Graphene oxide (GO) or reduced graphene oxide (rGO): Efficient catalysts for one-pot metal-free synthesis of quinoxalines from 2-nitroaniline

Article abstract of DOI:10.1016/j.tetlet.2015.10.065

A straightforward one-pot preparation of library of quinoxalines from 2-nitroanilines under entirely metal-free conditions is described. Initial reduction of nitroaniline with hydrazine hydrate is efficiently catalyzed by graphene oxide (GO) or reduced graphene oxide (rGO), and further one-pot tandem reactions with 1,2-dicarbonyl compounds or with α-hydroxy ketones afford quinoxalines in excellent yields. The catalyst is recovered, characterized, and found to be recyclable for consecutive four runs examined with appreciable conversions.

Full text of DOI:10.1016/j.tetlet.2015.10.065

Accepted Manuscript
Graphene oxide (GO) or reduced graphene oxide (rGO): Efficient catalysts for
one-pot metal-free synthesis of quinoxalines from 2-nitroaniline
Babli Roy, Sujit Ghosh, Pranab Ghosh, Basudeb Basu
PII:
S0040-4039(15)30262-8
DOI:
http://dx.doi.org/10.1016/j.tetlet.2015.10.065
TETL 46894
Reference:
Tetrahedron Letters
To appear in:
Received Date:
Revised Date:
Accepted Date:
29 August 2015
18 October 2015
19 October 2015
Please cite this article as: Roy, B., Ghosh, S., Ghosh, P., Basu, B., Graphene oxide (GO) or reduced graphene oxide
(rGO): Efficient catalysts for one-pot metal-free synthesis of quinoxalines from 2-nitroaniline, Tetrahedron
Letters (2015), doi: http://dx.doi.org/10.1016/j.tetlet.2015.10.065
This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers
we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and
review of the resulting proof before it is published in its final form. Please note that during the production process
errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.

Graphical Abstract
To create your abstract, type over the instructions in the template box below.
Fonts or abstract dimensions should not be changed or altered.
Graphene oxide (GO) or reduced graphene
oxide (rGO): Efficient catalysts for one-pot
metal-free synthesis of quinoxalines from 2-
nitroaniline
Leave this area blank for abstract info.
Babli Roy, Sujit Ghosh, Pranab Ghosh, Basudeb Basu*
N
N
R2
R3
NO2
NH2
GO or rGO / NH2-NH2 H2O
R1
R1
O
X
R2
R3
R2/R3 = H, alkyl,
aryl, heteroaryl
(26 examples)
X = O, or
X = H & OH
R1 = H, Me, OMe

