Site of Protonation in Aniline and Substituted Anilines in the Gas Phase: A Study via the Local Hard and Soft Acids and Bases Concept

Abstract

In this paper we address the long standing problem regarding the site for gas-phase protonation in aniline and substituted anilines. Our study reveals that DFT-based reactivity descriptors can reproduce the experimentally observed preferable protonation sites. However, it is found that the quantity / , termed “relative nucleophilicity” and a measure of “local polarizability”, produces more reliable results than the local softness, . The problem which sometimes arises in taking / as the reactivity descriptor is also discussed.

The proton affinities of saturated and unsaturated heterocyclic molecules

“…The proton affinities of the two molecules can be measured as well as calculated, with excellent correspondence. The calculations provide the additional information that it is more than 200 kJ mol −1 more favorable to protonate pyridine on nitrogen than on carbon, whereas it is slightly (4 kJ mol −1 ) more favorable for aniline to be protonated on C4 than on nitrogen [14][15][16][17][18][19][20][21][22][23][24]. Furthermore, systematic high-level computational studies can provide internally consistent results that make it possible to discover systematic trends in the properties of a series of compounds, and results that support contested experimental observations or, occasionally, that suggest reexamination of experimental data.…”

General and Theoretical Aspects of Phenols

“…Nevertheless, their scope of applicability was quite limited. More recently, the more local descriptors, including the Fukui function, local atomic softness or even orbital softness, have been employed in order to interpret the protonation sites 299,301,302 . The definitions 320, 321 and evaluations 322 -325 of DFT-based reactivity indices are well established.…”

Regioselective Anionic [3+2] Cyclizations of Isoxazole, Pyrazole and 1,2,4-Triazole Dinucleophiles − Efficient Synthesis of 2,4-Dihydroimidazo[4,5-b]quinoxalines, 3H-Imidazo[1,2-b]pyrazoles and 5H-Imidazo[2,1-c][1,2,4]triazoles

“…[11] The thermochemistry also favours 6 by 3.3 kcal mol Ϫ1 , most probably due to the absence of the longrange quadrupole CϪH···π interaction found in 6. [12] In addition, the bridgehead nitrogen atom of 7 is adjacent to an electron-withdrawing imino group and to an endocyclic, electron-withdrawing nitrogen atom.…”