The Syntheses of N-Methyl-4-aminopiperidine

Abstract

N-Methyl-4-aminopiperidine was prepared through the following three different methods: (1) The ring closure method starting with β, β′-dicarbomethoxy-diethyl-methylamine, (2) the treatment of N-methyl-4-pyridone-imine with sodium in boiling isoamyl alcohol, and (3) the catalytic hydrogenation of 4-acetaminopyridine-N-methiodide. The identities were established by m.p. and mixed m.p. of their dipicrates.
N-Methyl-4-pyridone-imine was hardly susceptible to catalytic hydrogenation in the usual solvents. 4-Nitropyridine-N-oxide and 4-acetaminopyridine-N-oxide were also resistant to the similar treatment, but their hydrogenations were effected in glacial acetic acid-acetic anhydride mixture.
It was also clarified that acetylation of 4-aminopyridine proceeded mostly towards 4-acetaminopyridine, because this formed an N-methiodide, which was converted into N-methyl-4-pyridone-imine on hydrolysis, and the N-methiodide was led to N-methyl-4-aminopiperidine by catalytic hydrogenation.
2-Aminopyridine showed the similar behavior. When the benzoylation was followed by treatment with methyl iodide, an N-methiodide was formed, and on hydrolysis, this was converted to N-methyl-2-pyridone-imine.