A Green Approach for the One-Pot, Three-Component Synthesis of 2-Arylpyrroloacridin-1(2H)-Ones using Lactic Acid as a Bio-based Catalyst under Solvent-Free Conditions

Article abstract of DOI:10.1002/jccs.201700128

A facile and benign synthetic strategy is proposed for the synthesis of 2-arylpyrroloacridin-1(2H)-ones via a lactic acid-catalyzed three-component reaction of dimedone, various anilines, and isatins under solvent-free conditions. Avoidance of hazardous o

Full text of DOI:10.1002/jccs.201700128

JOURNAL OF THE CHINESE
CHEMICAL SOCIETY
Article
A Green Approach for the One-Pot, Three-Component Synthesis of 2-
Arylpyrroloacridin-1(2H)-Ones using Lactic Acid as a Bio-based Catalyst under
Solvent-Free Conditions
a
a
a
b
*
Maryam Fatahpour, Nourallah Hazeri, Malek Taher Maghsoodlou and Mojtaba Lashkari
aDepartment of Chemistry, Faculty of Sciences, University of Sistan and Baluchestan, P.O. Box 98135-674,
Zahedan, Iran
bFaculty of Sciences, Velayat University, Iranshahr, Iran
(Received: April 9, 2017; Accepted: June 4, 2017; DOI: 10.1002/jccs.201700128)
A facile and benign synthetic strategy is proposed for the synthesis of 2-arylpyrroloacridin-1(2H)-
ones via a lactic acid-catalyzed three-component reaction of dimedone, various anilines, and isa-
tins under solvent-free conditions. Avoidance of hazardous organic solvents, the use of a one-pot
multicomponent procedure for the synthesis of 2-arylpyrroloacridin-1(2H)-ones, operational sim-
plicity, no need for column chromatography, lactic acid utilization as a bio-based organic com-
pound, reusability, homogeneity, and commercial availability of the catalyst, and superior
synthetic performance are some important aspects of this methodology to access a series of pyrro-
loacridine motifs with potentially biological scaffolds.
Keywords: Pyrroloacridine; One-pot synthesis; Three-component reaction; Lactic acid.
INTRODUCTION
Nitrogen heterocyclic compounds, especially with
acetate.7–11 Some of the pyrroloacridines were produced
by the reaction between isatins and enaminones, for
example, with refluxing in toluene in the presence of L-
proline as catalyst,12 using CAN in EtOH under ultra-
sound irradiation,13 using silica sulfuric acid (SSA) as
catalyst under microwave irradiation at 110ꢀC,14 and
with refluxing in AcOH under O2 and catalyzed by I2.15
These reactions suffer from certain drawbacks, including
hard reaction conditions and the use of volatile solvents.
Several methods have been reported for the three-
component synthesis of 2-arylpyrroloacridin-1(2H)-ones
from coupling dimedone, anilines, and isatins in the pres-
ence of various catalysts including the ionic liquid
[HMIm]HSO4,16 Ag NPs/rGO composite,17 SMSNP-
CA,18 tris(hydrogensulfato) boron [B(HSO4)3],19 and
Fe3O4@silica sulfonic acid nanocomposite.20
the core-acridine skeleton, are very promising and note-
worthy targets because of their remarkable array of bio-
activity profiles such as anti-helmintic1 and antitumor
activities.2 Acridnes are also biologically interesting com-
pounds with antibacterial3 and antifungal4 properties.
In this regard, pyrroloacridine derivatives have
shown notable therapeutic and pharmacological proper-
ties. Ascididemin and neoamphimedine (Figure 1),
which are both extracted from ascidians and sponges,
exhibit potent cytotoxic activities against tumor cells
via intercalation into their DNA.5 These properties
have made these compounds attractive targets for
developing new anticancer drugs. Acridine alkaloids
such as plakinidines A, B, and C (Figure 1) exist in
nature, of which the first two have demonstrated
in vitro activity against Nippostrongylus brastiliensis.
Also, plakinidine C has shown activity against reverse
transcriptase.1,6
Owing to the vast application potential of pyrro-
loacridines in the synthesis of bioactive compounds,
serious efforts are still needed for their synthesis using
novel methodologies.
Acridines have been synthesized using several
methods, of which many have utilized the Haunzch reac-
tion of dimedone, aldehyde, and aniline or ammonium
Nowadays, the utilization of the 12 principles of
green chemistry in chemical syntheses is a challenging
topic. To address the fifth principle, the use of any
*Corresponding author. Email: nhazeri@chem.usb.ac.ir
J. Chin. Chem. Soc. 2017
© 2017 The Chemical Society Located in Taipei & Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
1

Article
Fatahpour et al.
