Quinoxalinone-benzimidazole rearrangement: An efficient strategy for the synthesis of structurally diverse quinoline derivatives with benzimidazole moieties Dedicated to the 80th anniversary of Academician Oleg Nikolaevich Chupakhin

Article abstract of DOI:10.1016/j.tetlet.2014.06.023

A novel and efficient procedure for the synthesis of structurally diverse benzimidazolylquinolines has been realized through a new acid-catalyzed quinoxalinone-benzimidazole rearrangement of the spiro-quinoxalinone derivatives formed in situ from the reaction of 3-(2-aminophenyl)quinoxalin-2(1H)-ones and different ketones.

Full text of DOI:10.1016/j.tetlet.2014.06.023

Tetrahedron Letters 55 (2014) 4319–4324
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Tetrahedron Letters
journal homepage: www.elsevier.com/locate/tetlet
Quinoxalinone–benzimidazole rearrangement: an efficient strategy
for the synthesis of structurally diverse quinoline derivatives with
benzimidazole moieties
⇑
Vakhid A. Mamedov , Venera R. Galimullina, Nataliya A. Zhukova, Saniya F. Kadyrova,
Ekaterina V. Mironova, Il’dar Kh. Rizvanov, Shamil K. Latypov
A.E. Arbuzov Institute of Organic and Physical Chemistry, Kazan Scientific Center of Russian Academy of Sciences, Arbuzov str. 8, 420088 Kazan, Russian Federation
a r t i c l e i n f o
a b s t r a c t
Article history:
A novel and efficient procedure for the synthesis of structurally diverse benzimidazolylquinolines has
been realized through a new acid-catalyzed quinoxalinone–benzimidazole rearrangement of the spiro-
quinoxalinone derivatives formed in situ from the reaction of 3-(2-aminophenyl)quinoxalin-2(1H)-ones
and different ketones.
Received 30 March 2014
Revised 17 May 2014
Accepted 5 June 2014
Available online 12 June 2014
Ó 2014 Elsevier Ltd. All rights reserved.
Dedicated to the 80th anniversary of
Academician Oleg Nikolaevich Chupakhin
Keywords:
3-(2-Aminophenyl)quinoxalin-2(1H)-one
Ring contractions
Ring formation
Novel rearrangement
4-(Benzimidazol-2-yl)quinolines
Quinolines and their derivatives are very important biological
compounds that occur widely in natural products, examples of
which demonstrate antimalarial, anti-asthmatic, antihypertensive,
and antibacterial activities, and tyrosine kinase inhibition.1 Quino-
line derivatives can also be useful ligands and functional materials,2
and some of them have been applied in the study of bioorganic and
bioorgano-metallic processes.3 Therefore, quinoline derivatives
have become the synthetic targets of many organic and medicinal
chemists, and a variety of methods for their synthesis, such as the
Skraup, Doebner–Von Miller, Friedländer, and Combes methods
have been developed and extended.4 For example, the Friedländer
reaction is generally carried out either by refluxing an aqueous or
alcoholic solution of the reactants in the presence of a base, or by
heating a mixture of the reactants at 150–220 °C in the absence of
a catalyst.5 In order to improve the generality of the Friedländer
method, Bronsted acids such as hydrochloric acid,6 p-toluenesul-
fonic acid,7 dodecylphosphonic acid,8 and sulfuric acid modified
PEG-60009 have been employed. Modified methods, using Lewis
acids,10 inorganic salts,11 and ionic liquids,12 have also been
reported for this reaction. However, the principal shortcomings
(such as long reaction times, harsh reaction conditions, or the use
of volatile, and hazardous organic solvents) of these conventionally
named routes do not allow them to be used for synthesizing
quinoline derivatives with various types of the heterocyclic ring
systems directly attached to the quinoline core.
We have previously shown13a–p that due to the presence of an
imine function between the C3 and N4 atoms of the pyrazine ring,
the derivatives of quinoxalin-2(1H)-one Q depend on the nature of
substituents R1 at position 3; they behave like imino analogs of
a
-chloroketones [in the case of R1 = CH(Cl)Ph],13a
[in the case of R1 = CH(NH2)Ph],13b
R1 = CH(N3)(CH2)nPh],13c
a
-aminoketones
-azidoketones [in the case of
-diketones [in the case of R1 = C(O)Ar,
a
a
C(O)Alk],13d–k simple ketones [in the case of R1 = Me],13l and
b-diketones [in the case of R1 = CH2C(O)Ar],13m,n and are subject
to novel acid-catalyzed rearrangement13p,q in reactions with
various N-nucleophiles. In these cases they result in 2-hetero-
aryl-substituted benzimidazole derivatives (Scheme 1).
