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An “all-water” strategy for regiocontrolled
synthesis of 2-aryl quinoxalines†
Cite this: RSC Adv., 2015, 5, 11873
Babita Tanwar, Priyank Purohit, Banothu Naga Raju, Dinesh Kumar,
Damodara N. Kommi and Asit K. Chakraborti*
A new synthetic strategy of tandem N-aroylmethylation-nitro reduction–cyclocondensation has been
Received 17th December 2014
Accepted 9th January 2015
developed for the first and generalized regioselective synthesis of 2-aryl quinoxalines adopting “all water
chemistry.” Water plays the critical role through hydrogen bond driven ‘synergistic electrophile–
nucleophile dual activation’ for chemoselective N-aroylmethylation of o-nitroanilines, that underlines the
DOI: 10.1039/c4ra16568c
origin of the regioselectivity, as the use of organic solvents proved to be ineffective. Water also provides
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beneficial effects during the nitro reduction and the penultimate cyclocondensation steps.
Introduction
Quinoxalines exhibit a wide range of biological activities,1
represent the essential pharmacophoric feature of various
drugs (Scheme 1)2 and nd versatile applications in materials
science.3
These have triggered interest to develop synthetic methodologies for quinoxalines that involve the Lewis/Brönsted acid or
Lewis base promoted reaction of o-phenylenediamines
(commercially available or prepared in situ by reduction of the
corresponding o-nitroanilines or 1,2-dinitrobenzenes) with
various coupling partners such as 1,2-diketones (preformed or
prepared in situ from acetylene derivatives), 1,2-ketomonoximes, a-hydroxyketones/a-haloketones, 1,2-diols, a-methyleno
aldehydes/ketones, substituted epoxides, substituted nitroolens.4 However, regiocontrolled construction of the quinoxaline scaffold from unsymmetrical substrates (reacting/
coupling partners) remains elusive. Some of the reported
procedures5 form regioisomeric mixtures while in all others4 the
regioselectivity issue remained unaddressed/suppressed. It was
Scheme 1
realized that the reported procedures4,5 involve simultaneous
condensation of 1,2-bisnucleophiles with 1,2-bis-electrophilic
coupling partners (Scheme 2) and hence are ought to be associated with the regioselectivity problem.
This presses the necessity for a new synthetic design for
regioselective construction of the quinoxaline moiety. Herein
we present a new strategy of “all-water” tandem N-aroylmethylation–reduction–cyclocondensation process for one-pot
synthesis of 2-aryl quinoxalines in regiodened manner
(Scheme 3).
Results and discussion
As the N-aroylmethylation is the critical step, to test the feasibility of the metal and base-free C–N bond formation, in a
model study o-nitroaniline (1a) was treated with a-bromoacetophenone (2a) (Scheme 3, R ¼ H) in various solvents to form
2-[(2-nitrophenyl)amino]-1-phenylethanone (3a) (Table 1).
Excellent yields (91–92%) of 3a was obtained in water. The
comparable results in tap, pure, and ultra pure water (entries 2–
4, Table 1) indicate that the N-benzoylmethylation is not inuenced by any dissolved metallic/organic impurities. The specic
assistance of water in promoting the metal/base free N-benzoylmethylation is revealed by the fact that 3a was formed in
poor yield under neat condition (entry 1, Table 1) and in
hydrocarbon, halogenated hydrocarbon, ethereal, and aprotic
A few quinoxaline-based drugs.
Department of Medicinal Chemistry, National Institute of Pharmaceutical Education
and Research (NIPER), Sector 67, S. A. S. Nagar, 160 062, Punjab, India. E-mail:
akchakraborti@niper.ac.in; akchakraborti@rediffmail.com
† Electronic supplementary
10.1039/c4ra16568c
information
(ESI)
This journal is © The Royal Society of Chemistry 2015
available.
See
DOI:
Scheme 2
Regioselectivity in the synthesis of quinoxalines.
RSC Adv., 2015, 5, 11873–11883 | 11873
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Table 2 N-Benzoylmethylation of o-nitroaniline (1a) under different
conditiona
3 “All-water”
N-aroylmethylation–reduction–cyclocondensation strategy for regiocontrolled synthesis of quinoxalines.
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Scheme
polar solvents (entries 10–20, Table 1). Alcohols (protic polar
solvents) gave moderate yields (entries 5–9, Table 1).
Further studies on the variation of different reaction
parameters, such as the molar equivalents of 2a, amount of
water, temperature, and time revealed the use of 1.0 molar
equivalent of 2a in water (2 mL mmol 1 of 1a) at 110 C
(oil bath) for 3 h to be the optimal condition (entry 19, Table 2).
The synthetic potential of the water-assisted N-aroylmethylation of o-nitroanilines is demonstrated by the reaction of a few
substituted o-nitroanilines 1 with substituted a-bromoacetophenones 2 to form 3 (Table 3).
Table 1 Influence of the reaction medium for a metal/catalyst and
base-free selective N-monobenzoylmethylation of 1a with 2aa
Entry
Solvent
Temp ( C)
ab
bb
Yieldc (%)
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
18
19
20
None
Tap water
Pure waterd
Ultra pure watere
MeOH
EtOH
i
PrOH
t
BuOH
TFE
Toluene
Hexane
DCE
1,4-Dioxane
THF
Acetone
MeNO2
DMF
DMA
Formamide
MeCN
110
Reux
Reux
Reux
Reux
Reux
Reux
Reux
Reux
Reux
Reux
Reux
Reux
Reux
Reux
Reux
110
110
110
Reux
—
1.17
1.17
1.17
0.93
0.83
0.76
0.68
1.51
0.00
0.00
0.00
0.00
0.00
0.08
0.22
0.00
0.00
0.71
0.19
—
0.18
0.18
0.18
0.62
0.77
0.95
1.01
0.00
0.11
0.00
0.00
0.37
0.55
0.48
0.00
0.69
0.76
0.00
0.31
7
92
91
92
59
65
68
74
50
31
Trace
35
55
21
13
33
36
Nil
23
Trace
Entry
Water (mL)
Temp ( C)
Time (h)
Equiv. of 2ab
Yieldc (%)
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
5
5
5
5
5
5
0.5
1
2
3
4
2
2
2
2
2
2
2
2
2
5
2
2
2
110
110
110
110
110
110
110
110
110
110
110
rt
60
80
110
120
110
110
110
110
110
rt
80
120
5
5
5
5
5
5
5
5
5
5
5
5
5
5
5
5
1
2
3
4
2
12
8
2
1.0
1.1
1.2
1.3
1.4
1.5
1.0
1.0
1.0
1.0
1.0
1.0
1.0
1.0
1.0
1.0
1.0
1.0
1.0
1.0
1.0
1.0
1.0
1.0
92
92
92
93
92
92
68
79
92
92
92
0
Traces
41
92
92
28
75
92
92
84
Nil
35
87
a
a
1a (1 mmol) was treated with 2a (1.5 mmol, 1.5 equiv.) in the
appropriate solvent (5 mL), except for entry 1, under heating at 110 C
(oil bath) for 5 h. b The a and b values represent the hydrogen bond
donor (HBD) and hydrogen bond acceptor (HBA) property of the
solvent as provided under ref. 13. c Isolated yield. d Pure water was
obtained by purication of normal/tap water through reverse osmosis
and ionic/organic removal and has the resistivity of 15 MU at 25 C.
e
Ultrapure water was obtained by further subjecting pure water to UV
treatment (185/254 nm), deionization and ultra membrane ltration
(0.01 mm) under pressure up to 145 psi (10 bar) and has the resistivity
of 18.2 MU at 25 C.
11874 | RSC Adv., 2015, 5, 11873–11883
1a (1 mmol) was treated with 2a under different reaction condition in
the water as a reaction medium. b Molar equiv. with respect to 1a.
Isolated yield of 3a.
c
The reported method for the preparation of N-phenacyl-onitroanilines involve the use of base in DMF for 48 h.6 Anilines
are known to react with a-halogenated ketones to form indoles.7
The base/catalyst-free N-aroylmethylation of different onitroanilines (1) with different a-bromoacetophenones (2) in water to
form 3a
Table 3
Entry
R1
R2
R3
Time (h)
Yieldb (%)
1
2
3
4
5
6
H
H
Cl
H
CH3
CH3
H
H
H
Cl
H
H
H
Cl
H
H
H
OMe
3
3
4
4
3
3
92
91
89
90
92
90
a
1 (1 mmol) was treated with 2 (1 mmol, 1 equiv.) in water (2 mL) at
110 C (oil bath) for stipulated time period. b Isolated yield of 3.
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Thus, the results of Table 3 exemplify an excellent metal and
base-free C–N bond formation protocol for chemoselective
synthesis N-phenacyl-o-nitroanilines. The role of water can be
visualized by its ability to form hydrogen bond (HB) with the
NH2 hydrogen of 1 (nucleophilic activation). The second molecule of the water dimer8 in turn forms HB with the Br atom of 2
(electrophilic activation) and brings the bromomethylene
carbon in close proximity to the NH2 nitrogen of 1 in the
H-bonded species (Scheme 4). Further, the carbonyl oxygen of 2
also participates in HB formation with another water dimer in
which the second water molecule forms HB with the other NH2
hydrogen in 1. The array/network of HBs gives stability9 to the
H-bonded cluster (Scheme 4) and facilitates ‘amphiphile
nucleophilic–electrophilic dual activation.’10
The hydrogen-bond assisted/mediated formation of noncovalent adduct of the reactants and the promoter has been
invoked in various organo-catalytic chemical reactions/
synthesis.11
The physico-chemical parameters (acceptor/donor number
etc.) of the solvent oen play key role in organic reactions,12 and
the HB involving the reactant and the solvent has signicant
inuence.13 Therefore, the role of the reaction medium for
N-aroylmethylation can be visualized through the formation of
the HB adducts (Scheme 4) due to the hydrogen bond donor
(HBD) (a scale) and hydrogen bond acceptor (HBA) (b scale)
properties of the solvent.14 Although, the HBD property (a value)
is expected to play the predominant role in activating the
electrophile (2a) the HBA ability (b value) is also important as it
determines the ability of the solvent to activate the nucleophile
(amine nitrogen of 1a). Therefore, TFE gave inferior results due
to its poor b value (entry 9, Table 1).
