Atom-Economical and Tandem Conversion of Nitriles to N-Methylated Amides Using Methanol and Water

A cobalt complex catalyzed tandem conversion of nitrile to N -methylated amide is described using a methanol and water mixture. Using this protocol, several nitriles were directly and efficiently converted to the desired N -methylated amides. Kinetic experiments using H 2 O 18 and CD 3 OD suggested that water and methanol were the source of the oxygen atom and methyl group, respectively, in the final N -methylated amides. Importantly, the participation of active Co(I)–H species in this transformation was realized from the control experiment. The kinetic isotope effect (KIE) study suggested that the activation of the C–H bond of methanol was a kinetically important step. The Hammett plot confirmed that the reaction was faster with the electron deficient nitriles. In addition, the plausible pathway for the formation of N -methylated amides from the nitriles was supported by the computational study.