Microwave-assisted synthesis of 2-styryl-1,3,4-oxadiazoles from cinnamic acid hydrazide and triethyl orthoesters

Article abstract of DOI:10.1016/j.tetlet.2011.10.152

A novel and efficient synthesis of 2-styryl-1,3,4-oxadiazoles by cyclocondensation of cinnamic acid hydrazide and triethyl orthoesters under microwave irradiation is reported.

Full text of DOI:10.1016/j.tetlet.2011.10.152

Tetrahedron Letters 53 (2012) 76–77
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Tetrahedron Letters
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Microwave-assisted synthesis of 2-styryl-1,3,4-oxadiazoles from cinnamic
acid hydrazide and triethyl orthoesters
⇑
´
Agnieszka Kudelko , Wojciech Zielinski
Department of Chemical Organic Technology and Petrochemistry, The Silesian University of Technology, Krzywoustego 4, PL-44100 Gliwice, Poland
a r t i c l e i n f o
a b s t r a c t
Article history:
A novel and efficient synthesis of 2-styryl-1,3,4-oxadiazoles by cyclocondensation of cinnamic acid
hydrazide and triethyl orthoesters under microwave irradiation is reported.
Ó 2011 Elsevier Ltd. All rights reserved.
Received 24 August 2011
Revised 28 October 2011
Accepted 28 October 2011
Available online 4 November 2011
Keywords:
1,3,4-Oxadiazole
Cinnamic acid hydrazide
Microwave irradiation
Cyclization
1,3,4-Oxadiazoles belong to an important class of bioactive com-
pounds with a broad spectrum of pharmaceutical and agricultural
applications.1 Conjugated macrocyclic arrangements possessing a
1,3,4-oxadiazole backbone exhibit interesting electron-transfer or
luminescent properties and are used in organic light-emitting
diodes (OLED), optical brighteners, and laser dyes.2 One subgroup
of the 1,3,4-oxadiazole family of potential interest in display tech-
nology is 2-styryl-1,3,4-oxadiazole and its derivatives.3
The most common approach toward the preparation of this par-
ticular group of compounds involves coupling of acylhydrazides
with carboxylic acids in the presence of reagents such as CDI as
the activating agent and Ph3P/CBr4, cyanuric chloride as the coupling
reagent and an indium catalyst, or by the reaction of acylhydrazides
with N-acylbenzotriazoles.4 Another convenient method comprises
cyclodehydration of 1,2-diacylhydrazines promoted by POCl3.5
Recently, we reported on the selective and efficient synthesis of
2-(1-phenyl-1-N-protected-aminomethyl)-1,3,4-oxadiazoles via
the reactions of N-protected phenylglycine hydrazides and triethyl
orthoesters.6 In continuation of our interest on the application of
acid hydrazides as potent reagents for the synthesis of heterocy-
cles, we studied the preparation of 2-styryl-1,3,4-oxadiazoles uti-
lizing cinnamic acid hydrazide and triethyl orthoesters. To the
best of our knowledge, the synthesis of 2-styryl derivatives making
use of the above-mentioned reagents has not been reported.
The key compound in the synthesis of 2-styryl-1,3,4-oxadiazoles
was cinnamic acid hydrazide (2). This molecule was obtained from
commercially available cinnamic acid (1) according to a short
procedure described in the literature.7 First, acid 1 was converted
into its potassium salt and then treated with ethyl chloroformate
and finally hydrazine hydrate. The reaction conducted at low
temperature resulted in the formation of the desired hydrazide 2
in a 73% yield (Scheme 1). It is worth mentioning that typical syn-
thetic procedures for hydrazides, based on hydrazine hydrate and
acid derivatives such as esters or acid chlorides, failed in the case
of cinnamic acid hydrazide and gave 3-hydrazino-3-phenylpropi-
onic acid hydrazide, 3-phenyl-5-pyrazolidone,7 or symmetrically
substituted 1,2-bis(3-phenyl-2-propenoyl)hydrazine, respectively.8
Our first trials concerning the conventional heating (method A)
of the starting hydrazide 2 with excess triethyl orthoester (R = H,
Me, Et, Ph, Scheme 2) in glacial acetic acid, resulted in the forma-
tion of the desired 2-styryl-1,3,4-oxadiazoles in high yields (80–
95%, Table 1). Generally, the reaction yields increased with the
increasing bulk of the substituent on the orthoester and the best
result was obtained in the case of the reaction conducted with tri-
ethyl orthobenzoate (3d, 95%, Table 1). A similar trend was ob-
served in previously studied reactions starting from N-protected
a
-aminocarboxylic acids and orthoesters.6
However, long the reaction times (9–40 h, Table 1) and the
formation of side products made the conventional method less
attractive in comparison to others. We thus decided to carry out
O
O
Ph
OH
i-iii
Ph
NHNH2
(73%)
2
1
⇑
Corresponding author. Tel.: +48 32 2371729; fax: +48 32 2371021.
E-mail address: Agnieszka.Kudelko@polsl.pl (A. Kudelko).
Scheme 1. Synthesis of cinnamic acid hydrazide. Reagents and conditions: (i) KOH,
H2O; (ii) ClCOOC2H5, CH2Cl2, pyridine, 0 °C, 2 h; (iii) N2H4ꢀH2O, CH2Cl2, 0 °C, 12 h.
0040-4039/$ - see front matter Ó 2011 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2011.10.152

