Nucleophilic Substitution Reaction of Alkyl Halides: A Case Study on Density Functional Theory (DFT) Based Local Reactivity Descriptors

Abstract

Density functional theory (DFT) based local reactivity descriptors, e.g., condensed Fukui function (FF) indices (or condensed local softness) have been tested on the nucleophilic substitution reaction of alkyl halides. As the carbon atom of the C−X (X = Cl, Br, and I) bond (hereafter denoted as CC-X) is the center for nucleophilic substitution, it should emerge as the most preferable site for an attack by a nucleophile (hereafter denoted as Nu-). It was found out when local reactivity descriptors are evaluated from the atomic charges derived from Mulliken population analysis (MPA), the CC-X did not emerge out to be the strongest electrophilic center in majority of cases. However, when these local reactivity descriptors were evaluated by a newly proposed way in which the Mulliken charges on the H-atoms are summed up to those of the heavy atoms to which they are bonded, the results improved significantly. When the reactivity descriptors are evaluated employing the later method and at elongated C−X distances (thus mimicking the situation of the nucleophilic substitution of alkyl halides, in which case the C−X bond is gradually broken), the results show significant improvement. In addition, the present study demonstrates that as the C−X bonds are elongated the global softness values of the systems increase in nearly all cases, thus confirming the validity of maximum hardness principle (PMH).