Ultrasound-promoted greener synthesis of benzoheterocycle derivatives catalyzed by nanocrystalline copper(II) oxide

Article abstract of DOI:10.1016/j.ultsonch.2010.01.017

CuO nanoparticles provide an efficient, economic, and novel method for the synthesis of quinoxaline, benzoxazine, and benzothiazine under ultrasonic irradiation. The protocol offers advantages in terms of higher yields, short reaction times, and mild reaction conditions, with reusability of the catalyst.

Full text of DOI:10.1016/j.ultsonch.2010.01.017

Ultrasonics Sonochemistry 17 (2010) 764–767
Contents lists available at ScienceDirect
Ultrasonics Sonochemistry
journal homepage: www.elsevier.com/locate/ultsonch
Short Communication
Ultrasound-promoted greener synthesis of benzoheterocycle derivatives
catalyzed by nanocrystalline copper(II) oxide
*
Sodeh Sadjadi, Samaheh Sadjadi, Rahim Hekmatshoar
Department of Chemistry, School of Science, Alzahra University, Vanak, Tehran, Iran
a r t i c l e i n f o
a b s t r a c t
Article history:
Received 19 July 2009
Received in revised form 24 January 2010
Accepted 31 January 2010
Available online 12 February 2010
CuO nanoparticles provide an efficient, economic, and novel method for the synthesis of quinoxaline,
benzoxazine, and benzothiazine under ultrasonic irradiation. The protocol offers advantages in terms
of higher yields, short reaction times, and mild reaction conditions, with reusability of the catalyst.
Ó 2010 Elsevier B.V. All rights reserved.
Keywords:
CuO nanoparticles
Quinoxaline
Benzoxazine
Benzothiazine
Ultrasonic
1. Introduction
calls for clean procedures. Ultrasonic-assisted organic synthesis
(UAOS) as a green synthetic approach is a powerful technique that
1,4-Benzoxazin-3(4H)-one and 1,4-benzothiazin-3(4H)-one
derivatives are an interesting group of compounds both pharmaco-
logically and agriculturally. The 1,4-benzoxazin-3(4H)-one moiety
can be found in molecules which exhibit plant resistance factors
against microbial diseases and insects, analgesic, antimicrobial
and potassium channel modulating properties, whilst 1,4-benzo-
thiazin-3(4H)-ones, like semotiadil, are antihypertensive drugs,
calcium antagonists and highly potent inhibitors of LDL-oxidation
[1].
Quinoxaline not only shows their applications as dyes [2] and
building blocks in the synthesis of organic semiconductors, [3]
but also serves as useful rigid subunits in macrocyclic receptors
for molecular recognition [4] and chemically controllable switches
[5].
is being used more and more to accelerate organic reactions. UAOS
can be extremely efficient and it is applicable to a broad range of
practical syntheses. The notable features of the ultrasound ap-
proach are enhanced reaction rates, formation of purer products
in high yields, and easier manipulation. It is considered a process-
ing aid in terms of energy conservation and waste management.
When compared with traditional methods, this technique is more
convenient taking green chemistry concepts into account [10].
However, the use of ultrasound in heterocyclic system is not fully
explored. In order to expand the application of ultrasound in the
synthesis of heterocyclic compounds, we wish to report a general,
efficient and eco-friendly method for the synthesis of benzohetero-
cycle derivatives catalyzed by nanocrystalline copper(II) oxide
(Scheme 1).
Nanocrystalline metal oxides find excellent applications as ac-
tive adsorbents for gases and destruction of hazardous chemicals.
They are also gaining tremendous importance due to their distinct
catalytic activities for various organic transformations. Recently,
researchers have reported various [6–9] organic transformations
using different nanocrystalline metal oxides. These high reactivi-
ties are due to the high surface areas combined with unusually
reactive morphologies.
2. Experimental
2.1. Chemicals and apparatus
All the chemicals were obtained from Merck Company and used
as received. CuO nanoparticles were prepared according to our pre-
vious work (average size of the obtained CuO particle was 5 nm
and the mean value of surface area of the copper catalyst was
32.457 m2/g from BET analysis) [11]. Melting points were mea-
sured using a Barnstead Electrothermal melting point apparatus.
The ultrasound apparatus was cleaning bath Wiseclear 770 W
With increasing environmental consciousness in chemical re-
search and industry, the challenge for a sustainable environment
* Corresponding author. Tel.: +98 21 804 13 47; fax: +98 21 80478 61.
E-mail address: rhekmatus@yahoo.com (R. Hekmatshoar).
1350-4177/$ - see front matter Ó 2010 Elsevier B.V. All rights reserved.
doi:10.1016/j.ultsonch.2010.01.017

