DE962074C - Process for the preparation of 4- [2 ', 6', 6'-trimethylcyclohexylidene] -2-methylbutene- (2) -als- (1) (iso-C-aldehyde) or 4- [2 ', 6', 6'-trimethylcyclohexen- (2 ') - ylidene] -2-methylbutene- (2) -als- (1) (retrodehydro-C-aldehyde) - Google Patents

Description

Process for the preparation of 4- [2 ', 6', 6'-trimethylcyclohexylidene] -2-methylbutene- (2) -als- (l) (Iso-Ct4-aldehyde) respectively.

4- [2 '6', 6 '-Trimethylcyclohexen- (2') - ylidene] -L-methylbutene- (2) -as- (1) (retrodehydro-Ct4-aldehyde) The invention relates to a method for the preparation of 4- [2 ', 6', 6'-trimethylcyclohexylidene] -2-methylbutene- (2) -als- (I) and des 4- {2 ', 6', 6'-trimethylcyclohexen- (2 ') - ylidene] -2-methylbutene- (2) -as- (1), which are referred to below as iso-Cl4-aldehyde and retrodehydro-Clgaldehyd. That Process is characterized in that the aldehyde of the formula R = CH - CHO, wherein R is the 2,6,6-trimethylcyclohexylidene radical which is optionally dehydrogenated in the 2,3-position means, acetalized in a manner known per se, the acetal obtained in a known manner Way at low temperature in the presence of an acidic condensing agent with condensed a propenyl ether and the resulting condensation product according to the usual Methods hydrolyzed with acids.

Similar procedures leading to vitamin A series compounds are the subject of U.S. Patents 2,586,305 and 2,615,922. This is how the process leads the former, starting from ß-ionone, to vitamin A-aldehyde. In contrast to the present one procedure The reaction there is very inconsistent. In careful research it has been found that those formed by condensation of the starting ketals with vinyl ether Ether acetals very easily with the vinyl ether that is still present with the formation of di- and polyether acetals continue to react. An attempt was made to cause the side reactions Avoid using a multiple excess of starting ketal. As found now the previously known method leads to essentials in spite of this precautionary measure Proportions of undesirable polyether acetals in addition to the desired ether acetal. That The reaction product also contains a large amount of unchanged starting ketal.

The difficult and lossy work-up of the reaction mixture only leads to insignificant amounts of vitamin A-aldehyde.

In contrast, it has now surprisingly been found that in the implementation the a, jB-unsaturated acetals with a propenyl ether according to the registration no noteworthy Shares of higher condensation products arise. Got at low temperature you even get exclusively to the desired ether acetal, without an excess of the one reactant would have to be used. This can lead to the separation of unconverted raw materials and a lossy fractionation be waived. According to the registered process, therefore, yields can also be achieved of about 70 0Jo of theory.

The 2, 6, 6-trimethylcyclohexylidene required as starting material or 2, 6, 6-trimethylcyclohexen- (2) -ylidene acetaldehyde (iso- or retrodehydro-Cll-aldehyde) can be produced as follows: That by condensation of ethoxyacetylene with 2, 6, 6-trimethylcyclohexanone- (I) or 2, 6, 6-trimethylcyclohexen- (2) -one- (1) Ethoxyacetylenecarbinol obtained is attached to the triple bond in a manner known per se partially hydrogenated and treated with acid.

The 2,6,6-trimethylcyclohexylidene acetaldehyde obtained from trimethylcyclohexanone is a colorless oil with a boiling point of 10 ° / 12 mm; n25 = 1,496; UV absorption maximum at 237 to 238 m, le (in petroleum ether solution). The one obtained from trimethylcyclohexenone 2, 6, 6-Trimethylcyclohexen- (2) -ylidene acetaldehyde is a yellowish oil with a boiling point 1150113 mm; n25 = 1.53I; UV absorption maximum at 278 m, c (in petroleum ether solution).

For the manufacture of the raw materials, protection is provided within the framework of the present invention is not desirable.

