Synthesis of quinoxalines by a carbon nanotube-gold nanohybrid-catalyzed cascade reaction of vicinal diols and keto alcohols with diamines

Article abstract of DOI:10.1002/cctc.201402782

A one-pot oxidation-condensation method for the synthesis of quinoxalines from readily available benzoins or benzhydrols and 1,2-phenylenediamines or 2,3-diaminopyridine by use of a gold-carbon nanotube nanohybrid as a heterogeneous catalyst is reported. Quinoxalines are formed under mild conditions in air and in excellent yields. The simple and efficient methodology offers a safe and sustainable alternative to conventional acid and/or base-catalyzed thermal processes.

Full text of DOI:10.1002/cctc.201402782

CHEMCATCHEM
COMMUNICATIONS
DOI: 10.1002/cctc.201402782
Synthesis of Quinoxalines by a Carbon Nanotube–Gold
Nanohybrid-Catalyzed Cascade Reaction of Vicinal Diols
and Keto Alcohols with Diamines
Nimesh Shah,[a] Edmond Gravel,[b] Dhanaji V. Jawale,[b] Eric Doris,*[b] and
Irishi N. N. Namboothiri*[a]
A one-pot oxidation–condensation method for the synthesis of
quinoxalines from readily available benzoins or benzhydrols
and 1,2-phenylenediamines or 2,3-diaminopyridine by use of
a gold–carbon nanotube nanohybrid as a heterogeneous cata-
lyst is reported. Quinoxalines are formed under mild conditions
in air and in excellent yields. The simple and efficient method-
ology offers a safe and sustainable alternative to conventional
acid and/or base-catalyzed thermal processes.
aromatic 1,2-diamines were treated with 1,2-diols in the pres-
ence of 4.5 mol% ceria-supported Au nanoparticles (AuNPs) at
1408C for 20 h[8] and, in the other case, the reaction was per-
formed in the presence of 4 mol% [RuCl2(PPh3)3] in diglyme
under reflux conditions for 30 h.[9] In both cases, many exam-
ples of 2-substituted quinoxalines and selected examples of
2,3-disubstituted quinoxalines in moderate to good yields
were reported. There is also one report for the synthesis of 2,3-
diaryl quinoxalines in high yield from benzoin (1,2-ketoalcohol)
and aromatic 1,2-diamine by using 4 mol% of 4-aminothiophe-
nol-coated AuNPs in aqueous basic medium at 808C.[10]
Quinoxalines constitute a quintessential class of N-containing
heterocycles due to their wide range of applications as syn-
thetic intermediates, biological agents, and advanced materi-
als.[1] The diverse biological properties of functionalized qui-
noxalines as anticancer, antituberculosis and DNA intercalating
agents have generated considerable interest.[2] Quinoxalines
have also carved out a unique niche in materials science due
to their properties as luminescent materials, organic dye sensi-
tizers, and building blocks for the synthesis of cavitand-based
molecular switches, to name a few.[3] The condensation of an
aromatic 1,2-diamine with a 1,2-dicarbonyl compound is the
classical method for the synthesis of quinoxalines.[1,4] However,
more recently, readily available 1,2-ketoalcohols have been em-
ployed as reactants with aromatic 1,2-diamines in a cascade
oxidation–condensation process by using a multitude of cata-
lysts and conditions for the synthesis of 2-substituted[5] and
2,3-disubstituted quinoxalines.[6] Synthesis of substituted qui-
noxalines from aromatic 1,2-diamines and phenacyl bromide
through cyclization–oxidation has also been reported.[1,4,7]
Though quinoxalines can be synthesized in excellent yields by
some of the above methods, requirement of high temperature
and/or microwave irradiation, high catalyst loading, and poor
recyclability of the catalyst are major limitations. Surprisingly,
there are only two reports, to our knowledge, on the synthesis
of substituted quinoxalines directly from 1,2-diols. In one case,
Although the catalytic activity of AuNPs with a variety of
supports has been extensively investigated for over
a decade,[11] carbon nanotube (CNT)-supported AuNPs have
emerged as highly efficient and recyclable heterogeneous cata-
lysts only recently.[12–16] In this context, we have exploited the
robustness of CNTs and their ability to stabilize a metal’s transi-
ent higher oxidation states[17] in the development of an AuCNT
nanohybrid in which Au nanoparticles were stabilized by
a polyanionic–polycationic two-layer assembly around CNTs
(Figure 1). The exceptional catalytic efficiency of this nanohy-
Figure 1. TEM image of the AuCNT hybrid with the general reaction scheme
[a] Dr. N. Shah, Prof. Dr. I. N. N. Namboothiri
Department of Chemistry
of the reported organic transformation.
Indian Institute of Technology Bombay
Mumbai 400 076 (India)
E-mail: irishi@chem.iitb.ac.in
brid in comparison to other supported and colloidal AuNPs
has been demonstrated in the oxidation of silanes,[12] alco-
hols,[13] and phenols,[14] and in the reductive amination[15] and
N-formylation of aldehydes.[16] Building on this work, we de-
sired to develop an efficient methodology for the synthesis of
quinoxalines from 1,2-ketoalcohols and 1,2-diols by using our
AuCNT catalyst under simple and mild conditions. In our re-
[b] Dr. E. Gravel, Dr. D. V. Jawale, Dr. E. Doris
CEA, iBiTecS, Service de Chimie Bioorganique et de Marquage
91191 Gif-sur-Yvette (France)
E-mail: eric.doris@cea.fr
Supporting information for this article is available on the WWW under
http://dx.doi.org/10.1002/cctc.201402782.