Me
N
N
N
H
N
molecular motifs. Compared to organometallic cata-
lysts, enzymes or other bioorganic analogs have definite
advantages such as insensitivity to oxygen and moisture
in the atmosphere, extremely high enantioselectivities,
increased safety of catalysis due to the nontoxic and
environmentally friendly properties that lead to savings
in cost, time, and energy, simplicity of the procedure,
and decrease in chemical waste.27,28
As a part of our focused endeavors toward the
development of greener catalytic systems for important
organic conversions,29–33 here we report a new and effi-
cient three-component strategy for the rapid synthesis
of 2-arylpyrroloacridin-1(2H)-ones by coupling dime-
done 2, diverse anilines 1, and isatins 3 in the presence
of lactic acid as a catalyst in an environmentally benign
manner. Lactic acid, as a bio-based organocatalyst,
plays a fundamental role in different biochemical pro-
cesses. It is prepared commercially by the fermentation
of carbohydrates. Lactic acid is used in the pharmaceu-
tical industry (intravenous fluids), cosmetics (to adjust
acidity), and detergent industry (as a descaler and regis-
tered antibacterial agent). It is used as a food additive
in food preservatives, curing agent, and flavoring
agent.34–36 Therefore, lactic acid is an important and
N
O
R
H
O
N
N
O
O
N
N
N
O
N
NH
NH
Plakinidine A R = NHMe
Plakinidine B R = NMe2
Neoamphimedine
Plakinidine C
Ascidiemin
Fig. 1. Bioactive and natural products containing the
acridine skeleton.
solvent should be suitable for organic reactions.21 On
the other hand, solvent-free reactions present definite
benefits such as simplicity of work-up, decrease in reac-
tion time, and increase in yield.22 In addition, to accom-
plish green syntheses, multicomponent reactions
(MCRs) have gained prominent attention as a pivotal
tool for preparing libraries of diverse drug-like hetero-
cyclic compounds because of atom and step economy,
simple execution, excellent yields, and the minimum
number of work-up, extraction, and purification steps,
thereby eliminating the need for isolation of the inter-
mediates and reduced waste generation.23–26
In recent years, the development of new catalytic
methods based on using organocatalysis or small metal-
free organic molecules has blossomed in organic chem-
istry, especially in the field of medicinal chemistry, as
fundamental tools in the synthesis of complex
Table 1. Optimization of the reaction condition in the presence of different catalysts
Cl
NH2
O
O
N
O
O
Cat
O
+
N
H
Cl
N
4d
1
2
3
Entry
Condition
Temperature (ꢀC)
Time (h)
Isolated yield (%)
1
2
3
4
5
6
7
8
9
Al(H2PO4)3 (0.1 g)
ZnO (20 mol %)
ZnO NPs/EtOH
TiO2 (20 mol %)
La (NO3)3.6H2O (20 mol %)
CAN/EtOH
KHSO4 (20 mol %)
p-TSA (20 mol %)
Benzoic acid (20 mol %)
AcOH (0.1 mL)
70
80
70
80
80
70
80
80
80
70
70
70
5.0
6.0
6.0
7.0
6.5
8.0
7.0
5.5
3.0
2.0
1.5
1.5
48
28
32
20
25
21
26
50
59
69
63
82
10
11
12
Lactic acid (20 mol %)/EtOH
Lactic acid (35 mol %)
2
www.jccs.wiley-vch.de
© 2017 The Chemical Society Located in Taipei & Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
J. Chin. Chem. Soc. 2017

JOURNAL OF THE CHINESE
CHEMICAL SOCIETY
Synthesis of 2-Arylpyrroloacridin-1(2H)-Ones
R1
green catalyst because it is nontoxic, commercially
available, high-yielding, and inexpensive.
R1
1
O
N
NH2
+
O
O
R2
R2
Lactic acid
Solvent-free, 80°C
RESULTS AND DISCUSSION
O
N
N
4a-m
O
For monitoring the optimal reaction conditions, a
trial reaction as a model was carried out using dime-
done, 4-chloroaniline, and isatin. Initially, the reaction
was carried out at under different conditions (Table 1).
As can be seen from the table, acetic acid and lactic
acid gave higher yields than the other catalysts for this
reaction. Lactic acid was, however, found to be even
better than acetic acid not only from the viewpoint of
having better yield but also for using a small amount of
the material. Compared to acetic acid, its pKa is one
unit smaller and the acid strength is slightly higher.
Therefore, the separation of its proton is as comfortable
as with acetic acid and the reaction is carried out in the
presence of low concentrations of the COOH group.
Next, a test reaction was accomplished in the absence
of the catalyst at 80ꢀC. In this condition, the desired
product was not formed even after 24 h (Table 2, entry
1). In order to achieve the optimal conditions, the reac-
tion was performed using various quantities of the cata-
lyst at 80ꢀC (Table 2). The best result was obtained
with 35 mol% of lactic acid (Table 2, entry 3).
H
3
2
Scheme 1. Lactic acid-catalyzed one-pot synthesis of
2-arylpyrroloacridin-1(2H)-ones.
