Unexpected catalysis by trace metallic impurities
06 February 2004
Workers at Merck were investigating ways of converting a bromopyridine into an aminopyridine (see below). Palladium catalysed amination with benzophenone imine followed by hydrolysis worked well but generated more benzophenone than product. A direct amination with ammonium fluoride in methanol under pressure worked successfully (65% yield), but could not be repeated. An analysis of the liquors from the successful reaction showed traces of copper. This led to the development of an effective copper catalysed amination. Reaction conditions are as follows - 0.5mol% Cu²O, NH³, in ethylene glycol at 70°C, 75psi for 20 hours.
