FR2548178A1 - PROCESS FOR THE PREPARATION OF 29-HYDROXY-3,11-DIMETHYL-2-NONACOSANONE - Google Patents

Abstract

THE PRESENT INVENTION RELATES TO A NEW PROCESS FOR THE PREPARATION OF 29-HYDROXY-3,11-DIMETHYL-2-NONACOSANONE OF GENERAL FORMULA (I) BELOW: (CF DRAWING IN BOPI) WE OBTAIN THE PRODUCT (1) BY REACTING AN ALKYL 2,10-DIMETHYL-28-OCTACOSANOATE WITH A TRIALCOYLSILYLMETHYL LITHIUM TO OBTAIN AN INTERMEDIATE OF GENERAL FORMULA (III) FOLLOWING: (CF DRAWING IN BOPI) THEN PROCESSING THIS INTERMEDIATE PRODUCT. APPLICATION AS PHEROMONES.

Description

The present invention relates to a novel process for the preparation of

  29-hydroxy-3,11-dimethyl2-nonacosanone.

  It is known that 29-hydroxy-3,11-dimethyl-2-nona-cosanone represented by formula (I) below:

  HO-CH 2 (CH 2) 17-CH- (CH 2) 7 -CH-C-CH 3 (I)

He

CH 3 CH 3

  exerts a significant power-boosting reaction on

  the male cockroach (Blatella Germanica).

  The German Cockroach is an unpleasant pest haunting residential and industrial buildings Old, poorly maintained public utility buildings provide ideal hiding places for various species of insects.

  crawling especially for the cockroach difficult to exterminate.

  It has a short breeding season, so it spreads rapidly and also appears in the new cities. In addition to the aesthetic points of view that motivate the eradication of this pest, the direct damage caused by it is also considerable.

  it can spread viral infections.

  Men have been trying to eradicate this cockroach 25 for centuries Lately, highly toxic pesticides have been developed for cockroaches, but they often pose environmental hazards when used in effective concentrations On the other hand, effective eradication can only be expected by repeated application of toxic chemicals

  because the rapid reproduction of some surviving pests can reinfect the area in a short time.

  It is therefore advantageous to use pheromone-containing pieces to combat this pest because of the difficulties mentioned above. Traps baited with the pheromone of this pest are not toxic to higher animals and humans. trap pests that have survived eradication with chemical toxicants, so that pest outbreak can be prevented.

  Nishida et al. 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 Ishil: J Chem Ecol 2, 449 (1976); Agr Biol. Chem 40, 1407 (1976) 1 have studied the pheromone extraction from the German cockroach. They have isolated, from cuticular wax of sexually mature females, two components identified as 29-hydroxy-3,11- dimethyl2-nonacosanone represented by formula (I) and 3,1115 dimuthyl-2-nonacosanone represented by formula (XI) below: O il

  CH 3 (CH 2 17-CH- (CH 2) 7 -CH-C-CH 3 (XI

CH 3 CH 3

  These two compounds cause in adult males a

  response of change of direction and elevation of the wings.

  The compound of formula (I) proves to be the most active.

  Then Mori et al. Mori, T SUGURO and S Mashada: Tetrahedron 37, 1329 (1981); have synthesized all possible stereoisomers of the two components of the pheromone It has been shown that natural pheromones

  offer a configuration (3 S, 115).

  The compound of formula (I) was first synthesized by Nishida et al. Nishida, T Sato, Y Kuwahara, B Fukami and S Ishii: Arg Biol Chem 40 (7), 1407 (1976). The anion obtained in the reaction thereof is reacted with potassium tert-butoxide, with 1,6-dibromohexane, and 8-bromo-2-acetyl-2-methyloctanoate. The resulting ethyl is subjected to hydrolysis and subsequent decarboxylation to give 9-bromo-3-methyl-2-nonanone. This ketone is converted to its ethylene ketal, which is treated with an anion obtained from acetoacetate. ethyl Ethyl acetal of ethyl 2-acetyl-9-methyl-10-oxoundecanoate thus obtained, is subjected to alkaline hydrolysis and subsequent decarboxylation 3-methyl-2,11dodecanedion-2-ethyleneacétal thus prepared and supplemented with 18 tetrahydropyranyloxy -octadecyl magnesium obtained from 1,18dihydroxyoactadecane 10 during 4 Reaction Steps Ethyleneacetal of 3,11-dimethyl-11-hydroxy-29-tetrahydropyranyloxy-2-nonacosanone thus obtained is dehydrated and the resulting 3,11-dimethyl-29-hydroxy-11-nonacosen-2-ol is subjected to a catalytic hydrogenation for

  provide the component of formula (I) of the pheromone.

