One-pot, three component synthesis of 2,5-disubstituted 1,3,4-oxadiazoles catalyzed by heteropolyacid

Article abstract of DOI:10.1080/15533174.2012.740718

H₆[PMo₉V₃O₄₀] was used as an efficient catalyst for the preparation of 1-aroyl-2-arylidene hydrazines. 2,5-Disubstituted 1,3,4-oxadiazoles have been synthesized by oxidation of 1-aroyl-2-arylidene hydrazines with CrO₃ in excellent yields.

Full text of DOI:10.1080/15533174.2012.740718

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Synthesis and Reactivity in Inorganic, Metal-Organic,
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One-pot, Three Component Synthesis of 2,5-
Disubstituted 1,3,4-Oxadiazoles Catalyzed by
Heteropolyacid
Majid M. Heravi a , Vahideh Zadsirjan a , Khadijeh Bakhtiari a & Fatemeh F. Bamoharram b
a Department of Chemistry, School of Sciences, Alzahra University, Vanak, Tehran, Iran
b Department of Chemistry, Islamic Azad University -Mashhad Branch, Mashhad, Iran
Accepted author version posted online: 12 Nov 2012.
To cite this article: Majid M. Heravi , Vahideh Zadsirjan , Khadijeh Bakhtiari & Fatemeh F. Bamoharram (2012): One-pot,
Three Component Synthesis of 2,5-Disubstituted 1,3,4-Oxadiazoles Catalyzed by Heteropolyacid, Synthesis and Reactivity in
Inorganic, Metal-Organic, and Nano-Metal Chemistry, DOI:10.1080/15533174.2012.740718
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ACCEPTED MANUSCRIPT
One-pot, Three Component Synthesis of 2,5-Disubstituted 1,3,4-Oxadiazoles Catalyzed by
Heteropolyacid
Majid M. Heravi,1 Vahideh Zadsirjan,1 Khadijeh Bakhtiari,1and Fatemeh F.
Bamoharram2
1 Department of Chemistry, School of Sciences, Alzahra University, Vanak, Tehran, Iran
2 Department of Chemistry, Islamic Azad University -Mashhad Branch, Mashhad, Iran
H6[PMo9V3O40] was used as an efficient catalyst for the preparation of 1-aroyl-2-
arylidene hydrazines. 2,5-Disubstituted 1,3,4-oxadiazoles have been synthesized by
oxidation of 1-aroyl-2-arylidene hydrazines with CrO3 in excellent yields.
Keywords 2,5-Disubstituted 1,3,4-oxadiazoles, H6[PMo9V3O40], Vanadium mixed addenda
heteropolyacid. Click reaction.
INTRODUCTION
1,3,4-oxadiazoles have emerged as an important class of heterocycles that have attracted
significant pharmaceutical and biological properties such as anti-inflammatory, anticonvulsant,
analgesic activities,[1] antibacterial[2] and muscle relaxant properties.[3] A wide variety of methods
for the preparation of 1,3,4-oxadiazoles have been classified according to starting compounds.
The common route for the synthesis of these compounds involves cyclization of
diacylhydrazines with a variety of dehydrating reagents.[4-11] They have also been prepared by
oxidation of acylhydrazones with different oxidizing agents.[12-14] One-pot synthesis of 1,3,4-
oxadiazoles from acid hydrazides and hydrazine with an acid chloride,[15,16] as well as from
 Corresponding mmh1331@yahoo.com; Tel: 0098-21-88044051; Fax: 0098-21-88041344.
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hydrazines with carboxylic acids,[17] have also been reported in the literature. Recently, solid
phase syntheses of these compounds under mild conditions were also reported.[18-21]
Heteropolyacids, HPAs, catalyze a wide variety of reactions in homogeneous or heterogeneous
(liquid-solid, gas-solid or liquid-liquid biphasic) systems, offering strong options for more
efficient and cleaner processing compared to conventional mineral acids.[22-25]
Being stronger acids, heteropoly acids will have significantly higher catalytic activity than
conventional catalysts such as mineral acids, mixed-oxides, zeolites etc. In particular, in organic
media the molar catalytic activity of heteropoly acid is often 100-1000 times higher than that of
[24, 25]
H2SO4.
