A reaction for the synthesis of benzimidazoles and 1H-imidazo[4,5-b] pyridines via a novel rearrangement of quinoxalinones and their aza-analogues when exposed to 1,2-arylenediamines

Article abstract of DOI:10.1016/j.tet.2010.10.026

An efficient and one-step versatile method for the synthesis of benzimidazoles and 1H-imidazo[4,5-b]pyridines from quinoxalinones and their aza-analogues have been developed on the basis of the novel ring contractions of 3-aroyl-quinoxalinones and their a

Full text of DOI:10.1016/j.tet.2010.10.026

Tetrahedron 66 (2010) 9745e9753
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A reaction for the synthesis of benzimidazoles and 1H-imidazo[4,5-b]pyridines
via a novel rearrangement of quinoxalinones and their aza-analogues when
exposed to 1,2-arylenediamines
*
Vakhid A. Mamedov , Nataliya A. Zhukova, Tat’yana N. Beschastnova, Aidar T. Gubaidullin,
Alsu A. Balandina, Shamil K. Latypov
A.E. Arbuzov Institute of Organic and Physical Chemistry, Kazan Research Center of the Russian Academy of Sciences, Arbuzov str. 8, 420088 Kazan, Russia
a r t i c l e i n f o
a b s t r a c t
Article history:
Received 7 July 2010
Received in revised form 21 September 2010
Accepted 11 October 2010
Available online 15 October 2010
An efficient and one-step versatile method for the synthesis of benzimidazoles and 1H-imidazo[4,5-b]
pyridines from quinoxalinones and their aza-analogues have been developed on the basis of the novel
ring contractions of 3-aroyl-quinoxalinones and their aza-analogues with 1,2-arylenediamines.
Ó 2010 Elsevier Ltd. All rights reserved.
This work is dedicated to the 65th anniver-
sary of the foundation of the Institute,
the authors have the honor to do research
Keywords:
3-Aroyl-quinoxalinones
Pyrido[2,3-b]pyrazines 1,2-arylenediamines
Ring contractions
Ring formation
Benzimidazoles
1H-Imidazo[4,5-b]pyridines
NMR data
X-ray diffraction analysis
1. Introduction
preparation of these compounds is usually straightforward, and
a number of synthetic methods are already available.3ael However, it
The benzimidazole1aeg and imidazopyridine2aen moieties are
important pharmacophores, which have proven to be useful for
a number of biologically relevant targets. Compounds possessing
a benzimidazole moiety have shown significant activity against sev-
eral viruses, such as HIV,1d,e herpes (HSV-1),1d,f human cytomegalo-
virus (HCMV),1b,d,f and influenza.1g The compounds derived from the
imidazopyridine system have recently been evaluated as antagonists
of various biological receptors, including angiotensin-II,2def platelet
activating factor,2c,g,h and metabotropic glutamate subtype V.2i
Substituted imidazo[4,5-b]pyridines have also been tested for their
potential as anticancer,2b inotropic,2j,k and selective antihistamine
(H1) agents.2l Imidazo[4,5-b]pyridine derivatives were also reported
as Aurora kinases,2m and cyclic PDE inhibitors.2n Medicinal chemists
consider these heterocycles to be promising compounds. The
is observed that all these methods involve various disadvantages,
such as low yields, harsh reaction conditions, such as high reaction
temperatures (w200 ꢀC), use of toxic regents, such as POCl3, TMS-Cl,
and polyphosphoric acid, use of catalyst/oxidizing agents, such as Pb
(OAc)4, PCC, and Cu(OAc)2, and continuous O2 bubbling in the course
of reaction are also present. Hence, it is imperative to develop a con-
venient, efficient, and user friendly method for the synthesis of 2-
substituted-benzimidazoles and 1H-imidazo[4,5-b]pyridines.
Recently we have described a highly efficient and versatile
method for the synthesis of benzimidazoles 4 and 5 on the basis of
the novel ring contraction of 3-benzoyl-1a and 3-alkanoylquinox-
alin-2(1H)-ones 2 with 1,2-phenylenediamine 3a (Scheme 1)
correspondingly.4a,b
As is evident from the structure of compounds 4 and 5 the C(2)e
C(3)eC(O)Ph and NH2C]CNH2 fragments of quinoxalinone 1a (or
2) and 1,2-phenylenediamine 3a systems are correspondingly in-
volved in the construction of two new heterocyclic systems. These
* Corresponding author. E-mail address: mamedov@iopc.ru (V.A. Mamedov).
0040-4020/$ e see front matter Ó 2010 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2010.10.026

9746
V.A. Mamedov et al. / Tetrahedron 66 (2010) 9745e9753
It should be noted that carrying out the reaction in DMSO at room
R
O
R
AcOH,
reflux
temperature for 20 days or in a boiling solution of n-BuOH for 4.5 h
leads to the formation of ortho-aminoanylide quinoxaline 2-car-
boxylic acid 6, which when boiled in acetic acid for less than 1 min
quantitatively yields 2-benzimidazol-2-ylquinoxalines 4. This has
beenillustratedbythe reactions of 3-aroylquinoxalin-2(1H)-ones 1a
and 1d (Table 1). The structure of 6a was unambiguously confirmed
by the X-ray crystal analysis (see the Supplementary data) (Fig. 1).
N
NH2
NH2
N
N
O
+
- 2H2O
N
H
4a, 5
N
N
H
1a, 2
3a
R = Ph (1a, 4a); Alk (2, 5)
Scheme
1. A
new acid-catalyzed
rearrangement,
proceeding
in
the
‘quinoxalinoned1,2-phenylenediamine’ system.
benzimidazole and quinoxaline systems differ from the initial ones.
This one-step ring contraction process represents a conceptually
new method for the preparation of substituted benzimidazoles.
2. Results and discussion
We assumed that if instead of 3-benzoyl- and 3-alkanoyl-
quinoxalin-2-ones we use aroylquinoxalinones and their aza-
analoguesdaroylpyrido[2,3-b]pyrazines or aroylpyrimido[4,5-b]
pyrazines (aroylpteridines) in the reaction with 1,2-phenylenedi-
amines this new rearrangement can serve as a simple method for
synthesizing not only substituted benzimidazole derivatives but
their aza-analoguesd1H-imidazo[4,5-b]pyridines and purines as
well. Herein we have reported our results on the feasibility of the
above strategy.
Other 3-aroylquinoxalin-2(1H)-ones 1bef behave in a similar
way.5 When exposed to 1,2-phenylenediamine 3a in boiling acetic
acid solution they are converted into rearrangement products 4bef
with high yields (Table 1). Their structures were unequivocally
proved by a variety of 1D/2D NMR correlation methods6a,b (see
Supplementary data).
Fig. 1. ORTEP drawing one of the two independent 6a molecules. Displacement el-
lipsoids are drawn at the 30% probability level and H atoms are shown as small spheres
of arbitrary radii.