1
Tetrahedron Letters
Graphene oxide (GO) or reduced graphene oxide (rGO): Efficient catalysts for one-
pot metal-free synthesis of quinoxalines from 2-nitroaniline
Babli Roy, Sujit Ghosh, Pranab Ghosh, Basudeb Basu
Department of Chemistry, North Bengal University, Darjeeling 734013, India
E-mail: basu_nbu@hotmail.com
ARTICLE INFO
ABSTRACT
Article history:
Received
Received in revised form
Accepted
A straightforward one-pot preparation of library of quinoxalines from 2-nitroanilines under
entirely metal-free conditions is described. Initial reduction of nitroaniline with hydrazine
hydrate is efficiently catalyzed by graphene oxide (GO) or reduced graphene oxide (rGO), and
further one-pot tandem reactions with 1,2-dicarbonyl compounds or with -hydroxy ketones
afford quinoxalines in excellent yields. The catalyst is recovered, characterized and found to be
recyclable for consecutive four runs examined with appreciable conversions.
Available online
Keywords:
2009 Elsevier Ltd. All rights reserved.
Graphene oxide (GO)
Hydrazine hydrate
2-Nitroaniline
Quinoxaline
Reduced graphene oxide (rGO)
Heterocyclic compounds are ubiquitous in nature.1 Among
different N-heterocyclic compounds, quinoxaline and its
congeners have broad spectrum of biological activities such as
The primary demands of green synthesis include minimization
of steps i.e. one-pot tandem reactions as well as catalytic
processes under metal-free conditions.13 Since there is no method
developed for the one-pot and metal-free tandem synthesis of
quinoxalines from nitroaniline or dinitrobenzene, we were
interested to develop an alternative metal-free greener process for
the synthesis of quinoxalines directly from 2-nitroaniline. The
biomass derived carbon materials have been considered as
potential catalyst for diverse organic reactions.14 Since the
seminal report by Bielawski in 2010, the use of graphene oxide
(GO) as the ‘carbocatalyst’ in organic reactions has evolved
enormous interests among the synthetic organic chemists.14,15
While searching literature, we find that reduced graphene oxide
(rGO) in combination with large excess of hydrazine hydrate can
perform the reduction of nitrobenzene to aniline, which is as
good as commonly used noble metal catalyst like Pt/SiO2.16
antiviral,
anti-inflammatory,
antitumour,
antibacterial,
anthelmintic, kinase inhibitory, anti-HIV and anticancer
activities.2 In addition, these heterocycles are widely applied to
other technical fields. For example, in the preparation of dyes,3
metal complexes,4 organic semiconductors,5 cavitands,6
luminescent materials,7 chemically controllable switches,8 etc.
Owing to vast and outstanding applications, several synthetic
strategies have been developed for their synthesis over the years.9
The most common method involves the condensation of an aryl
1,2-diamine with 1,2-dicarbonyl compound.10 Since aryl 1,2-
diamines are carcinogenic and relatively unstable than its
precursor nitro compounds,11 a few methods are also reported in
the recent years via reduction of nitro compounds to anilines and
subsequent condensation reaction, preferably in one-pot
procedure, resulting in the formation of quinoxaline (Scheme
1).11,12 The reduction of nitro to amine has however been carried
out in the presence of different metal catalysts. For example,
ruthenium-catalyzed hydrogen transfer strategy,11 indium-acetic
acid or indium(III) chloride,12a in situ generated iron sulfide from
elemental sulfur and ferric chloride,12b gold NPs supported with
cerium oxide,12c stannous chloride in ethanol,12d etc have been
employed for the reduction of nitro group and subsequently,
synthesis of quinoxaline was achieved by the reaction with 1,2-
dicarbonyl compounds or analogues.
In connection with our interest to harness the utilization of
sustainable carbonaceous materials in catalyzing diverse organic
reactions,17 we envisioned that GO or rGO could serve as an eco-
friendly alternative catalyst for the synthesis of quinoxaline
through the metal-free tandem reduction-condensation in one-pot
protocol. Although the reported procedure using rGO for the
reduction of nitroaniline is quite useful, further one-pot
condensation with 1,2-dicarbonyl compound might lead to
multifarious results due to the presence of excess hydrazine in the
reaction mixture. In our strategy, it was therefore necessary to
find out an optimized condition that could avoid the excess use of
the reducing source hydrazine.
———
 Corresponding author. Tel.: +91-353-2776-381; fax: +91-353-2699-001; e-mail: basu_nbu@hotmail.com

