Synthesis of novel fluorescent benzo[a]pyrano[2,3-c]phenazine and benzo[a]chromeno[2,3-c]phenazine derivatives via facile four-component domino protocol

Article abstract of DOI:10.1016/j.tetlet.2014.04.072

An efficient and practical route to novel fluorescent benzo[a]pyrano[2,3-c] phenazine framework has been developed by one-pot, four-component reaction of 2-hydroxynaphthalene-1,4-dione, 1,2-phenylenediamines, aromatic aldehydes, and Meldrum's acid in glacial acetic acid at 70 °C. Photophysical studies of these compounds have been reported. Reactions involving cyclohexane-1,3-dione/5- methylcyclohexane-1,3-dione/dimedone in the place of Meldrum's acid yielded corresponding benzo[a]chromeno[2,3-c]phenazine derivatives. Crystal structure of 3k established the regioisomer formed. Mild reaction conditions, good yields, short reaction time, and easy separation are some of the salient features of the present protocol.

Full text of DOI:10.1016/j.tetlet.2014.04.072

Tetrahedron Letters xxx (2014) xxx–xxx
Contents lists available at ScienceDirect
Tetrahedron Letters
journal homepage: www.elsevier.com/locate/tetlet
Synthesis of novel fluorescent benzo[a]pyrano[2,3-c]phenazine
and benzo[a]chromeno[2,3-c]phenazine derivatives via facile
four-component domino protocol
⇑
Pooja Saluja, Ankita Chaudhary, Jitender M. Khurana
Department of Chemistry, University of Delhi, Delhi 110007, India
a r t i c l e i n f o
a b s t r a c t
Article history:
An efficient and practical route to novel fluorescent benzo[a]pyrano[2,3-c]phenazine framework has been
developed by one-pot, four-component reaction of 2-hydroxynaphthalene-1,4-dione, 1,2-phenylenedi-
amines, aromatic aldehydes, and Meldrum’s acid in glacial acetic acid at 70 °C. Photophysical studies
of these compounds have been reported. Reactions involving cyclohexane-1,3-dione/5-methylcyclohex-
ane-1,3-dione/dimedone in the place of Meldrum’s acid yielded corresponding benzo[a]chromeno
[2,3-c]phenazine derivatives. Crystal structure of 3k established the regioisomer formed. Mild reaction
conditions, good yields, short reaction time, and easy separation are some of the salient features of the
present protocol.
Received 1 February 2014
Revised 19 April 2014
Accepted 21 April 2014
Available online xxxx
Keywords:
Multi-component reaction
2-Hydroxynaphthalene-14-dione
12-Phenylenediamines
Meldrum’s acid
Ó 2014 Elsevier Ltd. All rights reserved.
Phenazine
Acetic acid
The development of convergent, atom-economic, expedient,
and eco-friendly chemical methods is of utmost interest in modern
synthetic chemistry. In particular, single-step or cascade reactions,
such as multi-component reactions (MCRs)1 often provide an
inherently more efficient approach to chemical synthesis than con-
ventional bimolecular reactions. MCRs provide a powerful tool for
the discovery of new chemical entities required by pharmaceutical
and agrochemical industries.2 Therefore, designing of novel MCRs
for the synthesis of diverse biologically active compounds has
commanded great attention.3
Phenazines are present in natural and synthetic products show-
ing a variety of biological functions, including antibiotic, antimi-
crobial, antimalarial and antiparasitic activities.4–7 By virtue of
their DNA intercalating ability, they exhibit antitumor activity in
leukemia and solid tumors. For example, pyridophenazinediones
and pyridazinophenazinedione derivatives are known for their
antitumor activities.8,9
phenazine derivatives are well reported, pyranophenazines incor-
porating both phenazine and pyran moieties have not received as
much attention.15 We therefore sought to develop a simple and
versatile procedure for the synthesis of a new class of pyranophen-
azine derivatives namely, benzo[a]pyrano[2,3-c]phenazines.
