A green one-pot pseudo-five-component sequential protocol for the synthesis of novel 6,6′-(arylmethylene)bis(benzo[a]phenazin-5-ol) derivatives

Article abstract of DOI:10.1002/jccs.202000354

A simple and efficient synthesis of novel 6,6′-(arylmethylene)bis(benzo[a]phenazin-5-ol) derivatives has been developed via a sequential one-pot, two-step, pseudo-five-component tandem reaction starting from 2-hydroxynaphthalene-1,4-dione, o-phenylenediam

Full text of DOI:10.1002/jccs.202000354

Received: 17 August 2020
Revised: 19 November 2020
Accepted: 20 November 2020
DOI: 10.1002/jccs.202000354
A R T I C L E
A green one-pot pseudo-five-component sequential protocol
0
for the synthesis of novel 6,6 -(arylmethylene)bis(benzo[a]
phenazin-5-ol) derivatives
1
1
1
2
Abolfazl Olyaei
| Atiye Aghajanzadeh | Elaheh Feizy | Mahdieh Sadeghpour
1
Department of Chemistry, Payame Noor
University (PNU), Tehran, Iran
Abstract
0
2
A simple and efficient synthesis of novel 6,6 -(arylmethylene)bis(benzo[a]
phenazin-5-ol) derivatives has been developed via a sequential one-pot, two-step,
pseudo-five-component tandem reaction starting from 2-hydroxynaphthalene-
Department of Chemistry, Takestan
Branch, Islamic Azad University,
Takestan, Iran
1,4-dione, o-phenylenediamine, and aromatic aldehydes in the presence of
Correspondence
ꢀ
Abolfazl Olyaei, Department of
Chemistry, Payame Noor University
2
-aminopyridine as co-catalyst and p-TsOH as catalyst at 90 C under solvent-free
conditions. This sequential green process offers several advantages, such as oper-
ational simplicity, high yield, low cost, easy handling, clean reactions, absence of
any tedious work-up, and purification of products by non-chromatographic
methods.
(
PNU), PO Box 19395-4697, Tehran, Iran.
Email: olyaei_a@pnu.ac.ir
Funding information
Payame Noor University
K E Y W O R D S
benzo[a]phenazin-5-ol, lawsone, methylenebis(benzo[a]phenazin-5-ol), polycycles, quinones
1
| INTRODUCTION
Recently, some synthetic routes to benzo[a]phenazine
derivatives such as pyrazolo/pyrimido/pyrano/chromeno/
Phenazine derivatives as nitrogen-containing heterocycles
are of the main building blocks of different compounds of
natural origin and synthetic organic molecules. Phenazine
systems are among the important scaffolds and show vari-
furo/oxazino-fused
indenopyrano[2,3-c]phenazines,
benzophenazines,
benzo[a]
benzo[a]phthalazino-
pyrazolo[3,4-c]phenazines under various conditions have
been reported in the literature. A sequential one-pot, two-
step tandem reaction starting from 2-hydroxy-1,-
4-naphthoquinone and o-phenylenediamines with alde-
hydes, malononitrile, lawsone, ketons, 1,3-dicarbonyl
compounds, cyanoalkyl acetate, tetracyanoethylene, acety-
lenic esters, pyrazolone, amines, isocyanide, phthal-
hydrazide, and others proceeded in the presence of various
catalysts such as L-proline, H PW O , La@guanine@
[
1]
ous pharmaceutical activities such as trypanocidal,
[
2]
[3]
antiplatet,
fungicidal,
antitumor, antimalarial, and
[
4]
antiphrastic. Moreover, fluorescent phenazine deriva-
tives are also of interest because of their applications such
as electrochemical and biosensors,
conductors, electroluminescence devices, and photo-
sensitizers in photodynamic therapy.
[5]
organic semi-
[
6]
[7]
[8]
3
12 40
Benzo[a]phenazines are structural subunits in a vari-
ety of important natural products and exhibit a variety of
pharmaceutical activities, such as anticancer, antimalar-
ial activities, and are also applied as useful substrates to
prepare pesticides, antibiotics, dyestuffs, dual inhibitors
of topoisomerase I and II, and are useful as antitumor
SBA-15, DABCO, p-TsOH, ionic liquids, H SO or pho-
2 4
sphotungestic acid, Fe O4 (MNPs), H PW O @nano-
3
3
12 40
10]
[
ZnO, and nano-γ-Fe O @SiO -SCH CO H.
2
3
2
2
2
Considering the importance of benzo[a]phenazine
derivatives and in continuation of our ongoing program
[
11]
for the synthesis of heterocyclic compounds,
herein
[9]
agents.
we wish to describe, for the first time, a new general
J Chin Chem Soc. 2020;1–9.
http://www.jccs.wiley-vch.de
© 2020 The Chemical Society Located in Taipei & Wiley-VCH GmbH
1

2
OLYAEI ET AL.
0
synthetic pathway for the synthesis of novel 6,6 -
arylmethylene)bis(benzo[a]phenazin-5-ol) derivatives
methylene)bis(benzo[a]phenazin-5-ol) (5a) has been
formed instead of compound 6a (Scheme 2).
(
via a domino, one-pot, two-step pseudo-five-component
condensation reaction between 2-hydroxynaphthalene-1,-
Therefore, it was decided to synthesize bis(benzo[a]
phenazin-5-ol) derivatives 5. In order to find optimization
conditions, the one-pot reaction of benzo[a]phenazine
(3) (1.0 mmol) and 4-nitrobenzaldehyde (0.5 mmol) was
carried out with different amount of p-TsOH (5, 10,
4
-dione, o-phenylenediamine, and aromatic aldehydes in
the presence of p-TsOH as catalyst and 2-aminopyridine
as co-catalyst under solvent-free condition.
