Conformational profile and vibrational assignments of hippuric and 4-aminohippuric acids

The structural stability of hippuric acid and 4-aminohippuric acid was investigated for comparison purpose by the DFT-B3LYP and ab initio MP2 calculations with the 6-311G** basis set. From the calculations at both levels of theory the near-planar Ctcnp structure was predicted to be the lowest energy minimum for the two acids. The stability of the corresponding planar structure (Ctcp) was predicted to significantly decrease (6 kcal/mol) as going from the parent acid to the 4-amino derivative. The Tgcnp structure was predicted to be about 1 kcal/mol higher in energy than the most stable Ctcnp structure in both acids. The NH2 inversion barrier was estimated from the planar Ctcp structure to be about 4 kcal/mol. The zwitterion structure was predicted to be about 45 and 50 kcal/mol higher in energy than the ground state conformation in the two acids, respectively, as a result of strong conjugation between the N atom of the NH moiety and the carbonyl CO of the benzoyl group. The vibrational frequencies of the lowest energy Ctcnp conformer of hippuric and 4-aminohippuric acids were computed at the B3LYP/6-311G** level of theory. A comparison of the vibrational assignments for the two acids was provided on the basis of combined experimental and theoretical data.