Silica supported dodecatungstophosphoric acid (DTP/SiO2): An efficient and recyclable heterogeneous catalyst for rapid synthesis of quinoxalines

Article abstract of DOI:10.1080/00397911.2021.1939060

A facile synthesis of quinoxalines by the cyclocondensation of substituted phenacyl bromides with o-pheneylenediamines using silica-supported dodecatungstophosphoric acid (DTP/SiO₂) as a recyclable heterogeneous catalyst is unveiled in this res

Full text of DOI:10.1080/00397911.2021.1939060

Synthetic Communications
An International Journal for Rapid Communication of Synthetic Organic
Chemistry
ISSN: (Print) (Online) Journal homepage: https://www.tandfonline.com/loi/lsyc20
Silica supported dodecatungstophosphoric
acid (DTP/SiO2): An efficient and recyclable
heterogeneous catalyst for rapid synthesis of
quinoxalines
Madhav J. Hebade, Tejshri R. Deshmukh & Sambhaji T. Dhumal
To cite this article: Madhav J. Hebade, Tejshri R. Deshmukh & Sambhaji T. Dhumal (2021) Silica
supported dodecatungstophosphoric acid (DTP/SiO2): An efficient and recyclable heterogeneous
catalyst for rapid synthesis of quinoxalines, Synthetic Communications, 51:16, 2510-2520, DOI:
10.1080/00397911.2021.1939060
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2021, VOL. 51, NO. 16, 2510–2520
https://doi.org/10.1080/00397911.2021.1939060
Silica supported dodecatungstophosphoric acid (DTP/SiO2):
An efficient and recyclable heterogeneous catalyst for
rapid synthesis of quinoxalines
Madhav J. Hebadea, Tejshri R. Deshmukhb, and Sambhaji T. Dhumalc
b
aDepartment of Chemistry, Badrinarayan Barwale Mahavidyalaya, Jalna, India; Department of
c
Chemistry, Dr. Babasaheb Ambedkar Marathwada University, Aurangabad, India; Department of
Chemistry, Ramkrishna Paramhansa Mahavidyalaya, Osmanabad, India
ABSTRACT
ARTICLE HISTORY
Received 12 May 2021
A facile synthesis of quinoxalines by the cyclocondensation of substi-
tuted phenacyl bromides with o-pheneylenediamines using silica-
supported dodecatungstophosphoric acid (DTP/SiO2) as a recyclable
heterogeneous catalyst is unveiled in this research work. This
method is practicable due to environmentally benign, easy workup,
high yield, less reaction time, low cost, mild reaction condition, and
recyclable heterogeneous catalyst. The catalyst can be easily recov-
ered from the reaction mixture only by filtration and reused up to
five catalytic cycles without significant loss of catalytic activity and
product yield. This leads to making the process more affordable.
KEYWORDS
Catalyst loading;
heterogeneous catalyst;
quinoxalines; recyclability
GRAPHICAL ABSTRACT
DTP
(Dodecatungstophosphoric
acid hexahydrate) is a polymer
composed of tungsten atoms in
purple, phosphorus are shown
in green, oxygen in red, and
hydrogen in pink.
A facile protocol has been reported for quinoxalines synthesis
from substituted phenacyl bromides and o-pheneylenedi-
amines using dodecatungstophosphoric acid (DTP/SiO2) as a
CONTACT Sambhaji T. Dhumal
sambhajirajedhumal@gmail.com
Department of Chemistry, Ramkrishna
Paramhansa Mahavidyalaya, Vidyanagar, Osmanabad 413501, India.
Supplemental data for this article can be accessed on the publisher’s website.
ß 2021 Taylor & Francis Group, LLC

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recyclable heterogeneous catalyst. This method is practicable
due to simple reaction conditions.
Introduction
Quinoxalines are nitrogen-containing heterocyclic compounds, which are well known
for their broad biological applications such as antibacterial,[1] anticancer,[2] antiviral,[3]
anti-HIV,[4] kinase inhibition,[5] and sensing of ions,[6–9] etc. Quinoxaline ring scaffold
was present in several drug molecules as a key structural motif[10] like clofazimine,
chloroquinoxaline sulfonamide, briminodine, quinacillin, varencline, echinomycin, lero-
mycin, and actinomycin as shown in Figure 1. Correspondingly, derivatives of quinoxa-
lines have several applications in dyes,[11] electroluminescent material,[12] organic
semiconductors,[13] dehydroannulenes,[14] and chemically controllable switches.[15]
Consequently, the renowned chemical and biological significance of quinoxalines have
been attracted the organic community to develop an ideal method for the synthesis of
quinoxalines and their derivatives.