15, 20 mol%) as catalyst in EtOH under reflux conditions.
The results are summarized in Table 1. As a result, low
yields were obtained in the presence of different amount
of catalyst after a prolonged time (Table 1, Entries 2–5).
We discovered that addition of 2-aminopyridine to
the reaction mixture showed better performance in terms
of reaction time as well as yield of the product. However,
the effect of amount of amine on the conversion and rate
2
| RESULTS AND DISCUSSION
Initially, benzo[a]phenazine (3) was synthesized in 85%
yield from the reaction of 2-hydroxynaphthalene-1,-
4
-dione (1) (1.0 mmol) and o-phenylenediamine (2)
ꢀ
(1.0 mmol) at 90 C under solvent-free condition for
3
0 min. In addition, the reaction was accomplished in
the presence of p-TsOH (20 mol%) for 15 min in the same
reaction conditions and the desired product 3 was
obtained in 89% yield (Scheme 1).
TABLE 1 Optimization of reaction conditions for the
synthesis of 5a in the presence of p-TsOH as catalyst
a
In order to investigate the reaction conditions for the
b
Entry
p-TsOH (mol%)
Time (hr)
Yield (%)
synthesis
of
6-((4-nitrophenyl)(pyridin-2-ylamino)
1
2
3
4
5
-
8
8
8
8
8
10
15
21
25
30
methyl)benzo[a]phenazin-5-ol (6a), we carried out the
reaction between benzo[a]phenazine (3) (1.0 mmol),
5
10
15
20
4
-nitrobenzaldehyde (1.0 mmol), and 2-aminopyridine
(1.0 mmol) as a model. We began this domino one-pot
three-component reaction in the absence of a catalyst in
EtOH under reflux and the product was obtained in 42%
yield after 6.0 hr. Interestingly, analysis of the obtained
a
All reactions were carried out using benzo[a]phenazine (3), (1.0 mmol) and
- nitrobenzaldehyde (0.5 mmol) in EtOH. (5 ml) under reflux conditions.
4
b
0
product indicated that product 6,6 -((4-nitrophenyl)
Isolated yield.
SCHEME 1 Synthesis of benzo[a]phenazine (3)
SCHEME 2 One-pot reaction of benzo[a]phenazine (3), 4-nitrobenzaldehyde and 2-aminopyridine

OLYAEI ET AL.
3
ꢀ
of the reaction was evaluated by varying the amount of
free conditions at 90 C (Table 3, Entry 7). So, a domino
one-pot reaction of benzo[a]phenazine (3) (1.0 mmol),
4-nitrobenzaldehyde (0.5 mmol) using 20 mol% of
p-TsOH as catalyst, and 2-aminopyridine (0.5 mmol) as
2
(
2
-aminopyridine (10, 25, 50, 75 mol%) as co-catalyst
Table 2). As it was shown from Table 2, 50 mol% of
-aminopyridine (0.5 mmol) as co-catalyst afforded prod-
ꢀ
uct 5a in 5.5 hr with 80% yield. Increasing the amount of
amine to more than 50 mol%, showed no substantial
improvement in the yield (Table 2, Entry 5).
co-catalyst at 90 C under solvent-free condition proved to
be the optimum conditions.
Using these optimized reaction conditions, the scope
Next, we examined the effect of different protic and
aprotic solvents and solvent-free conditions on the model
reaction. As Table 3 indicates, the best result was
obtained by heating the reaction mixture under solvent-
and efficiency of the reaction were explored for the syn-
0
thesis of
(arylmethylene)bis(benzo[a]phenazin-5-ol)
5 via one-pot two-step process. It should be noted that
the first step 2-hydroxynaphthalene-1,4-dione
1.0 mmol), o-phenylenediamine (1.0 mmol), and
a
wide variety of substituted 6,6 -
derivatives
(
ꢀ
p-TsOH (20% mol) were mixed at 90 C for 15 min until
an orange solid of benzo[a]phenazine (3) was formed
under solvent-free conditions. So, In the next step, aro-
TABLE 2 Optimization of reaction conditions for the
synthesis of 5a in the presence of 2-aminopyridine as co-catalyst
a
2
-Aminopyridine
matic aldehyde (0.5 mmol) and 2-aminopyridine
b
Entry
(mol%)
Time (hr)
Yield (%)
ꢀ
(
0.5 mmol) were added to the reaction mixture at 90 C
1
2
3
4
5
-
8
30
50
56
80
80
0
for the synthesis of novel 6,6 -(arylmethylene)bis(benzo
10
25
50
75
6
[a]phenazin-5-ol) derivatives 5a-i (Scheme 3). The results
6
are summarized in Figure 1. The influence of electron-
donating and electron-withdrawing substituents on the
aromatic ring of aldehydes upon the reaction yields was
investigated. As Figure 1 indicates, aromatic aldehydes
containing electron-withdrawing groups increased the
rate of reaction and gave higher yields than that with
electron-donating groups. After completion of the
5.5
5.5
a
All reactions were carried out using benzo[a]phenazine (3) (1.0 mmol),
- nitrobenzaldehyde (0.5 mmol) and p-TsOH (20 mol%) in EtOH. (5 ml)
4
under reflux conditions.
b
Isolated yield.
TABLE 3 Optimization of the
ꢀ
b
Entry
Solvent
Temperature ( C)
Time (hr)
Yield (%)
reaction conditions for the synthesis of
a
1
2
3
4
5
6
7
EtOH
Reflux
Reflux
Reflux
Reflux
Reflux
90
5.5
8
80
42
40
34
25
90
78
5
a under various conditions
3
CH CN
CHCl
3
8
THF
8
H
2
O
10
2
-
-
70
2
a
All reactions were carried out using benzo[a]phenazine (3) (1.0 mmol), 4- nitrobenzaldehyde (0.5 mmol),
-aminopyridine (0.5 mmol), and p-TsOH (20 mol%).