Following the results reported in our previous papers13a–n on
the new rearrangement of quinoxalin-2(1H)-one derivatives,13p,q
we assumed that 3-(2-aminophenyl)quinoxalin-2(1H)-one (1)
could be used as a heteroanalog of the ortho-amino aromatic
aldehydes employed in the Friedländer reaction, with the ketones
⇑
Corresponding author. Tel.: +7 843 2727304; fax: +7 843 2732253.
E-mail address: mamedov@iopc.ru (V.A. Mamedov).
http://dx.doi.org/10.1016/j.tetlet.2014.06.023
0040-4039/Ó 2014 Elsevier Ltd. All rights reserved.

4320
V. A. Mamedov et al. / Tetrahedron Letters 55 (2014) 4319–4324
H
N
N
R1
O
N
Het
H
H+
N-nucleophiles
Het
N
N
NH
- H2O
N
H
sQ
O
N
H
Q
acetone,
AcOH,
H
R2
R2
R2
N
N
N
BI
55 oC, 2 h
+
NH2
N
H
-2H2O
R1 = CH(Cl)Ar, CH(NH2)Ph, CH(N3)(CH2)nPh, C(O)Alk, C(O)Ar, Me, CH2C(O)Ar
N
H
O
N
1
2 (5%)a
3 (75%)a
N
N
aIsolated yield
N
NC
NC
N
N
N
Het
=
,
,
,
N
,
,
N
H
N
H
N
H
Scheme 2. The reaction of 3-(2-aminophenyl)quinoxalin-2(1H)-one derivative (1)
with acetone.
Scheme 1. Common presentation of the rearrangement for the synthesis of 2-
heteroaryl-benzimidazoles.
cyclocondensation of the quinoxaline derivative 1. The optimal
temperature for this reaction corresponds approximately to the
boiling temperature of acetone (55 °C). This temperature appears
to be optimal for the reaction of 3-(2-aminophenyl)quinoxalin-
2(1H)-one (1) with acetophenone (4a) and 4-bromoacetophenone
(4b). As can be seen from Table 1, in these cases, the optimal ratio
was 1:2 (1:4a and 1:4b) when the reactions were carried out for
five hours (entries 4 and 9), because when the ratio of the reagents
was 1:1, the yield of compound 2 increased and there was a
decrease in the overall yield of the mixture of compounds 2 and
5 (entries 1, 6 and 7). When the ratio of the starting compounds
was 1:10 or 1:5 (entries 5 and 10), despite the satisfactory yield
of the desired products, difficulties occurred during purification
of the final products.
To explore the scope and limitations of the reaction, the
procedure was extended to various acetophenones 4. As indicated
in Table 2, the reactions proceeded very efficiently, and led to the
formation of the corresponding 4-(benzimidazol-2-yl)quinolines
5a–f as the major and 6H-indolo[2,3-b]quinoxaline (2) as minor
products.
bearing an active a-methylene functionality, capable of providing a
two-carbon fragment in the construction of the quinoline system.
We assumed that the presence of a quinoline fragment with at
least one mobile hydrogen atom at position 3 of the quinoxalin-
2(1H)-one system was presumably the key factor for the acid-
catalyzed rearrangement as in the previous cases,13 and would
make it possible to synthesize 4-(benzimidazol-2-yl)quinolines 3
and 5. Because of the importance of these heterocycles and
significant enhancement expectations in their biological activity
in the presence of two different heterocyclic motifs in a single
molecule,14 we became interested in the synthesis of quinoline–
benzimidazole conjugates. Herein, we report the facile synthesis
of 4-(benzimidazol-2-yl)quinolines via the one-pot condensation
of 3-(2-aminophenyl)quinoxalin-2(1H)-one (1) with various
carbonyl compounds.
To optimize the process, we initially carried out the reaction of
3-(2-aminophenyl)quinoxalin-2(1H)-one (1) with acetone in acetic
acid with various ratios of reagents and different reaction times.
