Mechanistic investigation of the one-pot formation of amides by oxidative coupling of alcohols with amines in methanol

The one-pot formation of amides by oxidative coupling of alcohols and amines via intermediate formation of methyl ester using supported gold and base as catalysts was studied using the Hammett methodology. Determining the relative reactivity of four different para-substituted benzyl alcohol derivatives showed that the first step of the reaction generates a partial positive charge in the benzylic position (i.e. by hydride abstraction), while the second step of the reaction builds up negative charge in the rate determining step. The aminolysis of the methyl ester intermediate was further investigated by means of DFT/B3LYP. The transition state structures and energies were determined for both a concerted and a neutral two-step reaction mechanism. As expected, the base-promoted two-step mechanism was found to be the most energetically favourable and this reaction mechanism was used to construct a theoretical Hammett plot that was in good agreement with the one obtained experimentally. (C) 2012 Elsevier B. V. All rights reserved.