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Regioselective Synthesis of Novel [1,2,4]Triazolo[1,5‐ a ]pyridine Derivatives
Author(s) -
Hassen Manel Ben,
Masmoudi Fatma,
Zribi Lazhar,
Trigui Mohamed,
Ismaili Lhassane,
MarcoContelles José,
Chabchoub Fakher
Publication year - 2021
Publication title -
chemistryselect
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.437
H-Index - 34
ISSN - 2365-6549
DOI - 10.1002/slct.202004577
Subject(s) - chemistry , pyridine , regioselectivity , combinatorial chemistry , stereochemistry , aryl , medicinal chemistry , organic chemistry , catalysis , alkyl
Herein we report the reaction of 2‐(5‐aryl‐4 H ‐1,2,4‐triazol‐3‐yl)acetonitriles 1 a , b with appropriate Michael acceptors 2 – 4 to give novel [1,2,4]triazolo[1,5‐ a ]pyridines 5 – 8 , whose antioxidant properties have been investigated. A plausible reaction mechanism, supported by DFT calculations, has been proposed to explain the total observed regioselective formation of [1,2,4]triazolo[1,5‐ a ]pyridine derivatives depending on the type of substituents on the Michael acceptor. Triazoles are well‐known agents exhibiting antimicrobial, [1] antitumor, [2] anti‐inflammatory, [3] antihypertensive, [4] anticonvulsant, [5] antiviral [6] and analgesic [7] biological activities. On the other hand, pyridine is the key core of heterocyclic derivatives showing a variety of pharmacological properties. [8–12] Several studies have revealed that a combination of different bioactive molecules, having different mechanisms of action, is a current strategy affording useful therapeutic agents. [13] This is the case of the [1,2,4]triazolo[1,5‐ a ] pyridine heterocyclic motif, [14] present in a number of bioactive compounds, [15] and largely used in materials chemistry. [16] Accordingly, diverse synthetic methods have been described for the synthesis of differently substituted [1,2,4]triazolo[1,5‐ a ]pyridines. [17–24] Our group has recently reported the ultrasound‐promoted facile and convenient “one‐pot” procedure for the synthesis of novel [1,2,4]triazolo[1,5‐ a ]pyridines in short reaction times and high yields, based on the reaction of 2‐(5‐aryl‐4 H ‐1,2,4‐triazol‐3‐yl)acetonitriles, malononitrile (or ethyl cyanoacetate) and aromatic aldehydes, in absolute ethanol, in the presence of IRA‐400. [25]