Paweł Andrzej Wieczorkiewicz, Tadeusz M Krygowski, Halina Szatylowicz
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The obtained dataset contains information on substituent properties (cSAR – charge of the substituent active region method), delocalization (EDDB – electron density of delocalized bonds) and geometry. It follows that the positions of endocyclic N atoms relative to the substituent influence in the most profound manner its properties. N atoms in ortho positions significantly boost the electron-donation and weaken the electron-withdrawal by induction. Another factor is the resonance charge transfer from the substituents to N atoms, and then inductive interactions with further (non-ortho) N atoms. While substituent constants correctly describe the changes of their properties (including those attached to the heterocycles), a testimony to Hammett's genius, quantum chemical models must be used to quantify the exact properties. In most heterocycles, electron-donating substituents hinder the cyclic delocalization, except 4-pyrazole. 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引用次数: 0
摘要
五元 N-杂环是许多化合物的主要成分,在化学、生物化学或药物化学的各个领域都具有重要意义。因此,明确鉴定决定杂环分子上特定基团电子捐赠/抽取特性的结构因素,以及阐明取代引起的环状和非环状电子脱定位变化,已成为当务之急。因此,我们对吡咯、咪唑、吡唑、1,2,3- 和 1,2,4-三唑及其 C 取代单衍生物(X = NO2、CN、Br、Cl、F、SH、OH、NH2)进行了量子化学计算。所获得的数据集包含有关取代基性质(cSAR--取代基活性区电荷法)、脱局(EDB--脱局键电子密度)和几何形状的信息。由此可见,内环 N 原子相对于取代基的位置对其性质影响最大。位于正交位置的 N 原子通过诱导作用显著增强了电子捐赠作用,削弱了电子撤回作用。另一个因素是从取代基到 N 原子的共振电荷转移,然后与更多的(非正交)N 原子发生感应作用。虽然取代基常数能正确描述其性质(包括杂环上的取代基常数)的变化,证明了哈米特的天才,但量子化学模型必须用来量化确切的性质。在大多数杂环中,除 4-吡唑外,电子捐赠取代基都会阻碍环向脱钙化。最近应用的 EDDB 方法可以详细研究这一现象。由此可见,芳香性的变化源于取代基对环键的π电子效应,它以相关的方式改变了特定键的定位和脱定位。
Substituent effects and electron delocalization in five-membered N-heterocycles
Five-membered N-heterocycles are principal constituents of many compounds of vital importance in various fields of chemistry, biochemistry or pharmaceutical chemistry. For this reason, unequivocal identification of structural factors determining electron donating/withdrawing properties of specific groups attached to the heterocyclic moiety becomes an utmost need together with elucidation of the substitution-induced changes in cyclic and noncyclic electron delocalization. Thus, quantum-chemical calculations were performed for pyrrole, imidazole, pyrazole, 1,2,3- and 1,2,4-triazole, and their C-substituted mono-derivatives (X = NO2, CN, Br, Cl, F, SH, OH, NH2). The obtained dataset contains information on substituent properties (cSAR – charge of the substituent active region method), delocalization (EDDB – electron density of delocalized bonds) and geometry. It follows that the positions of endocyclic N atoms relative to the substituent influence in the most profound manner its properties. N atoms in ortho positions significantly boost the electron-donation and weaken the electron-withdrawal by induction. Another factor is the resonance charge transfer from the substituents to N atoms, and then inductive interactions with further (non-ortho) N atoms. While substituent constants correctly describe the changes of their properties (including those attached to the heterocycles), a testimony to Hammett's genius, quantum chemical models must be used to quantify the exact properties. In most heterocycles, electron-donating substituents hinder the cyclic delocalization, except 4-pyrazole. The applied recent EDDB method allows to study this phenomenon in detail. It follows that changes in aromaticity originate from the π-electronic effects of substituents on the ring bonds, changing the localization and delocalization of particular bonds in a correlated manner.
期刊介绍:
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