An efficient synthesis of pyrroline-fused acridine derivatives catalyzed by silica sulfuric acid

Article abstract of DOI:10.1002/jhet.2023

A simple and efficient synthesis of pyrrolo[2,3,4-kl]acridine-1-one derivatives via the cascade reaction of isatins with enaminones catalyzed by silica sulfuric acid (SSA) has been established. In this reactions, SSA shows a highly catalytic nature: easy to handle procedure, short reaction time, recycle exploitation, insensitivity to air and moisture, and excellent isolated yields. The catalyst could be recycled at least five times.

Full text of DOI:10.1002/jhet.2023

Month 2014 An Efficient Synthesis of Pyrroline-Fused Acridine Derivatives Catalyzed
by Silica Sulfuric Acid
*
*
Ming-Hua Hu, Wei Lin, Cheng-Pao Cao, Zhi-Bin Huang, and Da-Qing Shi
Key Laboratory of Organic Synthesis of Jiangsu Province, College of Chemistry, Chemical Engineering and Materials
Science, Soochow University, Suzhou 215123, People’s Republic of China
*
E-mail: zbhuang@suda.edu.cn or dqshi@suda.edu.cn
Received December 14, 2012
DOI 10.1002/jhet.2023
Published online 00 Month 2014 in Wiley Online Library (wileyonlinelibrary.com).
A simple and efficient synthesis of pyrrolo[2,3,4-kl]acridine-1-one derivatives via the cascade reaction of
isatins with enaminones catalyzed by silica sulfuric acid (SSA) has been established. In this reactions, SSA
shows a highly catalytic nature: easy to handle procedure, short reaction time, recycle exploitation, insensi-
tivity to air and moisture, and excellent isolated yields. The catalyst could be recycled at least five times.
J. Heterocyclic Chem., 00, 00 (2014).
INTRODUCTION
various chemical transformations processes by catalysts un-
der heterogeneous conditions has occurred. Among several
solid acid catalysts used in organic reactions, silica sulfuric
acid (SSA) is a versatile catalyst that makes reaction
processes convenient, more economic and environmentally
benign [11]. Owing to the numerous advantages associated
with this cheap and non-hazardous reagent, SSA has been
explored as a powerful catalyst for various organic transfor-
mations under mild conditions [12–16], which has been
used in catalytic Friedel–Crafts acylation reaction [17],
cross-Aldol condensation [18], selective oxidation [19],
and groups protecting [20]. In our previous works, SSA
was used as an efficient catalyst for the acetylation of alde-
hydes or sugars [21]. In this paper, we have the opportunity
to further explore the catalytic activity of SSA for the
synthesis of pyrrolo[2,3,4-kl]acridine-1-one derivatives.
Polycyclic-fused pyrroles are among the most ubiquitous
heterocycles in nature and often referred to as ‘privileged
structures’ in drug discovery because of their biological ac-
tivities such as antibacterial, antiviral, anti-inflammatory,
anti-tumoral, and antioxidant activities [1–5]. Pyrrolo
[2,3,4-kl]acridine is an important polycyclic-fused pyrroles.
In 1990, three novel pentacyclic alkaloids, Plakinidines A,
B, and C (Figure 1), were isolated from a Plakortis sponge
[6,7]. Plakinidines A and B exhibited in vitro activity against
Nippostrongylus brastiliensis, and Plakinidine A showed
weak activity against reverse transcriptase. Those alkaloids
possess a unique heterocyclic parent ring system, pyrrolo
[2,3,4-kl]acridine. Recently, there have been many studies
on the synthesis of these molecules. Gellerman et al. reported
the biomimetic synthesis of marine alkaloid related pyrido-
and pyrrolo[2,3,4-kl]acridines via the reaction between
b,b-diamenoketones and a variety cyclohexanediones and
quinines [8]. Kitahara et al. reported the synthesis of pyrrolo
[2,3,4-kl]acridine from 2-acetyl-30-nitrodiphenylamine in nine
steps [9]. The development of new convenient and step-
economical approaches to this family of heterocyclic com-
pounds, producing less waste and byproduct, continues to be
of considerable interest and important for modern organic
and medicinal chemistry, particularly, for drug discovery
and development.