Literature survey revealed that there are numerous synthetic methods have been reported
to constitute quinoxaline scaffold. The condensation of o-phenylenediamine with 1,2-dicar-
bonyl compounds,[16–19] 1,2-diazenylbutens[20] and oxidation trapping of a-hydroxy
ketones[21–23] are some of the reported synthetic methods. These synthetic methods were
involved the presence of various catalysts such as citric acid,[24] heteropoly acid,[25] cellulose
sulfuric acid,[26] PEG-400,[27] hypervalent iodine (III) in PEG-400,[28] polyaniline-sulfate
salt,[29] CAN,[18] MnO2,[22] fluorinated alcohols,[30] (NH4)6Mo7O24. 4H2O,[31] PVPPOTf,[32]
amberlite IR-120H,[33] and Ga(ClO4)3.[34]
Figure 1. Some quinoxaline derivatives with pharmacological activities.

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M. J. HEBADE ET AL.
Among these few synthetic methods of quinoxalines, one of the methods—the con-
densation of o-phenylenediamine with phenacyl bromides in the solid phase—is highly
preferred.[35] This method has been reported by using catalyst-free approach,[36] transi-
tion metal-catalyzed approaches[37–39] as well as with various heterogeneous catalysts like
HClO4-SiO2,[40] TMSCl,[41] b-cyclodextrin,[42] micellar SDS,[43] silica-supported phos-
phomolybdic acid,[44] T3PDMSO or T3P,[45] N-Bromosuccinimide[46] and DABCO.[47]
However, reported protocols are accompanying with some lacunas such as the use of
HClO4-SiO2 catalyst is hazardous in nature than its potential application,[40] the reac-
tion catalyzed by TMSCl required higher temperature and low product yield,[41] the
b-cyclodextrin and micellar SDS catalyzed reactions were required longer time while
DABCO catalyst is non-recyclable.[42,43,47] Considering these lacunas with synthetic
methods and used catalysts, still there is a need for designing appropriate synthetic
methods with the development of new catalysts having acidic strength and recyclability
to be environmentally benign.
Heteropolyacids are excellent alternatives for conventional reagents and are usually
used in various organic transformations. Solid acids as heterogeneous catalysts have
been extensively used and accepted stratagem in organic synthesis. Literature survey
shows that silica-supported heterogeneous catalyst DTP/SiO2 (dodecatungstophosphoric
acid) is better than the conventional homogeneous acid catalysts due to its low cost,
simple operation, low toxicity, and environmental compatibility.[48–50] In addition to
this, the catalyst can be easily recovered from the reaction mixture only by filtration
and reused, which leads to making the process affordable.
By considering all the above aspects regarding synthetic methods and catalysts used
to synthesize quinoxalines, herein, we have reported an efficient and convenient meth-
odology for the synthesis of quinoxalines by condensation of phenacyl bromides with o-
phenylenediamine using DTP/SiO2 as a green and recyclable heterogeneous catalyst.
Results and discussion
The synthesis of quinoxalines was carried out by reacting substituted phenacyl bromides
(2a–m) (0.001 moles) and o-pheneylenediamines (1a–b) (0.001 moles) in the presence of
DTP/SiO2 (20 mole%) as a catalyst. Further, the reaction mass was stirred at 90 ꢀC for
30–50 min. afforded quinoxalines (3a–s) with excellent yields and high purity, which is
outlined in Scheme 1.
The structures of all the synthesized quinoxalines (3a–s) are shown in Figure 2.
Optimization of the reaction parameters was performed by general model reaction of
o-pheneylenediamine (1a) and phenacyl bromide (2a) as shown below.
Initially, we have considered solvent parameters and studied reactions in different sol-
vents like water, methanol, and ethanol as protic solvents as well as dichloromethane,

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Scheme 1. Synthesis of quinoxalines using DTP/SiO2 catalyst.
Figure 2. Structures of all the synthesized quinoxalines (3a–s).
acetonitrile, and dimethylformamide as aprotic solvents. It was observed that the qui-
noxaline formation in dimethylformamide solvent proceeds with a high yield (Table 1,
entry 6). Whereas, the reaction in methanol, ethanol, dichloromethane, and acetonitrile
solvents afforded a low yield of the products (Table 1, entries 2–5). No reaction was
observed in presence of water used as a solvent (Table 1, entry 1).