This is the first report on the glacial acetic acid catalyzed four-
component condensation for the synthesis of highly functionalized
novel benzo[a]pyrano[2,3-c]phenazines (Scheme 1) and their
photophysical studies. The protocol could also be extended for
the synthesis of benzo[a]chromeno[2,3-c]phenazines (Scheme 2).
Recently synthesis of novel benzo[a]chromeno[2,3-c]phenazine
annulated heterocycles had been reported by our group.16
The optimization of the reaction conditions was evolved after
attempting model reactions of 2-hydroxynaphthalene-1,4-dione
(1.0 mmol), 1,2-phenylenediamine (1.0 mmol), 4-chlorobenzalde-
hyde (1.0 mmol), and Meldrum’s acid (1.0 mmol) using different
catalysts, different solvents, and also under solvent less conditions.
Initially, reactions were carried out in EtOH–H2O (1:1, v/v) as sol-
vent at 80 °C with catalytic amount (10 mol %) of p-TSA, HCl,
H2SO4, and InCl3. All the reactions were sluggish and discarded.
The reaction carried out in H2O at 100 °C using Gl. AcOH
(10 mol %) as catalyst went to completion and yielded a mixture
of products. The desired product 1-(4-chlorophenyl)-1H-
benzo[a]pyrano[2,3-c]phenazin-3(2H)-one (2a), characterized by
spectroscopic analysis was obtained in only 25% yield (Table 1,
entry 1).
Fluorescent phenazine derivatives both natural and synthetic,
are also of interest because of their rapidly expanding applications
as emitters for electroluminescence devices,10 organic semicon-
ductors,11 photo-sensitizers in photodynamic therapy,12 promoter
for proliferation,13 electrochemical, and biosensors.14 Though
⇑
Corresponding author. Tel.: +91 11 2766772; fax: +91 1 27667624.
E-mail addresses: jmkhurana1@yahoo.co.in, jmkhurana@chemistry.du.ac.in
(J.M. Khurana).
http://dx.doi.org/10.1016/j.tetlet.2014.04.072
0040-4039/Ó 2014 Elsevier Ltd. All rights reserved.
Please cite this article in press as: Saluja, P.; et al. Tetrahedron Lett. (2014), http://dx.doi.org/10.1016/j.tetlet.2014.04.072

2
P. Saluja et al. / Tetrahedron Letters xxx (2014) xxx–xxx
O
OH
O
O
O
O
O
R
NH2
NH2
Gl. AcOH
70 o
ArCHO,
O
O
+
OH
N
R
N
N
R
Gl. AcOH, 70 oC
N
Ar
C
R'
R = H, Cl
R' = H, Cl, CH3
R'
R'
2a-n
Scheme 1.
O
OH
O
O
O
R
NH2
NH2
ArCHO,
N
R
Gl. AcOH
70 oC
O
+
N
Ar
O
N
N
R
R'
OH
Gl. AcOH, 70 oC
3a-q
R'
R = H, R' = H, CH3
R'
O
O
O
O
=
O
,
O
,
O
O
I
II
III
Scheme 2.
Table 1
Optimization of reaction conditions for the synthesis of 1-(4-chlorophenyl)-1H-benzo[a]pyrano[2,3-c]phenazin-3(2H)-one (2a)
Entry
Solvent
Catalyst
Catalyst (mol %)
Temp (°C)
Time (h)
Yield (2a) (%)
1
2
3
4
5
6
7
8
H2O
H2O
EtOH–H2O
EtOH
CH3CN
—
Gl. AcOH
Gl. AcOH
Gl. AcOH
Gl. AcOH
Gl. AcOH
Gl. AcOH
Gl. AcOH
Gl. AcOH
10
10
10
10
10
10
5
100
100
80
80
70
70
70
70
5
6
6
6
6
3
6
3
25a,c
40b,d
53b,d
71b
50b,d
82b
—
—
68b,d
90b
20
a
2-Hydroxynaphthalene-1,4-dione (1.0 mmol), 1,2-phenylenediamine (1.0 mmol), 4-chlorobenzaldehyde (1.0 mmol), Meldrum’s acid (1.0 mmol), and catalyst (0.1 mmol)
were added simultaneously.
b
2-Hydroxynaphthalene-1,4-dione (1.0 mmol), 1,2-phenylenediamine (1.0 mmol), and catalyst were first allowed to stir in solvent at appropriate temp for 30 min,
followed by addition of 4-chlorobenzaldehyde (1.0 mmol) and Meldrum’s acid (1.0 mmol).
c
Mixture of products.
