Microwave accelerated solvent-free synthesis of 1,3,4-oxadiazoles using polymer supported dehydration reagent

Article abstract of DOI:10.1081/SCC-200026654

2-Aryl-5-(coumarin-3′-yl)-1,3,4-oxadiazoles are efficiently synthesized by microwave accelerated solvent-free procedure in high yield via the condensation of coumarin-3-carboxylic acid with (un)substituted benzoic acid hydrazides using poly(ethylene glyco

Full text of DOI:10.1081/SCC-200026654

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Microwave Accelerated
Solvent‐Free Synthesis
of 1,3,4‐Oxadiazoles
Using Polymer Supported
Dehydration Reagent
Zheng Li a , Jinlan Yu a , Runbo Ding a , Zhiyuan
Wang a & Xicun Wang a
a College of Chemistry and Chemical Engineering,
Northwest Normal University, Lanzhou, Gansu,
730070, P.R. China
Published online: 06 Jan 2011.
To cite this article: Zheng Li , Jinlan Yu , Runbo Ding , Zhiyuan Wang & Xicun
Wang (2004) Microwave Accelerated Solvent‐Free Synthesis of 1,3,4‐Oxadiazoles
Using Polymer Supported Dehydration Reagent, Synthetic Communications: An
International Journal for Rapid Communication of Synthetic Organic Chemistry,
34:16, 2981-2986, DOI: 10.1081/SCC-200026654
To link to this article: http://dx.doi.org/10.1081/SCC-200026654
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SYNTHETIC COMMUNICATIONSw
Vol. 34, No. 16, pp. 2981–2986, 2004
Microwave Accelerated Solvent-Free
Synthesis of 1,3,4-Oxadiazoles Using
Polymer Supported Dehydration Reagent
*
Zheng Li, Jinlan Yu, Runbo Ding, Zhiyuan Wang,
and Xicun Wang
College of Chemistry and Chemical Engineering, Northwest Normal
University, Lanzhou, Gansu, P.R. China
ABSTRACT
2-Aryl-5-(coumarin-30-yl)-1,3,4-oxadiazoles are efficiently synthesized
by microwave accelerated solvent-free procedure in high yield via the
condensation of coumarin-3-carboxylic acid with (un)substituted
benzoic acid hydrazides using poly(ethylene glycol) (PEG) supported
dichlorophosphate as dehydration reagent.
Key Words: 1,3,4-Oxadiazole; Polymer supported reagent; Microwave
irradiation; Solvent-free.
*
Correspondence: Zheng Li, College of Chemistry and Chemical Engineering, North-
west Normal University, Lanzhou, Gansu 730070, P.R. China; E-mail: lizheng@nwnu.
edu.cn.
2981
DOI: 10.1081/SCC-200026654
0039-7911 (Print); 1532-2432 (Online)
www.dekker.com
Copyright # 2004 by Marcel Dekker, Inc.

2982
Li et al.
INTRODUCTION
1,3,4-Oxadiazole derivatives have been of interest to the medicinal chem-
ists for many years because of their antimicrobial,[1] antimitotic,[2] antiinflam-
matory,[3] psychotropic,[4] antiaflatoxigenic,[5] and anticonvulsant[6]
activities. 1,3,4-Oxadiazoles have been synthesized by traditional method-
ology via several approaches, three of the more popular being the cyclization
of diacylhydrazides,[7] the cyclization of acylthiosemicarbazides,[8] and the
oxidation of acylhydrozones.[9] However, long reaction procedure, extended
reaction period at elevated temperature and harsh reagents, e.g., SOCl2,[7]
polyphosphoric acid[10] or sulfuric acid,[11] are usually encountered. Very
recently, Brain[12] has reported a mild strategy for 1,3,4-oxadiazoles, which
utilizes easily separated and recoverable polymer supported Burgess reagent
as condensation reagent, and therefore represents a good alternative to
1,3,4-oxadiazoles. In this paper, we report a one-step solvent-free protocol
for 1,3,4-oxadiazoles using more efficient poly(ethylene glycol) (PEG) supp-
orted dichlorophosphate as dehydration reagent.
The reaction of PEG-6000 with 2 eq. of phosphorus oxychloride in the
presence of triethylamine afforded PEG supported dichlorophosphate in
almost quantitative yield. The reaction proceeded at 0–58C at the beginning,
and at room temperature or 408C since then. The product was obtained only by
precipitation with ether. The finely mixed solid of coumarin-3-carboxylic acid
with equivalent of various (un)substituted benzoic acid hydrazides and 1.2 eq.
of PEG supported dichlorophosphate was irradiated in microwave oven to
readily afford 2-aryl-5-(coumarin-30-yl)-1,3,4-oxadiazoles (1a–i) in high
yield (Sch. 1). The whole courses of reactions were easily monitored by
TLC. All reactions can be completed within 6–8 min at 490-W microwave
power with slightly quick rate for aryl rings bearing electron-donating
groups and slightly slow for those bearing electron-withdrawing groups.
Scheme 1.