RESULTS AND DISCUSSION
In the preliminary study, a variety of different condi-
tions, including reaction solvents, temperature, catalyst,
and catalyst amount of SSA were investigated using isatin
(1a), 3-(4-methoxyphenylamino)-5,5-dimethylcyclohex-2-
enone (2d) as model reactants (Scheme 1). The results
are summarized in Table 1.
The optimization process revealed that the reaction
could not proceed in ethanol under catalyst-free conditions
(Table 1, entry 1). To our delighted, the target compound
3d was obtained in 73% yield in ethanol with the presence
of SSA (Table 1, entry 2). Subsequently, we further turned
to evaluate the effect of solvent. AcOH, ethanol, and THF
In recent years, the use of solid acid catalysts has gained
considerable attention in a wide range of organic transfor-
mations, for example, operational simplicity, environmen-
tal compatibility, non-toxicity, reusability, low cost, and
ease of isolation [10]. A tremendous upsurge of interest in
© 2014 HeteroCorporation

M.-H. Hua, W. Lin, C.-P. Cao, Z.-B. Huang, and D.-Q. Shi
Vol 000
was found that when increasing catalytic loading of SSA
from 0.01 to 0.03 g led to an increase in the yield from
76% to 92% (Table 1, entry 5, entry 11–12), which showed
that the catalyst concentration plays a major role in the
reaction. However, the yields decreased unexpectedly when
the addition of larger amounts of the catalyst (Table 1,
entries 13–14). Thus, 0.03 g of SSA is a suitable choice
for optimum yield of 3d. Finally, to identify the optimum
reaction temperature, the reaction was carried out with
0.03 g of SSA at 30ꢀC, 50ꢀC, 70ꢀC, 90ꢀC, and reflux tem-
perature, providing the product 3d in yields of 30%, 62%,
71%, 87%, and 92% (Table 1, entries 15–28 and 5), respec-
tively. The reaction time is about 40 min (Table 1, entry 5);
however, prolonging the reaction time did not improve the
yield of the product (Table 1, entry 23). Thus, the optimum
conditions required the use of 0.03 g of SSA in a toluene
solvent at reflux.
Figure 1. Structures of pyrrolo[2,3,4-kl]acridine derivatives in nature.
Scheme 1. Model reaction.
OCH3
O
O
O
H3CO
N
+
O
N
H
N
H
N
1a
3d
2d
To explore the application of this method, the scope of
the substrates was evaluated with a variety of isatins 1
and enaminone 2 on the optimization of reaction condi-
tions (Scheme 2). The results are summarized in Table 2.
As shown in Table 2, we were pleased to find that the
method was applicable to a broad substrate scope on both
substituted isatins 1 and enaminone 2. It can be seen that
this protocol can be applied not only to the enaminone 2
with electron-donating groups (such as methyl, methoxyl,
or tert-butyl groups) or electron-withdrawing groups
(such as halides or nitro groups) but also to the alkyl
groups that were well tolerated under the reaction
conditions. Meanwhile, it was particularly noteworthy that
the effects of different isatins were also investigated.
4-Chloroisatinremained intact and only the starting mate-
rials were recovered (Table 2, entry 24). This failure to react
was attributed to the effect of steric hindrance upon the reac-
tivity of carbonyl group. 5-Substituted or 6-substituted
isatins can give good yields.
Table 1
Optimizing the reaction conditions for the synthesis of compound 3d.