%), with the relative ratio of the substrate dimedone/4-
chloroaniline/isatin of 1.0 mmol :1.0 mmol: 1.0 mmol.
As a result, the reaction between dimedone, 4-chloroa-
niline, and isatin was carried out under the above opti-
mized condition.
For further evaluation of the scope and limitation
of this strategy, a variety of functionalized anilines (1)
were reacted with dimedone (2) and isatin or 5-
bromoisatin (3) under the optimized reaction conditions
(Scheme 1). The results are summarized in Table 3. As
expected, aromatic aldehydes containing electron-
donating and/or electron-withdrawing groups were
applied in the presence of lactic acid to form the corre-
sponding 2-arylpyrroloacridin-1(2H)-ones in good to
high yields (4a–4m).
In order to highlight the unique features of our
procedure, we have compared our results from the syn-
thesis of 2-arylpyrroloacridin-1(2H)-ones, catalyzed by
lactic acid, with those of other reported methods in the
Consequently, the optimal conditions for the best
results were found to be when the reaction was per-
formed at 80ꢀC in the presence of lactic acid (35 mol
Table 2. Effect of the catalyst level and temperature on the reaction between dimedone, 4-chloroaniline, and isatin
Cl
NH2
O
O
N
O
O
Lactic acid
O
+
N
H
Cl
N
4d
1
2
3
Entry
Temperature (ꢀC)
Catalyst (mol %)
Time (min)
Isolated yield (%)
1
2
3
4
5
6
7
8
80
80
80
80
80
70
60
r.t.
–
24 (h)
30
30
30
30
90
24 (h)
24 (h)
–
75
91
90
89
82
67
Trace
25
35
45
50
35
35
35
J. Chin. Chem. Soc. 2017
© 2017 The Chemical Society Located in Taipei & Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.jccs.wiley-vch.de
3

Article
Fatahpour et al.
Table 3. Synthesis of corresponding 2-arylpyrroloacridin-1(2H)-one derivatives
R1
O
NH2
O
N
O
O
R2
+
Lactic acid
R2
+
O
Solvent-free, 80°C
N
H
N
R1
1
2
3
4a-m
Me
MeO
C1
Br
O
O
O
N
O
O
N
N
N
N
N
N
N
N
N
4c, 25min, 88%
4a, 30min, 89%
4e, 30min, 93%
4d, 30min, 91%
4b, 25min, 90%
F
O2N
Me
Me
N
O2N
O
O
O
N
O
N
N
Br
N
N
N
N
4i, 30min, 91%
4h, 45min, 84%
4g, 35min, 88%
4f, 20min, 88%
Cl
CN
Br
Cl
Br
Cl
O
N
O
N
O
N
O
N
Br
N
N
N
N
4k, 30min, 89%
4j, 25min, 93%
4l, 35min, 85%
4m, 35min, 90%
literature,[12] as shown in Table 4. Pyrroloacridine deri-
vatives have extensively been used in the synthesis of
drugs and pharmaceuticals, so the elimination of resid-
ual metal species plays a pivotal role when a metal-
containing catalyst is applied. So, some of the advan-
tages of this method, when compared to existing meth-
ods, are the use of lactic acid as an efficient, nontoxic,
inexpensive organocatalyst, reusability and commercial
availability of the catalyst, avoidance of the use of any
solvent (solvent free conditions), and no hard
conditions.
The melting points as well as the IR and NMR
spectra all of known products clearly indicated the for-
mation of desirable compounds. The structures of the
products were confirmed through comparison with
those reported in the literature. The structures of new
1
products 4l and 4m were deduced from IR, H-NMR,
and 13C-NMR spectroscopic methods. For example,
Table 4. Comparison of the results obtained from the synthesis of 2-arylpyrroloacridin-1(2H)-ones using the reaction between
dimedone, 4-chloroaniline, and isatin in the presence of lactic acid with those obtained via other catalysts
Catalyst
Reaction condition
Time (min)
Yield (%)
Ref.
[HMIm]HSO4
Ag NPs/rGO
SMSNP-CA
[B(HSO4)3]
Fe3O4@SiO2-SO3H NPs
Lactic acid
80ꢀC
35
2
6 h
7
14
30
88
90
91
92
88
91
16
17
18
19
20
EtOH/MW
Reflux in EtOH
Reflux in EtOH
80ꢀC
80ꢀC/solvent-free
This work
4
www.jccs.wiley-vch.de
© 2017 The Chemical Society Located in Taipei & Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
J. Chin. Chem. Soc. 2017

JOURNAL OF THE CHINESE
CHEMICAL SOCIETY
Synthesis of 2-Arylpyrroloacridin-1(2H)-Ones
the 1H NMR spectrum of the new compound 4l
(Figure 2) showed one sharp singlet at 1.31 ppm, which
is related to the protons of the two methyl groups. A
singlet was observed at 3.19 ppm, which was related to
the methylene protons. The peak due to the vinyl pro-
ton appeared at 5.61 ppm as a singlet. The chemical
shift values and coupling constants of aromatic protons
have shown the presence of seven protons related to
aromatic protons. The 13C NMR spectrum of com-
pound 4l exhibited 21 signals, in agreement with the
suggested motifs. The IR spectrum of compound 4l
showed absorption bands at 1700 cm−1 for the carbonyl
groups and at 1655 cm−1 related to the C N group in
the cyclic system.
