CS233069B1 - Method of (8e,1%e)-8,1% dodecandien-1-ol preparation - Google Patents

Abstract

The invention relates to a method of preparation (8E, 10E) -dodecadien-1-ol, sexual pheromone cider (Cydia pomonella) applicable to the monitor occurrence and flight of apple caster in programs integrated plant protection or. \ t as a starting material for the preparation of others pheromones. The synthesis results from 3-bromo-2-propynyl tetrahydro-pyran, which breaks down zinc to 4-octen-6-yn-1-ol to which it is treated with toluenesulfonyl chloride and bromide magnesium, and the resulting isolated bromoctenin is treated with a Grignard reagent in the presence of a coupling agent, the methoxymethylated masking is then removed a group of reactions with ethylene glycol. The obtained 8-dodecen-10-in-1-ol was obtained hydrogenates to P2-Ni in ethanolic solution to dodecadienol with configuration 8E, 10Z, which isomerized at 60 to 10 ° C 120 ° C with thiophenol.

Description

The present invention relates to a process for the preparation of (8E, 10E) -8,10-dodecadien-1-ol, a sex pheromone of the apple wrapper (Cydia pomonella).

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 sophisticated and complex, although pheromone structures are mostly fairly simple. The practical application of pheromones for the monitoring or control of insects is often not the most successful also because little is known about either the exact composition of the pheromones or the behavior that is induced by pheromones. 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 (Chemical Ecology: Odor Communication and Animals; ed. FJRitter, Elsevier, Amaterdam 1979; Management of Insect Pests with Semi ochemicals) , published by ER Mitchell, Plenum Press, New York 1981).

Butterfly pheromones 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.

The sexual pheromone of the apple carnation (Cýdia pomonella) is (8E, 10E) -8,10-dodecadien-1-ol, the sexual pheromone of the pea carnation (Gydia nigricana) is (8E, 10E) -8,10-dodecadien-1-yl acetate , which also shows a high attractiveness to alfalfa (Gydia medicaginis). However, in the case of pea carnation populations occurring in Czechoslovakia, this acetate appears to be of little interest.

Since synthetic (8E, 10E) -8,10-dodecadienyl-ol has been shown to be very effective on male / apple cider and the corresponding acetate on male pea and alfalfa mug, it has gained considerable importance as a means of monitoring and controlling insect populations.

For this reason, a number of synthetic processes for the preparation of these compounds are described in the literature.

An overview of the synthetic possibilities of preparation is contained in review papers CAHenrick: The synthesis of insect sex pheromones, Tetrahedron 33, 1845 (1977), R. Rossi: Insect pheromones I, Synthesis of achiral components of insect pheromones, S. Synthesis 817 (1977) , and JM Srand et al.: Insect Pheromones: A Critical Review of Recent Advances in their Chemistry, Biology and Application, Fortchritte der Chem.org. ^iU aturst. 37, pp. 71-79.

Recent works include the largely stereospecific synthesis described by Decodts et al. (Synthesis 1979, 510) and the simple completely stereospecific synthesis (E, E) of 1,3-diene skeletons using the coordinating protective group Fe (CO) ^ (GR Knox and IGThom: JCS Chem (1981, 374).

233 069

The invention relates to a novel process for the preparation of (8E, 10E) -8,10-dodecadien-1-ol, starting from relatively inexpensive starting materials and which can be converted in high yield to the desired product using conventional reagents.

The present invention provides a process for the preparation of (8E, 10E) -8,10-dodecadien-1-ol, characterized in that 3-bromo-2-propynyl-tetrahydropyran of formula III

(III) reductively cleaves zinc in the presence of ammonium chloride in an aqueous solution at room temperature to the boiling point of the reaction mixture, formed by 4-octene-6-in-1-ol (IV)

is converted into the corresponding lp-toluenesulfonyloxy-4-octen-6-in by treatment with p-toluenesulfonyl chloride, which is converted without isolation into magnesium l-bromo-4-octene at 0 ° to boiling point. -6-in (V) (V), whereupon 1-bromo-4-octen-6-in is reacted with a Grignard reagent (VI) prepared from 4-chlorobutylmethoxymethyl ether

CIMg

(VI) at -10 ° C to 10 ° C in the presence of Id 2 CuCl 2 as coupling agent and the isolated product is reacted with ethylene glycol in

- 4 233 069 acidic ethanol is converted into 8-dodecen-10-in-1-ol (VII) at boiling point of the reaction mixture.

which is hydrogenated on P2-nickel catalyst in ethanolic solution to (8E, 10Z) -8,10-dodecadien-1-ol and isomerized the obtained crude residue with thiophenol at a temperature of 60 ° C to 120 ° C to prepare (8E, 10E) - 8,10-dodecadien-1-ol.

