A New Selective Method for the Synthesis of 1-Alkyl-3-nitro-1,2,4-triazol-5-ones
The chemistry of heterocyclic compounds has become one of the most dynamically developing fields of organic chemistry in recent decades. The role the heterocyclic compounds play in different areas of science and technology (chemistry, medicine, biology, electronics, etc.) can hardly be overestimated. In this regard, the development of new synthetic methods for functional derivatives of various heterocyclic compounds still holds relevance. 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. The design of novel drugs is based both on the directed synthesis of new drugs and on the screening of bioactive compounds derived by modifying the known drug molecules. 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 to the positional selectivity of all the reactions along a specified nitrogen atom. The strategy devised herein contributes to the progress in the theory of reactivity of ambident heterocycles and allows for selective synthesis of never-before-seen 1-substituted derivatives of NTO. The virtual screening of N-functionalized derivatives of 3-nitro-1,2,4-triazole and 3-nitro-1,2,4-triazole-5-one, which were obtained by the nucleophilic substitution of the nitro group, saponification and nitration, has shown their high biological activity in the most demanded areas of medicine - disease treatment, prevention and rehabilitation: cardiovascular diseases; diseases of the nervous system (neuromediators, neuroprotectors); anticancer drugs (cancer growth blockers). Therefore, such compounds arouse elevated interest among researchers in Russia and overseas.