From Formamide to Purine: a Self-Catalyzed Reaction Pathway Provides a Feasible Mechanism for the Entire Process

A formamide self-catalyzed mechanistic pathway that transforms formamide to purine through a five-membered ring intermediate has been explored by density functional theory calculations. The highlight of the mechanistic route detailed here is that the proposed pathway represents the simplest and lowest energy reaction pathway. All necessary reactants, including catalysts, are generated from a single initial compound, formamide. The most catalytically effective form of formamide is found to be the imidic acid isomer. The catalytic effect of formamide has been found to be much more significant than that of water. The self-catalytic mechanism revealed here provides a pathway with the lowest energy barriers among all reaction routes previously published. Several important reaction steps are involved in this mechanistic route: formylation–dehydration, Leuckart reduction, five- and six-member ring-closing, and deamination. Overall, a five-membered ring-closing is the rate-determining step in the present catalyti...