An Electron-Density-Based Study on the Ionic Reactivity of 1,3-Azoles

作者：Otero Nicolas; Estevez Laura; Mandado Marcos; Mosquera Ricardo A^*

来源：European Journal of Organic Chemistry, 2012, (12): 2403-2413.

DOI：10.1002/ejoc.201101407

• Computational chemistry
• Regioselectivity
• Reactive intermediates
• Heterocycles
• Resonance

Basic processes for the ionic chemistry of 1,3-azoles (protonation, nitration, hydride addition, and deprotonation) have been studied by analyzing B3LYP/6-311++G(2d,2p) 6d electron densities using the Quantum Theory of Atoms in Molecules (QTAIM) and delocalization indices in the gas phase and in aqueous solution modeled with the Polarizable Continuum Model (PCM) method. The most stable protonation site is N3 in all cases, and this takes place without a significant change in electron delocalization, whereas C5 is the preferred site for electrophilic substitution. Activating and deactivating effects on the carbon atoms of the imidazole ring were tested by analyzing the variation of atomic properties introduced by amino and nitro substituents, respectively. The largest activation was observed for C5 in 4-aminoimidazole. C2 is the most favored site for hydridation in all 1,3-azoles, which always results in loss of ring planarity and reduced electron delocalization in the ring. PCM calculations allow the experimentally observed preferred deprotonation C-site in water for these compounds to be modeled and reproduced. In all anions, QTAIM charges do not keep in line with the resonance forms; whereas QTAIM describes deprotonated carbon atoms as positive or nearly neutral in the gas phase, they should display negative charge according to the resonance model.

• 出版日期2012-4