The reduction of nitro group of 3a would form the intermediate 4a which on cyclocondensation would form the
2-phenyl quinoxaline 5a (Scheme 3, R ¼ H). However, treatment
of 3a with In (2.5 equiv.) and 12 N HCl (5 equiv.)15 in water
(2 mL) afforded 5a in 24% yield at 110 C (oil bath) aer 3 h
(Table 4). Further studies on standardization of the reaction
conditions revealed that the best result (90% yield) is obtained
in using 5 equiv. of 2 N HCl (entry 3, Table 4). Organic solvents
gave inferior results highlighting the benecial effect of water
on the reduction due to enhanced solvation of the In3+ cation in
water making the electron transfer more efficient.16
To nd out whether indium metal can be replaced by other
less costly metals such as Fe, Zn, Mg, Sn, or SnCl2$2H2O, 3a was
RSC Advances
The effect of solvent and the amount of aq. HCl and In metal
on the cascade reduction–cyclocondensation stepa
Table 4
Entry Solvent
In metal (mmol) aq. HCl (mL)
Equiv.b Yieldc,d (%)
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
18
2.5
2.5
2.5
2.5
2.5
2.5
2.0
1.5
2.5
2.5
2.5
2.5
2.5
2.5
2.5
2.5
2.5
2.5
5
5
5
4
3
2
5
5
5
5
5
5
5
5
5
5
5
5
Water
Water
Water
Water
Water
Water
Water
Water
EtOH
Toluene
Toluene
Dioxane
DCE
MeCN
DCE
THF
DMF
None
12 N (0.4 mL)
6 N (0.8 mL)
2 N (2.5 mL)
2 N (2 mL)
2 N (1.5 mL)
2 N (1 mL)
2 N (2.5 mL)
2 N (2.5 mL)
12 N (0.4 mL)
12 N (0.4 mL)
2 N (2.5 mL)
12 N (0.4 mL)
12 N (0.4 mL)
12 N (0.4 mL)
12 N (0.4 mL)
12 N (0.4 mL)
12 N (0.4 mL)
2 N (2.5 mL)
24
59
90e,f
67
42
21
64
44
Trace
42
27
Nil
Nil
Nil
Nil
Nil
Nil
14
a
To the mixture of 3a (1 mmol) in water (2 mL, entries 1–6) or the
specied organic solvent (4.1 mL, entries 7–15) was added In metal
(1.5–2.5 equiv. as indicated against each entry) and the indicated
amount (in ML) of aq. HCl at 110 C (oil bath) and the mixture was
stirred magnetically for 3 h. b Molar equiv. of HCl. c Isolated yield of
5a. d The unreacted 3a remained unchanged and could be recovered
wherever 5a was formed in poor yields. e Only trace amount of 5a was
formed in performing the reaction at room temperature (35–40 C).
f
5a was obtained in 63% yield in performing the reaction at 80 C.
Table 5 The effect of different metals/reducing agent on the cascade
reduction–cyclocondensation stepa
Entry
Metal
Isolated Yield
of 5a (%)
1
2
3
4
5
6
7
In
Fe
Zn
Mg
Al
Sn
SnCl2$2H2O
90
61
Traceb
Traceb
25b
64
65
a
The envisaged role of water in promoting N-aroylmethylation of 1 with 2 to form 3.
Scheme 4
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To the mixture of 3a (1 mmol) in water (2 mL) was added metal or the
indicated reducing agent (2.5 equiv.) and aq. HCl (2 N, 2.5 mL; 5 equiv.)
at 110 C (oil bath) and the mixture was stirred magnetically for 3 h.
b
The unreacted 3a remained unchanged and could be recovered.
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treated with different metals/reducing agent (2.5 equiv.) in aq.
HCl (2 N 2.5 mL, 5 equiv.) (Table 5).
Thus, the use of indium metal provided the best results. The
product isolation was found to be tedious in case of aluminium
due to gel formation in the reaction mixture. The use of Sn
metal or its popularly used salt SnCl2$2H2O was also less
effective.17
To determine whether Fe, Zn, Mg, Sn, or SnCl2$2H2O would
offer similar benecial effect compared to Fe, Zn, Mg, Sn, or
SnCl2$2H2O for the one pot tandem N-aroylmethylation–
reduction–condensation, 1a was sequentially treated with 2a in
water followed by different metals/reducing agent (2.5 equiv.) in
aq. HCl (2 N 2.5 mL, 5 equiv.) to form 5a (Table 6). The best
result was obtained in using indium metal. Herein also poor
yields were obtained with Sn metal and SnCl2$2H2O.17
The poor yields of 5a obtained in organic solvents (Table 4)
during the treatment of 3a with In/HCl raised the query as to
whether the use of aqueous medium exerts benecial effect only
for the nitro reduction or its benecial effect extends for the
subsequent cyclocondensation step as well. To distinguish any
role of water in the cyclocondensation of 4a to 5a, it was felt
necessary to treat the preformed 4a in water as well as in organic
solvents. However 4a could not be isolated by the In/HCl
reduction of 3a, although the MS spectra of the crude reaction
mixture exhibited ion peak corresponding to 4a. Attempts such
as (i) Pd/C mediated hydrogenation of 3a (Scheme 5), and (ii)
reaction of o-phenylenediamine (6) with 2a (Scheme 6) were
unsuccessful and resulted in the formation of 5a in 35 and 60%
yields, respectively.
Thus, it was planned to prepare 8a [pro-4a] which would
generate 4a in situ through N-Boc deprotection under acid/
metal-free condition (Scheme 7). Although a few methods18
The effect of different metals/reducing agent on the tandem
N-aroylmethylation–reduction–cyclocondensation during the reaction of 1a with 2a to form 5aa
Table 6
Entry
Metal
Isolated yield
of 5a (%)
1
2
3
4
5
6
7
In
Fe
Zn
Mg
Al
Sn
SnCl2$2H2O
84
59
Traceb
Traceb
15b
63
57
Pd-Catalysed hydrogenation of 2-[(2-nitrophenyl)amino]1-phenylethanone (3a).
Scheme 5
Scheme 6 Reaction of o-phenylenediamine (6) with a-bromoacetophenone (2a).
were reported for mono-N-Boc formation of 6, repetition of
some of these led to the mixture of the mono- and di-N-Boc
derivatives of 6 (Table 7).
The mono-N-Boc 7a was obtained in 71% yield following
modication of literature report18e and was treated with 2a in
water to form 8a (Scheme 7).
The acid/metal-free N-Boc deprotection is reported to take
place in water19 and triuoroethanol (TFE)20 under heating. The
treatment of 8a in water 110 C (oil bath) gave 5a in 82% yield
aer 2 h (Scheme 8). This indicated that the cyclocondensation
of the in situ formed 4a to 5a is promoted by water. However, 5a
was formed in 15% yield by the treatment of 8a in TFE under
reux for 24 h. No signicant amount of 5a was obtained by the
treatment of 8a in TFE under reux for 5 h. The treatment of 8a
in water (in place of TFE) under similar condition (80 C for 5 h)
afforded 5a in 71% yield. Thus, water is the best solvent for the
cyclocondensation step due its favourable a and b values that
render a better ‘dual activation’ ability of water compared to
organic solvents.
The generality of the new strategy of ‘all water’ one-pot
tandem
N-aroylmethylation–reduction–condensation
for
synthesis of 2-aryl quinoxalines is demonstrated by sequential
treatment of various o-nitroanilines with different a-bromoacetophenones in water under heating followed by treatment
with In/HCl (2 N) (Table 8).
Condensation of o-phenylenediamine with phenacyl
bromide has been reported in water as well as organic solvents
in the presence of organic/inorganic catalysts to form 2-phenylqunoxalines.4a,d–j,5c However, a catalyst-free protocol in water
that would reect the distinct inuence of water in the
N-aroylmethylation and subsequent cyclo-condensation step is
lacking. Thus, to evaluate any distinct advantage of water over
organic solvents 6 was treated with 2a in various solvents in the
a
1a (1 mmol) was treated with 2a in water (2 mL) at 110 C (oil bath) for
3 h followed by addition of the metal/reducing agent (2.5 equiv.) and aq.
HCl (2 N, 2.5 mL; 5 equiv.) at 110 C (oil bath) and the mixture was
stirred magnetically for further 3 h. b The unreacted 1a and 2a
remained unchanged.
Scheme 7
11876 | RSC Adv., 2015, 5, 11873–11883
Synthesis of 8a.
