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.
Molecules. 2013 Sep 25;18(10):11683-704. doi: 10.3390/molecules181011683.
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.
本文描述了 4-甲基-2-苯基嘧啶-N-酰腙化合物（aryl-NAH）的 NMR 实验和结构修饰，以探索其 1H 和 13C-NMR 谱中某些信号的重复是否与亚胺双键立体异构体（E/Z）或 CO-NH 键构象（顺式和反式稠合）的混合物有关。来自 NOEdiff、2D-NOESY 和不同温度下的 1H-NMR 光谱的 NMR 数据，以及异丙叉腙的合成揭示了 4-甲基-2-苯基嘧啶-N-酰腙衍生物中某些信号重复的性质，即两种构象在溶液中的混合物。进一步，我们研究了嘧啶环上取代基相对于羰基的邻位的立体电子影响，以及通过将嘧啶变为苯基对电子的影响。构象平衡归因于芳环和羰基的去平面化（由邻位烷基产生）和/或嘧啶环的吸电子性质。这两种效应都增加了 C-N 酰胺键的旋转势垒，这可以通过从动态 NMR 计算出的 DG(≠) 值来验证。据我们所知，这是首次描述了具有两种 CO-NH 键相关构象的 aryl-NAH 化合物。