The Keggin–type HPAs typically represented by the formula H8-x[XM12O40], when X is the
heteroatom (most frequently P+5 or Si+4), x is the oxidation state, and M is the addenda atom
(usually W+6 or Mo+6), are the most important for catalysis.[22-25] They have been widely used as
acid and oxidation catalysts for organic synthesis and found several industrial applications.
We have been interested in the synthesis of heterocyclic compounds,[26-28] for several years, and
the application of heteropoly anions in organic synthesis,[29-31] Herein, we wish to report the
synthesis of 2,5-disubstituted 1,3,4-oxadiazoles (2) via oxidation of 1-aroyl-2-arylidene
hydrazines (1) with CrO3 in very good yields. The efficient route is outlined in Scheme 1. As
shown, 1-aroyl-2-arylidene hydrazines (1) were obtained from the reaction of aryl hydrazide and
various aldehydes in the presence of a catalytic amount of vanadium mixed addenda heteropoly
acid. Under these conditions 1-aroyl-2-arylidene hydrazines (1) were obtained as sole products.
EXPERIMENTAL
Materials and Methods
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Melting points were measured by using the capillary tube method with an electro thermal
1
9200 apparatus. HNMR spectra were recorded on a Bruker AQS AVANCE-500 MHz
spectrometer using TMS as an internal standard (CDCl3 solution). IR spectra were recorded from
KBr disk on the FT-IR Bruker Tensor 27. All products were characterized by spectra and
physical data.
Preparation of 1-aroyl-2-arylidene hydrazines (1): General procedure
A mixture of 1mmol aldehyde, 1 mmol acid hydrazide, and H6[PMo9V3O40] (2mol%), in
3 mL acetic acid was refluxed for appropriate time; after completion of the reaction which was
monitored by TLC, the mixture was cooled to room temperature. The catalyst was filtered off.
The filtrate was successively diluted with 5% NaHCO3 (5 mL) and extracted with diethyl ether
(2×5 mL). The combined organic layers then washed with brine (2×5 mL), and dried over
MgSO4. The solvent was evaporated under reduced pressure and the pure product was obtained
by recrystallization from the suitable solvent. The products (1) were identified by comparison
with authentic samples by TLC, 1H NMR and IR spectroscopy.
Preparation of 2,5-disubstituted 1,3,4-oxadiazoles: General procedure
A mixture of 1mmol 1-aroyl-2-arylidene hydrazines (1) and 1mmol CrO3 was refluxed in
acetic acid for appropriate time. After completion of the reaction which was monitored by TLC,
the mixture was cooled to room temperature. The catalyst was filtered off. The filtrate was
successively diluted with 5% NaHCO3 (5 mL) and extracted with diethyl ether (2×5 mL). The
combined organic layers then washed with brine (2×5 mL), and dried over MgSO4. The solvent
was evaporated under reduced pressure and the pure product was obtained by recrystallization
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1
from EtOH. The products (1) were identified by comparison with authentic samples by TLC, H
NMR and IR spectroscopy.
One-pot preparation of 2,5-disubstituted 1,3,4-oxadiazoles: General procedure
A mixture of aldehyde (1mmol), acid hydrazide (1 mmol), and H6[PMo9V3O40] (2mol%),
in acetic acid (3 mL) was refluxed for appropriate time; after forming of 1-aroyl-2-arylidene
hydrazines (1) as intermediate, which was monitored by TLC, CrO3 was added to the mixture
and refluxed in the same condition. Upon completion of the reaction the mixture was cooled to
room temperature. The catalyst and oxidant were filtered off. The filtrate was successively
diluted with 5% NaHCO3 (5 mL) and extracted with diethyl ether (2×5 mL). The combined
organic layers then washed with brine (2×5 mL), and dried over MgSO4. The solvent was
evaporated under reduced pressure and the pure product was obtained by recrystallization from
the suitable solvent. The products (2) were identified by comparison with authentic samples by
TLC, 1H NMR and IR spectroscopy.
