Mapping the kinetic and thermodynamic landscape of formaldehyde oligomerization under neutral conditions.

Density functional theory calculations, including Poisson-Boltzmann implicit solvent and free energy corrections, are applied to study the thermodynamic and kinetic free energy landscape of formaldehyde oligomerization up to the C4 species in aqueous solution at pH 7. Oligomerization via C-O bond formation leads to linear polyoxymethylene (POM) species, which are the most kinetically accessible oligomers and are marginally thermodynamically favored over their oxane ring counterparts. On the other hand, C-C bond formation via aldol reactions leads to sugars that are thermodynamically much more stable in free energy than POM species; however, the barrier to dimerization is very high. Once this initial barrier is traversed, subsequent addition of monomers to generate trimers and tetramers is kinetically more feasible. In the aldol reaction, enolization of the oligomers provides the lowest energy pathway to larger oligomers. Our study provides a baseline free energy map for further study of oligomerization reactions under catalytic conditions, and we discuss how this will lead to a better understanding of complex reaction mixtures with multiple intermediates and products.

Glycolaldehyde monomer and oligomer equilibria in aqueous solution: comparing computational chemistry and NMR data.

A computational protocol utilizing density functional theory calculations, including Poisson-Boltzmann implicit solvent and free energy corrections, is applied to study the thermodynamic and kinetic energy landscape of glycolaldehyde in solution. Comparison is made to NMR measurements of dissolved glycolaldehyde, where the initial dimeric ring structure interconverts among several species before reaching equilibrium where the hydrated monomer is dominant. There is good agreement between computation and experiment for the concentrations of all species in solution at equilibrium, that is, the calculated relative free energies represent the system well. There is also relatively good agreement between the calculated activation barriers and the estimated rate constants for the hydration reaction. The computational approach also predicted that two of the trimers would have a small but appreciable equilibrium concentration (>0.005 M), and this was confirmed by NMR measurements. Our results suggest that while our computational protocol is reasonable and may be applied to quickly map the energy landscape of more complex reactions, knowledge of the caveats and potential errors in this approach need to be taken into account.