Substituent effects on the strength of the intramolecular hydrogen bond of thiomalonaldehyde

The effect of CH3, NH2, OH, and F substituents on the intramolecular hydrogen bond (IHB) of thiomalonaldehyde (TMA) was analyzed through the use of B3LYP density functional theory calculations. The geometries of the C1-, C2-, and C3-susbtituted enol and enethiol tautomers were optimized at the B3LYP/6-31G(d) level while their final energies were evaluated using a 6-311+G-(3df,2p) basis set expansion. In general Ci-substitution strengthens the IIIB of the enolic tautomer, while CS-substitution strengthens the IHB of the enethiolic form. These changes are related with an enhancement of the intrinsic acidity of the OH and the SH groups, respectively. Important cooperative effects are also present when the substituent can form an additional IHB with either the oxygen atom or the sulfur atom of TMA. However,the trends observed in the relative stabilities of the enol and the enethiol tautomers do not follow the changes observed in the strength of the IHB. C1-substitution specifically stabilizes the enethiol form, while C3-substitution stabilizes preferentially the enol tautomer. When substitution takes place at the central carbon atom, the enethiol tautomer is predicted to be slightly more stable than the enol counterpart. Substituent effects on the proton-transfer energy barrier are dramatic, and the interconversion between the enolic and the enethiolic forms of the C1- and the C3-substituted derivatives is barrier-free. In contrast, C2-substitution leads to an increase of the barrier.