As can be seen from Table 2, the reaction of 3-aroylquinoxalin-2
(1H)ones with nonsymmetric 1,2-phenylenediamine 3b proceeds
with the formation of almost equal amounts of the mixture of iso-
meric products, differing in the position of substituents of the ben-
zene ring of quinoxalinone system regardless of the nature of the
substituents in 1,2-phenylenediamine. However, in the reactions of
4-nitro-1,2-phenylenediamine 3b each one of the products, with
a high-melting point (>330 ꢀC) precipitated during its formation
from a boiling solution of acetic acid and the other one (with the
melting point <300 ꢀC) precipitated from the filtrate, after the
separation of an isomer with a high-melting point (Table 2).
Table 1
A versatile one-step method for the synthesis of benzimidazoles from quinox-
alinones and 1,2-phenylenediamine via a novel rearrangement
R
O
AcOH,
N
N
reflux
N
+
3a
Table 2
N
H
- 2H2O
N
N
H
O
R
An efficient one-step method for the synthesis of benzimidazoles from quinox-
alinones and 4-nitro-1,2-phenylenediamine via a novel rearrangement
4
1
O
DMSO (rt, 20 days)
or n-BuOH (reflux)
- H2O
N
NH2
NH2
+
N
H
1
O
R
AcOH,
reflux
O2N
- H2O
N
H
N
3b
N
AcOH,
reflux
- 4H2O
O
NH2
R
R
6
R
N
N
N
N
Entry
R
Substrates
Product, Yield (%)
+
1
2
3
4
5
6
7
8
9
F
1b
1c
1d
1e
1f
1a
1d
6a
6b
3a
3a
3a
3a
3a
3a
3a
4b, 94
4c, 97
4d, 95
4e, 93
N
H
7
N
H
N
N
NO2
Cl
Br
I
NO2
H
Br
H
Br
8
NO2
4f, 92
6a, 80a, 71b
6d, 83a
4a, 87
Entry
R
Substrate
Products, Yield (%)
1
2
3
4
F
Cl
1b
1c
1d
1e
7aD8a (47) (38)
7bD8b (42) (36)
7cD8c (45) (43)
7dD8d (44) (45)
4d, 85
a
Br
I
Obtained in refluxing n-BuOH for 4.5 h.
Obtained in DMSO for 20 days at rt.
b

V.A. Mamedov et al. / Tetrahedron 66 (2010) 9745e9753
9747
Unfortunately there is no significant difference in the 1H NMR
spectra of high- and low-melting isomers that could be directly
correlated with the isomeric structure. However, a combination of
different NMR experiments (see Supplementary data) makes it
possible to unambiguously establish the structures of these com-
pounds. Namely, although the protons of the quinoxaline moiety
resonate as ABX systems with practically identical chemical shifts in
both isomers (Fig. 2) theweakbut significant NOE’s between the aryl
ortho-protons and the nearest proton of the quinoxaline fragment
make it possible to assign exactly the H5 protons. Thus with taking
into account that H5 protons characteristically resonate in 7 (as AB
part of ABX systemwith CS ca. 8.4 ppm) and in 8 (as the X part of ABX
system with CS ca. 8.9 ppm) isomers the nitro group position (C7 or
C6) can be easily deduced.
withdrawing substituents (1560e1540 cmꢁ1) or to lower fre-
quencies (1550e1490 cmꢁ1) in the presence of electron-releasing
substituents.9a,b Taking into account that the benzimidazole sub-
stituent at position 2 of the quinoxaline system has a specific
deficient center, i.e., the
p-
m
-carbon atom, which bears a substantially
higher positive charge10 than that on the ipso-carbon atom of the
aryl substituent at position 3. It can be assumed that for low-
melting isomers with the NO2 group in position 6 the nas (NO2)
frequencies must be higher than those for the high-melting iso-
mers with the nitro group in position 7.
In order to confirm our conclusions about the structure of the
high- and low-melting isomers 7aed and 8aed, on the bases of
NMR spectroscopic data we have had X-ray diffraction analysis
performed for 7a and 8a. In fact, X-ray crystallographic analysis of
Fig. 2. Fragments of 1H NMR spectra (DMSO, 303 K) of 7a (a) and 8a (b). Observed NOE’s are shown schematically by arrows.
Besides, the carbon CSs of the quinoxaline system are sensitive
to the mutual position of aryl and NO2 moieties7 and can be used to
provide an additional support to the above conclusions on isomeric
structures by comparison with theoretically predicted data8a,b (e.g.,
for 7a/8a see Supplementary data). Thus, the high-melting isomers
(7aed) are in position 7 with the NO2 group while the low-melting
isomers (8aed) are in position 6 with the NO2 group.
On the whole, the IR spectra of both isomers are similar and
have absorption bands characteristic of these structures
(Experimental Section). At the same time, a comparison of the
spectra shows that the anti-symmetric vibrations of the NO2 group
are most sensitive to structural changes (Table 3).
7a and 8a demonstrated that the NO2 group in the high-melting
isomer is in position 7 (Fig. 3 a), and in the low-melting one it is
in position 6 (Fig. 3 b).
The use of pyrido[2,3-b]pyrazin-3(4H)-ones 9 instead of qui-
noxalinones 1 in the rearrangement considered here makes it pos-
sible to synthesize aza-analogues of benzimidazolesd1H-imidazo
[4,5-b]pyridines 10, which are not easily accessible by classical Fil-
lipseLadenburg3a,11a,b and Weidenhagen12aec reactions. The for-
mation of 2-(1H-imidazo[4,5-b]pyridin-2-yl)-3-arylquinoxalines
10aed from pyrido[2,3-b]pyrazin-2(1H)-ones 9aed and 1,2-phe-
nylenediamine 3a proceeds in AcOH under reflux for 35e47 h. It
should be noted, that carrying out the reaction with refluxed AcOH
for 3 h leads to the formation of 2-amino-3-azaanylide quinoxaline
3-phenyl-2-carboxylic acids 11. This has been illustrated by the re-
action of 2-(1H-imidazo[4,5-b]pyridin-2-yl)-3-phenylquinoxaline
9a and 1,2-phenylenediamine 3a (Table 4). Single crystal of 10a
suitable for X-ray diffraction study was obtained by recrystallization
from AcOH (Fig. 4).
Table 3
The value of nas (NO2) and ns (NO2) absorption bands of isomers 7 and 8 in IR spectra
(KBr)
n
/cmꢁ1
/cmꢁ1
IR,
n
Isomers
(KBr)
As evident from the 1H NMR data (see Experimental Section and
Supplementary data), compounds 10aed, in contrast to the com-
pounds 4aef, 7aed, and 8aed with the benzimidazole system in
the investigated solutions of DMSO-d6 exist as a tautomeric mix-
ture of 10aed%100aed, resulting in the dissymmetric 1H-imidazo
[4,5-b]pyridine system. Benzimidazoles as imidazoles with a ring
N-hydrogen are subjected to tautomerism, which becomes evident
in unsymmetrically substituted compounds.13 In the cases of imi-
dazo[4,5-b]pyridines 10aed the dissymmetry was caused by a ni-
trogen atom of the pyridine ring.
