Effect of Electron-Withdrawing Substituents on the Epoxide Ring: An Experimental and Theoretical Electron Density Analysis of a Series of Epoxide Derivatives

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• 作者：Simon Grabowsky ; Tanja Schirmeister ; Carsten Paulmann ; Thomas Pfeuffer ; Peter Luger
• 刊名：Journal of Organic Chemistry
• 出版年：2011
• 出版时间：March 4, 2011
• 年：2011
• 卷：76
• 期：5
• 页码：1305-1318
• 全文大小：1375K
• 年卷期：v.76,no.5(March 4, 2011)
• ISSN：1520-6904

文摘

A series of acceptor-substituted epoxide derivatives is scrutinized by means of experimental and theoretical electron-density investigations. Due to the possibility of nucleophilic ring-opening, the epoxide ring is not only a very useful functional group in organic synthesis, but acceptor-substituted epoxides are valuable building blocks for the design of protease inhibitors. Therefore, the electron-density analysis in this work focuses on two main aspects that can contribute to rational drug design: (i) the quantification of the electron-withdrawing substituent effects on the epoxide ring and (ii) the intermolecular interactions involving the epoxide ring in combination with different substituents. It can be shown that the electron-withdrawing properties of the substituents cause an elongation of the C鈭扖 bonds in the epoxide rings and the loss of electron density can be measured by an analysis of critical points, atomic charges, and the source function. The different strengths of the substituents are reflected in these properties. Covalent and electrostatic contributions to the intermolecular interactions and thus the lattice energies are depicted on different molecular surfaces.