HU180386B - Process for producing 11-dodecen-1-ol and 11-dodecen-1-yl-acetate of insect-feromone activity - Google Patents

Abstract

11-dodecen-1-ol and its acetic acid ester are prepared by reducing an alkyl dodec-12-enoate (V) and, optionally acetylating. The compounds (V) may be prepared from compounds of formula (IV> OCH-(CH2)9-COOR<1> (IV> by a method suitable for the formation of a vinyl group, and the compounds of formula (IV) may be prepared by the oxidation of an ester of the general formula (III> HO-CH2-(CH2)9-COOR<1> (III> wherein R<1> has the same meaning as above. Esters of formula (III) may be prepared in a variety of ways, such as the treatment of a corresponding haloester with a base, or the esterification of the corresponding acid. <IMAGE>

Description

The present invention relates to a process for the preparation of 11-dodecen-1-yl derivatives of the general formula (I). In the formula, R is hydroxyl or acetoxy. The compounds of formula (I) are present in the sexual attractants of several pest insects. and are useful in integrated pest management. For example, the red cotton bellworm / red bellworm was extracted; Diparopsis castanea / • Nesbitt, B.F. , Beevor, P.S., Cole, R.A., Lester, R. and Poppi, I.G .: Nbture, New'Bioi. 1973 244/137/208; Nesbitt, B.F., Colé, F., Beevor, R.A., Lester, R. and Poppi, R.G., J. Insect Physiol., 1975-1907; Marks, R.J. s Bull. Entonol. Gap. 1976 219; 'Marks, R.TT: Bull. Entomol. Gap. 1976, 427; Marks, RT3T7 Bull. Entomol. Gap. 1976, 24 J.J. and the saddleworm / Eupoecilia ambiguella / R. Saglio, R., Descoins, C., Gallois, M., Jaouen, D. and Mercier, J., C.R. Reun. Pheromones Sex. Lepid, 1976, 119; Saglio, P., Descoins,

C., Gallois, M., 'lettere, M., Jaouen, D. and Mercier, J.s Ann. Zool. Ecol. Arii. 1977, 553j from Pheromone Extract, and both species have been shown to have good sex appeal with substances of the above structure.

Compounds of formula (I), when used in combination with other pheromone components, have sexual attraction to specimens of Spargonothis pilleriana (Saglio, P., Priesner, E., Descoins, C. and Gallois, M.: C.R. Reun. Pheromones Sex. Lepik. 1976, 109j | and pheromone inhibitors have an effect on the price of alimonyone / Ádoxőphyies orane / £ J.S.Voerman and A.K. Minks: Environm. Entom. 1973 »751» S.Voerman, A.K. Minks and N. W. H. Houx, Environm. Entom. 1974 »7O1 '| ·

-1180.386

The compound of formula (I) wherein R is an acetoxy group was synthesized by Beatmaim et al. In our article summarizing their method / Chem. Bhys. Lipids 24, 335 (1979), with reference to unpublished results. The starting material of their process is 11-octadecenyl-1-ol acetate, a very hard-to-reach, naturally occurring material, from which 11-acetoxy-undecanol is obtained by expensive equipment and is used only as a laboratory micellar microscope, from which by reaction with the appropriate alkylidene phosphorane, the target compound can be obtained in poor yield.

Synthesis of a compound of formula (I) wherein R is hydroxy is not described in the literature.

It has now been found that the compounds of formula (I) can be advantageously prepared on an industrial scale by:

the. The 11-halo-undecanoic acid of formula (11), wherein Hal is halogen, can be reacted with a base and the 11-hydroxy-undecanoic acid formed is converted to the ester of formula (III), preferably in the presence of a catalytic amount of an aliphatic alcohol. wherein R ^{1 is C} 1 -C 4 alkyl, the ester is oxidized in a manner known per se, the resulting 10-formyl-decanoic acid alkyl ester of Formula IV, wherein R 1 is as defined above, is methylene iodide; with zinc triethylaluminum reactant enough to convert the 11-dodecen-1-yl acid ester of formula (V) wherein R ^x is as defined above, then reducing the resulting ester and, if desired, the resulting 11- dodecene-l-oligomers; acetylated, or