ꢀ 2014 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
ChemCatChem 2014, 6, 1 – 5 1
ÞÞ
These are not the final page numbers!

CHEMCATCHEM
COMMUNICATIONS
www.chemcatchem.org
cently reported procedure for the AuCNT-catalyzed oxidation
of benzylic and allylic alcohols,[13] the benzylic alcohols includ-
ed benzoin 2a and benzhydrol 3a. We envisioned that benzil
and other 1,2-diketones thus generated could be condensed
in situ with suitable aromatic 1,2-diamines to afford quinoxa-
lines. Such a one-pot cascade oxidation–condensation protocol
for the synthesis of polynitrogen-containing aromatic heterocy-
cles from readily available aromatic 1,2-diamines and a-hydroxy-
ketones or 1,2-diols at room temperature, in air, and in aque-
ous medium appeared very attractive.
that benzoin 2a reacted with 1,2-diamines 1b–e to provide
quinoxalines 4b–e in 87–91% yields in 28–30 h (entries 2–5,
path A). Benzhydrol 3a, on the other hand, required more time
(38–40 h), but delivered quinoxalines 4b–e in comparable
yields (88–92%, entries 2–5, path B). Notably, there was no ap-
preciable effect of substituent on the reaction time or isolated
yield. The above results encouraged us to study the scope of
benzoin 2 and benzhydrol 3 as well (Table 2 and Scheme 1).
Treatment of p-methoxybenzoin 2b with diamines 1a–d under
We began our experiments by treating 1,2-phenylenedia-
mine 1a with benzoin 2a under previously established oxida-
tion conditions[13] of AuCNT (0.2 mol%) in toluene/H2O (1:1
v/v) at room temperature (Table 1, entry 1). Much to our de-
Table 2. AuCNT-catalyzed one-pot synthesis of quinoxalines from aromat-
ic 1,2-diamines and methoxybenzoin or 4-methoxybenzhydrol.[a]
Table 1. AuCNT-catalyzed one-pot synthesis of quinoxalines from aromat-
ic 1,2-diamines and benzoin or benzhydrol.[a]
Entry 1,2-Diamine
Quinoxaline
Path
t
Yield[b]
[h] [%]
A
B
30 88
39 89
1
2
3
4
5
1a
1b
1c
1d
1e
4 f
4g
4h
4i
A
B
27 92
40 90
Entry 1,2-Diamine
Quinoxaline
Path
t
Yield[b]
[h] [%]
A
B
29 87
40 91
A
B
26 96
38 94
1
2
3
4
5
1a
1b
1c
1d
1e
4a
4b
4c
4d
4e
A
B
30 90
41 93
A
B
28 91
38 92
A
B
30 89
40 87
4j
A
B
28 87
39 90
[a] Conditions: 2b or 3b (0.1 mmol), 1,2-diamine 1 (0.1 mmol), AuCNT
(0.2 mol%), toluene/water 1:1 (1 mL), NaOH (3 equiv), RT, open flask (air).
[b] Yield of purified isolated product.
A
B
30 88
40 88
A
B
28 90
39 90
[a] Conditions: 2a or 3a (0.1 mmol), 1,2-diamine 1 (0.1 mmol), AuCNT
(0.2 mol%), toluene/water 1:1 (1 mL), NaOH (3 equiv), RT, open flask (air).
[b] Yield of purified isolated product.
light, quinoxaline 4a was isolated in 96% yield after 26 h of re-
action (entry 1, path A). This prompted us to probe the oxida-
tion of benzhydrol 3a and the in situ condensation of the re-
sulting benzil with 1,2-phenylenediamine 1a. Though this one-
pot transformation took longer (38 h), we were pleased to iso-
late quinoxaline 4a in 94% yield (entry 1, path B). The turnover
number (TON) and turnover frequency (TOF) calculated for the
above two experiments were 480 and 18 hꢀ1, respectively, for
path A and 470 and 12 hꢀ1, respectively, for path B.
Scheme 1. Synthesis of fused polycyclic quinoxalines from hydroxyketone
2c or diol 3c and selected diamines.
our standard conditions led to the formation of quinoxalines
4 f–j in 87–92% yields in 27–30 h (Table 2, entries 1–5, path A).
As in the case of benzhydrol 3a, reaction of benzhydrol 3b
with diamines 1a–e also took around 40 h and the yields of
quinoxalines 4 f–j were high (87–93%, path B).
