DE2549765A1 - Long chain cis alkene housefly sex attractant - prepd. from unsaturated fatty acid chloride by reaction with Grignard reagent then redn. - Google Patents

Abstract

Prodn. of long-chain (Z)-9-alkenes (I) comprises first reacting acid chlorides of formula (II) with a soln. of an n-alkyl Mg halide contg. a Cd salt to give the ketones of formula (III). (III) are then reduced conventionally to (I). (n = 7-11 and p = 11-n for prodn. of tricosenes, and n = 7-9 and p = 9-n for prodn. of heneicosenes). Specifically claimed are the novel (Z)-heneicos-12-en-4-one and (Z-tricos-14-en-6-one. The (Z)-9-tricosenes and heneicosenes are components of the sex attractant of the housefly. (I) are prepd. in good yields with high stereochemical purity. Pref. (II) are derived from erucic and oleic acids since these are readily available in pure form. Reaction with the Grignard is in ether, THF, dioxan etc. and the Cd salt is pref. the anhydrous chloride, bromide or iodide used at Cd:Mg atom ration >=0.5:1. The ketone is pref. reduced using a high boiling solvent (pref. glycols or glycol ethers) and solns. of alkali hydroxide and hydrazine hydrate at >=100 degrees C, esp. 100-200 degrees C.

Description

Process for the preparation of long-chain (Z) -9 alkenes

The present invention relates to a simple process for the preparation of in particular (Z) -9-tricoses and (Z) -9-heneicoses, the constituents the sexual attractant of the housefly (Musca domestica L.).

Founded by the discoverers of the Musca domestica pheromone, D.A.

Oarlson et al in Science 174, 76, (1971) reported synthesis of (Z) -9-Tricosen, which in a reaction of the phosphorane from l-bromotetradecane and Consists of triphenylphosphine with n-nonanal, leads to a mixture of cis-trans isomers, which have to be separated chromatographically in a complex manner. For a technical This method is not suitable for execution.

In D-OS 22 49 679 a synthesis of (Z) -9-tricoses is proposed, in which acetylides of l-pentadecine or l-iecine with l-bromooctane or l-bromotridecane are reacted and the 9-tricosine formed in the presence of a noble metal catalyst is partially reduced by hydrogen. The representation of the long-chain acetylides is, as explained in the DU-OS on page 3, problematic and with particular difficulties tied together. Because of the need to use metal acetylides and difficult Manageable metal alkyls for the formation of the long-chain alkynes and their linkage To use with the respective alkyl halides appears to be the multi-step process as technically very disadvantageous. The same applies to those in J.Org. Chem. 37, no. 24, 3971 (1972) given synthesis, in which erucic acid in the presence of o-phenanthroline is reacted with methyl lithium to the intermediate product (Z) -Tricos-14-en-2-one.

(Z) -9-Tricosen is also through a stereoselective cis-olefination according to Wittig, Chem.-Zt-g. 98, 3, 161 (1974) obtainable by adding a solution of potassium in hexamethylene phosphoric acid triamide with phosphonium salt to form the phosphorylide (C6H5) 3P + C-H (CH2) 7CH3 reacted and the solution of the ylid is reacted with n-2etradecanal. The yield of (Z) -9-tricosene is only 32%.

(Z) -9-Heneicosen is shown accordingly in 37 pointer Yield available.

According to Gribble et al, J. Chem. Soc., Chem. Commun. (19), 735, (1973) provides a mixed Kolbe electrolysis of oleic acid and enanthic acid in methanolic sodium methoxide solution after work-up and recycling of the by-products only 40% (Z) -9-2ricosen.

Finally, (E) / (Z) -9-tricosene isomer mixtures are produced by olefin cross-metathesis reactions synthesized. been, in which l-decene and l-tetradecene in chlorobenzene solution were brought to reduction in the presence of [(C6H5) 3P] 2Mo (NO) 2C12 and C2H5AlOl2 (La Chimica e L'Industria 57, No. 4, p. 242, (1975).

The yield of (E) / (Z) -isomers des-tricosene was only 26%.

Silica gel impregnated by column chromatography on silver nitrate the active (Z) -isomer was isolated therefrom, which still contains up to 8% of the inactive (E) isomers.

The (Z) isomer here is considered to be that in which the two long-chain organic radicals emanating from the double bond are in the cis position.

It has now been found that (Z) -9-uricoses and (Z) -9-heneicoses in particular can be prepared in a simple manner in good yield and high steric purity by starting from the chlorides of certain unsaturated fatty acids by means of a modified Grignard reaction The longer chain emanating from the double bond is built up in the form of the ketone corresponding to the target product in terms of double bond and chain length, after which the reduction to the (Z) -9-alkenes takes place in a manner known per se is the same, by reacting with the complementary alkyl magnesium halide either one of the two (Z) -9-alkenes or by reacting with the mixture of the two respective alkyl magnesium halides, a mixture of both (Z) -9-alkenes can be produced, the effect of which is known to be produced in the Application added.

