An efficient and recyclable nanoparticle-supported cobalt catalyst for quinoxaline synthesis

Article abstract of DOI:10.3390/molecules201119731

The syntheses of quinoxalines derived from 1,2-diamine and 1,2-dicarbonyl compounds under mild reaction conditions was carried out using a nanoparticle-supported cobalt catalyst. The supported nanocatalyst exhibited excellent activity and stability and it

Full text of DOI:10.3390/molecules201119731

Communication
An Efficient and Recyclable Nanoparticle-Supported
Cobalt Catalyst for Quinoxaline Synthesis
Fatemeh Rajabi *, Diego Alves and Rafael Luque 3
1
,
2
Received: 23 September 2015 ; Accepted: 12 November 2015 ; Published: 19 November 2015
Academic Editors: Nicola Cioffi, Antonio Monopoli and Massimo Innocenti
1
Department of Science, Payame Noor University, P. O. Box: 19395-4697, Tehran 19569, Iran
Laboratório de Síntese Orgânica Limpa—LASOL, Universidade Federal de Pelotas UFPEL, Pelotas,
2
CEP 96010-900, Brazil; diego.alves@ufpel.edu.br
Departamento de Quimica Organica, Universidad de Cordoba, Campus de Rabanales,
3
Edificio Marie Curie (C3), Ctra Nnal IV-A, Km 396, Cordoba E14014, Spain; q62alsor@uco.es
*
Correspondence: f_rajabi@pnu.ac.ir; Tel.: +34-957211050 (ext. 1050)
Abstract: The syntheses of quinoxalines derived from 1,2-diamine and 1,2-dicarbonyl compounds
under mild reaction conditions was carried out using a nanoparticle-supported cobalt catalyst. The
supported nanocatalyst exhibited excellent activity and stability and it could be reused for at least
ten times without any loss of activity. No cobalt contamination could be detected in the products by
AAS measurements, pointing to the excellent activity and stability of the Co nanomaterial.
Keywords: quinoxaline; catalysis; nanoparticles; cobalt; green chemistry
1
. Introduction
Quinoxaline derivatives are attractive N-containing heterocycles and these scaffolds have
attracted much attention, not only in synthetic chemistry [1–3] but also in the medicinal field [4–11].
These compounds exhibit diverse biological activities, such as antiviral [4,5], antibacterial [6],
anti-inflammatory [7], antitumoral [8,9] and anti-HIV properties [10,11]. Examples of quinoxaline-
containing pharmacological entities are shown in Figure 1. In addition, quinoxalines have been
applied as building blocks for the development of macrocyclic molecular receptors [12,13],
semiconducting materials [14–20], dyes [21], cavitands [22] and luminescent materials [23].
N
O
O
O
N
N
O
CH3
N
N
H
N
COOH
Cl
S
O
NCG555879-01
XK469 (NSC 697807)
COOH
Br
O
N
H
H
N
N
N
N
N
N
N
NH
H
O
N
N
COOH
N
varenicline
quinacilin
brimonidine
Figure 1. Biologically important quinoxalines.
Generally, quinoxalines can be prepared via a double condensation of 1,2-phenylenediamines
with 1,2-diketones [24–28]. A number of reagents have been shown to catalyze these reactions such
as acidic alumina [29], citric acid [30], magnetic Fe O nanoparticles in H O [31], silica-bonded
3
4
2
Molecules 2015, 20, 20709–20718; doi:10.3390/molecules201119731
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Molecules 2015, 20, 20709–20718
sulfonic acid [32], among others [33,34]. Other protocols to synthesize quinoxalines mainly
involve the oxidative trapping of vicinal diols or α-hydroxy ketones with 1,2-diamines [35–42],
1
2
,4-addition of 1,2-diamines to diazenylbutenes [43], coupling of epoxides with ene-1,2-diamines [44,45],
-nitroanilines with phenethylamines [46], alkynes or ketones with 1,2-diamines via a key oxidation
process [47–51]. Therefore, the development of efficient methods for accessing quinoxalines
derivatives continues to be an active area of research.
Nanoparticle-supported catalysts can offer important advantages as compared to homogeneous
transition metal systems and colloidal nanoparticles. These include a good reusability coupled
with high activities and specificities in different chemistries based on their excelling properties
(high surface areas, degenerated density of energy states and plasmon) [52–54]. In this regard,
Co/supported catalysts were previously reported to be highly active and versatile for acid and redox
catalyzed processes [54,55].
To the best of our knowledge, there is no protocol describing the preparation of quinoxaline
derivatives using a nanoparticle-supported cobalt catalyst. In view of the explained above, we
decided to examine the synthesis of substituted quinoxalines by reaction of 1,2-diketones with
1
,2-phenylenediamines using a nanoparticle-supported cobalt catalyst (Scheme 1).
Scheme 1. General scheme of the reactions.
