Mechanism of 4-methyl-1,2,4-triazol-3-thione reaction with formaldehyde

We have recently described theoretically the mechanism of the reaction between 4-methyl-1,2,4-triazol-3-thiol and formaldehyde that leads to the N-substituted product, N-1-hydroxymethyl-4-methyl-1,2,4-triazol-3-thione. New experimental findings indicate that the thione tautomeric form in reaction with formaldehyde also yields this product. This observation could not be explained on the basis of previous calculations, which predicted that the thione tautomer undergoes nucleophilic substitution at the sulfur atom, leading to the S-substituted product. We present theoretical explanation of the observed reactivity. We show that under experimental conditions this reaction proceeds with the intervention of the anionic form of the triazole with the Gibbs free energy of activation of only 1.8 kcal/mol. Copyright (C) 2008 John Wiley & Sons, Ltd.