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Synthesis of 1,2,4-oxadiazoles

Recent Literature


PTSA-ZnCl2 is an efficient and mild catalyst for the synthesis of 3,5-disubstituted-1,2,4-oxadiazoles from amidoximes and organic nitriles.
J. K. Augustine, V. Akabote, S. G. Hegde, P. Alagarsamy, J. Org. Chem., 2009, 74, 5640-5643.


A one-pot reaction between nitriles, hydroxylamine and Meldrum’s acids under microwave irradiation and solvent-free conditions gives 3,5-disubstituted 1,2,4-oxadiazoles in good to excellent yields.
M. Adib, M. Mahdavi, N. Mahmoodi, H. Pirelahi, H. R. Bijanzadeh, Synlett, 2006, 1765-1767.


Iron(III) nitrate mediates a selective synthesis of 3-acyl-1,2,4-oxadiazoles from alkynes and nitriles. A nitration of alkynes leads to α-nitroketones, dehydration of α-nitroketones provides the nitrile oxides, and a subsequent 1,3-dipolar cycloaddition of nitrile oxides with nitriles produces 3-acyl-1,2,4-oxadiazoles.
Q. Bian, C. Wu, J. Yuan, Z. Shi, T. Ding, Y. Huang, H. Xu, Y. Xu, J. Org. Chem., 2020, 85, 4058-4066.


Synthetically useful aminodioximes are prepared via a novel three-component reaction of Z-chlorooximes, isocyanides, and hydroxylamines. Furthermore, a Mitsunobu-Beckmann rearrangement of aminodioximes yields 1,2,3-oxadiazole-5-amines.
V. Mercalli, A. Massarotti, M. Varese, M. Giustiniano, F. Meneghetti, E. Novellino, G. C. Tron, J. Org. Chem., 2015, 80, 9652-9661.


2,2,2-trifluoroacetaldehyde O-(aryl)oxime releases CF3CN in quantitative yield under mildly basic conditions. 2,2,2-trifluoroacetaldehyde O-(aryl)oxime was successfully used in the synthesis of trifluoromethylated oxadiazoles.
B. Lin, Y. Yao, Y. Huang, Z. Weng, Org. Lett., 2022, 24, 2055-2058.


A series of α-amino acid-derived 1,2,4-oxadiazoles have been synthesized via a convenient and inexpensive one-pot protocol in good yields and in relatively short reaction times.
A. L. Braga, D. S. Lüdtke, E. E. Alberto, L. Dornelles, W. A. Severo Filho, V. A. Corbellini, D. M. Rosa, R. S. Schwab, Synthesis, 2004, 1589-1594.