A Simple Method for N-Phenoxyethylation of Anilines

The scarce previously reported preparations involved large excesses of some starting materials, relatively high temperatures and long reaction times [1,2]. We have recently reported a general procedure for that preparation [3] although at that stage only moderate yields were obtained. We describe here a better and simpler procedure for achieving not only compounds 1 in good yields, but also for extending the scope of the reaction to the synthesis of the related bis-N-(2-phenoxy-ethyl)anilines 2. In order to avoid β-elimination reactions in molecules bearing a phenoxyethyl group, the reaction was carried out precluding strong acidic or basic media, see Scheme.

Dependimng on the product desired, 1-bromophenoxyethanes (3) or anilines (4) were used in molar excess. To prepare mono-N-(2-phenoxyethyl)anilines (1) the reagent 4 was used in excess, yielding 70-80% (see Table), whereas an excess of 3 lead to 2 with yields ranging in 50-70%.

Reaction conditions involve typically 90 °C, DMSO as solvent and anhydrous K₂CO₃ as the base. Yields are substantially improved as compared with those already obtained using triethylamine [3]. New compounds 2b and 2c gave satisfactory analytical and spectroscopic data.