RESULT AND DISCUSSION
At first, the synthesis of 1,3,4-oxadiazoles was investigated through a two-step pathway.
For optimization of the reaction conditions, the reaction of PhCONHNH2 (1mmol) with
benzaldehyde (1mmol) in different solvents under reflux conditions in the presence of a catalytic
amount of vanadium mixed addenda heteropolyacid was studied (Scheme 1, Step 1). The results
are summarized in Table 1. Acetic acid was found to be a good solvent for this reaction. In this
stage, 1-aroyl-2-arylidene hydrazines (1) were obtained in very good yields in the presence of
H6[PMo9V3O40] as catalyst.
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To show the merits of our catalyst, the above reaction was also carried out in the absence
of H6[PMo9V3O40]. As can be seen in Table 1, no product was obtained even after long time
reaction.
These products were known and characterized by comparison of their spectral and
physical data with those already reported. The results are shown in Table 2.
One of the important factors affecting the oxidation capacity of polyanions is the energy
gap between the highest occupied molecular orbital (HOMO) and the lowest unoccupied orbital
(LUMO). It should be noted that all of the HOMOs and LUMOs of the polyoxoanions have very
high energy levels (3.0-9.0 and 6.0-12.0 eV, respectively) because of their large negative
charges. It is well known that these highly charged heteropolyanions do not exist in the gas phase
and that the external field generated by the solvent and the counterions is crucial to stabilize
them. Keep in mind that the heteropolyanions are easily reducible chemical species, and thus the
energy of the LUMO must be sufficiently low to accept the incoming electron in catalytic
reactions. The solvent molecules in dilute solutions stabilize these anions and place these
molecular orbitals at the appropriate level. Moreover, the metal substitution may modify the
energy and composition of the LUMO and thus also the redox properties of the cluster.[32]
Subsequently, compound (1) underwent oxidative cyclization using CrO3 under reflux condition.
(Scheme 1, Step 2) 2,5-Disubstituted 1,3,4-oxadiazoles were obtained in high yields within 3-7h.
Then, we decided to carry out the synthesis of 2,5-disubstituted 1,3,4-oxadiazoles in a one-pot
manner without isolation of compound (1) as intermediate. For this purpose, at the end of step 1
which monitored by TLC, CrO3 was added to the mixture and refluxed in the same condition for
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the appropriate time. After completion of the reaction the products were isolated and identified
by comparison of their spectra and physical data with those reported in the literature.
In order to show the general applicability of the protocol, we have applied this catalytic system
for the preparation of a variety of 2,5-disubstituted 1,3,4-oxadiazoles from different hydrazides
and aldehyde derivatives in acetic acid. We found that the reaction proceeds very efficiently with
benzaldehyde and electron-withdrawing and electron-donating substituted benzaldehydes. The
results are summarized in Table 3.
In conclusion, we have found an efficient route for the synthesis of unsymmetrical 2,5-
disubstituted 1,3,4-oxadiazoles in very good yields in the presence of H6[PMo9V3O40] as catalyst
and CrO3 as oxidant.
Since the reaction proceeds rapidly and selectively under relatively mild condition using green
catalyst in a one pot reaction, giving covalently link components of oxadiazoles, it can be
considered as a click reaction.
Acknowledgments
MMH is thankful to the Iran National Science Foundation for partial
financial support.
REFRENCES
1. Palaska, E., Sahin, G., Kelicen, P., Tugbadurlu, N., and Altinok, G. IL Farmaco, 2002,
57, 101-107.
2. Angelini, I., Angelini, L., and Sparaco, F. Brit. Pat. 1.161.801, 1966/1969, Chem Abstr,
1969, 71, 112937.
6
ACCEPTED MANUSCRIPT

ACCEPTED MANUSCRIPT
3. Yale, H.L., and Losee, K.A. 2-Amino-5-substituted 1,3,4-oxadiazoles and 5-imino-2-
substituted Δ2-1,3,4-oxadiazolines. A Group of novel muscle relaxants. J. Med. Chem.,
1966, 9, 478-483.
