A green synthesis of substituted coumarins using nano graphene oxide as recyclable catalyst

Article abstract of DOI:10.1002/jccs.201400349

One-pot synthesis of some pyranocoumarins and biscoumarins using graphene oxide nanosheets as efficient catalyst has been investigated. The green methods offer appealing attributes such as excellent yields, short reactions times, use of a safe and recycla

Full text of DOI:10.1002/jccs.201400349

JOURNAL OF THE CHINESE
CHEMICAL SOCIETY
Article
A Green Synthesis of Substituted Coumarins Using Nano Graphene Oxide as
Recyclable Catalyst
Saeed Khodabakhshi,a Farzaneh Marahel,b* Alimorad Rashidic and Masoud Khaleghi Abbasabadia
aDepartment of Chemistry, College of Basic Science, Yadegar-e-Imam Khomeini (RAH) Shahre-rey Branch, Islamic
Azad University, Tehran, Iran
bDepartment of Chemistry, Omidiyeh Branch, Islamic Azad University, Omidiyeh, Iran
cNanotechnology Research Center, Research Institute of Petroleum Industry, Tehran, Iran
(Received: Aug. 18, 2014; Accepted: Feb. 26, 2015; Published Online: ??; DOI: 10.1002/jccs.201400349)
One-pot synthesis of some pyranocoumarins and biscoumarins using graphene oxide nanosheets as effi-
cient catalyst has been investigated. The green methods offer appealing attributes such as excellent yields,
short reactions times, use of a safe and recyclable catalyst, and a simple workup procedure.
Keywords: Pyranocoumarins; Biscoumarins; Catalyst; Graphene oxide; Green.
INTRODUCTION
Heterocyclic compounds have gained remarkable at-
The Knoevenagel and Michael addition reactions
have various applications in the elegant synthesis of de-
sired chemicals.12 In continuation of our studies on the syn-
thesis of substituted coumarins via multicomponent reac-
tions (MCRs),13-15 herein, we present new and green meth-
ods to synthesize some biscoumarins and pyranocumarins.
tention due to their therapeutic properties in natural prod-
uct and medicinal chemistry. Coumarins as oxygen-con-
taining heterocycles have a wide range of biologically ac-
tivities such as anticoagulant,1 antidepressant,2 anti-HIV,3
antioxidant, and anti-inflammatory.4 Besides, some cou-
marins are used as additive in food and cosmetics, optical
brighteners, dispersed fluorescent, and laser dyes.5 Re-
cently, the methods for the synthesis of some substituted
coumarins such as pyrano[3,2-c]coumarins and bis-4-hy-
droxycoumarin have been reviewed by Ziarani and
Hajiabbasi.6
RESULTS AND DISCUSSION
A modified Hummers method was employed for the
preparation of graphene oxide (GO). The morphology of
the prepared GO nanoplatelets was observed by scanning
electron microscopy (SEM). Fig. 2(A) presents the SEM
image of GO nanoplatelets showing crumpled thin layers
with wrinkles and folds on the surface of GO. Fig. 2(B)
shows the XRD pattern of the bulk GO in its dry state. In
the XRD pattern, the clear diffraction bands are centered at
2q ~ 101 corresponding to the (002) plane of the GO with
an interlayer spacing about 0.87 nm.
Organic catalytic reactions have emerged as useful
tools for the synthesis of a wide spectrum of functionalized
compounds. Recently, carbocatalysts have been considered
for organic reactions due to their advantages over metal
catalysts, such as high efficiency, environmental compati-
bility, low energy consumption, and corrosion resistance.7
For example, graphene oxide (GO) is an inexpensive metal-
free material which has been recently used as an oxidative
catalyst in chemical transformations.8 Simplified structure
of a single layer of graphene oxide (GO) was proposed
(Fig. 1).9
The presence of functional groups on the aromatic
scaffold of GO allows these sheets to mediate ionic and
nonionic interactions with a wide range of molecules.10 On
the other hand, it has been recognized that GO possess in-
teresting and potentially useful reactivity and can act as ox-
idants and/or acids.11
Fig. 1. Structural model of graphene oxide (GO).
