4-Picoline N-oxide → (4-Methylpyridin-2-yl)methanol

Participants

Reaction Steps

A solution of 4-picoline-N-oxide (3.0 g, 27.52 mmol) in 90 ml of methylene chloride at room temperature is reacted with trimethyloxonium tetrafluoroborate (4.07 g, 27.52 mmol, 1.0 equiv.) for 1.5 h. The reaction mixture is concentrated directly at reduced pressure, the white solid dissolved in 60 ml of refluxing methanol and treated with ammonium persulfate (1.25 g, 5.50 mmol, 0.20 equiv.) in 5.5 ml of water with another addition of ammonium persulfate (0.625 g, 0.10 equiv.) in 2.5 ml of water 30 min later. After refluxing for an additional 40 min, the contents are concentrated at reduced pressure, treated with 75 ml of saturated brine plus 75 ml of water and finally 50 ml of 3N HCl. After stirring at room temperature for 1 h, the mixture is basified with 20 ml of 29% ammonium hydroxide, extracted 4 times with chloroform, dried the combined organic extracts with anhydrous Na2SO4 and concentrated in vacuo. Chromatography with 250 g of silica gel, packed and eluted with acetone-chloroform-methanol (1:2:2%), yielded 2.65 g (78%) of 2-hydroxymethyl-4-methylpyridine.

Provenance & Evidence