4. Kerr, V.N., Ott, D.G., and Hayes, F.N. Quaternary salt formation of substituted oxazoles
and thiazoles. J. Am. Chem. Soc., 1960, 82, 186-189.
5. Al-Talib, M., Tastoush, H., and Odeh, N.A. A convenient synthesis of alkyl and aryl
substituted bis-1,3,4-oxadiazoles. Synth. Commun., 1990, 20, 1811-1817.
6. Carlsen, P.H.J., and Jorgensen, K.B. Synthesis of unsymmetrically substituted 4H-1,2,4-
triazoles. J. Heterocycl. Chem., 1994, 31, 805-807.
7. Klinsberg, E. Synthesis of carboxylic acid hydrazides and s-triazoles of the
anthraquinone series. J. Am. Chem. Soc., 1958, 80, 5786-5789.
8. Liras, S., Allen, M.P., and Segelstein, B.E.A. A mild method for the preparation of 1,3,4-
oxadiazoles: Triflic anhydride promoted cyclization of diacylhydrazines. Synth.
Commun., 2000, 30, 437-443.
9. Brown, P., Best, D.J., Broom, N.J.P., Cassels, R., Bhanlon, P.J., Mitchell, T.J., sborne,
N.F., and Wilson, J.M. The chemistry of Pseudomonic Acid. 18. Heterocyclic
replacement of the α,β-unsaturated ester: Synthesis, molecular modeling, and
antibacterial activity. J. Med. Chem., 1997, 40, 2563-2570.
10. Tully, W.R., Gardner, C.R., Gillespie, R.J., and Westwood, R. 2-(oxadiazolyl)- and 2-
(thiazolyl)imidazo[1,2-a]pyrimidines as agonists and inverse agonists at benzodiazepine
receptors. J. Med. Chem., 1991, 34, 2060-2067.
7
ACCEPTED MANUSCRIPT

ACCEPTED MANUSCRIPT
11. Short, F.W., and Long, L.N. Synthesis of 5-aryl-2-oxazolepropionic acids and analogs.
Antiinflammatory agents. J. Heterocycl. Chem., 1969, 6, 707-712.
12. Balachandran, K.S., and George, M.V. Oxidation with metal oxides-VI: Oxidation of
benzoylhydrazones of aldehydes, ketones and 1,2-diketones with nickel peroxide.
Tetrahedron, 1973, 29, 2119-2128.
13. Chiba, T., and Okimoto, M. Electrooxidative cyclization of N-acylhydrazones of
aldehydes and ketones to Δ3-1,3,4-oxadiazolines and 1,3,4-oxadiazoles. J. Org. Chem.,
1992, 57, 1375-1379.
14. Yang, R., and Dai, L. Hypervalent iodine oxidation of N-acylhydrazones and N-
phenylsemicarbazone: an efficient method for the synthesis of derivatives of 1,3,4-
oxadiazoles and Δ3-1,3,4-oxadiazolines. J. Org. Chem., 1993, 58, 3381-3383.
15. Tandon, V.K., and Chhor, R.B. An Efficient one pot synthesis of 1,3,4-oxadiazoles.
Synth. Commun., 2001, 31, 1727-1732.
16. Mashraqui, S.H., Ghadigaonkar, Sh.G., and Kenny, R.S. An expeditious and convenient
one pot synthesis of 2,5-disubstituted-1,3,4-oxadiazoles. Synth. Commun., 2003, 33,
2541-2545.
17. Bentiss, F., Lagrenee, M., and Barbry, D. Rapid synthesis of 2,5-disubstituted 1,3,4-
oxadiazoles under microwave irradiation. Synth. Commun., 2001, 31, 935-938.
18. Brown, B.J., Clemens, I.R., and Neesom, J.K. Diisopropylcarbodiimide: A novel reagent
for the synthesis of 1,3,4-oxadiazoles on solid-phase. Synlett, 2000, 131-133.