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Table 7 Preparation of tert-butyl-(2-aminophenyl)carbamate (7a)a
Yieldb (%)
Entry
(Boc)2O
(equiv.)
Catalyst (mol%)
Solvent (amt)
Temp ( C)
Time (h)
7a
7b
1
2
3
4
5
1.2
1
1
1
1
Gu$HClc (15)
LiClO4 (20)
None
Iodine (10)
None
EtOH (1 mL)
DCM (2 mL)
DCM (1 mL)
Neat
EtOH (4 mL)
35–40
30–40
0
35–40
30
3
5
2
4
0.5
52
42
64
35
71
28
23
21
35
22
a
c
Treatment of 6 (1 mmol) under different reaction condition in different solvents at specied temperature for specied time.
Gu$HCl stands for guanidinium hydrochloride.
absence of any added base/acid catalyst at 110 C (oil bath)
(Table 9).
The best yield obtained in water clearly reect the distinct
advantage of water as the reaction medium for the tandem
N-aroylmethylation-cyclocondensation.
Comparable
yield
(74%) obtained in performing the reaction in water in the
presence of K2CO3 (1 equiv.) (Table 9, entry 2, footnote d) rules
out the possibility of any essential role of the liberated HBr
(during the initial N-aroylmethylation step) for the nal
cyclocondensation.
The signicant role of the solvent (Table 9) in the nal
cyclocondensation step can be demonstrated by the best results
are obtained in water that acts both as good hydrogen bond
donor and hydrogen bond acceptor with the second best results
obtained in EtOH. The lesser yield obtained in TFE compared to
that in water and EtOH is the clear reection of the inferior
hydrogen bond acceptor ability of TFE. The use of 1,4-dioxane
afforded the next best result due to its appreciable hydrogen
bond acceptor ability (to activate the amino group of the
intermediately formed 4a). The better result in 1,4-dioxane
compared to that of THF could be due to the chelation effect of
the two oxygen atoms in the former to form the HB with the NH2
group more effectively. The inferior yields in DMF, MeCN and
toluene are also reection of the unfavourable hydrogen bond
donor/acceptor ability of these solvents.
Although the quinoxaline formation by a direct condensation of 6 with 2a becomes feasible in water under catalyst-free
condition, the reaction of unsymmetrical o-phenylenediamine
with phenacyl bromide is expected to form regioisomeric
Scheme 8
Acid/metal-free cyclocondensation of 7a to form 5a.
This journal is © The Royal Society of Chemistry 2015
b
Isolated yield.
quinoxalines as has been observed in one of the literature
reports.5c However, the regioselectivity issue remained
unaddressed/suppressed in the other reported methodologies.4a,d–j To throw light on this regioselectivity issue and
establish the distinctiveness of the “all water” strategy of the Naroylmethylation–nitro reduction–cyclocondensation cascade
for regioselective synthesis of 2-aryl quinoxalines, the condensation of 4-chloro-1,2-phenylenediamine 9 with phenacyl
Table 8 ‘All water’ cascade synthesis of 2-aryl quinoxalinesa
Entry
R1
R2
R3
R4
Timeb (h)
Yieldc (%)
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
H
H
H
H
H
Cl
Cl
Cl
Cl
H
H
H
H
Me
Me
OMe
H
H
H
H
H
H
H
H
H
Cl
Cl
Cl
Cl
H
H
H
H
H
OMe
H
H
H
H
H
H
H
H
H
H
H
H
H
H
OMe
H
Cl
Br
H
OMe
Cl
Br
H
OMe
Cl
Br
OMe
Br
H
5
5
5
5
5
6
6
6
6
6
6
6
6
5
5
5
86
83
84
82
84
81
80
82
80
83
81
82
83
80
80
82
a
1 (1 mmol) was treated with 2 (1 mmol, 1 equiv.) in water (2 mL) at
110 C (oil bath) for 3 h followed by addition of In (2.5 mmol, 2.5
equiv.), 2 N HCl (2.5 mL, 5 mmol, 5 equiv.) and allowed to proceed
for remaining time. b Total time for the one-pot reaction. c Isolated
yield of 5.
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with literature reports.5i,l On the other hand, the reaction of
4-chloro-2-nitroaniline with phenacyl bromide following the
tandem
N-aroylmethylation–reduction–cyclocondensation
strategy resulted in exclusive formation of one of the regioisomeric quinoxalines without any concomitant formation of the
other regioisomer (entry 10, Table 8). This clearly demonstrates
the distinct advantage of this new synthetic strategy. The
unambiguous route of construction of the quinoxaline scaffold
under the present method forms the basis of regioselectivity
control.
Reaction of 6 with 2a in various solvents under catalyst-free
conditiona
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Table 9
Entry
Solvent
Temp ( C)
Yieldb (%)
1
2
3
4
5
6
7
8
9
Water
Water
EtOH
Toluene
1,4-Dioxane
THF
DMF
MeCN
TFE
80
Reux
Reux
Reux
Reux
Reux
110
Reux
Reux
62
79, 71c and 74d
65
40
61
47
52
45
40
Conclusions
A new synthetic strategy of ‘all water’ tandem aroylmethylation–
nitro reduction–cyclocondensation is reported for the rst and
generalized regioselective synthesis of 2-aryl quinoxalines.
Water plays the critical role through hydrogen bond driven
‘synergistic electrophile nucleophile dual activation’ during the
N-aroylmethylation and provides the basis of quinoxaline
formation in regiodened manner. Water also exerts benecial
effect during the nitro reduction–cyclocondensation cascade
and makes this synthetic strategy a true example of ‘all-water
chemistry.’
a
6 (1 mmol) was treated with 2a in the specic solvent (2 mL) at 80/
110 C (oil bath temperature) for 4 h (unless specied). b Isolated
yield of 5a. c The yield of 5a in performing the reaction for 3 h. d The
yield of 5a in performing the reaction for 3 h in the presence of
K2CO3 (1 equiv.).
Experimental section
bromide was performed in water as well as in organic solvents
under the reported reaction conditions4a,d–j,5c (Table 10). In all of
these cases the isolated product on being subjected to 1H NMR
analyses revealed to be a mixture of the regioisomeric products.
In each case, the pure regioisomers were isolated through ash
column chromatography and were identied as A and B based
on the spectral data of authentic compounds (products of
entries 6 and 10, respectively, of Table 8) and on comparison
General remarks
The glasswares used were thoroughly washed and dried in an
oven and the experiments were carried out with required
precautions. Chemicals and all solvents were commercially
available and used without further purication. The TLC
experiments were performed on silica gel GF-254 and visualized
under UV at 254 nm. Evaporation of solvent was performed at
Table 10 Reaction of I with 2a under the reported reaction conditionsa
Yieldd (%)
Entry
Catalystb (mol%)
Solvent
Temp ( C)
Time (h)
(A : B)c
A
B
1
2
3
4
5
6
7
8
9
Pyridine (10)
—
b-CD (1 equiv.)
TMSCl (1 equiv.)
CTAB (20)
HClO4–SiO2 (50 mg)
TBAB (20) + K2CO3 (2 equiv.)
DABCO (20)
—
THF
PEG-400
Water
Water
Water
MeCN
Water
THF
Water
rt
80
70
70
10
rt
Rt-70
rt
110
2
8
3
8
8
1
4.5
1
7
20 : 80
83 : 17
79 : 21
86 : 14
34 : 65
22 : 77
72 : 28
32 : 67
58 : 42
25
65
63
51
25
15
51
12
33
45
15
21
12
62
63
18
62
41e
a
I (1 mmol) was treated with 2a under the various reported reaction conditions. b Lit ref. 4a, e–j, and 5c for entries 1–8, respectively. c Regioisomeric
distribution based on Ha and Hb proton integration value in the 1H NMR of the crude reaction mixture. d Isolated yield aer ash column
chromatography. e Data generated under the condition of the present study.
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reduced pressure using a rotary evaporator. Melting points were
measured using a melting point apparatus and were uncorrected. The 1H and 13C NMR spectra were recorded on a
400 MHz NMR spectrometer in CDCl3 with residual undeuterated solvent (CHCl3: 7.26/77.0) using Me4Si as an internal
standard. The chemical shi (d) values are given in ppm and
J values are given in Hz. The 13C NMR spectra were fully
decoupled and were referenced to the middle peak of the
solvent CDCl3 at 77.00 ppm. Splitting pattern were designated
as s, singlet; bs, broad singlet; d, doublet; dd, doublet of
doublet; t, triplet; dt, doublet of triplet and m, multiplet. The
mass spectra (MS) were recorded under atmospheric pressure
chemical ionization (APCI) and electrospray ionization (ESI).
The high resolution mass spectra (HRMS) were recorded under
electrospray ionization (ESI). The infra-red (IR) spectra were
recorded in the range of 4000–600 cm 1 as KBr pellets for all
solid samples.
(M + H)+. HRMS (ESI) m/z calcd for C14H12N2O3Na+ [M + Na+],
279.0740; found 279.0740.
Preparation of pure water (15 MU cm resistivity at 25 C)
Typical procedure for ‘all water’ one-pot tandem Naroylmethylation–reduction–condensation for synthesis of
2-aryl quinoxalines
The pure water was prepared by subjecting the tap water for
reverse osmosis and ionic/organic removal by passing through
pre-packed cartridge.