b. 11-hydroxy-undecanoic acid with a C 1-4 aliphatic alcohol

- preferably in the presence of a catalytic amount of acid - is converted to an ester of formula (III) wherein R 1 is C 1 -C 4 alkyl - the ester is oxidized in a manner known per se, to give the resulting 10-formyl-decanoic acid alkyl ester - wherein R ¹ is as defined above, with the methylene iodide / zinc / triethylaluminum reactant mixture converted to the 11-dodecen-1-yl acid ester of formula (V) - wherein R ¹ is as defined above and then reducing the resulting ester and, if desired, acetylating the 11-do * decen-1-ol so prepared, or

c. oxidation of an 11-hydroxy undecanoic acid ester of formula (III) wherein R ¹ is as defined above is carried out in a manner known per se to give the resulting compound of formula (IV):

The alkyl ester of 10-formyl-decanoic acid, wherein R ¹ is as defined above, is converted into the methyl ester of formula II with the reactant mixture of methylene iodide zinc triethyl aluminum in the following formula: R ^ is as defined above and the resulting ester is reduced and optionally prepared

11-dodecene-1-ol is acetylated, or

d. / an alkyl ester of 10-formyl-decanoic acid of formula IV, wherein R ¹ is as defined above, with a reactant mixture of methylene iodide zinc triethyl aluminum in the general formula V

Is converted to the 11-dodecen-1-yl serine ester of formula-2180.386, wherein R ³ is as defined above, then the resulting ester is reduced and, if desired, the 11-dodecen-1-ol thus prepared is acetylated, or

e. II-dodecen-1-yl acid of formula (V). and R ¹ is as defined above and optionally acetylating the 11-dodecen-1-ol thus prepared.

The 11-halo-undecanoic acid (11) is commercially available. The base, preferably an alkali metal or alkaline earth metal hydroxide, can be converted to 11-hydroxy undecanoic acid. The alkali metal hydroxide is preferably sodium hydroxide. The reaction is preferably carried out in an aqueous medium. Preferably, a higher temperature, preferably the boiling point of the reaction mixture, is employed. The starting compound is preferably 11-bromo-undecanoic acid (II: Hal-Br). The 11-hydroxy undecanoic acid formed during the reaction is precipitated after acidification of the reaction mixture with acid / p.hydrochloric acid, sulfuric acid and can be removed by filtration.

Esterification of the resulting 11-hydroxy undecanoic acid yields the compound of formula (III). The reaction is preferably carried out using the appropriate alkanol, the excess of which may serve as the reaction medium. The reaction is preferably carried out with an acid, e.g. hydrochloric acid, sulfuric acid, phosphoric acid, p-toluenesulfonic acid / catalytic amount, preferably at elevated temperature, preferably at the reflux temperature of the reaction mixture. The compound of formula (111) thus obtained, with or without isolation, can be used for further reaction steps.

The oxidation of the ester of formula (III) may be advantageously carried out with pyridinium chlorochromate or bichromate or with active manganese carbonate 1. The reaction medium may be aprotic solvents. When oxidized with pyridinium chlorochromate, the reaction is preferably carried out in a halogenated aliphatic hydrocarbon such as dichloromethane, chloroform, carbon tetrachloride. When oxidized with manganese dioxide, the reaction medium is an aromatic hydrocarbon, e.g. benzene, toluene, xylene / are used. The reaction temperature between 0 and 60 ° C ^Ö - carried out - preferably at room temperature.

The resulting compound (IV) is converted to the ester (V) with methylene iodide / zinc / triethylaluminium reactant. Different ethers per reaction medium, e.g. diethyl ether. tetrahydrofuran, dioxane / alkalmazhatók.A reaction is carried out at a temperature between 0 ° and 60 ^°, preferably at room temperature.

The resulting compound (V) is then reduced to 11-dodecen-1-ol. Preferably, the reduction is carried out with a complex metal hydride, e.g. lithium aluminum hydride or sodium bis (2-methoxy-ethoxy) -aluminium hydride, or as an ether solvent, e.g. diethyl ether, tetrahydrofuran, di ⁴ oxane, or aromatic hydrocarbon, e.g. benzene, toluene, xylene / are used. Another preferred embodiment of the reaction is the reaction with metal sodium in the presence of alcohol. The reaction temperature may range from 0 ° C to 60 ° C; have advantages? The reaction is carried out at room temperature.

