反应详情

A solution of 5,6,7,8-tetrahydroquinoline (18.2 g, 137 mmol), benzaldehyde (17.67 g, 166.0 mmol), and acetic anhydride (24.5 mL, 254 mmol) was heated under a nitrogen environment at 165° C. for 16 hours. The reaction mixture was cooled to room temperature. Crushed ice was added, and the mixture was slowly basified with NaOH (solid then 2 N NaOH) to pH around 7. The aqueous layer was extracted with hexane/ethyl acetate (1:1 solution) 3 times. The pooled organic layers were dried over magnesium sulfate. The mixture was filtered, and the solvents were removed under vacuum to give 8-benzylidene-5,6,7,8-tetrahydro-quinoline (Intermediate 1) as a brown solid. A solution of Intermediate 1 in dichoromethane (100 mL) and methanol (500 mL) was cooled to −78° C. (dry ice/acetone bath), and charged with ozone/oxygen (3 psi, 1.5 ampere). The dark brown solution turned yellow after several hours. When Intermediate 1 was consumed (TLC), ozone/oxygen flow was stopped. The reaction mixture was purged with nitrogen for 10 minutes. Methyl sulfide (6 mL) was added, and the mixture was stirred for 30 minutes at room temperature. The solvents were removed under vacuum. The residue was dissolved in 1 N HCl (500 mL), and washed with diethyl ether (4×150 mL). The aqueous layer was basified to pH˜7 with NaOH (s), and extracted with ethyl acetate (2×200 mL). The pooled ethyl acetate layers were dried over magnesium sulfate. The mixture was filtered and the solvent was removed under vacuum. The residue was purified by chromatography on silica gel with 90% EtOAc:hexane to give a clean product. The aqueous layer was extracted with chloroform/isopropanol (3:1) several times. The pooled chloroform/isopropanol layers were dried over magnesium sulfate. The mixture was filtered and the solvents were removed under vacuum to give 6,7-dihydro-5H-quinolin-8-one (Intermediate 2), 17.89 g (122.0 mmol, 89% over 2 steps).

1. waitThe dark brown solution turned yellow after several hours
2. customWhen Intermediate 1 was consumed (TLC), ozone/oxygen flow
3. customThe reaction mixture was purged with nitrogen for 10 minutes
4. additionMethyl sulfide (6 mL) was added
5. customThe solvents were removed under vacuum
6. dissolutionThe residue was dissolved in 1 N HCl (500 mL)
7. washwashed with diethyl ether (4×150 mL)
8. extractionextracted with ethyl acetate (2×200 mL)
9. dry with materialThe pooled ethyl acetate layers were dried over magnesium sulfate
10. filtrationThe mixture was filtered
11. customthe solvent was removed under vacuum
12. customThe residue was purified by chromatography on silica gel with 90% EtOAc
13. customhexane to give a clean product
14. extractionThe aqueous layer was extracted with chloroform/isopropanol (3:1) several times
15. dry with materialThe pooled chloroform/isopropanol layers were dried over magnesium sulfate
16. filtrationThe mixture was filtered
17. customthe solvents were removed under vacuum