  According to the method of Burgstahler et al.

  Burgstahler, LO Weigel, ME Sanders, CG Shaefer, WJ Bell and SB Vuturo: J Org Chem 42, 566 (1977) 1, the 4-bromo-1-butanol benzyl ether is reacted with Lithium acetylide in the presence of ethylenediamine The lithic salt of the acetylene derivative thus obtained is alkylated with 1,12-dibromododecane. Thus, 1-bromo-1,8-benzyloxy-13-octadecyl is obtained which is converted to the corresponding phosphorane in the form of the The next step is a Wittig reaction between phosphorane and 9-bromo-2-nonanone. The brominated compound thus obtained is used for the alkylation of the anion obtained from 2-methylacetoacetate and sodium hydride. Subsequent catalytic hydrogenation provides 3,11-dimethyl-3-ethoxycarbonyl-29-hydroxy-2-nonacosanone which

  gives the desired compound of formula (I), after hydrolysis and decarboxylation.

  Next, Burgstahler et al developed an improved method for preparing the compound of formula (I) LA W; Burgstahler, ME Sanders, CG Shaefer, and O. Weigel: Synthesis, 405 (1977). They perform methylation with phase transfer of benzyl acetoacetate, with tetra-n-butylammonium acid sulfate as catalyst for benzyl 2-methyl-3-oxo-butanoate, followed by additional alkylation with 26-benzyloxy-8-methyl-8hexacosen-21-ynyl bromide to produce 5 -2-acetyl-2,10- The latter compound is then subjected to a catalytic reduction and the 2-acetyl-2,10-dimethyl-28-hydroxyoctacosanoic acid thus obtained, is decarboxylated to give a benzene-2-acetyl-2,10-dimethyl-28-hydroxyoctacosanoic acid.

  produce the component of formula (I) of the pheromone.

  Mori et al K Mori, S Mosuda, T. Sugara: Tetrahedron Letters, 3444 (1978); Tetrahedron, 37, 1329 (1981) 1 have published a method for the stereocontrolled zynthesis of all possible stereoisomers of 29-hydroxy-3,11-dimethyl-2-nonacosanone of formula (I) and 3,11-dimethyl-2-nonacosanone. The key step of their synthesis is the coupling of a chiral tosylate which is, in the case of the component of formula (I), pheromone, the 5 R 5 methyl and 5 23benzyloxy-8-tricosynyl respectively with a chiral reagent from Grignard

  derived from 4 R bromide and 4 S-methyl-5-hexenyl respectively, in the presence of copper-dilithium tetrachloride.

  To produce R-methyl-5-hexenyl bromide, which is one of the coupling components, R-7-dimethyl-6,7-epoxy-1-heptene is oxidized with periodic acid to give The corresponding aldehyde, which is then reduced with lithic alumino hydride. The 4 R-methyl-5-hexanol thus obtained is converted into the corresponding toxoxide, which is treated with lithium bromide in acetone to prepare the antipose of the thus obtained compound, the 7-phenyl-4-methyl-hexanoic ester is reacted with chromium (VI) oxide to form the half-ester. Its silver salt is subjected to a Hunsdiecker reaction for Methyl 4-methyl-6-bromohexanoate This is treated with onitroselenophenol, the selenyl group of the compound thus obtained is removed by oxidative removal and the olefinic acid and

25481 78

  obtained is reduced with alumino-lithic hydride to give the corresponding alcohol, of which the toxylate is converted

  in 4-S-methyl-5-hexenyl bromide according to a conventional method.

  In addition to the 4 R- and 4-S-methyl-5-hexenyl bromides thus obtained, the coupling components used are the S- and R-23-benzyloxy-5-methyltricos-8-ynyl toxoxates respectively to produce the R-toxylate. It converts tetradecane-1,14-diol to the corresponding monobenzyl ether. Its tosylate is treated with lithium bromide to give 14-benzyloxytetradecanyl bromide. A halogen exchange with sodium iodide provides the corresponding iodide. for the alkylation of R-citronellyl acetylene derived from R - (-) citronel lyle iodide The alkylation product is epoxidized with mchloroperbenzoic acid Oxidation of the epoxide thus obtained with periodic acid provides the 4-R-methyl-21-benzyloxy-7-henicosino The elongation of a carbon of this aldehyde, followed by reduction with alumino-alicillium hydride, gives 5 R-methyl-23-benzyloxy-8- tricosinol, which is toxic according to

a classic method.