´
77
A. Kudelko, W. Zielinski / Tetrahedron Letters 53 (2012) 76–77
O
R
O
O
method A and B
AcOH
+
NHNH2
R
Ph
O
N
N
3a-d
Ph
O
2
R = H, Me, Et, Ph
Scheme 2. Reaction of cinnamic acid hydrazide with triethyl orthoesters: method A—conducted using excess orthoester in the presence of AcOH (reflux, 9–40 h); method B—
conducted under microwave irradiation at 125 °C, 10 min.
Ronad, P.; Mamledesai, S.; Vishwanathswamy, A. H. M.; Satyanarayana, D. Med.
Chem. Res. 2010. doi:10.1007/s00044-010-9494-z; (e) Sangshetti, J. N.;
Chabukswar, A. R.; Shnide, D. B. Bioorg. Med. Chem. Lett. 2011, 21, 444; (f)
Bhandari, S. V.; Bothara, K. G.; Raut, M. K.; Patil, A. A.; Sarkate, A. P.; Mokale, V. J.
Bioorg. Med. Chem. Lett. 2008, 16, 1822; (g) Zheng, X.; Li, Z.; Wang, Y.; Chen, W.;
Huang, Q.; Liu, C.; Song, G. J. Fluorine Chem. 2003, 123, 163; (h) Zou, X. J.; Lai, L.
H.; Zhang, Z. X. J. Agric. Food Chem. 2002, 50, 3757.
Table 1
Products of the reaction of cinnamic acid hydrazide (2) with triethyl orthoesters
Product
R
Method A
Method B
Mp (°C)
Yielda (%) Time (h) Yielda (%) Time (min)
3a
3b
3c
3d
H
80
40
38
30
9
95
96
95
98
10
10
10
10
170–172
112–114
83–85
2. (a) Schulz, B.; Orgzall, I.; Freydank, A.; Xii, C. Adv. Colloid Interface Sci. 2005, 116,
143; (b) Chen, Z. K.; Meng, H.; Lai, Y. H.; Huang, W. Macromolecules 1999, 32,
4351; (c) Tamoto, N.; Adachi, C.; Nagai, K. Chem. Mater. 1997, 9, 1077; (d) Lv, H.
S.; Zhao, B. X.; Li, J. K.; Xia, Y.; Lian, S.; Liu, W. Y.; Gong, Z. L. Dyes Pigments 2010,
86, 25; (e) Tao, Y.; Wang, Q.; Shang, Y.; Yang, C.; Ao, L.; Qin, J.; Ma, D.; Shuai, Z.
Chem. Commun. 2009, 77.
Me 82
Et
Ph
86
95
128–1304c
a
Yield with respect to the starting hydrazide 2.
3. (a) Mikroyannidis, J. A.; Spiliopoulos, I. K.; Kasimiris, T. S.; Kulkarni, A. P.;
Jenekhe, S. A. Macromolecules 2003, 36, 9295; (b) Manjunatha, M. G.; Adhikari, A.
V.; Hedge, P. K.; Sandeep, C. S. S.; Philip, R. J. Electron. Mater. 2010, 39, 2711.
4. (a) Rajapakse, H. A.; Zhu, H.; Young, M. B.; Mott, B. T. Tetrahedron Lett. 2006, 47,
4827; (b) Kangani, C. O.; Day, B. W. Tetrahedron Lett. 2009, 50, 5332; (c)
Katritzky, A. R.; Mohapatra, P. P.; Huang, L. Arkivoc 2008, ix, 62.
the same reactions under microwave irradiation (method B). A ten-
minute irradiation time was sufficient to complete the reaction and
produce the title 1,3,4-oxadiazoles 3a–d exclusively, in excellent
yields, as summarized in Table 1. The new products were charac-
terized by elemental analysis and spectroscopic methods.9
In conclusion, we have developed an easy and efficient method