Finally, synthesis of fused polycyclic quinoxalines 4k–l was
performed under our reaction conditions by treating hydroxy-
ketone 2c and diol 3c with selected diamines 1a–
b (Scheme 1). As in the case of 2a–b, the reaction of hydroxy-
ketone 2c with diamines 1a–b required less time (27–28 h) to
Having confirmed the efficacy of our experimental condi-
tions, we investigated the scope of our one-pot protocol, first,
by screening various 1,2-diamines 1b–e with benzoin 2a and
benzhydrol 3a as model substrates for paths A and B, respec-
tively (Table 1, entries 2–5). Representative examples of dia-
mines with weakly electron-donating substituents 1b, elec-
tron-withdrawing substituents 1c and 1d, and a heteroaromat-
ic diamine 1e were chosen for our studies. It may be noted
ꢀ 2014 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
ChemCatChem 0000, 00, 1 – 5
&
2
&
ÞÞ
These are not the final page numbers!

CHEMCATCHEM
COMMUNICATIONS
www.chemcatchem.org
Table 3. Comparison of various Au sources in the synthesis of quinoxa-
lines from 1,2-phenylenediamine and benzoin or benzhydrol.[a]
Table 4. Recycling experiments with AuCNT catalyst for the reaction of
1,2-phenylenediamine and benzoin or benzhydrol.[a]
Path A
Yield[b] [%]
Path B
Yield[b] [%]
Entry
Catalyst
Path A
Yield[b] [%]
Path B
Yield[b] [%]
Entry
Catalyst
t [h]
t [h]
t [h]
t [h]
1
2
3
AuCNT
AuNP colloid
HAuCl4
26
48
48
96
trace
n.r.[c]
38
48
48
94
trace
n.r.
1
2
3
4
5
fresh
26
25
25
24
24
96
95
95
94
94
38
38
37
37
36
94
94
93
93
92
recycle 1
recycle 2
recycle 3
recycle 4
[a] Conditions: 2a or 3a (0.1 mmol), 1,2-diamine 1 (0.1 mmol), AuCNT
(0.2 mol%), toluene/water 1:1 (1 mL), NaOH (3 equiv), RT, open flask (air).
[b] Yield of purified isolated product. [c] No reaction.
[a] Conditions: 2a or 3a (0.1 mmol), 1,2-diamine 1 (0.1 mmol), AuCNT
(0.2 mol%), toluene/water 1:1 (1 mL), NaOH (3 equiv), RT, open flask (air).
[b] Yield of purified isolated product.
go to completion and afford quinoxalines 4k–l in excellent
yields (91–93%) compared to 3c, which took longer (37–39 h)
to reach complete conversion. Nevertheless, the reaction of 3c
with diamines 1a–b also delivered quinoxalines 4k–l in com-
parable (91–94%) yields. The catalytic efficiency of AuCNT was
compared to that of colloidal AuNPs and a Au salt by perform-
ing the reaction with identical loading (0.2 mol%) of the differ-
ent catalysts (Table 3, path A). As reported in Table 1, the
AuCNT-catalyzed reaction of diamine 1a with benzoin 2a pro-
vided quinoxaline 4a in 96% yield within 26 h (entry 1). On
the other hand, the colloidal AuNP-catalyzed reaction provided
only traces of 4a in 48 h (entry 2) and the use of HAuCl4 did
not lead to any product formation (entry 3). A similar trend
was observed on comparison of the catalytic activity of AuCNT
with that of other catalysts in the reaction of diol 3a with dia-
mine 1a (Table 3, path B).
The requirement of only very low catalyst loading and
simple and mild reaction conditions are attractive features of
our methodology. Another remarkable feature is the recyclabil-
ity of the catalyst. This was demonstrated by performing 5 con-
secutive reactions by using the same catalyst recovered by
centrifugation after each cycle. Reactions were completed in
25–26 h without any appreciable drop in the yield of quinoxa-
line 4a (94–96%) over the course of the experiment (Table 4,
path A). Similar results were obtained if benzoin 2a was re-
placed by benzhydrol 3a (Table 4, path B).
after 6 h. There was only 36% conversion to quinoxaline
4a at this point and further stirring the catalyst-free reac-
tion mixture for another 18 h did not improve the yield,
thus showing the heterogeneous nature of the catalysis.
3) Authentic benzil was treated with diamine 1a under the
above conditions but in the absence of the catalyst. After
24 h of reaction, only 12% conversion was observed. How-
ever, upon addition of the catalyst to the reaction mixture
and continued stirring, complete conversion was achieved
in just 1.5 h to afford quinoxaline 4a in 96% yield.
4) The above two-step process, involving oxidation and con-
densation, was evaluated further by performing a kinetic
experiment under the standard conditions. Thus the
AuCNT-catalyzed reaction of benzoin 2a with diamine 1a
was examined at specific intervals by withdrawing aliquots
at 1, 6, and 12 h. The yields were, respectively, 8, 35, and
55%. Almost complete conversion was achieved in 24 h to
1
give product 4a in 95% yield. The H NMR analysis of the
reaction mixture at the above intervals indicated no appre-
ciable amount of benzil in the reaction mixture, confirming
that the rate limiting step was the oxidation.
In summary, the synthesis of quinoxalines from readily avail-
able benzoins or benzhydrols and aromatic 1,2-diamines has
been performed in excellent yield under the catalytic influence
of a gold–carbon nanotube nanohybrid. This one-pot oxida-
tion-condensation sequence takes place under ambient heter-
ogeneous conditions in air and is a superior alternative to ex-
isting methods for the synthesis of quinoxalines, which are
ubiquitous structural units in many biologically active
compounds.