2
Tetrahedron Letters
We report herein our findings that finally established a
was high (HPLC) and the isolation of the desired quinoxaline
was achieved in excellent yield. A large variation of functional
groups attached with the aromatic rings of either of the
condensing partners was observed with excellent conversions to
quinoxalines (Scheme 1).
practical and clean procedure for the synthesis of quinoxalines
directly from 2-nitroaniline via one-pot reduction-condensation
reactions under metal-free condition. There was no other by-
product detected by analysis of the crude product, the conversion
Ru-cat.;11
1,2-di ol, 2-aryl
ethyl amine,
1,2-dicarbonyl,
-hydroxy ketone
In, InCl3/ AcOH;12a
Fe-cat./ S;12b
Au-cat.;12c Sn-cat.12d
(Reported methods)
(Reported methods)
R2
R3
2
N
N
R2
R3
NO2
NH2
NH2
X = NO2,
R1
R1
R1
1
GO or rGO Cat.
.
X = NH2
N2H4 H2O
Y
Y
X
100 oC, 3h
(Our method)
R2/ R3 = H, alkyl,
aryl, heteroaryl
R1 = H, alkyl,
alkoxy
(Our method)
1,2-dicarbonyl,
-hydroxy ketone
Scheme 1 One-pot reduction of nitro compounds and subsequent condensation resulting quinoxalines.
Our studies began with the reaction of 2-nitroaniline and
benzil in the presence of GO and hydrazine hydrate. Since benzil
can also react with hydrazine to form hydrazone,18 we set up the
reaction by adding the reacting components in a step-wise
manner and not in the multi-component reaction approach.19
Thus a neat mixture of 2-nitroaniline (1 mmol), graphene oxide
of the crude reaction mixture. Decreasing the temperature of the
reaction furnished the hydrazone again (Entry 8). Use of solvents
like water, methanol or ethyl acetate however resulted in
significant quantity of the hydrazone (Entries 9-11). Further
examination of the second step i.e. the condensation reaction
carried out at room temperature was not favorable but the same at
o
o
(5 mg) and hydrazine (6 mmol) was heated at 100 C for 3h (tlc
60 C afforded the quinoxaline in isolated yield (93%) (Entries
monitoring showed complete disappearance of the nitroaniline),
and then benzil (1 mmol) was added to the reaction mixture.
After stirring for another 3h at 100 oC, tlc showed complete
disappearance of benzil on tlc plate. Ethyl acetate was added to
the reaction mixture and the catalyst GO was separated out by
centrifugation. HPLC analysis of the crude mixture showed the
ratios of quinoxaline and dihydrazone derivative of benzil
(prepared separately for comparison) in 70:30 mixtures.
Separation of the crude mixture by column chromatography over
silica gel afforded the quinoxaline (68%). The observation is
presented in Table 1 (Entry 1). Further optimization of the
reaction conditions by changing the quantity of GO and/or
hydrazine hydrate led us to achieve only quinoxaline as the sole
product in 92% isolated yield (Entries 2-7). However, as in entry
7, there was un-reacted benzil (6%) observed by HPLC analysis
12 and 13). Since hydrazine can also reduce the GO to reduced
GO (rGO), we had separately prepared rGO using hydrazine,20
and used it for the same one-pot reaction. It was observed that the
rGO is also equally effective catalyst for the reduction of 2-
nitroaniline and subsequent condensation with benzil (Entry 14).
Control experiment without using GO did provide only trace
amount of quinoxaline (≤ 10%) signifying the catalytic role of
the graphene oxide (Entry 15). In another experiment, the
reaction was scaled up using 2-nitroaniline (5 mmol) and the
catalyst GO (50 mg), which afforded finally the quioxaline in
88% isolated yield (Entry 16). Thus the optimized condition was
found to be the reaction of 2-nitroaniline (1 mmol) hydrazine
hydrate (2.2 mmol) and GO (20 mg), stirring the mixture in neat
o
at 100 C for 3h, then benzil (1 mmol) was added and further
stirring at 60 oC for 3h.
Table 1. Optimization of reaction conditions for GO-catalyzed one-pot reduction and heterocyclization of 2-nitroaniline (1
mmol) and benzil (1 mmol)
Entry
no.
GO
Temp
Solvent
Hydrazine hydrate Time (h)
Conversion (%)a
(oC)
(mg)
(N2H4.H2O)
(mmol)
(Reduction &
Condensation)
Quinoxaline
(% Yield)
70 (68)
78 (76)
80 (78)
87 (85)
90 (88)
91 (89)
94 (92)
87 (81)
75 (71)
71 (68)
75 (68)
83 (81)
95 (93)
93 (91)
Hydrazonea
1
5
100
100
100
100
100
100
100
80
No
6
(3 & 2)
(3 & 2)
(3 & 2)
(3 & 2)
(3 & 2)
(3 & 2)
(3 & 2)
(3 & 2)
(4 & 2)
(4 & 2)
(4 & 2)
(3 & 12)
(3 & 3)
(3 & 3)
30
22
20
13
10
09
No
13
25
29
25
17
No
07
2
10
15
15
15
15
20
20
20
20
20
20
20
20
No
4
3
No
4
4
No
3
5
No
2.5
2.2
2.2
2.2
2.2
2.2
2.2
2.2
2.2
2.2
6
No
7b
No
8
No
9
100
100
100
100
100
100
Water
MeOH
EtOAc
No
10
11
12c
13d
14e
No
No

