal. [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 29-hydroxy-3,1 1 -dimethyl-2-nonacosanone of the formula/I/and and -dimethyl-2-nonacosanone of the formula /Xll. The key step of their synthesis is the coupling of a chiral tosylate - in case of the pheromone component of the formula /ilthe 5R- and SS-methyl-23-benzyloxy-8-tricosynyl tosylate, respectively - with a chiral Grignard reagent derived from 4R- and 4S-methyl-5-hexenyl bromide, respectively, in the presence of dilithium copper tetrachloride.In order to produce 4R-methyl-5-hexenyl bromide, one of the coupling components, 3R-7-dimethyl-6,7-epoxy-1 -heptene was oxidized with periodic acid to give the corresponding aldehyde, which was then reduced with lithium aluminium hydride. The 4R-methyl-5-hexanol thus obtained was converted into the corresponding tosylate, which 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 Nll 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.
Beside the thus-obtained 4R- and 4S-methyl-5-hexenyl bromide, S- and R-23-benzyloxy-5-methyltricos-8ynyl tosylate, respectively, were used as coupling components. To produce the R-tosylate, tetradecane-1,14diol was converted into the corresponding monobenzyl ether. Its tosylate was treated with lithium bromide to give 14-benzyloxytetradecanyl bromide. Halogen exchange with sodium iodide gave the corresponding iodide. This was used for the alkylation of R-citronellyl acetylene derived from R-/-/-citronellyl iodide. The alkylation product was epoxidized with m-chloroperbenzoic acid. Oxidation of the thus-obtained epoxide with periodic acid gave 4R-methyl-21 -benzyloxy-7-heneicosinal.One-carbon elongation of this aldehyde followed by reduction with lithium aluminium hydride gave 5R-methyl-23-benzyloxy-8-tricosinol, which was tosylated in the conventional manner.
To prepare S-23-benzyloxy-5-methyltricos-8-ynyl tosylate,7-formyl-5S-methylheptyl acetate was converted to an olefin by the Wittig reaction. Addition of bromide and subsequent elimination yielded /7-hydroxy-3S-methylheptyl/ acetylene, which was alkylated with 14-benzyloxytetradecanyl bromide. Acid treatment of the latter compound gave S-23-benzyloxy-5-methyltricos-8-ynol, which was converted into the desired tosylate.
To obtain all of the possible stereoisomers of the pheromone component of the formula 111, R- and S-23-benzyloxy-5-methyltricos-8-ynyl tosylate, respectively, was coupled with the Grignard reagent derived from R- and S-/-/-methylhex-5-enyl bromide, respectively.
In case of both pheromone components [formulae/l/ and /XI/] the compounds of /3S, 11Slconfiguration proved to be identical to 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 formula 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 compound of the formula 111, which can be more readily carried out also on an industrial scale.
According to the invention the 29-hydroxy-3,1 1-dimethyl-2-nonacosanone of the formula 111 is prepared from a new alkyl /2,1 0-dimethyl-28-octacosanoatel of the general formula/Ill,
wherein R represents a C15 alkyl group and Y stands for a tetrahydropyranyl or a 2-ethoxyethyl group, by a./ reacting an alkyl /2,1 0-dimethyl-28-octacosanoate/ of the formula/Ill with a triaikylsilylmethyl lithium in an ether-type solvent, preferably under cooling, reacting the thus-obtained intermediate of the general formula /III/,
wherein R1, R2 and R3 each represent a C14 alkyl group, preferably without isolation, with an aliphatic alcohol, treating the compound of the general formula IIVI thus obtained,
wherein Y is as defined above, with an acid; or b./ reacting an alkyl /2,10-dimethyl-28-octacosanoate/ of the general formula /II/, wherein R and Y are as defined above, with a solution of methylsulfinylmethyde in dimethylsulfoxide in an ether-type solvent, treating the compound thus obtained with a reducing agent, preferably aluminium amalgam, treating the thus-obtained compound of the general formula LIVY, wherein Y is as defined above, with an acid, and separating the compound of the formula Ill thus obtained from the reaction mixture.
According to variant a./ of the process according to the invention a compound of the general formula /II/ 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 /111/, it can be reacted in the reaction mixture where it has been formed with an aliphatic alcohol, preferably methanol. The protecting group of the thus-obtained compound of the general formula /IV/ can be removed by treatment with an acid /e.g. p-toluenesulfonic acid/.
