DE1038033B - Process for the preparation of non-cyclic carotenoids - Google Patents

Description

Process for the preparation of non-cyclic carotenoids subject of the present invention is a new process for making non-cyclic Carotenoids, especially of lycopene and 1,2,1 ', 2'-tetrahydrolycopene.

There are already several syntheses for the production of, B-carotene known, all of which are based on ßJonon as the starting material. In the first synthesis From Inhoffen, fl-Jonon was initially built up from a Clg-Aldebyd and on both sides attached to acetylenedimagnesium bromide (C19 + C2 + C19 = C40). Another synthesis von Inhoffen is based on the C18 + C4 + C18 = C40 structure, with 2 molecules , 8-CE8-ketone can be linked with diacetylene.

The other syntheses start from C6-acetylene compounds and octen- (4) -dione- (2,7) the end. In all of these syntheses, C40-acetylenediols are formed as intermediates or tetrole, which dehydrates in a cumbersome and usually very lossy manner Need to become.

For the production of lycopene, however, a technically useful one Synthesis not known at all. After that in Helv. Chim. Acta, 33 (1950), pp. In the process described in 1349, lycopene is obtained only in very low yield.

On the other hand, the process described below allows production of lycopene or 1,2,1 ', 2'-tetrahydrolycopene in good, technically usable condition.

It has been found that you can build up the carbon structure of a non-cyclic carotenoids, i.e. avoiding hydroxyl-containing intermediates can advantageously perform according to the new structure clo + C2o + Cio = C40.

The present invention relates to a method of production of non-cyclic carotenoids, especially lycopene and tetrahydrolycopene, which is characterized in that 2,6,11,15-tetramethyl-hexadecahexaene - (2,4,6,10,12, 14) -in- (8) -dial- (1,16) with an optionally hydrogenated geranylene-triaryl-phosphine, whose aryl groups can carry alkyl or alkoxy groups, in an inert solvent condensed and the medium permanent triple bond in a manner known per se subject to catalytic partial hydrogenation and isomerization.

The required starting products can be represented as follows: 2,6,11,1 5-tetramethylhexadecahexaen- (2,4,6,10,12,14) -in- (8) -dial- (1,16) (hereinafter C20-yne dialdehyde) 2,7-dimethyl-octadiene- (2,6) -yne- (4) -dial- (1,8) in a manner known per se, for. B. by means of ethyl orthoformate, in the presence a sour one Catalyst, such as p-toluenesulfonic acid, acetalized. The resulting diacetal is now in the presence of an acidic condensing agent, such as zinc chloride, with a Vinyl ethers, e.g. B. Ethylvinyläther implemented.

The 4,9-D imethyl-dodecadiene- (4,8) -in- (6) -dialkoxy- (3,10) obtained -diacetal- (1,12) is treated with acid, e.g. B. by heating with acetic acid to 1000 C, whereby hydrolysis and elimination of alcohol from the positions 2,3 and 10.11. The so obtained 4,9 - dimethyl - dodecatetraen - (2,4,8,10) - in- (6) -dial- (1.12) with a melting point of 1650 C with U.V. maxima at 371 and 391 mµ (in pure alcohol) is acetalized in an analogous manner, the resulting diacetal reacted with a propenyl ether and treated the condensation product with acid, where the C20 dialdehyde from melting point 190 to 1920 C, U.V. maxima at 410 and 436 mµ, E1cm1% 3070 or

3180 (in petroleum ether).

Geranylene triarylphosphine 1 mole geranyl halide or dihydrogeranyl halide, z. B. Dihydrogeranyl bromide (made from 6-methylheptanone- (2) by condensation with sodium acetylide in liquid ammonia, partial hydrogenation the Triple bond with a lead-poisoned palladium catalyst and bromination with Phosphorus tribromide), is added over the course of 1 hour with stirring at room temperature added to a solution of 1.1 mol of triarylphosphine in benzene. After stirring for 8 hours the eeranyI- or dihydrogeranyl-friaryI-phosphonium halide formed is filtered off, washed with benzene and petroleum ether and dried at 400 ° C. in a water jet vacuum. Recrystallization, accidents or taking off with solvents can result in pure Preparations obtained and possible isomeric forms separated. For the purpose of secession the phosphonium salts are suspended in absolute ether and of hydrogen halide mixed with the calculated amount of ethereal butyl or phenyllithium solution while stirring. Deeply colored solutions or suspensions are created, which lead to condensation directly can be used.

For - the production of the starting materials is within the scope of the present Invention not claiming patent protection.