The invention therefore relates to a process for the preparation of long-chain (Z) -9-alkenes, which is characterized in that an acid chloride of the formula is used to form (Z) -9-tricoses with cadmium salt-containing solutions of n-alkylmangesium halides of the C chain length - (CH2) m-CH3 to form ketones of the formula where n = 7 to 11 and in = 11 minus n, or means 4. to form (Z) -9-heneicosene an acid chloride of the same formula, in which n = 7 to 9, with cadmium salt-containing solutions of n-alkylmangesium halides of the C chain length - (CH2) p-CH3 to give ketones of the formula where n = 7 to 9 and p = 9 minus n, converts and.

the ketones by reduction in a known manner into various associated (Z) -9-alkenes convicted.

Accordingly, such an n-alkyl radical is chosen which contains the carbon atoms of the Acid chloride in the case of the (Z) -9-tricon to 23 and in the case of the (Z) -9-heneicosen added to 21.

In the case of the mixture of the two (Z) -9-alkenes, a mixture of both the X-Eette of each supplementary n-alkyl radicals in the ratio of the quantities to be produced (Z) -9-alkenes selected and reacted with e.i.nem acid chloride, in which n = 7 to 9.

Although in principle all acid chlorides of the formulas mentioned can be used are the chlorides of erucic acid and oleic acid because of accessibility these acids are preferred in their pure form.

The e ketones, which the (Z) -9-alkenes to be produced already with regard to correspond to the isomerism and position of the double bond, as well as the C chain lengths be converted into the associated (Z) -9-alkenes with all reducing agents, which only reduce the keto group.

The ketone is expedient by heating with high-boiling, preferably Solutions of alkali hydroxides and prepared with glycols and / or glycol ethers Hydrazine hydrate reduced at temperatures above 100 ° C.

In general, temperatures from 100 to 25,000 are preferred used from 100 to 2000C.

Acid chlorides of the general formula are easily accessible from the corresponding cis-unsaturated acids, which are components of natural oils and fats in the form of their glycerides, by known, simple processes, for example by reaction with thionyl chloride. The acid chloride in question can be used for the (Z) -9-alkene synthesis as a crude product, optionally dissolved in inert solvents, for example aromatic hydrocarbons.

The solutions of the n-Alkylmagnesiumihalogenide can after for the Preparation of such Grignard reagents using the usual method by reacting n-alkyl halides, which can be present as chlorides, preferably as bromides or iodides, with metallic Magnesium are produced.

Particularly suitable nucleophilic solvents are diethyl ether, higher dialkyl ethers with up to about 5 carbon atoms in the alkyl radical, tetrahydrofuran or dioxane, The preferred solvent is diethyl ether.

Oadmium salts are preferred, preferably as chloride if appropriate added as brimide or iodide to the anhydrous halides. They are added to the solutions added to the Grignard reagents after the metallic magnesium had dissolved. That The atomic ratio Od: Mg is at least 0.5: 1. An excess of cadmium salt affects the yield does not.

The amount of Grignard reagent should be equivalent to the acid chloride not or not significantly exceed.

The synthesis can be carried out in the following way: The addition the acid chlorides optionally dissolved in an inert solvent cis-unsaturated carboxylic acid of the structural formula given above for the solution of the Cadmiumslzhaltigen Grignard reagent takes place at room temperature with stirring, whereby the exotic reaction can be easily controlled by cooling the reaction vessel with water and the case of necessity is to be moderate. After the addition of the acid chloride is complete Approach on the reflux condenser to complete the reaction to the boiling point of the respective solvent heated.

In general, this temperature can range from 0 to 12000, preferably between 20 and 80 ° C.

After the Mg / Cd compounds have been broken down using diluted mineral acids the organic phase, which contains the keto in question, neutral washed, dried and the solvent was distilled off. The ketones can be destillative getting cleaned.

For example, (Z) -Tricos-14-en-2-one boils at 14,000 and 0.1 Torr. The subsequent reduction of the keto group requires distillation of the crude products but not absolutely necessary. The reduction of the ketone can be achieved by boiling with hydrazine hydrate in high-boiling, polar organic solvents in the presence made of alkali hydroxides. The preferred solvent is diethylene glycol.