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/Il/with methylsulfiny Imethyde 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 protecting group of the thus-obtained compound of the general formula /IV/ can be removed by treatment with an acid.
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 compounds of the general formula /II/ used as starting substances for the synthesis have not so far been described in the literature. For their preparation we have elaborated two methods. According to the first one lO-undecenic acid, a cheap commercial product, is reacted with an alkyl lithium, the dianion thus obtained is alkylated with methyl iodide, and the 2-methyl-1 0-undecenoic acid of the formula NI thus obtained
is converted into the corresponding ester. It is then converted with hydrogen peroxide, in the presence of catalytic amounts of a palladium salt, to a compound of the general formula Null,
wherein R is an alkyl group.The latter compound is then reacted with a phosphorane obtained from the phosphonium salt of the general formula Null/.
/C6H5/3P-CH2-/CH2/16-CH2-OY X- Null/ wherein X represents halogen and Y stands for a tetrahydropyranyl or a 2-ethoxyethyl group, with a strong base, preferably butyl lithium. The compound of the general formula /VIII/ thus obtained,
wherein R and Y have the above defined meanings, is subjected to catalytic reduction to obtain the compound of the general formula /II/.
According to our second method elaborated for the preparation of the compounds of the general formula Ill/an ester of 10-oxoundecanoic acid is reacted with a phosphorane derived from a phosphonium salt of the general formula /VII/. The thus-obtained compound of the general formula /IX,
wherein Y and R are as defined above, is subjected to catalytic reduction, and the compound of the general formula IXI thus obtained,
wherein Y and R are as defined above, is hydrolized into the corresponding carboxylic acid. The latter is converted into a dianion with a strong base, preferably methyl lithium. Subsequent reaction with methyl iodide affords the desired compound of the general formula /II/.
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 of29-hydroxy-3, 1 1-dimetnyi-2-nonacosanone /1/ a./ Preparation of 18-/24etrahydropyrany/oxy/-octadecanyl-triphenylphosphonium iodide Nll; X = I, Y=THP group/ as .13.0 g /0.01 mole/ 1 8-chlorooctadecanol are dissolved in 20 ml of anhydrous benzene, 1.0 g /0.012 mole, 1.1 ml/ of dihydropyran and 0.05 g of p-toluenesulfonic acid are added to the solution, and the reaction mixture is stirred at room temperature for 4 hours.Then it is diluted with ether, washed successively with 5 % sodium hydrogen carbonate solution, water and sodium chloride solution, dried over magnesium sulfate, the solvent is removed in vacuo and the residue is distilled.
Yield: 3.5 g /90 %/.
B.p.: 124-126"C/0.15 mm.
IR /film/: 1025,720 cm-1 .
aH-NMR/CDCI3/: 5 1.1S-2.0/38H, m, -CH2-/; 3.25-4.0/4H, m, -CH2-O/; 3.52/2H,t,J=7 Hz, -CH2-CI/; 4.57 /1 H, m, -O-CH-O/.
Analysis: C23H4502CI /389.067/ Calculated: C% = 71.00 H% = 11.66 CI% = 9.11 Found: C% = 71.21 H% = 11.51 Cl%=9.02 a2./ 1.95 g /0.005 mole/ 1 8-chlorooctadecanyltetrahydro-2-pyranyl ether are dissolved in 15 ml of methyl ethyl ketone, 1.12 g /0.0075 mole/ of porous sodium iodide are added to the solution and the mixture is boiled for 20 hours. Then it is cooled, the separated salt is filtered off and the filtrate is evaporated in vacuo.
The residue is taken up in ether, the ethereal solution is washed successively with water, 5 % sodium hydrogen sulfite solution and sodium chloride solution, dried over magnesium sulfate and evaporated in vacuo. The crude 1 8-iodooctadecanyltetrahydro-2-pyranyl ether is purified by chromatography /benzene- acetone 10:1/.
Yield: 1.9 g /90 %/.
TLC: Rf = 0.55/benzene-acetone 10:1/ IR /film/: 1025 cm~1.
1H-NMR/CDCI3/: 5 1.15-2.0/38H, m, -CH2-/; 3.05-4.0 /6H, m, -CH2O, -CH2-l/; 3,09/2H,t,J=6 Hz, -CH3-l/; 4.44/1 H, m, O-CH-O/.