19. Brain, C.T., and Brunton, Sh.A. Synthesis of 1,3,4-oxadiazoles using polymer supported
reagents. Synlett, 2001, 382-384.
8
ACCEPTED MANUSCRIPT

ACCEPTED MANUSCRIPT
20. Brain, C.T., Paul, J.M., Loong, Y., and Oakley, P.J. Novel procedure for the synthesis of
1,3,4-oxadiazoles from 1,2-diacylhydrazines using polymer-supported Burgess reagent
under microwave conditions. Tetrahedron Lett., 1999, 40, 3275-3278.
21. Wipf, P., and Venkatraman, S. An improved protocol for azole synthesis with PEG-
supported Burgess reagent. Tetrahedron Lett., 1996, 37, 4659-4662.
22. Izumi, Y., Urabe, K., and Onaka, M. Zeolite Clay and heteropoly acid in organic
Reactions, Kodansha/VCH, Tokyo. 1992.
23. Misono, M. Unique acid catalysis of heteropoly compounds (heteropolyoxometalates) in
the solid state. Chem. Commun., 2001, 1141-1152.
24. Kozhevnikov, I.V. Catalysis by heteropoly acids and multicomponent polyoxometalates
in liquid-phase reactions. Chem. Rev., 1998, 98, 171-198.
25. Kozhevnikov, I.V. Catalysts for fine chemicals, in: Catalysis by Polyoxometalates, vol 2,
Wiely, Chichester. 2002.
26. Heravi, M.M., Rahimzadeh, M., Bakavoli, M., and Ghassemzadeh, M. Pd–Cu catalyzed
heterocyclization during Sonogashira coupling: synthesis of 3-benzylthiazolo[3,2-
a]benzimidazole. Tetrahedron Lett., 2004, 45, 5747-5749.
27. Heravi, M.M., Rahimzadeh, M., Bakavoli, M., and Ghassemzadeh, M. Regioselective
synthesis of 6-benzylthiazolo[3,2-b]1,2,4-triazoles during Sonogashira coupling.
Tetrahedron Lett., 2005, 46, 1607-1610.
28. Heravi, M.M., Tajbakhsh, M., Ahmadi, A.N., and Mohajerani, B. Zeolites efficient and
eco-friendly catalysts for the synthesis of benzimidazoles. Monatsh. Chem., 2006, 137,
175-179.
9
ACCEPTED MANUSCRIPT

ACCEPTED MANUSCRIPT
29. Heravi, M.M., Bakhtiari, K., and Bamoharram, F.F. An efficient and chemoselective
synthesis of acylals from aromatic aldehydes and their regeneration, catalyzed by 12-
molybdophosphoric acid. Catal. Commun., 2006, 7, 499-501.
30. Heravi, M.M., Bakhtiari, K., and Bamoharram, F.F. 12-Molybdophosphoric acid: A
recyclable catalyst for the synthesis of Biginelli-type 3,4-dihydropyrimidine-2(1H)-ones.
Catal. Commun., 2006, 7, 373-376.
31. Bamoharram, F.F., Heravi, M.M., Roshani, M., Jahangir, M., and Gharib, A. Preyssler
catalyst, [NaP5W30O110]14−: A green, efficient and reusable catalyst for esterification of
salicylic acid with aliphatic and benzylic alcohols. Applied Catal. A: Gen., 2006, 302, 42-
47.
32. Wang, J., Hu, Ch., Jiana, M., Zhang, J. and Li, G. Catalytic oxidation performance of the
α-Keggin-type vanadium-substituted heteropolymolybdates: A density functional theory
study on [PVnMo12−nO40](3+n)− (n = 0–3). J. Catal., 2006, 240, 23–30.
33. Grekov, A.P., and Kulakova, L.N.Zh. Obshch. Khim., 1959, 29, 3054, Chem Abstr,
1960, 54, 13108g.
34. Rao, V.S., and Chandra Sekhar, K.V.G. Iodobenzene diacetate mediated solid state
synthesis of heterocyclyl 1,3,4-oxadiazoles. Synth. Commun., 2004, 34, 2153-2157.
