DD217800A5 - PROCESS FOR PREPARING 29-HYDROXY-3,11-DIMETHYL-2-NONACOZANONE - Google Patents

Abstract

The invention relates to a process for the preparation of 29-hydroxy-3,11-dimethyl-2-nonakozanon of the formula I, HO-CH 2 (CH 2) 17 -CH- (CH 2) 7 -CH-C-CH 3 (I) CH 3 CH 3 Odas thereby characterized in that one reacts either an alkyl (2,10-dimethyl-28-oktakozansaeure) derivative in an ether-type solvent with a Trialkylsylylmethyllithium and reacting the formed intermediate with an aliphatic alcohol and the protecting group from the resulting compound by acid treatment or converts an alkyl (2,10-dimethyl-28-oosphozansaeure) derivative in an ether-type solvent with the solution of the methylsulfinylmethyd formed strong base in dimethyl sulfoxide, the resulting product treated with a reducing agent and from the resulting compound the Protective group removed by acid treatment. The known compound of formula I is the sex pheromone of the insect Blattella Germamica.

Description

0β 029 58

Process for the preparation of 29-hydroxy-3? 11-dimethyl-2

-nonakozanon

Field of application of the invention: '

The invention relates to a novel process for the preparation of 29-hydroxy-3j-11-dimethyl-2-nonakozanori,

Characteristic of the known technical solutions:

It is known that the 2S-hydroxy-3 »11-dimethyl-2-nonakozanone of the formula I

HO-CH ₀ - (CH ₀ ) ₁₇ -CH- (CH ₀ ) ₇ ^ CH C-CH. (I)

CH _3; , CH ₃ Ό

ifl 984-0196777

has an attractant effect on the male individuals of the German cockroaches (Blattella Germanica), i. there's, 'sex pheromone of this insect. , '

The German cockroach (Blattella germanica) is an annoying parasite of urban dwellings. The urban areas, if neglected, are ideal hiding places for this insect. Due to the short growing season, the population starts to grow rapidly and as a result, this parasite appears very quickly even in new housing estates. y

The damage caused directly by the German cockroach (Blattella Germanica) is also significant. The control of this insect is also based on the esthetic aspects and the prevention of the yiral infections, whose mediator this parasite may be. · '...''

The control of this insect is made more difficult by the fact that the German cockroach is very resistant and. is resistant to several agents used for insect control. The use of high toxicity agents is extremely dangerous in inhabited areas. On the other hand, effective defense can only be achieved by means of a regular, repeated insect control in short periods of time, since the rapid increase of already some remaining insects is sufficient to re-infect the area within a short time.

Based on the above reasons, the use of pheromone traps against Blattella germanica has been proven. The traps containing the attractant of this insect are harmless to higher order organisms (such as humans). The traps are also used to trap for chemical insects.

insect repellent, and effectively prevent repeated insect replication.

The sex pheromone of the German cockroach (Blattelle germanica) was isolated from the sexually mature females by Nishida and coworkers (R. Nishida, H. Putami and S. Ishii: Experientia 30, 978 (1974); Appl. Ent. Zool., 10, 10 (1975); R. Nishida, T. Sato, Y. Kuwahara, H. Putami and S. Ishii: J. Chem. Ecol., 2, 449 (1976); Agr. Biol. Chem., 40, 1407 V / 1976 /). It has been found that the sexpheromone extract has two components - the 3 ', 11-dimethyl-2-nonakozanon of formula XI

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

ti

CH ₃ CH ₃ 0

and the 29-hydroxy-3,11-dimethyl-2-nonakozanon of the formula 1 - contains. The two compounds cause a characteristic sex pheromone reaction on the male Individeen the German cockroach, however, the compound of formula I has a stronger effect (K. Mori, T. Suguro and S. Masuda: Tetrahedron 21 * 1329/1981 /). The four . , possible optical isomers of the two pheromones were synthesized. The natural substances correspond to a (3S, 11S) configuration. The sexual attractiveness of the four optical isomers is almost the same size,

Nishida and coworkers (R. Nishida, T. Sato, Y. Kuwahara, H. Puhami and S. Ishii: Agr. Biol. Chem. 40, (7), 1407/1976 /) have the compound of formula I of FIG Ethyl ethylacetate. For this ester

will with. Kalium.tert * butylate formed an anion, which is reacted with 1,6-dibromo-ftexan. The. ethyl (8-bromo-2-acetyl-2-methyl-octanoate) obtained is hydrolyzed with hydrobromic acid and decarboxylated by heating. The obtained 9-bromo-3-methyl-2-nonanone is masked at the carbonyl group as Xthylenacetal and treated acetal formed with the anion formed from Acetecetester the Athylenacetalgruppe of the thus obtained A'thyl- (2-acetyl-9-methyl -Io-oxo-undekanoat) is hydrolyzed in alkaline medium and the product is decarboxylated. The resulting. ^ - Meiyl-.2, fi-dodefcandion-2-ethylenyl ^ is attached to the (18-Tetrahydropyranyloxy) -oktädecyl-magnesium bromide prepared from 1,18-dihydroxyoctadecane in four stages. The thus obtained 3 H-dimethyl-11-hydroxy-29- (tetrahydropyranyloxy) -2-nonakozanon-ethylene-acetal is dehydratiert by heating with an acid, and the resultant 3, _{11-dimethyl-29-hydroxy-11-l} nonakozen 2-one converted by catalytic hydrogenation in the desired pheromone compound of the formula I.

