Nucleophilicity of indole derivatives: activating and deactivating effects based on proton affinities and electron
Nicolás Otero1, Marcos Mandado, Ricardo A Mosquera
1Departamento de Química Física, Facultade de Química, Universidade de Vigo, 36310 Vigo, Galicia, Spain.
Abstract:
Activating and deactivating abilities of several substituents (-CH3, -F, -NH2, -NO2) in indole have been theoretically studied using a series of electron density based reactivity indices. Calculations have been performed at the B3LYP/6-311++G(2d,2p) level. An energetic criterion based on the proton affinities (PAs) has been employed to check the validity of these reactivity indices. Relative PAs reflect the ortho and para orientation ability of -CH3, -F, and -NH2 groups, whereas the large deactivating effect of -NO2 is mainly observed at these positions. Also, substitutions in carbons 2 and 6 (IUPAC nomenclature) activate/deactivate carbons 6 and 2, respectively. Inductive effects are also reflected on the values of the relative PAs. The -CH3 group is shown to have inductive electron-withdrawing character instead of electron-releasing with its activating ability being due to a small mesomeric electron-releasing character. pi atomic electron populations and the zz component of the atomic quadrupole electric tensor qualitatively explain the order of PAs. Fukui indices approximately predict the results obtained by the previous properties, whereas no correlation is found between the values of the (triangle down)2rho(r) at the secondary charge concentrations and the PA scale.
More Related Videos
14:11Synthesis of pH Dependent Pyrazole, Imidazole, and Isoindolone Dipyrrinone Fluorophores using a Claisen-Schmidt Condensation Approach
Published on: June 10, 2021
06:34Synthesis of Antiviral Tetrahydrocarbazole Derivatives by Photochemical and Acid-catalyzed C-H Functionalization via Intermediate Peroxides (CHIPS)
Published on: June 20, 2014
Related Concept Videos
ortho–para-Directing Activators: –CH3, –OH, –⁠NH2, –OCH3
ortho–para-Directing Deactivators: Halogens
meta-Directing Deactivators: –NO2, –CN, –CHO, –⁠CO2R, –COR, –CO2H
Basicity of Aromatic Amines
Relative Reactivity of Carboxylic Acid Derivatives
A key factor in assessing the reactivity of the acid derivatives is the basicity of the substituent or the leaving group. The lower the basicity of the leaving group, the higher the reactivity of the derivative. The basicity of the leaving group follows this order:
Halide ions < Acyloxy ions < Alkoxy ions < Amine ions
Basicity of Heterocyclic Aromatic Amines
