CS230350B1 - Process for preparing 7-dodecen-9-yn-1-ol - Google Patents

Abstract

The invention relates to a method for the preparation of 7-dodecen-9-yn-1-ol, which can be used as an intermediate for the preparation of sex pheromones of butterflies. The synthesis starts from 3-bromopropyl-methoxymethyl ether, which is converted into a Grignard compound with magnesium in tetrahydrofuran, which is then treated with 1-bromo- -1-nonen-6-yne in the presence of Li2CuCU. The protecting group is removed with ethylene glycol in an acidic ethanolic medium by boiling the mixture.

Description

The present invention relates to a process for the preparation of 7-dodecen-9-in-1-ol, an intermediate for the preparation of sexual pheromones, for example pheromone marbled pheromone (Lobesia botrana).

The reproductive behavior of the majority of insect species studied so far is mediated by sexual pheromones. Since the chemical identification of lepidopteran sex pheromone components has become quite routine, the number of isolated and identified pheromones is steadily increasing. However, it has been found that many, if not all, chemical communication systems are very complex, although pheromone structures are mostly fairly simple. The prakitic application of pheromones for the monitoring or control of insects is often not the most successful either because it is known to date either about the exact composition of pheromones or about the behavior that pheromones are induced. However, in many cases, one-component or multi-component active compositions can be successfully used to monitor the occurrence and flight of pests in integrated plant protection programs (FJ Ritter, Elsevier, Amsterdam 1979; Management of Insect Pests with Seiniochemicals; Publisher ER Mitchell, Plenum Press, New York 1981).

Sexual pheromones of butterflies are predominantly composed of unbranched aliphatic alcohols, aldehydes or acetates with 12 to 18 carbon atoms with 1 to 2 double bonds in different positions with geometric E or Z isomerism. Many insect species distinguish between isomers and small amounts of "incorrect" isomer may inhibit the reaction of insects to the "correct" isomer or the admixture of a small amount of one isomer in another causes interspecific resolution. Such stereospecificity requirements make syntheses of relatively simple compounds becoming nontrivial matters.

Sex pheromones are also a number of compounds containing a conjugated diene system in the molecule. Among them is (7E, 9Z) -7,9-dodecadien-1-yl acetate, the sex pheromone of marbled carob (Lobesia botrana). This compound can be prepared by reduction of (7E) -7-dodecen-9-in-1-ol.

A review of the synthetic possibilities of the preparation of this compound is contained in review papers by Henrick CA: The synthesis of insect sex pheromones, Tetrahedron 33, 1845 (1977), R. Rossi: Insect pheromones I. Synthesis of achiral components of insect pheromones, Synthesis 817 (1977) ), and

J. M. Brand et al.: Incest Pheromones: A Critical Review of Recent Advances in their Chemistry, Biology and Application, Fortschritte der Chem. org. Naturst. 37, pp. 71-79.

According to the process of the present invention, 7-dodecen-9-in-1-ol can be prepared in high yield from relatively inexpensive and available starting materials, particularly since a process for preparing a Grignard compound derived from Br (CHa) 3 OCH 2 -OCH 3 under the conditions customary for the preparation of Grignard compounds, it cannot be prepared.

The present invention provides a process for the preparation of 7-dodecen 9-in-1-ol, characterized in that the 3-bromopropylmethyl methoxymethyl ester of the formula is reacted with magnesium in tetrahydrofuran under an inert gas atmosphere at a temperature of -10 ^° C to 15 ^° C. The Grignard compound of formula is reacted with a 1-bromo-4-nonen-6-one of formula

at -10 ° C to 10 ° C in the presence of LiaCuCU as coupling reagent, and then deprotecting the isolated product by reaction with ethylene glycol in an acidic ethanolic medium at the boiling point of the reaction mixture.

The reaction is conveniently carried out by dropwise addition of 3-bromopropylpropylmethoxymethyl ether to the magnesium in tetrahydrofuran and an argon atmosphere such that the temperature does not exceed 10 ° C and the reaction is completed by stirring at this temperature. 1-bromo-4-nonen-6-in is added dropwise at a temperature of about 5 ° C to the thus obtained Grignard reagent solution, followed by the LizCuCl solution. The reaction was completed by standing overnight at 0 ° C. The product is isolated after decomposition of the reaction mixture with hydrochloric acid. The methoxymethy protecting group is cleaved from the isolated product by reaction with ethylene glycol in an acidic ethanolic solution and at the boiling point of the reaction mixture. The product isolated from the organic phase is purified by distillation and crystallization.

