Dynamic 1H NMR spectroscopic study of hindered internal rotation in selected N,N-dialkyl isonicotinamides: an experimental and DFT analysis

Dynamic H-1 NMR measurements were performed for a series of N,N-dialkyl isonicotinamides (alkyl=Me, Et, and i-Pr). Two complementary methods of the analysis of these spectra were used, targeting the estimation of rates of alkyl group exchange and thereby parameters for rotation around the C-N bond. The Gibbs free activation energy in DMSO, Delta G(exp)(not equal), was found to be 67.6, 65.3, and 61.4 kJ mol(-1), respectively. This finding was compared with related DFT and MP2 results on simulated solutions, Delta G(calcd)(not equal)s, in search of the best theoretical tool reflecting the observed trend that Delta G(exp)(not equal) reduces with an increasing bulkiness of the N-alkyl group. Especially, the DFT methods recommended for TS geometry and barrier height calculations were used. The barriers to C-ar-C(O) bond rotation were also computed, although not measured experimentally. An IRC analysis was also carried out. As a result, the above trend was rationalized by steric hindrance in the ground-state forms under study. The changes in their geometric parameters, including pyramidicity descriptors, are fully consistent with such explanation. Among all DFT methods tested, only the use of the BB1K/6-31+G(d,p)/IEF-PCM(DMSO) protocol afforded Delta G(calcd)(not equal)s fully comparable to the present DNMR determinations. (C) 2013 Elsevier Ltd. All rights reserved.