Nitration Mechanism of Aromatics: Lessons from Born-Oppenheimer Molecular Dynamics

The nitration of aromatic compounds is a fundamental transformation in organic chemistry, traditionally understood through the Ingold-Hughes polar mechanism and, more recently, via single-electron transfer (SET) pathways. In this work, Born-Oppenheimer molecular dynamics (BOMD) simulations were employed to explore the mechanistic features of toluene nitration in a protic polar medium, specifically a concentrated sulfonitric mixture (HNO₃/H₂SO₄). Simulations at 423 K revealed the spontaneous formation of the nitronium ion (NO₂ ⁺) via double protonation of HNO₃ by H₂SO₄. Several BOMD trajectories were analyzed for the reaction between toluene and NO₂ ⁺ at 300 K, leading to four different reaction outcomes: (i) no reaction, highlighting nucleophilic rather than protic solvation of NO₂ ⁺; (ii) nitration at the positions ortho and para via a V-shaped [NO₂·ArH]⁺ SET complex evolving into a σ-complex and ultimately the o- or p-nitrotoluene after deprotonation; (iii) oxygen transfer resulting in o-cresol and NO, initiated from a Λ-shaped [NO₂·ArH]⁺ SET complex; and (iv) the formation of a cyclohexadienone-NO complex via 1,2-hydride shift, also proceeding through a Λ-shaped [NO₂·ArH]⁺ intermediate. Electronic structure analyses (HOMO/LUMO, spin density, Bader charges) confirmed SET as the key step in all reacting pathways. No evidence of superelectrophilic solvation was observed under BOMD conditions. These results reinforce the role of SET in electrophilic aromatic nitration under strongly acidic conditions and reveal new oxygen transfer pathways dependent on the spatial orientation of the NO₂ ⁺ relative to the aromatic ring.