The invention is illustrated in more detail by the following non-limiting example.

Example 1

A. 3-Bromomagnesiumpropylmethoxymethyl ether

In a 250 ml flask equipped with a stirrer, a dropping funnel with a pressure equalizer, an argon inlet and placed in an ice bath, a solution was added to the magnesium (3.9 g; 0.16 mol)

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With iodine (100 mg) in tetrahydrofuran (25 mL). The apparatus was purged with argon and a solution of 3-bromopropyl-methoxymethyl ether (27.5 g; 0.15 mol) in tetrahydrofuran (75 mL) was added dropwise. Initially, about 15 ml of the solution was added and allowed to "start the reaction", which resulted in discoloration of the solution and an increase in the temperature of the reaction mixture, whereupon the remainder of the solution was added dropwise at such a rate. After the solution was added, the reaction mixture was still 60 min. stirred.

B. 1-Bromo-4-none-6-in

In a three-necked flask equipped with a stirrer, dropping funnel and reflux condenser, and a chlorine-calcium cap, a solution of 1,2-dibromomethane (93.9 g; 0.50 mol) in benzene- ether (500 mL; 1: 1). After the vigorous reaction subsided, the mixture was stirred for 2 hours and then poured from unreacted magnesium into a flask containing crude 1-p-toluenesulfonyloxy-4-none-6-in. A reflux condenser fitted with a chloro-calcium cap was mounted on the mixture and the tosyl derivative was stirred in magnesium bromide solution. The mixture is heated to gentle boiling by the reaction heat and a magnesium mixture of p-toluenesulfonic acid begins to precipitate almost immediately. The mixture was left at room temperature overnight and then poured into a mixture of water (3.5 mL) -hydrochloric acid (10 mL). After dissolving the magnesium p-toluenesulfonate, the organic layer was washed with water (100 mL), conc. ammonia (10 mL) and ammonium chloride (10 g), dried (MgSO 4) and concentrated through a column. The residue was purified by distillation to give a mana fraction, mp 55-60 ° C / 65 Pa. Yield 128.6 g (88%).

C, 7-dodecen-9-yn-1-ylmethoxymethyl ether

To a solution of the Grignard reagent prepared in Step A, a solution of 1-bromo-4-none-6-in from Step B (28.5 g; 0.136 mol) in tetrahydrofuran (70 ml) was added dropwise at a temperature below 5 ° C. then successively a 0.2 M solution of LiClCl (10 mL) at a rate such that the temperature of the reaction mixture did not exceed 5 ° C. The mixture was then stirred for an additional 2 hours in an ice bath and then left overnight at 0 ° C. After addition of a mixture of water (50 ml) and hydrochloric acid (10 ml), the organic phase is separated and washed with 5% sodium sulfite solution (50 ml), dried and concentrated.

D. 7-Dodecen-9-yn-1-ol

The residue from Step C. was dissolved in a mixture of ethanol (100 ml), ethylene glycol (20 g) and sulfuric acid (1 ml) and heated to boiling (20 min). Then ammonia (10 ml) was added and the reaction mixture was diluted with saturated sodium chloride solution (100 ml) and water (100 ml). The product was extracted from the reaction mixture with benzene (2X 50 mL), the extracts were dried and concentrated. The residue is then purified by distillation under vacuum. A fraction above 60 ° C was collected at 65 Pa and the distillation was terminated at an oil bath temperature of 140 ° C. Petroleum ether (100 ml) was added to the distillate thus obtained and the solution was allowed to crystallize at -35 ° C. After crystallization from petroleum ether three times, 12.1 g of pure product, m.p. 16 DEG -18 DEG C., were obtained, the IR, mass and NMR spectra of which were consistent with this structure.

Claims (1)

SUBJECT A process for the preparation of 7-dodecen-9-in-1-ol, characterized in that the 3-bromopropyl-methoxymethyl ether of formula (I) is reacted with magnesium in tetrahydrofuran under an inert gas atmosphere at a temperature of -10 ° C to 15 ° C. of the invention is reacted with 1-bromo-4-nonen-6-one of the formula at a temperature of -10 ° C to 10 ° C in the presence of LizCuCU as coupling reagent, followed by reaction of ethylene glycol in acidic ethanolic medium at boiling point. of the mixture cleaves the protecting group.