DE1011881B - Process for the preparation of 8- [2 ', 6', 6'-trimethylcyclohexen- (2 ') - ylidene] -2, 6-dimethyloctadien- (2, 6) -in- (4) -al- (1) and 8- [2 ', 6', 6'-trimethylcyclohexen- (2 ') - ylidene] -2, 6-dimethyloctatriene- (2, 4, 6) -al- (1) - Google Patents

Description

Process for the preparation of 8- [2 ', 6', 6'-trimethylcyclohexen- (2 ') - ylidene] -2, 6-dimethyloctadien- (2, 6) -in- (4) -al- (1) and 8- [2 ', 6', 6'-trimethylcyclohexen- (2 ') - ylidene] -2, 6-dimethyloctatriene- (2, 4, 6) -al- (1) The invention relates to a process for the production of 8- [2 ', 6', 6'-trimethylcyclohexen- (2 ') - ylidene] -2, 6-dimethyloctadiene- (2, 6) -in- (4) -al- (1) and 8- [2 ', 6', 6'-trimethylcyclohexen- (2 ') - ylidene] -2, 6-dimethyloctatriene- (2, 4, 6) -al- hereinafter retrodehydro-Cl9-acetylenic aldehyde or retrodehydro-Cl9-aldehyde called. The process is characterized in that 5- [2 ', 6', 6'-trimethylcyclohexene (l ') - yl] -3-methyl-3-oxy-pentene- (4) -in- (l) -in the following β-Cl5-acetylenecarbinol called-in a manner known per se by means of an organometallic reaction with an etherified or esterified 2-methyl-3-oxypropen- (2) -al- (l) condenses, the obtained in the 1-position etherified or esterified 8- [2 ', 6', 6'-trimethylcyclohexen- (l ') - yl] -2, 6-dimethyl-1, 3, 6-trioxyoctadiene- (1, 7) -in- (4) -in the following Cla-dioxyen ester or - called ether - treated with an acidic agent, with allyl rearrangement, Dehydration and hydrolysis of the retrodehydro-Cl9-acetylenaldehyde is formed, and the latter, if desired, on the triple bond in a manner known per se selectively hydrogenated.

Those used for each step of the present process Some of the methods are known per se.

So the elimination of water by means of sulfuric acid in an organic Solvent e.g. B. in J. Am. Chem.

Soc., Vol. 74, 1952, pp. 295 and 3807 ff., And Vol. 71, 1949, p. 2062 ff., described. In contrast, the claimed method follows an original and new construction principle. It is noteworthy that the propene derivative mentioned is used obtainable high yield.

The starting materials for the new process are prepared as follows : β-Cl5-acetylene carbinol with a melting point of 20.5 ° C., b.p. 0.5 = 84 ° C., nD ° = 1.5024 arises from ß-ionone by condensation with lithium acetylide in liquid ammonia.

2-Methyl-3-acyloxypropen- (2) -al- (1) results from the conversion of the sodium salt of methylmalondialdehyde with an acid chloride in an inert, anhydrous solvent. The 2-methyl-3-benzoxypropen- (2) -al- (l) with a melting point of 81 to 82 ° C. is obtained for example by adding dropwise benzoyl chloride to a suspension of the finely powdered Sodium salt in methylene chloride, the mixture being refluxed for some time boils, then the precipitated table salt is filtered off, the filtrate is concentrated and that 2-methyl-3-benzoxypropen- (2) -al- (l) which crystallizes out from a mixture recrystallized from methylene chloride and petroleum ether. The 2-methyl-3-acetoxypropene (2) -al- (1) with b.p. lo = 75 to 77 ° C and n20 = 1.4690 is created in an analogous way. It is purified by distillation and solidifies when it is cooled.

2-Methyl-3-alkyloxypropen- (2) -al- (1) is produced by reacting Methylmalondialdehyde with an alcohol at an elevated temperature in the presence of a acidic Catalyst. So you win z. B. 2-methyl-3-isopropoxypropene- (2) -al- (1) by heating a mixture of methylmalondialdehyde, isopropanol, benzene and a trace of p-toluenesulfonic acid, the water formed being distilled off azeotropically and is separated in a water separator. When the reaction is over, neutralized the catalyst is removed and the reaction product is purified by distillation; Kp. L3 = 83 ° nid = 1.4745. 2-methyl-3-ethoxypropene- (2) -al- (l) is produced in an analogous manner. Bp 13 = 78 to 80 °; nD4 = 1,4755.

