The alkylation of 4-pyridone

Abstract

2, 6-dimethyl-4-pyridones have been prepared from the reaction of 3-acetyl-4-hydroxy-6-methyl-2-pyrone (dehydroacetic acid) with various aqueous amines. These pyridones further react with alkyl halides, producing the halide salts of the quaternary cation.

Prepartion of alkyl derivatives from 2,6-dimethyl-4-pyridones as well as 2, 6-dimethyl-4-methoxypyridine have conclusively established alkylation upon the carbonyl oxygen atom. Furthermore, coincidence of the relative chemical shifts of N-alkyl and O-alkyl substituents has been clearly demonstrated.

The 4-pyridones possess two strong sp2 hybridized nucleophilic centers (i.e., the ring nitrogen and the carbonyl oxygen), and the alkylation may proceed upon either site. Previously, this reaction has not been investigated. Alkylation upon the nitrogen atom would reult in quaternization via the Menschutkin reaction, whereas attack upon the carbonyl oxygen would proceed analogous to the Williamson ether synthesis. Infrared studies alone of the compunds prepared were inconclusive in assignment of the alkylation site, since the complexity of the bands resulted in spectra remarkably similar to those of the non-alkylated initial reagents. Furthermore, the early results obtained from proton nmr spectra indicated the possibility of coincident relative chemical shifts (of N-alkyl vs. O-alkyl substituents) or rearrangement of the alkyl substituents to one specific nucleophilic site.