Synthesis of substituted 1,3,4-oxadiazoles under microwave irradiation

Article abstract of DOI:10.1080/10426500500269877

A series of substituted 1,3,4-oxadiazoles were synthesized by the cyclization of 2,6-pyridine dicarboxylic acid, 5-(4′-carboxyl-phenyl)-2- furanylcarboxylic acid, or p-phthalic acid, and aryl hydrazines in the presence of phosphorus oxychloride under the

Full text of DOI:10.1080/10426500500269877

Phosphorus, Sulfur, and Silicon, 181:627–630, 2006
Copyright © Taylor & Francis Group, LLC
ISSN: 1042-6507 print / 1563-5325 online
DOI: 10.1080/10426500500269877
Synthesis of Substituted 1,3,4-Oxadiazoles Under
Microwave Irradiation
Xicun Wang
Juan Liu
Zheng Li
Gansu Key Laboratory of Polymer Materials, Northwest Normal
University, Lanzhou, Gansu, P.R. China
A series of substituted 1,3,4-oxadiazoles were synthesized by the cyclization of 2,6-
pyridine dicarboxylic acid, 5-(4 ꢀ-carboxyl-phenyl)-2-furanylcarboxylic acid, or p-
phthalic acid, and aryl hydrazines in the presence of phosphorus oxychloride under
the condition of microwave irradiation.
Keywords 1,3,4-oxadiazoles; microwave irradiation; synthesis
INTRODUCTION
Substituted 1,3,4-oxadiazoles are widely applied in medicine and agri-
culture; for example, they are used as psychotropic drugs,1 antiinflam-
matory2 reagents, pesticides, and insecticidal,3 fluorescence,4 and plant
growth reagents5 etc. Meanwhile, pyridine and furan derivatives6 also
have attracted much attention due to their anticancer,2 antihyperte-
nsion,5 and antifungal7 activity.
The conventional methods of the synthesis of 1,3,4-oxadiazloes are as
follows: (1) the cyclization of 1,4-disubstituted thiosemicarbazide in the
presence of either I2/NaOH8 or dicyclohexycarbodiimide (DCC),9,10 and
(2) the condensation of acid hydrazide with aromatic acids or cyanogen
bromide under a severe condition. These methods are inconvenient as
Received February 15, 2005; accepted May 24, 2005.
The authors thank the Scientific and Technological Innovation Engineering depart-
ment of the Northwest Normal University (NWNU-KJCXGC-02-08); Natural Science
Foundation of Gansu Province (ZS021-A25-006-Z); Environmental Protection Foundation
of Gansu Province (GH-2003-19), and Youth Foundation of Northwest Normal University
(NWNU-03-01) for financial support of this work.
Address correspondence to Xicun Wang, Northwest Normal University, Gansu Key
Laboratory of Polymer Materials, College of Chemistry and Chemical Engineering,
Lanzhou, 730070 Gansu, P.R. China. E-mail: wangxicun@nwnu.edu.cn
627

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X. Wang et al.
they require heating of the reactants for an extended period of time.
Moreover, the yield is frequently only moderate or low.
Microwave technique, meanwhile, has been widely used for a va-
riety of organic reactions,11,12 such as Claisen, cyclization, oxidation,
Diels-Alder reaction, hydrolysis, esterification, etherification, and so
on. Many reviews13−15 have been published in favor of its considerable
accelerations of the reaction rates and satisfactory yields.
RESULTES AND DISCUSSION
In view of this, we report herein the preparation of a new series of substi-
tuted 1,3,4-oxadiazoles using a microwave technique with the objective
of obtaining new biologically active compounds. The synthetic route is
shown in Scheme 1.
SCHEME 1
The reaction of 2,6-pyridine dicarboxylic acid, p-phthalic acid, and 5-
(4ꢀ-carboxyl-phenyl)-2-furanylcarboxylic acid with aryl hydrazines cat-
alyzed by pyridine on exposure to microwave irradiation in the pres-
ence of phosphorus oxychloride resulted in a series of substituted 1,3,4-
oxadiazoles. The results are shown in Tables I and II.
EXPERIMENTAL
Melting points were determined on a XT-4 thermal apparatus and the
m.p. are uncorrected. 1H NMR spectra were obtained on a Avanci-D2X-
200 instrument using DMSO-d6 as a solvent and TMS as internal stan-
dard. IR spectra were recorded using KBr pellets on a Nicolet AVATAR
360 FT-IR. Elemental analyses were performed on a Carlo-Erba 1106
Elemental Analysis instrument. The acids and aroyl hydrazines16 were
prepared according to literature methods.