In the condensation stage, the C20-yne dialdehyde or the one from it .C ,, - en-dialdehyde obtained by partial hydrogenation and isomerization, namely 2,6,11,15 - tetramethyl - hexadecaheptaen - (2,4,6,8, 10,12,14) -dial- (1,16), condensed with the geranylene triaryl phosphine compound and the condensation product formed converted into the carotenoid compound with elimination of triarylphosphine oxide. It is best to use equivalent amounts of the components or one for the implementation Excess of the triarylphosphine compound and works in an inert solvent, such as ether, petroleum ether, benzene, dioxane, tetrahydrofuran, etc.

It is advantageous to mix the components in a stirred tank Room temperature or at an elevated temperature, in which case the air is expediently through an inert gas, e.g. B. nitrogen replaced. The condensation takes place during the addition a solution of the C20-in or. C20 ene dialdehyde to form a solution of geranyl triaryl phosphine, z. B. Geranylene triphenyl phosphine, instantaneous and exothermic. Depending on the choice of Solvent the condensation products formed remain in solution or they fall usually a lightening of the color takes place. In the preferred embodiment the condensation is the C2 «> - one or C20-ene dialdehyde in methylene chloride solution added to a suspension or to a solution of geranylene triphenyl phosphine, wherein both the C20 dialdehydes and the resulting condensation products are soluble. The condensation products gradually disintegrate on standing for a long time rapidly converts into the carotenoid compound and triarylphosphine oxide when their solutions are heated.

The decomposition succeeds very easily by boiling for several hours (40 up to 500 C) of the reaction mixture, preferably in methylene chloride solution. After completion The resulting carotenoids can be reacted by shaking the organic phase Separate with water from the resulting triarylphosphine oxide, whereupon the carotenoids crystallize on concentration of the dried solution. You can go through if necessary Recrystallization, solvent distribution or chromatography of adhering organic phosphorus compounds are freed. An advantageous work-up the carotenoids obtained consists in that the reaction solution with a lot of ethanol or methanol is added, the carotenoids precipitating in crystalline form and all by-products go into solution.

The partial hydrogenation and isomerization takes place in the same way as for carotenoid compounds usual way by adding a suspension or solution of the C20-in-dialdehyde or the 15,15'-dehydro compound of lycopene or 1,2,1 ', 2'-tetrahydrolycopene in one inert solvents, such as. B. ethyl acetate, toluene, petroleum ether, etc., with a lead-poisoned palladium catalyst is hydrogenated in the presence of quinoline.

The primarily resulting cis compounds are, preferably through Heat, isomerized to the all-trans compounds. Make the connections obtained valuable dyes; they are intended to be used in particular for coloring foodstuffs Find.

Example 1 Lycopene a) Partial hydrogenation and isomerization 50 parts by weight 2,6,11,15-tetramethyl-hexadecahexaen- (2,4,6,10,12,14) -in- (8) -dial- (1,16) suspended in 600 parts by volume of toluene and after adding 10 parts by weight of one Palladium-calcium carbonate catalyst poisoned with lead and 5 parts by volume of quinoline hydrogenated under normal conditions until the hydrogen uptake almost stopped has come. The hydrogenation mixture is filtered and the catalyst and the desired substance existing filter cake extracted with acetone. From the acetone solution 35 to 40 parts by weight of 2,6,11,15-tetramethylhexadecaheptaen- (2,4,6,8,10,12, 14) -dial- (1.16), F. 190 to 1910 C, U.V.-maxima at 408, 430 and 458 mll, El 2930, 5240 and 5820 (in petroleum ether). b) Condensation to a deep red solution of geranylene triphenylphosphine (prepared from 100 parts by weight of geranyltriphenylphosphonium bromideJ F. 188 bis 1890 C, and 16.8 parts by weight of phenyllithium in 1200 parts by volume of ether) is left within 5 minutes and in a nitrogen atmosphere the solution of 20 parts by weight 2,6,11,1 5-tetramethyl-hexadecaheptaen- (2,4,6, 8,10,12,14) -dial- (1,16) in 500 parts by volume Add methylene chloride dropwise. The mixture is stirred for about 15 minutes at 300 ° C. and then boiled the reaction mixture 2,6,11,15-tetramethylhexadecahexaene - (2,4,6,10,12, 5 hours under reflux. 600 parts by volume of methanol are then added to the warm reaction mixture and allowed to cool to 100 ° C. with stirring. - The crystal pulp is in a CO2 atmosphere suctioned off and washed with 200 parts by volume of methanol. The raw lycopene will now dissolved in 300 parts by volume of methylene chloride at a maximum of 400 C, warm at 500 parts by volume Methanol precipitated and cooled with ice water for 2 hours. That under carbon dioxide filtered product, washed with methanol, is dried at 400.degree. C. in vacuo. 25 parts by weight of lycopene, mp 172 to 1730 ° C., are obtained in the form of deep red needles.