2
b
Isolated yield.
0
SCHEME 3 Synthesis of 6,6 -(arylmethylene)bis(benzo[a]phenazin-5-ol) derivatives 5

4
OLYAEI ET AL.
FIGURE 1 Synthesis of compounds 5a-i
reaction, the reaction mixture was cooled to room tem-
15.11 ppm in agreement with an asymmetric structure in
1
3
perature and 50 ml of CHCl was added to this mixture.
which they have hydrogen bonding. In addition, the C-
NMR spectrum of compound 5a shows 37 types of car-
bon, which confirms the asymmetry of its structure.
3
Then the mixture was stirred in boiling CHCl and fil-
3
tered. The solvent was recovered by evaporation using a
rotary evaporator. The organic solid was washed with
cold EtOAc and dried to give the pure product 5.
When the reaction of benzo[a]phenazine (3) starting
from 2-hydroxynaphthalene-1,4-dione (1.0 mmol) and
A reaction mechanism consistent with the above
results is shown in Scheme 5. Initially, 2-hydroxy-1,-
4-naphthoquinone tautomerizes to intermediate 8. The
primary condensation of intermediate 8 with benzene-1,-
2-diamine (2) obtain benzo[a]phenazin-5-ol (3). On the
other hand, condensation of aromatic aldehyde with
2-aminopyridine in the presence of p-TsOH afforded
Schiff base as intermediate 9. Subsequently, nucleophilic
addition of 3 to intermediate 8 led to the formation of
intermediate 10. Intermediate 9 tautomerizes to interme-
diate 11. By leaving of 2-aminopyridine from intermedi-
ate 11, ortho-qinonemethide 12 was produced. It should
be noted that, 2-aminopyridine might act as a good leav-
ing group in the acidic environment. Finally, Michael
o-phenylenediamine
-methoxybenzaldehyde (0.5 mmol) was examined under
the same reaction conditions, after 150 min,
-(4-methoxy-16H-benzo[a]chromeno[2,3-c]phenazin-16-
yl)benzo[a]phenazin-5-ol (7) was obtained in good yield
80%) (Scheme 4). Structural assignments of the com-
(1.0 mmol)
with
2-hydroxy-
3
6
(
1
pounds have been made on the basis of FT-IR, H-NMR,
1
3
1
C-NMR, and Mass analysis. For example, the H-NMR
spectrum of compound 5a shows two singlet signals for
the hydroxyl groups localized at about δ = 14.60 and

OLYAEI ET AL.
5
SCHEME 4 Synthesis of compound 7
0
SCHEME 5 Proposed mechanism for the synthesis of 6,6 -(arylmethylene)bis(benzo[a]phenazin-5-ol) derivatives 5a-i and compound 7
addition of benzo[a]phenazin-5-ol (3) to o-QM 12 affords
the corresponding products 5. For the formation of com-
pound 7, initially, intermediate 5j was formed according
to the proposed mechanism for 5a-i. Then, intermediate
5j tautomerizes to the keto form 13, which undergoes
intramolecular cyclization via an oxygen atom attacking

6
OLYAEI ET AL.
to the carbonyl group and elimination of water to afford
the desired product 7.
Ar-H), 8.22 (t, 1H, J = 8.4 Hz, Ar-H), 8.31 (d, 1H,
J = 8.7 Hz, Ar-H), 8.47–8.62 (m, 2H, Ar-H), 9.21–9.23 (m,
1
3
2H, Ar-H), 14.60 (s, 1H, OH), 15.11 (s, 1H, OH);
C
NMR (75 MHz, DMSO-d ): δ = 38.73, 111.79, 112.38,
6
3
3
| EXPERIMENTAL
123.30, 124.24, 124.44, 124.60, 124.66, 125.01, 125.03,
1
28.16, 128.37, 128.55, 129.38, 129.44, 129.67, 129.77,
130.41, 130.52, 130.63, 130.90, 130.95, 131.21, 131.23,
36.95, 137.91, 139.38, 139.48, 140.87, 142.31, 142.57,
.1 | General information
1
All commercially available chemicals and reagents were
used without further purification. Melting points were
determined with an Electrothermal model 9100 appara-
143.66, 146.02, 147.50, 161.46, 162.93; MS m/z (%):
625 (M ) (<1%), 379 (0.6), 378 (0.8), 332 (2), 303 (1),
247 (7.5), 246 (40), 245 (3), 219 (3.3), 218 (19), 217 (9),
190 (6.5), 151 (1.6), 121 (0.6), 114 (3.5), 89 (6.8), 87 (11),
85 (65), 83 (100), 77 (9), 50 (10).
+
tus and are uncorrected. FT-IR spectra were recorded on
1
a
Shimadzu 4300 spectrophotometer. The H-and
C-NMR spectra were recorded in CDCl3 on Bruker
1
3
DRX-300 Avance spectrometers. Chemical shifts (δ) are
reported in parts per million and are referenced to the
NMR solvent. Mass spectra of the products were obtained
with a HP (Agilent technologies) 5973 Mass Selective
Detector.