Time Yielda
Entry
Solvent
Ethanol
Catalyst
-
T (ꢀC)
(min)
(%)
1
2
3
4
5
6
7
8
Reflux
Reflux
Reflux
Reflux
Reflux
Reflux
240
100
45
trace
73
78
Ethanol SSA (0.03 g)
AcOH
THF
SSA (0.03 g)
SSA (0.03 g)
Toluene SSA (0.03 g)
Toluene SiO2 (0.03 g)
Toluene SiO2-I2 (0.03 g) Reflux
Toluene SiO2-H2SO4
(0.03 g)
Toluene I2 (0.03 g)
Toluene SnCl2 (0.03 g)
Toluene SSA (0.01)
Toluene SSA (0.02)
Toluene SSA (0.04)
Toluene SSA (0.05)
Toluene SSA (0.03)
Toluene SSA (0.03)
Toluene SSA (0.03)
Toluene SSA (0.03)
Toluene SSA (0.03)
Toluene SSA (0.03)
Toluene SSA (0.03)
Toluene SSA (0.03)
Toluene SSA (0.03)
50
67
40
92
150
60
83
89
Reflux
90
59
9
Reflux
Reflux
Reflux
Reflux
Reflux
Reflux
30
50
70
90
Reflux
Reflux
Reflux
Reflux
Reflux
90
180
120
60
40
40
100
100
80
60
20
59
53
76
80
91
91
30
62
71
87
25
47
53
76
92
10
11
12
13
14
15
16
17
18
19
20
21
22
23
To expand the scope of the present method, N-substituted
3-aminocyclohex-2-enone, N-substituted
3-amino-5-
phenylcyclohex-2-enone, or N-substituted 3-amino-5-
methylcyclohex-2-enone (4) was examined to replace
N-substituted 3-amino-5,5-dimethylcyclohex-2-enone (2).
To our surprising, under the aforementioned optimized
conditions, the desired products 4,5-dihydropyrrolo
[2,3,4-kl]acridine derivatives 3 were not obtained. From
its 1H NMR spectrum, the signals of methylene group
25
30
35
45
SSA, silica sulfuric acid.
aYield was determined by HPLC-MS.
showed no superiority to toluene as solvents (Table 1,
entries 2–5). Several other catalysts were also evaluated
for their catalytic efficiency in the current reaction (Table 1,
entries 5–10). The reaction preceded in good yield 92%
(Table 1, entry 5) of 3d when SSA was used. The impor-
tant role of SSA in this reaction may be attributed to its
apropos acidity and has ability to form H-bond. We also
evaluated the amount of SSA required for this reaction. It
Scheme 2. The synthesis of 4,5-dihydropyrrolo[2,3,4-kl]acridine-one
derivatives 3.
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

Month 2014
An Efficient Synthesis of Pyrroline-Fused Acridine Derivatives Catalyzed by Silica
Sulfuric Acid
Table 2
Table 3
Synthesis of 4,5-dihydropyrrolo[2,3,4-kl]acridine-one derivatives 3.
Synthesis of pyrrolo[2,3,4-kl]acridine derivatives 5.