Analysis: C23H45021 /480.518/ Calculated: C% = 57.49 H% = 9.44 1% = 26.41 Found: C% = 57.63 H% = 9.52 1% = 26.12 a3./2.4 g of 18-iodooctadecanyltetrahydro-2-pyranyl ether/0.005 mole/and 1.31 g /0.005 mole/of triphenylphosphine are boiled in 50 ml of anhydrous acetonitrile for 50-70 hours. Then the solvent is evaporated in vacuo. The residual honey-like product is decanted several times with ether, the solvent is removed in vacuo and dried.
Yield: 2.2 g /60 %/ of a stiffening oil.
IR/film/: 1590,1110,730,690cm-1.
1H-NMR /CDCI3/: 3 1.1-2.0 /38H, m, -CH2-/, 3.1-4.1 /6H, m, -CH2-O, -CH2-P/, 4.56/1 H, m, O-CH-O/, 7.5-8.2 5H, m, aromatic/ Analysis: C41H60O2PI /742.614/ Calculated: C% = 66.29 H% = 8.14 P% = 4.17 1% = 17.08 Found: C% = 66.41 H% = 8.25 P% = 4.06 1% = 16.91 b./ Preparation of methyl[2, 10-dimethyl-28-12-tetrahydropyranyloxyl-10-octacosenoatejlVIII; R = CH3, Y = THP groupl 7.4 g /10 mmoles/ of 1 8-/2-tetrahydropyranyloxy/-octadecanyltriphenylphosphonium iodide are dissolved in 60 ml of anhydrous tetrahydrofuran, the solution is cooled to 10 C and 10 mmoles oF butyl lithium /6.3 ml, 15 % hexane solution/ are added to it under inert gas while cooling.The cherry-red solution is stirred at the same temperature for 30 minutes, and a solution of 2.2 g /10 mmoles/ of methyl /2-methyl-1 0- oxoundecanoate/NI; R=CH3/ in 10 ml of anhydrous tetrahydrofuran are added to it within 30 minutes. The reaction mixture is stirred for further 5 hours at room temperature. Then it is quenched with 10% ammonium chloride solution, extracted with petroleum ether, the organic phase is washed successively with 5 % sodium hydrogen carbonate solution, water and sodium chloride solution, dried over magnesium sulfate and evaporated. About 3.5 g of crude product are obtained.
The crude product can also be isolated by diluting the reaction mixture with 100 ml of hexane and subjecting the solution to flash-chromatography using a short Kieselgel column. When evaporating the thus-obtained solution in vacuo, about 2-2.5 g of crude product are obtained. It can be purified by column chromatography /benzene-acetone 10:0.5/.
Yield: 1.2g/21 %/of colourless oil.
TLC: Rf = 0.6 IR /film/: 1735 /CO/, 1460, 1375, 1160, 1030 cm-'.
'H-NMR /CDCI3/: 3 1.0-1.8 /54H, m, CH2-, 2-CH3/, 1.8-2.1 /4H, m, -CH2-C=/, 2.3/1 H, m, CH-COO/, 3.25-4.1 /4H, m, -CH2O-/, 3.68/3H,s, CH300C/, 4.5-4.65 /1 H, m, O-CH-O/, 5.1 /1 H, m, -CH =/.
Analysis: C36H6804 /564.94/ Calculated: C% = 76.54 H% = 12.13 Found: C%=76.67 H%=11.95 c./ Preparation of methyl[2, 1O-dimethyl-28-/2-tetrahydropyrany/oxy/-octacosanoatej /II; R = CH3, Y=THP group/ 0.56 g /1 m mole/of methyl [2,1 0-dimethyl-28-/2-tetrahydropyranyloxy/-1 O-octacosenoate] is dissolved in 20 ml of anhydrous methanol, and the solution is added to 0.3 g of palladium on bone coal catalyst mixed in 10 ml of anhydrous methanol, under inert gas.
The reaction mixture is stirred at room temperature under hydrogen. The catalyst is filtered off and the filtrate is evaporated.
Yield: 0.53 g /96%/of colourless oil.
IR /film/: 1735/CO/, 1460 cm-1.
1H-NMR/CDCI3/: #0.82 /3H, d, J = 6Hz, 10-CH3/, 1.0-1.8/58H, m, -CH2-, 2-CH3/. 2.3 /1H, m, CH-COO/, 3.2-4.1 /4H, m, -CH20/, 3.65/3H, s, CH300C/, 4.5-4.65 /1H, m, O-CH-O/.