S. Sadjadi et al. / Ultrasonics Sonochemistry 17 (2010) 764–767
765
H
N
NH2
XH
Y
1
Y
O
CuO nano particles
RO2C
CO2R
+
Ultrasonic irradiation
X
CO2R
2
3
X= S, O, NH R= CH3, C2H5
Y = N, CH
Scheme 1.
(Seoul, Korea). The operating frequency was 40 kHz and the output
power was 200 W, estimated calorimetrically.
Table 1
Study of catalyst effect on reaction using 1a and 2a under ultrasound conditions at
room temperature.
Entry
Catalyst
Time (min)
Yield (%)
2.2. General procedure
1
2
3
4
5
6
No catalyst
CuO nanoparticles
Bulk CuO
Al2O3
Basic Al2O3
MgO
15
15
15
15
15
15
17
94
61
53
64
58
A mixture of aromatic amine (1 mmol), dialkyl acetylenedicar-
boxylate (1 mmol) and CuO nanoparticles (0.03 mmol) in 10 mL
EtOH was irradiated by ultrasound at room temperature for the re-
quired reaction time. The progress of the reaction was monitored
by TLC using n-hexane:ethylacetate (4:1) as developer. The ultra-
sonic apparatus used showed the temperature automatically so
Table 2
The reactions of 2-aminothiophenol, 2-aminophenol and o-phenylenediamines with DMAD or DEAD under ultrasonic condition at room temperature.
Entry
a
1
2
3
Time (min)
15
Yield (%)
94
Mp (°C)
Ref. Mp (°C) [2]
226–227
227
NH2
NH2
MeO2C
CO2Me
H
N
O
N
H
CO2Me
b
c
15
20
10
91
89
98
218
150
264
218
NH2
NH2
H
EtO2C
MeO2C
MeO2C
CO2Et
CO2Me
CO2Me
N
O
N
H
CO2Et
O
150
NH2
OH
H
N
O
CO2Me
O
d
263–264
NH2
SH
H
N
S
CO2Me
e
10
20
96
90
221
117
221
NH2
SH
EtO2C
CO2Et
H
N
O
S
CO2Et
O
f
117–118
MeO2C
CO2Me
N
NH2
OH
H
N
N
O
CO2Me

766
S. Sadjadi et al. / Ultrasonics Sonochemistry 17 (2010) 764–767
the temperature was controlled and fixed at room temperature by
pouring cold water in the bath in the case of any elevation of tem-
perature. After completion of the reaction, the catalyst was sepa-
rated by simple centrifugation. After evaporating the solvent, the
crude product was obtained. The product was recrystallized from
ethanol.
All products are known compounds and were identified by
comparison of their physical and spectroscopic data with those re-
ported for authentic samples [2].
thesis of 3a (the reaction of o-phenylenediamine and dimeyhyl
acetylenedicarboxylate (DMAD)) as a model reaction was carried
out in various conditions. Attempts for the synthesis of 3a under
ultrasound irradiation were examined using MgO as catalyst and
the desired product was obtained in 58% yield. A variety of catalysts
were examined. By using basic Al2O3 and Al2O3 provided 3a in 64%
and 53% yield, respectively. Moreover, low yields were obtained in
the absence of a catalyst. The CuO nanoparticles showed the best
activity, and the product 3a was obtained in 94% yield (Table 1).
The efficiency of bulk CuO catalyst was also studied for this
reaction, but the model reaction did not go to completion in
the presence of this catalyst even after long reaction times (1 h,
68%).
The increased catalytic activity of nano CuO over commercially
available bulk CuO may be attributed to the higher surface area of
nano CuO than bulk CuO as well as the higher surface concentra-
tion of the reactive sites. As seen with other metal oxides, once
they are made into nanoparticles, their reactivity is greatly en-
hanced. This is thought to be due to the morphological differences;
whereas larger crystallites have only a small percentage of the
reactive sites on the surface, smaller crystallites will possess a
much higher surface concentration of such sites [12].
2.3. Recycling of the catalyst
After completing the model reaction, the catalyst was separated
by simple centrifugation and washed three times with 10 ml por-
tions of dichloromethane and dried at 150 °C overnight and sub-
jected to a second run of the reaction process with the same
substrate.
3. Result and discussion
In order to determine the most appropriate reaction conditions
and evaluate the catalytic efficiency of CuO nanoparticles, the syn-
Table 3
The reactions of 2-aminothiophenol, 2-aminophenol and o-phenylenediamines with DMAD or DEAD at room temperature.
Entry
a
1
2
3
Time (min)
45
Yield (%)
81
NH2
NH2
MeO2C
CO2Me
H
N
O
N
H
CO2Me
b
c
45
50
40
84
76
88
NH2
NH2
H
EtO2C
MeO2C
MeO2C
CO2Et
CO2Me
CO2Me
N
O
N
H
CO2Et
O
NH2
OH
H
N
O
CO2Me
O
d
NH2
SH
H
N
S
CO2Me
e
40
50
87
83
NH2
SH
EtO2C
CO2Et
H
N
O
S
CO2Et
O
f
MeO2C
CO2Me
N
NH2
OH
H
N
N
O
CO2Me