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Table 1. Screening of reaction condition with respect to solvent and catalyst loading 3aa.
Sr. No.
Solvent
Catalyst
Yieldb (%)
1
2
3
4
5
6
7
8
9
Water
Methanol
Ethanol
Dichloromethane
20% DTP/SiO2
20% DTP/SiO2
20% DTP/SiO2
20% DTP/SiO2
20% DTP/SiO2
20% DTP/SiO2
25% DTP/SiO2
30% DTP/SiO2
No catalyst
NR
60
64
70
75
94
94
93
03
Acetonitrile
Dimethylformamide
Dimethylformamide
Dimethylformamide
Dimethylformamide
aReaction conditions: Phenacyl bromide (0.001 mole), o-phenylenediamine (0.001 mol), 20% DTP/SiO2 in 10 ml DMF, at
90 ꢀC for 30 min. bIsolated yields.
NR: no reaction.
The solvent plays a key role in the activity and performance of the catalyst. In polar
protic solvent, substrates do not have a chance to come in contact with the catalyst.
Therefore, the presence of protic solvents gives a low yield of the product as compared
to aprotic solvents.
Here, we have observed promising results in dimethylformamide as a solvent over a
DTP/SiO2 catalyst, which allowed us to further evaluate catalyst loading and the results
are summarized in Table 1, entries 6–9. The results reveal that 20 mole% of DTP/SiO2
catalyst loading is sufficient for the desired conversion. While in the case of 25 and
30 mole% DTP/SiO2 loading did not show any considerable increase in the yield of
product (Table 1, entries 7 and 8). Under optimized conditions when the standard reac-
tion was performed in absence of DTP/SiO2 there was a negligible conversion of reac-
tants to products after heating for 3–4 h (Table 1, entry 9).
This result encourages us to explore the methodology scope for the synthesis of qui-
noxalines from substituted phenacyl bromides and o-pheneylenediamines in optimized
reaction condition 20 mole% of DTP/SiO2 catalyst and dimethylformamide (DMF)
as solvent.
We have also investigated the recyclability of DTP/SiO2 catalyst for the model reac-
tion of o-phenylenediamine (1a) and phenacyl bromide (2a) in DMF solvent at 90 ꢀC
for 30 min and results were depicted in Figure 3.
DTP/SiO2 catalyst was recovered simply by filtration and reused five times without
the loss of catalytic activity and the isolated yield of the product at the end of the 4th
recycle was much consistent in comparison with the fresh DTP/SiO2 catalyst.
The plausible mechanism for the synthesis of quinaxoline as shown in Scheme 2,
involves the protonation of the carbonyl group of phenacyl bromide over the DTP/SiO2
indicated as A, later it reacts with o-pheneylenediamine involves the dehydration and
dehalogenation resulted in the formation of cyclic product B, which is readily oxidized
in air to form desired product C.
Conclusion
In conclusion, we have developed a mild, efficient, and environmentally benign syn-
thetic method for quinoxalines (3a–s) from substituted phenacyl bromides and o-phe-
neylenediamines using heterogeneous dodecatungastophosphoric acid (DTP/SiO2) as a
green and recyclable catalyst. The key feature of the protocol involves simple reaction

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The recyclability of DTP/SiO2
in the synthesis of
quinoxalines
100
90
80
70
60
50
40
30
20
10
0
Cycles
Cycle 1 Cycle 2 Cycle 3 Cycle 4
Cycle 5
a
Figure 3. The recyclability of DTP/SiO2 in the synthesis of quinoxalines.
Scheme 2. Plausible mechanism for the synthesis of quinoxaline derivative.

2516
M. J. HEBADE ET AL.
conditions, no side reaction, and product formation in high yield. The present method
is an alternative to the conventional processes for the synthesis of quinoxalines.
The catalyst was recovered several times without loss of catalytic activity, which makes
the process cost-effective.
Experimental
General procedure for the preparation of DTP/SiO2
DTP impregnate SiO2 (20% DTP/SiO2) catalyst was prepared by an incipient wetness
technique.[48] Firstly, 2 gm of dry dodecatungstophosphoric acid (DTP) was dissolved in
10 ml of methanol. The solution was added in a small portion of 1 mL each time to the
silica with constant stirring with a glass rod properly. The solution was added at time
intervals of 2 min. Initially, on the addition of the DTP solution, silica was in a powdery
form but on complete addition, it formed a paste. The paste on further kneading for
20 min resulted in a free-flowing powder. The performed catalyst was dried at 120 ꢀC
for removal of water and other volatiles and subsequently calcinated at 285 ꢀC for 3 h.