2
. Results and Discussion
Initially, we chose 1,2-diphenylethanedione (1a)and 1,2-diamino-4-nitrobenzene (2a) as model
substrates to establish the best conditions for this reaction and some experiments were performed to
synthesize the corresponding quinoxaline 3a (Table 1). We started our studies reacting 1,2-diketone 1a
˝
(
1.0 mmol) with 1,2-phenylenediamine 2a (1.0 mmol) at 100 C for 2 h, without catalyst and solvent.
Under these conditions, product 3a was not obtained (Table 1, entry 1). Good results were obtained
however when the reactions of substrates 1a and 2a were carried out using H O as solvent in the
2
˝
˝
presence of Co NPs (2 mol %) as catalyst. Reactions performed at 100 C and 50 C gave the desired
product in 87% and 57% yield, respectively (Table 1, entries 2 and 3). A similar result was obtained
when the reaction was conducted at 100 C, however using 1 mol% of Co NPs (86% yield) (Table 1,
˝
entry 4). Good results were also found when the reactions were performed using EtOH as solvent
(
7
0
Table 1, entry 5–9). Excellent yields of product 3a were achieved in reactions carried out in EtOH at
8 C using 1 mol% of catalyst (Table 1, entries 7–8). When the amount of catalyst was reduced to
˝
.5 mol %, a decrease in the yield of product 3a was observed (Table 1, entry 9). Finally, the reaction
˝
performed using 1 mol % of Co NPs at 100 C and in absence of EtOH yielded the quinoxaline 3a in
7
1
2% yield (Table 1, entry 10).
Analyzing the results shown in Table 1, we established the best reaction conditions reacting
,2-diphenylethanedione (1a, 1.0 mmol, 0.033 g) with 1,2-diamino-4-nitrobenzene (2a, 1.0 mmol)
using supported CoNPs (1 mol %) as catalyst and EtOH (5 mL) as solvent. After that, the mixture
was stirred at reflux for 90 min in open atmosphere, affording 6-nitro-2,3-diphenylquinoxaline(3a) in
9
2% yield after crystallization.
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Molecules 2015, 20, 20709–20718
Table 1. Optimization of reaction condition a.
O
O N
2
NH2
NH2
O2N
N
N
Co NPs
solvent
+
O
1
time
a
2a
temperature
3
a
˝
Yield 3a (%) b
Entry
Catalyst (mol %)
Solvent
Temperature ( C)
Time (h)
1
2
3
4
5
6
7
8
9
-
2
2
1
2
2
1
1
0.5
1
-
100
100
50
100
78
50
78
78
78
2
2
2
2
2
2
2
1.5
1.5
2
-
H O
87
57
86
93
60
93
92
80
72
2
H O
2
H O
2
EtOH
EtOH
EtOH
EtOH
EtOH
-
1
0
100
a
Reactions are performed using, 1,2-diphenylethanedione 1a (1.0 mmol) and 1,2-diamino-4-nitrobenzene 2a
b
(
1.0 mmol) in open atmosphere. Yields are given for isolated product 3a after crystallization.
In order to extend the scope of the reaction, the best conditions were employed in reactions of
1
,2-diamino-4-nitrobenzene (2a) with other 1,2-diketones 1b–e with different patterns of substitution
and the results are summarized in Table 2. As it can be seen on Table 2 (Entries 1–5), our methodology
is suitable to a range of substituted 1,2-diketones containing electron-withdrawing groups, affording
excellent yields to desired products in all examples. In addition, the possibility of performing
the reaction of 1,2-diketones 1a–e with o-phenylenediamine (2b) was also investigated (Table 2,
entries 6–10). Using these substrates, a range of substituted quinoxalines was obtained in excellent
yields using the nanoparticle-supported cobalt catalyst under optimized reaction conditions.
Table 2. Generality of the reaction of 1,2-diketones with 1,2-diamines a.
Yield (%) b
˝
Entry
1,2-Diketone 1
1,2-Diamines 2
Product 3
M.P. ( C)
1
92
188–190
195–197
2
a
1
a
3
a
2
2a
92
1
b
3b
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Molecules 2015, 20, 20709–20718
Table 2. Cont.
1,2-Diamines 2 Product 3
Yield (%) b
˝
Entry
1,2-Diketone 1
M.P. ( C)
3
2a
2a
2a
92
173–175
175–177
143–145
127–129
1
c
3
c
4
5
6
90
88
92
1
d
3d
1
1
e
a
3
e
2
b
3
f
7
2b
96
127–129
1
b
3g
8
9
2b
2b
2b
94
94
94
133–135
190–192
134–135
1
c
3
h
1
d
3
i
1
0
1
e
3j
NH2
N
1
1
2
N
98
95
116–117
163–165
NH2
2
c
3
k
F
F
N
N
1
2c
3
l
a
Reactions were performed using 1,2-diketones 1a–e (1.0 mmol), 1,2-diamines 2a–b (1.0 mmol), supported
CoNPs (1 mol %, 0.033 g) and EtOH (5 mL) at reflux in open flask for 90 min. b Yields are given for isolated
products after crystallization.