Preparation of ultrapure water (18.2 MU cm resistivity at 25 C)
The ultrapure water was prepared by subjecting the pure water
for UV treatment (185/254 nm UV Lamp), deionization by
passing through deionization cartridge followed by ultra
membrane ltration (0.01 mm) under pressures up to 145 psi
(10 bar). Ultrapure water (UPW) is generally considered to be
$18.2 MU cm resistivity at 25 C, low ppt in metals, less than
50 ppt in inorganic anions and ammonia, less than 0.2 ppb in
organic anions, and below 1 ppb total organic carbon (TOC) and
silica (dissolved and colloidal).
Typical procedure for selective mono-N-benzoylmethylation of
o-nitroaniline (1a)
The mixture of o-nitroaniline 1a (138 mg, 1 mmol) and a-bromoacetophenone 2a (199 mg, 1 mmol, 1 equiv.) in water (2 mL)
was stirred magnetically at 110 C (oil-bath). Aer completion of
the reaction (3 h, TLC), the reaction mixture was extracted with
EtOAc (3 5 mL). The combined EtOAc extracts were dried
(anh Na2SO4), ltered, and the ltrate was concentrated under
rotary vacuum evaporation. The crude product was adsorbed on
silica gel (230–400 mesh size, 500 mg), charged on to a ash
chromatography column of silica-gel (230–400 mesh size, 2.5 g),
and eluted with hexane–EtOAc (95 : 5) to obtain analytically
pure 2-((2-nitrophenyl)amino)-1-phenylethanone (Table 2, entry
1) (3a) as yellow solid (236 mg, 92%); mp ¼ 147–149 C; IR (KBr)
nmax ¼ 3433, 2926, 2872, 1735, 1619, 1570, 1514, 1453, 1352,
1259, 1106, 951, 749 cm 1; 1H NMR (CDCl3, 400 MHz, TMS) d:
8.92 (bs, 1H), 8.25 (dd, J ¼ 1.5, 8.5 Hz, 1H), 8.07–8.05 (m, 2H),
7.69–7.65 (m, 1H), 7.58–7.48 (m, 3H), 6.84–6.82 (m, 1H),
6.76–6.72 (m, 1H), 4.80 (d, J ¼ 4.4 Hz, 2H); 13C NMR (CDCl3, 100
MHz, TMS) d: 192.71, 143.97, 136.22, 134.44, 134.22, 132.70,
129.04, 127.89, 127.08, 115.98, 114.14, 49.42; MS (APCI) m/z: 257
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Typical procedure for the cascade reduction–condensation of
3a to 5a
To the mixture of 2-[(2-nitrophenyl)amino]-1-phenylethanone
3a (256 mg, 1 mmol) in water (2 mL) was added In metal
(287 mg, 2.5 mmol, 2.5 equiv.) and 2 N HCl (2.5 mL, 5 mmol,
5 equiv.), and the mixture was stirred magnetically at 110 C
(oil-bath) for 3 h (TLC). The reaction mixture was extracted with
EtOAc (3 5 mL). The combined EtOAc extracts were dried
(anh Na2SO4), ltered, and the ltrate was concentrated under
rotary vacuum evaporation. The crude product was adsorbed on
silica gel (230–400 mesh size, 500 mg), charged on to a ash
chromatography column of silica-gel (230–400 mesh size, 2.5 g),
and eluted with hexane–EtOAc (99 : 1) to obtain analytically
pure 5a as a pale orange solid (185 mg, 90%)4a (Table 4).
Synthesis of 5a. The mixture of o-nitroaniline 1a (138 mg,
1 mmol) and a-bromoacetophenone 2a (199 mg, 1 mmol,
1 equiv.) in water (2 mL) was stirred magnetically at 110 C
(oil-bath) for 3 h followed by addition of In (287 mg, 2.5 mmol,
2.5 equiv.), 2 N HCl (2.5 mL, 5 mmol, 5 equiv.) and the reaction
mixture was allowed to stir till the completion of reaction
(2 h, TLC). The reaction mixture was extracted with EtOAc (3
5 mL). The combined EtOAc extracts were dried (anh Na2SO4),
ltered, and the ltrate was concentrated under rotary vacuum
evaporation. The crude product was recrystallized from EtOH to
afford analytically pure 2-phenylquinoxaline (Table 8, entry 1)
(5a) as a pale orange solid (177 mg, 86%). mp ¼ 75–76 C; nmax ¼
3005, 2325, 1275, 1260, 764, 750 cm 1; 1H NMR (CDCl3, 400
MHz, TMS) d: 9.26 (s, 1H), 8.15–8.05 (m, 4H), 7.72–7.65 (m, 2H),
7.52–7.45 (m, 3H); 13C NMR (CDCl3, 100 MHz, TMS) d: 151.68,
143.26, 142.21, 141.53, 136.69, 130.19, 130.13, 129.57, 129.45,
129.07, 127.48; MS (ESI) m/z: 207 (M + H)+.4a
In an alternative purication procedure the crude product
was adsorbed on silica gel (230–400 mesh size, 500 mg), charged
on to a ash chromatography column of silica-gel (230–400
mesh size, 2.5 g), and eluted with hexane–EtOAc (99 : 1) to
obtain analytically pure 2-phenylquinoxaline (Table 8, entry 1)
(5a) as a pale orange solid (173 mg, 84%).
In general, the purication was made by crystallization
except for low melting (<65 C) compounds wherein the purication was made through column chromatography.
Experimental procedure for the various attempts for the
synthesis of 2-((2-aminophenyl)amino)-1-phenylethanone (4a)
Pd-catalysed hydrogenation of 2-[(2-nitrophenyl)amino]-1phenylethanone (3a) (Scheme 5). Pd/C (5%) (10 mg) was
added to the of 3a (256 mg, 1 mmol) in toluene (10 mL) and kept
under H2 atmosphere at room temperature at 40 psi pressure.
Aer 6 h, the Pd/C was removed by ltration and the ltrate was
concentrated under rotary vacuum evaporation. The crude
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product was adsorbed on silica gel (230–400 mesh size, 500 mg),
charged on to a ash chromatography column of silica-gel
(230–400 mesh size, 2.5 g), and eluted with hexane–EtOAc
(99 : 1) to obtain analytically pure 5a as a pale orange solid
(72 mg, 35%).4a
Reaction of o-phenylenediamine (6) with a-bromoacetophenone (2a) (Scheme 6). To the mixture of o-phenylenediamine (6) (108 mg, 1 mmol) and a-bromoacetophenone (2a)
(199 mg, 1 mmol, 1 equiv.) in MeCN (2 mL) was added K2CO3
(276 mg, 2 mmol, 2 equiv.) and stirred magnetically under reux
condition. Aer completion of the reaction (4 h, TLC), the
reaction mixture was extracted with EtOAc (3 5 mL). The
combined EtOAc extracts were dried (anh Na2SO4), ltered, and
the ltrate was concentrated under rotary vacuum evaporation.
The crude product was adsorbed on silica gel (230–400 mesh
size, 500 mg), charged on to a ash chromatography column of
silica-gel (230–400 mesh size, 2.5 g), and eluted with hexane–
EtOAc (99 : 1) to obtain analytically pure 5a as a pale orange
solid (123 mg, 60%).4a
Experimental procedure for the synthesis of tert-butyl-(2-[(2oxo-2-phenylethyl)aminophenyl]carbamate (8a) (Scheme 7/
Table 7)
Step 1: preparation of tert-butyl-(2-aminophenyl)carbamate
(7a). o-Phenyldiamine (6) (108 mg, 1 mmol) was stirred at 30 C
in absolute EtOH (2 mL), and di-tert-butyl dicarbonate (218 mg,
1.1 mmol, 1.1 equiv.), dissolved in absolute EtOH (2 mL), was
added dropwise to the reaction mixture. Aer 30 min, the
solvent was evaporated to dryness, and the crude material. The
crude product was adsorbed on silica gel (230–400 mesh size,
500 mg), charged on to a ash chromatography column of
silica-gel (230–400 mesh size, 2.5 g), and eluted with hexane–
EtOAc (96 : 4) to obtain analytically pure tert-butyl-(2-aminophenyl)carbamate (7a) as a white solid (147 mg, 71%); mp ¼
110–113 C; IR (KBr) nmax ¼ 3414, 3356, 2973, 1896, 1682, 1595,
1490, 1456, 1387, 1366, 1162, 1054, 1027, 850, 749 cm 1; 1H
NMR (CDCl3, 400 MHz, TMS) d: 7.28–7.27 (m, 1H), 7.00 (dt, J ¼
1.36, 7.6 Hz, 1H), 6.81–6.75 (m, 2H), 6.35 (bs, 1H), 3.75 (bs, 2H),
1.52 (s, 9H); 13C NMR (CDCl3, 100 MHz, TMS) d: 153.91, 139.99,
126.13, 124.77, 119.56, 117.57, 80.50, 28.35; MS (ESI) m/z: 209
(M + H)+. HRMS (ESI) m/z calcd for C11H16N2O2Na+ [M + Na+],
231.1109; found 231.1114.18e
Di-tert-butyl-1,2-phenylenedicarbamate (7b). White solid
(65 mg, 22%); mp ¼ 105–106 C; IR (KBr) nmax ¼ 3307, 2978,
2931, 1699, 1601, 1527, 1457, 1248, 1158, 1049, 1025, 749 cm 1;
1
H NMR (CDCl3, 400 MHz, TMS) d: 7.47 (bs, 2H), 7.11 (s, 2H),
6.89 (s, 2H), 1.52 (s, 18H); 13C NMR (CDCl3, 100 MHz, TMS) d:
153.90, 130.29, 125.31, 124.22, 80.76, 28.46; MS (ESI) m/z:
309 (M + H)+.18a
Step 2 (Scheme 7): synthesis of tert-butyl-(2-[(2-oxo-2phenylethyl)aminophenyl]carbamate (8a) from 7a. The
mixture of tert-butyl-2-aminophenylcarbamate (7a) (208 mg,
1 mmol) and a-bromoacetophenone (2a) (199 mg, 1 mmol,
1 equiv.) in water (2 mL) was stirred magnetically at rt. Aer
completion of the reaction (12 h, TLC), the reaction mixture was
extracted with EtOAc (3 5 mL). The combined EtOAc extracts
11880 | RSC Adv., 2015, 5, 11873–11883
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were dried (anh Na2SO4), ltered, and the ltrate was concentrated under rotary vacuum evaporation. The crude product was
adsorbed on silica gel (230–400 mesh size, 500 mg), charged on
to a ash chromatography column of silica-gel (230–400 mesh
size, 2.5 g), and eluted with hexane–EtOAc (94 : 6) to obtain
analytically pure 8a as a light yellow solid (189 mg, 58%); mp ¼
130–132 C; IR (KBr) nmax ¼ 3368, 2925, 1698, 1607, 1498, 1449,
1356, 1248, 1166, 1048, 739 cm 1; 1H NMR (CDCl3, 400 MHz,
TMS) d: 8.03 (d, J ¼ 7.4 Hz, 2H), 7.64 (t, J ¼ 7.36 Hz, 1H), 7.53
(t, J ¼ 7.72 Hz, 2H), 7.39 (t, J ¼ 7.04 Hz, 1H), 7.15–7.11 (m, 1H),
6.81 (t, J ¼ 7.44 Hz, 1H), 6.74 (d, J ¼ 7.96 Hz, 1H), 6.27 (s, 1H),
4.99 (bs, 1H), 4.61 (bs, 2H), 1.56 (s, 9H); 13C NMR (CDCl3, 100
MHz, TMS) d: 195.22, 154.16, 141.16, 134.93, 133.89, 128.92,
127.78, 126.58, 125.60, 124.68, 118.59, 112.93, 80.57, 50.75,
28.36; MS (ESI) m/z: 237 (M + H)+. HRMS (ESI) m/z calcd for
C19H22N2O3Na+ [M + Na+], 349.1528; found 349.1545.
