Crystal structure, spectroscopic studies and theoretical studies of thiobarbituric acid derivatives: understanding the hydrogen-bonding patterns

In addition to their wide-ranging applications in the pharmaceutical industry, thiobarbituric acid (TBA) derivatives are also known to possess applications in engineering and materials science. 20 TBA derivatives, with diversity at the N and C-5 positions through acylation, Schiff base formation, Knoevenagel condensation, thioamide and enamine formation, were studied. The absolute configurations for six derivatives, namely 5-acetyl-1,3-diethyl-2-thioxodihydropyrimidine- 4,6(1H, 5H)-dione, C10H14N2O3S, A01, 1,3-diethyl-5-propionyl-2-thioxodihydropyrimidine- 4,6(1H, 5H)-dione, C11H16N2O3S, A02, tert-butyl [1-(1,3-diethyl-4,6-dioxo-2-thioxohexahydropyrimidin-5-yl)-3-methyl-1-oxobutan-2-yl] carbamate, C18H29N3O5S, A06, 1,3-diethyl-4,6-dioxo-2-thioxo-N-(p-tolyl)hexahydropyrimidine- 5-carbothioamide, C(16)H(19)N(3)O(2)S2, A13, 5-(1-aminoethylidene)- 1,3-diethyl-2-thioxodihydropyrimidine-4,6(1H, 5H)-dione, C10H15N3O2S, A17, and 5-(1-aminopropylidene)-1,3-diethyl-2-thioxodihydropyrimidine4,6(1H, 5H)-dione, C11H17N3O2S, A18, were confirmed by single-crystal X-ray crystallography, which indicates the formation of intramolecular hydrogen bonding in all six cases and intermolecular hydrogen bonding for A17. In A13, the presence of two intramolecular hydrogen bonds was observed. The stabilization of the enol form over the keto form was confirmed by computation. In order to convert the keto form to the enol form, an energy barrier of 55.05 kcal mol(-1) needs to be overcome, as confirmed by transition-state calculations.