  To prepare S-23-benzyloxy-5-methyltricos-8-ynyl tosylate, 7-formyl 5 S-methylheptyl acetate is converted to an olefin by a Wittag reaction. The addition of bromine and subsequent removal provide (7) -hydroxy-3-S-methylheptyl) acetylene which is alkylated with 14-benzyloxytetradecantl bromide.

  acid of the last compound gives S-23-benzyloxy-5-methyltricos-8-ynyl, which is converted to the desired tosylate.

  To obtain all the possible stereoisomers of the component of formula (I) of the pheromone, the tosylate of R and S-23-benzyloxy-5-methyltricos-8-ynyl are coupled, respectively, with the Grignard reagent derived from bromide.

  R and S - (-) - methyl-hex-5-enyl respectively.

  In the case of the two components of the pheromone (formula (I) and (XI), it turns out that the components having a configuration 3 S, 11 S are identical to the natural sexual bait of the pest The authors do not have found significant difference between the biological activities of the different stereoisomers.The known methods for preparing the pheromone component of formula (I) are neither favorable nor economically valid because they require a

  a large number of painful reaction steps and expensive reagents.

  The present invention aims to provide a more economical process for the preparation of the compound of formula (I), which can be more easily achieved also

on an industrial scale.

  According to the present invention, the 29-hydroxy-3,11-dimethyl-2-nonacosanone of formula (I) is prepared from a new alkyl 2,10-dimethyl-28-octacosanoate represented by the general formula (II) ci -after:

  YO-CH 2 (CH 2) 16-CH 2 -CH- (CH 2) -CH-CO (I)

CH 3 CH 3

  wherein R is C 1 -C 15 alkyl and Y is tetrhydropyranyl or 2-ethoxyethyl, a) reacting an alkyl 2,10-dimethyl-28-octacosanoate of formula (II) with a trialkylsilylmethyl lithium in a solvent, of ether type, preferably by cooling, treating the intermediate thus obtained represented by the following general formula (III): ## STR2 ## -C-CH 2 -Si-R 2 (III)

CH 3 CH 3 R 3

  in which R 1, R 2 and R 3 each represent a C 1 -C 4 alkyl group, preferably without the isolate, with an aliphatic alcohol, by treating the compound of general formula (IV) below thus obtained,

YO-CH 2- (CH 2) 17-CH- (CHC-CH (IV)

CH 3 CH 3

  o Y is as defined above, with an acid; or else b) by reacting an alkyl 2,10-dimethyl-28-octacosanoate of formula (II), where R and Y are as defined above, with a solution of methylsulphinylmethide in dimethylsulfoxide in a solvent of the type ether, treating the compound thus obtained with a reducing agent, preferably an amalgam of aluminum by treating with an acid the compound thus obtained of general formula (IV), where Y is as defined above, and separating the composed of

  formula (I) thus obtained from the reaction mixture.

  According to variant (a) of the process of the present invention, a compound of the general formula (II) is reacted with a trialkylsilylmethyl lithium in an ether solvent, preferably with cooling. It is not necessary to isolate the intermediate of general formula (III), thus obtained, it can be reacted in the reaction mixture in which it was formed, with an aliphatic alcohol and preferably methanol The protective group of the compound thus obtained of general formula (IV)

  can be removed by acid treatment (e.g., p-toluene sulfonic acid).

  According to variant (b) of the process according to the present invention, a compound of general formula (II) is reacted with a solution of methylsulfinylmethide in dimethylsulfoxide. Methylsulfinylmethide can be prepared from dimethylsulfoxide with a strong base, preferably sodium hydride at a temperature below 70 ° C. It is not necessary to isolate the intermediate obtained in the reaction of the compound of formula (II) with methylsulphinylmethyl, the reduction of which can be carried out The reduction is preferably carried out with an amalgam of aluminum derived from aluminum and mercuric chloride by a conventional method. The protecting group in which it has been formed.

  of the thus obtained compound of the general formula (IV) can be removed by treatment with an acid.