Incomplete reaction.
d
The above reaction was attempted by stepwise addition to
minimize formation of by-products. Therefore, a reaction of 2-
hydroxynaphthalene-1,4-dione (1.0 mmol) and 1,2-phenylenedi-
amine (1.0 mmol) was carried out initially in H2O at 100 °C using
Gl. AcOH (10 mol %) as catalyst followed by addition of 4-chloro-
benzaldehyde (1.0 mmol) and Meldrum’s acid (1.0 mmol) in the
same pot. The reaction was incomplete after 6 h, but afforded
40% of 2a after separation (Table 1, entry 2). Subsequently, the
reactions catalyzed by Gl. AcOH attempted in EtOH–H2O (1:1, v/
v), EtOH, and CH3CN, resulted in the formation of the desired prod-
uct 2a in 53%, 71%, and 50% yield, respectively (Table 1, entries 3–
5). The reaction attempted using Gl. AcOH (10 mol %) as catalyst in
the absence of any solvent at 70 °C was complete in 3 h and affor-
ded the desired product 2a in 82% yield after a simple work-up
(Table 1, entry 6 and Scheme 1).
acid using 20 mol % of Gl. AcOH as catalyst in the absence of any
solvent at 70 °C proved to be the optimum condition, wherein Mel-
drum’s acid serves as ketene equivalent.
The optimized reaction conditions were then applied to reac-
tions of equimolar amounts of 2-hydroxynaphthalene-1,4-dione,
1,2-phenylenediamine, and Meldrum’s acid with different alde-
hydes having electron withdrawing and electron releasing groups.
All the reactions proceeded smoothly to yield the novel
benzo[a]pyrano[2,3-c]phenazines (2b–i) in high yields (78–91%)
(Table 2, entries 1–9). Reactions carried out with 4,5-dichloroben-
zene-1,2-diamine and 4-methylbenzene-1,2-diamine instead of
1,2-phenylenediamine also afforded the corresponding benzo[a]
pyrano-[2,3-c]phenazines (2j–n) in high yields (80–92%) (Table 2,
entries 10–15 and Scheme 1). However no reactions were observed
with aliphatic aldehydes.
The above reaction performed using 5 mol % of Gl. AcOH at
70 °C was incomplete even after 6 h while a higher yield of 2a
was obtained using 20 mol % Gl. AcOH in the absence of any sol-
vent (Table 1, entries 7 and 8). The reactions carried out with
20 mol % Gl. AcOH at room temperature and also in the absence
of catalyst were not satisfactory even after 24 h. Therefore, a one
pot domino reaction of equimolar amounts of 2-hydroxynaphtha-
lene-1,4-dione, 1,2-phenylenediamine, aldehyde, and Meldrum’s
Further we explored the above optimized sequential four-com-
ponent domino protocol for the condensation of equimolar
amounts of 2-hydroxynaphthalene-1,4-dione, 1,2-phenylenediam-
ines, active methylene cyclic 1,3-diketones (I–III) instead of Mel-
drum’s acid with different aldehydes in the presence of 20 mol %
of Gl. AcOH at 70 °C. All the reactions were complete in 2–3.5 h
and resulted in the formation of the corresponding benzo[a]chro-
meno-phenazine derivatives (3a–q) (Scheme 2 and Table 3 entries
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P. Saluja et al. / Tetrahedron Letters xxx (2014) xxx–xxx
3
Table 2
The regioselectivity in the reaction arises due to initial attack of
more nucleophilic NH2 group which is para to the methyl group
of 4-methylbenzene-1,2-diamine on the more electrophilic carbon
of 2-hydroxynaphthalene-1,4-dione thus leading to the formation
of only one favorable regioisomer, which subsequently reacts with
aldehyde and Meldrum’s acid to give desired phenazine derivative.
Also, the synthesized phenazine derivatives were found to be opti-
cally inactive and thus believed to be racemic mixtures.