R1
O
OH
N
R2
R2
O
N
H
N
H
R2
O
N
-H2O
R2
R1
NH
O
HO
H
H2N
O
N
O
N
OH
R1
NH2
R1
A
r
R1
e
c
y
c
l
i
-H
2
z
t
i
o
O
R2
NH
n
O
O
HO
O
OH
N
O
H
R1
B
Scheme 2. Proposed mechanism for the synthesis of
2-arylpyrroloacridin-1(2H)-ones
using
A tentative mechanism for the synthesis of 2-aryl-
pyrroloacridin-1(2H)-ones is depicted in Scheme 2,
which is in agreement with those in the literature.11 At
first, enaminone is formed via the condensation of
dimedone and anilines, and subsequent addition of isa-
tins generates the intermediate A. Next, intermediate
A affords intermediate B with the elimination of one
H2O molecule. Finally, intermediate B undergoes sub-
sequent stages intramolecular cyclization/ring-opening/
recyclization to give the desired product (4a–m).
As shown in Figure 1, the reusability of lactic acid
was examined in the synthesis of 2-arylpyrroloacridin-1
(2H)-one 4d as an example. It was observed that the
yield of product gets reduced slightly in the fourth and
fifth runs.
lactic acid.
bio-based compound, which is a benign and commer-
cially available catalyst, under solvent-free conditions.
The unique aspects of this protocol are the simplicity
of operation, avoidance of the use of any hazardous
organic solvent, and the generation of the desired
product in high yields without any troublesome by-
products, in addition to the ease of work-up and
purification.
EXPERIMENTAL
General
Melting points and IR spectra of all compounds
were determined by an Electrothermal 9100 apparatus
and a JASCO-460 plus FT-IR spectrometer, respectively.
CONCLUSIONS
1
The H and 13C NMR spectra of the compounds were
In summary, with the aim of achieving green syn-
thesis, we have developed a one-pot, three-component,
and ecofriendly route to functionalize 2-arylpyrroloacri-
din-1(2H)-ones from the reaction of dimedone, various
anilines, and isatins in the presence of lactic acid as a
recorded on a Bruker DRX-400 Avance instrument in
DMSO at 300 MHz. All chemicals were obtained from
Merck (Darmastadt, Germany) and Fluka (Buchs,
Switzerland) and used without further purification.
8.66, dd, J = 8.1 Hz, J = 1.2 Hz, 129.7
7.60-7.67 , m, 125.4
7.60-7.67 , m, 128.0
Cl
O
133.3
Cl
126.3
166.3
8.15, d, J = 8.4 Hz,131.0
131.4
134.1
N
7.75, dt, J = 6.9 Hz, J = 1.5 Hz, 127.9
124.5
149.7
132.7
122.3
N
7.57, d, J = 8.7 Hz, 124.1
5.61 , S,118.5
154.4
7.36, dd, J = 8.7 Hz, J = 2.4 Hz, 129.5
3.19, S, 37.1
1.31, S,30.8
Fig. 3. Recyclability of the catalyst in the synthesis
of 4d over five runs.
Fig. 2. NMR data of compound 4l.
J. Chin. Chem. Soc. 2017
© 2017 The Chemical Society Located in Taipei & Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.jccs.wiley-vch.de
5

Article
Fatahpour et al.
General procedure for the preparation of 2-
arylpyrroloacridin-1(2H)-ones
(1H, dt, J = 7.6 Hz, J = 1.5 Hz, ArH), 8.19 (1H, d,
J = 8.0 Hz, ArH), 8.75 (1H, dd, J = 8.0 Hz,
J = 1.2 Hz, ArH).
A mixture of dimedone (1.0 mmol), anilines
(1.0 mmol), and isatins (1.0 mmol) in the presence of
lactic acid (35 mol %) was stirred at 80ꢀC under
solvent-free conditions in an oil bath for 20–45 min.
The completion of the reaction was monitored through
thin-layer chromatography (TLC). After cooling the
reaction mixture to room temperature, water was added
and the catalyst, and the solution was filtered to sepa-
rate the desired product. After washing with EtOH
(5 mL), and the product was separated. Finally, for
high purification, the solid product was recrystallized
from ethanol to give the products 4a–m. The solvent of
the aqueous layer was evaporated to obtain pure
lactic acid. The spectra of compounds have been
reported in supporting information.