0
3.4 | 6,6 -((3-Nitrophenyl)methylene)bis
(benzo[a]phenazin-5-ol) (5b)
ꢀ
−1
Orange powder; M.P. = 303–304 C; IR (KBr, cm ):
,444, 3,063, 2,905, 1,620, 1,590, 1,520, 1,455, 1,410, 1,376,
,347, 1,231, 1,065; H NMR (300 MHz, DMSO-d6):
3
1
1
3
.2 | General procedure for the synthesis
δ = 7.22 (t, 1H, J = 7.8 Hz, Ar-H), 7.39 (d, 1H, J = 7.5 Hz,
Ar-H), 7.46 (s, 1H, methine-H), 7.63–7.95 (m, 11H,
Ar-H), 8.19–8.26 (m, 2H, Ar-H), 8.32 (d, 1H, J = 8.4 Hz,
Ar-H), 8.47–8.50 (m, 1H, Ar-H), 8.60–8.63 (m, 1H, Ar-H),
9.20–9.24 (m, 2H, Ar-H), 14.60 (s, 1H, OH), 15.10 (s, 1H,
0
of 6,6 -(arylmethylene)bis(benzo[a]
phenazin-5-ol) derivatives 5
Initially, a mixture of 2-hydroxynaphthalene-1,4-dione
13
(
1) (1.0 mmol), o-phenylenediamine (2) (1.0 mmol), and
OH); C NMR (75 MHz, DMSO-d ): δ = 38.44, 111.86,
6
p-TsOH (20 mol%) was placed in a 25 ml round-bottomed
112.50, 121.12, 122.99, 124.43, 124.63, 124.81, 124.84,
125.19, 125.24, 128.32, 128.49, 128.95, 129.52, 129.59,
129.87, 129.95, 130.61, 130.69, 130.78, 131.11, 131.17,
131.32, 134.14, 137.18, 138.13, 139.57, 139.70, 141.05,
141.82, 142.55, 142.78, 143.94, 143.65, 161.55, 163.10; MS
flask mounted over a magnetic stirrer. The contents were
ꢀ
stirred magnetically in an oil-bath maintained at 90 C
until after 15 min benzo[a]phenazin-5-ol (3) was formed.
Then,
aromatic
aldehyde
(4)
(0.5 mmol),
+
2
-aminopyridine (0.5 mmol) were added to the above
m/z (%): 625 (M ) (<1%), 381 (4), 380 (20), 379 (76),
reaction mixture, which was heated further at the same
temperature for an appropriate time as shown in
Figure 1. The progress of the reaction was monitored by
thin-layer chromatography (TLC). After completion, the
reaction mixture was cooled to room temperature. The
crude product was dissolved in boiling chloroform
378 (63), 363 (8.5), 362 (31), 334 (12), 333 (51), 332 (86.5),
305 (16.5), 304 (32), 303 (44.3), 247 (40), 246 (100),
245 (14), 219 (14), 218 (75), 217 (39), 190 (22.7), 166 (15),
152 (8.3), 123 (8.7), 116 (8.3), 115 (7), 114 (9.9), 109 (8.3),
102 (10), 90 (9.3), 89 (15.5), 77 (19), 76 (10), 50 (4.5).
(
50 ml) and filtered. The solution was recovered via evap-
0
oration using a rotary evaporator and cold EtOAc (5 ml)
was added. The precipitate was filtered, washed with cold
EtOAc, and dried to give the pure products 5 and 7.
3.5 | 6,6 -(Phenylmethylene)bis(benzo[a]
phenazin-5-ol) (5c)
ꢀ
−1
Crimson powder; M.P. = 302 C dec.; IR (KBr, cm ):
,440, 3,065, 2,926, 1,638, 1,590, 1,528, 1,498, 1,448, 1,411,
1,373, 1,348, 1,322, 1,231, 1,063; H NMR (300 MHz,
3
0
1
3
(
.3 | 6,6 -((4-Nitrophenyl)methylene)bis
benzo[a]phenazin-5-ol) (5a)
DMSO-d ): δ = 7.05 (s, 5H, ph-H), 7.49 (s, 1H, methine-
6
H), 7.63–7.87 (m, 8H, Ar-H), 7.99–8.02 (m, 1H, Ar-H),
8.19–8.27 (m, 2H, Ar-H), 8.34 (d, 1H, J = 8.7 Hz, Ar-H),
8.51–8.62 (m, 2H, Ar-H), 9.23–9.25 (m, 2H, Ar-H), 14.51
ꢀ
−1
Crimson powder; M.P. >350 C; IR (KBr, cm ): 3,434,
3
1
,064, 2,902, 1,643, 1,620, 1,590, 1,516, 1,454, 1,413, 1,377,
,346, 1,231, 1,067; H NMR (300 MHz, DMSO-d6):
1
13
(s, 1H, OH), 15.11 (s, 1H, OH); C NMR (75 MHz,
δ = 7.24 (d, 2H, J = 8.7 Hz, Ar-H), 7.43 (s, 1H, methine-
H), 7.64–7.88 (m, 10H, Ar-H), 7.92 (d, 2H, J = 8.7 Hz,
DMSO-d ): δ = 38.54, 113.08, 114.07, 124.59, 124.69,
125.06, 125.11, 125.26, 125.71, 127.34, 127.79, 128.16,
6

OLYAEI ET AL.
7
+
+
1
1
1
1
28.33, 129.12, 129.15, 129.70, 129.85, 130.47, 130.57,
30.68, 130.95, 131.08, 131.25, 137.71, 138.70, 138.96,
39.65, 139.72, 139.75, 141.77, 142.42, 142.65, 144.59,
m/z (%): 660 (M + 2) (<1%), 658 (M ) (<1%), 414 (2.3),
413 (2), 379 (2.1), 333 (5.4), 332 (3.8), 331 (3), 305 (2.1),
304 (2.5), 303 (4.6), 299 (4.2), 272 (5.1), 262 (3.2),
261 (3.6), 260 (2.5), 259 (3.5), 246 (16), 218 (8.3), 193 (3.8),
192 (3.5), 155 (2.2), 154 (2.8), 152 (3), 123 (3.5), 116 (3.4),
115 (5.4), 94 (36), 85 (54), 83 (83), 79 (100), 78 (16.5),
77 (9), 67 (33), 52 (17).