The sodium salt of methylmalondialdehyde required is advantageously obtained by condensation of propenyl ether with ethyl orthoformate using boron trifluoride etherate, subsequent saponification of the tetraethyl acetal of methylmalondialdehyde obtained to methylmalondialdehyde and neutralization with aqueous sodium hydroxide solution. For isolation of the sodium salt, the aqueous solution is evaporated and the residue from alcohol recrystallized.

In the first stage of the process, ß-Cl5-acetylene carbinol and the etherified or esterified 2-methyl-3-oxypropen- (2) -al- (l) by means of a organometallic reaction condenses to the C19 dioxyenol ester or ether. In the The preferred embodiment is β-Cl5-acetylene carbinol with two equivalents of alkyl magnesium halide (e.g. B. Ethylmagnesiumbromid) implemented; the resulting magnesium compound is now with 2-methyl-3-benzoxypropen- (2) -al- (1) or 2-methyl-3-ethoxypropen- (2) -al (1) condensed in a manner known per se. The implementation succeeds in the usual solvents, for example in ethyl ether. For the complete implementation of the reactants, the The reaction mixture is preferably heated for some time; then hydrolyzed it. Treatment with aqueous ammonium acetate solution at 0 to is suitable for this purpose 10'C.

In this way, Cl9-dioxyenol ester or ether is obtained as a viscous one (51, which is determined by Zerewitinoff (two active hydrogen atoms) and the UV absorption maximum at 236 mp (pure alcohol) is characterized.

The second stage of the process according to the invention consists in that the Cl9-Dioxyenolester or

-ether with an acidic agent, such as sulfuric acid in aqueous acetone, treated. The tertiary hydroxyl group is split off with allyl rearrangement, whereby the retro configuration develops. At the same time the enol ester or ether becomes hydrolyzed, whereby the retrodehydro-C19-acetylenic aldehyde is formed. One special An advantageous embodiment of the process consists in that the crude Cl9-dioxyenol ester or ether boils under reflux for some time in aqueous acetone with sulfuric acid. It is advantageous to carry out this reaction in a homogeneous solution and with the exclusion of air, so as not to destroy the sensitive retrodehydro-C19-acetylenaldehyde that is formed. The crude aldehyde isolated in the usual way is expediently at low temperature purified by crystallization from petroleum ether or methanol.

The pure aldehyde forms yellow crystals with a melting point of 60 to 62 ° C with maxima in the ultraviolet spectrum in petroleum ether at 270 and 374 mF, a = 13 540 and 30,000.

Dinitrophenylhydrazone, m.p. = 219-220 ° C (from acetone); Phenylhydrazone, M.p. = 105 to 106 ° C (from alcohol); Phenylsemicarbazone, m.p. = 173 to 174 ° C (from methanol) ; Azine, m.p. 142 to 144 ° C (from methanol).

If desired, the retrodehydro-Cl9-acetylenic aldehyde is used in a third stage selective to retrodehydro-Cls-aldehyde at the triple bond in a manner known per se reduced. An advantageous embodiment of this reaction is that the crystalline retrodehydro-Cl9 acetylenaldehyde in petroleum ether, after addition a trace of quinoline and a lead-poisoned palladium catalyst under normal conditions hydrogenated. The hydrogenation product isolated in a gentle manner is a cis form of retrodehydro-Cl9-aldehyde; this shows in the ultraviolet spectrum that for such Polyene compounds typical cis maximum at 270 ml.

This is achieved by heating and treating with a trace of iodine Hydrogenation product rearranged into a mixture of an oily and a solid three-dimensional shape ; the latter melts at 105 to 107 ° C, UV maxima at 303, 383 and 403 mp; e = 30,000, 28,800 and 23,500 (in petroleum ether). Phenylsemicarbazone, m.p. = 187-189 ° C.