Analysis: C36H7004/566.958/ Calculated: C% = 76.26 H% = 12.44 Found: C% = 76.05 H% = 12.53 d./ Preparation of 1 1-dimethyl-29-/2-tetrahydropyrany/oxy/-2-nonacosanone /IV; Y=THP group/ To 10 ml of anhydrous ether 0.12 9/20 mmoles, 0.4 g/ of lithium dispersion in vaseline/containing 30 of lithium/ is added. 0.30 g /0.34 ml, 2.5 mmoles/ of trimethylsilymethylchloride is added to it under inert gas, and the mixture is boiled for 2.5 hours. Then it is cooled and allowed to settle. The residual lithium is separated from the trimethylsilylmethyl lithium solution by pressing the latter with inert gas into another flask.Then a solution of 0.5 g /1 mmolel of methyl [2,10-dimethyl-28-/2'-tetrahydropyranyloxy/] octacosanoate in 5 ml of anhydrous ether is added to the solution at 0 C. The reaction mixture is stirred at O "C for 2 hours, 2 ml of anhvdrous methanol are added to it under cooling, and the mixture is stirred at room temperature for 1.5 hours. It is quenched with water, extracted with ether, the ether solution is washed with ammonium chloride solution, water and sodium chloride solution, dried over magnesium sulfate and evaporated in vacuo. 0.5 g of crude product is obtained, which is purified by chromatography /benzene-acetone 10:0.2/.
Yield: 0.26 g /45%/of colourless oil.
IR /film/: 1705 /CO/, 1460, 1080, 1030 cm-1.
1H-NMR /CDCI3/: 8 0.82 /3H, d, J=6 Hz, 11 -CH2/, 1.05 /3H, d, J=7 Hz, 3-CH3/, 1.1-1.9 /55H, m, -CH2-/,2.05 /3H, s, CH3, CO/, 2.4/1 H, m, CHCO/,3.2-4.1 /4H, m, -CH2O/, 4.5-4.65/1 H, H, O-CH-O, m/.
Analysis: C36H7002 /550.95/ Calculated: C% = 78.48 H% = 12.80 Found: C% = 78.29 H% = 12.61 e./ Preparation of29-hydroxy-3, 1 l-dimethyl-2-nonacosanone /1/ 0.05 g of p-toluenesulfonic acid is dissolved in a mixture of 5 ml of methanol and 0.5 ml of water. 0.27 g /0.5 m mole/ of 3,11 -dimethyl-29-/2-tetrahydropyranyloxy/-2-nonacosanone /IV/ is added to the solution, and the reaction mixture is stirred at 60 C for 4 hours.Then it is cooled, the solvent is removed in vacuo, the residue is taken up in ether, washed successfully with 5 % sodium hydrogen carbonate solution, water and sodium chloride solution, dried over magnesium sulfate, and the solvent is removed in vacuo. 0.22 g of crude product is obtained /m.p.: 34-38 C/. It can be recrystallized from petroleum ether at 1-20/ - 1-30/ C.
Yield: 0.2 g /80 %I.
M.p.: 41-42 C [in the literature: 41-43 "C, A.W. Burgstahler et al., J. Org. Chem. 42,566/1977/].
IR/filml: 3350 /OH/,1715 1715/COl, 1040 cm-1.
1H-NMR /CDCI3/: #0.82 /3H, d, J=6 Hz, 11 -CH3/,1.04/3H, d, J=7 Hz, 3-CH3/, 1 .1-1.6/49H, m, -CH2-/, 2.01 /3H, s, CH3CO/, 2.34/1 H, m, CH-CO/, 3.52 /2H, t, J =6 Hz, -CH2O/.