Experimental procedure for the synthesis of 5a from 8a
(Scheme 8)
The mixture of tert-butyl-(2-[(2-oxo-2-phenylethyl)aminophenyl]carbamate (8a) (326 mg, 1 mmol) in water (3 mL) was stirred
magnetically at 110 C (oil-bath). Aer completion of the reaction (2 h, TLC), the reaction mixture was extracted with EtOAc
(3 5 mL). The combined EtOAc extracts were dried (anh
Na2SO4), ltered, and the ltrate was concentrated under rotary
vacuum evaporation. The crude product was adsorbed on silica
gel (230–400 mesh size, 500 mg), charged on to a ash chromatography column of silica-gel (230–400 mesh size, 2.5 g), and
eluted with hexane–EtOAc (99 : 1) to obtain analytically pure 5a
as a pale orange solid (168 mg, 82%).4a
Experimental procedure for the synthesis of 5a from 8a
(Scheme 8)
The mixture of tert-butyl-(2-[(2-oxo-2-phenylethyl)aminophenyl]carbamate (8a) (326 mg, 1 mmol) in TFE (3 mL) was stirred
magnetically at 90 C (oil-bath). Aer completion of the reaction
(24 h, TLC), the reaction mixture was extracted with EtOAc (3
5 mL). The combined EtOAc extracts were dried (anh Na2SO4),
ltered, and the ltrate was concentrated under rotary vacuum
evaporation. The crude product was adsorbed on silica gel
(230–400 mesh size, 500 mg), charged on to a ash chromatography column of silica-gel (230–400 mesh size, 2.5 g), and
eluted with hexane–EtOAc (99 : 1) to obtain analytically pure 5a
as a pale orange solid (31 mg, 15%).4a
1-(4-Chlorophenyl)-2-[(2-nitrophenyl)amino]ethanone
(Table 3, entry 2). Yellow solid (266 mg, 91%); mp ¼ 153–156
C; IR (KBr) nmax ¼ 2981, 1275, 1260, 1054, 1033, 764, 750 cm 1;
1
H NMR (CDCl3, 400 MHz, TMS) d: 8.87 (bs, 1H), 8.24 (dd, J ¼
1.52, 8.52 Hz, 1H), 7.99 (dd, J ¼ 1.84, 6.8 Hz, 2H), 7.53–7.46 (m,
3H), 6.81–6.72 (m, 2H), 4.76 (d, J ¼ 4.4 Hz, 2H); 13C NMR (CDCl3,
100 MHz, TMS) d: 191.64, 143.86, 140.80, 138.96, 136.24, 129.45,
129.30, 127.17, 116.17, 114.05, 49.43; MS (APCI) m/z: 291 (M + H)+.
HRMS (ESI) m/z calcd for C14H11ClN2O3Na+ [M + Na+], 313.0350;
found 313.0349.
2-[(4-Chloro-2-nitrophenyl)amino]-1-phenylethanone (Table
3, entry 3). Yellow solid (258 mg, 89%); mp ¼ 158–160 C; IR
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(KBr) nmax ¼ 3342, 3005.58, 1691, 1628, 1561.90, 1517, 1402,
1351, 1275, 1261, 1156, 1070, 808, 764, 750 cm 1; 1H NMR
(CDCl3, 400 MHz, TMS) d: 8.89 (bs, 1H), 8.24 (d, J ¼ 2.36 Hz, 1H),
8.04 (d, J ¼ 7.52 Hz, 2H), 7.67 (t, J ¼ 7.4 Hz, 1H), 7.55 (t, J ¼ 7.76
Hz, 2H), 7.44 (dd, J ¼ 2.36, 9.04 Hz, 1H), 6.79 (d, J ¼ 9.04 Hz,
1H), 4.77 (d, J ¼ 4.24 Hz, 2H); 13C NMR (CDCl3, 100 MHz, TMS)
d: 192.30, 142.62, 136.28, 134.38, 134.30, 129.11, 127.92, 126.32,
120.83, 115.54, 49.44; MS (APCI) m/z: 291 (M + H)+. HRMS (ESI)
m/z calcd for C14H11ClN2O3Na+ [M + Na+], 313.0350; found
313.0350.
2-[(5-Chloro-2-nitrophenyl)amino]-1-phenylethanone (Table
3, entry 4). Yellow solid (262 mg, 90%); mp ¼ 155–158 C; IR
(KBr) nmax ¼ 3362, 2924, 1695, 1623, 1491, 1275, 1259, 1078,
750 cm 1; 1H NMR (CDCl3, 400 MHz, TMS) d: 9.00 (bs, 1H), 8.20
(d, J ¼ 9.08 Hz, 1H), 8.06 (d, J ¼ 1.2 Hz, 2H), 7.69 (t, J ¼ 7.44 Hz,
1H), 7.57 (t, J ¼ 8 Hz, 2H), 6.84 (d, J ¼ 1.96 Hz, 1H), 6.72 (dd, J ¼
2, 9.14 Hz, 1H), 4.78 (d, J ¼ 4.28 Hz, 2H); 13C NMR (CDCl3,
100 MHz, TMS) d: 192.12, 144.41, 142.70, 134.41, 134.23, 130.17,
129.28, 129.11, 128.52, 128.32, 127.96, 116.48, 113.71 49.39; MS
(ESI) m/z: 291 (M + H)+. HRMS (ESI) m/z calcd for C14H11ClN2O3Na+ [M + Na+], 313.0350; found 312.1499.
2-[(4-Methyl-2-nitrophenyl)amino]-1-phenylethanone (Table 3, entry
5). Light yellow solid (248 mg, 92%); mp ¼ 162–164 C; IR (KBr) nmax ¼
3362, 2923, 1742, 1692, 1637, 1561, 1528, 1275, 1155, 750 cm 1; 1H
NMR (CDCl3, 400 MHz, TMS) d: 8.78 (bs, 1H), 8.06 (d, J ¼ 7.56 Hz, 3H),
7.67 (t, J ¼ 7.36 Hz, 1H), 7.56 (t, J ¼ 7.56 Hz, 2H), 7.33 (d, J ¼ 8.52 Hz,
1H), 6.75 (d, J ¼ 8.6 Hz, 1H), 4.78 (d, J ¼ 4.28 Hz, 2H), 2.31 (s, 3H); 13C
NMR (CDCl3, 100 MHz, TMS) d: 192.91, 142.19, 137.62, 134.52, 134.17,
132.33, 129.03, 127.89, 126.44, 125.59, 114.12, 49.55, 20.01; MS (APCI)
m/z: 271 (M + H)+. HRMS (ESI) m/z calcd for C15H14N2O3Na+ [M + Na+],
293.0897; found 293.0785.
