Ab initio quantum chemistry study of formamide-formamidic acid tautomerization

Ab initio electronic structure calculations using analytical energy derivative methods and automated potential energy surface walking techniques have been carried out on the tautomerization reaction path connecting formamide (F) H₂N-CHO, through a transition state (TS), to formamidic acid (FA) HN-CHOH. The zero-point corrected F → FA, and F → TS energy differences are predicted to be 12.1 and 48.9 kcal/mol, respectively, when configuration interaction methods are used to treat electron correlation. An imaginary frequency of 2391i cm^-1 is obtained along the reaction coordinate at the TS. Isotopic substitution of F to generate H₂N-CDO and subsequent calculation of the harmonic vibrational frequencies and eigenvectors allowed ambiguities in the assignment of the infrared spectrum of F to be resolved. The geometry of the F tautomer is found to be slightly nonplanar, but to have zero-point energy that permits the planar geometry to be dynamically accessed. Extensions to situations in which tautomerization is assisted by neighboring solvent molecule(s) are considered. In particular, the intimate involvement of a single H₂O solvent molecule reduces the zero-point-corrected F → FA and F → TS energy differences to 10.6 and 22.6 kcal/mol, respectively. Intimate solvent participation is thus found to much more strongly affect the activation energy than the overall thermodynamics in this case. The imaginary frequency corresponding to the reaction coordinate at the transition state changes to 2001i cm^-1 when a single H₂O is intimately involved.