Synthesis of 1,3,4-oxadiazoles
In a direct annulation of hydrazides with methyl ketones for the synthesis of 1,3,4-oxadiazoles, the use of K2CO3 as a base achieves an unexpected and highly efficient C-C bond cleavage. This reaction is proposed to go through oxidative cleavage of Csp3-H bonds, followed by cyclization and deacylation.
Q. Gao, S. Liu, X. Wu, J. Zhang, A. Wu, Org. Lett., 2015, 17, 2960-2963.
I2 promotes a metal-free domino protocol for the one-pot synthesis of 1,3,4-oxadiazoles in good yields via oxidative cleavage of C(sp2)-H or C(sp)-H bonds, followed by cyclization and deacylation. The use of K2CO3 is an essential factor in the cyclization and the C-C bond cleavage. This procedure offers good functional group compatibility.
Y. Fan, Y. He, X. Liu, T. Hu, H. Ma, X. Yang, X. Luo, G. Huang, J. Org. Chem., 2016, 81, 6820-6825.
2-Aryl- and 2-alkenyl-1,3,4-oxadiazoles were efficiently synthesized in high yields by treatment of 1,3,4-oxadiazoles with aryl or alkenyl halides, respectively, in the presence of copper(II) oxide nanoparticles as reusable catalyst.
N. S. Reddy, P. R. Reddy, B. Das, Synthesis, 2015, 47, 2831-2838.
A simple and efficient cationic Fe(III)/TEMPO-catalyzed oxidative cyclization of aroyl hydrazones in the presence of oxygen enables the synthesis of 2,5-disubstituted 1,3,4-oxadiazole derivatives in high yields. The reaction offers a broad scope and good functional-group tolerance.
G. Zhang, Y. Yu, Y. Zhao, X. Xie, C. Ding, Synlett, 2017, 28, 1373-1377.
The auto-oxidation of isobutyraldehyde in the presence of molecular oxygen generates acyloxy radicals, which in situ afford a hypervalent iodine compound with p-anisolyl iodide. A hypervalent iodine mediated reaction of N'-arylidene acetohydrazides provides substituted 1,3,4-oxadiazoles in good yields in parallel.
J. Chauhan, M. K. Ravva, S. Sen, Org. Lett., 2019, 21, 6562-6565.
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.
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.
A radical-promoted cross-dehydrogenative coupling strategy enables a metal- and base-free one-pot synthesis of 2,5-diaryl 1,3,4-oxadiazoles via N-acylation of aryl tetrazoles with aryl aldehydes, followed by thermal rearrangement. A broad range of aryl tetrazoles and aryl aldehydes deliver the corresponding products in good yields.
L. Wang, J. Cao, Q. Chen, M. He, J. Org. Chem., 2015, 80, 4743-4748.
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 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.
A photoredox-catalyzed decarboxylative cyclization reaction between commercially available α-oxocarboxylic acids and a hypervalent iodine(III) reagent provides 2,5-disubstituted 1,3,4-oxadiazoles in very good yields.
J. Li, X.-C. Lu, Y. Xu, J.-X. Wen, G.-Q. Hou, L. Liu, Org. Lett., 2020, 22, 9621-9626.
A one-pot sequential N-acylation/dehydrative cyclization between ethyl carbazate and N-acylbenzotriazoles in the presence of Ph3P-I2 as a dehydrating agent enables a convenient synthesis of 5-substituted-2-ethoxy-1,3,4-oxadiazoles. Subsequent treatment with a stoichiometric amount of alkyl halides provides 3,5-disubstituted 1,3,4-oxadiazol-2(3H)-ones in very good yields.
S. Wet-osot, W. Phakhodee, M. Pattawarapan, J. Org. Chem., 2017, 82, 9923-9929.
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.
A highly efficient eosin Y catalyzed oxidative heterocyclization of semicarbazones was established under visible-light photoredox catalysis using CBr4 as a bromine source. The protocol renders a rapid, mild, and efficient access to valuable 5-substituted 2-amino-1,3,4-oxadiazoles in an operationally simple way utilizing visible light and atmospheric oxygen.
R. Kapoorr, S. N. Singh, S. Tripathi, L. D. S. Yadav, Synlett, 2015, 26, 1201-1206.
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.
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.
A visible-light-induced [3 + 2] cycloaddition of a hypervalent iodine(III) reagent with α-ketoacids enables the construction of 5-CF3-1,3,4-oxadiazoles. The reaction proceeds smoothly without a photocatalyst, metal, or additive under mild conditions.
W.-W. Zhao, Y.-C. Shao, A.-N. Wang, J.-L. Huang, C.-Y. He, B.-D. Cui, N.-W. Wan, Y.-Z. Chen, W.-Y. Han, Org. Lett., 2021, 23, 9256-9261.
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.