General experimental procedure for the synthesis of quinoxalines
A mixture of phenacyl bromide (0.001 moles) and DTP/SiO2 (20 mole%) was stirred in
10 ml DMF solvent at room temperature for 5 min. Then o-phenylenediamine
(0.001 moles) was added slowly and the resultant mixture was stirred for 10 min at
room temperature and heated for a stipulated time. The completion of the reaction was
monitored by TLC. After completion of the reaction, the reaction mixture was diluted
with ethyl acetate (10 ml) and the catalyst was recovered by filtration. The filtrate was
washed with aqueous NaHCO3 and then with water followed by separation of aqueous
layer and organic layer. The organic layer is dried over anhydrous Na2SO4 and concen-
trated in a vacuum to give the crude product. The crude product was purified by crys-
tallization using ethanol to afford the pure quinoxaline. The melting points of the
products isolated in this study were found to be in good agreement with those reported
in the literature.[51–56]
2-(4-Bromophenyl)quinoxaline (3d)
The compound (3d) was obtained by DTP/SiO2 catalyzed reaction in between o-pheney-
lenediamine (1a) and phenacyl bromide (2d) as pale yellow solid; yield 94%; mp
1
138–139 ꢀC; H NMR (300 MHz, CDCl3) d (ppm): 7.76 (d, J ¼ 12 Hz, 1H), 7.78 (s, 1H),
7.81 (d, J ¼ 3 Hz, 2H), 8.08 (d, J ¼ 3 Hz, 1H), 8.13 (d, J ¼ 9 Hz, 3H), 9.30 (s, 1H); 13C
NMR (75 MHz, CDCl3) d (ppm): 125.14, 129.15, 129.32, 129.75, 129.97, 130.64, 132.51,
142.96, 150.81; HRMS (ESIþ) calcd. for C14H9BrN2 (M þ H)þ: 285.0024; found 285.0021.
2-(4-Chlorophenyl)-7-methylquinoxaline (3o)
The compound (3o) was obtained by DTP/SiO2 catalyzed reaction in between o-pheney-
lenediamine (1b) and phenacyl bromide (2c) as brown solid; yield 92%; mp 112–115 ꢀC;
1H NMR (300 MHz, CDCl3) d (ppm): 2.61 (s, 3H, CH3), 7.54 (d, J ¼ 6 Hz, 2H), 7.60

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(d, J ¼ 6 Hz, 1H), 7.91 (d, J ¼ 9 Hz, 1H), 8.03–8.15 (m, 3H, Ar-H), 9.25 (s, 1H); 13C
NMR (75 MHz, CDCl3) d (ppm): 22.03, 128.55, 128.77, 129.23, 129.49, 132.37, 132.95,
135.49, 141.21, 142.11, 142.91, 149.93, 150.65; HRMS (ESIþ) calcd. for C15H11ClN2
(M þ H)þ: 255.0689; found 255.0684.
1
Full experimental detail, HRMS/MS, H and 13C NMR spectra. This material can be
found via the “Supplementary Content” section of this article’s webpage.
Acknowledgments
The author MJH acknowledges UGC, New Delhi for FDP under FDP Program award F. No.31-
21/14 (WRO PUNE).
Declaration of interest
The authors declare no conflict of interest.
ORCID
Sambhaji T. Dhumal
http://orcid.org/0000-0003-3018-6179
References
[1] Seitz, L. E.; Suling, W. J.; Reynolds, R. C. J. Synthesis and Antimycobacterial Activity of
Pyrazine and Quinoxaline Derivatives. Med. Chem. 2002, 450, 5604–5606. DOI: 10.1021/
jm020310n.
[2] Lindsley, C. W.; Zhao, Z.; Leister, W. H.; Robinson, R. G.; Barnett, S. F.; Defeo-Jones, D.;
Jones, R. E.; Hartman, G. D.; Huff, J. D.; Huber, H. E.; et al. Allosteric Akt (PKB)
Inhibitors: Discovery and SAR of Isozyme Selective Inhibitors. Bioorg. Med. Chem. Lett.
2005, 15, 761–764. DOI: 10.1016/j.bmcl.2004.11.011.