Analysis: C31Hs202 /466.84/ Calculated: C% = 79.76 H% = 13.39 Found: C% = 79.62 H% = 13.61 EXAMPLE 2 Preparation of 29-hydroxy-3, 1 l-dimethyl-2-nonacosanone a.l Preparation of methyl 10-methyl-28-2-tetrahydropyrany/oxy/-10-octacosenoate]/IX; R = CH3, Y=THP groupl 7.4 g /10 mmoles/ of 18-/2-tetrahydropyranyloxy/-octadecanylphosphonium iodide VII; X=l, Y=THP group/ are dissolved in 60 ml of anhydrous tetrahydrofuran. The solution is cooled to 10 C, and 10 mmoles of butyl lithium /6.3 my, 15% hexane solution/ are added to it under argon, while stirring.The mixture is stirred at room temperature for 30 minutes, and a solution of 2.1 g /10 mmoles/ of methyl-/ 1 0-oxoundecanoatel in 10 ml of anhydrous tetrahydrofuran is added to it at 10 C within 30 minutes. The reaction mixture is stirred at room temperature for 5 hours, poured into 10% ammonium chloride solution and extracted with hexane. The hexane solution is washed successively with 5% sodium hydrogen carbonate solution, water and saturated sodium chloride solution, dried over magnesium sulfate and the solvent is distilled off. The residual product is purified by column chromatography.
Yield: 1.1 g/20%/oflight-coloured oil.
TLC: Rf = 0.58/benzene-acetone 10:0.5/ IR /film/: 1735 /CO/, 1460, 1375, 1160, 1030 cm~5.
1H-NMR /CDCl3/: 8 1.1-1.8/51 H, m, -CH2-/, 1.8-2.1 /4H, m, -CH2-C=/,2.28 /2H, t, J=8 Hz, -CH2-COO/, 3.25-4.1 /4H, m, -CH2-O/, 3.68 /3H, s, CH3OO0/, 4.5-4.65/1 H, H, m, O-CH-O/, 5.1/1 H, H, m, -CH=/.
Analysis: C35H6604 /550.91/ Calculated: C% = 76.30 H% = 12.07 Found: C% = 76.18 H% = 12.21 b./ Preparation of methyl [10-methyl-28-12-tetrahydropyranyloxyl-octacosanoatel IX; R = CH3, Y = TH P groupl A solution of 0.55 g /1 mmolel of methyl [1 0-methyl-28-/2-tetrahydropyranyloxy/-1 0-octacosenoate] in 20 ml of anhydrous methanol is hydrogenated over 0.3 g of palladium on bone coal catalyst. When the theoretic amount of hydrogen has been taken up /3 hours, 24 mIl, the catalyst is filtered off, washed with methanol, the methanol solutions are combined and evaporated in vacuo.
Yield: 0.52 g /95 %l IR /film/: 1735 /CO/, 1460, 1380, 1260, 1075, 1030 cm-'.
'H-NMR /CDCl3/: 8 0.8213H, d, J=8 Hz, 11 -CH3/, 1.0-1.9/55H, m, -OH2-/, 2.3 /2H, t, J=7 Hz, -CH2-COO/, 3.2-4.1/4, m, -CH20/, 3.65 /3H, s, CH300C/, 4.5-4.65 /1 H, m, O-CH-O/.
Analysis: C35H6804 /552.93/ Calculated: C% = 76.02 H% = 12.39 Found: C% = 75.88 H% = 12.53 c./ Preparation of 10-methyl-28-12-tetrahydropyranyloxyl-octacosanoic acid IX; R = H, Y = THP group/ A mixture of 0.55 g /1 mmole/ of methyl [1 0-methyl-28-/2-tetrahydropyranyloxy/-cotacosanoate] and 10 ml of 1N sodium hydroxide solution is stirred at room temperature for 6 hours. Then it is poured into 12 ml of 1 N hydrogen chloride solution, extracted with ethyl acetate, the organic phase is washed successively with water and sodium chloride solution, dried over magnesium sulfate and evaporated in vacuo. The residual stiffening product can be used for the further reaction steps without purification.
Yield: 0.45 g /83 %/.
IR /film/: 1715 /CO/, 1460, 1380, 1200, 1080, 1030 cm-7.