The polyene aldehydes obtained according to the process are valuable intermediates for the synthesis of carotenoids, for example bis-dehydro-ß-carotene and 4,4'-dioxy-B-carotene.

Example 1 Clfl-Dioxyenolester Made into a Grignard solution by converting 11 parts by weight of magnesium with 39 parts by volume of ethyl bromide in 200 parts of ether-leave one Solution of 43 parts by weight of 5- [2 ', 6', 6'-trimethylcyclohexen- (1 ') - yl] -3-methyl-3-oxypenten- (4) -yne- (1) in Add dropwise 100 parts of ether so quickly that the mixture remains boiling. After this everything has been added dropwise, the mixture is boiled for a further 2 hours and then cooled away. With very vigorous stirring, Mannun lets a solution of 36 parts by weight of 2-methyl-3-benzoyloxypropene (2) -al- (1) run in 550 parts of ether within 10 minutes, then boil the mixture is refluxed for 1 hour. After the reaction mixture with Ice water has been cooled, a solution of 60 parts by weight of ammonium acetate is left in: 350 parts by volume of water slowly add dropwise. After the addition is complete if the pale yellow ethereal layer is removed from the water, it is waxed once with bicarbonate solution and dry them with sodium sulfate, after filtering off the drying agent and Evaporation of the ether in vacuo remains 80.5 parts by weight of the 8- [2 ', 6', 6'-trimethylcyclohexen- (1 ') - yl] -2,6-dimethyl-3,6-dioxy-1-benzoyloxyoctadiene ( 1.7) -in- (4) as a viscous, honey-yellow oil that contains 2 active hydrogen atoms in the Zerewitinoff determination shows and in the ultraviolet absorption spectrum at 236 mµ # = 20,000 (pure alcohol) a maxima. having.

Retrodehydro-Cig-acetvienaldehyd ', 80.5 parts by weight 8- [2', 6 ', 6'-trimethylcyclohexen- (1 ') - yl] -2,6-dimethyl-3,6-dioxy-1-benzoyloxyoctadiene- (1,7) -yne- (4) are in a mixture of 300 parts by volume of acetone and 10 parts by volume of 20% sulfuric acid dissolved, mixed with a trace of hydroquinone and under nitrogen for 2 hours cooked in the steam bath. That. : The reaction product that has become dark is poured onto ice water ì, poured, taken up in ether and shaken with bicarbonate solution of Benzoic acid freed. The dried and filtered ether solution leaves behind the Concentrate 50 to 55 parts by weight of a viscous oil that is low-boiling in about 100 parts by volume Petroleum ether is absorbed. By external cooling with solid carbonic acid in acetone part of the 8- [2 ', 6', 6'-trimethylcyclohexen- (2 ') - ylidene] -2, 6-dimethyloctadiene (2, 6) -in- (4) -al precipitated in crystalline form. This product is sucked off, @ washed it with cold petroleum ether and dry it in a vacuum at 30 to 40 ° C; there are about 22 parts by weight. i Melting point 55 to 58 ° C. By recrystallization from petroleum ether or methanol, the melting point rises to 60 to 62 ° C. UV maxima (petroleum ether) at 270 mμ, # = 13 540, 374 mμ, # = 30,000. The aldehyde can be distilled in a high vacuum will. B.p. 0.02 = 155 ° C. There is still a considerable amount in the crystallization mother liquor Amount of aldehyde present. ; Retrodehydro-C ,,, - aldehyde 24 parts by weight 8- [2 ', 6 ', 6'-trimethylcyclohexene (2') - :! ylidene] -2, 6-dimethyloctadiene- (2,6) -in- (4) -al- (l) are) dissolved in 150 parts by volume of low-boiling petroleum ether and 1 after adding 0.5 parts by volume Quinoline and 5 weight percentages. i, share 5% palladium catalyst under normal conditions hydrogenated. After the calculated S: eñgH hydrogen has been absorbed, interrupts the hy-, i dration, filtered off from the catalyst and concentrated in. Var i! kuum at lower temperature. The residue 8- [2 ', 6' 6'-trimethylcyclohexen- (2 ') - ylidene] -2, 6-dimethylocta-b triene- (2, 4, 6) -alate in the following UV absorption maxuna.:. T 270, 381 and 402 mCu, E = 18 600, 34750 and 28400f (petrolatum). ' By distillation in a high vacuum em low-boiling fraction (boiling point 0.015 = 120 to 130 ° C), which crystallized from petroleum ether, f. = 105 to 107 ° C, and one higher boiling Fraction (boiling point 0.01 = 150 to 155 ° C.) which has maxima in the ultraviolet absorption spectrum at 273, 381 and 401 m; u owns. Yield 60%.