U.V. maxima at 446, 472 and 504mm, El9b ,, 2250, 3450 and 3150 (in Petroleum ether).

Example 2 Lycopene a) Condensation To a deep red solution of Geranylene triphenylphosphine (made from 100 parts by weight of geranyltriphenylphosphonium bromide and 16.8 parts by weight of phenyllithium in 1200 parts by volume of ether) are left within 5 minutes and in a nitrogen atmosphere, the solution of 20 (weight parts 2.6, 11, 15 - tetramethyl - hexadecahexaene (2,4,6,10,12, 14) -in- (8) -dial- (1,16) in Add dropwise 500 parts by volume of methylene chloride. The mixture is stirred at 300 for about 15 minutes C. and then the reaction mixture is refluxed for 5 hours. You give up to the warm reaction mixture 600 parts by volume of methanol and allowed to increase to 100 with stirring C to cool. The crystal pulp is sucked off in a CO2 atmosphere, with 200 parts Washed methanol and dried at 500 C in a high vacuum. 28 parts by weight are obtained 15.1 5'-dehydrolycopene. The melting point of the red leaflets is 190 to 1920 C, U.V. maxima at 453 and 484 m Et 2525 and 2165 (in petroleum ether). b) partial hydrogenation and isomerization For conversion to lycopene, 0.5 part by weight of 15,15'-dehydrolycopene is dissolved in 100 parts by volume of toluene and hydrogenated in the presence of 1 part by weight of one with Quinoline and lead deactivated palladium catalyst until hydrogen uptake comes to a standstill. The hydrogenation solution shows at 361 mm (in petroleum ether) the for 15.1 5'-cis-lycopene characteristic cis-peak. The filtered off from the catalyst Solution is concentrated and the residue is recrystallized from high-boiling petroleum ether, at the same time the isomerization to all-trans-lycopene takes place.

Example 3 1,2-1 ', 2'-Tetrahydrolycopene To a suspension of 100 Parts by weight of triphenyl - (3,7 - dimethyl - 2-octen-1-yl) phosphonium bromide vom Melting point 1850 C (produced by condensation of 6-methyl-heptanone- (2) with Lithium acetylide, partial hydrogenation of the triple bond, halogenation with phosphorus tribromide and reaction with triphenylphosphine) in 1000 parts by volume of aboslutem diethyl ether 200 parts by volume of an in-phenyllithium solution are added while stirring in a nitrogen atmosphere added dropwise in ether. The resulting deep red solution of triphenyl- (3,7-dimethyl-2-octene 1-ylidene) -phosphine is mixed with a solution of 18.5 parts by weight 2,6,11,1 5-tetramethyl-hexadecaheptaen- (2,4,6,8,10,12,14) -dial- (1,16) (prepared according to Example 1) added to 500 parts by volume of methylene chloride.

After everything has been entered, the reaction mixture is still 5 hours cooked with stirring. Then 600 parts by volume of methanol are added to the warm reaction solution poured and the mixture cooled.

The resulting crystals are placed under a carbon dioxide atmosphere separated off, washed with methanol and dried at 500 ° C. under vacuum.

10 parts by weight of 1,2-1 ', 2'-tetrahydrolycopene with a melting point are obtained 178 to 1800 C., U.V. maxima at 445, 472 and 503 m; Egg 2205, 3330 and 3000 (in Petroleum ether).

PATENT CLAIMS 1. Process for the production of non-cyclic Carotenoids, characterized in that 2,6,11,1 5-tetramethyl-hexadecahexaen- (2,4,6,10,12,14) -in- (8) -dial- (1,16) with an optionally hydrogenated geranylene-triaryl-phosphine, whose aryl groups can carry alkyl or alkoxy groups, in an inert solvent condensed and the central triple bond in a manner known per se subject to catalytic partial hydrogenation and isomerization.

Claims (1)

2. The method according to claim 1, characterized in that the Carries out condensation in the presence of methylene chloride. 3. Modification of the method according to claim 1 and 2, characterized in that that one 2,6,11,15-tetramethylhexadecahexaen - (2,4,6,10,12,14) -in- (8) -dial- (1,16) catalytically hydrogenated and the 2,6,1 1,15-tetramethylhexadecaheptaen- (2,4,6,8,10,12,14) obtained -dial- (1,16) with geranylene triphenylphosphine or with 6,7-dihydrogeranylene triphenylphosphine condensed. Older Patents Considered: German Patents No. 950 552, 951 212.