[3] Loriga, M.; Piras, S.; Sanna, P.; Paglietti, G. Quinoxaline Chemistry, Part 7, 2-
[Aminobenzoates]- and 2-[Aminobenzoylglutamate]-Quinoxalines as Classical Antifolate
Agents. Synthesis and Evaluation of In Vitro Anticancer, anti-HIV and Antifungal
Activity. Farmaco 1997, 52, 157–166.
[4] 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, 815–820. DOI: 10.1016/j.bmcl.2005.11.025.
[5] Kim, Y. B.; Kim, Y.; 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. DOI: 10.1016/j.bmcl.2003.09.086.
[6] Dey, S. K.; Kobaisi, M. A.; Bhosale, S. V. Functionalized Quinoxaline for Chromogenic
and Fluorogenic Anion Sensing. Chemistryopen 2018, 7, 934–952. DOI: 10.1002/open.
201800163.
[7] More, Y. W.; Padghan, S. D.; Bhosale, R. S.; Pawar, R. P.; Puyad, A. L.; Bhosale, S. V.;
Bhosale, S. V. Proton Triggered Colorimetric and Fluorescence Response of a Novel
Quinoxaline Compromising a Donor-Acceptor System. Sensors 2018, 18, 3433. DOI: 10.
3390/s18103433.
[8] Jia, H.; Schmid, B.; Liu, S.-X.; Jaggi, M.; Monbaron, P.; Bhosale, S. V.; Rivadehi, S.;
Langford, S. J.; Sanguinet, L.; Levillain, E.; et al. Tetrathiafulvalene-Fused Porphyrins via
Quinoxaline Linkers: Symmetric and Asymmetric Donor-Acceptor Systems. Chem. Phys.
Chem. 2012, 13, 3370–3382. DOI: 10.1002/cphc.201200350.

2518
M. J. HEBADE ET AL.
[9] Srivani, D.; Gupta, A.; La, D. D.; Bhosale, R. S.; Puyad, A. L.; Xiang, W.; Li, J.; Bhosale,
S. V.; Bhosale, S. V. Small Molecular Non-Fullerene Acceptors Based on
Naphthalenediimide and Benzoisoquinoline-Dione Functionalities for Efficient Bulk-
Hetero Junction Devices. Dyes. Pigm. 2017, 143, 1–9. DOI: 10.1016/j.dyepig.2017.04.014.
[10] Brown, J. D. The Chemistry of Heterocyclic Compounds, Quinoxalines; John Wiley and
Sons: Hoboken, NJ, 2004.
[11] Katoh, A.; Yoshida, T.; Ohkanda, J. Synthesis of Quinoxaline Derivatives Bearing the
Styryl and Phenylethynyl Groups and Application to a Fluorescence Derivatization
Reagent. Heterocycles 2000, 52, 911–920. DOI: 10.3987/COM-99-S61.
[12] Thomas, K. R. J.; Velusamy, M.; Lin, J. T.; Chuen, C. H.; Tao, Y. T. Chromophore-
Labeled Derivatives as Efficient Electroluminescent Materials. Chem. Mater. 2005, 17,
1860–1866. DOI: 10.1021/cm047705a.
[13] Dailey, S.; Feast, W. J.; Peace, R. J.; Sage, I. C.; Till, S.; Wood, E. L. Synthesis and Device
Characterization of Side-Chain Polymer Electron Transport Materials for Organic
Semiconductor Applications. J. Mater. Chem. 2001, 11, 2238–2243. DOI: 10.1039/
b104674h.
[14] Sascha, O.; Rudiger, F. Quinoxalinodehydroannulenes: A Novel Class of Carbon-Rich
Materials. Synlett 2004, 9, 1509–1512. DOI: 10.1055/s-2004-829098.
[15] Crossley, M. J.; Johnston, L. A. Laterally-Extended Porphyrin Systems Incorporating a
Switchable Unit. Chem. Commun. 2002, 10, 1122–1123. DOI: 10.1039/b111655j.
[16] 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. DOI: 10.
1016/j.tetlet.2005.08.080.
[17] More, S. V.; Sastry, M. N. V.; Wang, C. C.; Zhou, M. F.; Loh, T. P. Molecular Iodine: A
Powerful Catalyst for the Easy and Efficient Synthesis of Quinoxalines. Tetrahedron. Lett.
2005, 46, 6345–6348. DOI: 10.1016/j.tetlet.2005.07.026.
[18] 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. DOI: 10.1039/B510677J.
[19] Guo, W. X.; Jin, H. L.; Chen, J. X.; Chen, F.; Ding, J. C.; Wu, H. Y. An Efficient Catalyst-
Free Protocol for the Synthesis of Quinoxaline Derivatives under Ultrasound Irradiation.