* Corresponding author. Email: saeidkhm@yahoo.com
Supporting information for this article is available on the www under http://dx.doi.org/10.1002/jccs.201400349
J. Chin. Chem. Soc. 2015, 62, 000-000
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1

Article
Khodabakhshi et al.
action conditions, several fundamental experiments were
carried out based on the synthesis of compound 4a and 5a
as a model. The results are summarized in Table 1.
As can be seen from Table 1, the best conditions were
determined as GO (0.005 g) in H2O/EtOH (1:1) for 4a and
GO (0.005 g) in H2O for 5a. After optimization of the reac-
tion conditions, the reaction scope was extended by using
different arylaldehydes 1. The products 4 and 5 were ob-
tained in good yields and short reaction times. It should be
noted that arylaldehydes bearing both electron-withdraw-
ing or -donating groups could participate in the reactions
(Table 2).
Fig. 2. (A) SEM image of GO; (B) XRD pattern of GO.
As part of an ongoing research program aiming to
find green methods within organic chemistry, we have
previously utilized some environmentally-friendly cata-
lysts.16,17 Here, we describe a three-component condensa-
tion of arylaldehydes 1 and 4-hydroxycoumarin (2) with
malononitrile (3) in the presence of GO as a nanocatalyst to
produce pyranocoumarins 4 (Scheme 1). Also, the GO-cat-
alyzed reaction of 1 with 2 has been separately studied to
yield corresponding bis-4-hydroxycoumarins 5.
The main disadvantage of some reported methods for
the synthesis of 4 and 5 is that the catalysts are destroyed
during the work-up procedure and cannot be recovered or
reused. In this study, the recycled catalyst was used for four
cycles and no appreciable loss for the catalytic activity ob-
served after the last run (4a: 87%; 5a: 91%).
To demonstrate the merit of this method in compari-
son with previously reported results in literature, we pro-
vided the results in Table 3 and 4. These reactions can be ef-
ficiently carried out under our suggested conditions with
respect to reaction times and product yield.
Synthesis of pyranocoumarins and bis-4-hy-
droxycoumarins using GO
Scheme 1
EXPERIMENTAL
General: Chemicals were purchased from Aldrich. GO
was prepared using modified Hummers method from flake graph-
ite (Merck Company).18 The reactions were monitored by thin
layer chromatography (TLC; silica-gel 60 F254, n-hexane: ethyl
acetate). IR spectra were recorded on a FT-IR JASCO-680 and the
1H NMR spectra were obtained on a Bruker-Instrument DPX-400
MHz Avance 2 model. SEM studies of the nanostructures were
carried out with a JEOL JEM 3010 instrument operating at an ac-
The nature of the solvent and catalyst plays a signifi-
cant role in chemical transformations. Thus, development
of a safe, mild, and reusable catalytic system for the MCRs
remains of interest to the organic chemists. To optimize re-
Table 1. The effect of solvent and catalyst amounts on the synthesis of 4a under reflux
Time (min) Yield (%)
Entry Catalyst (g)
Solvent
4
5
4
5
1
5
5
-
180
10
180
17
25
87
80
50
95
30
90
92
-
33
80
72
93
93
-
2
EtOH
3
5
MeOH
16
25
4
5
H2O
180
10
5
5
H2O/EtOH (1:1)
H2O/EtOH (1:1)
H2O/EtOH (1:1)
H2O/EtOH (1:1)
H2O
14
10
6
-
180
Not tested
Not tested
Not tested
180
7
2
180
-
8
10
-
10
-
9
Not tested
Not tested
Not tested
45
77
90
10
11
2
H2O
180
-
10
H2O
12
2
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CHEMICAL SOCIETY
Synthesis of Coumarins Using Nano Graphene Oxide
Table 2. Synthesis of 4 and 5 using GO (0.005 g) under opti-
Table 4. Comparison of our method with other methods for the
mized conditions
synthesis of 5a
Time/Yield
(%)Ref.
