CS232849B1 - Process for the preparation of enjugated enines - Google Patents

Abstract

The invention relates to a method for the preparation of conjugated enynes of the general formula I where R is an alkyl with 1 to 5 carbon atoms, which are useful as intermediates for the production of pheromones. The essence of the synthesis is the reductive cleavage of 3-bromo-2-alkyl-tetrahydropyran, prepared by Grignard synthesis from 2,3-dibromotetrahydropyran and the reagent BrMg—CvC—R. The reductive cleavage is carried out with zinc in the presence of NHiCl

Description

The invention relates to a process for the preparation of conjugated enines, which are valuable intermediates for the production of butterfly pheromones or their analogs affecting the behavior of insects.

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 either because so far little is known about either the exact composition of 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 (FJ Ritter, Elsevier, Amsterdam 1979; Management of Insect Pests with Semiochemicals; Publisher ER Mitchel, Plenum Press New York 1981).

Sexual pheromones of butterflies are mainly predominantly unbranched aliphatic alcohols, aldehydes or acetates with 12 to 18 carbon atoms with 1 to 2 double bonds in different positions and geometric isomerism E or Z. 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 the synthesis of relatively simple compounds becoming non-trivial.

Sex pheromones are also a number of compounds containing a conjugated diene system in the molecule. Among them are, for example, (8E, 10E) -8,10-dodecadien-1-ol isolated from an apple moth (Cydia pomonella) and (7E, 9Z) -7,9-dodecadien-1-yl acetate from a marbled moth (Lobesia botrana) ).

A variety of syntheses are described for preparing compounds with a conjugated diene system, such as reactions between an α, β-unsaturated aldehyde and a saturated Wittig reagent or a saturated aldehyde and an olefinic or acetylenic Wittig reagent. By varying the solvent system and reaction conditions, the obtained E and Z ratios can be controlled. However, the purity of the E- and Z-isomers is not always sufficient and further purification is required. In some syntheses, a diene system is first prepared, which is then extended by a Grignard reaction or an alkali metal organo compound. For example, for the synthesis of (8E, 10E) -8,10-dodecadien-1-ol, sorbyl alcohol has been used as a starting diene precursor and is subjected to rearrangements during further reactions.

The preferred syntheses for preparing pheromones with conjugated diene systems appear to reduce the acetylenic bond of the conjugated enines. This reduction to the Z-olefin is carried out by Lindlar catalyst, P-2 nickel or, preferably, hydroboration protonolysis. The preparation of E, E dienes is preferably carried out by equilibration of the isomeric mixture of dienes in which the Ε, Ε-diene predominates.

The conjugated enines are prepared by rearrangement of allylic unconjugated eninols to produce mixtures of E and Z conjugated enines, which are separated prior to further reactions. Conjugated enines are also prepared by dehydration of α-inols, by Wittig reaction, via vinyl copper compounds or from alkenyl boranes. [For review, see C.A. Henrick: 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}).

The present invention relates to a process for preparing conjugated enines useful as intermediates for the production of pheromones, starting from a relatively cheap starting material 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 the conjugated enines of formula I-R (H wherein

R is C 1 -C 5 alkyl, characterized in that the dihydropyran is reacted with bromine in anhydrous ether at a temperature of -35 ^° C to 0 ° C, and the 2,3-dibromotetrahydropyran formed is reacted with a Grignard reagent of the formula II

BrMg-C = C-R (11) where

As defined above, in anhydrous ether at a temperature of from 0 ° C to the boiling point of the reaction mixture, preferably at room temperature, the obtained tetrahydropyran derivative of the general formula III

Br

C = C-R (ml

where

R is as defined above, is cleaved reductively with zinc in the presence of ammonium chloride in aqueous solution at room temperature to the boiling point of the reaction mixture.

The reaction is conveniently carried out by dropwise addition of freshly distilled dihydropyran in anhydrous ether with stirring and cooling to -35 ° C until a yellow color appears, which is then removed with a few drops of dihydropyran. The 2,3-dibromotetrahydropyran thus prepared was added dropwise at room temperature to a stirred mixture of a freshly prepared solution of the Grignard compound of the formula BrMg-C = C-R without isolation. The reaction is completed by stirring at room temperature for two hours. After quenching with dilute hydrochloric acid, the 3-bromo-2- (R-C-C) -tetrahydropyran (III) isolated from the organic phase is distilled in vacuo and added to the boiling aqueous mixture of ammonium chloride and zinc powder with stirring without further purification. . The reaction is completed by boiling for one hour.