10
ACCEPTED MANUSCRIPT

ACCEPTED MANUSCRIPT
35. Gilbert, E.C. The molecular rearrangment of some new unsymmetrical hydrazines. J. Am.
Chem. Soc., 1927, 49, 286-292.
36. Rostamizadeh, S., and Housaini, S.A. G. Microwave assisted synthesis of 2,5-
disubstituted 1,3,4-oxadiazoles. Tetrahedron Lett., 2004, 45, 8753-8756.
37. Dabiri, M., Salehi, P., Baghbanzadeh, M., and Bahramnejad, M. A facile procedure for
the one-pot synthesis of unsymmetrical 2,5-disubstituted 1,3,4-oxadiazoles. Tetrahedron
Lett., 2006, 47, 6983-6986.
TABLE 1.
Synthesis of 1-aroyl-2-arylidene hydrazines (1) at different conditions
Entry
Catalysis
Solvent
Time (h)
Yield (%)
1
H5[PMo10V2O40] (2
CH3COOH
2.15
60
mol%)
2
3
4
5
6
7
8
H6[PMo9V3O40] (2 mol%)
C2H5OH
PhCH3
2
49
42
H6[PMo9V3O40] (2 mol%)
2.5
1.15
1.45
24
H6[PMo9V3O40] (2 mol%)
CH3COOH
Ac2O
94
H6[PMo9V3O40] (2 mol%)
70
-
-
-
CH3COOH
PhCH3
Trace
Trace
-
24
C2H5OH
24
TABLE 2.
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Synthesis of 1-aroyl-2-arylidene hydrazines (1)
Time
(min)
Yield
(%)a
m.p. (oC)
Entry
Hydrazide
aldehyde
Found Reported
203-
202
CHO
1
2
3
75
80
85
89
88
88
205[37]
PhCONHNH2
PhCONHNH2
CHO
O2N
187
219
188 [37]
218-220
PhCONHNH2
Cl
CHO
[35]
240-242
PhCONHNH2
PhCONHNH2
O2N
Br
CHO
CHO
CHO
4
5
6
80
76
74
91
90
89
239
224
216
[35]
225 [36]
217 [35]
Me
PhCONHNH2
145 [35]
MeO
CHO
7
80
88
146
PhCONHNH2
PhCONHNH2
224 [36]
159[34]
CH3CHO
8
9
75
77
87
91
225
160
N
CONHNH2
CONHNH2
CHO
CHO
267[34]
N
10
75
90
268
O2N
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210 [34]
N
CONHNH2
Cl
CHO
11
80
91
211
a) Yields refer to isolated products.
TABLE 3.
Synthesis of 2,5- disubstituted 1,3,4- oxadiazoles in a one-pot reaction
Time
(h)
Yield
(%)a
m.p. (oC)
Found Reported
Entry
Hydrazide
aldehyde
139-140 [14]
143-146 [14]
CHO
1
2
6
89
90
139
145
PhCONHNH2
PhCONHNH2
CHO
6.5
O2N
160-162 [14]
202-204 [14]
167[ 33]
PhCONHNH2
PhCONHNH2
PhCONHNH2
Cl
CHO
CHO
CHO
3
4
5
5
7
89
90
88
161
203
166
O2N
Br
4.5
CHO
CHO
Me
6
3.5
87
147
145-146 [14]
PhCONHNH2
MeO
7
8
3
4
88
87
149
68
149-151[14]
67 [36]
PhCONHNH2
PhCONHNH2
CH3CHO
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N
CONHNH2
CHO
CHO
9
6
5
4
90
89
91
152
120
170
153 [34]
125 [34]
N
CONHNH2
10
11
O2N
168-170 [34]
N
CONHNH2
Cl
CHO
a) Yields refer to isolated products.
1) H6[PMo9V3O40]
N
N
2) CrO3
HOAc, reflux
(2 mol%)
Ar1CONH-N=CHAr2
Ar1CONHNH2 + Ar2CHO
HOAc, reflux
Ar1
Ar2
O
(2)
(1)
SCHEME 1.
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