The first stage of the process according to the invention consists in acetalization of iso- or retrodehydro-C11-aldehyde to 2, 6, 6-trimethylcyclohexylidene or 2, 6, 6-trimethylcyclohexen- (2) -ylidene acetaldehyde acetal (iso- or retrodehydro-C11-acetal). This takes place in a manner known per se. It is acetalized, for example, by means of of an orthocarboxylic acid ester in the presence of an acidic condensation agent, such as Boron trifluoride etherate, zinc chloride, ammonium nitrate, phosphoric acid or p-toluenesulfonic acid. The orthocarboxylic acid esters of lower aliphatic carboxylic acids are particularly suitable for this purpose with lower aliphatic alcohols, preferably methyl orthoformic acid, ethyl or n-butyl ester.

The acetals obtained are colorless oils. The Iso-Cll-acetals show in the UV spectrum over 225 m, there is no absorption maximum, whereas for the retrodehydro-C11-acetals such a bzi 240 mu is characteristic. For further processing there is a special cleaning of the acetals, e.g. B. by distillation, not required.

In the second stage of the process, the iso- or. Retrodehydro-C11-acetal in a known manner with a propenyl ether in the presence of an acidic condensing agent for 4- [2 ', 6', 6'-trimethylcyclohexylidene] - or 4- [2 ', 6', 6'-trimethylcyclohexen- (2 ') - ylidene] -2-methylbutane ether- (3) -acetal- (I) (Iso- resp.

Retrodehydro-Cl4-ether acetal) condensed. As a condensing agent boron trifluoride etherate, zinc chloride, titanium tetrachloride, - aluminum trichloride, Ferric chloride or tin tetrachloride. The propenyl ether is expediently used of the same alcohol with which the iso- or retrodehydro-C11-aldeliyd is acetalized was e.g. B. the methyl propenyl ether, ethyl propenyl ether or n-butyl propenyl ether. The condensation takes place at the lowest possible reaction temperature, whereby unwanted side reactions, such as polymerization and condensation of the formed Iso- or retro-dehydro-C14-ether acetals with propenyl ether, can avoid. the optimal reaction temperature depends on the choice of condensing agent and of the acetal and propenyl ether used for condensation between 0 and 500. In the preferred embodiment, approximately molar amounts of iso- or retrodehydro-C11-acetal are allowed and propenyl ether act on each other at 0 to 30 ° in the presence of zinc chloride. To a large extent pure iso- or retrodehydro-Cl4-ether acetals are obtained in an almost quantitative manner Yield. They are colorless oils.

In the UV spectrum, the Iso-Clg ether acetals show over 225 m, no absorption maximum on, whereas for the retrodehydro-Cl4-ether-acetals one at 235 mm is characteristic is. For further processing, special cleaning, e.g. B. by distillation, not mandatory.

The third stage of the process according to the invention consists in that the iso- or retrodehydro-Cl4-ether acetals in a known manner in acidic solution hydrolyzed. This reaction can advantageously be conducted in such a way that z. B. by heating that with simultaneous elimination of alcohol from the 2, 3-position of the iso- or retrodehydro-Cl4-aldehyde is formed. This reaction stage takes place in the presence of water-soluble, organic or inorganic acids, such as p-toluenesulfonic acid, acetic acid, propionic acid, oxalic acid, sulfuric acid, phosphoric acid, or acidic, water-soluble salts such as zinc chloride and sodium bisulfate. During the reaction, oxygen is advantageously excluded and an antioxidant, z. B. hydroquinone added. It is expedient to work under conditions under which the alcohol formed is continuously removed from the reaction mixture. Man a water-miscible solvent such as dioxane or tetrahydrofuran can be added to the reaction mixture or ethylene glycol dimethyl ether, add to a homogeneous Reaction mixture to obtain. The iso- or retrodehydro-Cl4-ether acetal is preferably diluted with Phosphoric acid in the presence of a water-miscible solvent or with acetic acid heated to about 1000 with the addition of an alkali acetate and a little water. When diluting the reaction mixture with water precipitates the oily iso- or retrodehydro-C14-aldehyde which can be purified by distillation.