J. Braz. Chem. Soc. 2009, 20, 1674–1679. DOI: 10.1590/S0103-50532009000900016.
[20] Aparicio, D.; Attanasi, O. A.; Filippone, P.; Ignacio, R.; Lillini, S.; Mantellini, F.; Palacios,
F.; de Losantos, J. M. Straightforward Access to Pyrazines, Piperazinones, and
Quinoxalines by 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. DOI: 10.
1021/jo060450v.
[21] Raw, S. A.; Wilfered, 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. DOI: 10.1039/b315689c.
[22] Kim, S. Y.; Park, K. H.; Chung, Y. K. Manganese (iv) Dioxide-Catalyzed Synthesis of
Quinoxalines under Microwave Irradiation. Chem. Commun. 2005, 91, 1321–1323. DOI:
10.1039/b417556e.
[23] Robinson, R. S.; Taylor, R. J. K. Quinoxaline Synthesis from a-Hydroxy Ketones via a
Tandem Oxidation Process Using Catalysed Aerobic Oxidation. Synlett 2005, 2005,
1003–1005. DOI: 10.1055/s-2005-864830.
[24] Mahesh, R.; Dhar, A. K.; Tara Sasank, T. V. N. V.; Thirunavukkarasu, S.; Devadoss, T.
Citric Acid: An Efficient and Green Catalyst for Rapid One Pot Synthesis of Quinoxaline
Derivatives at Room Temperature. Chin. Chem. Lett. 2011, 22, 389–392. DOI: 10.1016/j.
cclet.2010.11.002.
[25] Huang, T. K.; Shi, L.; Wang, R.; Guo, X. Z.; Lu, X. X. Keggin Type Heteropolyacids-
Catalyzed Synthesis of Quinoxaline Derivatives in Water. Chinese. Chem. Lett. 2009, 20,
161–164. DOI: 10.1016/j.cclet.2008.10.048.

R
SYNTHETIC COMMUNICATIONSV
2519
[26] Shaabani, A.; Rezayan, A. H.; Behnam, M.; Heidary, M. Green Chemistry Approaches for
the Synthesis of Quinoxaline Derivatives: Comparison of Ethanol and Water in the
Presence of the Reusable Catalyst Cellulose Sulfuric Acid. C. R. Chimie. 2009, 12,
1249–1252. DOI: 10.1016/j.crci.2009.01.006.
[27] Zhang, X. Z.; Wang, J. X.; Sun, Y. J.; Zhan, H. W. Synthesis of Quinoxaline Derivatives
Catalyzed by PEG-400. Chin. Chem. Lett. 2010, 21, 395–398. DOI: 10.1016/j.cclet.2009.12.
015.
[28] Lin, P. Y.; Hou, R. S.; Wang, H. M.; Kang, L. J.; Chen, L. C. Hypervalent Iodine(III)
Sulfonate Mediated Synthesis of Quinoxalines in Liquid PEG-400. J. Chinese Chemical Soc.
2009, 56, 683–687. DOI: 10.1002/jccs.200900102.
[29] 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, 265, 227–230. DOI: 10.1016/j.molcata.2006.10.018.
[30] Khaksar, S.; Rostamnezhad, F. A Novel One-Pot Synthesis of Quinoxaline Derivatives in
Fluorinated Alcohols. Bull. Korean. Chem. Soc. 2012, 33, 2581–2584. DOI: 10.5012/bkcs.
2012.33.8.2581.
[31] Hasaninejad, A.; Zare, A.; Mohammadizadeh, M. R.; Karami, Z. Synthesis of Quinoxaline
Derivatives via Condensation of Aryl-1,2-Diamines with 1,2-Diketones Using
(NH4)6Mo7O24.4H2O as an Efficient, Mild and Reusable Catalyst. J. Iranian Chem. Soc.
2009, 6, 153–158. DOI: 10.1007/BF03246514.
[32] Khaksar, S.; Tajbakhsh, M.; Gholami, M.; Rostamnezhad, F. A Highly Efficient Procedure
for the Synthesis of Quinoxaline Derivatives Using Polyvinylpolypyrrolidone Supported
Triflic Acid Catalyst (PVPPꢁOTf). Chin. Chem. Lett. 2014, 25, 1287–1290. DOI: 10.1016/j.
cclet.2014.04.008.