3
15f
16g
No
50
100
100
No
No
2.2
11
(6 & 3)
(4 & 3)
09
88
65
No
aConversion was checked by HPLC and yield of quinoxaline (in the parenthesis) represents the isolated product after column
chromatography.
bUn-reacted benzil (6%).
cCondensation with benzil was performed at room temperature.
dCondensation with benzil was performed at 60 oC and un-reacted benzil.
erGO was used instead of GO and condensation with benzil was performed at 60 oC.
fUn-reacted benzil (26%).
gReaction carried out with 2-nitroaniline (5 mmol).
With the optimized condition at our hand (as in Table 1, entry
13), we examined its practical applications with a variety of
nitroanilines and benzil derivatives. The results are presented in
Table 2. It can be seen that different nitroanilines undergo one-
pot reduction and condensation with benzils gave rise to the
formation of corresponding quinoxalines in excellent yields
(Table 2, Entries 1-8). Since the present reducing condition is
metal-free, it was interesting to examine whether halogen
substituents could survive the overall reaction conditions. We
employed 4,4'-dibromobenzil as the condensing partner and
indeed the corresponding bromo-substituted quinoxalines were
isolated in 90-95% yields (Entries 9-11). Heteroaromatic benzils
like -furil also yielded corresponding furyl-containing
quinoxaline derivatives in isolated yield (> 90%) (Entries 12-14).
Further studies with glyoxal, aliphatic 1,2-diketones and
phenylpropane-1,2-dione also resulted in the formation of
quinoxaline in good to excellent yields (Entries 15-19). Thus,
functional groups like methyl, methoxyl, furyl, or bromide being
present with either nitroaniline or dicarbonyl compounds as well
as the ketone or aldehyde functions worked without any
difficulty yielding the final quinoxalines in excellent yields. We
then examined similar reactions using 2-nitroaniline bearing an
electron-withdrawing group such as F or COPh (Entries 20, 21)
as well as with 1,2-dinitrobenzene (Entry 22). While 4-fluoro-2-
nitroaniline resulted in the formation of the desired quinoxaline
in excellent yield, 4-benzoyl-2-nitroaniline gave rise to a mixture
of four spots on tlc and one of those was matched with the
authentic
sample
[(phenyl(2,3-diphenylquinoxalin-6-
yl)methanone)].10b However, the desired quinoxaline could not be
separated and its actual yield was not obtained. Possibly, the
benzoyl group suffers from reaction with hydrazine causing an
inseparable mixture of products. In the case of 1,2-
dinitrobenzene, similar reaction was sluggish and the desired
quinoxaline was isolated in 48% yield. Since GO is known by its
intriguing properties as an oxidizing agent, dual role of GO might
be expected if -hydroxy ketone is used as the condensing
partner instead of 1,2-diketone. Acyloins are often considered as
the precursor of diketo equivalent compounds. The reaction with
benzoin indeed resulted in the formation of quinoxaline in
isolated yield (91%) (Entry 23). Substituted nitroanilines and
other variety of acyloin such as furoin also gave rise to the
formation of quinoxaline in 86-92% yields (Entries 24-28).
Table 2. GO-catalyzed reduction of various 2-nitroanilines and subsequent heterocyclization with 1,2-dicarbonyl compounds or
with -hydroxy ketones.a
Entry
2-Nitro aryl amine
1,2-Dicarbonyl
compound/ -Hydroxy
ketone
Temp
(oC)
Time
Product
Yield
(%)b
(h)
(Reduction &
(Reduction &
Condensation) Condensation)
O
C6H5
N
C6H5
NO2
1
2
100 & 60
100 & 60
3 & 3
3 & 3
93
91
O
O
C6H5
N
N
C6H5
NH2
NO2
C6H4-p-Me
C6H4-p-Me
O
O
C6H4-p-Me
N
C6H4-p-Me
C6H4-p-OMe
NH2
NO2
C6H4-p-OMe
N
3
4
100 & 60
100 & 60
3 & 3
4 & 3
92
89
N
C6H4-p-OMe
O
O
C6H4-p-OMe
NH2
NO2
Me
C6H5
Me
N
N
C6H5
C6H5
NH2
O
C6H5

4
Tetrahedron
Me
N
C6H4-p-Me
O
C6H4-p-Me
Me
NO2
5
6
7
100 & 60
4 & 3
4 & 3
4 & 3
91
90
90
N
N
C6H4-p-Me
O
O
C6H4-p-Me
C6H4-p-OMe
NH2
NO2
Me
C6H4-p-OMe
Me
100 & 60
100 & 60
O
C6H4-p-OMe
N
C6H4-p-OMe
NH2
MeO
MeO
N
N
C6H5
MeO
NO2
O
C6H5
C6H5
NH2
NO2
O
O
C6H5
N
C6H4-p-Me
C6H4-p-Me
MeO
8
9
100 & 60
100 & 60
4 & 3
88
95
N
C6H4-p-Me
O
O
C6H4-p-Me
C6H4-p-Br
NH2
NO2
NH2
N
N
C6H4-p-Br
3 & 3.5
C6H4-p-Br
O
O
C6H4-p-Br
C6H4-p-Br
Me
N
C6H4-p-Br
Me
NO2
10
100 & 60
4 & 3.5
92
90
O
O
C6H4-p-Br
C6H4-p-Br
N
C6H4-p-Br
C6H4-p-Br
NH2
NO2
MeO
N
MeO
11
12
100 & 60
100 & 60
4 & 3
3 & 3
N
C6H4-p-Br
NH2
O
C6H4-p-Br
NO2
NH2
O
O
O
N
N
O
91
O
O
Me
NO2
O
13
100 & 60
4 & 3
Me
N
N
O
O
O
90
NH2
O
O
MeO
NO2
O
14
100 & 60
4 & 3
MeO
N
O
O
89
85
NH2
N
O
O
O
O
NO2
NH2
H
H
N
N
15
100 & 60
3 & 2
O