According to the method of Burgstahler and coworkers (AW Burgstahler, L. 0. Weigel, ME Sanders, G, G. Shaefer, WJ Bell, SB Vuturo: J. Org. Chert. 42, 566/197? /) The 4- Bromo-1-butanol-benzyl ether reacted in the presence of ethylenediamine with lithium acetylide. The lithium salt of the resulting acetylene derivative is alkylated with an excess of 1,12-dibromo-dodecane. The resulting 1-bromo-IS-benzyloxy - ^ - octadecine is converted into the corresponding phosphonium salt, from which a phosphorane is formed with methyllithium and this product is reacted in a Wittig reaction with 9-bromo-2-nonanone. With the bromine compound thus obtained, the anion formed from 2-methyl-acetoacetate with sodium hydride is alkylated, After catalytic hydrogenation, the 3,11-dimethyl-3-ethoxycarbonyl-29-hydroxy-2-nonakozanon prepared by

, : ':''''. - 5 - ''

Decarboxylation carried out in alkaline medium is converted into the diastereomeric mixture of the compound of Pormel I. '· ''',''" ·. '.'. '.';':

After another method of Bürgstahler and his coworkers (AW Burgstahler, ME Sanders, CG Schaefer and L. 0. Weigel: Synthesis 1977 »405) the above synthesis is further developed. The acetoacetic acid benzyl ester s is meihylated with tetrabutylammonium bisulfate in the presence of a phase transfer catalyst. The resulting 2-methyl-acetoacetic acid benzyl ester is alkylated over the anion formed with sodium hydride with the above-prepared 26- (benzyloxy) -8-methyl-8-hexacotene-21-ynylbromide. The thus obtained benzyl (2-acetyl-2,10-dimethyl-28-benzyloxy-O-O-octato-23-ynoate) is catalytically hydrogenated and the resulting 2-acetyl-2,10-dimethyl-28 -hydroxy-oktakozansäure by heating to the pheromone compound of Pormel X decarbo-; 'xylated. '"' ... '.," -. '

Mori and co-workers (K. Mori, S. Mosuda, T. Sugara: Tetrahedron Letters 1978 , 3447, Tetrahedron 37, 1329/1981 /) have carried out the stereocontrolled synthesis of the four stereoisomers of the compounds of Formulas I and XI. The key step of this synthesis consists of the reaction of a chiral tosylate - in the case of the compound of formula XI, the 5R- or 5S-methyl trikozanyl-tosylate and in the case of the compound of formula I the 5R- or 5S-methyl- ^. 1-benzyloxy-S-tricyczyl-tosylate-with the Grignard reagent formed from 4R- or 4S-methyl-5-hexenyl bromide in the presence of lithium copper tetrachloride.

One of the above components - the 4R-methyl-5-hexenylbromide - is prepared as follows: 3R, 7-dimethyl-6,7-epoxy-1-heptene is cleaved with periodic acid, which is

  , , '"'" ''. '' - 6 -

reduced aldehyde with a metal hydride and the resulting 4R-methyl-5-hexanol over the tosylate with lithium bromide in acetone into the desired bromide transferred. To prepare its antipode, the 7-pbenyi-4R-methyl-b.exanoic acid ester is oxidized with chromic (IV) oxide. The silver salt of Dicarb'onsäurehalbesters is converted in a Hunsdiecker reaction in the methyl (4S-methyl-5-bromo-hexanoate). This compound is reacted with o-nitro-seleno-phenol, from the resulting compound, the selenyi-group is removed in an oxidative manner and the obtained methyl- (4S-methyl-5-hexenoate) by reduction with lithium aluminum hydride in the desired 4S ~ Converted to methyl-5-hexanol. From this compound, the '4S-methyl-bromide is prepared via the tosylate in a manner known per se. , ^: '''. : · ^: '