  The compound of formula (I) obtained in the reaction can be separated from the reaction mixture by methods

  known (for example, distillation, chromatography).

  The compounds of the general formula (II) used as starting materials for the synthesis have not been described in the literature so far. The applicant has developed two methods for their preparation. In accordance with the first one, an acid is reacted. -undecenic, which is an inexpensive industrial product, with an alkyl lithium, the dianion thus obtained is alkylated with methyl iodide and 2-methyl-10-undecenoic acid of formula (V) is converted into the corresponding ester; thus obtained,

CH 2 -CH (CH 2) 7 1 HCOOR (V)

CH 3

  The ester is then converted with hydrogen peroxide, in the presence of catalytic amounts of a palladium salt, to a compound represented by the following general formula (VI):

CH-CH (CH 2) 7-CH-COOR (VI)

3 7 Hcoo R

O CH 3

  This latter compound is then treated with a phosphorane to be released from the phosphonium salt of general formula (VII) below:

  (C 6 H 5) 3 P -CH 2 - (CH 2) 16 -CH 2 -OYX (VII)

  in which X represents a halogen atom and Y is a tetrahydropyranyl or 2-ethoxyethyl group, with a strong base, preferably butyl lithium. The compound thus obtained, represented by the general formula (VIII) below,

  YO-CH 2 (CH 2) 16-CH = C- (CH 2) 7 -CH-COOR (VIII)

1 O 1

CH 3 CH

3 3

  wherein R and Y are as defined above, is subjected to catalytic reduction to obtain the

general formula (II).

  According to the second method of the Applicant, prepared for the preparation of the compounds of general formula (II), an O-oxoundecanoic acid ester is reacted with a phosphorane salt derivative of phosphonium salt of general formula (VII) The compound thus obtained represented by the following general formula (IX), YO-CH 2 (CH 2) 16 -CH = C (CH 2) 8 COOR (IX) CH 3 O Y and R are as defined above. is subjected to a catalytic reduction and the compound thus obtained represented by the general formula (X) below,

  YO-CH 2- (CH 2) 17-CH- (CH 2) 8-COOR (X)

  CH 3 O Y and R are as defined above, is hydrolysed to the corresponding carboxylic acid The latter is converted to dianion with a strong base, preferably methyl lithium A subsequent reaction with methyl iodide

  provides the desired compound of general formula (II).

  The trialkylsilylmethyl lithium used for variant a) of the process according to the present invention is prepared from a trialkylsilylmethyl halide.

and lithium metal.

  In addition to the foregoing, the invention

  further comprises other provisions, which will emerge from the description which follows.

  The invention will be better understood with the aid of the additional description which follows, which refers to

  examples of implementation of the method which is the subject of the present invention.

  It should be understood, however, that these examples of implementation are given solely by way of illustration of the subject of the invention, of which they in no way constitute a limitation. EXAMPLE 1 Preparation of 29-hydroxy-3,11-dimethyl-2nonacosanone (I)

  a) Preparation of 18- (2-tetrahydropyranyloxy) octadecanyltriphenylphosphonium iodide (VII, X = I, Y = THP).

  18 g (0.01 l mole) of 18-chlorooctadecanol are dissolved in 20 ml of anhydrous benzene, 1.0 g (0.012 mole, 1.1 sl) of dihydropyran and 0.05 g of acid. p-toluenesulfonic acid are added to the solution and the reaction mixture is stirred at ambient temperature for 4 hours. It is then diluted with ether, washed successively with a 5% solution of sodium hydrogen carbonate, water and a solution of sodium chloride, dried over magnesium sulfate; the solvent is removed under vacuum and the residue

is distilled.

Yield: 3.5 g (90%).

mp: 124-126 ° C / 0.15 min.

  IR (film): 1025.720 cm H-RUN (CDCl 3): δ 1.15-2.0 (38H, m, -CH 2 O); 3.25-4.0 (4H, m,

  -CH 2-O); 3.52 (2H, t, J = 7Hz, -CH 2-C 1); 34.57% H -O-CH 2 O).

4.57 (1H, m, -O-CH-O).