The synthesis of benzo[a]pyranophenazine (2) is believed to be
proceeding via sequential condensation, Michael addition, cycliza-
tion, and elimination (Scheme 3). Initially, 2-hydroxynaphthalene-
1,4-dione and 1,2-phenylenediamine undergo condensation to
afford benzo[a]phenazin-5-ol (A). Simultaneously the Knoevenagel
condensation between an aldehyde and Meldrum’s acid yields the
arylidene Meldrum’s acid (B). Subsequently benzo[a]phenazin-5-ol
(A) undergoes Michael type addition to arylidene Meldrum’s acid
(B) to give intermediate (C) which undergoes cyclization with loss
of acetone and carbon dioxide simultaneously to afford the desired
compound 2.
Synthesis of benzo[a]pyrano[2,3-c]phenazine derivatives (2a–n) using Gl. AcOH as
catalyst at 70 °C
Entry
Product
Ar
R
R0
Time (h)
Yield (%)
1
2
3
4
5
6
7
8
2a
2b
2c
2d
2e
2f
2g
2h
2i
2j
2k
2l
2m
2n
4-ClC6H4
H
H
H
H
H
H
H
H
H
H
H
H
H
Cl
H
H
H
H
H
H
H
H
3
3
3
3
3.5
2.5
2
3.5
3
2
2
2.5
3
3
90
85
84
80
78
90
91
81
84
91
92
82
84
80
4-(NO2)C6H4
3-(NO2)C6H4
4-(CH3)C6H4
4-(OCH3)C6H4
4-FC6H4
4-(F3C)C6H4
2-(CH3)C6H4
C6H5
9
H
10
11
12
13
14
4-FC6H4
CH3
CH3
CH3
CH3
Cl
4-(F3C)C6H4
4-(CH3)C6H4
3,4,5-(CH3O)3C6H2
4-(NO2)C6H4
The formation of A was observed in the reaction. Also, the reac-
tion of pre-formed intermediates benzo[a]phenazin-5-ol (A) and
Knoevenagel adduct (B) independently under identical conditions
gave the product 2a thus supporting the proposed reaction path-
way (Scheme 4).
1–17). There is no significant effect of substituents both electron
withdrawing and donating on the reaction time and yield of the
products as evident from Table 3. Structural assignments have
been made on the basis of IR, 1H NMR, 13C NMR, and mass spectra.
The structure of the synthesized novel benzo[a]chromeno[2,3-
c]phenazine derivative (3k) has been confirmed by the single crys-
tal X-ray diffraction analysis to assign the position of the aromatic
methyl group when 4-methylbenzene-1,2-diamine was used
instead of symmetrical 1,2-phenylenediamine as two different
regioisomers are possible. All our attempts to obtain single crystals
of compounds 2 were not successful. Single crystal of 3k suitable
for X-ray diffraction was obtained by evaporation of CHCl3/heptane
solutions at ambient temperature. The structural resolution of 3k
showed that two disordered molecules of CHCl3 crystallization sol-
vent are located in channels in the crystal. The molecular structure
of 3k with atom labeling is reported in Figure 1. It crystallizes in
the P-1 space group. All bond lengths and angles are normal and
in agreement with similar compounds.17,18 The calculated struc-
ture provides accurate molecular shapes, with the pyran ring of
3k in pseudo boat conformation with atomic displacement of
0.133 Å (for O1) and 0.257 Å (for C24) from mean plane of C11,
C10, C23, and C18. Chiral carbon C20 deviates 0.777 Å from mean
plane of C19, C18, C23, C22, and C21. The angle between the two
planes containing C10, C11, C23, C18 and C25, C26, C27, C28,
C29, C30 is 86.24°. Compound 3k owns two chiral centers, with
‘R’ configuration at C20 and ‘S’ at C24 as revealed from the crystal
structure (Fig. 2).