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The 11-dodecen-1-ol can, if desired, be converted, after or after isolation, to 11-dodecen-1-yl acetate. Acetylation is carried out with acetic acid or a reactive derivative thereof, preferably acetyl chloride or acetic anhydride. When acetyl chloride is used, the reaction is carried out in an ethereal solvent, e.g. diethyl ether, dioxane, tetrahydrofuran. If acetic anhydride is used as the acylating agent, an excess thereof may serve as a reaction medium. The reaction 'is preferably carried out in the presence of an acid acceptor. For this purpose, alkali metal carbonates / e.g. sodium or potassium carbonate, alkali metal bicarbonates, e.g. sodium or potassium bicarbonate / or organic bases, e.g. pyridine, triethylamine. The reaction temperature is 0 ° C to 80 ^° C can vary from; the reaction is preferably carried out at a temperature between 20 ° C and 40 ° C.

The process of the present invention is illustrated by the following example:

In each case, the composition of the eluent used for chromatography is given in% by volume.

Example

Preparation of 11-dodecen-1-yl acetate / 1, R = CH2 COO-

a. / 11-Hydroxy undecanoic acid

13.25 g (0.05 mol) of 11-bromo-undecanoic acid (II, Holo = Br) are dissolved in 100 ml of 2 molar sodium hydroxide solution. After completion of the reaction, the solution is poured into 25 ml of concentrated hydrochloric acid, the precipitated crystalline material is filtered off and washed with water.

Yield: 9.1 S / 90% /

Mp. 69-70 ° C IR / KBr /: 3350, 1700 cm ^1. H-NMR / CDC1, /: 6.7 ^r s / br / 2H, OH / ^»P 3.65 / t <= T 10 Hz, 2H, CH2-O /; 2.35 (t, J = UHz, 2H, CH2-COO); 1.1-1.9 / m, 16 H, _-CH2 - /.

Analysis: ^{σ χχ Η} 22 ° ^3/202 »30 / theoretical: s 0 = 65.31% H = 10.96% Found e: s 0 = 65.10% H = II, 10%

b. Preparation of methyl II-hydroxy undecanoate III, R 1 -CH 2

To a solution of 11.1-hydroxy-undecanoic acid (10.1 g, 0.05 mol) in dry methanol (50 mL) was added sulfuric acid (0.31) and the solution was refluxed for 6 hours. The hot solution was neutralized with barium carbonate. * / Bowl (1.2 g), after cooling, filtered and the filtrate evaporated in vacuo.

Yield: 9.7 g / 90% /

IR / film /: 3400, 1735 ^{cm-1 1H-NMR} / CDCl / 3.70 / s + t, 5H, CH ₂ COOCH ^ + 0 /;

2.33 / t, J = 11 Hz, 2H, _CH2 -C00 / L

-4180.386

Analysis: 0 ₁₂ ^Η 24 ° 3 / 216.325 / Theory: C, 66.63; H, 11.18; Found: C, 66.42; H, 11.06;

c. Preparation of methyl 10-formyl decanoate IV, R RCH ^

6.46 g (0.03 ml) of pyridinium chlorochromate and 0.32 g (0.004 mol) of dry sodium acetate are mixed in 50 ml of dry dichloromethane and then 4.32 g / 0.02 mol / methyl -11-hydroxy undecancate was dissolved in dry dichloromethane (10 ml). date. The reaction mixture is stirred under an inert gas atmosphere (nitrogen or argon) at room temperature for 2.5 hours. *

The mixture is treated with 300 ml of dry ether and the ether solution is decanted from the precipitated sticky material and repeated several times with a little dry ether. The combined ethereal solution was filtered through a Bentonite filter pad, evaporated in vacuo and the residue distilled in vacuo.

Yield: 3.6 g 85% Fp77'111-113 ⁰ / 0.3 mm ng ³ = 1.6695 IR (film): 2720, 1735 cm @ -1 ¹ H-NMR (CDO 3): 9.83 / t , J-3Hz, 1H, CHO /;

3.68 (s, 3H, COOCH3); 2.32 / tt,

JsllHz, 4H, - CH ₂ CH ₂ 000 + -CH0 / |

1.1-1.9 (m, 14H, -CH-).