5
NO2
NH2
O
C6H5
N
N
C6H5
16
17
18
19
100 & 60
100 & 60
100 & 60
100 & 60
3 & 3
4 & 2
3 & 2.5
4 & 3
84
O
O
Me
H
Me
N
MeO
NO2
NH2
MeO
87
83
88
O
O
H
N
NO2
NH2
n-Pr
N
N
n-Pr
O
O
Me
Me
C6H5
Me
Me
N
C6H5
Me
NO2
O
Me
N
N
Me
Me
NH2
or
N
C6H5
F
NO2
NH2
O
C6H5
F
N
C6H5
20
100 & 60
100 & 60
100 & 60
4 & 4
5 & 4
4 & 3
87

O
O
C6H5
C6H5
N
C6H5
O
NO2
NH2
Inseparable mixture of
different products
20c
21d
22
C6H5
O
O
C6H5
C6H5
NO2
N
N
C6H5
C6H5
48
NO2
NO2
O
C6H5
O
N
N
C6H5
C6H5
OH
OH
C6H5
100 & 80
3 & 1.5
91
90
NH2
C6H5
O
O
Me
N
C6H5
C6H5
Me
NO2
NH2
23
24
C6H5
100 & 80
100 & 80
4 & 2
4 & 2
N
C6H5
MeO
NO2
MeO
N
C6H5
92
OH
C6H5
C6H5
NH2
N
C6H5

6
Tetrahedron
NO2
NH2
O
25
100 & 80
3 & 2
87
HO
O
N
N
O
O
O
O
Me
NO2
NH2
26
100 & 80
4 & 2
88
Me
N
N
HO
O
O
O
O
O
MeO
NO2
27
100 & 80
4 & 2
MeO
N
HO
O
O
86
NH2
N
O
O
aReaction conditions: A mixture of 2-nitro aryl amine (1 mmol), hydrazine monohydrate (2.2 mmol) and GO (20 mg) was heated in a
sealed tube with magnetic stirring for hours and then 1,2-dicarbonyl compound or -hydroxy ketone (1 mmol) was added to the
reaction mixture and stirred.
bIsolated yield after column chromatography.
cThe reaction furnished a non-separable mixture of compounds.
dThe reaction was carried out using 4.4 mmol of hydrazine hydrate.
3rd run
4th run
16
14
15
10
4 & 3
5 & 3
85
84
We also tested the reusability of the catalyst GO. The catalyst
was recovered from the reaction mixture as follows: The reaction
mixture was taken in water (2 mL), subjected to the
centrifugation (5000 rpm) and removed the supernatant liquid.
The residue was washed with ethyl acetate followed by acetone.
Drying under vacuum furnished the free-flowing powder, which
is visibly blackish as compared to the first-time used GO. We can
assume that the recovered catalyst may be the reduced graphene
oxide (rGO), which was confirmed by comparison of the FT-IR
spectroscopic characteristic absorption peaks (see SI, S3). The
average particle size of GO was measured by DLS studies and
found to be 544±37 nm (0.1 mg/mL H2O), which is comparable
with the literature report (see SI, S6).21
aFirst experiment was performed with 2-nitroaniline (2 mmol),
hydrazine hydrate (4.4 mmol), benzil (2 mmol) and GO (40 mg),
and subsequently in 1, 0.75 and 0.5 mmol scales.
bIsolated product after column chromatography.
Mechanistically, carbon-catalyzed reduction of nitrobenzene
to aniline by hydrazine is believed to involve four-electron
process
occurring
through
the
formation
a
of
phenylhydroxylamine.22 While hydrazine is
two-electron
reducing agent, the role of carbon materials such as graphite, GO
or rGO might be to serve as an adsorbent as well as the conductor
of electrons.16,22 In order to find out the possible involvement of
GO or rGO in the second step of condensation, we performed
few reactions starting from o-phenylenediamine. In the case of
After the first run, the recovered catalyst by weight was low,
which could possibly be attributed to the removal of several
oxygenated functional groups. It was then used in the second run
with nearly equal catalytic efficiency in the reduction and
subsequent condensation producing the quinoxaline product in
91% isolated yield. In the third and fourth runs, the quantity of
the recovered catalyst by weight was nearly equal (from the
second run) and indeed found to be significantly active with
appreciable conversions. The results are presented in the Table 3.
graphite-promoted
quinoxaline
formation
from
o-
phenylenediamine, it was postulated that the attack of amine N-
lone pair to the carbonyl group is facilitated by the presence of
graphite.23 At our hand, the condensation of o-phenylenediamine
with benzil in neat in the absence of GO afforded only 30%
conversion to quinoxaline after 3h at 60 oC, while the same
reaction carried out in ethyl acetate resulted in >90% conversion
to quinoxaline. Similarly, heating the neat reaction mixture of o-
phenylenediamine, benzoin and rGO at 80 oC gave nearly
complete conversions after 2h (analyzed by HPLC). The above
observations suggest that the catalyst GO or rGO plays a positive
role in promoting the second step of condensation as well as the
oxidation of benzoin to benzil. Although the exact function of
GO or rGO is not clearly understood, we tend to believe that GO
Table 3. Recycling of the catalyst tested with 2-nitroaniline
and benzil in one-pot reactions.
Entrya
Recovered
Catalyst (mg)
Catalyst
used (mg)
Time (h)
Yield
(%)b
(Reduction &
Condensation)
1st run