[33] Kamal, A.; Babu, K. S.; Hussaini, S. M. A.; Mahesh, R.; Alarifi, A. Amberlite IR-120H, an
Efficient and Recyclable Solid Phase Catalyst for the Synthesis of Quinoxalines: A Greener
Approach. Tetrahedron. Lett. 2015, 56, 2803–2808. DOI: 10.1016/j.tetlet.2015.04.046.
[34] Pan, F.; Chen, T. M.; Cao, J. J.; Zou, J. P.; Zhang, W. Ga(ClO4)3-Catalyzed Synthesis of
Quinoxalines by Cycloaddition of a-Hydroxyketones and o-Phenylenediamines.
Tetrahedron. Lett. 2012, 53, 2508–2510. DOI: 10.1016/j.tetlet.2012.02.113.
[35] Singh, S. K.; Gupta, P.; Duggineni, S.; Kundu, B. Solid Phase Synthesis of Quinoxalines.
Synlett 2003, 14, 2147–2150. DOI: 10.1055/s-2003-42065.
[36] Kumar, K.; Mudshinge, S. R.; Goyal, S.; Gangar, M.; Nair, V. A. A Catalyst Free, One Pot
Approach for the Synthesis of Quinoxaline Derivatives via Oxidative Cyclisation of 1,2-
Diamines and Phenacyl Bromides. Tetrahedron. Lett. 2015, 56, 1266–1271. DOI: 10.1016/j.
tetlet.2015.01.138.
[37] Mamedov, V. A. Quinoxalines: Synthesis, Reactions, Mechanisms and Structure; Springer:
New York, NY, 2016; pp 1–452.
[38] Pereira, J. A.; Pessoa, A. M.; Cordeiro, M. N. D. S.; Fernandes, R.; Prudencio, C.;
Noronha, J. P.; Vieira, M. Quinoxaline, Its Derivatives and Applications: A State of the
Art Review. Eur. J. Med. Chem. 2015, 97, 664–672. DOI: 10.1016/j.ejmech.2014.06.058.
[39] Bhunia, S.; Ghosh, P.; Patra, S. R. Gold-Catalyzed Oxidative Alkyne Functionalization by
N ꢂ O/S ꢂ O/C ꢂ O Bond Oxidants. Adv. Synth. Catal. 2020, 362, 3664–3708. DOI: 10.
1002/adsc.202000274.
[40] Das, B.; Venkateswarlu, K.; Suneel, K.; Majhi, A. An Efficient and Convenient Protocol
for the Synthesis of Quinoxalines and Dihydropyrazines via Cyclization-Oxidation
Processes Using HClO4ꢁSiO2 as a Heterogeneous Recyclable Catalyst. Tetrahedron. Lett.
2007, 48, 5371–5374. DOI: 10.1016/j.tetlet.2007.06.036.
[41] Wan, J. P.; Gan, S. F.; Wu, J. M.; Pan, Y. Water Mediated Chemoselective Synthesis of
1,2-Disubstituted Benzimidazoles Using o-Phenylenediamine and the Extended Synthesis
of Quinoxalines. Green Chem. 2009, 11, 1633–1637. DOI: 10.1039/b914286j.
[42] Madhav, B.; Murthy, S. N.; Reddy, V. P.; Rao, K. R.; Nageswar, Y. V. D. Biomimetic
Synthesis of Quinoxalines in Water. Tetrahedron. Lett. 2009, 50, 6025–6028. DOI: 10.
1016/j.tetlet.2009.08.033.

2520
M. J. HEBADE ET AL.
[43] Ghosh, P.; Mandal, A. Sodium Dodecyl Sulfate in Water: Greener Approach for the
Synthesis of Quinoxaline Derivatives. Green. Chem. Lett. Rev. 2013, 6, 45–54. DOI: 10.
1080/17518253.2012.703245.
[44] Tejeswararao, D. Synthesis of Quinoxaline Using Silica Supported Phosphomolybdic Acid
as Reusable Heterogeneous Catalyst. Asian J. Chem. 2016, 28, 2353–2356. DOI: 10.14233/
ajchem.2016.19533.
[45] Harsha, K. B.; Rangappa, K. S. One-Step Approach for the Synthesis of Functionalized
Quinoxalines Mediated by T3P-DMSO or T3P via a Tandem Oxidation-Condensation or
Condensation Reaction. RSC Adv. 2016, 6, 57154–57162. DOI: 10.1039/C6RA03078E.
