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Synthesis of 1,3,4-oxadiazoles
Recent Literature
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.
The combination of an organo acridinium photocatalyst and a cobaloxime
catalyst enables an efficient oxidant-free, photoredox-mediated cascade
cyclization of acylhydrazones to provide 1,3,4-oxadiazoles in good yields with H2
as the only byproduct. A one-pot gram-scale synthesis starting directly from
commercially available aldehydes and acylhydrazides is also described.
J.-L. Li, H.-Y. Li, S.-S. Zhang, S. Shen, X.-L. Yang, X. Niu, J. Org. Chem., 2023, 88,
14874-14886.
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 mechanochemical synthesis of 2,5-disubstituted 1,3,4-oxadiazoles is an
environmentally benign alternative to conventional solvent-based methods. In the
presence of triphenylphosphine and trichloroisocyanuric acid, N-acylbenzotriazoles
condense with acylhydrazides to provide oxadiazoles derivatives in very good
yields within minutes. A range of reactive functionalities was well tolerated.
D. Yamano, N. Wiriya, W. Phakhodee, S. Wet-osot, M. Pattarawarapan, Synlett, 2022,
33,
1458-1462.
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.
The reaction of carboxylic acids with N-isocyaniminotriphenylphosphorane
(NIITP) followed in situ by a copper-catalyzed coupling with aryl iodides
provides 2,5-disubstituted 1,3,4-oxadiazoles. An extension to the synthesis of
aminated 1,3,4-oxadiazoles using N-benzoyloxy amine coupling partners was
also demonstrated.
D. Matheau-Raven, D. J. Dixon, J. Org. Chem., 2022, 87,
12498-12505.
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 visible light-induced coupling cyclization reaction of α-diazosulfonium
triflates with α-oxocarboxylic acids or alkynes affords a diverse set of
important 2,5-disubstituted 1,3,4-oxadiazoles and 3,5-disubstituted-1H-pyrazoles
with excellent regioselectivity in a single step via in situ generated
diazomethyl radicals as key intermediates.
X.-C. Xu, D.-N. Wu, Y.-X. Liang, M. Yang, H.-Y. Yuan, Y.-L. Zhao, J. Org. Chem., 2022, 87,
16604-16616.
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.
An acid-catalyzed regioselective cyclization reaction of alkyl
2-(methylthio)-2-thioxoacetates or alkyl 2-amino-2-thioxoacetates with acyl
hydrazides provides 2,5-disubstituted-1,3,4-thiadiazoles and 1,3,4-oxadiazoles.
The reported methods are operationally simple and highly efficient with
metal-free conditions and demonstrate significant functional group compatibility.
C. Santhosh, K. R. Singh, K. Sheela, T. R. Swaroop, M. P. Sadashiva, J. Org. Chem., 2023, 88,
11486-11496.
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 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.