40
20
3 & 3
3 & 3
93
91
2nd run
28

7
5. Dailey, S.; Feast, W. J.; Peace, R. J.; Sage, I. C.; Till, S.; Wood,
is at first reduced to rGO and its electron-rich large surface area
might act favorably as the conductor of electrons thereby
facilitating release of hydrogen source from hydrazine that is
finally responsible for the reduction of nitro group,16,24 as well as
assisting to promote the condensation between the diamine and
diketone to form quinoxaline. Plausible mechanism is presented
in Scheme 2 indicating the role of GO or rGO.
E. L. J. Mater. Chem. 2001, 11, 2238-2243.
6. Sessler, J. L.; Maeda, H.; Mizuno, T.; Lynch, V. M.; Furuta, H. J.
Am. Chem. Soc. 2002, 124, 13474-13479.
7. (a) Lindner, B. D.; Zhang, Y.; Hoefle, S.; Berger, N.; Teusch, C.;
Jesper, M.; Hardcastle, K. I.; Qian, X.; Lemmer, U.; Colsmann,
A.; Bunz, U. H. F.; Hamburger, M. J. Mater. Chem. C 2013, 1,
5718-5724; (b) Thomas, K. R. J.; Velusamy, M.; Lin, J. T.;
Chuen, C.-H.; Tao, Y.-T. Chem. Mater. 2005, 17, 1860-1866.
8. Crossley, M. J.; Johnston, L. A. Chem. Commun. 2002, 1122-
1123.
9. (a) Nageswar, Y. V. D.; Reddy K. H. V.; Ramesh, K.; Murthy, S.
N. Org. Prep. Proc. Int. 2013, 45, 1-27; (b) Basu, B.; Mandal, B.
Sustainable Synthesis of Benzimidazole, Quinoxaline &
Congeners: Chapter 9; Elsevier: Oxford, 2014; pp 209-252.
10. (a) Ayaz M.; Xu Z.; Hulme C. Tetrahedron Lett. 2014, 55, 3406-
3409; (b) Paul, S.; Basu, B. Tetrahedron Lett. 2011, 52, 6597-
6602; (c) Huang, T. K.; Wang, R.; Shi, L.; Lu, X. X. Catal.
Commun. 2008, 9, 1143-1147; (d) Srinivas, C.; Kumar, C. N. S. S.
P.; Rao, V. J.; Palaniappan, S. J. Mol. Catal. A: Chem. 2007, 265,
227-230; (e) Darabi, H. R.; Mohandessi, S.; Aghapoor, K.;
Mohsenzadeh, F. Catal. Commun. 2007, 8, 389-392; (f) More, S.
V.; Sastry, M. N. V.; Wang, C. C.; Yao, C. F. Tetrahedron Lett.
2005, 46, 6345-6348; (g) Bhosale, R. S.; Sarda, S. R.; Ardhapure,
S. S.; Jadhav, W. N.; Bhusare, S. R.; Pawar, R. P. Tetrahedron
Lett. 2005, 46, 7183-7186; (h) Zhao, Z.; Wisnoski, D. D.;
Wolkenberg, S. E.; Leister, W. H.; Wang, Y.; Lindsley, C. W.
Tetrahedron Lett. 2004, 45, 4873-4876.
NH2
Condensation
promoted by
electron rich
surface of rGO
R
NO2
NH2
R
Overall 6e transfer
of N2H4 H2O (ref. 22a),
promoted by zigzag edge
and defects of rGO (ref. 16 )
NH2
+
O
R'
R'
N2H4 H2O
HO
N
R'
R'
GO or
rGO
O
O
R'
R'
rGO
ref. 20
R
ref. 15e
N
GO
+
N2H4 H2O
Scheme 2 Plausible mechanism
In summary, the present work demonstrates synthesis of bio-
active scaffold quinoxalines directly from 2-nitroaniline via one-
pot reduction-condensation reactions using hydrazine as the
reductant and GO/rGO as the catalysts under complete metal-free
