Theoretical mechanistic investigation of zinc(II) catalyzed oxidative amidation of benzyl alcohols with amines

Abstract

Density functional theory (DFT) calculations have been performed to investigate the mechanism of Zn(II)-catalyzed oxidative amidation of benzylic alcohol with amines. A two-step oxidation mechanism is proposed where oxidation of benzyl alcohol to benzaldehyde is the first step. In the 2nd step, hemiaminal generated from the aldehyde is converted to amide through oxidation. Inner sphere, out sphere and intermediate sphere mechanisms for the oxidation of benzyl alcohol to benzaldehyde, are investigated. The inner sphere mechanism is kinetically more demanding (Ea=30.59kcalmol−1), and not believed to contribute to the progress of the reaction under the experimental conditions (at 40°C). The activation barrier associated with outer sphere mechanism is 24.4kcalmol−1, which can be easily surpassed under the reaction conditions. Therefore, the more plausible mechanism is outer sphere mechanism. The oxidation of hemiaminal to amide is also kinetically highly favorable with Ea=7.88kcalmol−1 (outer sphere mechanism). The intermediate sphere mechanism involving transfer of hydrogen to tert-butyl hydrogen peroxide (TBHP) has activation barrier of 25.98kcalmol−1, and therefore cannot be excluded safely. The preference of zinc (II) for outer sphere mechanism is quite contrary to the other later transition metals (Ru, Ir, Pd) catalysis for the similar reaction where inner sphere mechanism is the predominant one.