Photophysical studies
Electronic absorption and photoluminescent properties of all
new benzo[a]pyranophenazine derivatives (2a–n) were studied
in CHCl3. The 1.0 ꢀ 10ꢁ5 mol Lꢁ1 solution of compounds (2a–n)
showed three absorption maxima, a strong band I in the region
of 275–290 nm and two weak bands II and III in the region of
380–430 nm (Fig. S1). Moreover, when these compounds were
excited at 280 nm (kmax), they exhibited strong photoluminescent
emissions with the emission maxima ranging from peaks varying
from 428 to 449 nm (Fig. S2). The spectrophotometric properties
of the compounds such as absorption maxima (kmax), emission
maxima (kem), molar extinction coefficient (e), and stokes shift
are listed in Table S1. The large magnitude of Stokes shift was
observed for all the benzo[a]pyranophenazine derivatives (2a–n)
which indicates that the excited state geometry could be different
from that of the ground state. Fluorescent compounds with partic-
ularly high Stokes shift possess application in fields, where long
optical path are required like sunlight collection,19 scintillation,20
and various biological applications. It can also be observed from
Table S1 that there is only a slight change in kem and the Stokes
Table 3
Synthesis of benzo[a]chromeno[2,3-c]phenazine derivatives (3a–q) using Gl. AcOH as catalyst at 70 °C
Entry
Product
Ar
R
R0
1,3-Dicarbonyl compound
Time (h)
Yield (%)
1
2
3
4
5
6
7
8
3a
3b
3c
3d
3e
3f
3g
3h
3i
3j
3k
3l
3m
3n
3o
3p
3q
4-(CH3O)C6H4
3,4,5-(CH3O)3C6H2
Thien-2-yl
2-Naphthyl
C6H5
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
I
I
I
I
I
I
I
II
II
II
II
II
III
III
III
III
III
2
2.5
3
2.5
2
2.5
3
2.5
2.5
2
2.5
2
3
3
2.5
2.5
2
85
88
80
82
86
90
85
81
84
80
86
84
80
81
80
85
82
H
4-FC6H4
CH3
CH3
H
H
H
CH3
CH3
H
H
H
4-(OH),3-(CH3O)C6H3
3,4-(CH3O)2C6H3
3,4,5-(CH3O)3C6H2
2-Naphthyl
3,4,5-(CH3O)3C6H2
2-Naphthyl
3,4-(CH3O)2C6H3
4-(OH),3-(CH3O)C6H3
2-Naphthyl
3,4,5-(CH3O)3C6H2
2-Naphthyl
9
10
11
12
13
14
15
16
17
CH3
CH3
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P. Saluja et al. / Tetrahedron Letters xxx (2014) xxx–xxx
Figure 1. X-ray crystallographic structure of 3k.
Figure 2. (a) Chemical structure of compound 3k showing stereochemistry; (b) a perspective view of compound 3k.
OH
O
O
O
O
OH
H2N
H2N
R
Gl.AcOH
Gl.AcOH
N
R
+
O
O
+
O
O
+
ArCHO
N
R'
Ar
O
O
N
(A)
(B)
R'
OH
O
O
O
OH
O
O
H+
O
O
N
R
N
R
Ar
N
R
N
Ar
-CH3COCH3
-CO2
O
O
N
Ar
O
R'
R'
(C)
R'
Scheme 3.
O
and the data are listed in Table S2. No significant shift was
observed in absorption spectra with varying solvent polarity. The
emission spectra were found to be more sensitive to the nature
of the solvents polarity, and hence a significant increase in Stokes
shift was observed with increasing solvent polarity (Table S2),
which indicates a larger charge transfer taking place in the excited
state in comparison to the ground state. The Stokes shifts of 2c in
solvents of different polarity have been correlated with solvent
HO
N
O
O
O
O
Gl. AcOH
70 oC
+
CH
Cl
N
N
O
N
(A)
(B)
2a
Cl
Scheme 4.
polarity parameter
solvent–fluorophore interaction (Fig. S3). The Lippert–Mataga plot
of the Stokes shift ( ) as a function of solvent polarity parameter
f) shows linear relationship suggesting that dipole–dipole inter-
Df in order to obtain an insight about specific
shift with changing substituents on the phenyl ring. Therefore, it
can be inferred that the luminescence of the products (2a–n) is a
result of their phenazine framework.