[46] Pardeshi, S. D.; Sathe, P. A.; Vadagaonkar, K. S.; Chaskar, A. C. One-Pot Protocol for the
Synthesis of Imidazoles and Quinoxalines Using N-Bromosuccinimide. Adv. Synth. Catal.
2017, 359, 4217–4226. DOI: 10.1002/adsc.201700900.
[47] Meshram, H. M.; Ramesh, P.; Kumar, G. S.; Reddy, B. C. One-Pot Synthesis of
Quinoxaline-2-Carboxylate Derivatives Using Ionic Liquid as Reusable Reaction Media.
Tetrahedron. Lett. 2010, 51, 4313–4316. DOI: 10.1016/j.tetlet.2010.05.099.
[48] Mulla, S. A. R.; Pathan, M. Y.; Chavan, S. S. A Novel and Efficient Synthesis of Azaarene-
Substituted 3-Hydroxy-2-Oxindoles via sp3 C–H Functionalization of 2-Methyl Azaarenes
and (2-Azaaryl)Methanes over a Heterogeneous, Reusable Silica-Supported Dodecatung
stophosphoric Acid Catalyst. RSC Adv. 2013, 3, 20281–20286. DOI: 10.1039/c3ra43515f.
[49] Mulla, S. A. R.; Pathan, M. Y.; Chavan, S. S.; Gample, S. P.; Sarkar, D. Highly Efficient
One-Pot
Multi-Component
Synthesis
of
a-Aminophosphonates
and
Bis-
a-Aminophosphonates Catalyzed by Heterogeneous Reusable Silica Supported
Dodecatungstophosphoric Acid (DTP/SiO2) at Ambient Temperature and Their anti-
Tubercular Evaluation against Mycobactrium Tuberculosis. RSC Adv. 2014, 4, 7666–7672.
DOI: 10.1039/c3ra45853a.
[50] Rode, C. V.; Garade, A. C.; Chikate, R. C. Solid Acid Catalysts: Modification of Acid Sites
and Effect on Activity and Selectivity Tuning in Various Reactions. Catal. Surv. Asia
2009, 13, 205–220. DOI: 10.1007/s10563-009-9078-4.
[51] Nagarapu, L.; Palem, J. D.; Reddy, A. R. K.; Bantu, R. A Facile and Efficient Synthesis of
Quinoxalines from Phenacyl Bromides and Ortho Phenylenediamine Promoted by
Zirconium Tungstate. Organic. Chem. Current Res. 2014, S4, 1–5. DOI: 10.4172/2161-
0401.S4-4001.
[52] Harsha, K. B.; Rangappa, S.; Preetham, H. D.; Swaroop, T. R.; Gilandoust, M.; Rakesh,
K. S.; Rangappa, K. S. An Easy and Efficient Method for the Synthesis of Quinoxalines
Using Recyclable and Heterogeneous Nanomagnetic-Supported Acid Catalyst under
Solvent-Free Condition. Chemistryselect 2018, 3, 5228–5232. DOI: 10.1002/slct.201800053.
[53] Lian, M.; Li, Q.; Zhu, Y.; Yin, G.; Wu, A. Logic Design and Synthesis of Quinoxalines via
the Integration of Iodination/Oxidation/Cyclization Sequences from Ketones and 1,2-
Diamines. Tetrahedron 2012, 68, 9598–9605. DOI: 10.1016/j.tet.2012.09.056.
[54] Khalafy, J.; Habashi, B. P.; Marjani, A. P.; Moghadam, P. N. The Synthesis of 2
Arylquinoxaline Derivatives. Curr. Chem. Lett. 2012, 1, 139–146. DOI: 10.5267/j.ccl.2012.
5.002.
[55] Jadhav, S. A.; Sarkate, A. P.; Shioorkar, M. G.; Shinde, D. B. Expeditious One Pot
Multicomponent Microwave Assisted Green Synthesis of Substituted 2-Phenyl
Quinoxaline and 7-Bromo-3-(4-Ethylphenyl)Pyrido[2,3-b]Pyrazine in water-PEG and
Water-Ethanol. Synth. Commun. 2017, 47, 1661–1667. DOI: 10.1080/00397911.2017.
1337153.
[56] Tanwar, B.; Purohit, P.; Raju, B. N.; Kumar, D.; Kommi, D. N.; Chakraborti, A. K. An
“All-Water” Strategy for Regiocontrolled Synthesis of 2-Aryl Quinoxalines. RSC Adv.
2015, 5, 11873–11883. DOI: 10.1039/C4RA16568C.