Studies on a General Method for the Demethylation of Quaternized Nitrogen Heterocycles

Abstract

Probably the best general method so far developed for the dealkylation of quaternized nitrogen heterocycles is the reaction of the iodide salts in an aprotic solvent in the presence of triphenylphosphine.^1,2 It has since been established³ that the iodide counterion is the active dealkylating agent, with the triphenylphosphine acting as a “methyl sponge”, preventing the reverse reaction from occurring. It follows, therefore, that any heterocycle (1) ought to be able to fulfil the same role as the triphenylphosphine with respect to the dealkylation of the quaternary salt of a less nucleophilic heterocycle (2). Since the reactivity to methylation of a large number of heterocycles with a reactivity range of ca 10⁶ is known⁴, the choice of a convenient heterocycle (1) to go with any heterocycle (2) is, in principle, a wide one.