Regardless of the molar ratio of the reagents (1:32, 1:16, 1:8,
1:4; 1:acetone) and the reaction time (6, 4 or 2 h) the reaction
proceeded in the same way with the formation of an ꢀ85% yield
of the crude product, which on the basis of the 1H NMR spectrum
contains ꢀ90% of the quinoline 3 and ꢀ10% of the quinoxaline
derivative 2 (Scheme 2).
Based on the known chemistry of amines,16 enolizable
ketones,17 enamines,18 quinoxalinones,19 and the previous
reports,13a–m a plausible mechanism for the formation of 4-(ben-
zimidazol-2-yl)quinolines 5 is proposed (Scheme 3). The reaction
starts with the condensation of the ketone with 3-(2-aminophe-
nyl)quinoxalin-2(1H)-one (1) to form imine A, which transforms
into the intermediate B by tautomerization. Subsequently, the
intermediate B is easily cyclized via intramolecular nucleophilic
The quinoline 3 is formed via the rearrangement, whereas
6H-indolo[2,3-b]quinoxaline (2) is the result of intramolecular
Table 1
Optimization of the reaction conditions
N
NH
O
N
N
AcOH
-2H2O
+
+
NH2
R1
N
H
N
N
H
1
O
N
2
R1
5a R1 = H
4a R1 = H
4b R1 = Br
1
5b
R
= Br
Entry
Substrate
Ratio of 1:4
Temp (°C)
Time (h)
Ratio of productsa
Total yieldb (%)
2 + 5
1
2
3
4
5
6
7
8
9
10
4a
4a
4a
4a
4a
4b
4b
4b
4b
4b
1:1
1:2
1:2
1:2
1:10
1:1
1:1
1:2
1:2
1:5
55
Reflux
55
55
55
55
55
55
55
2
2
2
5
5
2
6
2
5
5
2 + 5a (20:80)
2 + 5a (15:85)
2 + 5a (12:88)
2 + 5a (15:85)
2 + 5a (15:85)
2 + 5b (8:92)
2 + 5b (8:92)
2 + 5b (5:95)
2 + 5b (4:96)
2 + 5b (4:96)
54
52
75
95
80
40
46
79
86
72
55
a
Estimated on the basis of the 1H NMR spectra of the reaction mixture.
Yields based on the isolated mixture of products.
b

V. A. Mamedov et al. / Tetrahedron Letters 55 (2014) 4319–4324
4321
Table 2
addition to give the spiro-quinoxaline derivative C. The rearrange-
ment of the spiro-quinoxalinone C is then assumed to occur via
cascade reactions involving: (a) ring-opening with cleavage of
the C3–N4 bond in the spiro-compound D with the formation of
the intermediate quinoline derivative E, (b) intramolecular nucleo-
philic attack by the amino group on the carbonyl group with the
formation of the hydroxy-derivative F, and (c) the elimination of
water leading to formation of the final product 5. All the stages
of the reaction involve acid-catalyzed processes.
As can be seen, this chemistry is not limited to acetone and
acetophenones with various substituents; a ketone with an ester
group, viz. ethyl acetoacetate (6) was also an acceptable substrate
(Scheme 4). The latter case makes it possible to construct the
benzimidazolo[2,1-a]pyrrolo[3,4-c]quinolinone system 8,20 which
is difficult to access by other known methods.
Reaction of 3-(2-aminophenyl)-quinoxalin-2(1H)-one 1 with acetophenones 4a–f15
N
NH
O
AcOH,
55 oC, 5 h
2
+
+
1
-2H2O
N
R
4
5
R
Entry
Acetophenone 4
Products, yield (%)a
Mp (°C) 5
O
N
NH
All the compounds synthesized (3, 5a–f, and 8) were character-
ized by NMR, MS, and IR spectroscopy and elemental analyses. For
example, the mass spectra of quinolines 5e and 5b displayed char-
acteristic molecular ion peaks at 356 for M+ ([35Cl]) and 358 for M+
([37Cl]) (Fig. 1a) and 400 for M+ ([79Br]) and 402 for M+ ([81Br])
(Fig. 1b), respectively, consistent with the molecular structures.
