α-Alkylation of Nitriles with Alcohols in Air Catalyzed by Chromium Chloride under Microwave Irradiation and Ligand-Free Conditions

The commercially available 3<i>d</i> metal salt chromium(III) chloride (0.4 mol %) has demonstrated significant catalytic activity toward the highly selective α-alkylation of benzyl nitriles with benzyl alcohols in the presence of KO^<i>t</i>Bu (30 mol %) at 140 °C under conventional (99% yield, 24 h) as well as microwave (93% yield, 2 h) heating conditions. The methodology was well scrutinized for a large variation of substrates, which rendered moderate to good yields (up to 98%) with high selectivity. The experiment with elemental mercury suggests the involvement of molecular catalytic species in the reaction. The reaction exhibits a first-order rate dependence relative to the concentration of CrCl₃·6H₂O, KO^<i>t</i>Bu, and benzyl alcohol. However, in the case of benzyl nitrile, a linear dependence of the rate was observed only at low concentrations. This suggests the possibility of β-hydride elimination from Cr-benzyloxide as the rate-determining step of the catalytic cycle, with benzyl nitrile inhibiting the transition state. Not surprisingly, in instances where low α-alkylation activity was observed, the yields could be improved by the sequential addition of small portions of benzyl nitrile. Eyring plot analysis using the Arrhenius equation revealed the reaction to have an overall free energy barrier of about 28.6 kcal/mol.