2-(4-Chlorophenyl)-4,5-dihydro-4,4-dimethylpyrrolo[2,3,4-kl]
acridin-1(2H)-one (4d).
Yellow powder; M.p.:
184–187ꢀC (Lit.: 189–190ꢀC)16; IR (KBr, cm−1):
3046, 2966, 1703, 1649, 1494, 1345, 1090, 824, 774,
506., 1H NMR (300 MHz, CDCl3): 1.31 (6H, s,
2CH3), 3.19 (2H, s, CH2), 5.56 (1H, s, CH), 7.46
(4H, q, J = 7.8 Hz, ArH), 7.64 (1H, dt, J = 7.5 Hz,
ArH), 7.74 (1H, dt, J = 7.8 Hz, J = 1.2 Hz, ArH),
8.15 (1H, d, J = 8.1 Hz, ArH), 8.62 (1H, dd,
J = 7.9 Hz, J = 1.2 Hz, ArH).
2-(4-Bromophenyl)-4,4-dimethyl-4,5-dihydro-2H-pyrrolo[2,3,4-
kl]acridin-1-one
(4e).
Yellow
powder;
M.p.:
195–198ꢀC (Lit.: 191–192ꢀC)19; IR (KBr, cm−1): 3035,
1
2964, 1703, 1649, 1492, 1345, 1075, 822, 774, 501., H
NMR (300 MHz, CDCl3): 1.36 (6H, s, 2CH3), 3.24
(2H, s, CH2), 5.64 (1H, s, CH), 7.43 (2H, d,
J = 8.7 Hz, ArH), 7.67–7.72 (3H, m, ArH), 7.79 (1H,
dt, J = 7.2 Hz, J = 1.5 Hz, ArH), 8.20 (1H, d,
J = 8.4 Hz, ArH), 8.73 (1H, dd, J = 8.1 Hz,
J = 1.2 Hz, ArH).
Characterization data of selected compound
4,4-Dimethyl-2-phenyl-4,5-dihydropyrrolo[2,3,4-kl]acridin-1
(2H)-one (4a).
Yellow powder; M.p.: 189–191ꢀC
(Lit.: 191–193ꢀC)17; IR (KBr, cm−1): 3060, 2956, 1696,
1496, 1647, 1496, 1345, 1136, 777., 1H NMR
(300 MHz, CDCl3): 1.35 (6H, s, 2CH3), 3.24 (2H, s,
CH2), 5.65 (1H, s, CH), 7.41–7.45 (1H, m, ArH),
7.52–7.60 (4H, m, ArH), 7.68 (1H, t, J = 7.5 Hz, ArH),
7.78 (1H, dt, J = 7.6 Hz, J = 1.5 Hz, ArH), 8.19 (1H,
d, J = 8.0 Hz, ArH), 8.75 (1H, dd, J = 8.0 Hz,
J = 1.2 Hz, ArH).
2-(4-Fluorophenyl)-4,4-dimethyl-4,5-dihydro-2H-pyrrolo[2,3,4-
kl]acridin-1-one
(4f).
Yellow
powder;
M.p.:
195–197ꢀC (Lit.: 190–191ꢀC)20; IR (KBr, cm−1): 3069,
2958, 1700, 1638, 1511, 1224, 842, 774., 1H NMR
(300 MHz, CDCl3): 1.36 (6H, s, 2CH3), 3.24 (2H, s,
CH2), 5.60 (1H, s, CH), 7.26 (2H, t, J = 8.1 Hz, ArH),
7.48–7.53 (2H, m, ArH), 7.69 (1H, d, J = 7.6 Hz,
ArH), 7.79 (1H, dt, J = 7.0 Hz, J = 1.5 Hz, ArH), 7.79
(1H, d, J = 8.4 Hz, ArH), 8.73 (1H, dd, J = 7.9 Hz,
J = 1.2 Hz, ArH).
4,4-Dimethyl-2-p-tolyl-4,5-dihydro-2H-pyrrolo[2,3,4-kl]acridin-
1-one (4b).
Yellow powder; M.p.: 214–217ꢀC (Lit.:
218–220ꢀC)17; IR (KBr, cm−1): 3036, 2958, 1697, 1648,
1515, 1346, 1135, 820, 776., 1H NMR (300 MHz,
CDCl3): 1.35 (6H, s, CH3), 2.46 (3H, s, CH3), 3.23 (2H,
s, CH2), 5.62 (1H, s, CH), 7.37 (4H, q, J = 8.4 Hz,
ArH), 7.67 (1H, t, J = 6.9 Hz, ArH), 7.78 (1H, t,
J = 7.0 Hz, J = 1.5 Hz, ArH), 8.19 (1H, d, J = 8.4 Hz,
J = 1.5 Hz, ArH), 8.75 (1H, d, J = 7.2 Hz, ArH).