In addition to the thus prepared 4R or 4S-methyl-5-hexenyl bromide is the other component 5R- or 5S _; -Methyl-23-benzyloxy-8-trikdzinol tösylat used. The "R" compound is prepared in the following manner: the tetradecane-1,14-diol is converted to the corresponding monobenzene ether; from this alcohol, the T4-benzyloxy-tetradekanyl bromide is prepared via the tosylate with lithium bromide. This compound is converted to the corresponding iodo compound by halogen exchange. With this iodine compound, the R-citronellyl-acetylene obtained from the R - (-) - gitronellyl iodide prepared as described above is alkylated. The product obtained is oxidized in a conventional manner with m-Chlpr-perbenzoic acid and split with Pergodsäure \ u \. From the thus obtained 4R-methyl 1-21-benzyloxy-7-henejkozinal the desired SR-methyl- ^ S-benzyloxy-S-trikozinol is prepared by reduction, carried out with cyanide chain extension and reduction, which is tosylated in a known manner. ,

- 7 -

^; - '. '''· Ν ·. '·.'. - ⁷ - '· ",". '

To prepare the corresponding "S" compound, a 7'-pentamyl-5S-methylheptyl acetate prepared from R - (+) - citronellal as described above is formed by Wittig reaction to form a terminal double bond. Bromine is attached to this double bond. After an elimination reaction, the (7-hydroxy-3S-metbyl-heptyl) -acetylene is obtained, which is alkylated with 14-benzyloxy-tetradekanyl-bromide. After removal of the acyl group, the desired 5S-methyl-23-benzyloxy-tricotazo-8-in-1-oil is obtained, which is converted to the corresponding tosylate.

For the preparation of the four stereoisomers of the pheromone of formula I, the 5R- or 5S-methyl-23-benzyloxy-trikoza-8-in-i-ol-tosylate with that of 4R-- or 4S-methyl -5 Hexenyl bromide formed Grignard reagent reacted.

In the palm of the two compounds of formulas I and XI i i. For example, the derivatives having the (3S, 11S) configuration are identical to the naturally occurring substances. According to the authors, there is no significant difference in the biological activity of the different stereoisomers.

The above known processes for the preparation of the pheromone compound of the formula I are uneconomical because of the costly nature of the starting materials and the high number of process steps.

Aim of the invention;

The aim of the invention is to eliminate the disadvantages of the known processes and to provide a more economical process for the preparation of the compound of formula I.

- 8 Presentation of the essence of the invention:

It has been found that the 29-hydroxy-3,11 -dimethyl-2-nonakozanone of the formula I can be prepared in a simpler and more economical manner than heretofore by using as starting material a new alkyl (2-, 10-dimetyl) 28-oktakozansäure) derivative of general formula II

YO-GH ₂ (CH ₂ ) - - CH ₂ -CH-C CH ₂ ^ -CH-COOR (H)

wherein R is an alkyl group of 1-5 carbon atoms and Y is a tetrahydropyranyl or 2-ethoxyethyl group. ' ^! "''. ''

The invention therefore provides a process for the preparation of 29-hydroxy-3,11-dimetnyl-2-nonakozanon of the formula I, which is characterized in that

a) an alkyl (2,10-dimetbyl-28-oktakozansäure) derivative of general formula II, wherein R is an alkyl group having 1-5 carbon atoms and Y is a tetrahydropyranyl or 2-Ä'thoxyäthylgruppe, in a solvent of Äthertyps, preferably with cooling, with a Trialkylsylylmethyllithium reacts and the. Formed intermediate of the general formula III.

YO-CH ₂ - (CH ₂ ) ₁₇ -CH- (CH ₂ ) y -CH-C-CH ₂ -Si-R ₂ (III),. CH ₃ .. CH ₃ 0 _: ... " ^R 3 .., _:

^.-:; ; .. --V-; -9--:.,. : _, '-. · ,,

wherein R ₁ , Β '' and R 'independently of one another each represent an alkyl group having 1-4 carbon atoms and Y has the above meaning, expediently without isolation in the reaction mixture, with an aliphatic alcohol and the protective group of the resulting compound the general Forinel IV

Y is -CH ₂ (CH ₂ ) ₁₇ -CH- (CH ₂ ) ₇ -CH-C-CH ₃ \ (IV),

CH ₃ CH ₃ O ·

where Y has the above meaning removed by acidic treatment, or

b) an alkyl (2,10-dimethyl-28-oktakozansäure) derivative of the general formula II wherein R and'Y have the above meaning, in an ether-type solvent with the solution of the strong base -.-. . Hethylsulfinylmethyds in dimethyl sulfoxide, the product obtained with a reducing agent, preferably aluminum amalgam, treated and removed from the resulting compound of general formula IV, wherein Y has the above meaning, the protecting group by acid treatment; '

and isolating the compound of formula I 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 in a solvent of the ether type, preferably with cooling, with a trialkylsylylmethyllithium. It is not necessary, the formed intermediate of the general Formula III (wherein R _1, R ₂ and R ₃ are each a C ₁ _. Alkyl group,

^J.

: ··. ''. ^: ' · .- 10 -

to isolate). Rather, this compound may suitably be reacted in the reaction mixture, where it is formed, with an aliphatic alcohol conveniently with methanol. From the compound of the general formula TV thus obtained, the protective group can be obtained by acid treatment, ζ.Β. With p-toluenesulfonic acid, are easily removed.