Entry Product
Ar
Time (min) Yield (%)c Mp. (°C)
Entry
Conditions
1
4a
4b
4c
4d
4e
4f
Ph
1-Naphthyl
2-Cl-Ph
4-NO2-Ph
4-Cl-Ph
4-Br-Ph
4-MeO-Ph
H
14
20
12
17
20
12
15
10
12
20
17
18
22
25
95
88
92
90
93
90
90
93
95
95
93
90
94
90
261-263
262-264
264-266
260-262
262-264
256-258
240-242
229-231
253-255
263-265
232-234
241-243
226-228
264-266
1
2
3
GO/H2O/reflux
.
NaHSO4 SiO2/toluene/100 ºC
15 min/95a
30 min/8925
30 min/9225
2
3
Indion 190 resin/toluene/100 ºC
Silica-supported Preyssler
nanoparticles/EtOH/r.t.
4
5
4
30 min/9226
6
5
6
SO3H-functionalized ILs/70 ºC
H6[PMo9V3O40]/EtOH:H2O
Catslyst-free/microwave/H2O/150 W,
150 ºC
2 h/9527
15 h/3028
7
4g
5a
5b
5c
5d
5e
5f
8
9
4-Cl
7
9 min/ 8529
10
11
12
13
14
4-Br
a This work.
4-NO2
4-OMe
2-Cl
tra-pure water to give a brown dispersion, which was subjected to
dialysis to completely remove residual salts and acids. The result-
ing purified GO powders were collected by centrifugation and
air-dried. GO powders were dispersed in water to create a 0.05
wt% dispersion. The dispersion was then exfoliated through
ultrasonication for 1 h, which the bulk GO powders were trans-
formed into GO nanoplatelets.
5g
4-Me
Table 3. Comparison of the present work with other methods
reported in the literature for synthesis of 4a
Time/Yield
(%)Ref.
Entry
Conditions
1
2
GO (5 g), H2O:EtOH (1:1), Reflux
SDS (20 mol%), H2O, 60 °C
H6P2W18O62.18H2O (1 mol%), H2O:EtOH
(1:1)
14/95a
120/8519
General procedure for the synthesis of pyrano[2,3-c]-
coumarin: 4-Hydroxycoumarin (1 mmol), aromatic aldehyde (1
mmol), malononitrile (1.1 mmol) and GO (0.005 g) were added to
a mixture of 10 mL EtOH/H2O (50/50) in a 25 mL Pyrex flask and
refluxed for an appropriate time (Table 2). The reaction progress
was controlled by thin layer chromatography (TLC) using hex-
ane/EtOAc (1:1). After completion of the reaction, the solvent
was removed under vacuum and the residue was dissolved in hot
EtOH to separate catalyst. The crude 4 was obtained after recrys-
tallization from EtOH.
3
30/8920
4
5
MgO (0.2 g), EtOH, Reflux
DAHP (10 mol%), H2O:EtOH (1:1), rt
(S)-Proline (10 mol%), H2O:EtOH (1:1),
Reflux
32/8921
180/8122
6
240/7222
7
8
KF-Al2O3 (0.125 g), EtOH, Reflux
TEBA (0.07 g), H2O, 90 °C
240/9023
420/9624
a This work.
Preparation of bis-4-hydroxycoumarins: A mixture of
aromatic aldehydes 1 (1 mmol), 4-hydroxycoumarin (2 mmol),
and GO (0.005 g) in water (10 mL) was stirred and refluxed for an
appropriate time mentioned in Tables 2. The progress of the reac-
tion was monitored by TLC (hexane/EtOAc, 1:1). After comple-
tion of the reaction, the precipitate was filtered off and dissolved
in hot EtOH to separate catalyst. The crude 5 was afforded after
recrystallization from EtOH.
