Isatin → 3-Methyl-2-phenylquinoline-4-carboxylic acid

Participants

Reaction Conditions

Reaction Steps

3-Methyl-2-phenylquinoline-4-carboxylic acid was prepared by a Pfitzinger reaction (J. Org. Chem. 1950, 15:511–516). Propiophenone (3.3 mL, 1.2 equiv.) was added to a solution of isatin (3.00 g, 20.0 mmol) in ethanol (95%, 30 mL), followed by the addition of KOH pellets (86%, 3.91 g, 3 equiv.). The light brown mixture was stirred at 80° C. (oil bath temperature) for 40 hours. Solvent was removed in vacuo and the resulting solid residue was dissolved in water (50 mL), extracted with ether (30 mL×2) to remove any un-reacted starting materials. The aqueous layer was then cooled with an ice bath and acidified with concentrated aqueous HCl until pH˜3. The white precipitate was collected by suction filtration, washed with water and dried in a vacuum oven (30° C.) overnight. The white solid was essentially pure carboxylic acid (5.10 g, 97% yield) and was used for the next step without further purification. 1H NMR (300 MHz, DMSO-d6) δ 7.50–8.08 (m, 9H), 2.46 (s, 3H).

Provenance & Evidence