+
46.71, 152.62, 160.68, 161.78; MS m/z (%): 580 (M )
(<1%), 335 (11.8), 334 (55.5), 333 (100), 305 (18),
3
1
8
04 (7.5), 303 (12.7), 247 (13), 246 (73), 218 (40), 217 (20),
90 (15), 116 (7), 114 (7.5), 102 (7), 90 (7), 89 (13),
3 (7.5), 77 (18.5), 76 (8.2).
0
3
.8 | 6,6 -((4-(Dimethylamino)phenyl)
0
3
.6 | 6,6 -((4-Chlorophenyl)methylene)
methylene)bis(benzo[a]phenazin-5-ol) (5f)
bis(benzo[a]phenazin-5-ol) (5d)
ꢀ
−1
Brown powder; M.P. = 233 C dec.; IR (KBr, cm ): 3,402,
ꢀ
−1
Orange powder; M.P. = 304–306 C; IR (KBr, cm ):
3,062, 2,877, 2,797, 1,609, 1,590, 1,518, 1,455, 1,410, 1,373,
1,347, 1,230, 1,159, 1,066; H NMR (300 MHz, DMSO-d ):
δ = 2.74 (s, 6H, 2 x CH ), 6.44 (d, 2H, J = 9.0 Hz, Ar-H),
1
3
1
,433, 3,061, 2,910, 1,620, 1,589, 1,531, 1,488, 1,455, 1,411,
,370, 1,348, 1,283, 1,231, 1,068; H NMR (300 MHz,
6
1
3
DMSO-d ): δ = 6.98 (d, 2H, J = 8.7 Hz, Ar-H), 7.03
6.87 (d, 2H, J = 9.0 Hz, Ar-H), 7.42 (s, 1H, methine-H),
7.65–7.86 (m, 8H, Ar-H), 8.06–8.09 (m, 1H, Ar-H),
8.19–8.26 (m, 2H, Ar-H), 8.34 (d, 1H, J = 8.1 Hz, Ar-H),
8.53–8.62 (m, 2H, Ar-H), 9.22–9.25 (m, 2H, Ar-H), 14.48
6
(d, 2H, J = 8.7 Hz, Ar-H), 7.40 (s, 1H, methine-H),
7
8
8
1
.65–7.88 (m, 8H, Ar-H), 8.01–8.04 (m, 1H, Ar-H),
.20–8.28 (m, 2H, Ar-H), 8.34 (d, 1H, J = 8.7 Hz, Ar-H),
.50–8.62 (m, 2H, Ar-H), 9.24 (d, 2H, J = 5.7 Hz, Ar-H),
13
(s, 1H, OH), 15.12 (s, 1H, OH); C NMR (75 MHz,
13
4.56 (s, 1H, OH), 15.13 (s, 1H, OH); C NMR (75 MHz,
DMSO-d ): δ = 37.67, 40.86, 112.79, 113.63, 114.65,
6
DMSO-d ): δ = 38.13, 112.68, 113.51, 114.45, 114.83,
124.52, 124.63, 125.07, 125.35, 126.22, 126.71, 128.04,
128.21, 128.47, 128.94, 128.98, 129.11, 129.64, 129.79,
130.38, 130.48, 130.75, 130.96, 130.99, 131.04, 131.33,
137.86, 138.80, 139.10, 139.62, 139.67, 141.94, 142.37,
142.60, 144.71, 148.77, 160.45, 161.39; MS m/z (%):
6
1
1
1
1
1
15.74, 115.87, 124.57, 124.74, 124.89, 125.10, 125.14,
28.26, 128.44, 129.27, 129.32, 129.74, 129.88, 130.56,
30.65, 131.06, 131.09, 131.15, 131.20, 131.43, 137.50,
37.63, 138.49, 139.71, 141.45, 142.43, 142.97, 144.47,
+
+
52.32, 155.78, 160.94, 162.19; MS m/z (%): 616 (M + 2)
623 (M ) (<1%), 379 (6.3), 378 (4.5), 377 (16.7),
+
(<1%), 614 (M ) (<1%), 370 (11.5), 368 (25), 367 (46),
376 (19.8), 362 (4.4), 360 (4.2), 334 (3.5), 333 (9.6),
332 (3.4), 258 (5), 247 (10.4), 246 (54), 237 (30.4), 236 (14),
218 (28), 217 (14), 190 (10.5), 134 (12.5), 122 (9.5),
121 (100), 120 (37.8), 107 (21), 102 (4.2), 83 (4), 77 (12.5).
3
2
1
8
39 (8), 334 (5), 333 (22), 303 (14.6), 299 (15.7), 247 (14),
46 (78), 245 (6), 218 (39), 217 (22), 216 (9.6), 190 (14.5),
66 (18.5), 125 (4.5), 123 (8.2), 116 (8.7), 115 (9), 114 (9),
5 (65), 83 (100), 79 (73), 47 (36).
