DFT Study on Tautomerism of Dihydro‐2<i>H</i>‐1,5‐benzodiazepin‐2‐ones and Dihydro‐2<i>H</i>‐1,5‐benzodiazepine‐2‐thiones

Abstract

Abstract DFT calculations were performed to study the tautomeric rearrangements in the isolated, monoethanol‐ and diethanol‐solvated, and dimeric forms of 4‐methyl‐1,3‐dihydro‐2 H ‐1,5‐benzodiazepin‐2‐one and 4‐methyl‐1,3‐dihydro‐2 H ‐1,5‐benzodiazepine‐2‐thione. Molecular geometries of the tautomers and transition state structures were optimized at the B3LYP/6‐31G(d) and B3LYP/6‐311++G(d,p) levels of theory. The long‐range solvent effects on the geometrical and energy parameters of tautomerization were also analyzed by use of the PCM model. The calculated relative Gibbs free energies were used to estimate the equilibrium constants. It was shown that the keto forms are more stable than the enol tautomers both in the gas phase and in solution. The activation energies of tautomerization increase in the following order: lactim–lactam, keto–enol, and imine–enamine transformations. Proton transfer in the solvated complexes and dimers is virtually effortless in relation to that in the isolated tautomers. The bulk of solvent does not substantially affect either the activation energies or the equilibrium constants. The differences between the tautomerism in 4‐methyl‐1,3‐dihydro‐2 H ‐1,5‐benzodiazepin‐2‐one and in 4‐methyl‐1,3‐dihydro‐2 H ‐1,5‐benzodiazepine‐2‐thione are discussed.