D
m
(D
The absorption maxima (kmax), emission maxima (kem), and
stokes shift of 2c were studied in solvents of different polarities
actions and dipole-induced dipole interactions are involved
between solvent and fluorophore.
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P. Saluja et al. / Tetrahedron Letters xxx (2014) xxx–xxx
5
10. Lee, E. J.; Kim, T. H.; Kim, H. S. Repub. Korean Kongkae Taeho Kongbo 2012. KR
2012079411 A 20120712.
11. Wang, C.; Mitchell, W.; D’Lavari, M.; Tierney, S. PCT Int. Appl. 2012, WO
2012123058 A1 20120920.
12. Fischer, B. B.; Krieger-Liszkay, A.; Eggen, R. I. L. Environ. Sci. Technol. 2004, 38,
6307.
13. Katsuhei, Y.; Kazuhiko, S.; Haruka, E.; Kazutoshi, H. Jpn. Kokai Tokkyo Koho
2010. JP 2010088420 A 20100422.
In conclusion, we have developed an efficient, clean, and
confluent approach for the synthesis of novel benzo[a]pyrano
[2,3-c]phenazines and the protocol could be extended to
benzo[a]chromeno[2,3-c]phenazines via the reaction of 2-hydroxy-
naphthalene-1,4-dione, 1,2-phenylenediamines, aromatic alde-
hydes, and Meldrum’s acid/cyclic-1,3-dicarbonyl compounds in
the presence of Gl. AcOH at 70 °C in high yields.21 The diversified
phenazine derivatives are of great interest due to their fluorescent
and biological properties.
14. Pauliukaite, R.; Ghica, M. E.; Barsan, M. M.; Brett, C. M. A. Anal. Lett. 2010, 43,
1588.
15. (a) Mahdavinia, G. H.; Mirzazadeh, M.; Notash, B. Tetrahedron Lett. 2013, 54,
3487; (b) Hasaninejad, A.; Firoozi, S. Mol. Divers. 2013, 17, 499; (c) Hasaninejad,
A.; Firoozi, S.; Mandegani, F. Tetrahedron Lett. 2013, 54, 2791.
16. Khurana, J. M.; Chaudhary, A.; Lumb, A.; Nand, B. Green Chem. 2012, 14, 2321.
17. (a) Wang, S.-L.; Wu, F.-Y.; Cheng, C.; Zhang, G.; Liu, Y. P.; Jiang, B.; Shi, F.; Tu,
S.-J. ACS Comb. Sci. 2011, 13, 135; (b) Frickea, T.; Dickmans, A.; Jana, U.; Zabel,
M.; Jones, P. G.; Dix, I.; König, B.; Herges, R. Z. Naturforsch. 2002, 57b, 937.
18. Complete crystallographic data (excluding factors) have been deposited at the
Cambridge Crystallographic Data Centre under number CCDC 927007. Copies
may be requested free of charge from The Director, CCDC, 12 Union Road,
Cambridge CB2 IEZ, England, (Email: deposit@ccdc.cam.ac.uk).
19. (a) Lewis, N. S.; Nocera, D. G. Proc. Natl. Acad. Sci. U.S.A. 2006, 103, 15729; (b)
McNamara, W. R.; Snoeberger, R. C.; Li, G.; Schleicher, J. M.; Cady, C. W.;
Poyatos, M.; Schmuttenmaer, C. A.; Crabtree, R. H.; Brudvig, G. W.; Batista, V. S.
J. Am. Chem. Soc. 2008, 130, 14329.
Acknowledgements
P.S. and A.C. thank UGC and C.S.I.R., New Delhi, India respec-
tively for the Grant of Senior Research Fellowship.
Supplementary data
Supplementary data (Figs. S1–S3, Tables S1–S2, spectral data,
description of the crystal data and copies of 1H NMR and 13C
NMR spectra) associated with this article can be found, in the
online version, at http://dx.doi.org/10.1016/j.tetlet.2014.04.072.