According to variant b) of the process according to the invention, a compound of the general formula II is reacted with a solution of methylsulfinyl methoxide in dimethylsulfoxide The methylsulfinyl methoxide can be formed from dimethyl sulfoxide with a strong base, expediently with sodium hydride, at a temperature below 70 ^° C. it is not necessary to isolate the product formed from the compound of formula II with Methylsulfinylmethyd, but this ^can; compound in the reaction mixture where it was formed, re-, duced these reduction may preferably be carried out with aluminum amalgam the aluminum amalgam.. made of aluminum and mercury (II) chloride in a conventional manner., -

The compound of formula I formed in the above reactions can be isolated from the reaction mixture by methods known per se (e.g., distillation or chromatography).

The compounds of the general formula II used as starting material in the process according to the invention are novel, not described in the literature derivatives. These compounds can be prepared from 10-undecenoic acid, a cheap commercial product. From the 10-undenoic acid, a dianion is formed with alkyl lithium, which is alkylated with methyl iodide. The obtained 2-methyl-10-undecenoic acid of the formula V ^: >.

(V)

r '. , '.' · ''

is esterified and the resulting ester with hydrogen peroxide in the presence of a Palladlumsalz catalyst in a compound of general formula VI

₇ -CH-COOR (Vl)

where R is alkyl. The compound of the general formula VI is reacted with a, from a phosphonium salt of the general formula VII, ν

₃ P-CH ₂ - (CH ₂ O ₁₆ -CH ₂ -OY Χ ^θ > (VII)

(where X is halogen, Y is tetrahydropyranyl or 2-ethoxyethyl) with a strong base,

: "..: ' ^Λ .''

preferably treated with bufyllithium, formed phosphorane. The compound of general formula VIII obtained in this way

Y is -CH ₂ (CH ₂ ) ₁₆ -CH = C- (CH ₂ J ₇ -CH-COOR (VIII),

• t-. '-. ι ' ₍ .

CH ₃ CH ₃

- 12 - "

r- 12

wherein R and Y have the above meaning, is catalytically hydrogenated into the desired compound. my formula I transferred.

The compounds of the general formula II can also be prepared as follows: a 10-oxo-uhdecanoic acid ester is reacted with a phosphorane formed from a phosphonium salt of the general formula VII in which R and Y have the above meaning, the compound thus obtained general formula IX '·' .. "·, · ''

YO-CH ₀ - (CH ₀₎ ^ - CH = C (CH _{0) Q} -COOR (IX)

d £ ID d O.

CH-

is catalytically hydrogenated and the compound thus obtained

the general formulaX. ·, "

YO-CH ₀ (CH ₀ ) ' ₇ -CH- (CH _Q ) o -COOR (X)

''. '''' CH ₃ ,

hydrolyzed to the desired carboxylic acid. The so _ER: preserved carboxylic acid is converted with a strong base, preferably methyl lithium in a dianion, which is converted by reaction with methyl iodide in the compound of general formula II. , :

The trialkylsylylmethy1-lithium used in process variant a) can be prepared by reacting trialkylsylylmethyl chloride with metallic lithium.

The term used in the specification "AlkylgruppV 'includes both straight and branched Alkylgrup-' pen '*', '' -Y ';.... \''·..'.

Further details of the method according to the invention can be found in the following examples, without limiting the scope of protection to these examples.

Embodiments; • Example 1 ''.: .-. "'... ';. -. ' ^:

Preparation of 29-hydroxy-3,11-dimeth-2-nonakozone (I)

a) 18- (2-tetrahydropyranyloxy) -octadienyl-triphenylphosphine-iodonium iodide. '

/ TVII); X = iodine; Y = tetrahydropyranyl

1) 3.0 g (0.01 mol) of 18-chloro-octadecanol are dissolved in 20 ml of anhydrous benzene, whereupon 1.0 g (0 ^ 012 mol, 1.1 ml) of dihydropyran and 0.05 g of p-toluenesulfonic acid be added. The reaction mixture is stirred at room temperature for 4 hours. The reaction mixture is diluted with A'ther for workup, with a 5% sodium '.' bicarbonate solution, water and a sodium chloride solution washed neutral and dried over magnesium sulfate. The solvent is removed under reduced pressure and the residue is subjected to distillation. There are obtained 3.5 g of 18-chloro-octadecanyl-tetrahydro-2-pyranyl ether, yield 90 %, boiling point: 124-126 C ⁰ (0.15 mm Hg) IR (film): 1025, 720 cm " ¹

Analysis: C 23 ^H 45 ° 2 Cl calculated: C : 71 , 00; found: C : '71 , 21;

¹ H-ETAR (CDCl ₃ ); 1,15-2,0 (38H, in, -CHg-); '· 3,25-4,0

·. , - (4H, - 01, .-- CH ₂ -P) -; '3.52 .- (2H, t, J = 7Hz,. - CH ₂ Cl); 4.57 (1H, m, O-CH-O) ".

