DE2758882A1 - Cis-7,8-epoxy-2-methyl-octadecane prodn. - by electrochemical condensn. of pelargonic acid and cis-4-octene-di:oic acid ester, useful as insect sex attractant - Google Patents

Abstract

Prodn. of cis-7,8-epoxy-2-methyloctadecane (I) comprises first electrochemical condensn. of pelargonic acid with cis-4-octenedioic acid monomethyl ester to give methyl cis-4-pentadecenoate. This is then saponified and electro-chemically condensed with 4-methylvaleric acid to give cis-2-methyl-7loctadecene (II) which is converted to (I) by epoxidation with a peracid. (I) is the sex attractant of female Portheria dispar and can be used as a bait. This process uses readily available starting materials and provides high yields of pure (I) obviating the difficult sepn. of trans isomer.

Description

Process for the preparation of cis-7,8-epoxy-2-methylloctadecane

The present invention relates to a method of production of cis-7,8-epoxy-2-methyloctadecane.

cis-7,8-epoxy-2-methyloctadecane, known under the name Disparlure, is the sexual attractant of female animals of the forest pest Petria dispar of the order Lepidoptera (gypsy moth) (Science 1970, 87-89). The corresponding trans compound shows a biological activity which is weaker by a factor of 10.

Syntheses for the production of 7,8-poxy-2-methyl-octadecane are over Science 1970, 87, Chem. Ber. 109, 3375 (1976), Angew. Chem.

84, 67 (1972) and DT-AS 25 31 959 are known. A major disadvantage One of these syntheses is that they result in a mixture of the cis, trans isomers of the precursor 2-methyl-7-oceadecene and thus a mixture of the geometric isomers of the sex attractant result in low yields. The isomers can be separated by chromatography, however, the separation is complex and can only be carried out with small amounts. Furthermore prepares the procurement of expensive base products in larger quantities and the Carrying out the large number of reaction steps in the known processes, wherein it is, for example, a complicated reaction step, such as a Grignard reaction and reactions with butyllithium, difficulties.

The object of the invention was therefore to provide a simple and economical To find a process for the production of pure cis-7,8-epoxy-2-methyl-octadecane, which allows the production of the sex attractant on a larger scale.

It was found that cis-7,8-epoxy-2-methyloctadecane was in good yield can be obtained if pelargonic acid with cis-4-octenedioic acid monomethyl ester electrochemically condensed to methyl cis-4-pentadecenoate, the methyl cis-4-pentadecenoate saponified, the cis - pentadecenoic acid obtained in this way with 4-methylvaleric acid electrochemically condensed to cis-2-! 4ethyl-7-octadecene and the cis-2-methyl-7-octadecene with a Peracid is epoxidized to cis-7,8-epoxy-2-methyloctadecane.

The process according to the invention leads to the pure in good yield cis-7,8-epoxy-2-methyloctadecane, so that a separation of the geometric isomers not applicable. The starting products pelargonic acid used in the first reaction step and monomethyl cis-4-octenedioate are readily available. Besides, they are two electrochemical process steps without much confusion and inexpensive feasible.

The starting product used in the process according to the invention Monomethyl cis-4-octenedioate can be obtained by selective cleavage of a double bond of the easily accessible and inexpensive cis, cis-1,5-cyclooctadiene by ozonolysis (Chem. Abstr. 68, 12407e (1968); Armer. Chem. Soc. Div. Petrol. Chem., Preprints 12 (2), D-5 D-10 (1967)), oxidative work-up to cis-4-octenedioic acid and esterification can be obtained to the monomethyl ester.

Ozonolysis of the cis, cis-1,5-cyclooctadiene is expedient at a temperature in the range from -78 to + 50C, preferably in the range from -78 to -500C. Suitable solvents are aliphatic ketones, such as Acetone, methyl ethyl ketone, diethyl ketone, cycloaliphatic ketones, such as cyclohexanone, Cyclopentanone, and alcohols such as methanol, methanol, propanol, tert-butanol. Alcohols and less inert solvents can only be used to a limited extent, since they are used in addition to acids and esters provide a significant number of by-products. Preferred solvent is acetone.

To selectively cleave one of the two equivalent olefinic To achieve double bonds of cis, cis-1,5-cyclooctadiene, the diene must in large Excess exist, i.e. ozone may only be introduced into the reaction mixture for so long as long as there is excess diene. Appropriately directs 0.1 to 1 equivalent, preferably 0.2 to 0.4 equivalent, of ozone is used per ol of diene a. Unreacted diene can after adding water together with the solvent be dragged out of the reaction mixture.