The reaction is conveniently carried out by 3-bromo-2-propynyl tetrahydropyran (III), prepared from dihydropyran via 2-, 3-dibromotetrahydropyran followed by reaction with propynyl bromide, reductively cleaved by reaction with zinc in the presence of ammonium chloride while boiling in aqueous solution. . The 4-octen-6-yn-1-ol (IV) thus obtained is reacted in an alkaline medium with ρ-toluene sulfonyl chloride. The reaction is preferably carried out in a benzene solution in the presence of sodium hydroxide and triethylbenzylammonium chloride under cooling at room temperature. The resulting 1-p-toluenesulfonyloxy-4-octen-6-in is converted to 1-bromo-4-octen-6-in (V) by treatment with magnesium bromide. The reaction is carried out by mixing a solution of magnesium bromide in a mixture of benzene and ether (prepared by reacting magnesium with 1,2-dibromoethane) with the tosyl derivative prepared above, and allowing the reaction mixture to stand at room temperature overnight. After quenching the reaction mixture, 1-bromo-4-octen-6-in (V) is purified by distillation and then reacted with Grignard reagent (VI) prepared from 4-chlorobutylmethoxymethyl ether. The coupling reaction of the bromo derivative (V) and the Grignard reagent (VI) is conveniently performed by adding the bromo derivative (V) and the argon atmosphere to the Grignard reagent solution.

- 5,233,069, while stirring and cooling at 0 ° C was added a solution LigCuCl ^ in tetrahydrofuran at such a rate that the temperature did not exceed 5 DEG C. _About After addition of the coupling agent, the reaction mixture was allowed to stand for 12 hours at O ° C and then raakční decompose with aqueous hydrochloric acid. The methoxymethyl protecting group is removed 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. The reduction of 8-dodecen-10-in-1-ol to the corresponding diene is preferably accomplished by first preparing the Ζ, Ξ-isomer by hydrogenation with a P2-nickel catalyst which is then isomerized to (8B, 10E) by heating with thiophenol. -8,10-dodecadien-1-ol. The isomerization is carried out in the absence of solvent and the desired product crystallizes directly from the cooled reaction mixture after dilution with petroleum ether on standing at -35 ° C. The mother liquors after crystallization containing E, ZZ, E- and Ζ, Ζ-isomers can be re-isomerized after evaporation of the solvent to an equilibrium mixture in which the E, E-isomer predominates, which is again isolated by low-temperature crystallization (8E, 10E) - Further, 8,10-dodecadien-1-ol can be used as a starting compound for the preparation of (8E, 10E) -8,10-dodecadien-1-yl acetate, pea wrapper pheromone and alfalfa wrapper.

The invention is illustrated in more detail in the following example, which is not intended to limit it in any way.

- 6 233 069

A. Sodium Acetylide

Sodium (50.0 g; 2.2 mol) was melted under xylene (100 mL) in a four-necked sulfonation flask (2 L) equipped with a thermometer, a vortex mixer and a reflux condenser terminated with a paraffin oil-filled bubbler. Briefly starting the stirrer, the sodium was whisked to powder, and xylene (500 ml) and 1,2-diamino ether (2.0 ml) were added to the obtained suspension. The suspension was heated to 50 ° C and acetylene was introduced above the suspension level with vigorous stirring (gas from the bottle was washed with water and freeze-dried solid carbon dioxide-acetone). The reaction mixture is spontaneously heated by the reaction heat so that the acetylene feed is adjusted so that the temperature in the reaction vessel is in the range of 50-60 ° C (at the end of the reaction, the reaction mixture needs to be heated at this temperature). The initially pale violet sodium suspension changes when sodium is converted to acetylide to a white acetylide I suspension in a pale yellow solution. The conversion time depends on the degree of sodium dispersion and ranges from 2-6 hours.