4,4-Dimethyl-2-(4-nitrophenyl)-4,5-dihydropyrrolo[2,3,4-kl]acri-
din-1(2H)-one (4g).
Yellow powder; M.p.: 176–179ꢀC
(Lit.: 175–177ꢀC)19; IR (KBr, cm−1): 3071, 2961, 1708,
1
1652, 1524, 1344, 1081, 838, 774., H NMR (300 MHz,
CDCl3): 1.38 (6H, s, 2CH3), 3.26 (2H, s, CH2), 5.78
(1H, s, CH), 7.43 (1H, t, J = 7.2 Hz, ArH), 7.78–7.83
(3H, m, ArH), 8.21 (1H, d, J = 8.4 Hz, ArH), 8.44
(2H, d, J = 9 Hz, ArH), 8.71 (1H, d, J = 7.3 Hz, ArH).
2-(4-Methoxyphenyl)-4,4-dimethyl-4,5-dihydropyrrolo[2,3,4-kl]
acridin-1(2H)-one
(4c).
Yellow powder; M.p.:
186–188ꢀC (Lit.: 185–187ꢀC)18; IR (KBr, cm−1): 3053,
1
2-(2-Methyl-4-nitrophenyl)-4,4-dimethyl-4,5-dihydro-2H-pyr-
2954, 1712, 1651, 1514, 1348, 1257, 1117, 829, 777., H
rolo[2,3,4-kl]acridin-1-one (4h).
Yellow powder; M.p.:
NMR (300 MHz, CDCl3): 1.35 (6H, s, 2CH3), 3.23
(2H, s, CH2), 3.90 (3H, s, OCH3), 5.58 (1H, s, CH),
7.08 (2H, d, J = 8.9 Hz, ArH), 7.43 (2H, d,
J = 9.0 Hz, ArH), 7.68 (1H, t, J = 7.5 Hz, ArH), 7.78
182–185ꢀC (Lit.: 185–186ꢀC)16; IR (KBr, cm−1): 3065,
2960, 1714, 1650, 1465, 1349, 1142, 771., 1H NMR
(300 MHz, CDCl3): 1.35 (3H, s, CH3), 1.36 (3H,
6
www.jccs.wiley-vch.de
© 2017 The Chemical Society Located in Taipei & Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
J. Chin. Chem. Soc. 2017

JOURNAL OF THE CHINESE
CHEMICAL SOCIETY
Synthesis of 2-Arylpyrroloacridin-1(2H)-Ones
2-(2-Cyanophenyl)-4,5-dihydro-4,4-dimethylpyrrolo[2,3,4-kl]
s, CH3), 2.39 (3H, s, CH3), 3.26 (2H, s, CH2), 5.31 (1H,
s, CH), 7.52 (1H, d, J = 8.7 Hz, ArH), 7.71 (1H, t,
J = 7.5 Hz, ArH), 7.82 (1H, dt, J = 7.6 Hz,
J = 1.5 Hz, ArH), 8.21–8.27(2H, m, ArH), 8.33 (1H, s,
ArH), 8.71 (1H, dd, J = 7.9 Hz, J = 1.2 Hz, ArH).
acridin-1(2H)-one
(4m).
Brown powder; M.p.:
244–246ꢀC (This work); IR (KBr, cm−1): 3037, 2968,
2227, 1715, 1658, 1494, 1348, 1137, 841, 771., 1H
NMR (300 MHz, CDCl3): 1.30 (3H, s, CH3), 1.34 (3H,
s, CH3), 3.20 (1H, s, CH2), 3.22 (1H, s, CH2), 5.42 (1H,
s, CH), 7.55 (2H, t, J = 7.3 Hz, ArH), 7.59 (1H, t,
J = 7.2 Hz, ArH), 7.76 (2H, q, J = 7.5 Hz, ArH), 7.85
(1H, d, J = 7.5 Hz, ArH), 8.16 (1H, d, J = 8.4 Hz,
ArH), 8.67 (1H, d, J = 8.1 Hz, ArH). 13C NMR
(75.65 MHz, CDCl3): δ 30.8, 37.2, 44.1, 112.6, 116.1,
118.4, 122.4, 124.2, 124.5, 126.9, 128.0, 128.8, 129.4,
129.5, 129.7, 132.6, 133.9, 134.1, 137.3, 149.7, 154.5,
166.3; Anal. calcd for C23H17N3O: C, 78.61; H,
4.88; N, 11.96; Found: C, 78.99; H, 5.03; N, 12.19.
9-Bromo-2-(4-chlorophenyl)-4,4-dimethyl-4,5-dihydropyrrolo
[2,3,4-kl]acridin-1(2H)-one (4i).