The 1H NMR spectrum of 5e contains three groups of character-
istic signals for the benzimidazole, quinoline, and 4-ClC6H4
fragments. In this case, the protons of the benzene ring of
benzimidazole resonate as a strongly coupled AA0BB0 spin system
as multiplets at d 7.29–7.37 and d 7.70–7.78 due to H5+H6 and
H4+H7 of the benzimidazole fragment, respectively. The proton
of the NH group of the benzimidazole moiety resonates at d
13.36 as a characteristic singlet. The quinoline system is character-
ized by two doublet of doublet of doublets at d 7.68 and d 7.84, one
doublet at d 8.14, one doublet of doublets at d 9.14, and one singlet
at d 8.46 due to H6, H7, H8, H5, and H3 of the quinoline fragment.
The protons of the 4-chlorophenylene ring resonated as a simpli-
fied case of the AA0XX0 spin system with two doublets at d 7.60
and d 8.30. The 1H NMR spectra of 5a–d,f were very similar to that
of 5e, except for the signals of the protons of the phenyl groups.
The structures of the 2-methyl- (3) and 2-phenyl- (5a) 4-(ben-
zimidazol-2-yl)quinolines were further determined by X-ray crys-
tallographic analysis (Fig. 2).21–23
4a
1
2
3
230–232
228–231
223–225
2
+
+
+
N
5a
(6)
(80)
O
N
NH
Br
4b
2
N
5b
Br
Br
(4)
(76)
O
Br
N
NH
4c
2
N
5c
(4)
(78)
O
Br
The X-ray crystallographic analysis shows that both crystal
units of 3 and 5a include one water molecule and the geometrical
parameters of the heterocycles of both molecules 3 and 5a are
equivalent within experimental error. According to the PLATON
program calculations, the dihedral angles between the benzimid-
azole and quinoline planes in molecules 3 and 5a are 56.47(8)
and 50.5(1)°, respectively.24 The slight decrease of this angle in
5a could be due to the presence of the phenyl substituent, thus
N
NH
4d
Br
4
5
6
248–250
239–241
245–246
2
+
N
5d
(4)
(73)
O
increasing the delocalization of the p-system of the benzimidazole
N
NH
and quinoline heterocycles. In spite of this fact, the dihedral angle
between the quinoline and phenyl planes in molecule 5a is signif-
icant and equal to 30.6(1)°. We only found about 50 structures in
the Cambridge Structural Database25 with aromatic substituents
at 2 and 4 positions of the quinoline heterocycle. Some of these
are annelated structures, thus we chose five basic structures with
simple substituents in the corresponding positions in order to
compare the values of the dihedral angles.26–30 The values of the
dihedral angles between the substituent and quinoline planes are
3.87(5)–26.7(1)° for position 2, and 52.27(5)–89.7(1)° for position
4 (Table 3).
In conclusion, we have developed a cascade reaction involving
Friedländer/quinoxaline–benzimidazole rearrangement for the
facile synthesis of 4-(benzimidazol-2-yl)quinoline and benzimi-
dazolo[2,1-a]pyrrolo[3,4-c]quinoline derivatives. The mechanisms
for the formation of the resulting 4-(benzimidazol-2-yl)quinoline
and benzimidazolo[2,1-a]pyrrolo[3,4-c]quinoline derivatives are
proposed to involve a new acid-catalyzed rearrangement of the
Cl
4e
2
+
N
5e
Cl
(4)
(77)
O
Cl
N
NH
4f
Cl
2
+
N
5f
(4)
(71)
a
Isolated yields.

4322
V. A. Mamedov et al. / Tetrahedron Letters 55 (2014) 4319–4324
H
N
H
N
H
N
N
4, H
Ar
1
HN
H
Ar
H
HN
Ar
H
H
OH
- H2O
N
H
N
H
O
N
H
O
H
A
C
D
B
H
H
H
H
N
N
NH2
NH
OH
Ar
5
N
N
H
-H2O
-H+
H
N
H
O
H2O
N
N
F
E
Ar
Ar
Scheme 3. A plausible mechanism for the formation of 4-(benzimidazol-2-yl)quinolines 5.
AcOH, 55 oC, 6 h
then reflux, 3 h
N
O
O
HN
N
N
O
1
+
O
OEt
-2H2O
OEt
1 equiv
3 equiv
-EtOH
N
6
N
8
(75%)
7
Scheme 4. Reaction of 3-(2-aminophenyl)quinoxalin-2(1H)-one (1) with ethyl acetoacetate (6).
Figure 1. The characteristic molecular ion peaks for 4-(benzimidazol-2-yl)quinolines with the 4-chlorophenyl 5e (a) and 4-bromophenyl 5b (b) groups.