1-(4-Methoxyphenyl)-2-[(4-methyl-2-nitrophenyl)amino] ethanone(Table 3, entry 6). Yellowish orange solid (270 mg, 90%); mp ¼
128–130 C; IR (KBr) nmax ¼ 3364, 2912, 1676, 1632, 1600, 1560, 1524,
1424, 1348, 1262, 1241, 1181, 764 cm 1; 1H NMR (CDCl3, 400 MHz,
TMS) d: 8.75 (bs, 1H), 8.01 (s, 2H), 7.99 (d, J ¼ 1.96 Hz, 1H), 7.28 (dd, J
¼ 2, 14.5 Hz, 1H), 6.99 (d, J ¼ 1.9 Hz, 2H), 6.71 (d, J ¼ 8.6 Hz, 1H), 4.68
(d, J ¼ 4.4 Hz, 2H), 3.88 (s, 3H), 2.27 (s, 3H); 13C NMR (CDCl3, 100
MHz, TMS) d: 191.31, 164.26, 142.30, 137.59, 132.32, 132.20, 127.51,
126.42, 125.42, 114.18, 113.75, 55.61, 49.15, 20.00; MS (ESI) m/z: 301
(M + H)+. HRMS (ESI) m/z calcd for C16H16N2O4Na+ [M + Na+],
323.1008; found 323.1005.
2-(4-Methoxyphenyl)quinoxaline (Table 8, entry 2).5k Light
yellow solid (377 mg, 83%); mp ¼ 97–98 C; IR (KBr) nmax ¼
2926, 1606, 1584, 1274, 1252, 1175, 1028, 834, 763 cm 1; 1H
NMR (CDCl3, 400 MHz, TMS) d: 9.28 (s, 1H), 8.18–8.07 (m, 4H),
7.76–7.67 (m, 2H), 7.08–7.04 (m, 2H), 3.87 (s, 3H); 13C NMR
(CDCl3, 100 MHz, TMS) d: 161.45, 151.37, 143.04, 142.30,
141.20, 130.14, 129.39, 129.26, 129.07, 129.01, 128.95, 114.56,
55.41; MS (ESI) m/z: 237 (M + H)+.
2-(3-Methoxyphenyl)quinoxaline (Table 8, entry 3).5k Light
yellowish orange solid (198 mg, 84%); mp ¼ 87–88 C; IR (KBr)
nmax ¼ 3434, 2918, 2846, 2225, 1733, 1275, 1260, 1022, 750 cm 1;
1
H NMR (CDCl3, 400 MHz, TMS) d: 9.36 (s, 1H), 8.19–8.13
(m, 2H), 7.92 (dd, J ¼ 1.8, 7.64 Hz, 1H), 7.80–7.74 (m, 2H), 7.52–
7.48 (m, 1H), 7.22–7.17 (m, 1H), 7.09 (d, J ¼ 8.24 Hz, 1H), 3.93
(s, 3H); 13C NMR (CDCl3, 100 MHz, TMS) d: 157.40, 152.23,
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147.30, 142.71, 141.06, 131.61, 131.44, 129.76, 129.55, 129.37,
129.07, 126.56, 121.54, 111.43, 55.65; MS (ESI) m/z: 237 (M + H)+.
2-(4-Chlorophenyl)quinoxaline (Table 8, entry 4).4a Light
orange solid (197 mg, 82%); mp ¼ 120–122 C; IR (KBr) nmax ¼
3004, 2325, 1260, 1275, 764, 750 cm 1; 1H NMR (CDCl3, 400
MHz, TMS) d: 9.31 (s, 1H), 8.19–8.13 (m, 4H), 7.83–7.75 (m, 2H),
7.57–7.54 (m, 2H); 13C NMR (CDCl3, 100 MHz, TMS) d: 150.59,
142.87, 142.22, 141.66, 136.59, 135.19, 130.48, 129.79, 129.60,
129.41, 129.17, 128.78; MS (ESI) m/z: 241 (M + H)+.
2-(4-Bromophenyl)quinoxaline (Table 8, entry 5).5k Light
brown solid (238 mg, 84%); mp ¼ 138 C; 1H NMR (CDCl3, 400
MHz, TMS) d: 9.29 (s, 1H), 8.15–8.07 (m, 4H), 7.82–7.74 (m, 2H),
7.71–7.68 (m, 2H); 13C NMR (CDCl3, 100 MHz, TMS) d: 150.66,
142.83, 142.22, 141.68, 135.62, 132.80, 130.37, 131.88,
130.52, 129.84, 129.60, 129.18, 129.02, 125.00; MS (ESI) m/z: 284
(M + H)+.
7-Chloro-2-phenylquinoxaline (Table 8, entry 6).5i Light
orange solid (194 mg, 81%); mp ¼ 104–106 C; IR (KBr) nmax ¼
3047, 2922, 2852, 1606, 1539, 1483, 1449, 1404, 1314, 1131,
1073, 958, 913, 834, 758, 686, 666 cm 1; 1H NMR (CDCl3, 400
MHz, TMS) d: 9.30 (s, 1H), 8.20–8.14 (m, 3H), 8.04 (d, J ¼ 8.92
Hz, 1H), 7.68 (dd, J ¼ 2.16, 8.84 Hz, 1H), 7.58–7.55 (m, 3H); 13C
NMR (CDCl3, 100 MHz, TMS) d: 152.48, 143.38, 142.62, 140.07,
136.27, 136.07, 130.56, 130.48, 130.34, 129.21, 128.95, 128.49,
127.84, 127.60; MS (ESI) m/z: 240 (M)+.
7-Chloro-2-(4-methoxyphenyl)quinoxaline (Table 8, entry
7).5i Off-white solid (216 mg, 80%); mp ¼ 103–105 C; IR (KBr)
nmax ¼ 2922, 1607, 1539, 1487, 1258, 1225, 1181, 1125, 1071,
1025, 957, 914, 841, 827, 750, 571, 515 cm 1; 1H NMR (CDCl3,
400 MHz, TMS) d: 9.30 (d, J ¼ 5.92 Hz, 1H), 8.19 (dd, J ¼ 3.04,
8.76 Hz, 2H), 8.12 (dd, J ¼ 2.12, 10.88 Hz, 1H), 8.08–8.03
(m, 1H), 7.73–7.66 (m, 1H), 7.10 (d, J ¼ 8.72 Hz, 2H), 3.93 (s, 3H);
13
C NMR (CDCl3, 100 MHz, TMS) d: 161.77, 143.88, 143.15,
135.97, 131.21, 130.61, 130.29, 130.00, 129.10, 128.99, 128.79,
128.28, 128.03, 114.68, 55.49; MS (APCI) m/z: 271 (M + H)+.
HRMS (ESI) m/z calcd for C15H11ClN2ONa+ [M + Na+], 293.0452;
found 293.0452.
7-Chloro-2-(4-chlorophenyl)quinoxaline (Table 8, entry 8).
Light orange solid (225 mg, 82%); mp ¼ 180–182 C; IR (KBr)
nmax ¼ 2922, 1521, 1275, 1260, 1022, 764, 750 cm 1; 1H NMR
(CDCl3, 400 MHz, TMS) d: 9.30 (s, 1H), 8.18–8.15 (m, 3H), 8.07
(d, J ¼ 8.92 Hz, 1H), 7.72 (dd, J ¼ 2.32, 8.92 Hz, 1H), 7.58–7.55
(m, 2H); 13C NMR (CDCl3, 100 MHz, TMS) d: 151.30, 142.92,
142.56, 140.17, 137.01, 136.33, 134.70, 131.53, 130.77, 130.39,
129.48, 128.82, 128.73, 128.45; MS (APCI) m/z: 275 (M + H)+.
HRMS (ESI) m/z calcd for C14H8Cl2N2Na+ [M + Na+], 296.9957;
found 297.1305.
2-(4-Bromophenyl)-7-chloroquinoxaline (Table 8, entry 9).5c
Light brown solid (256 mg, 80%); mp ¼ 144–146 C; IR (KBr)
nmax ¼ 2922, 2075, 1633, 1421, 1176, 1075, 957, 880, 835, 775,
711 cm 1; 1H NMR (CDCl3, 400 MHz, TMS) d: 9.28 (s, 1H), 8.13
(d, J ¼ 2.24 Hz, 1H), 8.09–8.04 (m, 3H), 7.72–7.68 (m, 3H); 13C
NMR (CDCl3, 100 MHz, TMS) d: 151.40, 142.89, 142.58, 140.21,
136.37, 135.16, 132.46, 130.82, 130.41, 129.06, 128.97, 128.47,
128.13, 125.44; MS (APCI) m/z: 321 (M + 2H)+.
6-Chloro-2-phenylquinoxaline (Table 8, entry 10).5i Colorless
crystal (199 mg, 83%); mp ¼ 125–127 C; IR (KBr) nmax ¼ 3367,
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2162, 1276, 1256, 752 cm 1; 1H NMR (CDCl3, 400 MHz, TMS)
d: 9.34 (s, 1H), 8.21–8.19 (m, 2H), 8.13–8.09 (m, 2H), 7.74 (dd, J ¼
2.36, 8.96 Hz, 1H), 7.62–7.55 (m, 3H); 13C NMR (CDCl3, 100
MHz, TMS) d: 151.95, 144.16, 141.82, 140.85, 136.38, 135.26,
131.34, 130.85, 130.45, 129.24, 128.09, 127.53; MS (APCI) m/z:
241 (M + H)+.
