Journal Article

Expanding the chemical space of 3(5)-functionalized 1,2,4-triazoles

Zakharchenko, Borys V, Khomenko, Dmytro M, Ohorodnik, Yulia M, Dobrydnev, Alexey V, Vaschenko, Oleksandr V, Lampeka, Rostyslav D, Grygorenko, Oleksandr O, Ivanova, Hanna V, Doroshchuk, Roman O, Raspertova, Ilona V

2022

Overview

An efficient approach to the gram-scale synthesis of 3(5)-substituted, 1,3- and 1,5-disubstituted 1,2,4-triazole-derived building blocks is described. The key synthetic precursors – 1,2,4-triazole-3(5)-carboxylates (20 examples, 35–89% yield) were prepared from readily available acyl hydrazides and ethyl 2-ethoxy-2-iminoacetate hydrochloride. Further transformations were performed following the convergent synthetic strategy and allowed the preparation of 1,3- and 1,5-disubstituted 1,2,4-triazole-derived esters (16 examples, 25–75% yield), 3(5)-substituted, 1,3- and 1,5-disubstituted carboxylate salts (18 examples, 78–93% yield), amides (5 examples, 82–93% yield), nitriles (5 examples, 30–85% yield), hydrazides (6 examples, 84–89% yield), and hydroxamic acids (3 examples, 73–78% yield). Considering wide applications of the 1,2,4-triazole motif in medicinal chemistry, these compounds are valuable building blocks for lead-oriented synthesis; they have also great potential for coordination chemistry.

• Publisher: Springer Nature B.V
• Subject: Acids / Amides / Carboxylates / Chemistry / Dehydration / Esters / Hydrazides / Ligands / Molecular weight / Nitriles / Solvents / Substitutes / Synthesis / Triazoles