Table 3
The values of the dihedral angles between the quinoline system and the substituents
at the 2 and 4 positions of the selected structures26–30
Substituent at
position 2 of the
quinoline
Substituent at
position 4 of the
quinoline
Quinoline
heterocycle/
substituent 2
Quinoline
heterocycle/
substituent 4
Ref.
heterocycle
heterocycle
Ph
Ph
Ph
Ph
Ph
21.3(1)
23.05(7)
3.87(5)
18.1(1)
26.7(1)
65.0(1)
61.75(6)
52.27(5)
64.8(1)
89.7(1)
25
26
27
28
29
2-Py
4-ClC6H4
3-MeOC6H4
4-O2NC6H4
2-ClC6H4
spiro-quinoxalinones formed in situ from the reaction of 3-(2-ami-
nophenyl)quinoxalin-2(1H)-ones and ketones under modified
Friedländer reaction conditions. This method has the advantages
of mild conditions, simple work-up, high yields, and a wide sub-
strate scope, which should make it very useful for the synthesis
of multisubstituted and condensed quinolines.
Figure 2. ORTEP plots of compounds 3 (a) and 5a (b) and partial numbering
schemes. Displacement ellipsoids are drawn at the 30% probability level. H-atoms
are represented in stick mode for clarity. Solvent water molecules are omitted for
clarity.

V. A. Mamedov et al. / Tetrahedron Letters 55 (2014) 4319–4324
4323
Tetrahedron Lett. 2011, 52, 1228; (d) Ghandi, M.; Zarezadeh, N.; Taheri, A.
Tetrahedron 2010, 66, 8231.
Acknowledgments
15. Typical procedure for the synthesis of 2-aryl-4-(benzimidazol-2-yl)quinolines 5a–
f: 3-(2-Aminophenyl)quinoxalin-2(1H)-one (1) (0.20 g, 0.84 mmol) and
acetophenone 4a–f (2.36 mmol) in glacial AcOH (6 mL) were heated for 5 h
at 55 °C. The solvent was evaporated and the residue was triturated with Et2O
(5 mL). The resulting precipitate was filtered off and dried under air to yield
9.00–14.40 mg (5–8%) of compound 2. Purification by column chromatography
with hexane/i-PrOH (98:2) as the eluent afforded analytically pure 7.20,
10.80 mg (4.0, 6.0%) of 2 as white crystals, Rf 0.58 (CHCl3/n-C6H14/MeOH,
6:3:1), mp 299–300 °C (lit.31 294–295 °C). The ether filtrates were concen-
trated and the residues were purified by column chromatography with i-PrOH
or a mixture of n-C6H14/i-PrOH as eluents to give analytically pure compounds
5a,c,d,e. In the cases of acetophenones 4b and 4f, precipitation of crystals from
the reaction mixture occurred, which were filtered off and washed with Et2O
(3 ꢁ 5 mL), and dried under air to afford analytically pure quinolines 5b and 5f.
Additional amounts of quinolines 5b and 5f were obtained from the evapo-
rated ether mother solution on triturating with i-PrOH (in the case of 5b) and
Et2O (in the case of 5f).
This work was supported by the Russian Foundation for Basic
Research (grants no 13-03-00123-a, 14-03-31194-mol_a).
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6
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8
Ar
5e
Cl
Data for 5e: lilac crystals, Rf = 0.60, i-PrOH. IR (Nujol, cmꢂ1
) m 3362, 3152, 3052,
1595, 1546, 1436, 1339, 1273, 1094, 837, 770, 745. 1H NMR (400 MHz, DMSO-
d6) d 7.29–7.37 (m, 2H, H5+H6 BI), 7.60 (d, 2H, J = 8.6 Hz, H3+H5 Ar), 7.68 (ddd,
1H, J = 7.7, 7.7, 1.4 Hz, H6 Q), 7.70–7.78 (m, 2H, H4+H7 BI), 7.84 (ddd, 1H,
J = 7.6, 7.6, 1.6 Hz, H7 Q), 8.14 (d, 1H, J = 7.7 Hz, H8 Q), 8.30 (d, 2H, J = 8.6 Hz,
H2+H6 Ar), 8.46 (s, 1H, H3 Q), 9.14 (dd, 1H, J = 7.7, 1.3 Hz, H5 Q), 13.36 (s, 1H,
H1 BI); 13C NMR (100 MHz, DMSO-d6) d 112.5 (C7 BI), 118.9 (C3 Q), 120.0 (C4
BI), 123.4 (C5 BI), 124.1 (C6 BI), 124.3 (C4a Q), 126.9 (C5 Q), 128.2 (C6 Q),
129.50 (C3+C5 Ar), 129.53 (C2+C6 Ar), 130.1 (C8 Q), 131.0 (C7 Q), 134.9 (C7a
BI), 135.4 (C4 Ar), 136.4 (C4 Q), 137.5 (C1 Ar), 144.2 (C3a BI), 148.9 (C8a Q),
149.5 (C2 BI), 155.2 (C2 Q). MS (ESI) m/z 356 [M+H]+; HRMS (MALDI) m/z
[M+H]+ calcd for C22H15ClN3: 356.0949. Found: 356.0918. Calcd for C22H14-
ClN3: C, 74.26; H, 3.97; N, 11.81. Found: C, 74.47; H, 3.86; N, 11.65.