B. Propine

The obtained sodium acetylide suspension was heated to 90 [deg.] C. and dimethyl fulphate (126 ml; 1.33 mol) was added dropwise thereto at 90-110 [deg.] C. The resulting propyne gas (b.p. -23.3 ° C) was, after cooling in a reflux condenser, passed through a rubber hose to a freezer (cooled with solid carbon dioxide-acetone) equipped with a chlorine-calcium cap. The condensate obtained was distilled (fraction up to 20 ° C was collected). 59 g of propyne (55.4% calculated on dimethyl sulfate) were obtained sufficiently pure for the next operation.

233 069

G. Propynyl magnesium bromide solution

Magnesium (26.7 g; 1.1 mol) was placed in a three-necked flask (4 L) equipped with a stirrer, a reflux condenser with a chloro-calcium cap and an addition funnel. A solution of 1-bromobutane (157.5 g; 1.15 mol) in absolute ether (900 mL) was added dropwise to magnesium.

After the magnesium had dissolved, the reflux condenser was replaced with a dry ice condenser fitted with a chloro-calcium cap. To the obtained butylmagnesium bromide solution propyne (59 g;

1.47 mol). After propyne was distilled off, the reaction mixture was stirred under reflux (solid carbon dioxide-acetone) for 5 h and then left at room temperature overnight.

D. 2,3-Dibromo-tetrahydropyran

To a solution of freshly distilled dihydropyran (84.1 g;

1.0 mol) in absolute ether (300 ml) was added dropwise bromine (50.90 ml) dropwise with cooling to -35 to -10 ° C and stirring until the first yellow color. The solution was then bleached with a few drops of dihydropyran and used immediately for the next step.

E. 3-Bromo-2-propynyl tetrahydropyran (III)

In the obtained propynyl magnesium bromide solution, the dry ice cooler was replaced with a water reflux condenser equipped with a chloro-calcium cap and a solution of 2,3-dibromotetrahydropyran was added to the solution while stirring for 15 min. After the addition, the reaction mixture was stirred for a further 2 h and then a mixture of water (500 mL) with conc. Hydrochloric acid (25 mL) was added dropwise. The organic layer was separated, washed with water (500 mL), dried (ivIgSO4).

233 069 and concentrated at 40 ° G / 2.6 kPa. The product 111 was used in the next operation without further purification. j

4. 4-Octen-6-yn-1-ol (IV)

In a three-necked flask (2 L) equipped with a stirrer and reflux condenser, bromo derivative from the previous step was added to the boiling mixture (400 ml), ammonium chloride (100 g) and zinc powder (130 g). The mixture was heated to boiling with stirring and then cooled. To the cooled mixture was added conc. Ammonia (200 mL) with stirring.

Unreacted zinc (frit C 3) was filtered from the mixture. The filter material was washed with ether (2 x 100 mL) and the organic layer was separated from the filtrate. The aqueous layer was extracted with ether (2 x 100 mL), the organic layer and the extracts were combined, dried (MgSO 4) and concentrated. The product IV was purified by distillation, bp fraction was collected from 102 to 105 ° C / 2 _/ I? KPa, yield 97 g (78% calculated on the dihydropyran).

G. 1- p -Toluenesulfonyloxy-4-octen-6-in

In a three-necked flask (2 L) equipped with a vibrating stirrer and thermometer, was added a mixture of alcohol IV (94 g, 0.76 mol), 30% sodium hydroxide (250 mL), benzene (500 mL) and triethylbenzylammonium chloride (2 g). ) p-toluenesulfonyl chloride (164 g;) was added portionwise with vigorous stirring and cooling to 20-25 ° C;

0.86 mol). Stirring was continued until the β-disappearance. toluene sulfochloride (Control was performed by TLC-silufol UV 254; in benzene-5% ethyl acetate, UV detection).

After the disappearance of p-toluenesulfochloride, the reaction mixture was diluted with water (500 mL), the organic layer was dried (MgSO 4) and concentrated.

233 069 in a 2 L flask on a rotary evaporator at 2.66 kPa and 40 ° C. The product obtained was used in the next step without further purification.