Synthesis of Substituted 1,3,4-Oxadiazoles
629
TABLE I The Physical Data of 1,3,4-Oxadiazoles Under Microwave
Irradiation
Elemental Analysis % (Found)
Yield M.P.
(%)
Ar
Mol. formula
(◦C)
C
H
N
Id 3-O2NC6H4 C22H12N6O6
Ig 4-OCH3C6H4 C24H18N4O4
86
83
75
79
>300 57.86(57.90) 2.74(2.65) 18.31(18.41)
>300 67.66(67.60) 4.13(4.25) 13.19(13.14
>300 42.58(42.75) 2.01(1.96) 9.13(9.06)
>300 42.79(42.75) 1.84(1.96) 8.99(9.06)
>300 57.68(57.82) 2.47(2.54) 16.16(16.05)
>300 55.03(55.15) 2.35(2.42) 21.58(21.44)
>300 64.71(63.64) 3.98(4.01) 16.26(16.39)
Ih 2-IC6H4
Ii 4-IC6H4
IIb 2-ClC6H4
C22H12N4O2I2
C22H12N4O2I2
C21H11N5O2Cl2 85
IId 3-NO2 C6H4 C21H11N7O6
IIg 4-OCH3C6H4 C23H17N5O4
91
87
IIIa C6H5
C26H16N4O3
89 269–271 72.38(72.22) 3.70(3.73) 13.05(12.96)
IIIc 4-ClC6H4
IIIe 4-NO2 C6H4 C26H14N6O7
IIIf 3-CH3C6H4 C28H20N4O3
C26H14N4O3Cl2 72
>300 62.15(62.29) 2.69(2.81) 11.34(11.18)
74 279–281 59.63(59.78) 2.61(2.70) 16.14(16.09)
78 223–225 73.19(73.03) 4.35(4.38) 12.03(12.17)
General Procedure for the Preparation of 1,3,4-Oxadiazoles
A mixture of 5-(4ꢀ-carboxyphenyl)-2-furanylcarboxylic acid (1 mmol) or
2,6-pyridine dicarboxylic acid (1 mmol), aryl hydrazines (2 mmol), phos-
phorus oxychloride (6 mL), and 2 drops of pyridine was irradiated in a
microwave oven (490 W) for 8 min. When it was cooled to r.t., some pieces
of ice were added and the mixture stood for 2–4 h. The precipitate was
TABLE II The IR and 1H NMR Data of 1,3,4-Oxadiazoles Under
Microwave Irradiation
IR/cm−1
1HNMR
Entry
C
N
N
C
O
(DMSO-d6) δ
I-d
I-g
I-h
I-i
1623 1546 1487 1091 7. 62–8.31 (m, 12H, Ar-H)
1614 1530 1446 1074 3.93 (s, 6H, CH3) 7.41–8.12 (m, 12H, Ar-H)
1619 1534 1476 1083 7.54–8.17 (m, 12H, Ar-H)
1617 1538 1479 1085 7.52–8.19 (m, 12H, Ar-H)
II-b
II-d
II-g
1603 1530 1479 1095 8.32–8.51 (m, 3H, C5H3N) 7.63–8.24 (m, 8H, Ar-H)
1612 1533 1485 1091 8.37–8.65 (m, 3H, C5H3N) 7.75–8.37 (m, 8H, Ar-H)
1607 1529 1468 1089 3.86 (s, 6H, CH3) 8.39–8.52 (m, 3H, C5H3N) 7.58–8.18
(m, 8H, Ar-H)
III-a
III-c
III-e
III-f
1608 1537 1469 1087 7.24–8.30 (m, 16H, Ar-H, and Fu-H)
1613 1541 1457 1086 7.25-8.23 (m,14H, Ar-H, and Fu-H)
1607 1534 1466 1080 7.33-8.41 (m,14H, Ar-H, and Fu-H)
1612 1537 1465 1075 2.44 (s, 6H, CH3) 7.24–8.21 (m, 14H, Ar-H, and Fu-H)

630
X. Wang et al.
collected by filtration and washed with a saturated sodium carbonate
solution (2 × 10 mL) and water (3 × 10 mL). The product was recrys-
tallized from DMF and EtOH.
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