DFT studies on tautomerism of C5-substituted 1,2,4-triazoles

DFT (B3LYP/6-311++G**, B3PW91/6-311++G**) Gibbs free energy and single point CCSD(T)/6-311++G**//DFT total energy calculations were performed to investigate stability and tautomerism of C5-substituted 1,2,4-triazoles. Three different tautomers are possible for the substituted 1,2,4-triazoles: N1-H, N2-H, and N4-H. Unlike for the 1,2,3-triazoles, where the most stable is the N2-H tautomer regardless of substituent applied, for the 1,2,4-triazoles, the electron donating substituents (-OH, -F, -CN, -NH2, and -Cl) and the C5-cation stablize the N2-H tautomer, whereas the electron withdrawing substituents (-CONH2, -COOH, -CHO, -BH2, and -CFO) and the C5-anion stablize the NI-H tautomer. Except for the C5-anion and C5-cation, the N4-H form is the least stable tautomer. The relative stability of the C5-substituted 1,2,4-triazole tautomers is strongly influenced by attractive and/or repulsive intramolecular interactions between substituent and electron donor or electron acceptor centres of the triazole ring. (C) 2004 Elsevier B.V. All rights reserved.