H. 1-3-bromo-4-octen-6-in (V)

In a three-necked flask equipped with a stirrer, a dropping funnel and a reflux condenser with a chloro-calcium cap, a solution of 1,2-dibromoethane (93.9 g / 0.50 mol) in a propellant-ether mixture (500 ml) was added to magnesium (13.4 g; 0.55 moD). ml; 1: 1) After a vigorous reaction, the mixture was stirred for 2 hours and then poured from the unreacted mustard into a funnel containing the crude tosylderivative prepared in Step G. The flask was fitted with a chloro-calcium reflux condenser and stirred in the bromide solution. The mixture was heated to gentle boiling by reaction heat and the magnesium p -toluenesulfonic acid precipitated almost immediately and the mixture was left at room temperature overnight and then poured into water (3.5 L) -hydrochloric acid (10 L). After dissolving the magnesium p-toluenesulfonate, the organic layer was washed with a mixture of water (100 ml), conc. ammonia (10 ml) and ammonium chloride (10 g), dried. The residue was purified by distillation, collecting a fraction of b.p. 55-60 ° G / 65 fe, yield 128.6 g (88% calculated on alcohol IV).

Ch. 4-Chlorobutylmethoxymethyl ether

In a three-necked flask (4 L) equipped with a stirrer, dropping funnel, thermometer and chlorine-calcium cap, was added to a mixture of dichloromethane (900 mL), 4-chlorobutanol (326 g; 2 moles) and dimethylaniline (420.5 g, 440 mL; 47 mol) with ice cooling

233 069 water to 10-15 ° C dropwise with methanol methyl ether (288 g,

269 ml; 3.58 mol). After addition of chloromethyl methyl ether, the reaction mixture was stirred for an additional 1 hour in an ice bath, then water (500 ml) was added, the organic layer was separated, washed with mixed water (200 ml) - conc. Hydrochloric acid (100 ml), water (2 ml). 250 mL) and a mixture of water (150 mL) - ammonia (150 mL), dried (MgSO 4) and concentrated on a rotary evaporator at 40 ° C / 2.66 kPa. The product was purified by distillation, b.p. 38 ° C / 65 Pa (the receiver was cooled with ice water); yield 343 g (74.9%) of the title product.

I. 8-Dodecen-10-in-1-ol (VII)

In a three-necked flask (11) equipped with a bubbler-cooled reflux condenser, argon inlet, dropping funnel and magnetic stirrer, tetrahydrofuran (50 ml) and 1.2 dibromoethane (1.0 ml) were added to magnesium (24.3 g; 1 mol). ). The apparatus was purged with argon, and after the reaction was started, a solution of 4-chlorobutylmethoxymethyl ether prepared in CH (133.5 g; 0.875 mol) in tetrahydrofuran (250 mL) was added dropwise to the magnesium with stirring at such a rate that the reaction mixture boiled vigorously. . After the solution was added, the reaction mixture was heated to reflux for 20 minutes and then cooled.

The obtained Grignard reagent solution was poured from unreacted magnesium into a 2 L flask equipped with an argon inlet, a magnetic stirrer, a thermometer, and a whisper. To the Grignard reagent solution was added bromo derivative V, prepared in step H (129.1 g; 0.69 mol), and the apparatus was purged with argon and cooled to 233 ° C in water-ice. To the cooled mixture was added by syringe a solution of the coupling reagent prepared by dissolving anhydrous lithium chloride (8.46 g; 0.2 mol), and anhydrous copper chloride (13.45 g; 0.1 mol) in absolute peroxide free of tetahydrofuran (1000 mL). (13.4 mL) with stirring at a rate such that the temperature did not exceed 5 ° C. After addition of the coupling reagent, the reaction mixture was left at 0 ° C for 12 h. (Water-ice mixture). The reaction mixture was then quenched with water (800 mL) - end hydrochloric acid (30 mL), the organic layer was washed with water (200 mL), and dilute ammonia (100 mL, 1: 1), dried over MgSO 4 and concentrated to rotary. evaporator at 40 ° G / 2.66 kFa.

