Local Softness and Hardness Based Reactivity Descriptors for Predicting Intra- and Intermolecular Reactivity Sequences: Carbonyl Compounds

Abstract

The DFT-based reactivity descriptors “local softness” and “local hardness” are used as reactivity indices to predict the reactivity sequences (both intramolecular and intermolecular) of carbonyl compounds toward nucleophilic attack on them. The finite difference approximation is used to calculate local softness, whereas local hardness is approximated by −Vel/2N, where Vel is the electronic part of the molecular electrostatic potential. Both aldehydes and ketones, aliphatic and aromatic, have been selected as systems. Critical cases, e.g., C6H5CHCHCHO, CH3CHCHCHO, and CH2CHCHO, where a CC double bond is in conjugation with the CO group, are also considered. Two new reactivity descriptors are proposed, “relative electrophilicity” (sk+/sk-) and “relative nucleophilicity” (sk-/sk+), which will help to locate the preferable reactive sites. Our results show that local hardness can be used as a guiding parameter when constructing intermolecular reactivity sequences.