Categories: Synthesis of N-Heterocycles > benzo-fused N-Heterocycles >
Synthesis of 1,2,4-triazolo[4,3-a]pyridines
An environmentally benign synthesis of various 3,4,5-trisubstituted 1,2,4-triazoles and N-fused 1,2,4-triazoles via ceric ammonium nitrate catalyzed oxidative cyclization of amidrazones and aldehydes using polyethylene glycol as recyclable reaction medium is economic and potentially viable for commercial applications.
M. Nakka, R. Tadikonda, S. Rayavarapu, P. Sarakula, S. Vidavalur, Synthesis, 2015, 47, 517-525.
An operationally efficient CDI mediated tandem coupling and cyclization reaction provides [1,2,4]triazolo[4,3-a]pyridines. The methodology is suitable for batch mode as well as continuous process.
K. D. Baucom, S. C. Jones, S. W. Roberts, Org. Lett., 2016, 18, 560-563.
An efficient and convenient synthesis of [1,2,4]triazolo[4,3-a]pyridines involves a palladium-catalyzed addition of hydrazides to 2-chloropyridine, which occurs chemoselectively at the terminal nitrogen atom of the hydrazide, followed by dehydration in acetic acid under microwave irradiation.
A. Reichelt, J. R. Falsey, R. M. Rzasa, O. R. Thiel, M. M. Achmatowicz, R. D. Larsen, D. Zhang, Org. Lett., 2010, 12, 792-795.
An electrochemically induced desulfurative cyclization of 2-hydrazinopyridines with isothiocyanates provides a wide range of 3-amino-[1,2,4]-triazolo pyridines and related heterocycles under simple conditions without transition metals or external oxidants. This strategy offers broad substrate scope, good functional group compatibility, and gram-scale synthesis.
Y. Hu, L. Chen, C. Zou, J. He, L. Feng, J.-Q. Wu, W.-H. Chen, J. Hu, Org. Lett., 2022, 24, 5137-5142.
I2-mediated oxidative C-N and N-S bond formations in water enable a metal-free, environmentally benign and convenient strategy for the synthesis of 4,5-disubstituted/N-fused 3-amino-1,2,4-triazoles and 3-substituted 5-amino-1,2,4-thiadiazoles from isothiocyanates. The scalable protocols exhibited excellent substrate tolerance.
N. Jatangi, N. Tumula, R. K. Palakodety, M. Nakka, J. Org. Chem., 2018, 83, 5715-5723.