Cleavage of the methoxymethyl group: A mixture of ethanol (250 ml), ethylene glycol (62 g; 1 mol) and sulfuric acid (2.5 ml) was added to the residue, and the mixture was heated to boiling (20 min) and then neutralized with conc. ammonia (20 mL). After addition of water (300 mL) and saturated sodium chloride solution (300 mL), the organic layer was separated, dried (MgSO 4) and concentrated on a rotary evaporator at 40 ° C / 2.66 kPa. The product was purified by distillation, collecting a b.p. 70-125 ° C / 65 Pa (virtually everything comes in the range of 104-111 ° C). Yield 90.6 g (72.8% calculated on bromo derivative V and 50% on dihydropyran). A coupling reagent solution was prepared by dissolving anhydrous lithium chloride (8.48 g; 0.2 mol) and anhydrous copper chloride (13.45 g; 0.1 mol) in absolute tetrahydrofuran-free peroxide (1000 mL).

233 069

J. (8E, 10E) -8,10-Dodecadien-1-ol.

A hydrogenation apparatus adapted to circulate hydrogen and provided with a sepia cap was placed with a solution of nickel acetate (4.0 g) in ethanol (180 mL). The apparatus was purged with hydrogen and a solution of sodium boron hydride (640 mg) in water (4.0 mL) was added to the nickel acetate solution. After 10 min, 1,2-diaminoethane (4.0 mL) was added to the reaction mixture. Then the reaction mixture was cooled in water-ice, alcohol Vil (90, Ag) was added to the cooled mixture, and the mixture was hydrogenated under a slight positive pressure of hydrogen until practical hydrogen consumption was observed (the progress of hydrogenation was monitored by gas chromatography). After completion of the hydrogenation, the reaction mixture was filtered through diatomaceous earth and concentrated.

Water (200 mL), benzene (200 mL) was added to the residue, the organic layer was separated, dried over anhydrous magnesium sulfate, and concentrated on a rotary evaporator at 40 ° C / 2.66 kPa.

Isomerization: To the obtained residue was added thiophenol (1.0 mL) and the mixture was heated for 30 min. to 100 ° C and then. cooled. The cooled mixture was dissolved in petroleum ether (900 mL) and the solution was allowed to crystallize overnight at -35 ° C. The separated crystals were aspirated and recrystallized from petroleum ether (300 ml). The mother liquors were combined, concentrated on a rotary evaporator at 40 ° C / 2.66 kPa and the residue was reheated to 100 ° C for 30 min. After cooling, it was dissolved in petroleum ether (300 ml) and the solution was left *

crystallize. After aspiration, the precipitated product was recrystallized from petroleum ether (100 ml). The combined mother liquors were concentrated on a rotary evaporator at 40 ° C / 2.66 kPa and heated at 100 ° C for 30 min, dissolved after cooling in petroleum ether (100 mL) and cooled.

- 13 233 069 the precipitated product was recrystallized from petroleum ether (100 ml)

A total of 53 g of the title product was isolated by crystallization.

According to gas chromatography, the product is more than 99%. The .alpha., Red, NMR and mass spectra are consistent with the indicated structure.

Claims (1)

The subject of your finding 233 069 A process for the preparation of (8E, 10E) -8,10-dodecadien-1-ol, characterized in that 3-bromo-2-propynyltetrahydropyran of formula III (III) is reductively cleaved with zinc in the presence of ammonium chloride in aqueous solution at room temperature to temperature boiling the reaction mixture resulting from 4-octen-6-in-1-ol of formula IV HO (IV) is converted into the corresponding 1p-toluenesulfonyloxy-4-octen-6-in by treatment with p-toluenesulfonyl chloride in an alkaline medium, which is converted without isolation by reacting with magnesium bromide at 0 ° C to the boiling point of the reaction mixture to 1- of bromo-4-octen-6-in of formula V, and then 1-bromo-4-octen-6-in is reacted with a Grignard reagent of formula VI prepared from 4-chlorobutylmethoxymethyl ether at -10 ° C to 10 ° C in presence of LigCuCl2 as coupling agent and the isolated product by reaction with ethylene glycol in an acidic ethanolic solution at the boiling point of the reaction mixture // 233 069 is converted to 8-dodecen-10-in-1-ol of formula VII OH (VII) y which is hydrogenated on β-nickel catalyst in ethanolic solution to (8E, 102) -8,10-dodecadien-1-ol and isomerized the obtained crude residue with thiophenol at 60 ° C to 120 ° C to prepare ( 8E, 10E) -8,10-dodecadien-1-ol.