QTAIM study of the protonation of indole

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

“…Looking at N(Ω) values and their evolution upon protonation, Δ prot N(Ω), in the gas phase (Table 3, see also Tables S1 and S3 in the Supporting Information) we observe the following features: (i) in the most stable protonated species, the proton always displays the most positive charge, which, as in previous studies, [19][20][21] contradicts the Lewis structure usually employed to represent protonated heterocycles (positive charge on the imine nitrogen atom); (ii) in contrast, the proton gains a substantial amount of electron population (between 0.850 and 0.875 au) at C-sites (n+H2, n+H4, and n+H5 species); (iii) consequently, the most stable protonations of 1,3-azoles are accompanied by smaller electron reorganizations in the molecule; (iv) in all the protonations at N3, the loss of electron density experienced by the hydrogen atoms of the molecule represents more than 50 % of that gained by the proton. This percen- Table 3.…”

“…As previously found for other protonated compounds, [19,41] anions and cations, [39,42] hydrogen atoms allow a dispersal of charge excess. In fact, a significant part of the electron density gained by the attached proton is compensated for by the remaining hydrogen atoms.…”

“…Conjugated bases obtained after deprotonation at m are denoted as Bn(Hm). [19] All the calculations were performed with Gaussian 03. Tautomerism interconverting 1(4-X) and 1(5-X) species was considered for these compounds.…”

“…[12] The resonance model has been extensively employed in these systems, for instance, to explain why imidazole is a very much stronger base than thiazole or oxazole, and even ties introduced by amino and nitro substituents, respectively. This electron-density analysis is interesting for at least two reasons: (i) because previous QTAIM studies on diverse heterocycles have provided evidence that the resonance model displays significant shortcomings for describing electron-density evolutions along simple chemical reactions; [19][20][21] and (ii) although azoles are relatively common organic reagents, their electron density has not been the subject of modern electron-density studies. C2 is the most favored site for hydridation in all 1,3azoles, which always results in loss of ring planarity and reduced electron delocalization in the ring.…”

Friedel‐Crafts dealkylation reaction mediated by a stereoselective proton transfer in the fragmentation of protonated cyclic indolyl α‐amino esters

“…Previous studies of indole derivatives indicated that their most thermodynamically favored protonation sites are regulated by the substituted groups on the indole core. [15,22,[30][31][32] In the case of compound 1, it may be protonated at various positions, including the N 1 atom, C 2 atom, C 3 atom, C 4 atom, N 8 atom and O 9 atom (atoms are numerically designated for convenient reference as shown in Table 2). To gain insight into the preferred protonation site, theoretical calculations were carried out using the DFT method at the B3LYP/6-311G(d,p) level of theory.…”