Categories: Synthesis of N-Heterocycles >
Synthesis of 1,2,4-triazoles
A simple, efficient, and mild method for the synthesis of substituted 1,2,4-triazoles from hydrazines and formamide proceeds smoothly under microwave irradiation in the absence of a catalyst and shows excellent functional-group tolerance.
G. M. Shelke, V. K. Rao, M. Jha, T. S. Cameron, A. Kumar, Synlett, 2015, 26, 404-407.
A multicomponent process enables the synthesis of 1-aryl 1,2,4-triazoles directly from anilines, amino pyridines, and pyrimidines. The reaction scope was explored with 21 different substrates.
A. Tam, I. S. Armstrong, T. E. La Cruz, Org. Lett., 2013, 15, 3585-3589.
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 facile and versatile catalytic system involving copper catalyst, K3PO4 as the base, and O2 as the oxidant enables an efficient synthesis of 2,4,6-trisubstituted and 2,6-disubstituted 1,3,5-triazines and 1,3-disubstituted 1,2,4-triazoles from amidines with trialkylamines, DMSO, and DMF as the reaction partners, respectively. This protocol features an inexpensive catalyst, a green oxidant, good functional group tolerance, and high regioselectivity.
H. Huang, W. Guo, W. Wu, C.-J. Li, H. Jiang, Org. Lett., 2015, 17, 2894-2897.
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.
A general and metal-free synthesis of 1,3,5-trisubstituted 1,2,4-triazoles from hydrazones and aliphatic amines has been achieved under oxidative conditions via a cascade C-H functionalization, double C-N bonds formation, and oxidative aromatization sequence in the presence of iodine as catalyst.
Z. Chen, H. Li, W. Dong, M. Miao, H. Ren, Org. Lett., 2016, 18, 1334-1337.
Triflic anhydride activation followed by microwave-induced cyclodehydration enables a one-pot synthesis of 3,4,5-trisubstituted 1,2,4-triazoles from secondary amides and hydrazides. In addition, the 1,2,4-triazole moiety is shown to be a useful directing group for Ru-catalyzed C-H arylation. A Pd-catalyzed intramolecular C-H functionalization reaction allows access to 1,2,4-triazolophenanthridine.
W. S. Bechara, I. S. Khazhieva, E. Rodriguez, A. B. Charette, Org. Lett., 2015, 17, 1184-1187.
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.
Cu(II) catalyzes the construction of 4,5-disubstituted 1,2,4-triazole-3-thiones from arylidenearylthiosemicarbazides. Upon prolonging the reaction time, the in situ generated thiones are transformed to 4,5-disubstituted 1,2,4-triazoles via a desulfurization process.
A. Gogoi, S. Guin, S. Rajamanickam, S. K. Rout, B. K. Patel, J. Org. Chem., 2015, 80, 9016-9027.
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.
Hexafluorophosphoric acid promotes the formation of 1,3,4-oxadiazolium hexafluorophosphate salts from N′-acyl-N-aroyl-N-arylhydrazides or N′-acyl-N-acyl-N-arylhydrazides under mild conditions. A subsequent reaction with cyanamide in propan-2-ol in the presence of triethylamine generates 1,5-disubstituted 3-amino-1H-1,2,4-triazoles in good yields.
B. Wong, A. Stumpf. D. Carrera, C. Gu, H. Zhang, Synthesis, 2013, 45, 1083-1093.
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-cyanobenzimidate 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.