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DFT Study on Tautomerism of Dihydro‐2 H ‐1,5‐benzodiazepin‐2‐ones and Dihydro‐2 H ‐1,5‐benzodiazepine‐2‐thiones
Author(s) -
Okovytyy Sergiy I.,
Sviatenko Liudmyla K.,
Gaponov Alexandr A.,
Kasyan Liliya I.,
Tarabara Igor N.,
Leszczynski Jerzy
Publication year - 2010
Publication title -
european journal of organic chemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.825
H-Index - 155
eISSN - 1099-0690
pISSN - 1434-193X
DOI - 10.1002/ejoc.200900689
Subject(s) - tautomer , chemistry , enol , solvent effects , computational chemistry , kinetic isotope effect , solvent , gibbs free energy , keto–enol tautomerism , stereochemistry , medicinal chemistry , thermodynamics , organic chemistry , catalysis , physics , deuterium , quantum mechanics
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.