Time Yield
Time
R3 (min)
Yield
(%)
Entry Product
R1
R2
(min)
(%)
Entry Product
R1
R2
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
3r
3s
H
H
H
H
H
H
H
H
H
5-F
5-F
5-F
5-F
C6H5
4-ClC6H4
4-BrC6H4
50
60
70
45
40
120
100
45
50
45
45
45
40
40
60
45
40
45
45
40
60
60
50
120
90
90
93
91
92
87
83
92
90
91
92
94
91
90
91
91
92
92
90
91
89
91
90
NR
1
2
3
4
5
6
7
8
5a
5b
5c
5d
5e
5f
5g
5h
5i
5j
5k
5l
5m
5n
5o
5p
5q
5r
5s
H
H
H
H
5-F
5-F
5-F
C6H5
H
H
H
H
H
H
H
H
H
80
60
80
70
70
45
40
120
100
70
60
45
55
60
60
60
60
83
82
85
86
83
81
82
80
81
87
87
86
88
86
84
85
83
84
85
3,5-(CH3)2C6H3
3-Cl-4-FC6H3
2-ClC6H4
4-CH3OC6H4
4-ClC6H4
4-CH3OC6H4
4-CH3C6H4
4-NO2C6H4
3-Cl-4-FC6H3
3,5-(CH3)2C6H3
4-t-BuC6H4
4-ClC6H4
4-CH3C6H4
4-CH3OC6H4
4-t-BuC6H4
3,5-(CH3)2C6H3
n-C4H9
4-CH3C6H4
4-CH3OC6H4
4-ClC6H4
3,5-(CH3)2C6H3
4-t-BuC6H4
n-C4H9
3-Cl-4-FC6H3
5-CH3 2,5-Cl2C6H3
5-CH3 2-ClC6H4
5-Br
H
5-F
H
5-F
5-Cl
H
9
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
10
11
12
13
14
15
16
17
18
19
3,5-(CH3)2C6H3
C6H5
4-t-BuC6H4
4-ClC6H4
4-BrC6H4
2,4-(CH3)2C6H3 Ph
2,4-(CH3)2C6H3 Ph
C6H5
H
Ph
Ph
Ph
Ph
5-F
5-F
5-Cl
5-Cl
5-Cl
5-Cl
5-Cl
5-Cl
5-CH3
6-Br
4-Cl
5-Cl
H
H
Ph
CH3 70
CH3 70
C6H5
CH3C6H4
3t
3u
3v
3w
3x
3 h. The SSA was used as such reaction for the subsequent
catalytic runs. The catalytic system worked well up to five
catalytic runs without any loss of its activities (Figure 4).
In conclusion, we have developed a procedure for the
facile synthesis of a variety of potential, biologically active
pyrrolo[2,3,4-kl]acridine-1-one derivatives. Using this
method, a molecularly diverse pyrrolo[2,3,4-kl]acridine-1-
one derivatives library was rapidly constructed with good
yields by simply refluxing a reaction mixture of isatins
and enaminone in toluene catalyzed by SSA. Our protocol
is characterized by (i) faster reaction times; (ii) accessible
materials and handy manipulation (only one pot).
4-t-BuC6H4
4-CH3C6H4
C6H5
could not be detected; however, a new aromatic group
could be detected easily (Scheme 3). To further identify
its structure, the crystal structure of 5d was obtained
and confirmed by X-ray diffraction analysis. The result
indicated the corresponding oxidation products pyrrolo
[2,3,4-kl]acridine derivatives 5 (Table 3). The reaction path-
ways could therefore been controlled by varying the
enaminones with a different substituted pattern to give a
series of novel 4,5-dihydropyrrolo[2,3,4-kl]acridin-1-ones
and pyrrolo[2,3,4-kl]acridin-1-ones selectively.
EXPERIMENTAL
The structures of products 3 and 5 were identified from
their IR, H NMR, and HRMS spectra. The structures of
compounds 3p and 5d were further confirmed by X-ray
analysis (Figures 2 and 3).
All reagents were purchased from commercial sources and used
without further purification. Melting points are uncorrected. IR spec-
tra were recorded on Varian F-1000 spectrometer (Varian Inc., Palo
1
1
Alto, CA) in KBr with absorptions in cmꢂ1. H NMR was deter-
We also investigated the recycling of the catalyst
SSA using a model reaction of isatin (1a) and 3-(4-
methoxyphenylamino)-5,5-dimethylcyclohex-2-enone (2d).
After completion of the reaction, the reaction mixture was
concentrated, and the precipitate was dissolved in ethanol.
The mixture was filtered for separation of the catalyst SSA.
The SSA was washed four times with ethanol (4ꢁ 5 mL),
and then recovered catalyst was dried in oven at 100ꢀC for
Scheme 3. The synthesis of pyrrolo[2,3,4-kl]acridine-one derivatives 5.
