NEW INTERMEDIATES FOR THE VITAMIN A SYNTHESIS

Abstract

The present invention relates to the compound of formula (I). The invention further relates to the compound of formula (II). The invention further relates to the synthesis of these compounds as well as to their use in organic synthesis, especially in the synthesis of vitamin A or p-carotene and derivatives thereof, e.g. canthaxanthin, astaxanthin or zeaxanthin.

##STR00001##

Claims

1. A compound of formula (I) ##STR00013##

2. A compound of formula (II) ##STR00014##

3. A process of production of the compound of formula (II) ##STR00015## wherein the compound of formula (IV) ##STR00016## is reacted with acetic acid anhydride or similar to form the compound of formula (II).

4. A process of production of the compound of formula (I), ##STR00017## wherein the compound of formula (II) ##STR00018## is catalytically rearranged.

5. Use of the compound of formula (I) in organic synthesis.

6. Use according to claim 5, wherein the vitamin A or -carotene are produced (preferably vitamin A).

7. Use of the compound of formula (II) in organic synthesis.

8. Use according to claim 7, wherein the vitamin A or -carotene are produced (preferably vitamin A).

Description

EXAMPLES

Example 1: Synthesis of -cyclogeranyllinalool

[0028] Under inert gas atmosphere, 22 mmol of (E)-6-methyl-8-(2,6,6-trimethylcyclohex-1-en-1-yl)oct-5-en-2-one (III) were dissolved in 22 ml of anhydrous THF. The solution was cooled to 0-5 C. with an ice-bath. Over 2 hours, 33 mmol vinyl magnesium bromide solution (1 M in THF) were added dropwise so that the temperature remains between 0-5 C. After complete addition, stirring was continued for 1 hour. After that the ice-bath was removed and the reaction was warmed to room temperature. After 1 hour at 24 C., sat. NH.sub.4Cl-solution (30 ml) was added dropwise over 10 min (exothermic). After stirring for another 30 min the mixture was diluted with methylene chloride (100 ml) and washed with brine (245 ml). The aqueous layers were re-extracted with methylene chloride (2100 ml). The combined organic layers were dried over sodium sulfate, filtered and concentrated under reduced pressure. The crude product was purified by column chromatopgraphy (SiO.sub.2, cyclohexane/diisopropyl ether 8:2).

Example 2: Synthesis of -cyclogeranyllinalool Acetate

[0029] Under inert gas atmosphere, 3.44 mmol -cyclogeranyllinalool were dissolved in 6.9 ml of toluene. At room temperature, 8.61 mmol of triethylamine and 1.722 mmol of dimethyl aminopyridine (DMAP) were added. To the colorless solution were added 8.61 mmol of acetic acid anhydride. Then the reaction mixture was warmed to 50 C. and stirred for 2 hours.

[0030] The reaction mixture was cooled to room temperature, transferred into a separation funnel and diluted with 15 ml of diethyl ether. The organic layer was subsequently washed with semi-saturated NaHCO.sub.3 solution (30 ml), water (30 ml) and brine (30 ml). The aqueous layers were re-extracted with diethyl ether (30 ml). The combined organic layers were dried over Na.sub.2SO.sub.4, filtered and concentrated under reduced pressure. The crude product was purified by column chromatography (SiO.sub.2, cyclohexane/diisopropyl ether 8:2). The purified product was obtained as colorless liquid in 81% yield.

Example 3: Synthesis of -cyclogeranylgeraniol Acetate

[0031] Under inert gas atmosphere, 0.05 mmol bis(acetonitrile)-dichloropalladium were dissolved in 1 ml of anhydrous THF. At room temperature, a solution of 1 mmol of -cyclogeranyllinalool acetate in 4 ml of anhydrous THF was added within 20 min. After stirring for 4 hours at room temperature, the reaction was complete. The solvent was removed and the crude product was purified by column chromatography (SiO.sub.2, n-hexane/ethyl acetate 95:5). The purified product was obtained as yellow liquid in 50% yield.