16. Smith, M.B.; March, J. In: March’s Advanced Organic Chemistry, 5th ed.; Wiley:
New York, 2001; pp 1185–1187.
17. Wang, Z. Comprehensive Organic Name Reactions and Reagents; Wiley: Hoboken,
New Jersey, 2009; pp 1137–1142, vol. 1.
18. Rappoport, Z. The Chemistry of Enamines; Wiley: Chichester, 1994.
19. Cheeseman, G. W. H.; Cookson, R. F. Condensed Pyrazines; Wiley-Interscience
Publication: New York, 1979.
20. Synthesis of 8-methyl-7H-benzimidazolo[2,1-a]pyrrolo[3,4-c]quinolin-7-one (8).
3-(2-Aminophenyl)quinoxalin-2(1H)-one (1) (0.20 g, 0.84 mmol) and ethyl
acetoacetate (6) (0.33 g, 2.53 mmol) in AcOH (6 mL) were heated for 6 h at
55 °C. The mixture was heated further for 3 h at reflux. After completion of the
reaction, the solvent was evaporated and the residue was purified through a
short pad of silica gel eluting with hexane/i-PrOH (96:4) to afford 0.18 g (75%)
11. Arcadi, A.; Chiarini, M.; Giuseppe, S. D.; Marinelli, F. Synlett 2003, 203.
12. Palimkar, S. A.; Siddiqui, S. A.; Daniel, T.; Lahoti, R. J.; Srinivasan, K. V. J. Org.
Chem. 2003, 68, 9371.
13. (a) Mamedov, V. A.; Saifina, D. F.; Gubaidullin, A. T.; Saifina, A. F.; Rizvanov, I.
Kh. Tetrahedron Lett. 2008, 49, 6231; (b) Mamedov, V. A.; Khafizova, E. A.;
Gubaidullin, A. T.; Murtazina, A. M.; Adgamova, D. I.; Samigullina, A. I.;
Litvinov, I. A. Russ. Chem. Bull., Int. Ed. 2011, 60, 368; (c) Mamedov, V. A.;
Zhukova, N. A.; Sykaev, V. V.; Gubaidullin, A. T.; Beschastnova, T. N.; Adgamova,
D. I.; Samigullina, A. I.; Latypov, Sh. K. Tetrahedron 2013, 69, 1403; (d) Kalinin,
A. A.; Mamedov, V. A.; Levin, Ya. A. Chem. Heterocycl. Compd. 2000, 36, 882; (e)
Mamedov, V. A.; Kalinin, A. A.; Gubaidullin, A. T.; Chernova, A. V.; Litvinov, I. A.;
Levin, Ya. A. Russ. Chem. Bull., Int. Ed. 2004, 53, 164; (f) Kalinin, A. A.; Isaikina, O.
G.; Mamedov, V. A. Chem. Heterocycl. Compd. 2007, 43, 1307; (g) Mamedov, V.
A.; Saifina, D. F.; Rizvanov, I. Kh.; Gubaidullin, A. T. Tetrahedron Lett. 2008, 49,
4644; (h) Mamedov, V. A.; Zhukova, N. A.; Beschastnova, T. N.; Gubaidullin, A.
T.; Balandina, A. A.; Latypov, Sh. K. Tetrahedron 2010, 66, 9745; (i) Mamedov, V.
A.; Kalinin, A. A.; Gubaidullin, A. T.; Gorbunova, E. A.; Litvinov, I. A. Russ. J. Org.