The catalytic role of AuCNT nanohybrid and its heterogene-
ous nature were verified through a series of experiments:
1) The AuCNT-catalyzed oxidation of benzoin 2a and benzhy-
drol 3a was performed in the absence of 1,2-phenylenedi-
amine 1a. After 24 h, the catalyst was removed by centrifu-
gation, which was followed by addition of 1,2-phenylenedi-
amine 1a. After stirring the catalyst-free reaction mixture
overnight (12 h) at room temperature, quinoxaline 4a was
isolated in only 22 and 18% yields, respectively, for benzoin
2a and benzhydrol 3a. This result indicated that the nano-
hybrid catalyst was also active in the condensation step.
2) The reaction between benzoin 2a and diamine 1a in the
presence of the catalyst under our standard conditions was
interrupted by removing the catalyst by centrifugation
Experimental Section
Catalyst preparation
The AuCNT hybrid was prepared according to a previously de-
scribed procedure.[12] The catalyst was obtained as an aqueous sus-
ꢀ 2014 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
ChemCatChem 0000, 00, 1 – 5
&
3
&
ÞÞ
These are not the final page numbers!

CHEMCATCHEM
COMMUNICATIONS
www.chemcatchem.org
pension with a Au concentration of 4 mm (determined by induc-
tively coupled plasma MS).
2,3-Bis(4-methoxy-phenyl)-6-methylquinoxaline (4g):[18] Pale yellow
solid; yield 90% (32 mg) from diol, 92% (32.8 mg) from a-hydroxy-
ketone; m.p. 147–1488C (Ref. [18]: 148–1498C); H NMR (400 MHz,
1
CDCl3): d=2.59 (s, 3H), 3.83 (s, 6H), 6.86 (d, J=8.7 Hz, 4H), 7.47 (d,
J=8.8 Hz, 2H), 7.48 (d, J=8.8 Hz, 2H), 7.54 (dd, J=8.5, 1.6 Hz, 1H),
7.91 (d, J=1.6 Hz, 1H), 8.01 ppm (d, J=8.5 Hz, 1H); 13C NMR
(CDCl3, 100 MHz): d=22.0, 55.5 (ꢁ2), 113.9 (ꢁ2), 128.0, 128.6, 131.4,
131.4, 131.9, 131.9, 132.1, 139.7, 140.3, 141.2, 152.3, 153.0, 160.2,
160.3 ppm.
Synthesis of quinoxaline 4
General procedure: To a stirred solution of benzoin 2 (0.1 mmol) or
benzhydrol 3 (0.1 mmol) and diamine 1 (0.1 mmol) in a 1:1 (v/v)
mixture of toluene/water was added NaOH (12 mg, 0.3 mmol,
3 equiv) and aqueous AuCNT (50 mL, 0.2 mol%). The reaction mix-
ture was stirred until complete consumption of the starting materi-
al (monitored by TLC). The aqueous layer was then extracted with
EtOAc (3ꢁ10 mL). The combined organic layer was dried (anhy-
drous Na2SO4), filtered, and concentrated under vacuum. The crude
residue was directly subjected to column chromatography (5–15%
EtOAc/petroleum ether, gradient elution) to afford pure quinoxa-
line 4.
6-Chloro-2,3-Bis(4-methoxy-phenyl)-quinoxaline (4h):[21] Pale yellow
solid; yield 91% (34 mg) from diol, 87% (32.8 mg) from a-hydroxy-
ketone; m.p. 150–1518C (Ref. [21]: 1518C); 1H NMR (400 MHz,
CDCl3): d=3.83 (s, 6H), 6.87 (d, J=8.7 Hz, 4H), 7.48 (d, J=8.7 Hz,
2H), 7.49 (d, J=8.7 Hz, 2H), 7.65 (dd, J=8.9, 2.0 Hz, 1H), 8.04 (d,
J=8.9 Hz, 1H), 8.11 ppm (d, J=2.0 Hz, 1H); 13C NMR (CDCl3,
100 MHz): d=55.5 (ꢁ2), 114.0 (ꢁ2), 128.0, 130.4, 130.6, 131.4 (ꢁ2),
131.4, 131.5, 135.3, 139.7, 141.5, 153.3, 154.0, 160.5, 160.6 ppm.
6,7-Dichloro-2,3-Bis(4-methoxy-phenyl)-quinoxaline (4i):[22] Pale
yellow solid; yield 93% (38 mg) from diol, 90% (36.8 mg) from a-
hydroxyketone; m.p. 169–1708C (Ref. [22]: 168–1708C); 1H NMR
(400 MHz, CDCl3): d=3.83 (s, 6H), 6.87 (d, J=8.7 Hz, 4H), 7.47 (d,
J=8.7 Hz, 4H), 8.21 ppm (s, 2H); 13C NMR (CDCl3, 100 MHz): d=
55.5, 114.0, 129.7, 131.1, 131.4, 134.0, 139.9, 154.2, 160.7 ppm.
