A critical evaluation of the s-cis-trans isomerism of 2-acetylpyrrole and its N-methyl derivative through infrared and NMR spectroscopies and theoretical calculations

Literature data are controversial regarding the conformational equilibria of 2-acetylpyrrole (AP) and its N-methyl derivative (AMP). Now, a detailed study through infrared spectroscopy and theoretical calculations has shown that previous data were erroneously interpreted, since only a N,O-cis conformer is present in solution and that it is the stable conformer in the isolated state (Delta Etrans-cis = 5.05 kcal mol(-1), for AP; Delta Etrans-cis = 7.14 kcal mol(-1), for AMP). Carbonyl and N-H absorption data in different solvents, supported by theoretical results taking into account the solvent effects [at IEFPCM-B3LYP/6-311++G(3df,3p) level of theory] clearly demonstrated that only the N,0-cis conformer is present in solution. However, a doublet was observed for AP, in CCl4, which can be attributed to this conformer and the lowest wavenumber component to the cis dimer form, stabilized through intermolecular hydrogen bonds (NH...O=C). The overall preference for the N,O-cis conformer, in AP and AMP, as interpreted by the NBO analysis, indicated that the hyperconjugative effect is the main contribution to stabilize this rotamer, overcoming the possible steric repulsion. C-13 NMR experiments at low temperature in two different solvents (CS2/CDCl2 and acetone-d(6)) confirmed the occurrence of a single conformer since no separated signals were observed. (C) 2013 Elsevier B.V. All rights reserved.