Yellow powder; M.p.:
214–217ꢀC (Lit.: 219–221ꢀC)16; IR (KBr, cm−1): 3043,
2959, 1699, 1645, 1505, 1365, 1091, 826, 499., 1H
NMR (300 MHz, CDCl3): 1.35 (6H, s, 2CH3), 3.21
(2H, s, CH2), 5.67 (1H, s, CH), 7.45–7.55 (4H, m,
ArH), 7.83 (1H, d, J = 8.4 Hz, ArH), 8.03 (1H, d,
J = 8.9 Hz, ArH), 8.85 (1H, s, ArH).
9-Bromo-2-(4-bromophenyl)-4,4-dimethyl-4,5-dihydropyrrolo
[2,3,4-kl]acridin-1(2H)-one (4j).
Yellow powder; M.p.:
184–186ꢀC (Lit.: 184–186ꢀC)12; IR (KBr, cm−1): 3067,
2957, 1699, 1645, 1505, 1364, 825, 498., 1H NMR
(300 MHz, CDCl3): 1.36 (6H, s, 2CH3), 3.21 (2H, s,
CH2), 5.68 (1H, s, CH), 7.41 (2H, d, J = 8.4 Hz, ArH),
7.69 (2H, d, J = 8.7 Hz, ArH), 7.84 (1H, dd,
J = 9.0 Hz, J = 2.1 Hz, ArH), 8.03 (1H, d, J = 9.0 Hz,
ArH), 8.86 (1H, s, ArH).
ACKNOWLEDGMENTS
We gratefully appreciate the financial support
from the Research Council of the University of Sistan
and Baluchestan.
Supporting information
Additional supporting information is available in
the online version of this article.
9-Bromo-4,4-dimethyl-2-(p-tolyl)-4,5-dihydropyrrolo[2,3,4-kl]
acridin-1(2H)-one
(4k).
Yellow powder; M.p.:
199–202ꢀC (Lit.: 204–206ꢀC)16; IR (KBr, cm−1): 3039,
2959, 1701, 1645, 1515, 1365, 828, 498., 1H NMR
(300 MHz, CDCl3): 1.34 (6H, s, 2CH3), 2.46 (3H, s,
CH3), 3.20 (2H, s, CH2), 5.65 (1H, s, CH), 7.38 (4H, s,
ArH), 7.83 (1H, dd, J = 8.4 Hz, J = 1.5 Hz, ArH),
8.03 (1H, d, J = 8.9 Hz, ArH), 8.89 (1H, s, ArH).
REFERENCES
1. W. D. Inman, M. O’Neill-Johnson, P. Crews, J. Am.
Chem. Soc. 1990, 112, 1.
2. A. Chilin, G. Marzaro, C. Marzano, L. D. Via,
M. Grazia Ferlin, G. Pastorini, A. Guiotto, Bioorg. Med.
Chem. 2009, 17, 523.
3. M. Wainwright, J. Antimicrob. Chemother. 2001, 47, 1.
4. P. J. McCarthy, T. P. Pitts, G. P. Gunawardana,
M. Kelly-Borges, S. A. Pomponi, J. Nat. Prod. 1992,
55, 1664.
5. N. Dias, H. Vezin, A. Lansiaux, C. Bailly, Top. Curr.
Chem. 2005, 253, 89.
6. R. R. West, C. L. Mayne, C. M. Ireland, L. C. Brinen,
J. Clardy, Tetrahedron Lett. 1990, 31, 3271.
7. M. Kaya, Y. Yildirir, Y. G. Celik, Med. Chem. Res.
2011, 20, 293.
8. S. T. Tu, Z. Lu, D. Shi, C. Yao, Y. Gao, C. Guo, Synth.
Commun. 2002, 32, 2181.
9. D. Binoyargha, N. Sibaji, K. P. Amarta, Tetrahedron
Lett. 2014, 55, 5236.
10. K. Ahmed, B. Dubey, S. Nadeem, B. Shrivastava,
P. Sharma, Chin. Chem. Lett. 2016, 27, 721.
11. M. A. Zolfigol, N. Bahrami-Nejad, S. Baghery, J. Mol.
Liq. 2016, 218, 558.
2-(3,4-Dichlorophenyl)-4,5-dihydro-4,4-dimethylpyrrolo[2,3,4-
kl]acridin-1(2H)-one (4l).