Characterization data
2,3-Diphenylquinoxaline (4a):[18] White solid; yield 94% (26.5 mg)
from diol, 96% (27 mg) from a-hydroxyketone; m.p. 126–1288C
1
(Ref. [18]: 128–1298C); H NMR (400 MHz, CDCl3): d=7.31–7.39 (m,
6H), 7.50–7.54 (m, 4H), 7.78 (dd, J=6.4, 3.4 Hz, 2H), 8.19 ppm (dd,
J=6.4, 3.4 Hz, 2H); 13C NMR (CDCl3, 100 MHz): d=128.4, 128.9,
129.3, 130.0, 130.1, 139.2, 141.4, 153.6 ppm.
2,3-Bis(4-methoxyphenyl)pyrido[2,3-b]pyrazine (4j):[20] Pale yellow
solid; yield 87% (29.8 mg) from diol, 89% (30.5 mg) from a-hydroxy-
1
6-Methyl-2,3-diphenylquinoxaline (4b):[18] White solid; yield 92%
(27.2 mg) from diol, 91% (26.9 mg) from a-hydroxyketone; m.p.
116–1178C (Ref. [18]: 117–1188C); 1H NMR (400 MHz, CDCl3): d=
2.61 (s, 3H), 7.30–7.37 (m, 6H), 7.49–7.52 (m, 4H), 7.60 (dd, J=8.6,
1.8 Hz, 1H), 7.96 (d, J=1.8 Hz, 1H) 8.08 ppm (d, J=8.6 Hz, 1H);
13C NMR (CDCl3, 100 MHz): d=22.0, 128.1, 128.3 (ꢁ2), 128.7, 128.7
(ꢁ2), 129.9, 129.9, 132.3, 139.3 (ꢁ2), 139.7, 140.5, 141.3, 152.6,
153.3 ppm.
ketone; m.p. 137–1388C; (Ref. [20]: 137–1388C); H NMR (400 MHz,
CDCl3): d=3.88 (s, 6H), 6.83 (d, J=8.7 Hz, 2H), 6.86 (d, J=8.7 Hz,
2H), 7.51 (d, J=8.7 Hz, 2H), 7.60 (d, J=8.7 Hz, 2H), 7.63 (d, J=
8.4 Hz, 1H), 8.41 (dd, J=8.4, 1.7 Hz, 1H), 9.07 ppm (d, J=1.7 Hz,
1H); 13C NMR (CDCl3, 100 MHz): d=55.4, 55.4, 113.7, 114.0, 124.9,
130.8, 131.2, 131.3, 131.9, 135.9, 137.9, 149.9, 153.6, 154.3, 155.9,
160.1, 160.8 ppm.
Acenaphtho[1,2-b]quinoxaline (4k):[18] Pale yellow solid; yield 90%
(22.9 mg) from diol, 93% (23.7 mg) from a-hydroxyketone; m.p.
242–2458C (Ref. [18]: 241–2428C); 1H NMR (400 MHz, CDCl3): d=
7.77 (dd, J=6.3, 3.4 Hz, 2H), 7.86 (dd, J=8.2, 7.0 Hz, 2H), 8.12 (d,
J=8.2 Hz, 2H), 8.22 (dd, J=6.3, 3.4 Hz, 2H), 8.44 ppm (d, J=7.0 Hz,
2H); 13C NMR (CDCl3, 100 MHz): d=122.0, 128.8, 129.3, 129.6,
129.7, 130.1, 131.9, 136.6, 141.4, 154.2 ppm.
6-Chloro-2,3-diphenylquinoxaline (4c):[18] White solid; yield 90%
(28.4 mg) from diol, 87% (27.5 mg) from a-hydroxyketone; m.p.
115–1168C (Ref. [18]: 115–1168C); 1H NMR (400 MHz, CDCl3): d=
7.31–7.41 (m, 6H), 7.49–7.53 (m, 4H), 7.71 (dd, J=9.0, 2.3 Hz, 1H),
8.11 (d, J=9.0 Hz, 1H), 8.17 ppm (d, J=2.3 Hz, 1H); 13C NMR
(CDCl3, 100 MHz): d=128.1, 128.3 (ꢁ2), 129.1, 129.1, 129.9, 129.9,
130.4, 130.9, 135.6, 138.7, 138.7, 139.7, 141.5, 153.6, 154.2 ppm.
9-Methyl-acenaphtho[1,2-b]quinoxaline (4l):[18] Pale yellow solid;
yield 92% (24.7 mg) from diol, 91% (24.4 mg) from a-hydroxyke-
6,7-Dichloro-2,3-diphenylquinoxaline (4d):[19] White solid; yield
88% (30.8 mg) from diol, 88% (31 mg) from a-hydroxyketone; m.p.
154–1568C (Ref. [19]: 154–1558C); 1H NMR (400 MHz, CDCl3): d=
7.31–7.41 (m, 6H), 7.47–7.52 (m, 4H), 8.28 ppm (s, 2H); 13C NMR
(CDCl3, 100 MHz): d=128.6, 129.3, 129.8, 129.9, 134.4, 138.4, 139.9,
154.4 ppm.
