Nucleophilicity and Site Selectivity of Commonly Used Arenes and Heteroarenes

Abstract

By using the inverse concept of electrophilicity and nucleophilicity and with four different available equations from literature for electrophilicity and electrodonating power, the nucleophilicity values of 69 commonly used arenes and heteroarenes have been calculated at the B3LYP/6-311+G(d,p) level of theory. The linearity between the nucleophilicity and Hammett sigma and sigma(p) values has been chosen as a test to judge the goodness of the methods used. Finally four different arene and heteroarene series (substituted indoles, phenols, pyrroles, and anisoles) have been subjected to local nucleophilicity analysis in order to predict the site selectivity in electrophilic aromatic substitution reactions (EAS). In each case we have obtained excellent correlation with the experimental result.

Understanding and Improving the Activity of Flavin-Dependent Halogenases via Random and Targeted Mutagenesis

“…2C). Calculated HalA values correlate well with experimentally observed product ratios for reactions proceeding via EAS and previous computational work describing the relative nucleophilicity of different compounds (25). …”

“…It has been proposed that the absence of this residue in the latter cases is due to the greater electronic activation of these substrates relative to the indole benzo ring; further activation by the enzyme is not needed for EAS (44). HalA calculations (23) and nucleophilicity studies (25) indicate that pyrroles are indeed more activated than the benzo positions of indole, but neutral phenols are not (Fig. 2C).…”

Betti Reaction of Cyclic Imines with Naphthols and Phenols – Preparation of New Derivatives of Betti's Bases

“…In the case of 3-aminophenol (1g), this observation is also in accord with the calculated local nucleophilicity index reported in the literature. [14] The analysis of the reaction path by DFT calculations shows that the transition state [15] corresponds to the protonation of the imine by the phenolic hydrogen. IRC calculation [16] performed starting from this transition state indicated the formation of the sp 3 intermediate at the alpha position of naphthalene without any additional transition state.…”

A theoretical thermodynamic investigation of cascade reactions in dinuclear octa-azacryptates involving carbon dioxide

“…The global nucleophilicity (N) is the reciprocal electrophilicity (ω), which is calculated using the following equation [30]:…”

“…[31]. To evaluate the nucleophilic power of the reactive sites within the molecule, a local nucleophilicity index was evaluated using the following equation [30]:…”