1H-NMR /CDCI3/: #0.82 0.8213H, d, J=8 Hz, 11 -CH3/, 1.0-1.9 /55H, m, -CH2/, 2.3 12H, t, J=7 Hz, -CH3-OOO/, 3.2-4.1 /4H, m, -CH20/, 4.5-4.65 /1H, m, O-OH-OI.
d./ Preparation of methyl[2,10-dimethy/-28|2-tetrahydropyrany/oxy/-octacosanoate]II; R = CH3, Y = THP group/ 0.31 g /3 mmolesl of 0.43 ml/ of diisopropylamine and 1.9 ml /3 mmoles/ of 15 % hexane buthyl lithium solution are measured to 10 ml of anhydrous tetrahydrofuran under inert gas. A solution of 0.54 g/1 mmolel of 10-methyl-28-12-tetrahydropyranyloxyl-octacosanoic acid in 3 ml of hexamethylphosphoramide is added to the reaction mixture at O C, and it is stirred at a temperature between 0 "C and 5 "C for 20 minutes. The mixture is allowed to warm up to room temperature, 0.17 g /1.1 mmole, 0.08 ml/ of methyl iodide is added to it, and the reaction mixture is stirred for 2 hours. Then it is quenched by pouring it into 10% ammonium chloride solution and extracted with ethyl acetate. The organic phase is washed successively with ammonium chloride solution, water and brine, dried over magnesium sulfate and evaporated in vacuo, 0.4 g of crude acid is obtained, which is esterified with diazomethane, and the thus-obtained ester is purified by chromatography Ibenzene-acetone 10:0.5/.
0.35 g /65%/of colourless oily product is obtained, which is identical with the product obtained according to Example 1/c. It can be converted into the pheromone component of the formula /1/ in the way described in Example 1.

Claims (7)

1. A process for the preparation of 29-hydroxy-3,1 1 -dimethyl-2-nonacosanone of the formula 111,
characterized by a./ reacting an alkyl /2,1 O-dimethyl-28-octacosanoate/ of the formula II II,
wherein R represents a Ois alkyl group and Y stands for a tetrahydropyranyl or a 2-ethoxyethyl group, with a trialkylsilymethyl lithium in an ether-type solvent, preferably under cooling, reacting the thus-obtained intermediate of the general formula /III/,
wherein R1, R2 and R3 each represent a Oi4 alkyl group, preferably without isolation, with an aliphatic alcohol, treating the compound of the general formula IlVlthus obtained,
wherein Y is as defined above, with an acid; or b./ reacting an alkyl /2,1 0-dimethyl-28-octacosanoate/ of the general formula /II/, wherein R and Y are as defined above, with a solution of methylsulfinylmethyde in dimethylsulfoxide in an ether-type solvent, treating the compound thus obtained with a reducing agent, preferably aluminium amalgam, treating the thus-obtained compound of the general formula IIVI, wherein Y is as defined above, with an acid, and separating the compound of the formula /thus obtained from the reaction mixture.
2. A process according to variant a./ of claim 1, characterized by using as trialkylsilylmethyl lithium trimethylsilylmethyl lithium.
3. A process according to variant a./ of claim 1, characterized by using methanol as aliphatic alcohol.
4. A process according to variant b./ of claim 1, characterized by using p-toluenesulfonic acid as acid.
5. Compounds of the general formula/Ill, wherein Rand Y are as defined in claim 1.
6. A process as claimed in claim 1 substantially as hereinbefore described in Example 1.
7. 29-hydroxy-3,1 1 -dimethyl-2-nonacosanone of the formula (I) when produced by a process as claimed in any one of claims 1 to 4 or 6.
GB08416630A 1983-07-01 1984-06-29 Process for the preparation of the pheromone of 29-hydroxy-3,11-dimethyl-2-nonacosanone Expired GB2142633B (en)

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
HU832389A HU193540B (en) 1983-07-01 1983-07-01 Process for production of 29-hydroxi-3,11-dimethil-2-nonakozanons

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GB8416630D0 GB8416630D0 (en) 1984-08-01
GB2142633A true GB2142633A (en) 1985-01-23
GB2142633B GB2142633B (en) 1986-10-01

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JP (1) JPS6051143A (en)
CS (1) CS247084B2 (en)
DD (1) DD217800A5 (en)
DE (1) DE3424270A1 (en)
FR (1) FR2548178B1 (en)
GB (1) GB2142633B (en)
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IT8421696A1 (en) 1985-12-29
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FR2548178A1 (en) 1985-01-04
HUT35626A (en) 1985-07-29
PL248480A1 (en) 1985-09-24
GB8416630D0 (en) 1984-08-01
DD217800A5 (en) 1985-01-23
FR2548178B1 (en) 1987-03-06
JPS6051143A (en) 1985-03-22
GB2142633B (en) 1986-10-01
CS247084B2 (en) 1986-11-13
DE3424270A1 (en) 1985-01-03
HU193540B (en) 1987-10-28

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