(389.067)

, H: 11.66; Cl: '9.11 H: 11.51; Cl: 9.02.

2) 1.95 g (.05.05 mol) of i8-chloro-octadecanoyl-tetrahydro-2-pyranyl ether are dissolved in .15 ml of methyl ethyl ketone, whereupon 1.12 g: (0.0075 mol) of powdered sodium iodide are added become". The reaction mixture is heated to boiling for 20 hours and then cooled, the precipitated salt is filtered off and the filtrate is concentrated under reduced pressure. The residue is taken up in ether, the ethereal solution washed with water, a 5% sodium bisulfite solution and a sodium chloride solution, dried over magnesium sulfate and concentrated under reduced pressure. The crude 18-iodo-octadecanoyl-tetrahydro-2-pyranyl ether obtained is purified by chromatography (a 10: 1 benzene-acetone mixture). Yield 1.9 g, 20 %, thin layer chromatography: Rf. 0.55 (benzene-acetone = 1: 1) IR (film): 1025 cm ^-1 . \.

¹ H-MR (CDCl ₃ ) - 1.15-2.0 (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 (iH, m,... 0-CH-O) '·,

Analysis: ^σ 23 ^Η 45 ° 2 ^Γ (480.518). ·· '

calculated: C: 57.49; H: 9.44; I :, 26.41 · Found: C: 57.6-3; H: 9.52; I: 26.12.

3) A mixture of .2,4. g (0.005 PIoI) 18-iodo-octadecanyl- '. ~ tetrahydro-2-pyranyl ether, 1.31 g (0.005 mol) of triphenylphosphine and 50 ml of anhydrous acetonitrile are heated to boiling for 50-70 hours. At the end of the reaction, the solvent is removed under reduced pressure. The

· '' ..., ' ^: - '15 -

Resinous residue is washed with anhydrous ether several times by decantation, carefully made solvent-free under reduced pressure and dried. There are obtained in the form of a solidifying oil, 2.2 g of 18- (2-Tetrahydrppyr any lo ^) - o'ktadekanyl-.tr.i phenyl-phosphonium-iodine '. .- '....'

Yield: 60 % _y

IR (PiIm) -: 1590, 1110, 1030, 730, 690 cnT ¹ , ¹ H-MR (CDCl ₃ ): 1.1-2.0 (38H, m, -CH ₂ -); 3.1 to 4.1

'(6H, 111, .-- CHgO, - CH ₂ -P); 4.56 (1H, m,

, 0-CH-O); 7.5-8.2 (15H, m, aromatic) Analysis: C ₄₁ Hg ₀ O ₂ PI (742.814) calcd. C: 66.29; H: ^8V , 14; P: 4,17; I: 17.08 found: C: 66.41; H: 8.25; P: 4.06; I: 16.91.

b) Methyl / 2,10-dimethyl-28- (2-tetrahydropyranyloxy) -10-octacozenoate /

/ T ¥ III); R = CH ₃ ; Y = tetrahydropyranyl /:

7.4 g (10 millimoles) of 18- (2-tetrahydropyranyloxy) -octadekanyl-triphenylphosphonium iodide / TVII); X = iodine; Y = tetrahydropyranyl7 are dissolved in 60 ml of anhydrous tetrahydrofuran, whereupon the solution is cooled to 10 ° C. and 10 millimoles of butyl lithium (6.3 ml of a 15% solution formed with hexane) are added under inert gas and cooling. The resulting red solution is stirred at this temperature for 30 minutes, at which time a solution of 2.2 g (10 millimoles) of methyl (2-methyl-i0-oxb-undecanoate) / Tvi) at 10 ° C over 30 minutes; R = CH ₃ J in 10 ml of anhydrous tetrahydrofuran is added. The mixture is stirred at room temperature for a further 5 hours. The reaction mixture is poured into a 10% ammonium chloride solution for decomposition and extracted with petroleum ether. The organic phase is washed with a 5% sodium bicarbonate solution, water and a

The reaction mixture can also be worked up by diluting the mixture with 100 ml of hexene and precipitating the solution on a short column of silica gel with a solution of sodium chloride solution, dried over magnesium sulfate and concentrated The resulting solution is evaporated under reduced pressure. The resulting crude product (about 2-2.5 g) is purified by column chromatography (10: 0.5 benzene-acetone mixture) in the form of a colorless oil, 1.2 g of the title compound, Yield 21%

Thin Layer Chromatography: 0.6 (benzene-acetone - 10: 0.5) IR (Film): 1735 (CO), 1460, 1375, 1160, 1030 cm ^-1 ' ¹ H-NMR (CDCl ₃ ): 1.0- 1.8 (54 H, m, CH ₂ -, 2-CH _3);