  Analysis: C 23 H 4502 C 1 (389.067) Values calculated: C% = 71.00 H% = 11, 66 C 1% = 9.11 Found values: C% = 71.21 H% = 11.51 C 1 % = 9.02 to 2.95 g (0.005 mole) of 18-chlorooctadecanyltetrahydro-2-pyranyl ether is dissolved in 15 ml of methyl ethyl ketone, 1.12 g (0.0075 mole) of sodium iodide. Porous is added to the solution and the mixture is heated to boiling for 20 hours. The mixture is then cooled, the salt which has separated off is filtered and the filtrate is evaporated under vacuum. The residue is taken up in ether, the solution ether is washed successively with water, a 5% solution of sodium hydrogen sulphite and a solution of

  The crude 18-iodooctadecanyltetrahydro-2-pyranyl ether is purified by chromatography (benzeneacetone 10: 1).

Yield: 1.9 g (90%).

  TLC: Rf = 0.55 (10: 1 benzene-acetone) IR (film): 1025 cm -1 H-NMR (CDCl3): 6 1.1 L 5-2.0 (38H, m, -CH 2-); 3.05-4.0 (6H, m, -CH 2 O, -CH 2-I); 3.09 (2H, t, J = 6Hz,

  -CH 3-I); 4.44 (1H, m, 0-CH-O). Analysis: C H 23,450 (480.518).

23 45 2

  Calculated values: C% = 57.49 H% = 9.44 I% = 26.41 Found values: C% = 57.63 H% = 9.52 I% = 26.12 to 3 * 2.4 g Iodine-dioctadecanyltetrahydro-2-pyranyl ether (0.005 moles) and 1.31 g (0.005 moles) of triphenylphosphine are boiled in 50 ml of anhydrous acetonitrile for 50 to 70 hours. The solvent is

  Then evaporated in vacuo The residual honey-like product is decanted several times with ether, stripped of the solvent in vacuo and dried.

2548178 '

  Yield: 2.2 g (60%) of an oil solidifying.

  IR (film): 1590, 1110, 730, 690 cm -1 H NMR (CDCl3): δ1.1-2.0 (38H, m, -CH2), 3.1-4.1 (6H NMR (CDCl3):? H, m, -CH 2 -O, -CH 2 -P), 4.56 (1H, m, O-CH-O), 7.58.2 (15H, m, aromatic) C 41 H analysis 6002 Pl (742.614)

  Calculated: C% = 66.29 H% = 8.14 P% '= 4.17 I% = 17.08 Values found: C% = 66.41 H% = 8.25 P% = 4.06 I % = 16.91 b) Preparation of 2,10-dimethyl-28- (2-tetrahydropyranyl D).

  methyl octocosenoate (VIII; R = CH 3, Y = THP group> 7.4 g (10 mmol) of 18- (2-tetrahydropyranyloxy) octadecanyltriphenylphosphonium iodide are dissolved in ml of anhydrous tetrahydrofuran, the solution is cooled; at 10 ° C. and 10 mmol of butyl lithium (6.3 ml, hexane solution at 15%) are added under an inert gas atmosphere and cooling. The cherry-red solution is stirred at the same temperature for 30 minutes and a solution of 2, 2 g (10 mmol) of methyl 2-methyl-10-oxoundecanoate (VI; R = CH 3) in 10 ml of anhydrous tetrahydrofuran is added over a period of 30 minutes. The reaction mixture is stirred for a further 5 hours at room temperature. Then, it is quenched with a 10% solution of ammonium chloride, extracted with petroleum ether, the organic phase is washed successively with a 5% solution of sodium hydrogen carbonate, water and a solution of sodium chloride, on magnesium sulphate

  and evaporated. About 3.5 g of crude product are collected.

  The crude product can also be isolated by diluting the reaction mixture with 100 ml of hexane and subjecting the solution to flash chromatography with a short Kieselgel column. When the solution thus obtained is evaporated under vacuum, about 2-2.5 g of

  crude product This can be purified by column chromatography (benzene-acetone 10: 0.5).

  Yield: 1.2 g (21%) of colorless oil.

  TLC: Rf = 0.6 -1 IR (film): 1735 (CO), 1460, 1375, 1160, 1030 cm

  H-NMR (CD C 13): 1.0-1.8 (54H, m, CH 2, 2-CH 3), 1.8-2.1 (4H, m, CH 2 -C) =), 2.3 (1H, m CH-COO), 3.25-4.1 (4H, m, -CH 2 O-), 3.68 (3H, s, CH 300 C), 4.5-4.65 (1H, m, 0-CH-O), 5.1 (1H, m, -CH =).