Oxidizing agents are suitable for the oxidative processing of the mono-ozonide such as hydrogen peroxide, peracids, oxygen in the presence of a catalyst that for example silver oxide, chromic acid and silver oxide. Very suitable oxidizing agents are silver oxide, chromic acid and oxygen in the presence of catalytic amounts of Silver oxide in an alkaline medium. The preferred oxidizing agent is chromic acid, there this under the reaction conditions mentioned with that still present after ozonolysis olefinic double bond does not react and is much cheaper than silver oxide.

The oxidation to cis-4-octenedioic acid can be achieved with chromic acid a temperature in the range from 0 to 200C, expediently that for ozonolysis suitable solvent acetone. After separating the solvent and of the unconverted cyclooctadiene can the unsaturated diacid with ether extract from the aqueous phase. The yield of cis-4-octenedioic acid reached approx. 55%.

The cis-4-octenedioic acid monomethyl ester can in a conventional manner by partial esterification or by esterification to the dimethyl ester and subsequent partial saponification can be obtained.

For the preparation of the dimethyl ester, cis-4-octenedioic acid is advantageously used with absolute methanol in the presence of a catalytic lot Acid, for example conc. Sulfuric acid, hydrochloric acid or p-toluenesulfonic acid Esterified at room temperature.

After the usual work-up, the diester is obtained in a 70% yield. The cis-4-Cctendisäuredimethylester can then with an equivalent methanolic Potassium hydroxide solution at room temperature in a conventional manner and with a Yield of about 80 s are partially saponified.

The electrochemical condensation of pelargonic acid with the cis-4-octenedioic acid monomethyl ester is made using solvents such as lower alcohols, for example Methanol, which can contain 10 to 20% water, carried out.

The electrochemical conversion takes place under known conditions carried out. For example, 10 to 30 percent by weight solutions of the Starting components. A degree of neutralization turns out to be, for example is adjusted with potassium hydroxide, of less than 5 OK, preferably 1 to 2 %, and at the same time a current density of 150 to 300 mA / cm2 is advantageous.

In general, cell voltages of 30 to 200 V, in particular from 80 to 100 V, worked. The cell voltage decreases during electrolysis, while the pH rises. When a pH value of 8 is reached, the electrolysis completed.

Since the yield drops sharply at higher temperatures, it is recommended to work at temperatures below 40 0C. The reaction temperature becomes usually between 10 and 300 ° C., in particular between 15 and 25 ° C., held.

It is advisable to use one of the two starting materials in large excess use in order to achieve the highest possible yield of unsymmetrical in the condensation Achieve product. Favorable molar ratios are in the range from 1: 3 to 1 : 20, in particular in the range from 1:10 to 1:15. The yield of asymmetrical product fluctuates between 45 and 65 s.

Platinum, platinum-rhodium, Platinum-iridium or platinum-coated titanium. The cathode material is not critical. It should only not corrode in the weakly acidic electrolyte when de-energized. Platinum, Faelstahl, graphite or titanium are suitable.

A conventional cell made of a glass vessel is used as the electrolysis cell with cooling jacket, side flange for reflux condenser and a Teflon stopper with holes for thermometers and electrode leads. As an electrode material For example, platinum sheets with a thickness of 0.05 mm are suitable.

The use of this cell type is not a requirement, it may be possible other cells can also be used.

After the electrolysis, the reaction mixture, which in addition to methyl cis-4-pentadecenoate still contains n-hexadecane, in the usual way, e.g. with 5N ethanolic potassium hydroxide solution, be saponified, whereby n-Mexadecane is formed after the alcohol has been spun off with petroleum ether can be extracted. The potassium salt of cis-4-pentadecenoic acid can be dissolved in water and converted into the acid by acidification, which is then extracted with ether and can be purified by distillation. The yield of free acid is between 30 and 50%.

For carrying out the electrochemical condensation of cis-4-pentadecenoic acid with 4-methyl-valeric acid apply to the electrochemical condensation of Pelargonic acid with cis-4-octenedioic acid monomethyl ester made statements.

After the electrolysis has ended, the electrolyzate is expediently mixed with water and potassium carbonate. After brief stirring, this solution becomes with Petroleum ether extracted. After distilling off of the solvent can the condensation products 2,7-dimethyloctane, cis, cis-11,17-octacosadiene and cis-2-methyl-7-octadecene are separated by distillation. cis-2-methyl-7-octadecene falls in yields of 60 - 65% on.

