Synthesis of 1,3,4-oxadiazoles
A direct access to symmetrical and unsymmetrical 2,5-disubstituted [1,3,4]-oxadiazoles has been accomplished through an imine C-H functionalization of N-arylidenearoylhydrazide using a catalytic quantity of Cu(OTf)2. These reactions can be performed in air atmosphere and moisture making it exceptionally practical for application in organic synthesis.
S. Guin, T. Ghosh, S. K. Rout, A. Banerjee, B. K. Patel, Org. Lett., 2011, 13, 5976-5979.
A transition-metal-free condensation of semicarbazide/thiosemicarbazide with aldehydes followed by I2-mediated oxidative C-O/C-S bond formation provides 2-amino-substituted 1,3,4-oxadiazoles and 1,3,4-thiadiazoles in an efficient and scalable fashion.
P. Niu, J. Kang, X. Tian, L. Song, H. Liu, J. Wu, W. Yu, J. Chang, J. Org. Chem., 2015, 80, 1018-1024.
Stoichiometric molecular iodine mediates a practical and transition-metal-free oxidative cyclization of acylhydrazones into 1,3,4-oxadiazoles in the presence of potassium carbonate. Even crude acylhydrazone substrates obtained from the condensation of aldehydes and hydrazides can be converted. A series of symmetrical and asymmetrical 2,5-disubstituted 1,3,4-oxadiazoles can be conveniently generated in an efficient and scalable fashion.
W. Yu, G. Huang, Y. Zhang, H. Liu, L. Dong, X. Yu, Y. Li, J. Chang, J. Org. Chem., 2013, 78, 10337-10343.
Efficient palladium-catalyzed sequential isocyanide insertions into N-H and O-H bonds of hydrazides followed by oxidative annulation provide a convenient access to valuable 2-amino-1,3,4-oxadiazoles and their derivatives.
T. Fang, Q. Tan, Z. Ding, B. Liu, B. Xu, Org. Lett., 2014, 16, 2342-2345.
A facile and general protocol for the preparation of 2-amino-1,3,4-oxadiazoles relies on a tosyl chloride/pyridine-mediated cyclization of thiosemicarbazides that consistently outperforms the analogous semicarbazide cyclizations. Various 5-alkyl- and 5-aryl-2-amino-1,3,4-oxadiazoles have been prepared in good yields.
S. J. Dolman, F. Gosselin, P. D. O'Shea, I. W. Davies, J. Org. Chem., 2006, 71, 9548-9551.
A 2-iodoxybenzoic acid/tetraethylammonium bromide mediated oxidative cyclization of hydrazide-hydrazones generated in situ from aryl glyoxal and hydrazides enables an efficient and high-yielding protocol for the preparation of α-keto-1,3,4-oxadiazoles under mild conditions in short reaction times.
D. Kumar, M. Pilania, V. Arun, B. Mishra, Synlett, 2014, 25, 1137-1141.
An oxidative desulfurization approach enables the construction of oxadiazole and thiadiazole heterocycles in the presence of iodobenzene and Oxone. The use of iodobenzene and the inexpensive readily available oxidant Oxone makes the reaction system simple and versatile for desulfurization.
K. N. Patel, N. C. Jadhav, P. B. Jagadhane, V. N. Telvekar, Synlett, 2012, 23, 1970-1972.
The reaction of a thiosemicarbazide intermediate with EDC·HCl in DMSO or p-TsCl, triethylamine in N-methyl-2-pyrrolidone gives the corresponding 2-amino-1,3,4-oxadiazoles and 2-amino-1,3,4-thiadiazoles through regioselcective cyclization processes.
S.-J. Yang, S.-H. Lee, H.-J. Kwak, Y.-D. Gong, J. Org. Chem., 2013, 78, 438-444.
N-Isocyaniminotriphenylphosphorane, aldehydes, and benzoic acids undergo a one-pot, three-component reaction under mild conditions to afford 2-aryl-5-hydroxyalkyl-1,3,4-oxadiazoles in good yields.
M. Adib, M. R. Kesheh, S. Ansari, H. R. Bijanzadeh, Synlett, 2009, 1575-1578.
Symmetric and unsymmetric 1,3,4-oxadiazoles were synthesized in situ from hydrazine hydrate and the corresponding 2-acyl-4,5-dichloropyridazin-3-ones as acylating agents in polyphosphoric acid (PPA) or BF3·OEt2 in excellent yields.
Y.-D. Park, J.-J. Kim, H.-A. Chung, D.-H. Kweon, S.-D. Cho, S.-G. Lee, Y.-J. Yoon, Synthesis, 2003, 560-564.
A simple and straightforward method for the direct carboxylation of aromatic heterocylces such as oxazoles, thiazoles, and oxadiazoles using CO2 as the C1 source requires no metal catalyst and only Cs2CO3 as the base. A good functional group tolerance is achieved.
O. Vechorkin, N. Hirt, X. Hu, Org. Lett., 2010, 12, 3567-3569.