  Analysis: C 36 H 6804 (564.94) Calculated: C% = 76.54H% = 12.13 Found: C% = 76.67H% = 11.95 c) Preparation of 2, 10-dimethyl Methyl 28- (2-tetrahydropyranyloxy) -octacosanoate (II; R = CH 3, Y = THP). 0.56 g (1 mmol) of methyl 2,10-dimethyl-28- (2-tetrahydropyranyloxy) -10-octacosenoate is dissolved in 20 ml of anhydrous methanol and the solution is added to 0.3 g of palladium on charcoal. of bone as a catalyst

  mixed in 10 ml of anhydrous methanol under an inert gas atmosphere.

  The reaction mixture is stirred at room temperature under hydrogen. The catalyst is separated by

  filtration and the filtrate is evaporated.

  Yield: 0.53 g (96%) of colorless oil.

  -1 IR (film): 1735 (CO), 1460 cm H-NMR (CDCl 3): δ 0.82 (3H, d, J = 6 Hz, 10-CH 3), 1.0-1.8 (58H, m, -CH 2-, 2-CH 3), 2.3 (1H, m, CH-COO), 3.2-4.1 (4H, m, -CH 2 O), 3.65 (3 hours, 30 minutes

  s, CH 300 C), 4.5-4.65 (1H, m, O-CH-O).

Analysis: C 36 H 7004 (566.958)

Y 36 70 4 ('5)

  Calculated values: C% = 76.26 H% = 12.44 Found values: C% = 76.05 H% = 12.53

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  d) Preparation of 3,1-dimethyl-29- (2-tetrahydropyranyloxy) -2-nonacosanone (IV, Y = THP).

  1 ml of anhydrous ether are added with 0.12 g (20 mmol, 0.4 g) of lithium dispersion in petrolatum, containing 30% of lithium. 0.30 g (0.34 ml, 2.5 ml) is added thereto. mmol) of trimethylsilylmethyl chloride under an inert gas atmosphere and the mixture is boiled for 2.5 hours Then cooled and allowed to settle The residual lithium is separated from the trimethylsilylmethyl lithium solution by introduction of the In another flask under the pressure of an inert gas A solution of 0.5 g (1 mmol) of 2,10-dimethyl-28- (2'-tetrahydropyranyloxy) octacosanoate is then added to the OC solution. of methyl in 5 ml of anhydrous ether. The reaction mixture is stirred at 0 ° C. for 2 hours, 2 ml of anhydrous methanol are added under cooling and the mixture is stirred at room temperature for 1.5 hours. It is quenched with water and extracted with ether. the ethereal 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. we purify

  by chromatography (benzene-acetone 10: 0.2).

  Yield: 0.26 g (45%) of colorless oil.

  -1 IR (film): 1705 (CO), 1460, 1080, 1030 cm, ¹-NMR (CDCl 13): δ 0.82 (3H, d, J = 6Hz, 11-CH 2), 1, 05 (3H, d, J = 7Hz, 3-CH 3), 1.1-1.9 (55H, m, -CH 2-), 2.05 (3H, s, CH 3, CO ), 2.4 (1H, m, CHCO), 3.2-4.1 (4H, m, -CH 2 O), 4.5-4.65 (1H, O-CH-O) , m).

Analysis: C 36 H 7002 (550.95).

  Calculated values: C% = 78.48 H% = 12.80 Found: C% = 78.29 H% = 12.61 e) Preparation of 29-hydroxy-3,11-dimethyl-2nonacosanone (I) dissolve 0.05 g of p-toluenesulfonic acid

  in a mixture of 5 ml of methanol and 0.5 ml of water.

  0.27 g (0.5 mole) of 3,11-dimethyl-29- (2-tetrahydropyranyloxy) -2nonacosanone (IV) is added to the solution and the

  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 successively with 5% sodium bicarbonate solution, water and dried sodium chloride solution on magnesium sulphate and the solvent is removed under vacuum. 0.22 g of crude product (mp: 34-38 ° C.) is obtained.

  recrystallized from petroleum ether at -20.degree.-30.degree. C. Yield: 0.2 g (80%).

  mp: 41-42 ° C in literature: 41-43 ° C, AW Burgstahler et al, J Org Chem 42, 566 (1977), IR (film): 3350 (OH), 1715 (CO), 1040 cm HRMN (CDCl 3): δ 0.82 (3H, d, J = 6Hz, 11-CH 3), 1.04 (3H, d, 20);

  J = 7Hz, 3-CH 3), 1.1-1.6 (49H, m, -CH 2 O), 2.01 (3H, s, CH 3 CO), 2.14 (1H). , m, CH-CO), 3.52 (2H, t, J = 6Hz, -CH 2 C).