The epoxidation of this olefin to cis-7,8-epoxy-2-methyl-octadecane takes place in the usual way by means of at least an equimolar amount of a peracid, such as peracetic acid, perbenzoic acid, m-chloroperbenzoic acid. Advantageously epoxidized one with solutions of m-chloroperbenzoic acid in chloroform or methylene chloride, the one at temperatures of -20 to + 10 ° C, preferably at 0 ° C, to solutions of cis-2-methyl-7-octadecene is added dropwise in the same solvent. After a reaction time of 3 to 5 hours at 0 ° C., any precipitated m-chloroperbenzoic acid is filtered off, the The solvent is drawn off and the residue is taken up in ether. The ether phase is washed with dilute alkali and water, dried and a distillation subjected to pure cis-7,8-epoxy-2-methyl-octadecane in yields of 85 to 95% can be obtained.

The synthetic attractant can be due to its biological activity to be used in the areas infested by Porthetria dispar to attract a pest population, in order to then, if necessary, use insecticides or destroy it in some other way. To this end, the attractant can be in highly diluted solutions such as benzene, hexane, petroleum ether, etc.

applied, if necessary with antioxidants or stabilizers offset, come into use. This type of pest control is environmentally friendly and technically advanced, since the classic pesticides are not more need to be spread over large areas.

Examples 1. Preparation of the starting product monomethyl cis-4-octenedioate a) Preparation of cis-4-octenedioic acid Using a solution of 27.05 g of cis, cis-1,5-cyclooctadiene an oxygen-ozone mixture is passed into 250 ml of acetone at -780C for 94 minutes. After adding 100 ml of water and 1 ml of conc. Sulfuric acid is not distilled converted starting materials together with acetone and water up to a temperature of 7300 from. The remaining ronozonide is taken in 50 ml over potassium permanganate distilled acetone and so long a solution of chromic acid drips at 0 -0 5 0 in sulfuric acid (267 g of chromic acid in 230 ml of conc. sulfuric acid, to 1 liter with water filled up) until a brown color persists. Leaves the entire mixture you then stand for 5 minutes at room temperature and then add 150 ml of ice water added. The product is then taken up in 400 ml of ether, the ether phase is with 240 ml of a 5 strength sodium hydroxide solution extracted, the aqueous phase with conc.

Hydrochloric acid acidified to pH 2 and continuously with for 24 hours Ether extracted. After drying the ether phase over sodium sulfate and spinning off of the ether one receives cis-4-octenedioic acid, which recrystallizes from ether / petroleum ether (1: 7) will.

Yield: 7.35 g, corresponding to 57% of theory; M.p .: 96-980C.

Unconverted cis, cis-1,5-cyclooctadiene can be quantitatively restored can be recovered by adding enough water to the distillate until all of the acetone is in the aqueous phase. The separation of the phases delivers then the diene, which can be purified by distillation. Likewise can also the acetone salted out with potassium carbonate and the diene after separation from the aqueous phase are purified by distillation.

b) Preparation of the cis-4-octenedisuremonomethyl ester 5.5 g of cis-4-octenedioic acid and 60 ml absol. Methanol are concentrated with the addition of 2 ml. Sulfuric acid 24 hours stirred for a long time at 200C. The reaction mixture is then neutralized with a saturated sodium bicarbonate solution, draws the main amount of methanol under reduced Pressure off and extracted the residue with ether. The ether extract is mixed with water washed, dried over magnesium sulfate; after removing the ether, the residue becomes distilled. 4.46 g of dimethyl cis-4-octenedioate are obtained, corresponding to one Yield of 70% of theory, boiling point 740C / 0.01 Torr.

To 4.42 g of dimethyl cis-4-octenedioate in 8 ml of absolute methanol a solution of 1.24 g of potassium hydroxide in 8 ml of absolute Methanol added dropwise. The reaction mixture then remains at room temperature for 24 hours stand and is then reduced to half. Extracted after adding water the entire solution several times with pentane to dimethyl cis-4-octenedioate to remove from the reaction mixture. The aqueous phase is then mixed with 20 ml of carbon tetrachloride offset and with conc. Hydrochloric acid acidified to pH 3.

After the organic phase has been separated off, carbon tetrachloride is added several times (4 x 40 ml) extracted. After drying over calcium chloride and distilling off the Solvent, 2.24 g of monomethyl cis-4-octenedioate are obtained in one purity of 94%, yield 78.9% of theory; nD23 = 1.4609.

