Methanol → 2-(Hydroxymethyl)pyridine-4-carbonitrile

Participants

Reaction Steps

A solution of 4-cyanopyridine (5.20 g, 50.0 mmol) in 90 ml of methanol is treated with a mixture of H2SO4 (6.42 g, 65.5 mmol, 1.31 equiv.) and water (45 ml) at once followed by the addition of (NH4)2S2O8 (22.8 g, 100 mmol, 2.0 equiv.). The contents were heated to reflux at which point vigorous refluxing ensued for several minutes. After refluxing for 24 h, the reaction mixture is partially concentrated to remove most of the methanol, treated with ice-water mixture and basified with ammonium hydroxide (20 ml, 29% aq). The residue is extracted four times with chloroform, the combined extracts are dried with anhyrous Na2SO4 and concentrated at reduced pressure. Chromatography is accomplished using 300 g of silica gel packed and eluted with acetone-methylene chloride (1:6) to provide 2.65 g (39.5%) of 4-Cyano-2-hydroxymethylpyridine.

Provenance & Evidence