Convenient synthesis of 6-Amino-2-naphthol by Copper-catalyzed Ullmann reaction

Abstract

A strategic approach towards the synthesis of 6-amino-2-naphthol for energy efficient and consistent yield was exploited by two protocols: (a) a direct amination, and (b) a cascade synthetic approach involving methylation, amination, and demethylation of 2-bromo-6-naphthol by replacing naphthyl bromide with an –NH2 group. A modified copper-catalyzed Ullmann- type CN bond formation reaction at a controlled temperature (80–120 °C) was adopted for the amination reaction in both protocols. Amination reaction of two different substrates 2-bromo-6-methoxynapthalene and 2-bromo-6-naphthol were performed. Two different aminating reagents, namely, aq·NH3 (28–30%) and NaN3 were explored. Copper catalysts were elemental Cu, CuI, Cu2O, CuO, and CuSO4·5H2O. Extensive method optimization revealed that the combination of CuSO4•5H2O, l-proline, and Na-ascorbate is the superior catalyst when employed with NaN3 and NaOH at 120 °C affording the highest coupling yield of 61%. 6-amino-2-naphthol was obtained following both protocols however, the latter afforded a higher overall yield (53%). Thus, an Ullmann reaction strategy with a stable, environmentally friendly, earth-abundant, easy-to-handle, and inexpensive catalyst CuSO4•5H2O in combination with Na-ascorbate makes the amination reaction of bifunctional naphthyl bromide simple, sustainable, energy-efficient and convenient with consistent yield.