7a
8a
7b
8b
7c
8c
7d
8d
nas (NO2)
ns (NO2)
1520
1348
1532
1350
1519
1348
1531
1347
1519
1347
1534
1348
1519
1346
1532
1344
Unlike the frequencies of ns (NO2), which are virtually identical
in the spectra of both compounds, the frequencies nas (NO2) for
high-melting isomers are w15 cmꢁ1 higher than those for low-
melting isomers. Asymmetric vibrations of NO2, which are known
to be sensitive to the electronic properties of the para substituent,
are shifted to higher frequencies in the presence of electron-

9748
V.A. Mamedov et al. / Tetrahedron 66 (2010) 9745e9753
On the basis of the known chemistry of quinoxalinones,14aed 1,2-
R
R
phenylenediamines15 and above data (the formation of compounds
6a,b and 11a) it is reasonable to assume that the formation of
2-benzimidazol-2-ylquinoxaline 4 involves addition of the amino
group of 3 at the C(3) atom of quinoxalin-2(1H)-one 1 as the first
step. The next step involves the nucleophilic attack of the second
amino group of 3 at the benzoyl carbonyl group to form the spiro-
quinoxaline derivative 60. Rearrangement of the spiroquinox-
alinone 60 is then assumed to occur according to Scheme 2, which
proceeds by cascade reactions involving: (a) acid catalysis ring-
opening with cleavage of the C(3)eN(4) bond in spiro-compound 60
with the intermediate formation of quinoxaline derivative 6, (b)
intramolecular nucleophilic attack by the amino group on the
carbonyl group with the intermediate formation of hydroxy-de-
4
7
H
N3
N 1
N
N
N
N
N
N 3
N
N
H1
2-(1H-imidazo[5,4-b]pyridin-2-yl)-
3-arylquinoxalines
2-(1H-imidazo[4,5-b]pyridin-2-yl)-
3-arylquinoxalines
10a-d
10'a-d
Fig. 3. ORTEP drawing of 7a (a) and 8a (b) molecules. Displacement ellipsoids are drawn at the 30% probability level. H atoms are represented by circles of arbitrary radii. The
solvent molecule in (a) was omitted for clarity.
Table 4
A new 1H-imidazo[4,5-b]pyridine synthesis from pyrido[2,3-b]pyrazin-2(1H)-ones
and 1,2-phenylenediamine via a novel rearrangement
R
O
AcOH,
N
N
N
N
reflux
N
+
3a
N
H
- 2H2O
N
N
H
O
R
10
9
DMSO (rt, 20 days)
or n-BuOH (reflux)
- H2O
Fig. 4. ORTEP plot of compound 10a. Displacement ellipsoids are drawn at the 30%
probability level. The solvent water molecules were omitted for clarity.
AcOH
reflux
- H2O
N
H
N
N
rivative A, and (c) elimination of water leading to the formation of
the final product 4 (Scheme 2).
O
This proposed mechanism of the rearrangement is indirectly
confirmed by the formation of spiro-compounds with a structure
similar to that of 60 in the reactions of quinoxalinones with other
binucleophilic compounds14c,d and in the reactions of aza-quinox-
alinones with 1,2-phenylenediamine.The formation of quinoxaline
derivative 6 in the reaction of quinoxalin-2(1H)-ones with 1,2-
phenylenediamine in DMSO at room temperature, and in boiling n-
BuOH, also occurs.
N
NH2
11
R
Entry
R
Substrates
Product, Yield (%)
1
2
3
4
5
6
H
F
Cl
Br
H
H
9a
9b
9c
9d
9a
11a
3a
3a
3a
3a
3a
10a, 69
10b, 44
10c, 41
10d, 43
11a, 64a, 72b
10a, 84
3. Conclusion
a
To summarize, we have found an efficient and versatile one-step
method for the preparation of a series of benzimidazoles as well as
Obtained in refluxing pyridine.
Obtained in refluxing AcOH.
b

V.A. Mamedov et al. / Tetrahedron 66 (2010) 9745e9753
9749
H
N
H2O
Ar
H2N
OH
H2N
O
Ar
Ar
NH
NH
NH
H+
N
N
1 + 3a
N
H
H
O
H2
NH
O
NH
NH
O
- H2O,
- H+
NH2
Ar
NH Ar
Ar
N
O
H
N
N
H
N
N
H
N
HO
N
H
4
N
N
- H2O
NH
O
A
6'
6
Scheme 2. A probable mechanism of the rearrangement.
1H-imidazo[4,5-b]pyridines. This was accomplished by the novel
rearrangement of 3-aroylquinoxalin-2(1H)-ones and their aza-ana-
logues of benzimidazoles on exposure to 1,2-phenylenediamines. The
reaction is readily applicable to large scale synthesis. Application of
thismethodologytothesynthesisofotherheterocyclicringsystems is
currently under investigation and the results will be published in due
time.
crystals of 4 that precipitated were collected by suction filtration
and compound 4 was obtained in w90% yield. The filtrate was
evaporated and the residue was treated with water. The crystals
formed were filtered off, washed with water, and dried. An addi-
tional 3e5% compound 4 was thus obtained.
R
34
33
32
31
4. Experimental section
4.1. General methods
24
N44a
23a
3
23
N
25
26
5
2
22
6
27a N21
1N 8a
NMR investigations were carried out in the NMR Department of
the Federal Collective Spectral Analysis Center for the physical and
chemical investigations of the structure, properties, and compo-
sition of matter and materials. All NMR experiments were per-
27
H
4
8
7
formed with
a Bruker AVANCE-600 spectrometer (14.1 T)
4.2.1. 2-(Benzimidazol-2-yl)-3-(4-fluorophenyl)quinoxaline
(4b). Pale orange crystals, mp 251e253 ꢀC; [found C, 74.22; H, 3.89;
N, 16.40. C21H13FN4 requires C, 74.11; H, 3.85; N, 16.46%]; nmax (KBr)
3243, 3066, 1697, 1513, 1429, 1361, 1338, 1284, 1272, 1223, 845,
equipped with a 5 mm diameter gradient inverse broad band
probehead and a pulsed gradient unit capable of producing mag-
netic field pulse gradients in the z-direction of 53.5 G cmꢁ1. Fre-
quencies are 400 MHz in 1H, 100 MHz in 13C, and 60 MHz in 15N
744 cmꢁ1
;
dH3(400 MHz, DMSO-d6) 7.20e7.26 (2H, m, H25, H26),
experiments. Chemical shifts are reported in the
d (ppm) scale
3
relative to the 1H and 13C signals of tetramethylsilane (TMS)
(0.00 ppm). 15N, 19F chemical shifts were referenced to the 15N
signal of CH3CN (235.50 ppm) and 19F signal of C6F6 (ꢁ164.9 ppm),
respectively. The ab initio quantum chemical calculations were
performed using Gaussian 98.16 Chemical shifts were determined
by the GIAO method within the DFT framework using a hybrid
exchange-correlation functional, B3LYP, at the 6-31G(d) level if not
commented otherwise. All data were referred to TMS (0.00 ppm)
for 1H and 13C chemical shifts calculated in the same conditions.
Melting points were determined on a Boetius hot-stage apparatus.
IR spectra were recorded on a Bruker Vector-22 FT-IR spectrometer
in KBr pellets. Mass spectra of electron ionization (EI) were mea-
sured on a Thermo Fisher Sci. DFS mass spectrometer. The in-
sertion of the sample was performed with direct injection
combined with a water cooling system. The peaks of fragment ions
with the intensity of less than 10% are omitted. The elemental
analyses were given for the pure compounds after removing the
solvate molecule and were carried out at the Microanalysis Labo-
ratory of the Arbuzov Institute of Organic and Physical Chemistry,
Russian Academy of Sciences.