0
3
.9 | 6,6 -((4-Methoxyphenyl)methylene)
0
3
.7 | 6,6 -((4-Bromophenyl)methylene)
bis(benzo[a]phenazin-5-ol) (5g)
bis(benzo[a]phenazin-5-ol) (5e)
ꢀ
−1
Crimson powder; M.P. = 307–308 C; IR (KBr, cm ):
ꢀ
−1
Orange powder; M.P. = 295 C dec.; IR (KBr, cm ):
3,443, 3,061, 2,948, 2,830, 1,619, 1,589, 1,530, 1,508, 1,454,
1,407, 1,371, 1,348, 1,245, 1,178, 1,067; H NMR
(300 MHz, DMSO-d ): δ = 3.63 (s, 3H, OCH ), 6.60
1
3
1
,431, 3,060, 2,910, 1,620, 1,589, 1,531, 1,484, 1,455, 1,410,
,376, 1,348, 1,284, 1,231, 1,067; H NMR (300 MHz,
1
6
3
DMSO-d ): δ = 6.93 (d, 2H, J = 8.1 Hz, Ar-H), 7.16 (d,
(d, 2H, J = 8.7 Hz, Ar-H), 6.94 (d, 2H, J = 8.7 Hz, Ar-H),
7.42 (s, 1H, methine-H), 7.63–7.87 (m, 8H, Ar-H),
8.02–8.05 (m, 1H, Ar-H), 8.19–8.26 (m, 2H, Ar-H), 8.34
(d, 1H, J = 8.1 Hz, Ar-H), 8.51–8.62 (m, 2H, Ar-H),
6
2
H, J = 8.1 Hz, Ar-H), 7.38 (s, 1H, methine-H), 7.67–7.88
(
(
(
(
m, 8H, Ar-H), 8.01–8.04 (m, 1H, Ar-H), 8.20–8.28
m, 2H, Ar-H), 8.34 (d, 1H, J = 8.7 Hz, Ar-H), 8.50–8.53
m, 1H, Ar-H), 8.59–8.62 (m, 1H, Ar-H), 9.23–9.25
9.21–9.24 (m, 2H, Ar-H), 14.52 (s, 1H, OH), 15.12 (s, 1H,
13
13
m, 2H, Ar-H), 14.56 (s, 1H, OH), 15.13 (s, 1H, OH);
C
OH); C NMR (75 MHz, DMSO-d ): δ = 37.82, 55.28,
6
NMR (75 MHz, DMSO-d ): δ = 38.21, 119.56, 124.06,
113.56, 114.28, 124.55, 124.68, 125.10, 125.25, 127.53,
128.15, 128.33, 128.82, 129.10, 129.14, 129.68, 129.83,
130.47, 130.58, 130.71, 130.76, 130.93, 131.01, 131.06,
131.09, 131.28, 137.69, 138.66, 139.37, 139.61, 139.68,
140.20, 141.74, 142.65, 152.93, 157.56, 160.67, 161.72,
6
1
1
1
1
1
24.25, 124.58, 124.74, 124.89, 125.09, 125.14, 128.24,
28.45, 129.28, 129.34, 129.68, 129.88, 130.55, 131.19,
38.16, 138.21, 138.48, 139.62, 143.23, 144.12, 145.14,
47.50, 151.93, 153.06, 153.50, 153.95, 154.46, 155.56,
56.16, 157.33, 157.69, 158.16, 160.11, 160.20; MS
+
165.11; MS m/z (%): 610 (M ) (<1%), 379 (5.7), 364 (25),

8
OLYAEI ET AL.
3
3
2
1
8
63 (44.9), 349 (11), 333 (21.7), 329 (9), 321 (9.6),
20 (15.8), 313 (7), 299 (34.6), 292 (19.8), 247 (20),
46 (100), 236 (18.3), 218 (50), 217 (26.5), 190 (22),
52 (11), 123 (16), 109 (16), 98 (33), 97 (25.5), 95 (21),
9 (22), 85 (28), 84 (38), 83 (44), 79 (26), 77 (29), 51 (9.3).
246 (100), 218 (53.5), 217 (28), 190 (21.5), 118 (10.3),
116 (10.5), 114 (12), 94 (51.3), 89 (19.6), 83 (22), 79 (12),
77 (22.6), 76 (11.4), 67 (48), 51 (13).
3
.12 | 6-(4-Methoxy-16H-benzo[a]
chromeno[2,3-c]phenazin-16-yl)benzo[a]
0
3
.10 | 6,6 -(p-Tolylmethylene)bis(benzo
phenazin-5-ol (7)
[
a]phenazin-5-ol) (5h)
ꢀ
−1
Brown powder; M.P. = 286–287 C; IR (KBr, cm ): 3,396,
ꢀ
−1
Crimson powder; M.P. = 280 C dec.; IR (KBr, cm ):
3
1
3,057, 2,933, 1,585, 1,531, 1,497, 1,459, 1,414, 1,342, 1,270,
1,220, 1,096, 1,059; H NMR (300 MHz, DMSO-d6):
δ = 4.01 (s, 3H, OCH ), 6.71–6.73 (m, 2H, methine-H,
1
,431, 3,058, 2,918, 1,620, 1,590, 1,531, 1,505, 1,454, 1,410,
,372, 1,348, 1,286, 1,233, 1,067; H NMR (300 MHz,
1
3
DMSO-d ): δ = 2.16 (s, 3H, CH ), 6.85 (d, 2H, J = 8.1 Hz,
Ar-H), 7.49–8.01 (m, 12H, Ar-H), 8.21 (d, 1H, J = 8.4 Hz,
Ar-H), 8.43 (d, 1H, J = 9.0 Hz, Ar-H), 8.64 (d, 1H,
J = 8.1 Hz, Ar-H), 8.89 (d, 1H, J = 7.8 Hz, Ar-H), 9.11 (d,
1H, J = 7.8 Hz, Ar-H), 9.22 (d, 1H, J = 7.8 Hz, Ar-H),
12.94 (s, 1H, OH); C NMR (75 MHz, DMSO-d6):
δ = 32.77, 56.68, 110.68, 111.16, 119.88, 120.68,
123.11,123.42, 124.14, 125.04, 125.37, 125.81, 126.11,
126.97, 128.08, 128.21, 128.75, 129.01, 129.10, 129.18,
129.23, 129.78, 129.94, 130.38, 130.55, 130.66, 130.95,
131.54, 139.63, 140.29, 140.49, 141.06, 141.88, 141.95,