Analysis: ^G 12 ^S 22 ° 3 / 214-, 30 (theory) c ₌ 67.25% H = 10.35% found. 0 = 67.10 s% H = 10.28 s%

d. Preparation of methyl II-dodecenoate / V, AcHy

8739 g / H, ³3mot; To a mixture of 2.53 ml / dioiodomethane and 5.88 g / O, 9 molar zinc powder in 50 ml dry tetrahydrofuran is added 0.69 g / 0.006 mol under vigorous stirring under inert gas; 0.83 ml / triethylaluminium was added and the reaction mixture was stirred for 20 minutes. The reaction mixture was cooled to room temperature and a solution of 2.14 g (0.01 M) methyl 10-formyldecanoate in 10 ml dry tetrahydrofuran was added dropwise over 15-20 minutes and the mixture was stirred at room temperature for 1 hour.

--------- The reaction mixture is diluted with 100 ml of ether, water is added to 1 ml of dm-hydrochloric acid, the mixture is decanted from the zinc and the aqueous phase is separated. The aqueous phase was extracted twice with a total of 60 µl of ether. The combined organic layers were washed with 1 mol dm5 hydrochloric acid, dried with 5% sodium bicarbonate, 5% sodium bisulfite solution, water, saturated sodium chloride solution and then magnesium sulfate. The ether is distilled off in vacuo and the residue is distilled off in vacuo.

-5180.386

Yield: 1.85 g / 87% /

Fp. : 110-112 ° C / 0.3 mm n * ⁵ = 1.4395

IR (film): 1745, 1640 cm @ ^-1 (CDCl3): 5.5-6.5 (m, 1H, 11-H); 4.7-5.5 (tn, 2H, 12-H); 3.65 / s, 3 H, COOCH ^ / 2.32 t / t, J = llHz, 2H, _CH2 C00 /; 2.2 (t, J = 15 Hz, 2H, 10-H); 1.1-1.9 / m, 14H, -CH ₂ - /.

Analysis: Found: C, 73.54; H, 11.39; Preparation of C = 73.58 s% H = 11.21 s% ------------- _e 11 -Dodecen-1-ol / 1, R = OH /

To a suspension of lithium aluminum hydride (0.23 g, 0.006 mol) in dry ether (20 ml) was added dropwise a solution of 2.12 g (0.01 mol) of methyl II-dodecenoate in dry ether (5 ml) under inert gas for 15 minutes. and stirred at room temperature for one hour.

The reaction mixture was quenched with water with vigorous cooling, acidified with 1 mol dm hydrochloric acid, and the upper ether phase separated. The aqueous layer was extracted with ether and the combined aqueous portions were washed with 1 mol / d hydrochloric acid, 5% sodium bicarbonate, water, brine, and magnesium sulfate. dried. The ether was distilled off in vacuo and the residue was purified by column chromatography (Kieselgel 60, benzene: acetone 10: 2).

Yield: 1.6 g / 88% /

Rf = 0.28 (benzene: acetone 10: 1) (IR) (film): 3550, 1640 cm @ ^-1 @ 1 H-NMR (CDCl3): 5.5-6.3 (m. 1H, 11-H); 4.7-5.3 (m, 2H, 12-H); 3.65 / t, J = 10Hz, 2H, -CH ₂ -0 /; 2.10 (m, 2H, 10-H); 1.1-1.9 / m, 17 H, -0H ₂ - + 0H /.

H, 13.12 Found: C, 78.06; H, 13.17;

f. Preparation of 11-Dodecen-1-yl acetate (1, R = CH3 CO00)

1.84 g / 0.01 mol II-dodecen-1-ol and 1.19 g / 0.015 mol;

0.86 g / 0.011 mol to a solution of 1.2 ml / dry pyridine in dry ether (25 ml); Acetyl chloride (0.71 mL) was added and the mixture was stirred at room temperature for 10 hours.

The reaction mixture is diluted with ether / 50 .mu.l / .times.

Wash with -6180.386 dm hydrochloric acid, 5% sodium bicarbonate, water again, saturated sodium chloride solution, and dry over magnesium sulfate. The solvent was distilled off and the residue was distilled in vacuo.

