PROCESS FOR PRODUCTION OF VITAMIN A

Abstract

The present invention relates to a new process for the production of vitamin A and/or its derivatives.

Claims

1. Process for the production of a compound of formula (formula (I) ##STR00032## wherein R is H or ##STR00033## and wherein R.sub.1 is a linear or branched C.sub.1-C.sub.18 alkyl moiety, characterized in that in a first step (step (i)) the compound of formula (II) ##STR00034## is reacted with a compound of formula (III) ##STR00035## wherein R (and also R.sub.1) has the same meanings as defined for the compound of formula (I), and then in a second step (step (ii)) the reaction product of step (i), which is the compound of formula (IV) ##STR00036## wherein R (and also R.sub.1) has the same meanings as defined for the compound of formula (I), is converted into the compound of formula (I) by heating the reaction mixture.

2. The process according to claim 1, wherein the reaction of step (i) is carried out in at least one inert solvent.

3. The process according to claim 2, wherein the at least one inert solvent is a polar aprotic or a non-polar aprotic solvent.

4. The process according to claim 2, wherein the at least one inert solvent is chosen from the group consisting of cyclopentyl methyl ether, tert-butyl methyl ether, MeTHF, toluene, heptane and n-hexane.

5. The process according to claim 1, wherein the reaction of step (i) is carried out in the presence of at least one strong base.

6. The process according to claim 5, wherein the pK.sub.B value of strong base (or mixture of bases) is below 2.

7. The process according to claim 5, wherein the at least one strong base is used in an amount of 0.8 to 2.5 mol-equivalent in regard to the compound of formula (III).

8. The process according to claim 1, wherein the reaction of step (i) is carried out at a temperature of 90 C. to 25 C.

9. The process according to claim 1, wherein, step (ii) the reaction product of step (i), which is the compound of formula (IV) ##STR00037## wherein R has the same meanings as defined for compound of formula (I), is dissolved in at least one inert solvent.

10. The process according to claim 9, wherein the at least one inert solvent is a polar aprotic or a non-polar aprotic solvent.

11. The process according to claim 9, wherein the at least one inert solvent is chosen from the group consisting of THF, diethyl ether, cyclopentyl methyl ether, tert-butyl methyl ether, MeTHF, toluene, heptane and n-hexane.

12. The process according to claim 1, wherein the reaction of step (ii) is carried out at an elevated temperature.

13. The process according to claim 12, wherein the reaction of step (ii) is carried out at a temperature of 40 C. to 120 C.

14. Compounds of formula (IV) ##STR00038## wherein R is H or ##STR00039## and wherein R.sub.1 is a linear or branched C.sub.1-C.sub.18 alkyl moiety.

15. Compounds of formula (Vb) ##STR00040## wherein R is H or ##STR00041## and wherein R.sub.1 is a linear or branched C.sub.1-C.sub.18 alkyl moiety.

Description

EXAMPLES

Example 1: Retinyl Acetate Via Compound of Formula (IVa)

[0070] In a two-necked round bottom flask C.sub.14-aldehyde ((II), (E)-2-methyl-4-(2,6,6-trimethylcyclohex-1-en-1-yl)but-2-enal) (260 mg) and (3-methyl-1,1-dioxido-2,5-dihydrothiophen-2-yl)methyl acetate (268 mg) were dissolved in anhydrous THF (3.75 ml). Under inert gas atmosphere, the reaction mixture was cooled to 75 C. A 2M solution of LDA in THF/n-hexanes (1.25 ml, 2.08 eq.) was added dropwise and stirring was continued for another 10 min at 75 C. The cooling bath was removed and semi-saturated NH.sub.4Cl-solution (12.5 ml) was added. The two-phasic mixture was transferred into a separation funnel and extracted with diethyl ether (225 ml). The combined organic extracts were washed subsequently with water (212.5 ml) and brine (12.5 ml), filtered and concentrated under reduced pressure (40 C., 5 mbar). The crude product (521 mg) was obtained as a yellow oil. After purification by column chromatography (SiO.sub.2, cyclohexane/ethyl acetate 8:2) 163.3 mg of the compound of formula (IVa)

##STR00030##

was obtained.

[0071] The oil was placed in a dried two necked round bottom flask and dissolved in toluene (5 mL) under an argon atmosphere. The reaction mixture was heated to reflux for 4 h. All volatiles were evaporated under reduced pressure (40 C., 5 mbar) to obtain retinyl acetate.

Example 2: Compound of Formula (IVb)

[0072] In a two-necked round bottom flask, C.sub.14-aldehyde ((II), (E)-2-methyl-4-(2,6,6-trimethylcyclohex-1-en-1-yl)but-2-enal) (260 mg) and (3-methyl-1,1-dioxido-2,5-dihydrothiophen-2-yl)methyl propionate (281 mg) were dissolved in anhydrous THF (3.75 ml). Under inert an acetone/dry-ice cooling bath to 75 C. A 2M solution of LDA in THF/n-hexanes (1.25 ml, 2.08 eq.) was added dropwise and stirring was continued for another 10 min at 75 C. The cooling bath was removed and semi-saturated NH.sub.4Cl-solution (12.5 ml) was added. The two-phasic mixture was transferred into a separation funnel and extracted with diethyl ether (225 ml). The combined organic extracts were washed subsequently with water (212.5 ml) and brine (12.5 ml), filtered and concentrated under reduced pressure (40 C., 5 mbar). The crude product was obtained as a yellow oil. After purification by column chromatography (SiO.sub.2, cyclohexane/ethyl acetate 8:2) 115 mg of the compound of formula (IVb)

##STR00031##

was obtained.