Rapid synthesis of 2,5-disubstituted 1,3,4-oxadiazoles under microwave irradiation

Article abstract of DOI:10.1081/SCC-100103330

A number of symmetrically 2,5-disubstituted 1,3,4-oxadiazoles are quickly prepared by the reaction of aromatic acids with hydrazine dihydrochloride in a mixture of orthophosphoric acid and phosphorus pentoxide under microwave irradiation.

Full text of DOI:10.1081/SCC-100103330

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RAPID SYNTHESIS OF 2,5-
DISUBSTITUTED 1,3,4-
OXADIAZOLES UNDER
MICROWAVE IRRADIATION
Fouad Bentiss , Michel Lagrenée & Didier Barbry a
a Université des Sciences et Technologies de Lille,
Laboratoire d’Ingénierie Moléculaire, UPRES EA
2699, Villeneuve d’Ascq, F-59655, France
Version of record first published: 09 Nov 2006.
To cite this article: Fouad Bentiss , Michel Lagrenée & Didier Barbry (2001):
RAPID SYNTHESIS OF 2,5-DISUBSTITUTED 1,3,4-OXADIAZOLES UNDER MICROWAVE
IRRADIATION, Synthetic Communications: An International Journal for Rapid
Communication of Synthetic Organic Chemistry, 31:6, 935-938
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SYNTHETIC COMMUNICATIONS, 31(6), 935–938 (2001)
RAPID SYNTHESIS OF 2,5-DISUBSTITUTED
1,3,4-OXADIAZOLES UNDER
MICROWAVE IRRADIATION
Fouad Bentiss,1 Michel Lagrenee,1 and Didier Barbry2,
*
1Laboratoire de Cristallochimie et Physicochimie du
Solide, CNRS UPRESA 8012 ENSCL, B.P. 108, F-59652
Villeneuve d’Ascq Cedex, France
2Laboratoire d’Ingenierie Moleculaire, UPRES EA 2699,
Universite des Sciences et Technologies de Lille, F-59655
Villeneuve d’Ascq, France
ABSTRACT
A number of symmetrically 2,5-disubstituted 1,3,4-oxa-
diazoles are quickly prepared by the reaction of aromatic
acids with hydrazine dihydrochloride in a mixture of ortho-
phosphoric acid and phosphorus pentoxide under microwave
irradiation.
Recent papers on the synthesis of 1,3,4-oxadiazoles1,2 prompt us to
report our results.Our interest in the preparation of these compounds stems
from their use as corrosion inhibitors.3,4 These derivatives can be prepared
by several methods under anhydrous conditions.Refluxing 1,2-diacyl-
hydrazines in phosphorus oxychloride5,6 or thionyl chloride7 affords 1,3,4-
oxadiazoles as cyclization products.In recent years, the use of microwave
irradiation to promote reactions has received considerable attention and
dramatic rate enhancements have been reported.8–11 1,3,4-Oxadiazoles
* Corresponding author.
935
Copyright & 2001 by Marcel Dekker, Inc.
www.dekker.com

936
BENTISS, LAGRENEE, AND BARBRY
have been prepared by cyclodehydration of a range of 1,2-diacylhydrazines
using flash-heating by microwave irradiation.1,12
The reaction between aromatic acids and hydrazine derivatives leads to
symmetrical 2,5-disubstituted 1,3,4-oxadiazoles.13,14 However, this reaction
requires a large amount of polyphosphoric acid and the high viscosity of the
latter makes the isolation of the final product quite difficult.This synthesis
has been carried out in an easier fashion by treatment of aromatic acids with
hydrazine dihydrochloride in a mixture of orthophosphoric acid, phos-
phorus pentoxide, and phosphorus oxychloride.15 In an attempt to increase
the rate of heterocyclization of aromatic acids to 1,3,4-oxadiazoles, the
above reaction was carried out under microwave irradiation as shown in
the Scheme.The phosphorus oxychloride proved to be unsuitable under
these reaction conditions.This method allows the synthesis of the solely
symmetrically 2,5-disubstituted 1,3,4-oxadiazoles.We report that this reac-
tion takes place in good yields and rapidly under microwave irradiation.
Generally, complete conversion of the aromatic acids to the oxadiazoles was
achieved within several minutes (Table).No significant by-products were
detectable by NMR spectroscopy.Superheating of the solvent under micro-
wave irradiation may lead to the observed rate enhancement.16
a Ar ¼ C6H5
g Ar ¼ 4-HOC6H4
h Ar ¼ 3-CH3C6H4
i Ar ¼ 4-CH3C6H4
j Ar ¼ 2-ClC6H4
k Ar ¼ 4-ClC6H4
b Ar ¼ 3-CH3OC6H4
c Ar ¼ 4-CH3OC6H4
d Ar ¼ 3-pyridyl
e Ar ¼ 4-pyridyl
f Ar ¼ 2-HOC6H4
EXPERIMENTAL
A mixture of the corresponding aromatic acid 1 (0.01 mole) and hydra-
zine dihydrochloride (1.05 g, 0.01 mole) was slowly added under stirring to a
mixture of orthophosphoric acid 85% (6.5 mL) and phosphorus pentoxide
(4.26 g, 0.015 mole) in a quartz cylindrical flask, and then was introduced in
a Synthewave 402 monomode microwave oven under a reflux condenser and
irradiated for 2–5 min (60 W) at 130ꢀC.After cooling, the reaction mixture

1,3,4-OXADIAZOLES
937
Table 1. Data for the Synthesis of 2.5-Diaryl-1,3,4-oxadiazoles 2a–k Under
Microwave Irradiation
Microwave
Irradiation
Classical
Heating14
M.p. (ꢀC)
Time
(min)
Yield
(%)
Time
(h)
Yield
(%)
This
Work
Lit
(ref)
Compound
Ar
2a
2a
2b
2c
2d
2e
2f
2g
2h
2i
C6H5
C6H5
3-CH3OC6H4
4-CH3OC6H4
3-pyridyl
2
5
5
5
5
5
5
5
5
5
5
5
80
94
91
92
67
72
64
30
97
98
96
95
1.5
92
138
13814
87.5
161.5
188
189
209
350
72
175
95
242
87.515
16217
18814
18915
20914
35015
7215
17414
9413
24213
2.5
2
60
30
4-pyridyl
2-HOC6H4
4-HOC6H4
3-CH3C6H4
4-CH3C6H4
2-ClC6H4
2j
2k
4-ClC6H4
was poured over crushed ice with stirring to yield a solid product that was
filtered off, washed with a 5% solution of sodium hydrogen carbonate and
water, dried in air, and recrystallized from ethanol.Yields are given in Table
1.Products were identified by 1H and 13C NMR, MS, and IR spectroscopy.
Data were in agreement with literature values.
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938
BENTISS, LAGRENEE, AND BARBRY
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Received in the U.K. March 16, 2000