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Molecules 2015, 20, 20709–20718
Reused runs were carried out under similarly optimized conditions using 5 mmol
1
,2-diphenylethanedione (1a), 5 mmol of 1,2-diamino-4-nitrobenzene (2a) and supported cobalt
˝
catalyst (0.05 mmol, 0.165 g) at 78 C in 10 mL of ethanol. The catalyst showed excellent recoverability
and reusability over ten successive runs under the same conditions as the first run. It is quite
remarkable that all materials discussed in this study exhibited outstanding structural stability by
TGA (results not shown). The cobalt catalyst was found to be highly stable and reusable under
the investigated conditions (up to 12 runs) without any significant loss of its catalytic activity
(
(
Table 3). Indeed, ICP analysis of both reaction filtrate and catalyst showed no detectable Co leaching
<0.5 ppm) in the reaction filtrate upon reaction completion, with an almost identical Co content for
both fresh and reused catalyst (0.30 vs. 0.29 mmol of Co per gram of catalyst for fresh and 10-time
reused material, respectively).
Table 3. Reuses of the supported CoNP catalyst in the reaction of 1,2-diphenylethanedione (1a) with
1
,2-diamino-4-nitrobenzene (2a).
Run No. a
1
2
3
4
5
6
7
8
9
10
Yield (%) b
94
94
92
92
92
90
91
90
90
87
a
Reaction conditions: 1,2-diphenylethanedione (5.0 mmol) and 1,2-diamino-4-nitrobenzene (5.0 mmol),
b
supported CoNPs ( 0.05 mmol, 0.165 g) in EtOH (10 mL) at reflux conditions for 90 min. Isolated yields.
The study of the scale-up reaction (from 1 to 20 mmol of substrate) was also investigated under
the optimized reaction conditions. When the amount of 1a and 2a was increased to 20 mmol, the same
conversion was obtained after 90 min under optimized conditions.
The catalytic performance of our system was eventually compared to reported literature data.
As can be seen in Table 4, our recoverable catalytic system possesses remarkably improved activities
as compared to those of related previously reported heterogeneous systems.
Table 4.
Comparison of the result in the reaction of 1,2-diphenylethanedione (1a) with
1
,2-diaminobenzene (2a) with our method and the previous literature.
Entry
Condition
Time (min) Yield (%)
Reference
1
2
3
4
5
6
7
8
9
Polyaniline-sulfate salt (5 wt %), DCE, r.t.
CAN (5 mol %), H2O, r.t.
20
10
35
5
2
1
150
5
5
5
90
95
98
95
99
96
94
95
96
99
97
92
[25]
[26]
[27]
[28]
[29]
[30]
[31]
[32]
[33]
I2 (10 mol %), DMSO, r.t.
˝
MeOH:AcOH (9:1), MW, 160
C
˝
Acidic alumina, 80
C
Citric acid (10 mol %), EtOH, r.t.
Fe3O4NPs (10 mol %), H2O, r.t.
Silicabonded S-sulfonicacid (3.4 mol %), EtOH/H2O (70/30), r.t.
Ga(OTf)3 (1 mol %), EtOH, r.t.
1
1
0
1
Bi(OTf)3 (10 mol %), H2O, r.t.
CoNP (1mol %), EtOH, reflux
[34]
Our work
3
. Experimental Section
3
.1. General Information
Unless otherwise stated, all reagents and chemicals in this study were used as received and
were not further purified (Sigma-Aldrich Chemie GmbH, Taufkirchen, Germany). Melting point
recorded on a RY-1 microscopic melting apparatus (Hangzhou Chincan Trading Co., Shanghai, China)
and uncorrected. 1H-NMR and C-NMR spectra were respectively recorded on 500 MHz and 125
MHz by using a Bruker Avance 500 spectrometer (Bruker BioSpin GmbH, Rheinstetten, Germany).
Metal content in the materials was determined using inductively coupled plasma (ICP) in a Philips
PU 70000 sequential spectrometer (Philips, Almelo, The Netherlands) equipped with an Echelle
13
monochromator (0.0075 nm resolution). Samples were digested in HNO and subsequently analyzed
3
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Molecules 2015, 20, 20709–20718
by ICP Nitrogen adsorption measurements (Philips) were carried out at 77 K using an ASAP 2000
volumetric adsorption analyzer from Micromeritics (Micromeritics, Norcross, GA, USA). The samples
˝
were outgassed for 24 h at 100 C under vacuum (p b 10–2 Pa) and subsequently analyzed.