To avoid substance loss through polymerization and decomposition it is recommended to avoid temperatures above 1200 during the entire procedure and in particular intermediate products, namely iso- or retrodehydro-Cll-acetal and the iso- or retrodehydro-C14 ether acetal, to be further processed undistilled.

The iso-Cl4-aldehyde obtained by the present process boils at 82 ° / 0.05 mm. In the UV spectrum it has an absorption maximum at 287 to 288 m, u on; E1 @ = 1.400 (in petroleum ether solution).

The retrodehydro-C14-aldehyde boils at 94 ° / 0.05 mm. He shows im UV spectrum has an absorption maximum at 318 mμ; E11 = 1670 (in petroleum ether solution).

The iso-C14-aldehyde and the retrodehydro-C14-aldehyde are valuable Intermediate products for the synthesis of vitamin A or vitamin A2 and jB-carotene or of carotenoids. They represent fragrances with fixing properties, which are reminiscent of ß-Jonon.

Example I Retrodehydro-C11-acetal A solution of 16 parts by weight 2,6,6-Trimethylcyclohexen- (2) -ylidene acetaldehyde in 18 parts by volume of ethyl orthoformate is absolute with a solution of 0.3 parts by volume of orthophosphoric acid in 3 parts by volume Ethanol added and left to stand at 20 to 250 hours for 15 hours. Then you add 5 room parts Pyridine and pour the mixture into a mixture of 20 parts by weight of 5% Sodium bicarbonate solution and 10 parts by weight of ice. The reaction product is taken in petroleum ether, shake the petroleum ether solution with sodium bicarbonate solution and dries them over potash. After concentrating the petroleum ether solution, the Residue in vacuo at 70 ° of excess ethyl orthoformate and the resulting Liberated formic acid ethyl ester.

22 parts by weight of crude 2,6,6-trimethylcyclohexen- (2) -ylidene acetaldehyde diethyl acetal are obtained, that is pure enough for further processing. By distillation you can get a colorless product obtained; Boiling point 130 to 132 ° / 13 mm; nD23 = 1.4805; UV absorption maximum at 240 mµ (in petroleum ether solution).

Retrodehydro Cl4 ether acetal 20 parts by weight of 2, 6, 6-trimethylcyclohexen- (2) -ylidene acetaldehyde diethyl acetal be with I part by volume of a solution of zinc chloride in ethyl acetate offset. It is then added simultaneously over the course of 2 hours at 25 ° to 35 ° with stirring 8 parts by volume of propenyl ethyl ether and 6 parts by volume of an I / O solution of zinc chloride in ethyl acetate and the mixture is then left for a further 15 hours Stand room temperature. The reaction product is then taken up in petroleum ether and washed the solution with dilute caustic soda and dries it over potash. After this Distilling off the solvent gives 28 parts by weight of crude 4- [2 ', 6', 6'-trimethylcyclohexen- (2 ') ylidene] -2-methylbutane ether- (3) -diethylacetal- (I), which can be implemented further without further purification. Can by distillation a colorless product with a boiling point of 120 to 125010.3 mm can be obtained; nD2 = 1.4715; UV absorption maximum at 235 nyl (in petroleum ether solution).

Retrodehydro-Cl4-aldehyde 28 parts by weight of 4- [2 ', 6', 6'-T @ imethylcyclohexen- (2 ') - ylidene] -2-methylbutane ether- (3) -diethylacetal- (1-be) with 60 parts by volume of glacial acetic acid, 6 parts by weight of sodium acetate and 3 parts by volume of water added and after adding a trace of hydroquinone for 6 hours in a nitrogen atmosphere heated to 95 °. The mixture is then cooled to 30 to 40 ° and poured it to 50 parts by weight of ice and 50 parts by volume of water.

The oily reaction product is taken up in petroleum ether, the washes Solution with sodium bicarbonate solution and with water and dry it over sodium sulfate.

After concentrating the petroleum ether solution, the residue is in a high vacuum distilled. 14 parts by weight of 4- [2 ', 6', 6'-trimethylcyclohexen- (2 ') ylidene] -2-methylbutene- (2) -as- (1) are obtained with a boiling point of 94 ° / 0.05 mm; nD24 = 1.610; UV absorption maximum at 318 m; E11 = I670 (in petroleum ether solution).