2. Production of methyl cis-4-pentadecenoate The electrochemical Condensation takes place in an electrolytic cell from a 150 ml glass vessel with cooling jacket, side ground joint for reflux condenser and a Teflon stopper for thermometers and electrode leads. The electrodes are 0.05 mm thick platinum sheets with a surface area of 4 cm2 are used.

2.7 g of cis-4-octenedioic acid monomethyl ester and 22.9 g of pelargonic acid become in 80 ml absolute Dissolved methanol, neutralized to 1 Z with potassium hydroxide and at a current density of 240 mA / cm2 until reaching pH 8 at one temperature electrolyzed from i5 to 30 0C. The yield determined by gas chromatography ethyl cis-4-pentadecenoate is 65%, based on the monomethyl cis-4-octenedioate used, with a total yield of 72 S of methyl cis-4-pentadecenoate and n-hexadecane, which also occurs as a condensation product.

C, H Analysis: 16 30 2 Calcd .: C 75.53 H 11.88 (254.41) Found: C 75.84 H 11.81 1H-NMR spectrum at 100 MHz in CCl4: 5.34 (m, 2H, -CH = CH-); 3.62 (s, 3H, -C02CH3); 2.3 (mc, 4H, -CH2-CH: CH-CH2); 2.08 (m, 2H, -CH2-CO2H); 1.3 (mc, 16H, -OH2-); 0.9 (m, 3H, -CH3).

3. Production of cis-4-pentadecenoic acid After completion of the electrolysis the solution with 25 g of potassium hydroxide in 100 ml of ethanol over 5 hours in the usual way Way saponified. After the solvent has been stripped off, n-hexadecane is continuously added Separated extraction of the salt precipitate with petroleum ether. The potassium salt will then dissolved in water, the aqueous solution is made with conc. Acidified hydrochloric acid and extracted with ether. After drying the ether phase over sodium sulfate and stripping of the solvent is obtained by distillation from 1.76 g of cis-4-pentadecenoic acid Bp 131-13500 / 0.04 torr; Yield 48% of theory

4. Production of cis-2-methyl-octadecene in an electrolysis cell, how to make the cis-4 Methyl pentadecenoate is used, 1.0 g of cis-4-pentadecenoic acid and 4.52 g of 4-methyl-valeric acid are used in 80 ml absolute

Dissolved methanol, neutralized to 1 S with 0.048 g of potassium hydroxide and with a current density of 250 mA / cm2 until reaching pH 8 at one temperature Electrolyzed from 15 to 300C.

After the electrolysis has ended, the electrolyzate is mixed with 100 ml of water and 10 g of potassium carbonate are added and the mixture is stirred for 5 minutes. Then the solution Extracted continuously with petroleum ether for 15 hours. A separation by distillation gives 0.64 g of cis-2-methyloctadecene, bp 126-1290C / 0.2 Torr; Yield 62% d.Th. GC-MS coupling allows 2,7-dimethyloctane and cis, cis-11,17-octacosadiene in addition to cis-2-methyl-octadecene.

5. Preparation of cis-7,8-epoxy-2-methyl-octadecane To a solution of 0.4 g of cis-2-methyl-7-octadecene in 20 ml of absol.

Methylene chloride is added dropwise while cooling with ice and stirring 0.345 g of m-chloroperbenzoic acid dissolved in 10 ml of absol. Methylene chloride. The mixture is stirred for 5 hours while cooling with ice, the solvent is distilled off and the residue is taken up in 30 ml of ether. The ether solution is washed with sodium hydroxide solution and then with water, dried over sodium sulfate, the ether is stripped off under reduced pressure and the residue is distilled. 0.38 g of cis-7,8-epoxy-2-methyl-octadecane are obtained, corresponding to a yield of 89% of theory. Bp 138-140 ° C / 0.2 Torr; nD ° = 1.4470; 1H-NMR spectrum at 100 MHz in CCl &:

Claims (1)

Claim process for the production of cis-7,8-epoxy-2-methyloctadecane, characterized in that pelargonic acid is monomethyl esterified with cis-4-octenedioic acid Electrochemically condensed to methyl cis-4-pentadecenoate, methyl cis-4'-pentadecenoate saponified, the cis - pentadecenoic acid obtained in this way with 4-methylvaleric acid electrochemically condensed to cis-2-ethyl-7-octadecene and the cis-2-methyl-7-octadecene with a Peracid is epoxidized to cis-7,8-epoxy-2-methyloctadecane.