3
.2. Preparation of the Supported Cobalt Catalyst
CoNPs was synthesized as previously reported [55]. Briefly, salicylaldehyde (2 mmol, 0.244 g)
was added to an excess of absolute MeOH, to which 3-aminopropyl(trimethoxy)silane (2 mmol,
.352 g) was subsequently added. The color of the solution instantly changed to yellow indicating
0
imine formation. After 3 h, cobalt (II) acetate, Co(OAc) ¨ 2H O (1 mmol, 0.248 g) was added to the
2
2
solution, and the mixture stirred for three additional hours to allow the new ligands to complex the
cobalt. A color change from pink to olive green is observed. SBA-15 (3 g) was activated by refluxing
in concentrated hydrochloric acid (6 M) and then washed thoroughly with deionized water and
dried before undergoing chemical surface modification. This activation treatment readily hydrolyses
the siloxane Si-O-Si bonds to Si-OH species which will be key to anchor the cobalt complex. Both
complex and activated silica were then mixed and the mixture was stirred overnight. The solvent
˝
was removed using a rotary evaporator, and the resulting olive green solid dried at 80 C overnight.
The final product was washed with MeOH and water (to remove all physisorbed metal species) until
˝
the washings were colourless. Further drying of the solid product was carried out in an oven at 80 C
´
1
for 8 h. The loading of cobalt was calculated about 0.3 mmol¨ g and surface analysis showed cobalt
2
´1
oxide species well dispersed on the surface of SBA-15 with 450 m ¨ g surface area and pore size of
3
´1
3
.6 nm with 0.77 cm ¨ g mesoporous pore volume.
3
.3. General Reaction Procedure
To a mixture of 1,2-dicarbonyl compound 1a–e (1.0 mmol) and 1,2-diamine 2a–b (1.0 mmol) in
ethanol (5 mL), supported CoNP (0.033g, 1 mol%) was added and the mixture was refluxed in an
open flask for 90 min. Reactions were monitored by thin layer chromatography (TLC) until total
disappearance of the starting material. After completion of the reaction, the reaction mixture was
cooled to room temperature, and resulting solid was collected by filtration and dissolved in ethyl
acetate (10 mL). The supported catalyst was recovered by filtration. After evaporation of solvent, the
resulting solid product was purified by crystallization in ethanol.
3
.4. Selected Spectroscopic Data
-Nitro-2,3-diphenylquinoxaline (Table 2, Entry 1, 3a). Yellow solid; m.p. 188–190 C (lit. [56]
˝
6
1
˝
93–194 C). H-NMR (CDCl ): δ 7.38 (m, 6H, Ar-H), 7.56 (m, 4H, Ar-H), 8.28 (m, 1H, Ar-H), 8.45
3
1
13
(m, 1H, Ar-H), 9.02 (m, 1H, Ar-H); C-NMR (CDCl ): δ 123.27, 125.51, 128.45, 129.67, 129.85, 129.95,
3
1
30.66, 137.95, 139.87, 143.39, 147.80, 155.62, 156.18.
,3-Diphenylquinoxaline (Table 2, Entry 6, 3f). White solid; m.p. 127–129 C (lit. [26] 126–127 C).
˝
˝
2
1
H-NMR (CDCl ): δ 7.35 (m, 6H, Ar-H), 7.56 (m, 4H, Ar-H), 7.76 (m, 2H, Ar-H), 8.20 (m, 2H, Ar-H);
3
13
C-NMR (CDCl ): δ 128.29, 128.89, 129.13, 129.915, 130.10, 138.92, 141.15, 154.38.
3
˝
,3-Bis(4-Fuorophenyl)quinoxaline (Table 2, Entry 8, 3h). White solid; m.p. 133–135 C (lit. [56]
2
1
˝
35–137 C). H-NMR (CDCl ): δ 7.06 (m, 4H, Ar-H), 7.52 (m, 4H, Ar-H), 7.80 (q, J = 9.5 Hz, 1H,
3
1
1
3
Ar-H), 8.16 (q, J = 9.1 Hz, 1H, Ar-H); C-NMR (CDCl ): δ 115.45, 115.61, 129.14, 130.22, 131.70,
3
1
31.82, 134.90, 135.02, 141.21, 152.16, 161.54, 164.80.
˝
2
1
2
1
,3-Bis(4-Chlorophenyl)quinoxaline (Table 2, Entry 9, 3i).White solid; m.p. 190–192 C (lit. [32]
˝
1
95–196 C). H-NMR (CDCl ): δ 7.32 (m, 4H, Ar-H), 7.49 (m, 4H, Ar-H), 7.72 (m, 2H, Ar-H), 8.11 (m,
H, Ar-H); C-NMR (CDCl ): δ 128.50, 128.62, 129.05, 129.11, 129.17, 130.05, 130.13, 130.26, 131.30,
3
13
3
34.12, 137.36, 138.62, 140.09, 141.11, 153.02, 153.18.
