A New Selective Method for the Synthesis of 1-Alkyl-3-nitro-1,2,4-triazol-5-ones

Pharmaceuticals such as trazodone, nefazodone, aprepitant, itraconasole and others, which comprise the 1,2,4-triazol-5-one moiety, are widely used in modern medicine and pharmacy. The synthesis and characterization of the compounds of this series are of theoretical and practical interest. Here we report two methods that give access to 3-nitro-1,2,4-triazol-5-one (NTO) alkyl derivatives, which is not possible via other common approaches. The success of our methods is due to the use of preparatively obtainable starting substrates and the positional selectivity of all the reactions along a specified nitrogen atom. The developed approach contributes to the progress of the theory of reactivity of ambident heterocycles and allows for selective synthesis of previously unknown 1-substituted derivatives of NTO.