1
tone; m.p. >3008C (Ref. [18]: >3008C); H NMR (400 MHz, CDCl3):
d=2.53 (s, 3H), 7.45 (dd, J=8.5, 1.8 Hz, 1H), 7.67 (t, J=8.4 Hz, 2H),
7.84 (d, J=1.8 Hz, 1H), 8.05 (dd, J=8.4, 2.0 Hz, 1H), 7.95 (d, J=
8.5 Hz, 1H), 8.22 ppm (dd, J=8.4, 2.0 Hz, 2H); 13C NMR (CDCl3,
100 MHz): d=21.8, 121.6, 121.8, 128.6, 128.6, 128.8, 129.1, 129.2,
129.4, 130.0, 131.4, 132.0, 139.6, 139.7, 141.3, 153.4, 154.1 ppm.
2,3-Diphenylpyrido[2,3-b]pyrazine (4e):[20] Yellow solid; yield 90%
(25.5 mg) from diol, 90% (25.5 mg) from a-hydroxyketone; m.p.
142–1438C (Ref. [20]: 141–1438C); 1H NMR (400 MHz, CDCl3): d=
7.30–7.42 (m, 6H), 7.53–7.66 (m, 4H), 7.74 (dd, J=8.0, 2.9 Hz, 1H),
8.55 (d, J=8.0 Hz, 1H), 9.17 ppm (d, J=2.9 Hz, 1H); 13C NMR
(CDCl3, 100 MHz): d=125.4, 128.3, 128.6, 129.6, 129.8, 130.0, 130.5,
136.3, 138.0, 138.5, 138.9, 149.4, 153.7, 155.2, 156.8 ppm.
Recycling
To a stirred solution of benzoin 2a (0.1 mmol, 21.2 mg) or benzhy-
drol 3a (0.1 mmol, 21.4 mg) and o-phenylenediamine 1a
(0.1 mmol, 10.8 mg) in a 1:1 mixture of toluene/water was added
NaOH (12 mg, 0.3 mmol, 3 equiv) and aqueous AuCNT (50 mL,
0.2 mol%). The reaction mixture was stirred until complete con-
sumption of the starting material (monitored by TLC, Table 4) at RT.
The catalyst was then recovered by simple centrifugation and
reused without further purification.
2,3-Bis(4-methoxy-phenyl)quinoxaline (4 f):[18] Pale yellow solid;
yield 89% (30.5 mg) from diol, 88% (30 mg) from a-hydroxyke-
tone; m.p. 148–1508C (Ref. [18]: 148–1498C); 1H NMR (400 MHz,
CDCl3): d=3.82 (s, 6H), 6.87 (d, J=9.6 Hz, 4H), 7.49 (d, J=9.6 Hz,
4H), 7.72 (dd, J=6.3, 3.4 Hz, 2H), 8.12 ppm (dd, J=6.3, 3.4 Hz, 2H);
13C NMR (CDCl3, 100 MHz): d=55.5, 114.0, 129.2, 129.7, 131.4,
131.9, 141.2, 153.2, 160.3 ppm.
ꢀ 2014 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
ChemCatChem 0000, 00, 1 – 5
&
4
&
ÞÞ
These are not the final page numbers!

CHEMCATCHEM
COMMUNICATIONS
www.chemcatchem.org
skaia, A. Lieb, Y. Lill, F. Marotti, A. Schlegel, R.R. Schlittler, P.J. Skinner, P.
Seiler, Y. Yamakoshi, Adv. Funct. Mater. 2006, 16, 147.
TON and TOF
To a stirred solution of benzoin 2a (0.1 mmol, 21.2 mg) or benzhy-
drol 3a (0.1 mmol, 21.4 mg) and o-phenylenediamine 1a
(0.1 mmol, 10.8 mg) in a 1:1 mixture of toluene/water was added
NaOH (12 mg, 0.3 mmol, 3 equiv) and aqueous AuCNT (50 mL,
0.2 mol%). The reaction mixture was stirred until complete con-
sumption of the starting material (monitored by TLC) at RT, then
the catalyst was removed by centrifugation and the supernatant
worked up as described above. The crude residue was directly sub-
jected to silica gel column chromatography to afford pure 4a in
96% yield from 2a (path A) or 94% yield from 3a (path B). TONs
and TOFs were calculated as shown in Equations (1)–(4):
[4] Selected recent reviews on synthesis: a) V. A. Mamedov, N. A. Zhukova,
Prog. Heterocycl. Chem. 2013, 25, 1; b) V. A. Mamedov, N. A. Zhukova,
Prog. Heterocycl. Chem. 2012, 24, 55; c) Y. V. D. Nageswar, K. H. V. Reddy,
K. Ramesh, S. N. Murthy, Org. Prep. Proc. Int. 2013, 45, 1; d) M. Ahmed I-
brahim, Heterocycles 2011, 83, 2689; e) D. F. Saifina, V. A. Mamedov,
Russ. Chem. Rev. 2010, 79, 351; f) D. Bharagava, G. Garg, J. Pharm. Res.
2012, 5, 130.