7.21 (2H, dd, JHH 9.1, JHF 9.1 Hz, 2ꢂH33), 7.53e7.59 (2H, m, H24,
H27), 7.66 (2H, dd, 3JHH 9.1, 4JHF 5.6 Hz, 2ꢂH32), 7.93e7.99 (2H, m,
H6, H7), 8.19e8.25 (2H, m, H5, H8), 13.20 (1H, br s, H21); dC
(100 MHz, DMSO-d6) 114.6 (d, 2JFC 21.8 Hz, C33), 117.0 (br, C24, C27),
122.7 (br C25, C 26), 128.6 (C8), 128.9 (C5), 130.9 (C6), 131.5 (C7),
131.7 (d, 3JFC 8.6 Hz, C32), 135.1 (d, 4JFC 3.4 Hz, C31), 139.0 (br, C23a,
C27a), 139.7 (C8a), 140.8 (C4a), 143.3 (C2), 149.2 (C22), 152.3 (C3),
162.6 (d, 1JFC 246 Hz, C34); dF (376 MHz, DMSO-d6) 112.8 (F34).
4.2.2. 2-(Benzimidazol-2-yl)-3-(4-chlorophenyl)quinoxaline
(4c). Off-white crystals, mp 233e235 ꢀC; [found C, 70.61; H, 3.71; N,
15.66. C21H13ClN4 requires C, 70.69; H, 3.67; N, 15.70%]; nmax (KBr)
3203, 3061, 1690, 1429, 1364, 1336, 1293, 1094, 1011, 838, 742 cmꢁ1
;
dH (400 MHz, DMSO-d6) 7.16e7.30 (2H, m, H25, H26), 7.40 (2H, d, J
8.6 Hz, 2ꢂH33), 7.42e7.56 (2H, m, H24, H27), 7.57 (2H, d, J¼8.6 Hz,
2ꢂH32), 7.90e7.94 (2H, m, H6, H7), 8.13e8.16 (1H, m, H5), 8.17e8.20
(1H, m, H8), 13.20 (1H, br s, H21); dC (100 MHz, DMSO-d6) 115.0 (br,
C24, C27), 122.9 (C25, C26), 127.7 (C33), 128.7 (C8), 128.8 (C5), 131.1
(C6, C32), 131.7 (C7), 133.8 (C34), 137.3 (C31), 138.8 (br, C23a, C27a),
139.7 (C8a), 140.7 (C4a), 143.1 (C2), 149.1 (C22), 152.0 (C3).
4.2. Typical procedure 1: synthesis of 2-(benzimidazol-2-yl)-
3-arylquinoxalines 4
4.2.3. 2-(Benzimidazol-2-yl)-3-(4-bromophenyl)quinoxaline
(4d). Yellow crystals, mp 234e236 ꢀC; [found C, 62.72; H, 3.23; N,
13.90. C21H13BrN4 requires C, 62.86; H, 3.27; N, 13.96%]; nmax (KBr)
3297, 3241, 3063, 3027, 2881, 1712, 1479, 1428, 1341, 1263, 768,
A solution of 3-aroylquinoxaline-2(1H)one 1 (0.93 mmol) and
1,2-phenylenediamine 3a (0.93 mmol) in acetic acid (9 mL) was
heated at reflux for 1 h. After cooling to room temperature, the
746 cmꢁ1
;
dH (400 MHz, DMSO-d6) 7.16e7.19 (1H, m, H25),
7.26e7.28 (1H, m, H26), 7.52e7.64 (6H, m, 2ꢂH32, 2ꢂH33, H24,

9750
V.A. Mamedov et al. / Tetrahedron 66 (2010) 9745e9753
H27), 7.93e7.96 (2H, m, H6, H7), 8.17e8.23 (2H, m, H5, H8), 13.20
(1H, br s, H21); dC (100 MHz, DMSO-d6) 111.9 (br, C27), 119.7 (br,
C24), 121.9 (br, C25), 122.5 (C34), 123.6 (br, C26), 128.6 (C8), 128.9
(C5), 130.6 (C32), 131.1 (C6), 131.47 (C33), 131.52 (C7), 134.4 (br,
C27a), 137.9 (C31), 139.7 (C8a), 140.7 (C4a), 143.2 (C2), 143.4 (br,
C23a), 149.1 (C22), 152.1 (C3).
4JHF 5.5 Hz, 2ꢂH32), 8.40 (1H, d, J 9.3 Hz, H5), 8.61 (1H, dd, J 9.3,
2.5 Hz, H6), 8.95 (1H, d, J 2.5 Hz, H8), 13.30 (1H, br s, H21); dC
(100 MHz, DMSO-d6) 114.8 (d, J 21.9 Hz, C33), 112.1 (br, C27), 120.0
(br, C24), 122.2 (br, C25), 124.1 (br, C26), 124.4 (C6), 124.5 (C8), 130.9
(C5), 132.0 (d, J 8.9 Hz, C32), 134.4 (br, C27a), 134.4 (d, J 3.1 Hz, C31),
138.5 (C8a),143.1 (C4a),143.4 (br, C23a),145.3 (C2),147.9 (C7),148.4
(C22), 155.1 (C3), 163.0 (d, J 247.2 Hz, C34); dF (376 MHz, DMSO-d6)
ꢃ
4.2.4. 2-(Benzimidazol-2-yl)-3-(4-iodophenyl)quinoxaline
(4e). Light-yellow crystals, mp 264e265 ꢀC; [found C, 56.16; H, 2.95;
N, 12.55. C21H13IN4 requires C, 56.27; H, 2.92; N, 12.50%]; nmax (KBr)
3393, 3049, 1711, 1479, 1417, 1387, 1334, 1323, 1196, 1141, 997, 765,
111.6 (F34); m/z 385 (26 Mþ ), 384 (60), 354 (100), 353 (14), 339
(14), 338 (44), 337 (16), 326 (13), 177 (13), 169 (13%).
4.3.2. 2-(Benzimidazol-2-yl)-3-(4-fluorophenyl)-6-nitroquinoxaline
(8a). Bright-yellow powder, mp 246e249 ꢀC (i-PrOH); [found C,
65.34; H, 3.09; N, 18.12. C21H12FN5O2 requires C, 65.45; H, 3.14; N,
18.17%]; nmax (KBr) 3073, 2968, 2929, 1602, 1532 (nas (NO2)), 1514,
747 cmꢁ1
; dH (400 MHz, DMSO-d6) 7.20e7.26 (2H, m, H25, H26), 7.42
(2H, d, J 8.0 Hz, 2ꢂH32), 7.55e7.59 (2H, m, H24, H27), 7.77 (2H, d, J
8.0 Hz, 2ꢂH33), 7.94e7.99 (2H, m, H6, H7), 8.18e8.25 (2H, m, H5, H8),
13.21 (1H, br s, H21); dC (100 MHz, DMSO-d6) 95.9 (C34), 122.8 (br,
C25, C26),128.6(C8),128.9(C5),131.1 (C6),131.5(C7, C32),136.5 (C33),
138.2 (C31),139.7 (C8a),140.8 (C4a),143.2 (C2),145.8 (br, C23a, C27a),
149.1 (C22),152.3 (C3), the signals of C24, C27 are extremely broaded.
