Green halogenation of aromatic heterocycles using ammonium halide and hydrogen peroxide in acetic acid solvent

Abstract

The green generation of X+ (X = Br, I) using hydrogen peroxide in aqueous acetic acid allows access to aromatic heterocyclic halides in yields and purities comparable to syntheses employing N-bromosuccinimide. In activated and unsubstituted thiophene rings, regioselectivity is quantitative for positions α to the sulfur; pyrroles also give quantitative reactions, at least initially. Deactivated rings, including furans and thiazoles, as well as thiophenes with strongly electron-withdrawing groups showed little to no reactivity under the conditions investigated. The reaction shows remarkable functional group tolerance (to alcohol, nitro, alkyl, halo, and carbonyl groups), as shown through reaction with substituted phenols. In all bromination reactions, reaction yields and regiochemistry were very similar to reactions involving N-bromosuccinimide in tetrahydrofuran solvent.