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Molecules 2015, 20, 20709–20718
˝
-Methyl-2,3-diphenylquinoxaline (Table 2, Entry 11, 3k). Brown solid; m.p. 116–118 C (lit. [33]
6
1
7
1
˝
1
17–118 C). H-NMR (CDCl ): δ 2.61 (s, 3H, Ar-CH ), 7.35 (s, 6H, Ar-H), 7.55 (d, J = 6.5, 4H, Ar-H),
3
3
13
.60 (s, 1H, Ar-H) 7.98 (s, 1H, Ar-H), 8.09 (d, J = 8.4, 1H, Ar-H); C-NMR (CDCl ): δ 21.95, 128.04,
3
28.24, 128.67, 128.73, 129.90, 129.92, 132.32, 139.24, 139.73, 140.49, 141.29, 152.55, 153.29.
4
. Conclusions
In summary, we have developed an environmentally friendly and highly active cobalt
nanoparticle on mesoporous SBA-15 material for the synthesis of quinoxalinesin excellent yields from
,2-diamine and 1,2-dicarbonyl compounds. Reactions could efficiently afford the target products
1
after short reaction times and were run under air and mild reaction conditions and require low
loadings of the supported catalyst. The catalyst was found to be highly reusable for at least ten
reaction runs under the investigated conditions.
Acknowledgments: F.R. is grateful to Payame Noor University for support of this work.
Author Contributions: F.R. conducted all experimental work, D.A. and R.L. supervised, discussed and
completely wrote the manuscript.
Conflicts of Interest: The authors declare no conflict of interest.
References
1
.
Brown, D.J. Quinoxalines: Supplement II. In The Chemistry of Heterocyclic Compounds; John Wiley & Sons:
Princeton, NJ, USA, 2004.
2.
3.
4.
Katritzky, A.R.; Pozharskii, A.F. Handbook of Heterocyclic Chemistry; Pergamon: Oxford, UK, 2000.
Eicher, T.; Hauptmann, S.; Speicher, A. The Chemistry of Heterocycles; Wiley-VCH: Weinheim, Germany, 2003.
Moorthy, N.; Hari, N.S.; Manivannan, E.; Karthikeyan, C.; Trivedi, P. 6H-Indolo[2,3-b]quinoxalines: DNA
and protein interacting scaffold for pharmacological activities. Mini Rev. Med. Chem. 2013, 13, 1415–1420.
[CrossRef] [PubMed]
5.
6.
7.
8.
Rong, F.; Chow, S.; Yan, S.; Larson, G.; Hong, Z.; Wu, J. Structure–activity relationship (SAR) studies of
quinoxalines as novel HCV NS5B RNA-dependent RNA polymerase inhibitors. Bioorg. Med. Chem. Lett.
2
007, 17, 1663–1666. [CrossRef] [PubMed]
Parhi, A.K.; Zhang, Y.; Saionz, K.W.; Pradhan, P.; Kaul, M.; Trivedi, K.; Pilch, D.S.; LaVoie, E.J. Antibacterial
activity of quinoxalines, quinazolines, and 1,5-naphthyridines. Bioorg. Med. Chem. Lett. 2013, 23, 4968–4974.
[CrossRef] [PubMed]
Smits, R.A.; Lim, H.D.; Hanzer, A.; Zuiderveld, O.P.; Guaita, E.; Adami, M.; Coruzzi, G.; Leurs, R.;
Esch, I.J.P. Fragment based design of new H receptor-ligands with anti-inflammatory properties in vivo.
4
J. Med. Chem. 2008, 51, 2457–2467. [CrossRef] [PubMed]
Hazeldine, S.T.; Polin, L.; Kushner, J.; Paluch, J.; White, K.; Edelstein, M.; Palomino, E.; Corbett, T.H.;
Horwitz, J.P. Design, synthesis, and biological evaluation of analogues of the antitumor agent,
2
-{4-[(7-chloro-2-quinoxalinyl)oxy]phenoxy}propionic acid (XK469). J. Med. Chem. 2001, 44, 1758–1776.
[CrossRef] [PubMed]
9
.
Rajule, R.; Bryant, V.C.; Lopez, H.; Luo, X.; Natarajan, A. Perturbing pro-survival proteins using
quinoxaline derivatives: A structure–activity relationship study. Bioorg. Med. Chem. 2012, 20, 2227–2234.
