Microwave-assisted one-step synthesis of 2,5-disubstituted-1,3,4- oxadiazoles using 1,4- bis(triphenylphosphonium)-2-butene peroxodisulfate

Article abstract of DOI:10.13005/ojc/290448

A series of 1,3,4-oxadiazoles were efficiently synthesized from the cyclization-oxidation reaction of acyl hydrazones by using 1,4- bis(triphenylphosphonium)-2-butene peroxodisulfate as an oxidant in solvent-free medium under microwave irradiation.

Full text of DOI:10.13005/ojc/290448

ISSN: 0970-020 X
CODEN: OJCHEG
2013, Vol. 29, No. (4):
Pg. 1627-1630
ORIENTAL JOURNAL OF CHEMISTRY
An International Open Free Access, Peer Reviewed Research Journal
www.orientjchem.org
Microwave-Assisted One-Step Synthesis of 2,5-Disubstituted-
1,3,4-Oxadiazoles Using 1,4- Bis(triphenylphosphonium)-2-
Butene Peroxodisulfate
MARYAM GORJIzADEH1*, MOzHGAN AFSHARI1 and SIMIN NAzARI2
1Department of Chemistry, Shoushtar Branch, Islamic Azad University,
Shoushtar Iran, 64517-41117, Iran.
2Department of Chemistry, Sousangerd Branch, Islamic Azad University, Sousangerd, Iran.
*Corresponding author. E-mail: gorji80@yahoo.com
http://dx.doi.org/10.13005/ojc/290448
(Received: September 29, 2013; Accepted: November 09, 2013)
ABSTRACT
A series of 1,3,4-oxadiazoles were efficiently synthesized from the cyclization–oxidation
reaction of acyl hydrazones by using 1,4-bis(triphenylphosphonium)-2-butene peroxodisulfate as
an oxidant in solvent-free medium under microwave irradiation.
Key words: Oxadiazole, Thiadiazole, 1,4-bis(triphenylphosphonium)-2-butene peroxodisulfate,
Microwave irradiation, Solvent-free synthesis.
INTRODUCTION
advantage of rapid reaction rate, high yield and
simple work-up procedure.
Since 1960 when Toda et al.,1 first
reported the application of solid supports in organic
chemistry, the use of this technique has been under
investigation.2 Organic oxides such as silica gel,
alumina, etc. are used as solid acidic catalysts in
a variety of condensation reactions.3 Microwave
energy has also developed into a useful technique
for a variety of applications in organic synthesis,4
especially for the solvent-free reactions5 since the
solvent-free MW-assisted reactions can provide an
opportunity to work with open vessels thus avoiding
the risk of high pressure development and increasing
the potential of such reaction to upscale, and has
In recent years 1,3,4-oxadiazole derivatives
have received significant attention and have been
increasingly investigated due to their diverse range
of biological properties. They exhibit, for example,
antimicrobial,6 antimycobacterial,7 anticancer,8-9
antiinflammatory,10 carbonic anhydrase inhibiting
effect,11 antianxiety, antidepressant.12 Several
methods have been reported in the literature
for the synthesis of 1,3,4-oxadiazoles. These
protocols are routinely multi step in nature. The
most general method involves the cyclization of
diacylhydrazides with a variety of reagents, such