6-Chloro-2-(4-methoxyphenyl)quinoxaline (Table 8, entry
11).5i Off-white solid (219 mg, 81%); mp ¼ 140–142 C; IR (KBr)
nmax ¼ 2930, 2837, 1674, 1606, 1577, 1538, 1519, 1454, 1309,
1287, 1273, 1257, 1171, 1066, 1026, 957, 827, 764, 750, 570, 515
cm 1; 1H NMR (CDCl3, 400 MHz, TMS) d: 9.29 (s, 1H), 8.18
(dd, J ¼ 1.84, 7 Hz, 2H), 8.09 (d, J ¼ 2.2 Hz, 1H), 8.05 (d, J ¼ 8.96
Hz, 1H), 7.71 (dd, J ¼ 2.28, 8.92 Hz, 1H), 7.09 (dd, J ¼ 1.76, 6.92
Hz, 2H), 3.92 (s, 3H); 13C NMR (CDCl3, 100 MHz, TMS) d: 161.68,
151.53, 143.84, 141.42, 140.87, 134.66, 131.18, 130.60, 128.97,
128.86, 128.02, 114.67, 55.46; MS (APCI) m/z: 271 (M + H)+.
HRMS (ESI) m/z calcd for C15H11ClN2ONa+ [M + Na+], 293.0452;
found 293.0451.
6-Chloro-2-(4-chlorophenyl)quinoxaline (Table 8, entry 12).
Yellowish orange solid (225 mg, 82%); mp ¼ 130–132 C; IR
(KBr) nmax ¼ 2917, 2849, 1275, 1260, 750 cm 1; 1H NMR (CDCl3,
400 MHz, TMS) d: 9.32 (s, 1H), 8.17 (dd, J ¼ 1.92, 6.72 Hz, 2H),
8.14 (d, J ¼ 2.28 Hz, 1H), 8.09 (d, J ¼ 8.96 Hz, 1H), 7.76 (dd, J ¼
2.28, 8.96 Hz, 1H), 7.57 (dd, J ¼ 1.96, 6.68 Hz, 2H); 13C NMR
(CDCl3, 100 MHz, TMS) d: 150.70, 143.67, 141.88, 140.76,
139.29, 136.88, 135.55, 134.77, 131.55, 130.80, 129.49, 128.73,
128.12, 114.07; MS (APCI) m/z: 275 (M + H)+. HRMS (ESI) m/z
calcd forC14H8Cl2N2Na+ [M + Na+], 296.9957; found 297.1298.
2-(4-Bromophenyl)-6-chloroquinoxaline (Table 8, entry 13).
Off-white solid (257 mg, 83%); mp ¼ 175–177 C; IR (KBr) nmax ¼
3049, 2923, 2849, 1604, 1539, 1476, 1328, 1275, 1176, 1004, 919,
825, 750, 569 cm 1; 1H NMR (CDCl3, 400 MHz, TMS) d: 9.27
(s, 1H), 8.09 (d, J ¼ 2.24 Hz, 1H), 8.06 (d, J ¼ 8.48 Hz, 3H), 7.73–
7.67 (m, 3H); 13C NMR (CDCl3, 100 MHz, TMS) d: 150.74, 143.61,
141.90, 140.76, 135.58, 135.20, 132.45, 131.56, 130.81, 130.40,
129.04, 128.95, 128.12, 125.29; MS (APCI) m/z: 321 (M + H)+.
HRMS (ESI) m/z calcd for C14H8BrClN2Na+ [M + Na+], 340.9452;
found 341.1820.
2-(4-Methoxyphenyl)-7-methylquinoxaline (Table 8, entry
14).4e Light yellow solid (200 mg, 80%); mp ¼ 52–57 C; IR (KBr)
nmax ¼ 2917, 2857, 2307, 1956, 1739, 1618, 1451, 1384, 1179,
1050, 746 cm 1; 1H NMR (CDCl3, 400 MHz, TMS) d: 9.26 (s, 1H),
8.19–8.16 (m, 2H), 8.01 (dd, J ¼ 8.52, 12.32 Hz, 1H), 7.97 (d, J ¼
14.28 Hz, 1H), 7.62–7.55 (m, 1H), 7.10 (d, J ¼ 8.44 Hz, 2H), 3.92
(s, 3H), 2.62 (s, 3H); 13C NMR (CDCl3, 100 MHz, TMS) d: 161.30,
142.99, 142.19, 139.57, 132.48, 131.37, 129.51, 128.92, 128.82,
128.58, 128.29, 127.97, 114.56, 55.45, 21.80; MS (ESI) m/z: 251
(M + H)+.
2-(4-Bromophenyl)-7-methylquinoxaline (Table 8, entry 15).5c
Yellowish orange (238 mg, 80%); mp ¼ 96–98 C; IR (KBr) nmax ¼
2920, 2851, 1624, 1587, 1488, 1436, 1131, 1072, 1009, 960, 834,
777 cm 1; 1H NMR (CDCl3, 400 MHz, TMS) d: 9.22 (s, 1H), 8.06
(dd, J ¼ 1.92, 6.64 Hz, 2H), 7.99 (d, J ¼ 8.56 Hz, 1H), 7.91 (s, 1H),
7.68 (dd, J ¼ 1.84, 6.72 Hz, 2H), 7.58 (dd, J ¼ 1.84, 8.56 Hz, 1H),
2.61 (s, 3H); 13C NMR (CDCl3, 100 MHz, TMS) d: 150.58, 142.31,
141.92, 141.11, 140.21, 135.82, 132.32, 132.18, 128.97, 128.89,
128.66, 128.43, 124.83, 21.91; MS (APCI) m/z: 299 (M + H)+.
11882 | RSC Adv., 2015, 5, 11873–11883
Paper
HRMS (ESI) m/z calcd for C15H11BrN2Na+ [M + H+], 299.0106;
found 299.0178.
7-Methoxy-2-phenylquinoxaline (Table 8, entry 16).5i Colorless crystal (193 mg, 82%); mp ¼ 86–88 C; IR (KBr) nmax ¼ 2917,
2840, 1733, 1459, 1260, 1078, 1025, 750 cm 1; 1H NMR (CDCl3,
400 MHz, TMS) d: 9.19 (s, 1H), 8.20–8.18 (m, 2H), 8.02 (d, J ¼
9.12 Hz, 1H), 7.61–7.54 (m, 3H), 7.45 (d, J ¼ 2.72 Hz, 1H), 7.42
(dd, J ¼ 2.76, 9.12 Hz, 1H), 4.02 (s, 3H); 13C NMR (CDCl3, 100
MHz, TMS) d: 161.09, 151.98, 143.99, 140.79, 137.81, 137.03,
130.06, 129.14, 127.53, 122.92, 106.90, 55.86; MS (ESI) m/z: 237
(M + H)+.
Acknowledgements
Financial support from UGC (SRF to BT) and CSIR (RA to DK),
New Delhi is thankfully acknowledged.
Notes and references
1 (a) A. Cartra, P. Corona and M. Loriga, Curr. Med. Chem.,
2005, 12, 2259; (b) A. Cartra, S. Piras, G. Loriga and
G. Paglietti, Mini-Rev. Med. Chem., 2006, 6, 1179; (c)
R. M. Rajurkar, V. A. Agrawal, S. S. Thonte and
R. G. Ingale, Pharmacophore, 2010, 1, 65; (d) M. González
and H. Cerecetto, Expert Opin. Ther. Pat., 2012, 22, 1289; (e)
R. G. Ingle and R. P. Marathe, Pharmacophore, 2012, 3, 109.
2 Varenicline (a) S. D. Shah, L. A. Wilken, S. R. Winkler and
S. J. Lin, J. Am. Pharm. Assoc., 2003, 2008(48), 659,
Carbadox; (b) B. Emmert, S. Schauder, H. Palm, E. Hallier
and S. Emmert, Ann. Agric. Environ. Med., 2007, 14, 329,
Brimonidine; (c) C. B. Toris, C. B. Camras and
M. Yablonski, Am. J. Ophthalmol., 1999, 128, 8.
3 Fluorescent dyes (a) N. D. Sonawane and D. W. Rangnekar,
J. Heterocycl. Chem., 2002, 39, 303; Electroluminescence; (b)
C. T. Chen, J. S. Lin, M. V. R. K. Moturu, Y. W. Lin, W. Yi,
Y. T. Tao and C. H. Chien, Chem. Commun., 2005, 3980,
Semiconductor; (c) S. Dailey, J. W. Feast, R. J. Peace,
I. C. Sage, S. Till and E. L. Wood, J. Mater. Chem., 2001, 11,
2238, Chemically controllable switches; (d) S. Ott and
R. Faust, Synlett, 2004, 1509, Electron transport materials;
(e) D. O'Brien, M. S. Weaver, D. G. Lidzey and
D. D. C. Bradley, Appl. Phys. Lett., 1996, 69, 881.
4 (a) S. B. Wadavrao, R. S. Ghogare and A. V. Narsaiah, Org.