142.12, 142.37, 143.90, 147.66, 151.64, 152.87; MS m/z
6
3
Ar-H), 6.92 (d, 2H, J = 8.1 Hz, Ar-H), 7.43 (s, 1H,
methine-H), 7.63–7.87 (m, 8H, Ar-H), 8.02–8.05 (m, 1H,
Ar-H), 8.19–8.27 (m, 2H, Ar-H), 8.33 (d, 1H, J = 7.5 Hz,
Ar-H), 8.52–8.62 (m, 2H, Ar-H), 9.24 (d, 2H, J = 5.4 Hz,
13
13
Ar-H), 14.50 (s, 1H, OH), 15.12 (s, 1H, OH); C NMR
(75 MHz, DMSO-d ): δ = 21.06, 38.18, 113.32, 114.13,
6
1
1
1
1
1
24.59, 124.69, 125.06, 125.09, 125.19, 127.65, 128.11,
28.27, 128.90, 129.09, 129.14, 129.69, 129.83, 130.46,
30.57, 130. 74, 130.91, 131.02, 131.07, 131.32, 135.08,
35.76, 137.63, 138.61, 139.58, 139.66, 141.74, 142.43,
+
+
42.66, 144.53, 160.79, 161.87; MS m/z (%): 594 (M )
(%): 608 (M ) (<1), 364 (9.2), 299 (12), 246 (32),
(
<1), 349 (6), 348 (25.6), 347 (56.7), 334 (17.7), 333 (68),
218 (17.8), 171 (32), 115 (8.2), 105 (12.6), 94 (56.5),
85 (66.8), 83 (100), 79 (11.6), 77 (20), 67 (54.5), 57 (16.8),
48 (21), 47 (40).
3
2
1
7
19 (9), 299 (11.3), 247 (18), 246 (100), 245 (7), 218 (48.3),
17 (25), 190 (20.4), 174 (13.7), 166 (11.9), 123 (11),
15 (11), 114 (10.6), 102 (10), 90 (10.6), 89 (22), 79 (11.4),
7 (27.2), 76 (14), 51 (7).
4
| CONCLUSIONS
0
3
(
.11 | 6,6 -(Furan-2-ylmethylene)bis
In summary, we have demonstrated a green, simple,
efficient, and environment-friendly one-pot pseudo-
five-component procedure for the synthesis of novel
benzo[a]phenazin-5-ol) (5i)
ꢀ
−1
0
Crimson powder; M.P. = 283–285 C; IR (KBr, cm ):
,442, 3,052, 2,961, 1,620, 1,590, 1,530, 1,502, 1,455, 1,411,
,371, 1,350, 1,324, 1,287, 1,233, 1,067; H NMR
300 MHz, DMSO-d ): δ = 5.87 (dd, 1H, J = 0.9, 1.8 Hz,
Ar-H), 6.18–6.20 (dd, 1H, J = 1.2, 3.0 Hz, Ar-H),
.11–7.13 (dd, 1H, J = 0.9, 1.5 Hz, Ar-H), 7.29 (s, 1H,
methine-H), 7.68–7.87 (m, 8H, Ar-H), 8.14 (d, 1H,
J = 8.4 Hz, Ar-H), 8.23(t, 2H, J = 7.8 Hz, Ar-H), 8.33
6,6 -(arylmethylene)bis(benzo[a]phenazin-5-ol) deriva-
3
1
(
tives via the reaction of 2-hydroxynaphthalene-1,-
4-dione, benzene-1,2-diamine, aromatic aldehydes by
using 2-aminopyridine as co-catalyst and a catalytic
1
6
ꢀ
amount of p-TsOH (20 mol%) at 90 C under solvent-free
7
conditions. In this process, addition of 2-aminopyridine
as co-catalyst to the reaction mixture showed better per-
formance in terms of reaction time as well as yield of
the product. Moreover, simple experimental, clean reac-
tion profile, avoidance of hazardous organic solvents,
easy work-up as well as an isolation of the pure
products without chromatography with high yields
make it a useful protocol for the green synthesis of these
compounds.
(
9
d, 1H, J = 8.1 Hz, Ar-H), 8.54–8.62 (m, 2H, Ar-H),
.19–9.23 (m, 2H, Ar-H), 14.44 (s, 1H, OH), 15.19 (s, 1H,
13
OH); C NMR (75 MHz, DMSO-d ): δ = 34.60, 107.46,
6
1
1
1
1
1
09.43, 110.39, 110.46, 110.73, 110.77, 111.73, 112.51,
24.62, 124.76, 125.11, 127.99, 128.16, 128.79, 129.24,
29.28, 129.77, 129.85, 130.50, 130.57, 130. 77, 131.07,
31.13, 131.28, 137.42, 138.14, 139.44, 139.46, 141.15,
41.58, 142.48, 142.60, 143.50, 152.90, 162.08, 162.18; MS
m/z (%): 570 (M ) (<1), 325 (5.7), 324 (22.4), 296 (10.5),
ACKNOWLEDGMENTS
The authors thank the Research Council of Payame Noor
University for financial support.
+
2
95 (31.8), 283 (33.8), 270 (13.3), 266 (22.8), 247 (19),

OLYAEI ET AL.
9
ORCID
(i) A. S. Choudhary, N. Sekar, J. Fluoresc. 2015, 25, 675. (j) A.
Hasaninejad, S. Firoozi, Mol. Divers. 2013, 17, 499. (k) R.
Mohebat, A. Y. E. Abadi, M. -T. Maghsoodlou, M.
Mohammadi, Res. Chem. Intermed. 2016, 42, 5915. (l) R.