to synthesize 5-substituted 2-styryl-1,3,4-oxadiazoles from cin-
namic acid hydrazide and commercially available triethyl orthoes-
ters.9 This method has the advantage of providing the desired
products rapidly and in high yields which makes it a useful addi-
tion to the existing synthetic procedures.
5. Ignatenko, O. A.; Kuznetsov, M. A.; Selivanov, S. I. Russ. J. Org. Chem. 2007, 43,
1042.
´
6. Kudelko, A.; Zielinski, W. Tetrahedron 2009, 65, 1200.
7. Godtfredsen, W. O.; Vangedal, S. Acta Chem. Scand. 1955, 9, 1498.
8. Wagner-Jauregg, T.; Zirngibl, L.; Demolis, A.; Günther, H.; Tam, S. W. Helv. Chim.
Acta 1969, 52, 1672.
9. Representative procedure—(method B): A reaction mixture composed of cinnamic
acid hydrazide (2) (0.50 g, 3.0 mmol), triethyl orthopropionate (1.2 mL, 1.06 g,
6.0 mmol), and glacial AcOH (2 mL) was placed into a 10 mL thick-walled glass
tube and crimp-sealed. The reaction vessel was placed in a CEM Discover
microwave-enhanced synthesis system operating at 125 5 °C, power 250 W
and irradiated for 10 min. After cooling, the excess orthoester and AcOH were
evaporated under reduced pressure. The crude product was purified by column
chromatography over silica gel using an eluent of benzene/AcOEt, 1:5, v/v. The
pure 5-ethyl-2-styryl-1,3,4-oxadiazole (3c) was obtained in a 95% yield as a
white solid; mp 83–85 °C; Rf (benzene/AcOEt, 1:5 v/v) 0.55; [Found: C, 71.89; H,
5.98; N, 13.95. C12H12N2O requires C, 71.97; H, 6.05; N, 13.98%]. 1H NMR
(300 MHz, DMSO-d6): d 1.29 (3H, t, J 7.5 Hz, CH2CH3), 2.89 (2H, q, J 7.5 Hz,
CH2CH3), 7.29 (1H, d, J 16.2 Hz, Ph–CH@CH–), 7.37–7.45 (3H, m, Ph: H30, H40,
H50), 7.53 (1H, d, J 16.2 Hz, Ph–CH@CH–), 7.73–7.77 (2H, m, Ph: H20, H60). 13C
NMR (DMSO-d6): d 10.4 (CH2CH3), 18.4 (CH2CH3), 110.2 (Ph–CH@CH–), 127.7,
Supplementary data
Supplementary data associated with this article can be found, in
the online version, at doi:10.1016/j.tetlet.2011.10.152.
References and notes
1. (a) Suwin´ ski, J.; Szczepankiewicz, W. In Comprehensive heterocyclic chemistry III;
Katritzky, A. R., Ramsden, C. A., Scriven, E. F. V., Taylor, R. J. K., Eds.; Elsevier
Science Ltd: Oxford, 2008; Vol. 5, p 398; (b) Amir, M.; Shikha, K. Eur. J. Med.
Chem. 2004, 39, 535; (c) Almasirad, A.; Tabatabai, S. A.; Faizi, M.; Kebriaeezadeh,
A. Bioorg. Med. Chem. Lett. 2004, 14, 6057; (d) Ingale, N.; Maddi, V.; Palkar, M.;
128.9, 129.8, 134.7 (Ph), 138.1(Ph–CH@CH–), 163.8 (C2), 167.0 (C5). IR (ATR)
3159, 3060, 2940, 2161, 1979, 1648, 1570, 1524, 1479, 1446, 1397, 1380, 1188,
1075, 1032, 1001, 991, 976, 923, 856, 801, 788, 757, 707, 688, 674 cmꢁ1
m:
.