Mannich Reactions of Methoxythiophens

Abstract

As far as we are aware no genuine Mannich reaction of the thiophen nucleus has been reported. A Mannich-like reaction of thiophen, formaldehyde and ammonium chloride or hydroxylamine salts has been described by Hartough and his co-workers ^1–4 but the reaction failed with amines (eg morpholine). It is well known that the more electron rich nuclei of pyrrole ⁵ and indole⁶ undergo the reaction. It seemed to us that the introduction of an electron-releasing group into the thiophen ring might increase its reactivity to a similar level, and this has proved to be the case.