NO121907B - - Google Patents

Description

Process for the production of unsaturated primary alcohols of the vitamin A series.

It is known that unsaturated, primary

or secondary alcohols, particularly of the vitamin A series, can be produced by reduction of the corresponding aldehydes or ketones using lithium aluminum hydride, sodium borohydride or similar metal hydrides containing two metal atoms. For example, it is known that crotyl alcohol can be produced by reducing crotylaldehyde with the help of lithium aluminum hydride. In a similar way, vitamin A can be produced by reducing vitamin A aldehyde.

It has now been found that unsaturated alcohols of the vitamin A series can also be produced using dialkyl aluminum hydrides and trialkyl aluminum. The advantage of using these instead of the expensive lithium compounds is that a cheaper production of very important alcohols becomes possible. Furthermore, it was found that when dialkyl or trialkyl aluminum hydride is used, the reaction conditions, as regards the choice of solvents and reaction temperature, are far less

critical than when using LiAlH4.

Dialkyl or trialkyl aluminum hydrides are known per se. It has also become

asserted that these compounds have reducing properties similar to those of lithium aluminum hydride (Angewandte Chemie, 67,

424-425 (1955). It has also been stated that

alkyl aluminum compounds can react

with saturated aliphatic compounds while forming addition products.

According to the present invention, it has been found that the latter

action with unsaturated compounds does not or almost does not occur if dialkyl aluminum hydrides or trialkyl aluminum are allowed to react with unsaturated aldehydes or ketones of the vitamin A series.

In this reaction, almost exclusively primary resp. secondary alcohols, which contain the same number of double bonds as the starting materials. The invention is therefore based on a method for producing unsaturated primary alcohols of the vitamin A series and is characterized by the fact that aldehydes or ketones of the vitamin A series are reduced by means of dialkyl aluminum hydrides or trialkyl aluminum.

It is advantageous to carry out the reduction in the absence of oxygen. It is therefore preferably carried out in a nitrogen atmosphere. Furthermore, it is important that the temperature is kept low during the reaction. The temperature range in which the reaction proceeds satisfactorily is between -f-50 and + 50° C. Furthermore, it is recommended not to use any larger amount of the reducing agent than is necessary for the reduction of the aldehyde or ketone group to the corresponding primary alcohol group. For the reaction of 1 mol of unsaturated aldehyde or ketone, you will e.g. use approx. 1 mol dialkyl aluminum hydride or 1 mol trialkyl aluminum.

Very good results are obtained by reducing with a dialkyl aluminum hydride or a trialkyl aluminum compound in which the number of carbon atoms in each of the alkyl groups is between 1 and 6. The alkyl group can e.g. be an ethyl, isobutyl or butyl group.

The reduction is preferably carried out in an inert solvent, e.g. in n-hexane, cyclohexane, benzene, toluene or petroleum ether. Not only these aliphatic or aromatic hydrocarbons, but also aliphatic or cyclic ethers, such as e.g. diethyl, methylethyl, dipropyl, diisopropyl ethers, or dioxane or tetrahydrofuran, can be used as solvent during the reduction.

To carry out the reduction, one can either add the compound to be reduced, or a solution thereof, to a solution of the reducing agent, or one can add a solution of the reducing agent to the compound to be reduced or to a solution thereof.

After completion of the reduction, the remainder of the reducing agent can be carefully decomposed with moist ether, with water and, if necessary, with acidified water.

The method according to the invention can be used to reduce unsaturated aldehydes or ketones of the vitamin A series, so that the corresponding primary alcohols are formed. The invention is of importance for the production of primary alcohols of the vitamin A series, in particular for the production of p-ionylidene ethanol, 1-(2'2'6'-trimethylcyclohexane(-6-yl)-1-3-methyl -octatriene l,2,4-ol-7 and vitamin A itself. For the production of these three substances (3-jonylidene-acetaldehyde, the so-called (3-C38-ketone, i.e. l-(2' 2'6'-trimethyl-cyclohexen-6-yl-1)3-methyl-octatriene

1,2,4, on-7 resp. vitamin A aldehyde.

Execution examples: 1) 10.9 g (0.05 mol) of p-jonylidene acetaldehyde was dissolved in 75 ml of benzene and the solution was cooled to 5° C. To this solution was added a similarly cooled solution of 1.7 g (0.5 mol) of diisobutyl aluminum hydride, with stirring. After everything had been added, the stirring was continued for ½ hour at an elevated temperature (approx. 35° C.).

The reaction mixture was then cooled (0° C.) and very carefully cleaved by dropwise addition of moist diethyl ether and then water with a small amount of dilute sulfuric acid. The solution of p-ionylidene ethanol obtained in this way was washed with water, dried over sodium sulphate and evaporated in vacuo. The residue was distilled in vacuo. The boiling point at 0.005 mm Hg was 98-101° C. The absorption spectrum in ethanol had two maxima at 240 and

265 m(A. The e-values were 12,400 and 12,700 respectively.

2) In a similar way as in example 1, 14.2 g (0.05 mol) of vitamin A aldehyde in cyclohexane was reduced with 7.1 g (0.05 mol) of diisobutyl aluminum hydride, so that vitamin A was formed. Amax = 325/mjx, e = 31,000. The vitamin content, determined according to Carr and Price, was 1,980,000 I.E./g. 3) In a similar manner as in example 1, 10.9 g (0.05 mol) of p-ionylidene acetaldehyde in cyclohexane was reduced with 9.9 g (0.05 mol) of triisobutyl aluminium. The reaction mixture was worked up as in example 2, and by distillation gave a product which was identical to that obtained in example 2. 4) In a similar way as in example 2, a solution of 5.68 g (0.02 mol) vitamin A aldehyde in n-hexane was reduced using a solution of 2.28 g (0.02 mol) triethyl- aluminum in n-hexane. The reaction mixture was worked up as in example 1. The crude end product had an absorption spectrum in ethanol at 325 m^. e = 32,600. The vitamin content, determined by means of antimony trichloride (Carr and Price) was 2,060,000 I.E./g. 5) A solution of 7.74 g (0.03 mol) of C18 ketone in petroleum ether was reduced with a solution of 5.94 g (0.03 mol) of triisobutyl aluminum in petroleum ether. The reaction mixture was worked up as in Example 1. The crude reaction product had an absorption spectrum in ethanol with a maximum at 290 m 2 . e = 25,400.

Claims (2)

1. Process for the production of unsaturated primary alcohols of the vitamin A series by reduction of aldehydes or ketones of the vitamin A series, characterized in that a dialkyl aluminum hydride or trialkyl aluminum hydride is used as reducing agent. 2. Process according to claim 1, characterized in that the reduction is carried out with one of the mentioned reducing agents in which each alkyl group contains 1-6 carbon atoms, in equimolar amounts in the presence of an inert solvent, e.g. an aliphatic or aromatic hydrocarbon, such as n-hexane, cyclohexane, petroleum ether, benzene, or toluene or an aliphatic or cycloaliphatic ether, such as diethyl, methylethyl, dipropyl, diisopropyl ether, dioxane or tetrahydrofuran, at a temperature between 50 and + 50° C.