  Analysis: C 31 H 6202 (466.84) Calculated values: C% = 79.76 H% = 13.39 Found values: C% = 79.62 H% = 13.61

Example 2

  Preparation of 29-hydroxy-3,11-dimethyl-2-nonacosanone a) Preparation of methyl 10-methyl-28- (2-tetrahydropyranyloxy) -10-octacosenoate (IX; R = CH 3, Y = THP group) ).

  7.4 g (10 mmol) of 18- (2-tetrahydropyranyloxy) octadecanylphosphonium iodide (VII, X = I, Y = THP group) are dissolved in 60 ml of anhydrous tetrahydrofuran The solution is cooled to 10 ° C. and 10 mmol of butyl lithium (6.3 ml, 15% solution in hexane) are added under argon and with stirring. The mixture is stirred at room temperature for 30 minutes, then a solution of 2.1 g (10 mmol) of Methyl 10-oxoundecanoate in 10 ml of anhydrous tetrahydrofuran is added at 10 ° C. in the course of 30 minutes. The reaction mixture is stirred at ambient temperature for 5 hours, poured into a solution of 10% ammonium chloride and The hexane solution was washed successively with 5% sodium hydrogen carbonate solution, water and saturated sodium chloride solution, dried over magnesium sulfate, and the solvent was removed by evaporation.

  distillation The residual product is purified by column chromatography.

  Yield: 1.1 g (20%) of slightly colored oil.

  TLC: Rf = 0.58 (benzene-acetone 10: 0.5) -1 IR (film): 1735 (CO), 1460, 1375, 1160, 1030 cm H-NMR (CDCl3): 1.8 (51H, m, -CH 2), 1.8-2, 1 (4H, m, -CH 2 -C =), 2.28 (2H, t, J = 8Hz, -CH 2-COO),

  3.25-4.1 (4H, m, -CH 2 -O), 3.68 (3H, s, CH 3 OOC), 4.5-4.65 (1H, m, 0-CH). -O), 5.1 (1H, m, -CH =).

  Analysis: C 35 H 6604 (550.91) Calculated: C% = 76.30 H% = 12.07 Found: C% = 76.18 H% = 12.21 b) Preparation of 10-methyl-28 - (2-tetrahydropyranyloxy) octacosanoate

  methyl (X, R = CH 3, Y = THP group).

  A solution of 0.55 g (1 mole) of methyl 10-methyl-2- (2-tetrahydropyranyloxy) -10-octacosenoate in 20 ml of anhydrous methanol is hydrogenated over 0.3 g of

  catalyst consisting of palladium on animal charcoal.

  When the theoretical amount of hydrogen has been removed (3 hours, 24 ml) the catalyst is filtered off, washed with methanol, the methanolic solutions are

  combined and evaporated under vacuum.

  Yield: 0.52 g (95%) -1 IR (film): 1735 (CO), 1460, 1380, 1260, 1075, 1030 cm -1 H NMR (CDCl 3): δ 0.82 (3H, m.p. d, J = 8 Hz, 11-CH 3), 1.0-1.9 (55H, m, -CH 2), 2.3 (2H, t, J = 7Hz,

  -CH 2 -COO), 3.2-4.1 (4, m, -CH 2 O), 3.65 (3H, s, CH 3 C), 4.5-4.65 (1H, m, O-CH-O).

Analysis: C 35 H 6804 (552.93).

  Calculated values: C% = 76.02 H% = 12.39 Found values: C% = 75.88 H% = 12.53 c) Preparation of 10-methyl-28- (2-tetrahydro) pyranyloxy acid - octacosanol (X, R = H, Y = THP), A mixture of 0.55 g (1 mole) of methyl 10-methyl-28 (2-tetrahydropyranyloxy) -octacosanoate and 1 ml of normal sodium hydroxide solution. sodium, is stirred at room temperature for 6 hours then poured into 12 ml of a standard solution of hydrochloric acid, extracted with ethyl acetate; the organic phase is washed successively with water and a solution of sodium chloride, dried over magnesium sulphate and evaporated under vacuum. The product which becomes thus obtained can be used for the steps

  subsequent reaction without prior purification.

