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Synthesis of 1,2,4-triazoles

Recent Literature

A copper-catalyzed reaction under an atmosphere of air provides 1,2,4-triazole derivatives by sequential N-C and N-N bond-forming oxidative coupling reactions. Starting materials and the copper catalyst are readily available and inexpensive. A wide range of functional groups are tolerated.
S. Ueda, H. Nagasawa, J. Am. Chem. Soc., 2009, 131, 15080-15081.

A highly regioselective one-pot process provides rapid access to highly diverse 1,3,5-trisubstituted 1,2,4-triazoles from reaction of carboxylic acids, primary amidines, and monosubstituted hydrazines.
G. M. Castanedo, P. S. Seng, N. Blaquiere, S. Trapp, S. T. Staben, J. Org. Chem., 2011, 76, 1177-1179.

An effective 1,3-dipolar cycloaddition for the synthesis of 1,3,5-trisubstituted 1,2,4-triazole derivatives by reaction of oximes with hydrazonoyl hydrochlorides using triethylamine as a base gave the desired 1,3,5-trisubstituted 1,2,4-triazoles in good yields. The reaction was applicable to aliphatic, cyclic aliphatic, aromatic and heterocyclic oxime substrates.
L.-Y. Wang, W.-C. Tseng, H.-Y. Lin, F. F. Wong, Synlett, 2011, 1467-1471.

A series of new oxamide-derived amidine reagents can be accessed in excellent yield with minimal purification necessary. A subsequent reaction of these reagents with various hydrazine hydrochloride salts efficiently generates 1,5-disubstituted-1,2,4-triazole compounds in good yields. Both aromatic and aliphatic hydrazines react readily with the amidine reagents under very mild reaction conditions.
Y. Xu, M. McLaughlin, E. N. Bolton, R. A. Reamer, J. Org. Chem., 2010, 75, 8666-8669.

3-N,N-Dialkylamino-1,2,4-triazoles can be prepared from S-methylisothioureas and acyl hydrazides in good yields. The reaction conditions are relatively mild and tolerate a broad range of functional groups.
D. V. Batchelor, D. M. Beal, T. B. Brown, D. Ellis, D. W. Gordon, P. S. Johnson, H. J. Mason, M. J. Ralph, T. J. Underwood, S. Wheeler, Synlett, 2008, 2421-2424.

S. Ueda, H. Nagasawa, J. Am. Chem. Soc., 2009, 131, 15080-15081.

A mild, one-pot cyanoimidation of aldehydes using cyanamide as a nitrogen source and NBS as an oxidant was achieved in high yields without the addition of a catalyst. Subsequently, the substituted N-cyanobenimidate products may also undergo a cyclization reaction to give 1,2,4-triazole derivatives in high yields.
P. Yin, W.-B. Ma, Y. Chen, W.-C. Huang, Y. Deng, L. He, Org. Lett., 2009, 11, 5482-5485.

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.

[1,2,4]Triazolo[1,5-a]pyridines have been prepared in good yields from 2-aminopyridines by cyclization of N-(pyrid-2-yl)formamidoximes under mild reaction conditions with trifluoroacetic anhydride.
E. Huntsman, J. Balsells, Eur. J. Org. Chem., 2005, 3761-3765.