Yellow powder; M.p.:
188–191ꢀC (This work); IR (KBr, cm−1): 3047, 2961,
1703, 1650, 1479, 1227, 1088, 825, 776., 1H NMR
(300 MHz, CDCl3): 1.31 (6H, s, CH3), 3.19 (2H, s,
CH2), 5.61 (1H, s, CH), 7.36 (1H, dd, J = 8.7 Hz,
J = 2.4 Hz, ArH), 7.57 (1H, d, J = 8.7 Hz, ArH),
7.60–7.67 (2H, m, ArH), 7.75 (1H, dt, J = 6.9 Hz,
J = 1.5 Hz, ArH), 8.15 (1H, d, J = 8.4 Hz, ArH), 8.66
(1H, dd, J = 8.1 Hz, J = 1.2 Hz, ArH), 13C NMR
(75.65 MHz, CDCl3):
δ 30.8, 37.1, 44.0, 118.5,
122.3,124.1, 124.5, 125.4, 126.3, 127.9, 128.0,
129.5,129.7 ,131.0, 131.4, 132.7, 133.3, 134.1,
149.7, 154.4, 166.3; Anal. calcd for C22H16Cl2N2O:
C, 66.85; H, 4.08; N, 7.09; Found: C, 67.13; H,
4.21; N, 7.26.
J. Chin. Chem. Soc. 2017
© 2017 The Chemical Society Located in Taipei & Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.jccs.wiley-vch.de
7

Article
Fatahpour et al.
12. H. Wang, L. Li, W. Lin, P. Xu, Z. Huang, D. Shi, Org.
Lett. 2012, 14, 4598.
25. R. C. Cioc, E. Ruijter, R. V. A. Orru, Green Chem. 2014,
16, 2958.
13. L. L. Li, H. Y. Wang, W. Lin, Z. B. Huang, D. Q. Shi,
J. Hetercyclic Chem. 2014, 51, 1778.
26. R. W. Armstrong, A. P. Combs, P. A. Tempest,
S. D. Brown, T. A. Keating, Acc. Chem. Res. 1996,
29, 123.
27. D. W. C. Macmillan, Nature 2008, 455, 304.
28. P. I. Dalko, L. Moisan, Angew. Chem. Int. Ed. 2001,
40, 3726.
29. M. Fatahpour, N. Hazeri, M. T. Maghsoodlou,
M. Lashkari, Iran. J. Sci. Technol. Trans. Sci. 2016. DOI:
https://doi.org/10.1007/s40995-016-0064-1.
30. M. Kangani, N. Hazeri, M. T. Maghsoodlou, J. Saudi
Chem. Soc. 2017, 21, 160.
14. C. Cao, C. Xu, W. Lin, X. Li, M. Hu, J. Wang,
Z. Huang, D. Shi, Y. Wang, Molecules 2013, 18, 1613.
15. W. J. Hao, J. Q. Wang, X. P. Xu, S. L. Zhang,
S. Y. Wang, S. J. Ji, J. Org. Chem. 2013, 78, 12362.
16. H. Kefayati, F. Narchin, K. Rad-Moghadam, Tetrahe-
dron Lett. 2012, 53, 4573.
17. A. Dandia, A. Sharma, V. Parewa, B. Kumawat,
K. S. Rathoreb, A. Sharmab, RSC Adv. 2015, 5, 91888.
18. S. Ray, A. Bhaumik, M. Pramanikb, C. Mukhopadhyay,
RSC Adv. 2014, 4, 15441.
31. N. Hazeri, M. T. Maghsoodlou, S. M. Habibi-
Khorassani, J. Aboonajmi, S. S. Sajadikhah, J. Chin.
Chem. Soc. 2013, 60, 355.
19. Z. Karimi-Jaberi, A. Jaafarizadeh, J. Res. Chem. Interme-
diat. 2015, 41, 4913.
20. M. A. Ghasemzadeh, B. Mirhosseini-Eshkevari, J. Chem.
Res. 2015, 39, 380.
21. P. G. Jessop, S. Trakhtenberg, J. Warner, ACS Sym. Ser.
2009, 1000, 401.
22. R. Ghorbani-Vaghei, S. Noori, Z. Toghraei-Semiromi,
Z. Salimi, RSC Adv. 2014, 4, 47925.
32. N. Hazeri, M. T. Maghsoodlou, N. Mahmoudabadi,
R. Doostmohammadi, S. Salahi, Curr. Organocatal. 2014,
1, 45.
33. N. Hazeri, S. S. Sajadikhah, M. T. Mghsoodlou,
S. Mohamadian-Souri, M. Norouzi, M. Moein, J. Chin.
Chem. Soc. 2014, 61, 217.
23. G. B. Dharma Rao, B. Anjaneyulu, M. P. Kaushik,
RSC Adv. 2014, 4, 43321.
24. C. de Graaff, E. Ruijter, R. V. A. Orru, Chem. Soc. Rev.
2012, 41, 3969.
34. V. Romero-Gil, P. García-García, A. Garrido-Fernandez,
F. N. Arroyo-Lopez, Food Microbiol. 2016, 54, 72.
35. V. Juturu, J. C. Wu, Crit. Rev. Biotechnol. 2016, 36, 967.
36. J. Yang, J. N. Tana, Y. Gu, Green Chem. 2012, 14, 3304.
8
www.jccs.wiley-vch.de
© 2017 The Chemical Society Located in Taipei & Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
J. Chin. Chem. Soc. 2017