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

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Reaction Steps

4-methylpyridine-N-oxide (3.7 g) was dissolved in methylene chloride (68 ml), trimethyloxonium tetrafluoroborate (5.0 g) was added to the mixture, and the mixture was stirred for 90 minutes at room temperature. The solvent was removed under reduced pressure, the obtained residue was dissolved in methanol, and an aqueous solution (6.8 ml) of ammonium peroxodisulfate (1.54 g) was added under heat reflux. An aqueous solution (3.4 ml) of ammonium peroxodisulfate (0.77 g) was further added to the mixture after 30 minutes, and the mixture was stirred for 1 hour. After allowing the mixture to be cooled to room temperature, the solvent was removed under reduced pressure, and the obtained residue was purified by silica gel column chromatography, to give (4-methyl-2-pyridinyl)methanol (2.9 g). (4-methyl-2-pyridinyl)methanol (2.5 g) was dissolved in methylene chloride (25 ml), DMF (3 droplets) was added to the mixture, thionyl chloride (3.8 ml) was added to the mixture at 0° C. and the mixture was stirred for 16 hours at room temperature. The solvent was removed under reduced pressure, and a solution (9.1 ml) of the obtained residue in water was added dropwise to an aqueous solution (64 ml) of 4-aminothiophenol (1.82 g) and sodium hydroxide (1.74 g) in methanol. The mixture was stirred for 1 hour at room temperature, the solvent was removed under reduced pressure, and the residue was extracted with ethyl acetate. The organic layer was washed with saturated brine, and dried over magnesium sulfate. The solvent was removed under reduced pressure, and the obtained residue was purified by silica gel column chromatography, to give 4-[[(4-methyl-2-pyridinyl)methyl]sulfanyl]aniline (2.0 g).

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