[CrossRef] [PubMed]
1
0. Hui, X.; Desrivot, J.; Bories, C.; Loiseau, P.M.; Franck, X.; Hocquemiller, R.; Figadere, B. Synthesis and
antiprotozoal activity of some new synthetic substituted quinoxalines. Bioorg. Med. Chem. Lett. 2006, 16,
8
15–820. [CrossRef] [PubMed]
1
1. Kim, Y.B.; Kim, Y.H.; Park, J.Y.; Kim, S.K. Synthesis and biological activity of new quinoxaline antibiotics of
echinomycin analogues. Bioorg. Med. Chem. Lett. 2004, 14, 541–544. [CrossRef] [PubMed]
2. Sessler, J.L.; Maeda, H.; Mizuno, T.; Lynch, V.M.; Furuta, H. Quinoxaline-Bridged Porphyrinoids. J. Am.
Chem. Soc. 2002, 124, 13474–13479. [CrossRef] [PubMed]
1
20715

Molecules 2015, 20, 20709–20718
1
1
1
3. Azov, V.A.; Beeby, A.; Cacciarini, M.; Cheetham, A.G.; Diederich, F.; Frei, M.; Gimzewski, J.K.; Gramlich, V.;
Hecht, B.; Jaun, B.; et al. Resorcin[4]arenecavitand-based molecular switches. Adv. Funct. Mater. 2006, 16,
1
47–156. [CrossRef]
4. Champion, R.D.; Cheng, K.-F.; Pai, C.-L.; Chen, W.-C.; Jenekhe, S.A. Electronic properties and field-effect
transistors of thiophene-based donor–acceptor conjugated copolymers. Macromol. Rapid Commun. 2005, 26,
1
835–1840. [CrossRef]
5. Wang, E.; Hou, L.; Wang, Z.; Hellström, S.; Zhang, F.; Inganäs, O.; Andersson, M.R. An easily synthesized
blue polymer for high-performance polymer solar cells. Adv. Mater. 2010, 22, 5240–5244. [CrossRef]
[PubMed]
1
6. Chang, D.W.; Lee, H.J.; Kim, J.H.; Park, S.Y.; Park, S.-M.; Dai, L.; Baek, J.-B. Novel quinoxaline-based organic
sensitizers for dye-sensitized solar cells. Org. Lett. 2011, 13, 3880–3883. [CrossRef] [PubMed]
1
7. Zhang, X.; Shim, J.W.; Tiwari, S.P.; Zhang, Q.; Norton, J.E.; Wu, P.-T.; Barlow, S.; Jenekhe, S.A.; Kippelen, B.;
Brédas, J.-L.; et al. Dithienopyrrole–quinoxaline/pyridopyrazinedonor-acceptorpolymers: Synthesis and
electrochemical, optical, charge-transport, and photovoltaic properties. J. Mater. Chem. 2011, 21, 4971–4982.
[CrossRef]
1
8. Zhuang, W.; Zhen, H.; Kroon, R.; Tang, Z.; Hellström, S.; Hou, L.; Wang, E.; Gedefaw, D.; Inganäs, O.;
Zhang, F.; et al. Molecular orbital energy level modulation through incorporation of selenium and fluorine
into conjugated polymers for organic photovoltaic cells. J. Mater. Chem. A 2013, 1, 13422–13425. [CrossRef]
9. Wang, K.; Zhang, Z.-G.; Fu, Q.; Li, Y. Synthesis and photovoltaic properties of a D–A copolymer based
on the 2,3-di(5-hexylthiophen-2-yl)quinoxaline acceptor unit. Macromol. Chem. Phys. 2014, 215, 597–603.
1
[CrossRef]
2
2
2
0. Chen, S.; Zhang, Q.; Zhang, J.; Gu, J.; Zhang, L. Synthesis of two conjugated polymers as TNT chemosensor
materials. Sens. Actuators B 2010, 149, 155–160. [CrossRef]
1. Brock, E.D.; Lewis, D.M.; Yousaf, T.I.; Harper, H.H. Reactive Dye Compounds. U.S. Patent WO1999051688
A1, 14 October 1999.
2. Lindner, B.D.; Zhang, Y.; Hoefle, S.; Berger, N.; Teusch, C.; Jesper, M.; Hardcastle, K.I.; Qian, X.; Lemmer, U.;
Colsmann, A.; et al. N-fused quinoxalines and benzoquinoxalines as attractive emitters for organic light
emitting diodes. J. Mater. Chem. C 2013, 1, 5718–5724. [CrossRef]
2
2
2
3. Thomas, K.R.J.; Velusamy, M.; Lin, J.T.; Chuen, C.-H.; Tao, Y.-T. Chromophore-labeled quinoxaline
derivatives as efficient electroluminescent materials. Chem. Mater. 2005, 17, 1860–1866. [CrossRef]
4. Ayaz, M.; Xu, Z.; Hulme, C. Novel succinct routes to quinoxalines and 2-benzimidazolylquinoxalines via
the Ugi reaction. Tetrahedron Lett. 2014, 55, 3406–3409. [CrossRef] [PubMed]
5. Srinivas, C.; Kumar, C.N.S.S.P.; Rao, V.J.; Palaniappan, S. Efficient, convenient and reusable
polyaniline-sulfate salt catalyst for the synthesis of quinoxaline derivatives. J. Mol. Catal. A Chem. 2007,
2
65, 227–230. [CrossRef]
2
2
2
2
3
3
6. More, S.V.; Sastry, M.N.V.; Yao, C.-F. Cerium(IV) ammonium nitrate(CAN) as a catalyst in tap water: A
simple, proficient and green approach for the synthesis of quinoxalines. Green Chem. 2006, 8, 91–95.