1431, 1350 (ns (NO2)), 1334, 1309, 1230, 849, 751 cmꢁ1
; dH (400 MHz,
DMSO-d6) 7.18 (1H, dd, J 8.0, 8.0 Hz, H26), 7.26 (2H, dd, 3JHH 8.6, 3JHF
8.6 Hz, 2ꢂH33), 7.30 (1H, dd, J 8.0, 8.0 Hz, H25), 7.53 (1H, d, J 8.0 Hz,
3
4
H24), 7.61 (1H, d, J 8.0 Hz, H27), 7.73 (2H, dd, JHH 8.5, JHF 5.6 Hz,
2ꢂH32), 8.40 (1H, d, J 9.1 Hz, H8), 8.61 (1H, dd, J 9.1, 2.4 Hz, H7), 8.95
(1H, d, J 2.4 Hz, H5), 13.32 (1H, br s, H21); dC (100 MHz, DMSO-d6)
112.1 (C27), 114.6 (d, J 21.8 Hz, C33), 120.0 (C24), 122.2 (C25), 1124.1
(C7), 124.2 (C26), 124.9 (C5), 130.5 (C8), 131.9 (d, J 9.0 Hz, C32), 134.5
(C31, C27a), 139.5 (C4a), 142.2 (C8a), 143.5 (C23a), 145.7 (C2), 148.1
(C6), 148.4 (C22), 154.4 (C3), 162.9 (d, J 246.6 Hz, C34); dF (376 MHz,
4.2.5. 2-(Benzimidazol-2-yl)-3-(4-nitrophenyl)quinoxaline
(4f). Bright-yellow crystals, mp 304e306 ꢀC; [found C, 68.52; H,
3.52; N, 18.99. C21H13N5O2 requires C, 68.66; H, 3.57; N, 19.06%];
nmax (KBr) 3384, 3056, 1510, 1480, 1348, 1324, 1201, 855, 765, 740,
704 cmꢁ1
; dH (400 MHz, DMSO-d6) 7.13e7.29 (2H, m, H25, H26),
ꢃ
7.47e7.61 (2H, m, H24, H27), 7.90 (2H, d, J 8.9 Hz, 2ꢂH32),
7.94e8.02 (2H, m, H6, H7), 8.20e8.28 (2H, m, H5, H8), 8.27 (2H, d, J
8.9 Hz, 2ꢂH33), 13.24 (1H, br, H21); dC (100 MHz, DMSO-d6) 111.9
(br, C27), 119.8 (br, C24), 121.9 (br, C25), 122.6 (C33), 123.7 (br, C26),
128.5 (C8), 129.0 (C5), 130.8 (C32), 131.5 (C6, C7), 134.3 (br, C27a),
140.0 (C8a), 140.5 (C4a), 142.8 (C2), 143.3 (br, C23a), 145.6 (C31),
147.4 (C34), 148.7 (C22), 151.4 (C3).
DMSO-d6) 112.0 (F34); m/z 385(6 Mþ ), 384 (15), 355 (9), 354 (100),
338 (11), 337 (16), 177 (11%).
4.3.3. 2-(Benzimidazol-2-yl)-3-(4-chlorophenyl)-7-nitroquinoxaline
(7b). Orange powder, mp 338e339 ꢀC (AcOH); [found C, 62.85; H,
2.99; N,17.35. C21H12ClN5O2 requires C, 62.77; H, 3.01; N,17.43%]; nmax
(KBr) 3369, 3095, 1615, 1519 (nas (NO2)), 1348 (ns (NO2)), 1330,
740 cmꢁ1
; dH (400 MHz, DMSO-d6) 7.18e7.32 (2H, m, H25, H26), 7.48
(2H, d, J 8.7 Hz, 2ꢂH33), 7.52e7.64 (2H, m, H24, H27), 7.70 (2H, d, J
8.7 Hz,2ꢂH32), 8.39 (1H, d,J9.3Hz, H5), 8.60(1H, dd, J9.3,2.4Hz, H6),
8.93 (1H, d, J 2.4 Hz, H8),13.34 (1H, br s, H21); dC (100 MHz, DMSO-d6)
115.9(br, C24,C27),122.7(C25,C26),124.1(C6),124.3(C8),127.5(C33),
130.7 (C5),131.3 (C32), 134.3 (C34), 136.8 (C31),138.5 (C8a), 139.3 (br,
C23a, C27a),142.9 (C4a),145.5 (br, C2),147.9 (C7),148.6 (br, C22),154.8
4.3. Typical procedure 2: synthesis of 2-(benzimidazol-2-yl)
quinoxalines 7 and 8
A solution of 3-aroylquinoxaline-2(1H)one 1 (0.65 mmol) and 4-
nitro-1,2-phenylenediamine 3b (0.65 mmol) in acetic acid (7 mL)
was refluxed for 1.5 h. After ca. 30 min the precipitation of crystals
occurred, which was completed during the following 1 h. The crys-
tals were collected by hot suction filtration. Thus, 40% of the ana-
lytically pure sample of a high-melting isomer 7 was obtained. After
evaporation of the solvent from the filtrate under reduced pressure
the resulting solid was refluxed at 80 ꢀC for 10 min in i-PrOH and was
hot filtered. After cooling the filtrate to room temperature the pre-
cipitated crystals of isomer 8 were collected by suction filtration and
ca. a 40% compound 8 was obtained. 5e10% of the solid residue,
which was not dissolved in refluxed i-PrOH proved to be isomer 7.
ꢃ
(C3); m/z 403 (6), 402 (20), 401 (17 Mþ ), 400 (57), 372 (32), 371 (28),
370 (100), 369 (11), 356 (12), 355 (12), 354 (34), 168 (11%).
4.3.4. 2-(Benzimidazol-2-yl)-3-(4-chlorophenyl)-6-nitroquinoxaline
(8b). Orange red crystals, mp 291e292 ꢀC (i-PrOH); [found C, 62.89;
H, 3.04; N, 17.36. C21H12ClN5O2 requires C, 62.77; H, 3.01; N, 17.43%];
nmax (KBr) 3394, 2926, 1615, 1531 (nas (NO2)), 1347 (ns (NO2)), 1332,
738 cmꢁ1
; dH (400 MHz, DMSO-d6) 7.16e7.34 (2H, m, H25, H26), 7.49
(2H, d, J 8.7 Hz, 2ꢂH33), 7.52e7.64 (2H, m, H24, H27), 7.69 (2H, d, J
8.7 Hz, 2ꢂH32), 8.40 (1H, d, J 9.3 Hz, H8), 8.61 (1H, dd, J 9.3, 2.4 Hz,
H7), 8.95 (1H, d, J 2.4 Hz, H5),13.37 (1H, s, H21); dC (100 MHz, DMSO-
d6) 115.9 (br, C24, C27), 123.2 (C25, C26), 124.2 (C7), 124.9 (C5), 127.7
(C33),130.5 (C8),131.4 (C32),134.2 (C34),137.0 (C31),138.6 (br, C23a,
C27a), 139.5 (C4a), 142.3 (C8a), 145.7 (C2), 148.2 (C6), 148.4 (C22),
R
R
34
34
33
32
31
33
32
31
24
27
24
27
23
N44a
N44a
ꢃ
154.3 (C3); m/z 403 (4), 402 (11), 401 (11 Mþ ), 400 (27), 373 (11), 372
23a
23a
3
3
23
N
N
25
26
25
26
5
5
2
2
(40), 371 (34), 370 (100), 354 (15), 335 (12), 154 (14%).
