NEW PROCESS FOR THE PRODUCTION OF RETINAL

Abstract

The present invention relates to a new process for the production of retinal or hydrogenated form of retinal.

Claims

1. Process for the production of the compounds of formula (I) ##STR00012## by selective dehydrogenation of the compounds of formula (II) ##STR00013## wherein R is —CHO or —CH.sub.2OH, wherein the dehydrogenation is carried out in the presence of at least one transition metal catalyst.

2. Process according to claim 1, wherein the transition metal catalyst is a Pd catalyst.

3. Process according to claim 1, wherein the transition metal catalyst is Pd(OAc).sub.2.

4. Process according to claim 1, wherein the amount of the catalyst goes from 0.01 mol-equivalent up to 0.5 mol-equivalent (in relation to compound of formula (II)).

5. Process according to claim 1, wherein the process is carried out in the presence of air and/or O.sub.2.

6. Process according to claim 1, wherein the process is carried out in the presence of at least one base.

7. Process according to claim 6, wherein the strong base is K.sub.2CO.sub.3 or pyridine.

8. Process according to claim 6, wherein the strong base is present in an amount of 0.01 mol-equivalent up to 0.5 mol-equivalent (in relation to compound of formula (II)).

9. Process according to claim 1, wherein the process is carried out in an inert solvent.

10. Process according to claim 9, wherein the inert solvent is DMF.

11. Process according to claim 1, wherein the process is carried out a temperature of from 0° C.-100° C.

12. Compound of formula ##STR00014##

13. Compound of formula ##STR00015##

14. Compound of formula ##STR00016##

15. Compound of formula ##STR00017##

16. Compound of formula ##STR00018##

Description

EXAMPLES

Example 1

[0042] A 2-necked flask equipped with a stirring bar, thermometer and a dimroth condenser was charged with K.sub.2CO.sub.3 (16 mg, 0.15 eq), Pd(OAc).sub.2 (16 mg), 11,12-dihydroretinal (190 mg, 1.0 eq), DMF (3.0 mL) and pyridine (5 μL, 0.1 eq). The yellow suspension was stirred at 60° C. for 6 h, applying a constant air stream. The reaction mixture was cooled to room temperature and diluted with Et.sub.2O (10 mL) and washed with H.sub.2O (10 mL×3). The organic phase was concentrated under reduced pressure (40° C./ 30 mbar). Purification by column chromatography afforded the product as orange solid (85 mg, yield 46%).

Example 2

[0043] A 4-necked flask equipped with a stirring bar, thermometer and a dimroth condenser was charged with K.sub.2CO.sub.3 (150 mg, 0.17 eq), Pd(OAc).sub.2 (150 mg), 7,8,11,12-tetrahydroretinal (1.8 g, 1.0 eq). DMF (30.0 mL) and pyridine (50 μL, 0.1 eq). The yellow suspension was stirred at 60° C. for 6.5 h, applying a constant air stream. The reaction mixture was cooled to room temperature and diluted with Et.sub.2O (100 mL) and washed with H.sub.2O (100 mL×3). The organic phase was concentrated under reduced pressure (40° C./30 mbar). Purification by column chromatography afforded the product (11,12-dihydroretinal) as orange oil (0.66 g, yield 40%).

Example 3

[0044] A 3-necked flask equipped with a stirring bar, thermometer and a dimroth condenser was charged with K.sub.2CO.sub.3 (166 mg, 0.17 eq), Pd(OAc).sub.2 (189 mg), 11,12-dihydroretinol (2.1 g, 1.0 eq), DMF (30.0 mL) and 1,2-bis(diphenylphosphino)-ethane (416mg, 0.14 eq). The yellow suspension was stirred at 60° C. for 6 h, applying a constant air stream. The reaction mixture was cooled to room temperature and diluted with Et.sub.2O (100 mL) and washed with H.sub.2O (100 mL×3). The organic phase was concentrated under reduced pressure (40° C./30 mbar). Purification by column chromatography afforded the product as orange solid (0.39 g, yield 18%).

Example 4

[0045] A 3-necked flask equipped with a stirring bar thermometer and a dimroth condenser was charged with K.sub.2CO.sub.3 (168 mg, 0.16 eq), Pd(OAc)2 (190 mg), 7,8,11,12-tetrahydroretinol (2.2 g, 1.0 eq), DMF (30.0 mL) and 1,2-bis(diphenyl-phosphino)ethane (418 mg, 0.14 eq). The yellow suspension was stirred at 60° C. for 24 h, applying a constant air stream. The reaction mixture was cooled to room temperature and diluted with Et.sub.2O (100 mL) and washed with H.sub.2O (100 mL×3). The organic phase was concentrated under reduced pressure (40 ° C./30 mbar). Purification by column chromatography afforded the product (7,8-dihydroretinal) as orange oil (0.45 g, yield 21%).

Example 5

[0046] A 2-necked flask equipped with a stirring bar (1.5 cm) and a dimroth condenser was charged with K.sub.2CO.sub.3 (16 mg, 0.18 eq), Pd(OAc).sub.2 (23 mg), 7,8,11,12,13,14-hexahydroretinal (250 mg, 1.0 eq), DMF (3.0 mL) and pyridine (7 μL, 0.1 eq). The yellow suspension was stirred at 60° C. for 31 h, applying a constant air stream. The reaction mixture was cooled to room temperature and diluted with Et.sub.2O (10 mL) and washed with H.sub.2O (10 mL×3). The organic phase was concentrated under reduced pressure (40° C./30 mbar). Purification by column chromatography afforded the product as orange oil (48 mg, yield 19%).

Example 6

[0047] A 2-necked flask equipped with a stirring bar (1.5 cm) and a dimroth condenser was charged with K.sub.2CO.sub.3 (18 mg, 0.18 eq), Pd(OAc).sub.2 (18 mg), 11,12,13,14-tetrahydroretinal (200 mg, 1.0 eq), DMF (3.0 mL) and pyridine (6 μL, 0.1 eq). The yellow suspension was stirred at 60° C. for 48 h, applying a constant air stream. The reaction mixture was cooled to room temperature and diluted with Et.sub.2O (10 mL) and washed with H.sub.2O (10 mL×3). The organic phase was concentrated under reduced pressure (40° C./30 mbar). Purification by column chromatography afforded the product as orange solid (29 mg, yield 15%).