20. (a) Birks, J. B. The Theory and Practice of Scintillation Counting; Pergamon Press:
Oxford, 1967; (b) Zorn, C.; Bowen, M.; Majewski, S.; Walker, J.; Wojcik, R.;
Hulburt, C.; Moser, W. Nucl. Instrum. Methods Phys. Res., Sect. A 1988, 273, 108.
21. General procedure for the synthesis of benzo[a]pyrano[2,3-c]phenazine (2a–n) and
benzo[a]chromeno[2,3-c]phenazine (3a–q) derivatives:
hydroxynaphthalene-1,4-dione (1.0 mmol), 1,2-phenylenediamine/4-
methylbenzene-1,2-diamine/4,5-dichlorobenzene-1,2-diamine (1.0 mmol)
A
mixture of 2-
References and notes
and Gl. AcOH (20 mol %) was placed in a 50 mL round-bottomed flask and
the contents were stirred magnetically in an oil-bath maintained at 70 °C. An
orange solid of benzo[a]phenazin-5-ol was obtained after 30 min and TLC
showed complete disappearance of diamine. Aldehyde (1.0 mmol) and
1. (a) Toure, B. B.; Hall, D. G. Chem. Rev. 2009, 109, 4439; (b) Ganem, B. Acc. Chem.
Res. 2009, 42, 463.
2. Hulme, C.; Gore, V. Curr. Med. Chem. 2003, 10, 51.
3. (a) Orru, R. V. A.; De Greef, M. Synthesis 2003, 1471; (b) Weber, L. Curr. Med.
Chem. 2002, 9, 2085; (c) Bienayme, H.; Hulme, C.; Oddon, G.; Schmitt, P. Chem.
Eur. J. 2000, 6, 3321; (d) Abboub, F.; Amari, M.; Kolli, B. J. Soc. Alg. Chim. 2001,
11, 223.
4. Laursen, J. B.; Nielsen, J. Chem. Rev. 2004, 104, 1663.
5. Price-Whelan; Dietrich, L. E. P.; Newman, D. K. Nat. Chem. Biol. 2006, 2, 71.
6. Mavrodi, D. V.; Blankenfeldt, W.; Thomashow, L. S. Annu. Rev. Phytopathol.
2006, 44, 417.
7. Mavrodi, D. V.; Peever, T. L.; Mavrodi, O. V.; Parejko, J. A.; Raaijmakers, J. M.;
Lemanceau, P.; Mazurier, S.; Heide, L.; Blankenfeldt, W.; Weller, D. M.;
Thomashow, L. S. Appl. Environ. Microbiol. 2010, 76, 866.
8. Lee, H. J.; Kim, J. S.; Park, S. Y.; Suh, M. E.; Kim, H. J.; Seo, E. K.; Lee, C. O. Bioorg.
Med. Chem. 2004, 12, 1623.
Meldrum’s
acid/cyclohexane-1,3-dione/5-methylcyclohexane-1,3-dione/
dimedone (1.0 mmol) were then added to the above reaction mixture which
was heated further for an appropriate time as shown in Tables 2 and 3. The
progress of the reaction was monitored by TLC (eluent: methanol–chloroform,
10:90, v/v). After completion of the reaction, the reaction mixture was allowed
to cool at room temperature and was quenched with water (ꢂ5 mL). The
precipitate formed was collected by filtration at pump and washed with water
to remove residual AcOH. The crude product so obtained was dissolved in
chloroform: ethyl acetate (3:1 v/v) and heated. After complete dissolution,
petroleum ether was added dropwise to precipitate out the pure phenazine
derivatives (2 and 3). The products were identified by spectral data. 13C NMR
data of all benzo[a]pyrano[2,3-c]phenazine derivatives (2a–n) could not be
recorded due to their low solubility. 13C NMR data of representative products
2b and 2d were recorded with very high number of scans.
9. Kim, J. S.; Rhee, H.-K.; Park, H. J.; Lee, I.-K.; Lee, S. K.; Suh, M.-E.; Lee, H. J.; Ryu,
C.-K.; Park Choo, H. Y. Bioorg. Med. Chem. 2007, 15, 451.
Please cite this article in press as: Saluja, P.; et al. Tetrahedron Lett. (2014), http://dx.doi.org/10.1016/j.tetlet.2014.04.072