Synthesis of a New Series of Nitrogen/Sulfur Heterocycles by Linking Four Rings: Indole; 1,2,4-Triazole; Pyridazine; and Quinoxaline

Abstract

A new series of nitrogen and sulfur heterocyclic systems were efficiently synthesized by linking the following four rings: indole; 1,2,4-triazole; pyridazine; and quinoxaline hybrids. The strength of the acid that catalyzes the condensation of 4-amino-5-(1H-indol-2-yl)-2,4-dihydro-3H-1,2,4-triazole-3-thione 1 with aromatic aldehydes controlled the final product. Reflux in glacial acetic acid yielded Schiff bases 2–6, whereas concentrated HCl in ethanol resulted in a cyclization product at C-3 of the indole ring to create indolo-triazolo-pyridazinethiones 7–16. This fascinating cyclization approach was applicable with a wide range of aromatic aldehydes to create the target cyclized compounds in excellent yield. Additionally, the coupling of the new indolo-triazolo-pyridazinethiones 7–13 with 2,3-bis(bromomethyl)quinoxaline, as a linker in acetone and K2CO3, yielded 2,3-bis((5,6-dihydro-14H-indolo[2,3-d]-6-aryl-[1,2,4-triazolo][4,3-b]pyridazin-3 ylsulfanyl)methyl)quinoxalines 19–25 in a high yield. The formation of this new class of heterocyclic compounds in high yields warrants their use for further research. The new compounds were characterized using nuclear magnetic resonance (NMR) and mass spectral analysis. Compound 6 was further confirmed by the single crystal X-ray diffraction technique.

Synthesis, Properties and Biological Potential Some Condensed Derivatives 1,2,4-Triazole

“…In addition, 1,2,4-triazole derivatives have low toxicity, good pharmacokinetic and pharmacodynamic parameters [8]. The synthesis of new condensed 1,2,4-triazole derivatives can improve existing biological properties or contribute to the emergence of new valuable properties [14].…”

Novel indolyl 1,2,4-triazole derivatives as potential anti-proliferative agents: in silico studies, synthesis, and biological evaluation

“…Compounds II, III and IV were prepared according to previously reported methods. [28][29][30][31][32][33][34][35] 4.2.2. Preparation of 1H-indole-3-carbohydrazide (II).…”

Vanillin: A Promising Biosourced Building Block for the Preparation of Various Heterocycles

“…To carry out the transformation, vanillin was reacted with 3,5-di-tert-butylbenzene-1,2-diol, ammonium acetate and an iron (III)-Salen complex as catalyst generating compound 15. Boraei and coworkers have reported the synthesis of a heterocycle containing three fused rings: indole, 1,2,4-triazole and quinoxaline ( Boraei et al, 2020 ). The preparation is carried out in a one-step multicomponent involving 4-amino-5-(1H-indol-2-yl)-2,4-dihydro-3H-1,2,4-triazole-3-thione with vanillin in concentrated HCl, affording compound 16 and yielding exclusively the targeted compound.…”