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GORJIzADEH et al., Orient. J. Chem., Vol. 29(4), 1627-1630 (2013)
as triphenylphosphine,13 tosylchloride/pyridine14 or Darmstadt, Germany.The purity determination of the
phosphorous oxychloride,15-16 usually under harsh products and reaction monitoring were accomplished
reaction conditions.The oxidation of acylhydrazones by TLC on polygram SILG/UV 254 plates.
with diûerent oxidizing agents is another synthetic
route to these compounds.17 Few reliable and General Procedure for the one-pot Synthesis of
operationally facile examples have been reported 1,3,4-Oxadiazoles
for the one step synthesis of 1,3,4-oxadiazoles,
The mixture of acyl hydrazide (1 mmol),
especially from readily available aldehydes and acid aromatic aldehyde (1 mmol), BTPPDS (1 mmol) and
hydrazides.However, these protocols use expensive silica gel (3g) were finely ground with a mortar and
catalysts, and require longer times for the completion pestle.The mixture was then subjected to microwave
of the reactions.
irradiation in an open Pyrex beaker for 25 min at
450W.Cold water (5 mL) was added and the mixture
Peroxodisulfateionisanexcellentandversatile was extracted with dichloromethane. The combined
oxidant; used mostly for the oxidation of compounds in organic layers solution was dried over MgSO4. The
aqueous solution.18 In spite of the great convenience solvent was concentrated in vacuo; the resulting
of using K2S2O8, Na2S2O8 or (NH4)2S2O8 and product was recrystallized from dichloromethane to
relatively high oxidation potential, many oxidations give the desired product (Table 1).
by peroxodisulfate do not proceed at a convenient
rate. The decomposition of the peroxodisulfate ion
requires strong mineral acids and heavy metal ions19
as catalysts and also protic and polar solvents are
RESULTS AND DISCUSSION
1,4-bis(triphenylphosphonium)-2-butene
needed, so the modification of K2S2O8, Na2S2O8 or peroxodisulfate was readily prepared by adding an
(NH4)2S2O8 has attracted a great deal of attention.
aqueous solution of potassium peroxodisulfate to a
solution of 1,4-bis(triphenylphosphonium)-2-butene
Recently 1,4- bis(triphenylphosphonium)- dichloride in water.It is a very stable white solid which
2-butene peroxodisulfate (BTPPDS), 20 as an can be stored for months without losing its activity. It
inexpensive and environmentally safe oxidation
Table 1: One-pot synthesis of
reagent has been used for synthesis of ²-nitrato
alcohols, iodination of aromatic compound, and
aromatization of Hantzsch 1,4-dihydropyridines in
high yields.In this paper, we describe an eco-friendly
new method that utilizes BTPPDS on the surface of
silica gel as an oxidant for the one-pot synthesis of
2,5-disubstituted 1,3,4-oxadiazoles under solvent-
free and microwave irradiation condition.
2,5-disubstituted 1,3,4-oxadiazolesa
No.
R
Yieldb (%)
1
2
3
4
5
6
7
8
Ph
68
80
88
67
79
85
90
76
81
87
75
76
35
40
4-Cl–C6H4
4-Me–C6H4
4-MeO–C6H4
4-O2N–C6H4
3-O2N–C6H4
4-I–C6H4
2,4-Cl2–C6H3
3-Cl–C6H4
4-Br–C6H4
2-Furyl
EXPERIMENTAL
All products were characterized by
comparison of their physical data, IR, 1HNMR, and
13C NMR spectra with authentic samples.21-22 1
H
9
NMR and 13C NMR spectra were taken on a 400
MHz Brucker Spectrometer. Microwave reactions
were conducted in a microwave oven (Milestone-
MicroSynth, USA).
10
11
12
13
14
3-Pyridyl
n-Propyl
n-Heptyl
1,4-Bis(triphenylphosphonium)-2-butene
peroxodisulfate was prepared as described in
our previous papers18 and other chemicals were
purchased from the Merck Chemical Company,
a Products were identified by comparison of their physical
and spectral data with those of authentic samples
b Isolated yields based on the aldehyde

GORJIzADEH et al., Orient. J. Chem., Vol. 29(4), 1627-1630 (2013)
1629
Scheme 1
is soluble in acetonitrile, methanol, dichloromethane,
chloroform and ethyl acetate and slightly soluble in
CCl4 and diethyl ether.
their corresponding products in high isolated yields
(Scheme 1, Table 1).
This method appeared to be rapid and
economical, with a wide range of applications. The
reaction was found to proceed smoothly under
microwave irradiation within 25 min whereas under
reflux conditions, 12 h were required.19The products
were isolated by simple cold aqueous work-up
followed by either solvent extraction or precipitation
and were finally purified by column chromatography
wherever necessary, to afford pure 2,5- disubstituted
1,3,4-oxadiazole.
First, optimization of the reaction conditions
for preparation of 1,3,4-oxadiazoles was investigated.
Therefore, benzaldehyde (1 mmol) was reacted with
acyl hydrazide using different solid supports including
silica gel, alumina, and montmorillonite K10.Different
combinations of 1,4- bis(triphenylphosphonium)-2-
butene peroxodisulfate, and irradiation power were
also studied to achieve the maximum chemical yield.
From these results, it appeared that when silica gel
was the solid support and the microwave power was
450 W, the reaction gave the highest yield within
25 min. According to obtained results, this oxidant
acted very efficiently and 1 mmol of the oxidant is
enough to convert different aldehydes (1 mmol)
carrying electron donating or withdrawing groups to
Aliphatic aldehydes were also investigated
in this reaction but unfortunately, a mixture of
compounds was produced and the desired
oxadiazoles were obtained in low yields (Table 1,
entries 13 and 14).
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