conditions. The conditions are straightforward, mild and no other
side-products are obtained. Green process of preparation of
quioxalines from 2-nitroaniline is developed that could override
existing metal-catalyzed reaction conditions.
11. Xie, F.; Zhang, M.; Jiang, H.; Chen, M.; Lv, W.; Zhenga, A.;
Jiana, X. Green Chem. 2015, 17, 279-284.
12. (a) Go, A.; Lee, G.; Kim, J.; Bae, S.; Lee, B. M.; Kim, B. H.
Tetrahedron 2015, 71, 1215-1226; (b) Nguyen, T. B.; Retailleau,
P.; Al-Mourabit, A. Org. Lett. 2013, 15, 5238-5241; (c) Climent,
M. J.; Corma, A.; Hernández, J. C.; Hungría, A. B.; Iborra, S.;
Martínez-Silvestre, S. J. Catal. 2012, 292, 118-129; (d) Shi, D.-
Q.; Dou, G.-L.; Ni, S.-N.; Shi, J.-W.; Li, X.-Y. J. Heterocyclic.
Chem. 2008, 45, 1797-1801.
Acknowledgments
13. (a) Allais, C.; Grassot, J.-M.; Rodriguez, J.; Constantieux, T.
Chem. Rev. 2014, 114, 10829-10868; (b) Thomas, J.; John, J.;
Parekh, N.; Dehaen, W. Angew. Chem. Int. Ed. 2014, 53, 10155-
10159.
14. For review: see (a) Navalon, S.; Dhakshinamoorthy, A.; Alvaro,
M.; Garcia, H. Chem. Rev. 2014, 114, 6179-6212; (b) Su, C.; Loh,
K. P. Acc. Chem. Res. 2013, 46, 2275-2285.
BR and SG thank the UGC, New Delhi, for award of their
fellowships under UGC-FDP program.
Notes and references
15. (a) Chua, C.K.; Pumera, M.; Chem. Eur. J. 2015, 21, 1-14; (b) H.
Hu, J. H. Xin, H. Hu, X.Wang, Y. Kong, App. Catal. A: General
2015, 492, 1-9; (c) Dreyer, D.R.; Todd, A. D.; Bielawski, C.W.
Chem. Soc. Rev. 2014, 43, 5288-5301; (d) Dreyer, D. R.;
Bielawski, C.W. Chem. Sci. 2011, 2, 1233-1240; (e) Dreyer, D.
R.; Jia, H.-P.; Bielawski, C. W. Angew. Chem. Int. Ed. 2010, 49,
6813-6816.
1. (a) Brahmachari, G. Green Synthetic Approaches for Bilologically
Relevant Heterocycles; Elsevier: Oxford, 2014; pp 632. (b)
Alvarez-Builla, J.; Vaquero, J. J.; Barluenga, J. Modern
Heterocyclic Chemistry; John Wiley & Sons: Germany, 2011;
Vol. 1, pp 2530.
2. (a) Pereira, J. A.; Pessoa, A. M.; Cordeiro, M. N. D. S.; Fernandes,
R.; Prudencio, C.; Noronha J. P.; Vieir, M. Eur. J. Med. Chem.,
2014, 1-9; (b) Rodrigues, F. A. R.; Bomfim, I. S.; Cavalcanti, B.
C.; Pessoa, C. Ó.; Wardell, J. L.; Wardell, S. M. S. V.; Pinheiro,
A. C.; Kaiser, C. R.; Nogueira T. C. M.; Low, J. N.; Gomes, L. R.;
de Souza, M. V. N. Bioorg. Med. Chem. Lett. 2014, 24, 934-
939.(c) Hari Narayana Moorthy, N. S.; Manivannan, E.;
Karthikeyan, C.; Trivedi, P. Mini-Rev. Med. Chem. 2013, 13,
1415-1420 ;(d) Parhi, A. K.; Zhang, Y.; Saionz, K. W.; Pradhan,
P.; Kaul, M.; Trivedi, K.; Pilch, D. S.; LaVoie, E. J. Bioorg. Med.
Chem. Lett. 2013, 23, 4968-4974; (e) Smits, R. A.; Lim, H. D.;