'1.8-2.1 Utf, m, -CHp-C =), 2.3 (1H, m,

CH-COO); 3.25-4.1 (4H, m, -CH ^ O-);

3.68 (3H, s, CH ₃ OOC); 4.5-4.65 OH, m,

0-CH-O); 5.1 (1H, tn, -CH =) analysis; Calculated C ₃₆ Hg ₈ O ₄ (564.94): C, 76.54; H: 12.13 found: C: 76.67; H: 11.95

c) methyl / 2,10-dimethyl-28- (2-tetrahydropyranyloxy) -ozozozanoate / / TlI); R = CHO? Y = Tetrahydropyranyl7

0.56 g (1 millimole) of methyl / 2,10-dimethyl-28- (2-tetrahydropyranyloxy) -10-o-quinzenium Jt7 / TVIII); R = CH ₃ ; Y = Tetrahydropy.ran.yl7 are dissolved in 20 ml of anhydrous methanol. The solution is added to 10 ml of anhydrous methanol, whereupon o, 3 g of a; Palladium / carbon catalyst are added under inert gas

.. .. '. · ...... · - 17 - -; , 'V. ... \

The mixture is stirred at room temperature under a slight excess of hydrogen pressure for 3 hours (theoretical hydrogen uptake 24 ml). At the end of the reaction, the catalyst is filtered off and the filtrate is concentrated. There is obtained, in the form of a colorless oil, 0.53 g of the titled compound, yield, 96 % IR (film): 1735 (CO) 1460 cm -1. ¹

¹ H-UTJIR (CDCl ₃ ): 0.82 (3H, d, J = 6Hz, 10-CH-); 1., 0.-1.8 ^ _; (58HVmZ-CH ₂ -, 2-CH _3);

2,3 (1H, m, CH-COO); 3.2-4.1 (4H, _m, -CH ₉ O);

3.65 (3H, s, CH ₃ OOC); 4.5-4.65 (1H, m,

0-CH-O)

Analysis: C ₃₆ H ₇₀ O ₄ .. = (566,959)

calculated: C: 76.26; H ^ 12,44 '

found: C: 76.05; H: 12.53

d) 3,11-dimethyl-29- (2-tetrahydropyranyloxy) -2-nonanoanone / TlV); Y = tetrahydropyranyl /

0.12 g of a lithium dispersion (20 millimoles, 0.4 g, 30 %, in petrolatum) is added to 10 ml of anhydrous ether, Under inert gas are added 0.30 g (0.34 ml, 2.5 ml-lim) Trimethylsylylmethylchlorid added, after which the reaction mixture is heated to boiling for 2.5 hours The mixture is cooled and allowed to stand; The trimethylsilylmethyl lithium solution is carried from the settled lithium to another flask with an inert gas. To the above reagent is added, at 0 ° C, a solution of 0.5 g (1 millimole) of methyl /?, 10-dimethyl-28- (2 tetrabydropyranyloxy) -ozozozoanite added in 5 ml of anhydrous ether. The reaction mixture is stirred for 2 hours at 0 ° C., after which 2 ml of anhydrous methanol are added with cooling

'\. ''. ' ^: ~. · "- 18 -

At the end of the reaction, the reaction mixture is decomposed with water, extracted with ither, the ethereal solution with ammonium chloride solution, water and washed with sodium chloride solution, dried over magnesium sulfate and concentrated under reduced pressure. The crude product obtained (0.5 g) is purified by chromatography (a 10: 0.2 benzene- _r acetone mixture). 0.26 g of the title compound are obtained in the form of a colorless oil, yield 45 % IE (PiIm): 1705 (CO), 1460, 1080, 1030 cm ^-1 , ¹ H-NMR (CDCl ₃ ): 0 , 82 (3H, d, J = 6Hz, 11-CH ₂ ):

1.05 (3HY d, J = 7Hz, 3-CH _3); 1.1-1.9.

(55H, m, -CH ₂ -); 2.05 (3H, s, CH ₃ CO),

2.4 (iH, m, CHCO); 3.2-4.1 (4H, m, -CH ₂ O);

4.5-4.65 (1H, '0-CH-O, m). · ":

Analysis: C ₃₆ H ₇₀ O ₂ (550.95) Calcd: C: 78.48 H: 12.80 Found: C :, 78.29 H: 12.61, '

e) 29-hydroxy-3,11-dimethyl-2-nonakozanone (I)

0.05 gp ~ toluenesulfonic acid is dissolved in a mixture of 5 ml of methanol and 0.5 ml of water. To the solution are added o, 27 g (0.5 mmol) of 3,11-dimethyl-29- (2-tetrahydropyranyloxy) - 2-nonakozanon; / TLV); Y = tetrahydropyranyl / added where .- ,,;, raufhin the reaction mixture for 4 hours at 60 ⁰ C stirred v / ill .. wax cooling, the solvent is removed under reduced pressure, the residue taken up in ether, with a 5 f washed sodium bicarbonate solution, water and a sodium chloride solution, dried over magnesium sulfate and distilled off under reduced pressure- It Vorrderder, in the form of a solidifying substance 0.22 g of Robpro-