Example 2 Iso-C14-aldehyde A solution of 110 parts by weight of 2, 6,6-TA-methylcyclohexylidene acetaldehyde from 120 parts by volume of ethyl orthoformate is absolute with a solution of 2 parts by volume of orthophosphoric acid in 18 parts by volume Ethanol is added and the mixture is left to stand for 15 hours at 20 to 25 ". Then zo Parts by volume of pyridine and poured the mixture onto a mixture of 200 parts by weight 5% sodium bicarbonate solution and 100 parts by weight of ice. The reaction product is taken in petroleum ether, shake the solution with sodium bicarbonate solution and dry them about potash. After concentrating the petroleum ether solution, the residue is im Vacuum at 70 ° of excess ethyl orthoformate and ethyl formate formed freed. The residue consists of 150 parts by weight of 2,6,6-trimethylcyclohexylidene acetaldehyde diethylacetal vom nD23 = 1.464, which has no absorption maximum above 225 m, ez in the W spectrum. This product is condensed with propenyl ether without further purification. To this The purpose is to add g parts by volume of a 10% solution of zinc chloride in ethyl acetate to, then added simultaneously with stirring at 30 to 35 ° over the course of 2 hours 65 parts by volume of propenyl ethyl ether and 43 parts by volume of a 10% solution of zinc chloride in ethyl acetate and the mixture is then stirred for a further 20 hours Room temperature. The obtained 4- [2 ', 6', 6'-trimethylcyclohexylidene] -2-methylbutane ether- (3) -diethylacetal- (1) of nD23 = 1.459 is used for saponification and separation of alcohol to a mixture of 450 parts by volume of glacial acetic acid, 45 parts by weight of sodium acetate and 22 parts by volume of water were added and the mixture was heated to 95 ° in a nitrogen atmosphere for 6 hours. It is then cooled to 30 to 400 and poured onto 400 parts by weight of ice and 400 parts by volume of water. The oily reaction product is taken up in petroleum ether, washes the solution with 50% sodium bicarbonate solution and with water and dries them over sodium sulfate. After concentrating the petroleum ether solution, the residue becomes distilled in a high vacuum. Go parts by weight of 4- [2 ', 6', 6'-trimethylcyclohexylidene] -2-methylbutene- (2) -as- (X) are obtained from the boiling point 82 to 840.10.05 mm; nD23 = 1.547; UV absorption maximum at 288 mµ, E: = I400 (in petroleum ether solution).

Claims (5)

PATENT CLAIMS: I. Process for the preparation of 4- [2 ', 6', 6'-TA-methylcyclohexylidene] -2-methylbutene- (2) - as- (I) (iso-Cl4-aldehyde) or 4- [2 ', 6', 6'-trimethylcyclohexene (2 ') -ylidene] -2-methylbutene- (2) -als- (1) (retrodehydro-Cl4-aldehyde), characterized in that that the aldehyde of the formula R = CH-CHO, in which R is optionally in the 2, 3-position means dehydrated 2, 6, 6-trimethylcyclohexylidene radical, known per se Acetalized manner, the acetal obtained in a known manner in the presence of an acidic Condensing agent at a temperature of o to 50 °, preferably o to 30 °, condensed with a propenyl ether and the resulting condensation product in the usual Way hydrolyzed with an acid. 2. The method according to claim I, characterized in that the Starting compound with the orthocarboxylic acid ester of lower aliphatic carboxylic acids acetalized with lower aliphatic alcohols and the acetal obtained with the Condensed propenyl ether of the same lower alcohol. 3. The method according to claim I and 2, characterized in that one the equivalent amount of propenyl ether in the presence of zinc chloride on the acetal can act. 4. The method according to claim I, characterized in that the obtained condensation product hydrolyzed with acetic acid in the presence of sodium acetate. 5. The method according to claim I, characterized in that the Intermediate products are further processed undistilled. References considered: U.S. Patents No. 2,586 305, 2 6I5 922.