Role of Acid in the Co-oligomerization of Formaldehyde and Pyrrole.

Building on previous work (J. Phys. Chem. A 2017, 121, 8154-8166) under neutral conditions, we examined the co-oligomerization of CH2O and pyrrole to form porphryinogen under acidic conditions using density functional theory (B3LYP//6-311G**). Thermodynamically, we found that azafulvene intermediates were significantly stabilized under highly acidic conditions. Kinetically, energy barriers were lowered for C-C bond formation, discriminating in favor of reactions that lead to porphyrinogen. However, it was challenging to satisfactorily combine our thermodynamic and kinetic profiles into a unified free-energy profile because of difficulties in optimizing transition states of cationic species involving proton hops. Instead, we used neutral carboxylic acids as a proxy to study how energy barriers changed. By combining data from both neutral and acidic conditions, we estimate a free-energy profile for the initial steps of oligomerization under milder acidic conditions more relevant to prebiotic chemistry.