S. Sadjadi et al. / Ultrasonics Sonochemistry 17 (2010) 764–767
767
Fig. 1. IR spectra of CuO: (a) newly prepared; (b) used 3 times.
In order to demonstrate the efficiency and the applicability of
the present method, we performed the reaction of a variety of dim-
eyhyl acetylenedicarboxylate (DMAD) or diethyl acetylenedicar-
boxylate (DEAD) with o-phenylenediamine, 2-amino-phenol and
2-amino-benzenethiol in ethanol at room temperature and in the
presence of CuO nanoparticles under ultrasonic irradiation.
All the reactions proceed to completion at the time indicated in
the Table 2 and the yield data are for the isolated products. As
shown in Table 2, a series of 1 reacted with 2 to give the corre-
sponding products 3 in good yields.
To investigate the role of ultrasonic irradiation in this method,
the reactions were carried out in the presence of the same amount
of CuO nanoparticles under stirring condition in EtOH at room tem-
perature. The results are summarized in Table 3. It is clear that, un-
der the same reaction conditions, reactions under ultrasonic
irradiation led to relatively higher yields and shorter reaction
times.
of o-phenylenediamine and dimeyhyl acetylenedicarboxylate
(DMAD) afforded corresponding quinoxaline 3a in 94, 91, and 89
% yields over three successive runs.
4. Conclusion
This work demonstrates a novel and highly efficient methodol-
ogy for the synthesis of benzoheterocycle derivatives in presence
of CuO nanoparticles under ultrasound irradiation. In addition of
efficiency and simplicity, this protocol provides a very fast and
low cast procedure for the synthesis of these products.
Acknowledgements
The authors are thankful to Alzahra University Research Council
for the partial financial support.
It is presumed that the efficiency using ultrasound irradiation is
due to the cavitation phenomena. An ultrasonic wave is a pressure
wave with alternate compressions and rarefactions which is able to
break the intermolecular forces maintaining the cohesion of the li-
quid and produces a cavity in the rarefaction section of the wave.
The chemical and physical effects of ultrasound derive primarily
from acoustic cavitation which includes formation, growth and col-
lapse of the cavity [13–15]. Bubble collapse in liquids results in an
enormous concentration of energy from the conversion of kinetic
energy of liquid motion into heating of the contents of the bubble.
The high local temperatures and pressures produced by cavitation
lead to a diverse set of applications of ultrasound such as acceler-
ating the rate of the reaction, changing the reaction pathway,
enhancing chemical reactivity and important uses in synthetic or-
ganic compounds. [16]. Catalyst regeneration is essential for indus-
trial production. The recycled catalyst could not be used directly
because some organic matter was adsorbed on the catalyst. The
recycled catalyst was first washed with dichloromethane to get
rid of most organic adsorbents and dried at 150 °C overnight. IR
spectra of the resulting solids indicate that the catalyst can be
recovered without structural degradation (Fig. 1).
References
[1] C.L. Lee, K.P. Chan, Y. Lam, Y.S. Lee, Tetrahedron Lett. 42 (2001) 1167.
[2] Q.-Y. Zhang, B.-K. Liu, W.-Q. Chen, Q.Wu, X.-F. Lin, Green Chem. 10 (2008)
972.
[3] D. O’Brien, M.S. Weaver, D.G. Lidzey, D.D.C. Bradley, Appl. Phys. Lett. 69 (1996)
881.
[4] A.H.M. Elwahy, Tetrahedron 56 (2000) 897.
[5] M.J. Crossley, L.A. Johnston, Chem. Commun. (2002) 1122.
[6] B.M. Choudary, K.V.S. Ranganath, J. Yadav, M.L. Kantam, Tetrahedron Lett. 46
(2005) 1369.
[7] M.L. Kantam, S. Laha, J. Yadav, B.M. Choudary, B. Sreedhar, Adv. Synth. Catal.
348 (2006) 867.
[8] M.L. Kantam, S. Laha, J. Yadav, B. Sreedhar, Tetrahedron Lett. 47 (2006)
6213.
[9] B.M. Choudary, K. Mahendar, M.L. Kantam, K.V.S. Ranganath, T. Athar, Adv.
Synth. Catal. 348 (2006) 1977.
[10] A.R. Khosropour, Ultrason. Sonochem. 15 (2008) 659–664.
[11] S.J. Ahmadi, S. Sadjadi, M. Hosseinpour, M. Outokesh, R. Hekmatshoar, Catal.
Commun. 10 (2009) 1423.
[12] T. Adschiri, Y. Hakuta, K. Arai, Ind. Eng. Chem. Res. 39 (2000) 4901.
[13] P.R. Gogate, A.B. Pandit, Adv. Environ. Res. 26 (2003) 17.
[14] T.J. Mason, Ultrason. Sonochem. 10 (2003) 175.
[15] T.J. Mason, L. Paniwnyk, J.P. Lorimer, Ultrason. Sonochem.
253.
3 (1996)
The nano-CuO catalyst could be reused for three cycles with
only a gradual decrease in its activity. For example, the reaction
[16] M.H. Entezari, A. Asghari, F. Hadizadeh, Ultrason. Sonochem. 15 (2008)
119.