Faculty of Chemistry, Nicolaus Copernicus University in Toruń, Gagarina 7, 87100 Toruń, Poland.
Institute of Computational Chemistry and Catalysis and Department of Chemistry, University of Girona, Campus de Montilivi, 17003 Girona, Spain.
Molecules. 2023 Jan 22;28(3):1101. doi: 10.3390/molecules28031101.
In this study, the tautomeric equilibrium of a sequence of 1-benzamidoisoquinoline derivatives was investigated with the tools of NMR spectroscopy and computational chemistry. The equilibrium between different tautomers in these systems could be controlled via the substitution effect, and the relative content of the amide form varied from 74% for the strong electron-donating NMe2 substituent to 38% for the strong electron-accepting NO2 group in the phenyl ring. In contrast to the previously investigated 2-phenacylquinoline derivatives, the most stable and thus most abundant tautomer in the 1-benzamidoisoquinoline series except the two most electron-accepting substituents was an amide. The intramolecular hydrogen bond present in the enol tautomer competed with the intermolecular hydrogen bonds created with the solvent molecules and thus was not a sufficient factor to favor this tautomer in the mixture. Although routinely computational studies of tautomeric equilibrium are performed within the continuum solvent models, it is proven here that the inclusion of the explicit solvent is mandatory in order to reproduce the experimental tendencies observed for this type of system, facilitating strong intermolecular hydrogen bonds.
在这项研究中，使用 NMR 光谱学和计算化学工具研究了一系列 1-苯甲酰胺异喹啉衍生物的互变异构平衡。这些体系中不同互变异构体的平衡可以通过取代效应来控制，酰胺形式的相对含量从强给电子 NMe2 取代基的 74%变化到苯环上强吸电子 NO2 基团的 38%。与之前研究的 2-苯乙酮基喹啉衍生物不同，在 1-苯甲酰胺异喹啉系列中，除了两个最吸电子的取代基之外，最稳定且因此含量最多的互变异构体是酰胺。烯醇互变异构体中存在的分子内氢键与溶剂分子形成的分子间氢键竞争，因此不是在混合物中有利于这种互变异构体的充分因素。尽管通常在连续溶剂模型中进行互变异构平衡的计算研究，但这里证明为了重现观察到的这种体系的实验趋势，必须包括显式溶剂，从而有利于形成强的分子间氢键。