Commun., 2013, 6, 23; (b) Y. Chen, K. Li, M. Zhao, Y. Li and
B. Chen, Tetrahedron Lett., 2013, 54, 1627; (c) M. J. Climent,
A. Corma, J. C. Hernández, A. B. Hungrı́a, S. borra and
S. I. Martı́nez-Silvestre, J. Catal., 2012, 292, 118; (d)
P. Ghosh and A. Mandal, Tetrahedron Lett., 2012, 53, 6483;
(e) L. Nagarapu, R. Mallepalli, G. Arava and L. Yeramanchi,
Eur. J. Chem., 2010, 1, 228; (f) B. Madhav, S. Narayan
Murthy, V. Prakash Reddy, K. Rama Rao and
Y. V. D. Nageswar, Tetrahedron Lett., 2009, 50, 6025; (g)
J.-P. Wan, S.-F. Gan, J.-M. Wu and Y. Pan, Green Chem.,
2009, 11, 1633; (h) T. Huang, Q. Zhang, J. Chen, W. Gao,
J. Ding and H. Wu, J. Chem. Res., 2009, 761; (i) D. Changjiang, W. Yan, Z. Wei-wei, L. Li, L. Yong-jiu and D. De-wen,
Chem. Res. Chin. Univ., 2009, 25, 174; (j) B. Das,
This journal is © The Royal Society of Chemistry 2015
View Article Online
Published on 09 January 2015. Downloaded by KU Leuven University Library on 22/01/2015 09:59:33.
Paper
5
6
7
8
9
10
K. Venkateswarlu, K. Suneel and A. Majhi, Tetrahedron Lett.,
2007, 48, 5371, Reviews; (k) V. A. Mamedov and
N. A. Zhukova, Prog. Heterocycl. Chem., 2012, 24, 55; (l)
V. A. Mamedov and N. A. Zhukova, Prog. Heterocycl. Chem.,
2013, 25, 1; (m) Y. V. D. Nageswar, K. H. V. Reddy,
K. Ramesh and S. N. Murthy, Org. Prep. Proced. Int., 2013,
45, 1.
(a) S. A. Raw, C. D. Wilfred and R. J. K. Taylor, Org. Biomol.
Chem., 2004, 2, 788; (b) C. Neochoritis, J. StephanidouStephanatou and C. A. Tsoleridis, Synlett, 2009, 302; (c)
H. M. Meshram, G. S. kumar, P. Ramesh and B. C. Reddy,
Tetrahedron Lett., 2010, 51, 2580; (d) S. Paul and B. Basu,
Tetrahedron Lett., 2011, 52, 6597; (e) L. J. Martin,
A. L. Marzinzik, S. V. Ley and I. R. Baxendale, Org. Lett.,
2011, 13, 320; (f) W. Wang, Y. Shen, M. Zhao, Y. Chen and
B. Chen, Org. Lett., 2011, 13, 4514; (g) F. Pan, T.-M. Chen,
J.-J. Cao, J.-P. Zhou and W. Zhang, Tetrahedron Lett., 2012,
53, 2508; (h) C. Zhang, Z. Xu, L. Zhang and N. Jiao,
Tetrahedron, 2012, 68, 5258; (i) J. Song, X. Li, Y. Chen,
M. Zhao, Y. Dou and B. Chen, Synlett, 2012, 2416; (j)
M. Lian, Q. Li, Y. Zhu, G. Yin and A. Wu, Tetrahedron,
2012, 68, 9598; (k) T. B. Nguyen, P. Retailleau and A. AlMourabit, Org. Lett., 2013, 15, 5238; (l) K. Aghapoor,
F.
Mohsenzadeh,
A.
Shakeri,
H.
R.
Darabi,
M. Ghassemzadeh and B. Neumüller, J. Organomet. Chem.,
2013, 743, 170.
J. Machin and D. M. Smith, J. Chem. Soc., Perkin Trans. 1,
1979, 1371.
(a) V. Sridharan, S. Perumal, C. Avendaño and
J. C. Menéndez, Synlett, 2006, 91; (b) Y. Vara, E. Aldaba,
A. Arrieta, J. L. Pizarro, M. L. Arriortua and F. P. Cossı́o,
Org. Biomol. Chem., 2008, 6, 1763.
I. Vilotijevic and T. F. Jamison, Science, 2007, 317, 1189.
(a) A. Shokri, J. Schmidt, X.-B. Wang and S. R. Kass, J. Am.
Chem. Soc., 2012, 134, 2094; (b) A. Shokri, A. Abedin,
A. Fattahi and S. R. Kass, J. Am. Chem. Soc., 2012, 134, 10646.
Organic reactions promoted through HB formation with
water: (a) S. V. Chankeshwara and A. K. Chakraborti, Org.
Lett., 2006, 8, 3259; (b) G. L. Khatik, R. Kumar and
A. K. Chakraborti, Org. Lett., 2006, 8, 2433; (c)
A. K. Chakraborti, S. Rudrawar, K. B. Jadhav, G. Kaur and
S. V. Chankeshwara, Green Chem., 2007, 9, 1335; (d)
N. Parikh, D. Kumar, S. Raha Roy and A. K. Chakraborti,
Chem. Commun., 2011, 47, 1797; (e) D. N. Kommi,
D. Kumar, R. Bansal, R. Chebolu and A. K. Chakraborti,
Green Chem., 2012, 14, 3329; (f) D. N. Kommi,
P. S. Jadhavar, D. Kumar and A. K. Chakraborti, Green
Chem., 2013, 15, 798; (g) D. N. Kommi, D. Kumar and
A. K. Chakraborti, Green Chem., 2013, 15, 756; (h)
D. N. Kommi, D. Kumar, K. Seth and A. K. Chakraborti,
Org. Lett., 2013, 15, 1158; (i) D. Kumar, K. Seth,
This journal is © The Royal Society of Chemistry 2015
RSC Advances
11
12
13
14
15
16
17
18
19
20
D. N. Kommi, S. Bhagat and A. K. Chakraborti, RSC Adv.,
2013, 3, 15157; (j) K. Seth, S. Raha Roy, B. V. Pipaliya and
A. K. Chakraborti, Chem. Commun., 2013, 49, 5886.
(a) D. Kumar, D. N. Kommi, A. R. Patel and
A. K. Chakraborti, Eur. J. Org. Chem., 2012, 6407; (b)
A. Sarkar, S. Raha Roy, D. Kumar, C. Madaan, S. Rudrawar
and A. K. Chakraborti, Org. Biomol. Chem., 2012, 10, 281;
(c) A. Sarkar, S. Raha Roy, N. Parikh and A. K. Chakraborti,
J. Org. Chem., 2011, 76, 7132; (d) S. Raha Roy,
P. S. Jadhavar, K. Seth, K. K. Sharma and
A. K. Chakraborti, Synthesis, 2011, 2261; (e) A. Sarkar,
S. Raha Roy and A. K. Chakraborti, Chem. Commun., 2011,
47, 4538; (f) S. Raha Roy and A. K. Chakraborti, Org. Lett.,
2010, 12, 3866; (g) A. K. Chakraborti and S. Raha Roy,
J. Am. Chem. Soc., 2009, 131, 6902; (h) A. K. Chakraborti,
S. Raha Roy, D. Kumar and P. Chopra, Green Chem., 2008,
10, 1111.
(a) A. K. Chakraborti, S. Rudrawar, L. Sharma and G. Kaur,
Synlett, 2004, 1533; (b) A. K. Chakraborti, L. Sharma and
M. K. Nayak, J. Org. Chem., 2002, 67, 6406; (c)
A. K. Chakraborti, M. K. Nayak and L. Sharma, J. Org.
Chem., 1999, 64, 8027; (d) L. Sharma, M. K. Nayak and
A. K. Chakraborti, Tetrahedron, 1999, 55, 9595; (e)
M. K. Nayak and A. K. Chakraborti, Tetrahedron Lett., 1997,
38, 8749.
(a) R. Chebolu, D. N. Kommi, D. Kumar, N. Bollineni and
A. K. Chakraborti, J. Org. Chem., 2012, 77, 10158; (b)
A. K. Chakraborti, L. Sharma and M. K. Nayak, J. Org.
Chem., 2002, 67, 2541; (c) M. K. Nayak and
A. K. Chakraborti, Chem. Lett., 1998, 27, 297.
M. J. Kamlet, J. M. Abboud, M. H. Abraham and R. W. Ta,
J. Org. Chem., 1983, 48, 2877.
J. G. Lee, K. I. Choi, H. Y. Koh, Y. Kim, Y. Kang and Y. S. Cho,
Synthesis, 2001, 81.
N. G. Connelly and W. E. Geiger, Chem. Rev., 1996, 96, 877.
(a) E. Lellmann and A. Donner, Chem. Ber., 1890, 23, 166; (b)
D. C. Blaildey, D. W. Currie, D. M. Smith and S. A. Watson,
J. Chem. Soc., Perkin Trans. 1, 1984, 367.
(a) F. Jahani, M. Tajbakhsh, H. Golchoubian and S. Khaksar,
Tetrahedron Lett., 2011, 52, 1260; (b) A. Heydari and
S. E. Hosseini, Adv. Synth. Catal., 2005, 347, 1929; (c) L. Xi,
J.-Q. Zhang, Z.-C. Liu, J.-H. Zhang, J.-F. Yan, Y. Jin and
J. Lin, Org. Biomol. Chem., 2013, 11, 4367; (d) R. Varala,
S. Nuvula and R. Srinivas, J. Org. Chem., 2006, 71, 8283; (e)
D. A. Stolfa, A. Stefanachi, J. M. Gajer, A. Nebbioso,
L. Altucci, S. Cellamare, M. Jung and A. Carotti,
ChemMedChem, 2012, 7, 1256.
J. Wang, Y. L. Liang and J. Qu, Chem. Commun., 2009, 5144.
J. Choy, S. Jaime-Figueroa, L. Jiang and P. Wagner, Synth.
Commun., 2008, 38, 3840.
RSC Adv., 2015, 5, 11873–11883 | 11883