22
22
6
6
27a N21
27a N21
H
7
1N 8a
NO2
1N 8a
H
8
7
8
7
8
4.3.5. 2-(Benzimidazol-2-yl)-3-(4-bromophenyl)-7-nitroquinoxaline
(7c). Orange yellow powder, mp 343e345 ꢀC (AcOH); [found C,
56.41; H, 2.68; N, 15.64. C21H12BrN5O2 requires C, 56.52; H, 2.71; N,
15.69%]; nmax (KBr) 3360, 3096, 3066, 2919, 1519 (nas (NO2)), 1347 (ns
NO2
4.3.1. 2-(Benzimidazol-2-yl)-3-(4-fluorophenyl)-7-nitroquinoxaline
(7a). Bright-orange powder, mp 336e337 ꢀC (AcOH); [found C,
65.39; H, 3.18; N, 18.15. C21H12FN5O2 requires C, 65.45; H, 3.14; N,
18.17%]; nmax (KBr) 3360, 1602, 1520 (nas (NO2)), 1348 (ns (NO2)),
(NO2)),1329,1071, 746 cmꢁ1
; dH (400 MHz, DMSO-d6) 7.16e7.34 (2H,
m, H25, H26), 7.54e7.66 (2H, m, H24, H27), 7.60e7.66 (4H, m,
2ꢂH32, 2ꢂH33), 8.39 (1H, d, J 9.3 Hz, H5), 8.60 (1H, dd, J 9.1, 2.4 Hz,
H6), 8.94 (1H, d, J 2.4 Hz, H8), 13.32 (1H, br s, H21); dC (100 MHz,
DMSO-d6) 111.9 (br, C27), 119.8 (br, C24), 122.0 (br, C25), 123.1 (C34),
123.9 (br, C26), 124.2 (C6), 124.3 (C8), 130.5 (C32), 130.8 (C5), 131.5
(C33), 134.3 (br, C27a),137.2 (C31), 138.5 (C8a), 142.9 (C4a), 143.3 (br,
1331, 1309, 1224, 1205, 1160, 1069, 833, 743 cmꢁ1
; dH (400 MHz,
3
3
DMSO-d6) 7.18e7.32 (2H, m, H25, H26), 7.26 (2H, dd, JHH 8.8, JHF
8.8 Hz, 2ꢂH33), 7.52e7.64 (2H, m, H24, H27), 7.74 (2H, dd, 3JHH 8.8,

V.A. Mamedov et al. / Tetrahedron 66 (2010) 9745e9753
9751
C23a),145.1 (C2),147.9 (C7),148.1 (C22),154.9 (C3); m/z 447 (13), 446
heated at reflux for 4.5 h. After cooling to room temperature the
precipitated crystals were collected by suction filtration, washed
with i-PrOH (2ꢂ5 mL), and dried in air, providing an analytically
pure sample of compound 6.
ꢃ
(37), 445 (14 Mþ ), 444 (36), 417 (30), 416 (100), 415 (36), 414 (99),
400 (20), 398 (19), 336 (28), 335 (38), 334 (22), 168 (33), 154 (14%).
4.3.6. 2-(Benzimidazol-2-yl)-3-(4-bromophenyl)-6-nitroquinoxaline
(8c). Yellow crystals, mp 287e289 ꢀC (AcOH); [found C, 56.71; H,
2.68; N, 15.63. C21H12BrN5O2 requires C, 56.52; H, 2.71; N, 15.69%];
nmax (KBr) 3236, 3103, 2924, 1708, 1534 (nas (NO2)), 1430, 1361, 1348
4.4.1. 2-Aminoanylide quinoxaline 3-phenyl-2-carboxylic acid
(6a). Light-yellow crystals, mp 203e204 ꢀC; [found C, 74.49; H,
4.67; N, 16.34. C21H16N4O requires C, 74.10; H, 4.74; N, 16.46%]; nmax
(KBr) 3362, 3238, 1660, 1638, 1537, 1503, 1449, 1326, 1309, 1103,
(
ns (NO2)), 1334, 1292, 1072, 756, 741 cmꢁ1
; dH (400 MHz, DMSO-d6)
7.16e7.34 (2H, m, H25, H26), 7.54e7.64 (2H, m, H24, H27), 7.60e7.66
(4H, m, 2ꢂH32, 2ꢂH33), 8.38 (1H, d, J 9.3 Hz, H8), 8.59 (1H, dd, J 9.2,
2.4 Hz, H7), 8.91 (1H, d, J 2.4 Hz, H5), 13.30 (1H, br s, H21); dC
(100 MHz, DMSO-d6) 112.1 (br, C27), 119.3 (br, C24), 122.9 (br, C25,
C26), 123.1 (C34), 124.2 (C7), 124.9 (C5), 130.5 (C8), 130.7 (C32), 131.7
(C33), w134.0 (br, C27a),137.4 (C31),139.5 (C4a),142.3 (C8a), w143.0
(br, C23a),145.6 (C2), 148.2 (C22), 148.3 (C6), 154.3 (C3); m/z 447 (9),
762, 700 cmꢁ1
; dH (400 MHz, DMSO-d6) 4.84 (2H, br s, H24), 6.61
(1H, dd, J 7.1, 7.6 Hz, H27), 6.77 (1H, d, J 7.6 Hz, H25), 6.97 (1H, dd, J
7.1, 7.2 Hz, H26), 7.30 (1H, d, J 7.6 Hz, H28), 7.50e7.62 (3H, m,
2ꢂH33, H34), 7.88e7.90 (2H, m, 2ꢂH32), 7.94e8.02 (2H, m, H6,
H7), 8.18e8.28 (2H, m, H5, H8), 10.05 (1H, br s, H22); dC (100 MHz,
DMSO-d6) 115.9 (C25), 116.3 (C27), 122.3 (C23), 124.8 (C28), 126.4
(C26), 128.4 (C33), 128.6 (C32), 128.8 (C8), 128.9 (C5), 129.5 (C34),
130.8 (C7), 131.5 (C6), 137.4 (C31), 139.0 (C8a), 141.3 (C4a), 141.7
(C24), 149.2 (C2), 151.4 (C3), 165.0 (C21).
ꢃ
446 (22), 445 (9 Mþ ), 444 (21), 417 (27), 416 (100), 415 (31), 414 (99),
400 (13), 398 (12), 336 (24), 335 (32), 334 (21), 168 (23), 154 (25%).
