Formation of 2-methylaminopyridine-3-carbaldehyde and the corresponding methylimine by ring-opening and ring-closing reactions of 3-cyano-1-methylpyridinium iodide in N-sodium hydroxide

Abstract

Steam distillation of a solution of 3-cyano-1-methylpyridinium iodide in N-sodium hydroxide yields a mixture of 2-methylaminopyridine-3-carbaldehyde (I) and the corresponding methylimine (II). The formation of the former most probably proceeds via ring opening of the pseudo-base to give 2-formyl-5-methylaminopenta-2,4-dienenitrile (III)(or a tautomer). Ring closure of this intermediate should give 1,2-dihydro-2-imino-1-methyl-pyridine-3-carbaldehyde (IV), which under the reaction conditions would undergo the Dimroth rearrangement. Methylamine is also a reaction product, and could be formed by hydrolysis either of the intermediate (III) or of 2-methylaminomethylene-5-oxopent-3-enenitrile, the latter being formed by an initial attack at the 6-position. The methylimine (II) could be formed by the reaction of compound (I) with methylamine. Assignment of structure (I) is based on n.m.r. spectrometry and the fact that a Cannizzaro reaction yields an alcohol and a carboxylic acid, the latter giving 2-methylaminopyridine on decarboxylation. Further, the reaction of compound (I) with methyl iodide yields 3-formyl-1-methyl-2-methylaminopyridinium iodide, which on treatment with sodium hydroxide is converted into 1,2-dihydro-1-methyl-2-methyliminopyridine-3-carbaldehyde. Bromination and nitrosation of compound (I) yield 5-bromo-2-methylaminopyridine-3-carbaldehyde and 2-methyl(nitroso)-aminopyridine-3-carbaldehyde, respectively.