~ 19 ~

: '' - · ¹⁹ - '.

domestic product (P: 34-38 C °).. The obtained product can be obtained by order - '' crystallization from petroleum ether '(zwischen.-20 ° C and -30 C ⁰⁾ to be cleaned. 0.2 g of the title compound are obtained, yield 80 % P: 41-42 C ⁰ (literature: 41-43.0 °, AW Burgstahler et al,

J Org, Chem, _4_2, 566/1977 /) IR (film): - 3350 (OH), 1751 (CO), 1040 cm ^{"1 1} H-NMR _(CDCl3): 0.82 (3H, d, J = 6 Hz, 11-CH _3). \ 1.04 (3H, d, J = 7 Hz, 3-CH ₃ O; 1.1-1.6

49H, m, -CH ₂ -); 2.01 (3H, s, CH ₃ CO);

2.34 (1H, m, CH-CO); 3.52 (2H, t, J = 6Hz,

C ₃₁ H ₆₂ -CH ₂ 0) (466, 84) 3 , 39 Analysis: C: ° 2 H: 1 3 , 61, calculated: C: 79, 76; H: 1 found: 79, 62 Example 2

Preparation of 29-hydroxy-3,11-dimethyl-2-nonakozanone (I)

a) Methyl- / T0-methyl ~ 28- (2-tetrahydropyranyloxy) -10- -oquozoite / '

/ ""(IX); R = CH ₃ ; Y = Tetrahydropyranyl7

7, ä. G (TOMillimol) 18- (2-Tetrahydropyranyloxy) -octadekanylphosphonium iodide / (VII); X = iodine: Y = Tetrahydropyranyl7 are dissolved in 60 ml of anhydrous tetrahydrofuran, after which the solution to 10 C ⁰ is cooled. Under argon, 10 mmol of butyllithium (6.3 ml, in the form of a formed with hexane followed by 15 solution) was added dropwise thereto under cooling, the mixture is stirred at room temperature for 30 minutes, then at 10 C ⁰ within 30 minutes 2.1 g (10 millimoles) methyl (10-oxo-undecanoate),

The reaction mixture is stirred at room temperature for 5 hours, then poured into a 10% ammonium chloride solution and extracted with hexane. The hexane solution is washed with a 5% sodium bicarbonate solution, water and a sodium chloride solution, dried over magnesium sulfate, and evaporated. The residue is purified by column chromatography. There are obtained in the form of a light oil, 1.1 g of the title compound, yield 20.% .. ' _r,. ' Thin layer chromatography: Rf = 0.58 (benzene-acetone =

: Γ. ^: '-10: 0.5)' - ^;

IR (PiIm): 1735 (CO), 1460, 1375, 1160, 1030cm " ¹

¹ H-MTR (CDCl ₃ ): .1-1-1.8 (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, -CHg-O); 3.68 (3H, s, CH ₃ OOC); 4.5-4.65. (1H, m, O-CH-O); 5.1 (1H, m, -CH =).

Analysis: Calculated C ₃₅ H ₆₆ O ₄ (550.91): 'G: 76.30; H: 12.07

found: . C: 76.18; H: 12.2t.

b) Methyl- / 10-methyl-28- (2-tetrahydropyranyloxy) -

- ' oktakozanoajb7' / "(X); R = CH-; ^ tetrahydropyranyl /

~~ J: ' ''-'

0.55 g (1 millimole) of methyl / T0-methyl-28- (2-tetrahydropyranyl-oxy) -10-octacozenoate 7 / * ~ (IX); R = CH-; Y = Tetre.hydr.opyrany 1_7 are hydrogenated in 20 ml of anhydrous methanol in the presence of 0.3 g of a palladium / carbon catalyst. After taking up the theoretical amount of hydrogen (3 hours, 24 ml), the catalyst is filtered off, washed with methanol, and the combined methanoliseben solutions are under reduced. Concentrated by evaporation. There are obtained 0.52 g of the title compound, yield 95 ^ ₉

- 21 - '' '' '' '

.3J? ' ₍ (Pilm): 1735 (CO), 146O, 1380, 1? 60, 1075, 1030 cm ^{-1 ) 1-} H-MR (ODOl ₃ ): 0.8? (3H, d, J = 8H7., H- CH ₃ );

ί, 0 ~ · ΐγ9 (55H, m, -CH ^ -): 2,3 (2H, t, J = 7Hz, -CHp-GOO); 3.2-4.1 (4, m, -CH 2 O); ; 3.65 (3H, θ, CH ₃ OOC); 4.5-4.65 (IH, m,

0-CH-O):