Synthesis of 1,3,4-Oxadiazoles
2983
The desired products were easily isolated by washing away the polymer
reagent with water, and the PEG was readily recovered from the aqueous sol-
ution by extraction. The results are outlined in Table 1.
In conclusion, we have devised a rapid, one-step and high yielding proto-
col for the preparation of 1,3,4-oxadiazoles including coumarin substituent.
The features of simple work-up procedure, utilization of easily preparative
and recoverable polymer supported reagent make this method suitable to
high throughput and combinatorial synthesis of 1,3,4-oxadiazoles.
EXPERIMENTAL
IR spectra were recorded using KBr pellets on a Nicolet AVATAR 360
FT-IR spectrophotometer and 1H NMR spectra on a Avanci-D2X-200 instru-
ment using CDCl3 as solvent and Me4Si as internal standard. Mass spectra
were recorded on a QP-1000A GC-MS using the impact mode (70 eV).
Elemental analyses were performed on a Vario El Elemental Analysis instru-
ment. Melting points were determined with an electrothermal micromelting
point apparatus and uncorrected. (Un)substituted benzoic acid hydrazides[13]
were prepared according to literature procedure.
Preparation of PEG Supported Dichlorophosphate
To a solution of POCl3 (0.93 mL, 10 mmol) in 20 mL of CH2Cl2, the
mixture of PEG-6000 (30 g, 10 mmol OH) and Et3N (1.67 mL, 12 mmol) in
Table 1. Solvent-free synthesis of 1a–i under MWI using PEG supported reagent.
Reaction time
(min)
M.p.
(8C)
Yield
(%)a
Compound
R
1a
1b
1c
1d
1e
1f
H
2-Cl
7
8
8
8
8
6
6
7
6
194–195
205–207
245–246
252–254
.300
223–224
202–203
294–296
.300
76
81
75
90
75
81
87
85
83
4-Cl
3-O2N
4-O2N
4-CH3O
3-CH3
4-I
1g
1h
1i
2-HO
aYields refer to the isolated products.