Chem. 2006, 42, 1532; (j) Mamedov, V. A.; Zhukova, N. A.; Beschastnova, T. N.;
Zakirova, E. I.; Kadyrova, S. F.; Mironova, E. V.; Nikonova, A. G.; Latypov, Sh. K.;
Litvinov, I. A. Tetrahedron Lett. 2012, 53, 292; (k) Mamedov, V. A.; Zhukova, N.
A.; Beschastnova, T. N.; Gubaidullin, A. T.; Rakov, D. V.; Rizvanov, I. Kh.
Tetrahedron Lett. 2011, 52, 4280; (l) Mamedov, V. A.; Saifina, D. F.; Gubaidullin,
A. T.; Ganieva, V. R.; Kadyrova, S. F.; Rakov, D. V.; Rizvanov, I. Kh.; Sinyashin, O.
G. Tetrahedron Lett. 2010, 51, 6503; (m) Mamedov, V. A.; Murtazina, A. M.;
Gubaidullin, A. T.; Hafizova, E. A.; Rizvanov, I. Kh. Tetrahedron Lett. 2009, 50,
5186; (n) Mamedov, V. A.; Murtazina, A. M.; Gubaidullin, A. T.; Khafizova, E. A.;
Rizvanov, I. Kh.; Litvinov, I. A. Russ. Chem. Bull., Int. Ed. 2010, 59, 1645; (o)
Mamedov, V. A.; Murtazina, A. M. Russ. Chem. Rev. 2011, 80, 397; (p) Mamedov,
V. A.; Zhukova, N. A. In Progress in Heterocyclic Chemistry; Gribble, G. W., Joule, J.
A., Eds.; Elsevier: Amsterdam, 2013; pp 1–45, vol. 25, Chapter 1; (q) Hassner,
A.; Namboothiri, I. Organic Syntheses Based on Name Reactions, 3th ed.; Elsevier:
Amsterdam, 2012; pp 299–300.
of analytically pure 8 as an orange powder.
3
2
4
5
1a
1 N
5a
6
BI
13c
13b
N
13
10
13a
O
12
11
7
7a
Q
8
9a
N
9
8
Data for 8: Rf 0.55, mp 216–218 °C. IR (KBr, cmꢂ1
) m 3422, 1753, 1618, 1561,
1483, 1429, 1365, 1290, 1129, 771, 748. 1H NMR (DMSO-d6, 400 MHz) d 2.94 (s,
3H, CH3), 7.24 (ddd, 1H, 3J = 7.7, 7.4 Hz, 4J = 1.1 Hz, H3), 7.33 (ddd, 1H, 3J = 7.8,
7.6 Hz, 4J = 1.1 Hz, H4), 7.60 (br dd, 1H, 3J = 8.5, 7.8 Hz, H12), 7.69 (br d, 1H,
3J = 7.7 Hz, H2), 7.70 (br d, 1H, 3J = 7.7 Hz, H5), 7.79 (ddd, 1H, 3J = 8.5, 7.8 Hz,
4J = 1.2 Hz, H11), 7.97 (d, 1H, 3J = 8.5 Hz, H10), 8.60 (d, 1H, 3J = 8.5 Hz, H13);
13C{1H} NMR (DMSO-d6, 100 MHz) d 21.2 (CH3), 112.1 (C5), 119.8 (C13a), 121.4
(C2), 123.8 (C7a), 124.8 (C3), 125.2 (C13), 127.2 (C4), 128.0 (C12), 128.7 (C10),
129.1 (C5a), 133.1 (C11), 138.9 (C13b), 149.2 (C1a), 150.8 (C9a), 154.6 (C13c),
155.8 (C8), 160.5 (C7); 15N NMR (DMSO-d6, 60 MHz) d 316.1 (N9). MS (ESI) m/z
286 [M+H]+, HRMS (MALDI) m/z [M+H]+ Calcd for C18H12N3O: 286.0975.
Found: 286.0961. Calcd for C18H11N3O: C, 75.78; H, 3.89; N, 14.73. Found: C,
75.53; H, 3.77; N, 14.55.
21. The X-ray diffraction data for crystals of 3 were collected on a Bruker AXS
Smart APEX II CCD diffractometer at 296 K. Crystallographic data for 3.