celerating voltage of 300 kV. X-Ray diffraction (XRD, D8, Ad-
vance, Bruker, AXS) patterns were obtained for characterization
of the heterogeneous catalyst. Melting points were measured on
an electrothermal KSB1N apparatus. All products were charac-
terized by comparison of their spectra and physical data with
those reported in the literature.19-29
Preparation of GO catalyst: A flask containing graphite
(1 g) and NaNO3 (0.75 g) was placed in an ice-water bath. H2SO4
(75 mL) was added with stirring and then KMnO4 (4.5 g) was
slowly added over about 1 h. After vigorously stirring for 5 days
at room temperature, 5% H2SO4 (140 mL) aqueous solution was
added over about 1 h with stirring, and the temperature was kept
at 98 ºC. The temperature was reduced to 60 ºC, 3 mL of H2O2 (30
wt% aqueous solution) was added, and the mixture was stirred for
2 h at room temperature. As-prepared GO was suspended in ul-
Characterization data for selected compounds
Compound 4b: IR (KBr): 3340, 3312, 2188, 1697, 1669,
1598, 1379, 1066 cm-1. 1H NMR (DMSO, 400 MHz): d 8.44 (d,
1H, J = 6.4 Hz), 7.96 (d, 2H, J = 8.0 Hz), 7.83 (d, 1H, J = 8.0 Hz),
7.76-7.33 (m, 8H), 5.48 (s, 1H). 13C NMR (DMSO-d6, 100 MHz):
d 159.55, 157.83, 153.80, 152.07, 133.26, 132.93, 130.93,
128.47, 127.43, 126.10, 126.00, 125.85, 125.75, 124.74, 123.43,
122.43, 119.15, 116.61, 112.96, 104.65, 58.49. Compound 4f: IR
J. Chin. Chem. Soc. 2015, 62, 000-000
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3

Article
Khodabakhshi et al.
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(KBr): 3396, 3321, 3195, 2202, 1706, 1671, 1607, 1381, 1053
cm-1. 1H NMR (DMSO-d6, 400 MHz): d 7.90 (dd, 1H, J = 7.8, 1.2
Hz), 7.75-7.70 (m, 1H), 7.52-7.43 (m, 6H), 7.30-7.28 (m, 2H),
4.50 (s, 1H). 13C NMR (DMSO-d6, 100 MHz): d 159.55, 157.94,
153.70, 152.18, 146.02, 132.99, 130.69, 130.39, 130.05, 126.94,
124.65, 122.54, 121.68, 119.05, 116.57, 112.98, 103.15, 57.31,
36.59. Compound 5b: 1H NMR (DMSO-d6, 400 MHz): d 10.70
(b, 1H), 9.99 (s, 1H), 7.89 (d, 2H, 8 Hz), 7.58 (t, 2H, J = 8 Hz),
7.40-729 (m, 6H), 7.12 (d, 2H, J = 8.4 Hz), 6.28 (s, 1H). 13C NMR
(DMSO-d6, 100 MHz): d 165.89, 164.55, 152.26, 140.22, 132.69,
132.28, 131.72, 131.22, 130.74, 129.08, 123.93, 123.53, 123.16,
118.31, 116.35, 115.84, 103.60, 90.95, 35.72. Compound 5d. 1H
NMR (CDCl3, 400 MHz): d 11.57 (s, 1H), 11.35 (s, 1H), 8.08 (d,
1H, J = 8 Hz), 8.03 (d, 1H, J = 8 Hz), 7.68-7.64 (m, 2H), 7.44 (d,
4H, J = 8 Hz), 7.21 (dd, 2H, J = 8 Hz, 5.2 Hz), 7.03 (t, 2H, J = 8
Hz), 6.07 (s, 1H). 13C NMR (CDCl3, 100 MHz): d 169.23, 166.86,
165.93, 164.63, 162.94, 160.50, 152.54, 152.29, 133.01, 130.87,
130.84, 128.22, 128.14, 124.98, 128.14, 124.98, 124.41, 116.87,
116.68, 116.39, 115.63, 115,41, 105.49, 103.95, 35.68.
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CONCLUSIONS
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In summary, the GO was used as a recyclable and wa-
ter-tolerant nanocatalyst for the green synthesis of substi-
tuted coumarins via the one-pot reactions. The present
methods may have some advantages over the previously re-
ported ones, such as the use of a safe catalyst, avoidance of
toxic solvents, high product yields, short reaction times,
and an easy work-up procedure.
19. Mehrabi, H.; Abusaidi, H. J. Iran. Chem. Soc. 2010, 78,
90-894.
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ACKNOWLEDGEMENTS
The authors gratefully acknowledge partial support
of this work by the Islamic Azad University, Omidiyeh
Branch (Iran).
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