[CrossRef]
7. Bhosale, R.S.; Sarda, S.R.; Ardhapure, S.S.; Jadhav, W.N.; Bhusare, S.R.; Pawar, R.P. An efficient protocol
for the synthesis of quinoxaline derivatives at room temperature using molecular iodine as the catalyst.
Tetrahedron Lett. 2005, 46, 7183–7186. [CrossRef]
8. Zhao, Z.; Wisnoski, D.D.; Wolkenberg, S.E.; Leister, W.H.; Wang, Y.; Lindsley, C.W. General
microwave-assisted protocols for the expedient synthesis of quinoxalines and heterocyclic pyrazines.
Tetrahedron Lett. 2004, 45, 4873–4876. [CrossRef]
9. Jafarpour, M.; Rezaeifard, A.; Danehchin, M. Easy access to quinoxaline derivatives using alumina as
an effective and reusable catalyst under solvent-free conditions. Appl. Catal. A Gen. 2011, 394, 48–51.
[CrossRef]
0. Mahesh, R.; Dhar, A.K.; Sasank, T.V.N.V.T.; Thirunavukkarsu, S.; Devadoss, T. Citric acid: An efficient and
green catalyst for rapid one pot synthesis of quinoxaline derivatives at room temperature. Chin. Chem. Lett.
2
011, 22, 389–392. [CrossRef]
1. Lü, H.-Y.; Yang, S.-H.; Deng, J.; Zhang, Z.-H. Magnetic Fe O nanoparticles as new, efficient, and reusable
3
4
catalysts for the synthesis of quinoxalines in water. Aust. J. Chem. 2010, 63, 1290–1296. [CrossRef]
20716

Molecules 2015, 20, 20709–20718
3
3
3
3
2. Niknam, K.; Saberi, D.; Mohagheghnejad, M. Silica bonded S-sulfonic acid: A recyclable catalyst for the
synthesis of quinoxalines at room temperature. Molecules 2009, 14, 1915–1926. [CrossRef] [PubMed]
3. Cai, J.-J.; Zou, J.-P.; Pan, X.-Q.; Zhang, W. Gallium(III) triflate-catalyzed synthesis of quinoxaline derivatives.
Tetrahedron Lett. 2008, 49, 7386–7390. [CrossRef]
4. Yadav, J.S.; Subba Reddy, B.V.; Premlatha, K.; Shankar, K.S. Bismuth(III)-catalyzed rapid synthesis of
2
,3-disubstituted quinoxalines in water. Synthesis 2008, 3787–3792. [CrossRef]
5. Hille, T.; Irrgang, T.; Kempe, R. The Synthesis of benzimidazoles and quinoxalines from aromatic diamines
and alcohols by iridium-catalyzed acceptorless dehydrogenative alkylation. Chem. Eur. J. 2014, 20,
5
569–5572. [CrossRef] [PubMed]
3
3
3
3
4
4
6. Cho, C.S.; Oh, S.G. A new ruthenium-catalyzed approach for quinoxalines from o-phenylenediamines and
vicinal-diols. Tetrahedron Lett. 2006, 47, 5633–5636. [CrossRef]
7. Jeena, V.; Robinson, R.S. An environmentally friendly, cost effective synthesis of quinoxalines: The influence
of microwave reaction conditions. Tetrahedron Lett. 2014, 55, 642–645. [CrossRef]
8. Sithambaram, S.; Ding, Y.; Li, W.; Shen, X.; Gaenzler, F.; Suib, S.L. Manganese octahedral molecular sieves
catalyzed tandem process for synthesis of quinoxalines. Green Chem. 2008, 10, 1029–1032. [CrossRef]
9. Robinson, R.S.; Taylor, R.J.K. Quinoxaline synthesis from α-hydroxy ketones via a tandem oxidation process
using catalysed aerobic oxidation. Synlett 2005, 1003–1005.
0. Kim, S.Y.; Park, K.H.; Chung, Y.K. Manganese(IV) dioxide-catalyzed synthesis of quinoxalines under
microwave irradiation. Chem. Commun. 2005, 1321–1323. [CrossRef] [PubMed]
1. Raw, S.A.; Wilfred, C.D.; Taylor, R.J.K. Tandem oxidation processes for the preparation of
nitrogen-containing heteroaromatic and heterocyclic compounds. Org. Biomol. Chem. 2004, 2, 788–796.