[5] a) Pd(OAc)2 or RuCl2-(PPh3)3-TEMPO: R. S. Robinson, R. J. K. Taylor, Synlett
2005, 1003; b) Excess MnO2/reflux: S. A. Raw, C. D. Wilfred, R. J. K. Taylor,
Chem. Commun. 2003, 2286; c) Catalytic MnO2/MW: S. Y. Kim, K. H. Park,
Y. K. Chung, Chem. Commun. 2005, 1321.
[6] Selected recent articles: a) microwave–(NH4)6Mo7O24·4H2O–polyethy-
lene glycol (PEG) 300: K. Aghapoor, F. Mohsenzadeh, M. Mohebi Morad,
H. R. Darabi, C. R. Chim. 2012, 15, 764; b) FeCl3-Morpholine: W. Song, P.
Liu, M. Lei, H. You, X. Chen, H. Chen, L. Ma, L. Hu, Synth. Commun.
2012, 42, 236; c) V. K. Akkilagunta, V. P. Reddy, R. R. Kakulapati, Synlett
2010, 2571; d) KMnO4/CuSO4: A. Khorramabadi-Zad, M. Azadmanesh, S.
Mohammadi, South Afr. J. Chem. 2013, 66, 113; e) Et3N, O2: C. Zhang, Z.
Xu, L. Zhang, N. Jiao, Tetrahedron 2012, 68, 5258; f) CaO: T. Hara, Y.
Takami, N. Ichikuni, S. Shimazu, Chem. Lett. 2012, 41, 488; g) Silica,
H2SO4 –PEG: T. Huang, D. Jiang, J. Chen, W. Gao, J. Ding, H. Wu, Synth.
Commun. 2011, 41, 3334; h) KF-Al2O3: S. Paul, B. Basu, Tetrahedron Lett.
2011, 52, 6597; i) MW: V. Jeena, R. S. Robinson, Tetrahedron Lett. 2014,
55, 642; j) Ga(ClO4)3: F. Pan, T.-M. Chen, J.-J. Cao, J.-P. Zou, W. Zhang, Tet-
rahedron Lett. 2012, 53, 2508; k) NHC: L. Gao, R. Liu, C. Yu, C. Yao, T. Li,
Z. Xiao, Res. Chem. Intermed. 2014, 40, 2131; l) Nano-BF3-silica: B. B. F.
Mirjalili, A. Bamoniri, A. Akbari, Chem. Heterocycl. Compd. 2011, 47, 487;
m) Graphite: H. K. Kadam, S. Khan, R. A. Kunkalkar, S. G. Tilve, Tetrahe-
dron Lett. 2013, 54, 1003.
product ½mmolꢁ
catalyst ½mmolꢁ
0:096
0:0002
ð1Þ
ð2Þ
ð3Þ
ð4Þ
TON2a
TOF2a
TON3a
TOF3a
¼
¼
¼
¼
¼
¼ 480
TON2a 480
¼
¼ 18 hꢀ1
26
t ½hꢁ
product ½mmolꢁ
catalyst ½mmolꢁ
0:094
0:0002
¼
¼ 470
TON3a 470
¼
¼ 12 hꢀ1
38
t ½hꢁ
Acknowledgements
[7] 2,3-Disubstituted quinoxalines from phenacyl bromide by using
CeCl3·7H2O-PEG-400: F.-W. Wu, R.-S. Hou, H.-M. Wang, I.-J. Kang, L.-C.
Chen, Heterocycles 2011, 83, 2313.
[8] M. J. Climent, A. Corma, J. C. Hernꢂndez, A. B. Hungrꢃa, S. Iborra, S. J.
Martꢃnez-Silvestre, J. Catal. 2012, 292, 118.
[9] C. S. Cho, S. G. Oh, Tetrahedron Lett. 2006, 47, 5633.
[10] T. Bhattacharya, T. K. Sarma, S. Samanta, Catal. Sci. Technol. 2012, 2,
2216.
[11] a) A. S. K. Hashmi, G. J. Hutchings, Angew. Chem. Int. Ed. 2006, 45, 7896;
Angew. Chem. 2006, 118, 8064; b) A. Corma, H. Garcia, Chem. Soc. Rev.
2008, 37, 2096; c) Y. Mikami, A. Dhakshinamoorthy, M. Alvaro, H. Garcıa,
Catal. Sci. Technol. 2013, 3, 58; d) C. Della Pina, E. Falletta, L. Prati, M.
Rossi, Chem. Soc. Rev. 2008, 37, 2077; e) Y. Zhang, X. Cui, F. Shi, Y. Deng,
Chem. Rev. 2012, 112, 2467; f) C. Della Pina, E. Falletta, M. Rossi, Chem.
Soc. Rev. 2012, 41, 350; g) S. Carrettin, M. C. Blanco, A. Corma, A. S. K.
Hashmi, Adv. Synth. Catal. 2006, 348, 1283.
Support from the Indo-French Centre for the Promotion of Ad-
vanced Research (IFCPAR)/Centre Franco-Indien pour la Promo-
tion de la Recherche Avancꢀe (CEFIPRA) is gratefully acknowl-
edged (Project no. 4705-1). The TEM-team platform (CEA, iBiTec-
S) is acknowledged for help with TEM images. The “Service de
Chimie Bioorganique et de Marquage” belongs to the Laboratory
of Excellence in Research on Medication and Innovative Thera-
peutics (ANR-10-LABX-0033-LERMIT).
Keywords: carbon
·
gold
·
heterogeneous catalysis
·
nanotubes · oxidation
[12] J. John, E. Gravel, A. Hagꢄge, H. Li, T. Gacoin, E. Doris, Angew. Chem. Int.