Example 2 Clo-Dioxyenolether Prepared to a Grignard solution by converting 11 parts by weight of magnesium with 39 parts by volume of ethyl bromide in 200 parts by volume of ether, a solution of 43 parts by weight of 5- [2 ', 6', 6'-trimethylcyclohexene Add dropwise (1 ') - yl] -3-methyl-3-oxypenten- (4) -in- (1) in 100 parts by volume of ether so quickly that that the mixture remains boiling. After everything has dripped in, the mixture is boiled continue for another 2 hours and then cool it down.

Then a solution of 24.5 parts by weight of 2-methyl-3-ethoxypropene (2) -al- (1) Add ether in 100 parts by volume within 10 minutes and boil the mixture then a further 1 hour under reflux. After the reaction mixture is cooled with ice water has been left a solution of 60 parts by weight of ammonium acetate in 350 parts by volume Slowly add water dropwise.

After the addition is complete, the light yellow ether layer is separated from the Water off, wash them once with bicarbonate solution and dry them with sodium sulfate. After filtering off the drying agent and evaporation of the ether in vacuo about 65 parts by weight of the 8- [2 ', 6', 6'-trimethylcyclohexen- (1 ') - yl] -2 remain, 6-dimethyl-3, 6-dioxy-1-ethoxyoctadiene- (1, 7) -in- (4) as a tough, honey-yellow oil, which shows 2 active hydrogen atoms in the Zerewitinoff determination and in the ultraviolet absorption spectrum at 236 m; u E = 20,000 (pure alcohol) has a maximum. This product will as in the case of game 1 hydrolyzed to retrodehydro-Ci9-acetylenaldehyde and rearranged.

Claims (1)

PATENT CLAIM: 1. Process for the preparation of 8- [2 ', 6', 6'-trimethylcyclohexene (2 ') - ylidene] -2, 6-dimethyloctadiene- (2, 6) -in- (4) -al- (1) and 8- [2', 6 ', 6'-trimethylcyclohexene- (2 ') - ylidene] -2, 6-dimethyloctatriene- (2, 4, 6) -al- (1), characterized in that one 5- [2 ', 6', 6'-trimethylcyclohexen- (1 ') - yl] -3-methyl-3-oxypenten- (4) -yne- (1) in a manner known per se by means of an organometallic reaction with an etherified one or esterified 2-methyl-3-oxypropen- (2) -al condensed, the one obtained in the 1-position etherified or esterified 8- [2 ', 6', 6'-trimethylcyclohexen- (l ') - yl] -2, 6-dimethyl-1, 3, 6-trioxyoctadiene- (1,7) -in- (4) with an acidic agent such as sulfuric acid in aqueous Acetone, treated with allyl rearrangement, dehydration and hydrolysis 8- [2 ', 6', 6'-Trimethylcyclohexen- (2 ') - ylidene] -2, 6-dimethyloctadien- (2, 6) -in- (4) -al- (l) is formed, and this aldehyde, if desired, in a manner known per se selectively hydrogenated at the triple bond. ' 2. The method according to claim 1, characterized characterized in that the 5- [2 ', 6', 6'-trimethylcyclohexen- (1 ') - yl] -3-methyl-3-oxypenten- (4) -in- (1) by means of a Grignard reaction with a 2-methyl-3-alkoxypropen- (2) -al is condensed. References considered: J. Am. Chem. Soc., Vol. 74, 1952, pp. 295 and 3807 ff.; Vol. 71, 1949, pp. 2062 ff.