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. A process for the production of a compound of formula (I): ##STR00012## wherein the process comprises conducting selective dehydrogenation of a compound of formula (II): ##STR00013## wherein R is CHO or CH.sub.2OH, wherein the selective dehydrogenation is carried out in the presence of at least one transition metal catalyst.

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

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

4. The process according to claim 1, wherein the catalyst is present in an amount from 0.01 mol-equivalent to 0.5 mol-equivalent in relation to the compound of formula (II).

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

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

7. The process according to claim 6, wherein the at least one base comprises K.sub.2CO.sub.3 or pyridine.

8. The process according to claim 6, wherein the at least one base is present in an amount of 0.01 mol-equivalent to 0.5 mol-equivalent in relation to the compound of formula (II).

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

10. The process according to claim 9, wherein the inert solvent is dimethylformamide (DMF).

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

12. A compound of formula (II); ##STR00014##

13. A compound of formula (II): ##STR00015##

14. A compound of formula (III): ##STR00016##

Description

EXAMPLES

Example 1

(1) 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 L, 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 mL3). 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

(2) 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 L, 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 mL3). 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

(3) 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 (416 mg, 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 mL3). 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

(4) 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).sub.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 mL3). 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

(5) 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 L, 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 mL3). 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

(6) 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 L, 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 mL3). 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%).