4.3.7. 2-(Benzimidazol-2-yl)-3-(4-iodophenyl)-7-nitroquinoxaline
(7d). Orange crystals, mp 338e340 ꢀC (AcOH); [found C, 51.33; H,
2.42; N, 14.14. C21H12IN5O2 requires C, 51.14; H, 2.45; N, 14.20%];
nmax (KBr) 3361, 3098, 3053, 1585, 1519 (nas (NO2)), 1346 (ns (NO2)),
4.5. Typical procedure 4: synthesis of 2-(1H-imidazo[4,5-b]
pyridin-2-yl)-3-arylquinoxalines 10
A
solution of 2-aroylpyrido[2,3-b]pyrazin-3(4H)one
9
1332, 743 cmꢁ1
; dH (400 MHz, DMSO-d6) 7.20e7.32 (2H, m, H25,
(1.59 mmol) and 1,2-phenylenediamine 3a (1.59 mmol) in acetic
acid (15 mL) was heated at reflux for 35e47 h. After cooling to room
temperature, the precipitated crystals of compound 10 were col-
lected by suction filtration, washed with i-PrOH, dried in air and an
analytically pure sample of compound 10 was obtained in yields
indicated in Table 4.
H26), 7.48 (2H, d, J 8.5 Hz, 2ꢂH32), 7.56e7.64 (2H, m, H24, H27),
7.81 (2H, d, J 8.5 Hz, 2ꢂH33), 8.39 (1H, d, J 9.3 Hz, H5), 8.61 (1H, dd, J
9.3, 2.5 Hz, H6), 8.94 (1H, d, J 2.5 Hz, H8), 13.30 (1H, br s, H21); dC
(100 MHz, DMSO-d6) 109.5 (C34), 112.4 (br, C27), 120.2 (br, C24),
122.2 (br, C25), 124.2 (br, C26), 124.5 (C6, C8), 130.9 (C5), 131.6
(C32), 134.1 (br, C27a), 136.5 (C33), 137.6 (C31), 138.5 (C8a), 142.8
(br, C23a),143.1 (C4a),145.2 (C2),148.0 (C7),148.3 (C22),155.2 (C3);
R
ꢃ
m/z 493 (20 Mþ ), 492 (51), 463 (32), 462 (100), 446 (20), 337 (12),
34
33
336 (50), 335 (50), 334 (25), 320 (10), 319 (20), 168 (23), 155 (11%).
32
31
24
N
4.3.8. 2-(Benzimidazol-2-yl)-3-(4-iodophenyl)-6-nitroquinoxaline
(8d). Yellow crystals, mp 283e285 ꢀC (AcOH); [found C, 50.97; H,
2.41; N, 14.25. C21H12IN5O2 requires C, 51.14; H, 2.45; N, 14.20%]; nmax
(KBr) 3238, 3099, 3066, 2922, 1706, 1532 (nas (NO2)), 1430, 1344 (ns
3
23
N4
N
25
26
5
2
22
6
N21
1N
27
H
10
(NO2)), 1333, 1292, 999, 756, 740 cmꢁ1
; dH (400 MHz, DMSO-d6)
8
7
7.18e7.22 (1H, m, H25), 7.28e7.32 (1H, br, H26), 7.46 (2H, d, J 8.5 Hz,
2ꢂH32), 7.56e7.64 (2H, m, H24, H27), 7.79 (2H, d, J 8.5 Hz, 2ꢂH33),
8.38 (1H, d, J 9.2 Hz, H8), 8.59 (1H, dd, J 9.2, 2.3 Hz, H7), 8.92 (1H, d, J
2.3 Hz, H5), 13.30 (1H, br s, H21); dC (100 MHz, DMSO-d6) 96.6 (C34),
112.1 (C27), 120.1 (C24), 122.2 (C25), 124.2 (C7, C26), 124.9 (C5), 130.5
(C8), 131.6 (C32), 134.5 (C27a), 136.5 (C33), 137.6 (C31), 139.5 (C4a),
142.2 (C8a), 143.5 (C23a), 145.6 (C2), 148.2 (C6), 148.3 (C22), 154.5
4.5.1. 2-(1H-Imidazo[4,5-b]pyridin-2-yl)-3-phenylquinoxaline
(10a). Gray brown crystals, mp 267e270 ꢀC; [found C, 74.37; H,
4.01; N, 21.71. C20H13N5 requires C, 74.29; H, 4.05; N, 21.66%]; nmax
(KBr) 3054, 2978, 2793, 1590, 1480, 1428, 1408, 1277, 1253, 1216,
ꢃ
(C3); m/z 493 (36 Mþ ), 492 (100), 463 (18), 462 (63), 447 (11), 446
1090, 950, 772, 760, 695, 528 cmꢁ1
; dH (400 MHz, DMSO-d6)
(35), 336(12), 335(21), 334(13), 320(12), 319(28),168(12),160(14%).
7.25e7.32 (2H, m, 2ꢂH25), 7.37e7.47 (6H, m, 4ꢂH33, 2ꢂH34),
7.57e7.63 (4H, m, 4ꢂH32), 7.96e8.03 (6H, m, 2ꢂH6, 2ꢂH7, 2ꢂH27),
8.22e8.27 (4H, m, 2ꢂH5, 2ꢂH8), 8.39 (2H, dd, J 4.8, 1.6 Hz, 2ꢂH26),
13.40 (1H, br s, H21), 13.70 (1H, br s, H21).
4.4. Typical procedure 3: synthesis of the 2-aminoanylide
quinoxaline 3-aryl-2-carboxylic acid 6
4.5.2. 2-(1H-Imidazo[4,5-b]pyridin-2-yl)-3-(4-fluorophenyl)quinoxa-
line (10b). Light-graycrystals,mp313e314 ꢀC(DMF);[foundC,70.45;
H, 3.52; N, 20.46. C20H12FN5 requiresC, 70.37;H, 3.54; N, 20.52%];nmax
(KBr) 3112, 3061, 3018, 2956, 1593, 1513, 1479, 1433, 1408, 1275, 1255,
7
8
8a
6
5
1N
4a
H
N
22
28
25
1220, 1164, 952, 841, 776, 761, 524 cmꢁ1
; dH (400 MHz, DMSO-d6)
21
23
24
N4
27
26
2
3
7.20e7.32 (6H, m, 4ꢂH33, 2ꢂH25), 7.60e7.70 (4H, m, 4ꢂH32),
7.96e8.03 (6H, m, 2ꢂH6, 2ꢂH7, 2ꢂH27), 8.22e8.27 (4H, m, 2ꢂH5,
2ꢂH8), 8.39 (2H, dd, J 4.6,1.6 Hz, 2ꢂH26), 13.40 (1H, br s, H21), 13.80
(1H, br s, H21); dF (376 MHz, DMSO-d6) 112.5 (F34), 112.8 (F340).
