Modified Atomic Orbital Overlap: Molecular Level Proof of the Nucleophilic Cleavage Propensity of Dinitrophenol-Based Probes

Out
of six possible positional isomers of dinitrophenol, only 2,4-DNP
has been used extensively by many researchers for developing reactive
molecular probes. But the question remains unanswered: why has only
the 2,4-isomer emerged as a labile protecting group? To answer this
question, six molecular probes using available DNP isomers were developed
and investigated to evaluate the effect of the extent of atomic orbital
overlap on their reactivity. We have proved for the first time at
the molecular level that the o-NO2 group
contributes less compared to the p-NO2 group toward the reactivity of 2,4-DNP-based probes. Crystal structure
analysis revealed that the 2p orbital of N atom and the 2p orbital
of the adjacent ring C atom to which the o-NO2 is attached are inclined at >30° to each other, leading
to substantial reduction in π overlap (as these two p-orbitals loose coplanar state) resulting in a very weak
−M effect of the o-NO2 group, whereas
the 2p orbitals of the N atom of the p-NO2 group and the adjacent ring C atom are almost coplanar (11°
inclined to each other), leading to strong π overlap. Hence,
the p-NO2 group contributes largely toward
the molecular reactivity through its −M effect.