Mohebat, A. Yazdani Elah, M. -T. M. Abadi, Res. Chem. Inter-
med. 2016, 42, 6039. (m) R. Mohebat, A. Y.-E. Abadi, M. T.
Maghsoodlou, N. Hazeri, Chin. Chem. Lett. 2017, 28, 943.
Abolfazl Olyaei https://orcid.org/0000-0003-2976-9481
REFERENCES
[
1] S. A. Gamage, J. A. Spicer, G. W. Rewcastle, W. Dangerfield,
P. Mistry, N. Vicker, P. A. Charlton, W. A. Denny, J. Med.
Chem. 2002, 45, 740.
(
2
n) R. Mohebat, A. Yazdani-Elah-Abadi, Chin. Chem. Lett.
017, 28, 1340. (o) M. Rajeswari, G. Khanna, A. Chaudhary,
[
[
2] M. Muller, T. Sorrell, Prostaglandins 1995, 50, 301.
3] J. Ligon, S. Dwight, P. Hammer, N. Torkewitz, D. Hofmann,
H. Kempf, K. Pee, Pest Manag. Sci. 2000, 56, 688.
4] J. B. Laursen, J. Nielsen, Chem. Rev. 2004, 104, 1663.
5] R. Pauliukaite, M. E. Ghica, M. M. Barsan, C. M. A. Brett,
Anal. Lett. 2010, 43, 1588.
J. M. Khurana, Synth. Commun. 2015, 45, 1426. (p) A.
Yazdani-Elah-Abadi, R. Mohebat, M. Lashkari, Polycycl.
Aromat. Compd. 2020, 40, 268. (q) A. Chaudhary, J. M.
Khurana, Res. Chem. Intermed. 2018, 44, 1045. (r) R. Mohebat,
P. Dehgan, A. Yazdani-Elah-Abad, J. Chin. Chem. Soc. 2018,
[
[
[
[
[
[
6] C. Wang, W. Mitchell, M. D'Lavari, S. Tierney, WO
65, 1259.
2
012123058A1 20120920, 2012.
7] E. J. Lee, T. H. Kim, H. S. Kim, KR 2012079411 A 20120712,
012.
[
11] (a) A. Olyaei, M. S. Shahsavari, M. Sadeghpour, Res. Chem.
Intermed. 2018, 44, 943. (b) A. Olyaei, R. Mohammad
Ebrahimi, A. Adl, M. Sadeghpour, Chem. Heterocycl. Compd.
2
8] B. B. Fischer, A. Krieger-Liszkay, R. I. L. Eggen, Environ. Sci.
Technol. 2004, 38, 6307.
2019, 55, 1104. (c) F. Noruzian, A. Olyaei, R. Hajinasiri, Res.
Chem. Intermed. 2019, 45, 4383. (d) R. Khoeiniha, A. Olyaei,
M. Saraei, J. Heterocycl. Chem. 2017, 54, 1746. (e) R.
Khoeiniha, A. Olyaei, M. Saraei, Synth. Commun. 2018, 48,
9] (a) H. N. Hafez, M. I. Hegab, I. S. Ahmed-Farag, A. B. A. El-
Gazzar, Bioorg. Med. Chem. Lett. 2008, 18, 4538. (b) S. A.
Gamage, J. A. Spicer, G. W. Rewcastle, J. Milton, S. Sohal, W.
Dangerfield, P. Mistry, N. Vicker, P. A. Charlton, W. A.
Denny, J. Med. Chem. 2002, 45, 740. (c) J. G. Tangmouo, A. L.
Meli, J. Komguem, V. Kuete, F. N. Ngounou, D. Lontsi, V. P.
Beng, M. I. Choudhary, B. L. Sondengam, Tetrahedron Lett.
1
1
55. (f) A. Olyaei, M. Saraei, R. Khoeiniha, Synlett 2018, 29,
589.
SUPPORTING INFORMATION
Additional supporting information may be found online
in the Supporting Information section at the end of this
article.
2
006, 47, 3067. (d) N. Vicker, L. Burgess, I. S. Chuckowree, R.
Dodd, A. J. Folkes, D. J. Hardick, T. C. Hancox, W.
Dangerfield, C. Liddle, P. Mistry, A. J. Stewart, W. A. Denny,
J. Med. Chem. 2002, 45, 721.
[
10] (a) S. Abolghassem, S. Molaei, S. Javanshir, Heliyon 2019, 5,
e02036. (b) G. Kaupp, M. Reza Naimi-Jamal, Eur. J. Org.
Chem. 2002, 2002, 1368. (c) S. Abbasi Pour, A. Yazdani-Elah-
Abadi, M. Afradi, Appl. Organometal. Chem. 2017, 31, e3791.
How to cite this article: Olyaei A,
Aghajanzadeh A, Feizy E, Sadeghpour M. A green
one-pot pseudo-five-component sequential protocol
for the synthesis of novel 6,6 -(arylmethylene)bis
(
d) M. Nikoorazm, M. Khanmoradi, M. Mohammadi, Appl.
0
Organometal. Chem. 2020, 34, e5504. (e) A. Shaabani, R.
Ghadari, M. Arabieh, Helv. Chim. Acta 2014, 97, 228. (f) A.
Yazdani-Elah-Abadi, R. Mohebat, M. Kangani, J. Chin. Chem.
Soc. 2017, 64, 690. (g) M. Mohammadrezaei, R. Mohebat, M.
Tabatabaee, J. Chin. Chem. Soc. 2018, 65, 1007. (h) G. M.
Rehberg, J. L. Rutherford, J. Heterocycl. Chem. 1995, 42, 1643.
(benzo[a]phenazin-5-ol) derivatives. J Chin Chem
Soc. 2020;1–9. https://doi.org/10.1002/jccs.
202000354