[CrossRef] [PubMed]
4
2. Aparicio, D.; Attanasi, O.A.; Filippone, P.; Ignacio, R.; Lillini, S.; Mantellini, F.; Palacios, F.;
Santos, J.M. Straightforward access to pyrazines, piperazinones, and quinoxalinesby reactions of
1
,2-diaza-1,3-butadienes with 1,2-diamines under solution, solvent-free, or solid-phase conditions. J. Org.
Chem. 2006, 71, 5897–5905. [CrossRef] [PubMed]
4
3. Ibrahim, M.M.; Grau, D.; Hampel, F.; Tsogoeva, S.B. α-Nitro epoxides in organic synthesis: development
of a one-pot organocatalytic strategy for the synthesis of quinoxalines. Eur. J. Org. Chem. 2014, 1401–1405.
[CrossRef]
4
4
4. Antoniotti, S.; Dunach, E. Direct and catalytic synthesis of quinoxaline derivatives from epoxides and
ene-1,2-diamines. Tetrahedron Lett. 2002, 43, 3971–3973. [CrossRef]
5. Nguyen, T.B.; Retailleau, P.; Al-Mourabit, A. A simple and straightforward approach to quinoxalines by
iron/sulfur-catalyzed redox condensation of o-nitroanilines and phenethylamines. Org. Lett. 2013, 15,
5
238–5241. [CrossRef] [PubMed]
4
6. Xu, Y.; Wan, X. Ruthenium-catalyzed oxidation of alkynes to 1,2-diketones under room temperature and
one-pot synthesis of quinoxalines. Tetrahedron Lett. 2013, 54, 642–645. [CrossRef]
4
7. Shi, S.; Wang, T.; Yang, W.; Rudolph, M.; Hashmi, A.S.K. Gold-catalyzed synthesis of glyoxals by oxidation
of terminal alkynes: one-pot synthesis of quinoxalines. Chem. Eur. J. 2013, 19, 6576–6580. [CrossRef]
[PubMed]
4
8. Okumura, S.; Takeda, Y.; Kiyokawa, K.; Minakata, S. Hypervalent iodine(III)-induced oxidative [4+2]
annulation of o-phenylenediamines and electron-deficient alkynes: Direct synthesis of quinoxalines from
alkyne substrates under metal-free conditions. Chem. Commun. 2013, 49, 9266–9268. [CrossRef] [PubMed]
9. Chen, C.-Y.; Hu, W.-P.; Liu, M.-C.; Yan, P.-C.; Wang, J.-J.; Chung, M.-I. Efficient synthesis of quinoxalines
with hypervalent iodine as a catalyst. Tetrahedron 2013, 69, 9735–9741. [CrossRef]
4
5
0. Zhang, C.; Xu, Z.; Zhang, L.; Jiao, N. Et N-catalyzed oxidative dehydrogenative coupling of
3
α-unsubstituted aldehydes and ketones with aryl diamines leading to quinoxalines using molecular oxygen
as oxidant. Tetrahedron 2012, 68, 5258–5262. [CrossRef]
51. Campelo, J.M.; Luna, D.; Luque, R.; Marinas, J.M.; Romero, A.A. Sustainable preparation of supported
metal nanoparticles and their applications in catalysis. ChemSusChem 2009, 2, 18–45. [CrossRef] [PubMed]
52. White, R.J.; Luque, R.; Budarin, V.; Clark, J.H.; Macquarrie, D.J. Supported metal nanoparticles on porous
materials. Methods and applications. Chem. Soc. Rev. 2009, 38, 481–494. [CrossRef] [PubMed]
53. Astruc, D.; Lu, F.; Aranzaes, J.R. Nanoparticles as recyclable catalysts: The frontier between homogeneous
and heterogeneous catalysis. Angew. Chem. Int. Ed. 2005, 44, 7852–7872. [CrossRef] [PubMed]
20717

Molecules 2015, 20, 20709–20718
5
5
5
4. Rajabi, F.; Feiz, A.; Luque, R. An efficient synthesis of coumarin derivatives using a SBA-15 supported
Cobalt(II) nanocatalyst. Catal. Lett. 2015, 145, 1621–1625. [CrossRef]
5. Rajabi, F.; Raessi, M.; Arancon, R.A.D.; Saidi, M.R.; Luque, R. Supported cobalt oxide nanoparticles as
efficient catalyst in esterification and amidation reactions. Catal. Commun. 2015, 59, 122–126. [CrossRef]
6. Heravi, M. M.; Taheri, S.; Bakhtiari, K.; Oskooie, H. A. Zn[(L)proline]: A powerful catalyst for the very fast
synthesis of quinoxaline derivatives at room temperature. Catal. Commun. 2007, 8, 1341–1344. [CrossRef]
Sample Availability: Samples of the compounds 3a–l are available from the authors.
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2015 by the authors; licensee MDPI, Basel, Switzerland. This article is an open
access article distributed under the terms and conditions of the Creative Commons by
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