Analysis: ^C 35 ^H 68 ° 4 (552.93)

calculated: C: 76.02; H: 12.39 found:. C: 75.88; H: 12.53-

c) 10-Meth-28- (2-tetrahydropyranyloxy) -oquaporazane / (X); R = H; Y = Tetrahydropyranyl7

0.55 g (1 mmol) of methyl / ~ 10-methyl-28 ~ (2-tetrahydropyra-nyloxy) -ozozozanoate ^ 7 are stirred in 10 ml of a 1 N sodium hydroxide solution for 6 hours at room temperature. The reaction mixture is poured into 12 ml of 1 N hydrochloric acid and extracted with ethyl acetate. The organic layer is washed with water and a sodium chloride solution, dried over magnesium sulfate and concentrated under reduced pressure. The solidifying substance is further processed without purification. There are obtained Ό, 45 g of the titled compound, yield 83 % IR (film): 1715 (CO), 146O, 1380, 1200, 1080, 1030 cm ^-1 ', ¹ H-MMR (CDCl ₃ ) O, 82 (3H, d, J = 8Hz, H-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), 4.5-4.65 (1H, m, O-CH-O), - "

d) methyl-, 1'-O-dimethyl-1'-tetrahydropyreiiyloxy) -ozozozozate_7

/""(.II)·-; R = CH- ,; Y Tetrabydropyranyl7

- j .

0.31 g (3 mmol, 0.43 ml) of diisopropylamine and 1.9 ml (3 mmol) of a 15% butyllithrum solution formed in hexane are added to 10 ml of anhydrous tetrahydrofuran under inert gas at OC ⁰ . To the mixture is added, at 0 °, a solution of 0.54 g (1 mmol) of 10-methyl-28- (2-tetra-jiydropyranyloxy) -ozozoic acid / (X); R = H; Y = tetrahydropyranyl-7 in 3 ml of hexamethylphosphoric triamide; whereupon the Reaktionegemisch at 0-5 C was stirred for ⁰ 20 minutes long. the cooling is interrupted and at room temperature 0.17 g (1.1 millimoles, 0,0,8 ml) Metbyljodid be zugege'ben. the reaction mixture is for the purpose of The organic layer is washed with an ammonium chloride solution, water and a sodium chloride solution, dried over anhydrous magnesium sulfate and evaporated under reduced pressure to give the resulting crude acid (0.4 g) esterified immediately with diazomethane and the resulting ester purified by chromatography (10: 0.5 benzene-acetone mixture).

There are obtained 0.35 g of a colorless oily product (yield 65%), which is identical to the compound prepared according to Example 1 in all properties.

This product can be converted into the pheromone compound of the formula I in the manner described in Example 1,.

Claims (2)

Claims:. 1. Procedure for hearing from m ? ⁰ S - hydroxy-3,11-dime t-butyl-2-oxonocozanone; Formula 1, ' HO-CH ₂ - (GHp) ₁₇ -CH- (CH ₂ ) ₇ -CH ~ C-CH,. (I) CH ₃ .. 0 · characterized in that one a) an alkyl ~ (2,10-dimethyl-28-oktakozansäure) · derivative of the general formula II YO-CH ₀ (CH ₀₎ C-CH ₀ -CH (CH ₀₎ ^ - CH-COOR (Jl) ₀ ( ₀ CH-, CH- wherein ^ represents an alkyl group having 1-5 carbon atoms and Y is a tetrahydropyranyl or 2-Äthoxyä'tb3rlgruppe, in a solvent of ether type, preferably, under KlIhlung. with a Trialkylsylylmethyllithium, and dae formed intermediate of the general formula 'in,. , : '' · YD -CH ₀ - (CH ₂ ) ^ γ-CH- (CH ₂ ) γ-CH * - O-CHp-SI- R ₂ (IU) CH ₃ 0 ''. λ. - ^2Λ -. '. · ·. '. ' wherein R ₁ , Rp and R independently of one another each represent an alkyl group having 1-4 carbon atoms and Y has the above meaning, suitably without Isolation in the reaction mixture with an aliphatic alcohol and the protective group of the resulting compound of the general formula IVV (CHg) ₁₇ -CH- (CHP) ₇ -CH --- C-CH _3. (IV), wherein Y has the above meaning removed by acid treatment; or b) an alkyl - (2,10-dimetyl-28-oktakozanoic acid) derivative of the general formula II wherein R and Y are as defined above, in an ether-type solvent with the solution of a strong one Reacting methylsulf inylmethyds formed in dimethyl sulfoxide, the resulting product with a reducing agent, preferably Aluminiumamalgam, treated and removed from the resulting compound of general formula IV, wherein Y has the above meaning, the protecting group by acid treatment: and isolating the compound of formula I thus obtained from the reaction mixture 2, Method according to claim. 1, variant a), characterized in that an ester of the general formula II first with trimethylsylylmethyllithium and thereafter , , treated with methanol.