2984
Li et al.
80 mL of CH2Cl2 was added dropwise at 0–58C. Then the resulting solution
was stirred for 2 hr at room temperature and refluxed for additional 5 hr. The
insoluble solid was removed by filtration and the solution was concentrated to
a third of its volume. Then appropriate ether was added and the precipitate was
filtered to afford product as a white solid. Yield: 98%. M.p.: 52–538C. IR
(KBr, n, cm21): 1036 (P55O).
General Procedure for the Preparation of Compound 1a–i
The mixture of coumarin-3-carboxylic acid (1 mmol), (un)substituted
benzoic acid hydrazides (1 mmol), and PEG supported dichlorophosphate
(1.2 mmol) was mixed using a pestle and mortar until a fine and homogeneous
powder was obtained. Then the mixture was irradiated in a microwave oven
for 6–8 min irradiating time at 490-W power by means of 1 min irradiation
then 30 sec interval. The completion of reactions was monitored by TLC
using ethyl acetate, acetone, and petroleum ether (1 : 1 : 2) as eluent. Then dis-
tilled water (20 mL) was added to the resulting mixture, and the precipitate
was collected by filtration and recrystallized from EtOH to afford product.
The physical and spectral data of compounds are shown below:
1
1a. White solid. H NMR (CDCl3, 200 MHz) d 8.68 (s, 1H, 55CH),
6.89–8.04 (m, 9H, Ar-H). MS: m/z, 290 (Mþ). IR (KBr, n, cm21): 1732
(C55O), 1611, 1496 (C55N). Anal. Calcd. for C17H10N2O3: C, 70.34; H,
3.47; N, 9.65. Found: C, 70.22; H, 3.56; N, 9.71.
1
1b. White solid. H NMR (CDCl3, 200 MHz) d 8.72 (s, 1H, 55CH),
7.05–8.19 (m, 8H, Ar-H). MS: m/z, 324 (Mþ). IR (KBr, n, cm21): 1749
(C55O), 1619, 1508 (C55N). Anal. Calcd. for C17H9ClN2O3: C, 62.88; H,
2.79; N, 8.63. Found: C, 62.96; H, 2.70; N, 8.75.
1c. White solid. 1H NMR (CDCl3, 200 MHz) d 8.73 (s, 1H,55CH), 7.04–
8.20 (m, 8H, Ar-H). MS: m/z, 324 (Mþ). IR (KBr, n, cm21): 1749 (C55O),
1618, 1509 (C55N). Anal. Calcd. for C17H9ClN2O3: C, 62.88; H, 2.79; N,
8.63. Found: C, 62.79; H, 2.75; N, 8.56.
1
1d. White solid. H NMR (CDCl3, 200 MHz) d 8.76 (s, 1H, 55CH),
7.10–8.29 (m, 8H, Ar-H). MS: m/z, 335 (Mþ). IR (KBr, n, cm21): 1758
(C55O), 1626, 1516 (C55N). Anal. Calcd. for C17H9N3O5: C, 60.90; H,
2.71; N, 12.53. Found: C, 60.81; H, 2.67; N, 12.64.
1e. White solid. 1H NMR (CDCl3, 200 MHz) d 8.78 (s, 1H,55CH), 7.11–
8.30 (m, 8H, Ar-H). MS: m/z, 335 (Mþ). IR (KBr, n, cm21): 1759 (C55O),
1628, 1517 (C55N). Anal. Calcd. for C17H9N3O5: C, 60.90; H, 2.71; N,
12.53. Found: C, 60.99; H, 2.65; N, 12.45.
1f. White solid. 1H NMR (CDCl3, 200 MHz) d 8.70 (s, 1H,55CH), 7.02–
8.15 (m, 8H, Ar-H), 3.91 (s, 3H, OCH3). MS: m/z, 320 (Mþ). IR (KBr, n,

Synthesis of 1,3,4-Oxadiazoles
2985
cm21): 1746 (C55O), 1617, 1500 (C55N). Anal. Calcd. for C18H12N2O4: C,
67.50; H, 3.78; N, 8.75. Found: C, 67.62; H, 3.70; N, 8.68.
1
1g. White solid. H NMR (CDCl3, 200 MHz) d 8.66 (s, 1H, 55CH),
6.82–8.01 (m, 8H, Ar-H), 2.39 (s, 3H, CH3). MS: m/z, 304 (Mþ). IR (KBr,
n, cm21): 1729 (C55O), 1610, 1493 (C55N). Anal. Calcd. for C18H12N2O3:
C, 71.05; H, 3.97; N, 9.21. Found: C, 70.92; H, 3.91; N, 9.14.
1
1h. White solid. H NMR (CDCl3, 200 MHz) d 8.77 (s, 1H, 55CH),
7.08–8.25 (m, 8H, Ar-H). MS: m/z, 416 (Mþ). IR (KBr, n, cm21): 1751
(C55O), 1619, 1512 (C55N). Anal. Calcd. for C17H9IN2O3: C, 49.06; H,
2.18; N, 6.73. Found: C, 48.93; H, 2.15; N, 6.66.
1i. White solid. 1H NMR (CDCl3, 200 MHz) d 8.72 (s, 1H,55CH), 7.04–
8.16 (m, 8H, Ar-H). MS: m/z, 306 (Mþ). IR (KBr, n, cm21): 1748 (C55O),
1619, 1502 (C55N). Anal. Calcd. for C17H10N2O4: C, 66.67; H, 3.29; N,
9.15. Found: C, 66.76; H, 3.35; N, 9.08.
ACKNOWLEDGMENT
The authors thank the Scientific and Technological Innovation Engineer-
ing of Northwest Normal University (NWNU-KJCXGC-02-08), Natural
Science Foundation of Gansu Province (ZS021-A25-006-Z), Environmental
Protection Foundation of Gansu Province (GH2002-16) for the financial sup-
port of this work.
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Received in Japan January 19, 2004