Figure 2. The crystal structure of compound 3p.
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

M.-H. Hua, W. Lin, C.-P. Cao, Z.-B. Huang, and D.-Q. Shi
Vol 000
ArH), 8.53 (d, J = 7.2 Hz, 1H, ArH); HRMS calcd. for
C22H18ClN2O [M+ H]: 361.1108, found: 361.1099.
2-(4-Bromophenyl)-4,5-dihydro-4,4-dimethylpyrrolo[2,3,
4-kl]acridin-1(2H)-one (3c). Mp 188–189ꢀC; IR (KBr, cmꢂ1):
2952, 2359, 1704, 1494, 1342, 1121, 1008, 959, 821, 772,
644; 1H NMR (400 MHz, DMSO-d6):
d (ppm) 1.28 (s,
6H, 2 ꢁ CH3), 3.15 (s, 2H, CH2), 5.80 (s, 1H, CH), 7.51
(d, J=8.4 Hz, 2H, ArH), 7.71–8.11 (m, 4H, ArH), 8.12 (d,
J=8.4 Hz, 1H, ArH), 8.51 (d, J=8.0 Hz, 1H, ArH); HRMS calcd.
for C22H17BrN2ONa [M + Na]: 427.0422, found: 427.0392.
4,5-Dihydro-2-(4-methoxyphenyl)-4,4-dimethylpyrrolo[2,3,
4-kl]acridin-1(2H)-one (3d). Mp 162–164ꢀC; IR (KBr, cmꢂ1):
2958, 1613, 1473, 1363, 1273, 1171, 1070, 998, 910, 827, 701,
628; 1H NMR (400 MHz, DMSO-d6):
d (ppm) 1.26 (s,
Figure 3. The crystal structure of compound 5d.
6H, 2 ꢁ CH3), 3.14 (s, 2H, CH2), 3.83 (s, 3H, CH3O), 5.64
(s, 1H, CH), 7.11 (d, J=8.8 Hz, 2H, ArH), 7.42 (d, J=8.8 Hz, 2H,
ArH), 7.71 (t, J=7.6 Hz, 1H, ArH), 7.79 (t, J=7.6 Hz, 1H, ArH),
8.11 (d, J = 7.6 Hz, 1H, ArH), 8.52 (d, J = 7.6 Hz, 1H, ArH);
HRMS calcd. for C23H21N2O2 [M+ H]: 357.1603, found:
357.1595.
4,5-Dihydro-4,4-dimethyl-2-p-tolylpyrrolo[2,3,4-kl]acridin-
1(2H)-one (3e). Mp 177–178ꢀC; IR (KBr, cmꢂ1): 2948, 1703,
1
1638, 1516, 1457, 1351, 1209, 1087, 910, 879, 804; H NMR
(400 MHz, DMSO-d6): d (ppm) 1.21 (s, 6H, 2 ꢁ CH3), 2.34 (s,
3H, CH3), 3.10 (s, 2H, CH2), 5.63 (s, 1H, CH), 7.31–7.37 (m,
4H, ArH), 7.68 (t, J = 6.8 Hz, 1H, ArH), 7.76 (t, J = 7.6Hz, 1H,
ArH), 8.07 (d, J = 8.4 Hz, 1H, ArH), 8.48 (d, J = 7.6 Hz, 1H,
ArH); HRMS calcd. for C23H21N2O [M+ H]: 341.1654, found:
341.1632.
4,5-Dihydro-4,4-dimethyl-2-(4-nitrophenyl)pyrrolo[2,3,4-kl]
acridin-1(2H)-one (3f). Mp 137–138ꢀC; IR (KBr, cmꢂ1): 2945,
1637, 1488, 1369, 1288, 1182, 1093, 951, 818, 693; H NMR
1
Figure 4. Recycling experiments. [Color figure can be viewed in the
online issue, which is available at wileyonlinelibrary.com.]