C
17H13N3ꢃH2O, colorless prisms, formula weight 277.32, triclinic, Pꢂ1,
14. (a) Ghandi, M.; Zarezadeh, N.; Taheri, A. Tetrahedron Lett. 2012, 53, 3353; (b)
Yang, Y.; Gao, M.; Wu, L.-M.; Deng, C.; Zhang, D.-X.; Gao, Y.; Zhu, Y.-P.; Wu, A.-
X. Tetrahedron 2011, 67, 5142; (c) Ghandi, M.; Zarezadeh, N.; Taheri, A.
a = 7.284(1) Å, b = 9.172(2) Å, c = 11.855(2) Å,
c
l
a = 97.961(2)°, b = 100.902(2)°,
= 111.339(2)°,
V = 705.5(2) Å3,
F(000) = 292,
Z = 2,
reflections
q
calc = 1.305 g cmꢂ3
collected = 9000,
,
(kMoK ) = 0.84 cmꢂ1
,
a

4324
V. A. Mamedov et al. / Tetrahedron Letters 55 (2014) 4319–4324
unique = 2771, R(int) = 0.0380, full matrix least squares on F2, parameters = 203,
restraints = 0. Final indices R1 = 0.0528, wR2 = 0.1190 for 1715 reflections with I
to CCDC, 12 Union Road, Cambridge CB2 1EZ, UK [fax: +44 (0)1223 336033 or
e-mail: deposit@ccdc.cam.ac.uk].
24. Spek, A. L. Acta Cryst. (A) 1990, 46, 34.
25. Cambridge Structural Database. Version 5.32. University of Cambridge, UK.
26. Ahmet, M. T.; Miller, J. R.; Osborne, A. G.; Warmsley, J. F. Acta Cryst. (C) 1995,
51, 2105.
>2r
(I); R1 = 0.0979, wR2 = 0.1426 for all data, goodness-of-fit on F2 = 1.012,
largest difference in peak and hole (0.310 and –0.165 e Åꢂ3).
22. The X-ray diffraction data for crystals of 5a were collected on a Bruker AXS
Smart APEX II CCD diffractometer at 296 K. Crystallographic data for 5a.
C
22H15N3ꢃH2O, colorless prisms, formula weight 339.39, monoclinic,
P21/c, a = 13.514(3) Å, b = 10.286(2) Å, c = 13.488(3) Å, b = 105.677(3)°,
V = 1805.0(6) Å3, Z = 4, calc = 1.249 g cmꢂ3 (kMoK ) = 0.79 cmꢂ1, F(000) = 712,
27. Zhu, R.-T.; Jin, S.; Liu, B.; Guo, J.-P.; Huaxue Yanjiu Chin. Chem. Res. 2006, 17, 35.
28. Chen, X.; Qiu, D.; Ma, L.; Cheng, Y.; Geng, Y.; Xie, Z.; Wang, L. Transition Met.
Chem. 2006, 31, 639.
q
, l
a
reflections collected = 13321, unique = 3543, R(int) = 0.0669, full matrix least squares
29. Rotzoll, S.; Willy, B.; Schönhaber, J.; Rominger, F.; Müller, T. J. J. Eur. J. Org.
Chem. 2010, 18, 3516.
on F2, parameters = 247, restraints = 0. Final indices R1 = 0.0540, wR2 = 0.1183 for
1652 reflections with I >2
r(I); R1 = 0.1430, wR2 = 0.1566 for all data, goodness-of-fit
30. Mohammdpoor-Baltork, I.; Tangestaninejad, S.; Moghadam, M.; Valiollah, M.;
Salma, A.; Arsalan, M. Synlett 2010, 3104.
31. Sarkis, G. Y.; Al-Badri, H. T. J. Heterocycl. Chem. 1980, 17, 813; (b) Shibinskaya,
M. O.; Kutuzova, N. A.; Mazepa, A. V.; Lyakhov, S. A.; Andronati, S. A.; Zubritsky,
M. Ju.; Galat, V. F.; Lipkowski, J.; Kravtsove, V. Ch. J. Heterocycl. Chem. 2012, 49,
678.
on F2 = 0.992, largest difference in peak and hole (0.188 and ꢂ0.174 e Åꢂ3).
23. Crystallographic data (except structure factors) for the compounds 3 and 5a in
this Letter have been deposited with the Cambridge Crystallographic Data
Centre as supplementary publication numbers CCDC 930952 and 930953,
respectively. Copies of the data can be obtained, free of charge, on application