The process of the invention is illustrated by the following examples illustrated: Example 1;,. A Grignard solution produced by reaction of 12.2 g (0.5 mol) of magnesium turnings with the solution of 48 g (0.5 mol) of methyl bromide had been prepared in 300 ml of diethyl ether, after the addition of 55 g (0.3 Mol) anhydrous cadmium chloride with a solution of 152 g (0.425 mol) erucic acid chloride added in 250 ml of anhydrous benzene with stirring and cooling of the reaction flask. The duration of the dropwise addition of the acid chloride solution was 2 hours. To complete the reaction was the batch for a further hour at a reflux temperature of 65 0 stirred. After pouring the cooled reaction mixture to 200 g of granulated Ice and acidification with 20% sulfuric acid, the organic phase was washed neutral. Drying took place with anhydrous magnesium sulfate. The solvent was distilled off, finally under vacuum of 10 Torr. The yield of crude ketone was 138 g (96.5% of theory, based on the erucic acid chloride used). For the subsequent Re-reduction, it was used without purification.

138 g of the crude ketone (approx. 0.41 mol) were with a solution of 96 g potassium hydroxide and 66 g hydrazine hydrate (content: 80% by weight) in 1 liter Diethylene glycol heated on a water separator. The temperature was raised during 90 minutes steadily increased up to 1960 G. At this temperature the light yellow solution became Stirred for a further 4 hours. The cooled reaction mixture was granulated to 300 g Poured ice and acidified with 6N HCl. The hydrocarbon was washed with petroleum ether shaken out. The petroleum ether solution was washed neutral and dried with anhydrous magnesium sulfate. After the petroleum ether has been distilled off 111 g of crude 9-tricosene remained (84% of theory). After a lead of 6 g up to 51 ° C at O> 1 Torr, the main amount went between 151 and 152.5 ° C at 0.1 Torr above. The acid number and the saponification number of the distillate were 0, the iodine number was 78.2 (calc. 78.7). A (Z) -olefinic double bond appeared in the IR spectrum associated band at 1650 cm-1. The (Z) -9-tricosene content was after GC analysis at least 96% .nD23 = 1.4520.

Example 2 A solution of 135.4 g (0.45 mol) of oleic acid chloride in 200 ml of anhydrous toluene was prepared as in Example 1 for 2 hours and with 0.3 mol of cadmium chloride, Grignard solution of 0.5 mol of metallic Magnesium and 0.5 mol of n-amyl iodide were added dropwise, with a water bath for cooling the temperature was limited to a maximum of 3000. Then the approach was still Stirred for 3 hours at boiling temperature (76Q0) on the reflux condenser. The work-up of the ketone (Z) -Tricos-14-en-6-one (crude yield 96% of theory, based on the Acid chloride) and its reduction were carried out as described in Example 1. the The yield of crude 9-2ricosen was 138 g (95% of theory, based on the amount used Acid chloride).

After a short run, the main run distilled between 150 and 152 ° C at 0.1 torr. The key figures of the distillate were: acid number and saponification number O; Iodine number 78.5 (calc.

78.7); nD23 = 1.4520; Band in the IR spectrum at 11650 cm-1 according to the gas chromatogram the product contained more than 96% of (Z) -9-tricosene.

Example 3 For the preparation of (2) -9-heneicoses from oleic acid chloride was carried out according to the procedure of Example 2 using the methods given there Proceed with quantities and substances, however, one prepared from 0.5 mol of n-propyl bromide Gridnard solution modified with CdOl2 was used. That obtained as a ketone - (Z) -Heneicos-12-en-4-one (crude yield about 95%) was reductive according to example 1 converted into (z) -9-heneicosene with high yield, which IR spectrometry was identified.

Claims (7)

Patent claims 1. A process for the preparation of long-chain (Z) -9-alkenes, characterized in that an acid chloride of the formula is used to form (Z) -9-tricoses (n = 7 to 11) with cadmium salt-containing solutions of n-alkylmangesium halides of carbon chain length - (CH2) m-CH3 to give ketones of the formula where n = 7 to 11 and m = 11 minus n, or for the formation of (Z) -9 "heneicosene an acid chloride of the same formula where n = 7 to 9 with cadmium salt-containing solutions of n-alkylmangesium halides of C. -Chain length - (CH2) p-CH3 to ketones of the formula where n = 7 to 9 and p = 9 minus n, is reacted and the Eetones are converted into the associated (Z) -9-alkenes by reduction in a known manner. 2. The method according to claim 1, characterized in that the Ketones can be bought by rit hochs' eden d £ n, preferably with glycols and / or glycol ethers prepared solutions of alkali hydroxides and hydrazine hydrate at temperatures above 1000C reduced. 3. The method according to any one of claims 1 or 2, characterized in that that erucic acid chloride and methyl magnesium halide are used. 4. The method according to any one of claims 1 or 2, characterized in that that oleic acid chloride and n-pentylmangesium halide are used. 5. The method according to any one of claims 1 to 4, characterized in that that the halides are used as cadmium salts. 6. (Z) -Heneicos-12-en-4-one. 7. (Z) -Tricos-14-en-6-one.