Yield: 0.45 g (83%).

  IR (film): 1715 (CO), 1460, 1380, 1200, 1080, 1030 cm H-NMR (CDCl3): δ 0.82 (3H, d, J = 8Hz, 11-CH 3) , 1.0-1.9 (55H, m, -CH 2), 2.3 (2H, t, J = 7Hz,

  -CH 3-COO), 3.2-4.1 (4H, m, -CH 2 O), 4.54.65 (1H, m, O-CH-O).

  d) Preparation of methyl 2,10-dimethyl-28- (2-tetrahydropyranyloxy) octacosanoate (II; R = CH 3, Y = THP group) 0.31 g (3 mmol or 0.43 ml) of diisopropylamine and 1.9 ml (3 mmol) of a hexanic solution containing 15% butyl lithium are introduced into 10 ml of anhydrous tetrahydrofuran, under an inert gas. A solution of 0.54 g (1 mole) of 10-methyl acid is added. (2-Tetrahydropyranyloxy) -octacosone in 3 ml of hexamethylphosphoramide in the reaction mixture at 0 ° C and stirred at 0 ° to 5 ° C. for 20 minutes. The mixture is allowed to warm to room temperature. 0.17 g (1.1 mmol, 0.08 ml) of methyl iodide are added and the reaction mixture is stirred for 2 hours. The mixture is then quenched by pouring into a 10% solution of ammonium chloride, then extracted with ethyl acetate The organic phase is washed successively with a solution of ammonium chloride, water, e brine, dried over magnesium sulfate and evaporated in vacuo. 0.4 g of crude acid is collected and esterified with diazomethane; the ester thus obtained is then purified by chromatography (benzene-acetone

: 0.5).

  0.35 g (65%) of a colorless oily product, which is identical to the product prepared in Example 1, is obtained. (C) It can be converted into a component of formula (I 1) of

  pheromone according to the procedure described in Example 1.

  As is apparent from the above, the invention is not limited to those of its modes of implementation, implementation and application which have just been described more explicitly; on the contrary, it embraces all variants that may come to the express of the technician in the field, without departing from the framework, nor

  of the scope of the present invention.

19 25 42548178

Claims (4)

  Process for the preparation of 29-hydroxy-3,11-dimethyl-2nonacosanone represented by formula (I) below: O II   HO-CH 2 (CH 2) 17-CH- (CH 2) 7 -CH-C-CH 3 (I) CH 3 CH 3   characterized in that: a) an alkyl 2,10-dimethyl-28octacosanoate of the following formula (II) is reacted: YO-CH 2 (CH 2) 16 -CH 2HH- (CH 2) 7 CH-COOR (II) CH 3 CH 3   wherein R is a C 5 alkyl group and Y is a tetrahydropyranyl or 2-ethoxyethyl Cla group, with a trialkylsilylmethyl lithium in an ether solvent, preferably with cooling, the intermediate thus obtained represented by the formula General (III) below: 0 R 1 It /   YO-CH 2- (CH 2) 17-CH- (CH 2) 7 C CH -R 2 (III) CH 3 CH 3 R 3 3 3 R   in which R 1, R 2 and R 3 are each a C 1 to C 4 alkyl group, preferably without isolating it, with an aliphatic alcohol, the acid is treated with an acid of the general formula (IV) thus obtained O il   YO-CH 2 - (CH 2) 17-CH- (CH 2) 7 -CH-C-CH 3 (IV) CH CH 3 3   in which Y is as defined more; or b) an alkyl 2,10-dimethyl-28-octacosanoate of the general formula (II) in which R and Y are as defined above is reacted with a solution of methylsulfinylmethide in dimethylsulfoxide in a ether-type solvent, the compound thus obtained is treated with a reducing agent, preferably an amalgam of aluminum, treated with an acid the compound thus obtained of general formula (IV), where Y is as defined above, then the compound of formula (I) thus obtained is separated from reaction mixture.   Process according to variant (a) of claim 1, characterized in that trimethylsilylmethyl lithium is used as trialkylsilylmethyl lithium.   Process according to variant (a) of claim 1, characterized in that methanol is aliphatic alcohol.   Process according to variant b) of claim 1, characterized in that p-toluenesulphonic acid is used as the acid.   Compounds of general formula (II), wherein R and Y are as defined in claim 1.