An advantage of the process according to the invention is that relatively cheap, commercially available starting materials are used as starting materials, the reactions proceed in high yield and the product can be directly used for subsequent pheromone synthesis reactions without purification.

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

He did

A. Sodium Acetylide

Sodium (50.0 g) 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 topped with a paraffin oil bubbler.

2.2 mol). Briefly starting the stirrer, the sodium was whisked to dust, and xylene (500 ml) and 1,2-diamino ether (2.0 ml) were added to the obtained suspension. The slurry was heated to 50 ° C and acetylene was introduced above the slurry with vigorous stirring (bottle gas was washed with water and freeze-dried solid carbon dioxide-acetone). The reaction mixture is spontaneously heated by reaction heat so that the acetylene feed is adjusted so that the temperature in the reaction vessel is in the range of 50 to 60 ° C (at the end of the reaction, the reaction mixture needs to be heated to 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 to 6 hours.

B. Fropiti

The obtained acetylide suspension was heated to 90 ° C and dimethyl sulfate (126 ml; 1.33 mol) was added dropwise thereto at a temperature of 90 to 110 ° C. The resulting propyne gas (i.e., -23.3 ° C) was cooled through a rubber hose to a freezer (solid carbon dioxide-acetone cooled) equipped with a chloro-calcium cap after cooling in the reflux condenser. 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.

C. Propynylmagnesium bromide (II) 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. Propyne (59 g; 1.47 mol) was added to the obtained butylmagnesium bromide solution. After propyne was distilled, the reaction mixture was stirred under reflux (solid carbon dioxide-acetone) for 5 h and then left at room temperature overnight.

D. 2,3-Dibromotetrahydropyran

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) while cooling to -35 to -10 ° C until stirring for the first yellow color. The solution was then bleached with a few drops of dihydropyran and used immediately in the next step.

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

For the propynylmagnesium bromide (II) solution obtained in Step C, the dry ice cooler was replaced with a water reflux condenser equipped with a chlorine-calcium cap and the solution was stirred for 15 min. a solution of 2,3-dibromotetrahydropyran is added dropwise. The reaction mixture was stirred for a further 2 h. A mixture of water (500 mL) was added dropwise with conc. hydrochloric acid (25 mL). The organic layer was separated, washed with water (500 mL), dried (MgSO 4) and concentrated at 40 ° C / 2.6 kPa. The product (III) was used in the next operation without further purification. Analysis by gas chromatography on OV-17 showed the title compound to be 96.5%.

F. 4-Octen-6-yn-1-ol (I) (R = CH3)

In a three-necked flask (2 L) equipped with a stirrer and a reflux condenser, a bromo derivative from the previous step was added to a boiling mixture of water (400 mL), ammonium chloride (100 g) and zinc powder (130 g). The mixture was heated to boiling with stirring for 1 h and then cooled. To the cooled mixture was added conc. ammonia (200 mL). Unreacted zinc (frit C 3) was filtered from the mixture, the filter pad 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 was purified by distillation, collecting a fraction of m.p. 102-115 ° C / 2.0 kPa, yield 97 g (78% based on dihydropyran). The infrared and mass spectra are in accordance with the stated structure.

Example 2

4-Nonen-6-yn-1-ol

The procedure of Example 1 was followed except that in step B diethyl sulfate was used instead of dimethyl sulfate. In step F, a fraction of 118 to 125 degrees C / 2.0 kPa (72 g yield) was collected as product. The infrared and mass spectra are in accordance with the stated structure.

Claims (1)

SUBJECT OF THE INVENTION A process for preparing the conjugated enines of formula I (n wherein R is C 1 -C 5 alkyl, characterized in that the dihydropyran is reacted with bromine in anhydrous ether at a temperature of -35 ° C to 0 ° C, and the 2,3-dibromotetrahydropyran formed is reacted with a Grignard reagent of formula II BrMg-C = C-R (II) where R is as defined above, in anhydrous ether at 0 ° C to the boiling point of the reaction mixture, preferably at room temperature, then the tetrahydropyran derivative of the general formula III obtained Br C = C-R (ml where R as defined above, is reductively resolved with zinc in the presence of ammonium chloride in aqueous solution at room temperature to the boiling point of the reaction mixture. Severography, n. P., Plant 7, Most