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Characterization of Amide Bond Conformers for a Novel Heterocyclic Template of N-acylhydrazone Derivatives
Laboratório de Avaliação e Síntese de Substâncias Bioativas (LASSBio), Universidade Federal do Rio de Janeiro, CCS, Cidade Universitária, P.O. Box 68.023, Rio de Janeiro 21941-902, RJ, Brazil
Programa de Pós-Graduação em Química, Instituto de Química, Universidade Federal do Rio de Janeiro, Rio de Janeiro 21949-900, RJ, Brazil
Instituto de Macromoléculas Professora Eloisa Mano, Universidade Federal do Rio de Janeiro, Cidade Universitária, Ilha do Fundão, Rio de Janeiro CEP 21941-598, RJ, Brazil
Departamento de Química, Instituto de Ciências Exatas, Universidade Federal Rural do Rio de Janeiro, Seropédica 23.890-000, RJ, Brazil
Programa de Pesquisa em Desenvolvimento de Fármacos, Instituto de Ciências Biomédicas, Universidade Federal do Rio de Janeiro, PO Box 68023, Rio de Janeiro 21941-902, RJ, Brazil
* Authors to whom correspondence should be addressed.
Received: 4 August 2013; in revised form: 10 September 2013 / Accepted: 13 September 2013 / Published: 25 September 2013
Abstract: Herein we describe NMR experiments and structural modifications of 4-methyl-2-phenylpyrimidine-N-acylhydrazone compounds (aryl-NAH) in order to discover if duplication of some signals in their 1H- and 13C-NMR spectra was related to a mixture of imine double bond stereoisomers (E/Z) or CO-NH bond conformers (syn and anti-periplanar). NMR data from NOEdiff, 2D-NOESY and 1H-NMR spectra at different temperatures, and also the synthesis of isopropylidene hydrazone revealed the nature of duplicated signals of a 4-methyl-2-phenylpyrimidine-N-acylhydrazone derivative as a mixture of two conformers in solution. Further we investigated the stereoelectronic influence of substituents at the ortho position on the pyrimidine ring with respect to the carbonyl group, as well as the electronic effects of pyrimidine by changing it to phenyl. The conformer equilibrium was attributed to the decoplanarization of the aromatic ring and carbonyl group (generated by an ortho-alkyl group) and/or the electron withdrawing character of the pyrimidine ring. Both effects increased the rotational barrier of the C-N amide bond, as verified by the DG≠ values calculated from dynamic NMR. As far as we know, it is the first description of aryl-NAH compounds presenting two CO-NH bond- related conformations.
Keywords: N-acylhydrazones; pyrimidines; conformers; stereochemistry; NMR
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Lopes, A.B.; Miguez, E.; Kümmerle, A.E.; Rumjanek, V.M.; Fraga, C.A.M.; Barreiro, E.J. Characterization of Amide Bond Conformers for a Novel Heterocyclic Template of N-acylhydrazone Derivatives. Molecules 2013, 18, 11683-11704.
Lopes AB, Miguez E, Kümmerle AE, Rumjanek VM, Fraga CAM, Barreiro EJ. Characterization of Amide Bond Conformers for a Novel Heterocyclic Template of N-acylhydrazone Derivatives. Molecules. 2013; 18(10):11683-11704.
Lopes, Alexandra B.; Miguez, Eduardo; Kümmerle, Arthur E.; Rumjanek, Victor M.; Fraga, Carlos A.M.; Barreiro, Eliezer J. 2013. "Characterization of Amide Bond Conformers for a Novel Heterocyclic Template of N-acylhydrazone Derivatives." Molecules 18, no. 10: 11683-11704.