Theoretical investigation of reaction kinetics and thermodynamics of the keto-enol tautomerism of 1, 3, 5-triazin-2, 4(1H, 3H)-dione and its substituted systems utilizing density functional theory and transition state theory methods

Abstract

This article reports the thermodynamics and kinetics of keto-enol tautomerization in 1, 3, 5-triazin-2, 4(1H, 3H)-dione (R) and its tautomers at Density Functional Theory (DFT) – B3LYP/6-311++G (d, p) level. In the chosen system, five keto-enol tautomerization reactions are possible namely R ↔ P1 (Channel 1), R ↔ P2 (Channel 2), R ↔ P3 (Channel 3), P3 ↔ P4 (Channel 4), and P1 ↔ P4 (Channel 5). The reactant has three pathways leading to three different tautomers (P1, P2, and P3). Both P1 and P3 can tautomerize to a fourth product P4 through two additional pathways. The four tautomers namely P1, P2, P3, and P4 are defined as 6-Hydroxy-1H-[1,3,5]Triazine-2-one, 4-Hydroxy-5H-[1,3,5]Triazine-2-one, 4-Hydroxy-1H-[1,3,5]Triazine-2-one, and [1,3,5]Triazine-2,4-diol, respectively. Conventional Transition State Theory (TST) calculations were carried out to determine pre-exponential factor (A) and activation energy (Ea) of all the five tautomerization reactions. One of the hydrogens bonded to the 6th carbon atom (according to IUPAC nomenclature) of the tri-heterocyclic triazine system (R) was replaced by six substituents (F, Cl, OH, NH2, CH3, and C2H5) consecutively to understand their influence on the kinetics and thermodynamics of the tautomerization processes. All substituents investigated enhances the reaction rate constants of the first channel by reducing the barrier height, for example, ortho-para directing and activating substituent NH2 reduces it by 3.55 kcal mol−1. Application of Mulliken population analysis for the distribution of π electron density indicates that the electron donating OH, NH2, and C2H5 substituents increases the stability of TS’s for the third channel by enhancing the aromaticity of triazine ring which leads to increased rate constants.