Thermodynamic and solvent effects on manganese-mediated oxidation of substituted piperidones: A spectrophotometric study

The oxidation of nitrogen-containing heterocycles plays a pivotal role in synthetic, medicinal, and mechanistic chemistry. In this study, a comprehensive kinetic and thermodynamic investigation was carried out to explore the manganese-mediated oxidation of substituted piperidones, focusing on the effects of both temperature variation and solvent polarity. Using UV-Visible spectrophotometry, the oxidation reactions of 2,6-diphenylpiperidine-4-one and its 3-methyl-substituted analog were monitored under pseudo-first-order conditions with Mn(III), Mn(IV), and Mn(VII) as oxidants in acidic media. The influence of solvent polarity was studied by systematically varying the dielectric constant using mixtures of water and glacial acetic acid, allowing precise observation of medium effects on the reaction rate and transition state behavior.The kinetic data, recorded across a temperature range of 298-323 K, were analyzed using the Eyring equation to calculate the activation parameters-*enthalpy (ΔH), *entropy (ΔS), and Gibbs free energy (ΔG)**. Mn(IV) showed the highest reactivity and positive entropy of activation, suggesting a disordered, inner-sphere transition state, while Mn(VII) exhibited a more ordered, outer-sphere mechanism with negative ΔS. Substitution at the 3-position of the piperidone ring with a methyl group resulted in reduced reactivity due to steric hindrance and electronic effects, further supporting the structure-reactivity relationship. The study also revealed that decreasing solvent polarity led to increased rate constants for Mn(III) and Mn(IV), indicating that polar or charge-separated transition states are stabilized in less polar environments.These findings collectively provide valuable mechanistic insights into how thermodynamic and solvent parameters influence manganese-mediated oxidations. The results enhance our understanding of redox behavior in nitrogen heterocycles and offer a predictive framework for designing oxidation protocols in both academic and pharmaceutical settings.