Computational Insights Into Pyridine Chlorination by Molecular Chlorine: Cooperative Effects of Solvent Polarity and Bimolecular Assistance

Abstract

The mechanism of pyridine chlorination by molecular chlorine was investigated in detail using quantum chemical methods (M06‐2X/def2‐TZVP) in both the gas phase and acetonitrile solution. The reaction mechanisms involve the heterolytic dissociation of Cl 2 , facilitated by the prior formation of the halogen‐bonded complex Cl 2 ·Py. The reactivity of this system is highly sensitive to the reaction environment. In the gas phase, the most favorable pathway is a three‐step mechanism of meta ‐carbon chlorination involving heterolytic Cl─Cl cleavage, followed by Cl + migration from N to meta ‐carbon and final HCl elimination, where the second step presents the rate‐determining barrier of 173 kJ·mol −1 (Δ G ° 298 ‡ = 220 kJ·mol −1 ). In acetonitrile, the combination of solvent polarity and the participation of a second pyridine molecule provides the most feasible pathway for ortho‐chlorination. Here, the polar solvent enables near‐barrierless heterolytic dissociation of chlorine and stabilizes transition states, while a second pyridine acts as a proton shuttle, collectively lowering the kinetic barrier to 110 kJ·mol −1 , although the Gibbs free energy barrier remains high (189 kJ·mol −1 at 298 K) due to the entropic cost of bringing the two pyridine molecules together.