Substituent effects on the strength of the intramolecular hydrogen bond ofthiomalonaldehyde

The effect of CH3, NH2, OH, and F substituents on the intramolecular hydrog en bond (IHB) of thiomalonaldehyde (TMA) was analyzed through the use of B3 LYP 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 III B of the enolic tautomer, while CS-substitution strengthens the IHB of the enethiolic form. These changes are related with an enhancement of the intri nsic acidity of the OH and the SH groups, respectively. Important cooperati ve 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-substitu tion specifically stabilizes the enethiol form, while C3-substitution stabi lizes preferentially the enol tautomer. When substitution takes place at th e central carbon atom, the enethiol tautomer is predicted to be slightly mo re stable than the enol counterpart. Substituent effects on the proton-tran sfer energy barrier are dramatic, and the interconversion between the enoli c 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 bar rier.