Alkylation of salts of pyridinols, quinolinols and isoquinolinols

Abstract

The ratio of N- to O-alkylation has been determined for reaction of the sodium salts of pyridin-2-ol, 6-methylpyridin-2-ol, pyridin-4-ol, quinolin-2-ol, quinolin-4-ol, 2-methylquinolin-4-ol, isoquinolin-1-ol and 3-methylisoquinolin-1-ol with ethyl iodide and diethyl sulphate in aprotic solvents. N-Alkylation is generally favoured. Reaction at the nitrogen is subject to steric hindrance by adjacent groups (methyl or benzo), but in the benzo-fused compounds this effect is opposed by an electronic one arising from the naphthalene nature of the compounds. This results in a greater charge density on the nitrogen than is the case in the analogous pyridines.