Acetaldehyde → 3-(3-Quinolyl)propenal

Participants

Reaction Conditions

Reaction Steps

To a 500-mL round-bottom flask, equipped with mechanical stirrer, dropping funnel and temperature bath was charged 30.9 g (0.2 mol) quinoline 3-carboxaldehyde and acetaldehyde (50 mL). The mixture was cooled to −10° C. and a solution of sodium hydroxide (500 mg) in methanol (8 mL) was added dropwise keeping the temperature below 10° C. The mixture was stirred at 0° C. for 30 min. Acetic anhydride (50 mL) was added and the mixture was heated to 70° C. (methyl acetate formed in the reaction was removed). After 1 hour, the mixture was cooled to 30° C. and 100 mL 3N HCI (50 mL conc. HCI in 100 mL water) was added. The mixture was heated to 80° C. for 45 min. and neutralized with 10% sodium carbonate solution. (The organic layer, containing product, was checked by TLC, system isopropyl acetate, visualize under short UV). At the end of the reaction, the mixture was cooled to <30° C., diluted with 200 mL water and it was washed with 2×150 mL isopropyl acetate. To the aqueous layer was then added isopropyl acetate (500 mL) and the pH was brought to >8 by neutralization with sodium carbonate. The organic layer was separated and concentrated to a small volume until the product starts to crystallize. The mixture was stirred for 30 min. filtered and dried to give 18.5 g product as a light yellow solid. A second crop (5.4 g) was collected by concentration of the mother liquor and filtration of the solid product followed by washing with MTBE (25 mL). Total yield, 23.9 g (66%). The NMR of the product was consistent with the proposed structure.

Provenance & Evidence