Hanzer, A.; Zuiderveld, O. P.; Guaita, E.; Adami, M.; Coruzzi, G.;
Leurs, R.; de Esch, I. J. P. J. Med. Chem. 2008, 51, 2457-2467;
(f) Rong, F.; Chow, S.; Yan, S.; Larson, G.; Hong, Z.; Wu, J.;
Bioorg. Med. Chem. Lett. 2007, 17, 1663-1666; (g) Hui, X.;
Desrivot, J.; Bories, C.; Loiseau, P. M.; Franck, X.; Hocquemiller,
R.; Figadere, B. Bioorg. Med. Chem. Lett. 2006, 16, 815-820; (h)
Kim, Y. B.; Kim, Y. H.; Park, J. Y.; Kim, S. K. Bioorg. Med.
Chem. Lett. 2004, 14, 541-544; (i) Hazeldine, S. T.; Polin, L.;
Kushner, J.; Paluch, J.; White, K.; Edelstein, M.; Palomino, E.;
Corbett, T. H.; Horwitz, J. P. J. Med. Chem. 2001, 44, 1758-1776.
3. (a) Brock, E. D.; Lewis, D. M.; Yousaf, T. I.; Harper, H. H. The
Procter and Gamble Company, USA, WO9951688, 1999; (b)
Katoh, A.; Yoshida, T.; Ohkanda, J. Heterocycles 2000, 52, 911-
920.
16. Gao, Y.; Ma, D.; Wang, C.; Guan, J.; Bao, X. Chem. Commun.
2011, 47, 2432-2434.
17. (a) Kundu, S.; Basu, B. RSC Adv., 2015, 5, 50178-50185; (b) Roy,
B.; Sengupta, D.; Basu, B. Tetrahedron Lett. 2014, 55, 6596-6600;
(c) Sengupta, D.; Saha, J.; Basu, B.; De. G. RSC Adv., 2014, 4,
35442-35448; (d) Basu, B.; Kundu, S.; Sengupta, D. RSC Adv.,
2013, 3, 22130-22134.
18. Lakshmi, B.; Avaji, P.G.; Shivananda, K. N.; Nagella, P.;
Manohar, S. H.; Mahendra, K. N.; Polyhedron 2011, 30, 1507-
1515.
19. (a) Cioc, R. C.; Ruijter, E.; Orru, R. V. A. Green Chem. 2014, 16,
2958-2975; (b) Rotstein, B.H.; Zaretsky, S.; Rai, V.; Yudin, A. K.
Chem. Rev. 2014, 114, 8323-8359.
20. Stankovich, S.; Dikin, D. A.; Piner, R. D.; Kohlhaas, K. A.;
Kleinhammes, A.; Jia, Y.; Wu Y.; Nguyen, S. T.; Ruoff, R. S.
Carbon 2007, 45, 1558-1565.
21. Zangmeister, C. D.; Ma, X.; Zachariah, M. R. Chem. Mater. 2012,
24, 2554-2557.
22. (a) Larsen, J. W.; Freund, M.; Kim, K. Y.; Sidovar, M.; Stuart, J.
L. Carbon 2000, 38, 655-661; (b) Han, B. H.; Shin, D. H.; Cho, S.
Y. Tetrahedron Lett. 1985, 26, 6233-6234.
23. Kadam, H. K.; Khan S.; Kunkalkar, R. A.; Tilve, S. G.
Tetrahedron Lett. 2013, 54, 1003-1007.
24. Karim, M. R.; Hatakeyama, K.; Matsui, T.; Takehira, H.;
Taniguchi, T.; Koinuma, M.; Matsumoto, Y.; Akutagawa, T.;
Nakamura, T.; Noro, S.-ichiro ; Yamada, T. ; Kitagawa, H. ;
Hayami, S. J. Am. Chem. Soc. 2013, 135, 8097-8100.
4. Granifo, J.; Garland, M. T.; Baggio, R. Inorg. Chim. Acta 2003,
348, 263-270.

8
Tetrahedron
Supplementary Material
Clickhere to remove instruction text...
Supplementary material that may be helpful in the review
process should be prepared and provided as a separate electronic
file. That file can then be transformed into PDF format and
submitted along with the manuscript and graphic files to the
appropriate editorial office.