Ed. 2011, 50, 7533; Angew. Chem. 2011, 123, 7675.
[13] R. Kumar, E. Gravel, A. Hagꢄge, H. Li, D. Jawale, D. Verma, I. N. N. Nam-
boothiri, E. Doris, Nanoscale 2013, 5, 6491.
[14] D. V. Jawale, E. Gravel, V. Geertsen, H. Li, N. Shah, I. N. N. Namboothiri, E.
Doris, ChemCatChem 2014, 6, 719.
[15] R. Kumar, E. Gravel, A. Hagꢄge, H. Li, D. Verma, I. N. N. Namboothiri, E.
Doris, ChemCatChem 2013, 5, 3571.
[16] N. Shah, E. Gravel, D. V. Jawale, E. Doris, I. N. N. Namboothiri, Chem-
CatChem 2014, 6, 2201.
[17] Other properties such as low cost, inertness, high surface area and tun-
able topography are also attractive features of CNT as a catalyst sup-
port: J. John, E. Gravel, I. N. N. Namboothiri, E. Doris, Nanotechnol. Rev.
2012, 1, 515.
[18] N. Khodabakhsh, S. Dariush, M. Maleki, Molecules 2009, 14, 1915.
[19] M. Lian, Q. Li, Y. Zhu, G. Yin, A. Wu, Tetrahedron 2012, 68, 9598.
[20] G. R. Bardajee, R. Malakooti, I. Abtin, H. Atashin, Microporous Mesopo-
rous Mater. 2013, 169, 67.
[21] S. V. More, M. N. V. Sastry, C.-F. Yao, Green Chem. 2006, 8, 91.
[22] S. Ahmad, M. Ali, Chin. J. Chem. 2007, 25, 818.
[1] Selected books: a) Quinoxalines: Supplement I in Chem. Heterocycl.
Compound (Ed.: D. J. Brown), Wiley, Hoboken 2004, p. 510; b) J. E. Simp-
son, Condensed Pyridazine and Pyrazine (Cinnolines, Phthalazines, and
Quinoxalines), Interscience Publications, New York, 1953, 398 pp. For
a general review: c) M. Fultz, W. Rollyson, Heterocyclic Chemistry in Drug
Discovery (Ed.: J. J. Li), Wiley, Hoboken, 2013, p. 536.
[2] Selected recent reviews on biological properties: a) Anticancer: I. Balde-
ras-Renteria, P. Gonzalez-Barranco, A. Garcia, B. K. Banik, G. Rivera, Curr.
Med. Chem. 2012, 19, 4377; b) Anti-tuberculosis: E. Vicente, R. Villar, S.
Perez-Silanes, I. Aldana, R. C. Goldman, A. Monge, Infect. Disord. Drug
Targets 2011, 11, 196; c) DNA intercalating agents: N. S. Hari Narayana
Moorthy, E. Manivannan, C. Karthikeyan, P. Trivedi, Mini-Rev. Med. Chem.
2013, 13, 1415; d) A. Husain, D. J. Madhesia, Pharm. Res. 2011, 4, 924;
e) A. K. Patidar, M. Jeyakandan, A. K. Mobiya, G. Selvam, Int. J. PharmTech
Res. 2011, 3, 386; f) C. J. Dhanaraj, J. Johnson, J. Joseph, R. S. J. Josey-
phus, Coord. Chem. 2013, 66, 1416; g) M. Gonzꢂlez, H. Cerecetto, Expert
Opin. Ther. Pat. 2012, 22, 1289; h) R. M. Rajurkar, V. A. Agrawal, S. S.
Thonte, R. G. Ingale, Pharmacophore 2010, 1, 65.
[3] Selected recent reviews: a) Luminescent materials: S. Achelle, C. Baude-
quin, N. Ple, Dyes Pigm. 2013, 98, 575; b) Organic dye sensitizers: Y. Wu,
W. Zhu, Chem. Soc. Rev. 2013, 42, 2039; c) Cavitand-based molecular
switches: V. A. Azov, A. Beeby, M. Cacciarini, A. G. Cheetham, F. Dieder-
ich, M. Frei, J. K. Gimzewski, V. Gramlich, B. Hecht, B. Jaun, T. Latychev-
Received: September 29, 2014
Published online on && &&, 0000
ꢀ 2014 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
ChemCatChem 0000, 00, 1 – 5
&
5
&
ÞÞ
These are not the final page numbers!

COMMUNICATIONS
N. Shah, E. Gravel, D. V. Jawale, E. Doris,*
I. N. N. Namboothiri*
Mild and free: A one-pot oxidation–
condensation method for the synthesis
of quinoxalines from readily available
benzoins or benzhydrols and aromatic
1,2-diamines is achieved by use of
a gold–carbon nanotube nanohybrid.
Quinoxalines are formed under mild
conditions in air and in excellent yields.
&& – &&
Synthesis of Quinoxalines by a Carbon
Nanotube–Gold Nanohybrid-Catalyzed
Cascade Reaction of Vicinal Diols and
Keto Alcohols with Diamines
ꢀ 2014 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
ChemCatChem 0000, 00, 1 – 5
&
6
&
ÞÞ
These are not the final page numbers!