31
O
32
33
NH2
34
6
R
4.5.3. 2-(1H-Imidazo[4,5-b]pyridin-2-yl)-3-(4-chlorophenyl)qui-
noxaline (10c). Gray brown crystals, mp 337e338 ꢀC; [found C,
67.41; H, 3.43; N, 19.48. C20H12ClN5 requires C, 67.14; H, 3.38; N,
19.57%]; nmax (KBr) 3060, 2957, 2788, 1592, 1477, 1431, 1406, 1274,
A solution of 3-aroylquinoxaline-2(1H)one 1 (0.81 mmol) and
1,2-phenylenediamine 3a (0.81 mmol) in n-BuOH (10 mL) was

9752
V.A. Mamedov et al. / Tetrahedron 66 (2010) 9745e9753
1091, 951, 837, 775, 759, 528 cmꢁ1
;
dH (400 MHz, DMSO-d6)
structures were solved by direct method and refined by the full
matrix least-squares using SHELXTL20 and WinGX21 programs. All
non-hydrogen atoms were refined anisotropically. Hydrogen atoms
of NH and NH2 groups of the two independent 6a molecules were
found from differential electron density map and were refined
isotropically. Hydrogen atom of NH group of 7a molecule and OH
group of solvate molecule were found from differential electron
density map and were refined isotropically. Hydrogen atom of NH
group of 8a molecule was found from differential electron density
map and refined by using the riding model. Hydrogen atom of NH
group of the molecule 10a was found from differential electron
density map and refined by using the riding model, the hydrogen
atoms of two solvate water molecules were found from the calcu-
lated scheme of hydrogen bonds and were refined with fixed posi-
tional and temperature parameters. One of two independent water
molecules is disordered over two position with relative occupancies
0.74:0.26. All other hydrogen atoms of compounds 6a, 7a, 8a, 10a
were placed in idealized positions and refined by using the riding
model. X-ray crystal structure data for compounds 6a (CCDC
774493), 7a (CCDC 774491), 8a (CCDC 774494), and 10a (CCDC
774492) were deposited with the Cambridge Crystallographic Data
Center (CCDC). Copies of the data can be obtained, free of charge, on
application to CCDC, 12 Union Road, Cambridge CB2 1EZ, UK, (fax:
þ44 (0)1223 336033 or e-mail: deposit@ccdc.cam.ac.uk).
7.25e7.33 (2H, m, 2ꢂH25), 7.47 (2H, d, J 8.5 Hz, 2ꢂH33), 7.49 (2H, d,
J 8.5 Hz, 2ꢂH33), 7.62 (2H, d, J 8.2 Hz, 2ꢂH32), 7.66 (2H, d, J 8.2 Hz,
2ꢂH32), 7.96e8.04 (6H, m, 2ꢂH6, 2ꢂH7, 2ꢂH27), 8.20e8.28 (4H,
m, 2ꢂH5, 2ꢂH8), 8.40 (2H, br d, J 4.4 Hz, 2ꢂH26).
4.5.4. 2-(1H-Imidazo[4,5-b]pyridin-2-yl)-3-(4-bromophenyl)qui-
noxaline (10d). Gray green crystals, mp 334e336 ꢀC; [found C, 59.98;
H, 2.96; N,17.49. C20H12BrN5 requires C, 59.72;H, 3.01;N,17.41%]; nmax
(KBr) 3058, 2971, 2791, 1591, 1478, 1431, 1408, 1278, 1254, 1217, 1091,
950, 835, 801, 761, 528 cmꢁ1
; dH (400 MHz, DMSO-d6) 7.26e7.33 (2H,
m, 2ꢂH25), 7.55 (2H, d, J 8.6 Hz, 2ꢂH33), 7.58e7.62 (4H, m, 2ꢂH32,
2ꢂH33), 7.63 (2H, d, J 8.6 Hz, 2ꢂH32), 7.99e8.03 (6H, m, 2ꢂH6, 2ꢂH7,
2ꢂH27), 8.22e8.27 (4H, m, 2ꢂH5, 2ꢂH8), 8.40 (2H, br d, J 4.7 Hz,
2ꢂH26), 13.46 (1H, br, H21), 13.82 (1H, br, H21).
4.6. Synthesis of the 2-amino-3-azaanylide quinoxaline 3-
phenyl-2-carboxylic acid (11a)
7
8
6
5
8a
1N
4a
H
N
22
28
21
23
24
N4
27
26
2
3
Acknowledgements
31
O
32
33
N
NH2
This work was supported by the Russian Foundation for Basic
Research (grants No 10-03-00413-a, 09-03-00123-a).
25
34
11a
Supplementary data
A solution of 2-benzoylpyrido[2,3-b]pyrazin-3(4H)one 9a
(0.42 mmol) and 1,2-phenylenediamine 3a (0.42 mmol) in acetic acid
(3 mL) was heated at reflux for 3 h. After evaporation of the solvent,
the residue was triturated with water, the precipitated crystals were
collected by suction filtration, then washed with water, dried in air,
and an analytically pure sample of compound 11a was obtained as
a brown powder in 0.21 g (72%) yields, mp 216e218 ꢀC; [found C,
70.62; H, 4.38; N, 20.38. C20H15N5O requires C, 70.37; H, 4.43; N,
20.52%]; nmax (KBr) 3471, 3261, 3102, 3027, 2928, 1655, 1637, 1596,
Characterization data, 1D and 2D NMR spectra for all new
compounds, calculated CSs for compounds 7a, 8a, and X-ray crys-
tallographic file (CIF) for compounds 6a, 7a, 8a and 10a. Supple-
mentary data associated with this article can be found in online
version at doi:10.1016/j.tet.2010.10.026. These data include MOL
files and InChIKeys of the most important compounds described in
this article.
References and notes
1528, 1476, 777, 765, 701, 533 cmꢁ1
; dH (400 MHz, DMSO-d6) 5.78
(2H, br s, H24), 6.63 (1H, dd, J 7.8, 4.8 Hz, H27), 7.51e7.55 (3H, m,
2ꢂH33, H34), 7.73 (1H, dd, J 7.8, 1.8 Hz, H28), 7.84e7.88 (3H, m,
2ꢂH32, H26), 7.95e8.02 (2H, m, H6, H7), 8.22e8.27 (2H, m, H5, H8),
10.10 (1H, br s, H22); dC (100 MHz, DMSO-d6) 112.3 (C27),117.7 (C23),
128.4 (C32), 128.6 (C31), 128.8 (C8), 129.0 (C5), 129.5 (C34), 130.9
(C7),131.3 (C28),131.7 (C6),137.3 (C31),139.0 (C8a),141.4 (C4a),144.5
(C26), 148.7 (C2), 151.4 (C3), 152.7 (C24), 165.4 (C21); dN (60 MHz,
DMSO-d6) 125.9 (N22), 268.7 (N25), 323.5 (N1), 328.6 (N4).
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Ar
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O
NH2
NH2
N
CI
AcOH, rt
CI
+
Ar
OAlk
- H2O,
- ROH
N
H
O
O
DMF, rt NaN3
Ar
Ar
O
N
N
N
aq. AcOH, reflux
N3
O
- H2O,
- NH3
N
H
O
H
18. APEX2 (Version 2.1), SAINTPlus. Data Reduction and Correction Program (Version 7.
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1
1b (Ar = p-FC6H4, mp 257-259 oC); 1c (Ar = p-ClC6H4, mp 242-244 oC);
1d (Ar = p-BrC6H4, mp 263-265 oC); 1e (Ar = p-IC6H4, mp 274-276 oC);
1f (Ar = p-O2NC6H4, mp 270-272 oC)
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