Synthesis of 4-aminopyridine and 4- Acetylaminopyridine by Reduction of 4-nitropyridinen- Oxide with Iron and Mineral Acids

The usual way of commercial 4-aminopyridine preparation is a two-stage synthesis starting from pyridine and including 1-(4-pyridyl)pyridinium chloride hydrochloride as an intermediate. The total yield is 36- 40% [1, 2, 3]. A semipreparative scale three-stage synthesis including pyridine-N-oxide and 4-nitropyridine-N-oxide as an intermediates is preferable. At the third stage 4-nitro-pyridine-N-oxide was reduced with iron and acetic acid at reflux temperature to produce 4-aminopyridine in quantitative yield. The reaction demands continuous extraction with diethyl ether of the title compound. The total yield is 65% [4].