Study of the Gas-Phase Pyrolysis of N-Aryl-3-Oxobutanamides and the 2-Aryl Hydrazone Derivatives: A Novel Computational Approach Including DFT with Multivariant Analysis

In this work, we carried out a computational study of the gas-phase thermal decomposition of N-aryl-3-oxobutanamides (β-ketoamides) and the 2-arylhydrazone derivatives. We performed calculations using density functional theory (DFT) at the B97D-GD3BJ/deft2tzvp level, with multivariant analysis including descriptors of global reactivity, e.g., ionization energy (I), electron affinity (A), molecular hardness (η) and electrophilicity (ω). The objective was to elucidate the reaction mechanism. To this end, we modeled the structures of reactants, transition state structures (TSs) and products and studied the effect of substituents on the N-aryl and the 2-aryl aromatic ring on the energy of activation. The synchronicity of the process and the nature of non-covalent interactions were studied to gain insight into the reactivity and selectivity of these molecules. We examined the reactivity of 2-arylhydrazone derivatives, which show reaction rates about three orders of magnitude slower than the parent β-ketoamide. We evaluated two competing mechanisms involving cyclic TSs of six and four members. This study included electronic descriptors, e.g., NBO analysis, IGM/IBSI, Wiberg bond indexes, and intrinsic reaction coordinate calculations (IRCs). We introduce a new descriptor, Dynamic Synchronicity, SyD, for mechanistic and kinetic characterization. To the best of our knowledge, this work is the first comprehensive theoretical study of the system ketoamide/aryl hydrazone. Multivariate statistical methods, i.e., principal component analysis (PCA) and hierarchical cluster analysis (HCA), are useful tools for the selection of the atoms involved in the TSs.