Ethanol → 5-phenylpyridine-2-carboxylic Acid

Participants

Reaction Steps

A mixture of toluene (20 mL) and water (5 mL) was degassed with argon for 5 minutes. Sodium carbonate (1.53 g, 0.01444 mole) was then added and the mixture was degassed with argon for a further 5 minutes. Phenyl boronic acid (1.126 g, 0.00866 mole) and 5-chloro-pyridine-2-carbonitrile (1 g, 0.00722 mole) were added and the resulting mixture was degassed with argon for a further 5 minutes. tetrakis(triphenylphosphine)palladium(0) (1.67 g, 0.00144 mole) was added and the resulting mixture was degassed with argon for a further 5 minutes. The reaction mixture was then heated to reflux for 3 hours. The reaction mixture was diluted with ethyl acetate. The ethyl acetate layer was washed with water followed by brine solution, dried over sodium sulfate and concentrated under reduced pressure. The resulting residue was purified by column chromatography using silica gel 60-120 mesh (4% ethyl acetate in hexane) to afford 0.9 g (69%) of 5-phenyl-pyridine-2-carbonitrile. LCMS: 181.07 (M+1)+, 28.90%, 1H NMR (DMSO-d6): δ 9.1 (s, 1H), 8.4-8.3 (m, 1H), 8.2-8.1 (m, 1H), 7.9-7.78 (m, 2H), 7.6-7.4 (m, 3H). To a stirred solution of 5-phenyl-pyridine-2-carbonitrile (0.9 g, 0.005 mol) in a mixture of ethanol (10 mL) and water (5 mL) was added NaOH (1 g, 0.025 mol) and the resulting mixture was stirring overnight. The reaction mixture was then concentrated under reduced pressure. The residue was dissolved in water, washed with ether and the aqueous layer was acidified with citric acid. The acidified aqueous solution was extracted with ethyl acetate. The ethyl acetate layer was washed with brine solution, dried over sodium sulfate and concentrated under reduced pressure to afford 0.75 g (75%) of 5-phenyl-pyridine-2-carboxylic acid. LCMS: 200.06 (M+1)+, 97.53%, 1H NMR (DMSO-d6): δ 13 (bs, 1H), 9.1-9.0 (d, 1H), 8.3-8.2 (dd, 1H), 8.2-8.1 (d, 1H), 7.8 (d, 1H), 7.6-7.4 (m, 3H).

Provenance & Evidence