Yield: 1.7 g / 75% / B.p .: 96-98 ° / 0.3 mm, n = ⁵ ^ 1.4398

GC; R _fc = 20 min. / SE 30; 3% Ch-AWSr 80-100 ,; 150 ° C /

IR / film / s 1740, 1635, 1230 ^{cm-1 1H-NMR} / CDCiy ·, 5.5-6.3 / m, 1H, 11-H /;

4.7-5.3 (m, 2H, 12-H); 4.18 / t, J = 10 Hz, 2H, CH ₂ 0 /; 2.05 / s + m, 5H, C00H ₅ + 10 _CH2 /; 1.1-1.9 / m, 16 H, _-CH2 - /.

Analysis: θΐ4 ^Μ ρθθ2 226.36 Found: C = 74.29% H = 11.58 Found: C = 74.11% H = 11.40%.

Claims (5)

A process for the preparation of 11-dodecen-1-yl derivatives of the general formula (I) in which R represents a hydroxy group or an acetoxy group, characterized in that the 11-halo-undecanoic acid of the formula II / ⁷ - Hal is a halogen atom, which is reacted with a base to form the resulting 11-hydroxy undecanoic acid with a C 1 -C 4 aliphatic alcohol, preferably in the presence of a catalytic amount of the acid / in / ester, where R ¹ The C 1 -C 4 alkyl group is the oxidation of the ester in itself, and the resulting 10-formate decanoic acid alkyl ester of formula IV, wherein R ¹ is as defined above, is methylene iodide / zinc / triethylaluminium. reaktánselegygyel converted to / V / formula 11-dodecen-l-yl acid ester - wherein ^R1 is as defined above - and then reducing the resulting ester, if desired, the thus obtained II-dodecene-l-ol was acetylated, or t> ./ 11-hydroxy-undecanoic C1-4 aliphatic alcohol> - forming / 111 / ester of the formula - -, preferably a catalytic amount of acid in the presence of the ^R1 1-4 CB-C alk alkyl, the ester is oxidized in a manner known per se, the resulting 10-formyl-decaneave alkyl ester of formula IV, wherein R ¹ is as defined above with a ~ methylene iodide / zinc / triethylaluminum reactant mixture converting the compound of formula (V) to the II-dodecen-1-yl sev-ester space in the formula. R is as defined above, followed by the ester obtained -7180.386 and optionally acetylating the 11-dodecen-1-ol so prepared, or c. an 11-hydroxy-undecanoic acid ester of formula (III) wherein R ¹ is as defined above is known per se; oxidizing manner, the received / IV / Formula 10-formyl-1-decanoic acid alkyl ester - wherein R ^ ^- is as stated above - with methylene iodide / zinc / triethylaluminum mixture of reactants * XbaI to / V / Formula Is converted to the 11-dodecen-1-yl acid ester - wherein R ¹ is as defined above and the resulting ester is reduced and optionally acetylated with the 11-dodecen-1-ol thus obtained, or d. / a 10-forryl decanoic acid alkyl * ester of formula IV wherein R 1 is as defined above, with methylene iodide / zinc / triethylaluminum reagent reactant 11-dodecen-1-yl of formula V converted to the acid ester - in the formula r! and the resulting ester is reacted and, if desired, acetylated with the 11-dodecen-1-ol so prepared, or an 11-dodecen-1-yl acid ester of the formula: wherein R 1 is reduction of the above-mentioned and optionally acetylation of the 11-dodecen-1-ol thus obtained, 2, A method according to claim 1, variant a /! Method, characterized in that the / 11 / general terms but needle ⁷ - reagéItatjuk - wherein Hal ..... are as defined above, - 11-halo-undecanoic alkali metal or alkaline earth metal hydroxide - preferably sodium hydroxide. 3. A method of concatenating the process according to claims a) and variant b), wherein the 11-hydroxy undecanoic acid and the 1- The C4 aliphatic alcohol is reacted in the presence of a catalytic amount of sulfuric acid, hydrochloric acid, phosphoric acid or p-toluenesulfonic acid. . The method of synthesizing the process according to the variant of claim 1, characterized by _? wherein the 11-dodecen-1-yl acid ester of formula (V) is reduced with femhydride, preferably lithium aluminum hydride, or metal sodium in the presence of an alcohol. The method of claim 1, variant (a) to (e)! characterized in that the acetylation of 11-dodecen-1-ol is carried out with acetic acid or a reactive derivative thereof, preferably acetic acid halide.