(400 MHz, DMSO-d6): d (ppm) 1.30 (s, 6H, 2 ꢁ CH3), 3.18 (s,
2H, CH2), 5.99 (s, 1H, CH), 7.74 (t, J = 8.0 Hz, 1H, ArH), 7.82 (t,
J = 8.4 Hz, 1H, ArH), 7.86 (d, J = 9.2 Hz, 2H, ArH), 8.14 (d,
J = 8.4 Hz, 1H, ArH), 8.44 (d, J = 8.8 Hz, 2H, ArH), 8.53 (d,
J = 8.0 Hz, 1H, ArH); HRMS calcd. for C22H18N3O3 [M+ H]:
372.1348, found: 372.1327.
2-(3-Chloro-4-fluorophenyl)-4,5-dihydro-4,4-dimethylpyrrolo
[2,3,4-kl]acridin-1(2H)-one (3g). Mp 168–170ꢀC; IR (KBr, cmꢂ1):
2958, 1710, 1462, 1356, 1171, 1100, 880, 755, 639; 1H NMR
(400 MHz, DMSO-d6): d (ppm) 1.29 (s, 6H, 2 ꢁ CH3), 3.19 (s,
2H, CH2), 5.83 (s, 1H, CH), 7.57–7.59 (m, 1H, ArH), 7.66
(t, J = 8.8 Hz, 1H, ArH), 7.75–7.77 (m, 1H, ArH), 7.81–7.86
(m, 2H, ArH), 8.14 (d, J = 8.4 Hz, 1H, ArH), 8.52 (d,
J = 8.0 Hz, 1H, ArH); HRMS calcd. for C22H17N2OFCl
[M + H]: 379.1013, found: 379.0985.
4,5-Dihydro-4,4-dimethyl-2-(3,5-dimethylphenyl)pyrrolo
[2,3,4-kl]acridin-1(2H)-one (3h).Mp 204–206ꢀC; IR (KBr, cmꢂ1):
3065, 1718, 1639, 1500, 1389, 1327, 1257, 1183, 1092, 1018, 777;
1H NMR (300 MHz, CDCl3): d (ppm) 1.41 (s, 6H, 2 ꢁ CH3), 2.43
(s, 6H, 2 ꢁ CH3), 3.76 (s, 2H, CH2), 5.82 (s, 1H, CH), 7.07–7.09
(m, 2H, ArH), 7.25–7.27 (m, 1H, ArH), 7.86–7.88 (m, 1H, ArH),
7.98–8.00 (m, 1H, ArH), 8.61–8.63 (m, 1H, ArH), 8.83–8.87 (m,
1H, ArH); HRMS calcd. for C24H23N2O [M + H]: 355.1810, found:
355.1815.
2-(4-Tert-butylphenyl)-4,5-dihydro-4,4-dimethylpyrrolo
[2,3,4-kl]acridin-1(2H)-one (3i). Mp 173–174ꢀC; IR (KBr, cmꢂ1):
2930, 1690, 1448, 1332, 1075, 959, 891, 831, 700; 1H NMR
(300 MHz, CDCl3): d (ppm) 1.34 (s, 6H, 2 ꢁ CH3), 1.40 (s, 9H, C
(CH3)3), 3.22 (s, 2H, CH2), 5.64 (s, 1H, CH), 7.42–7.45 (m, 2H,
ArH), 7.55–7.58 (m, 2H, ArH), 7.66–7.69 (m, 1H, ArH), 7.73–
mined on Varian Inova-300 or Inova-400 MHz spectrometers in
CDCl3 or DMSO-d6 solution. J values are in Hz. Chemical shifts
are expressed in ppm downfield from internal standard TMS. HRMS
data were obtained using Bruker micrOTOF-Q instrument (Bruker
Daltonics Inc., Billerica, MA). X-Ray diffraction was recorded on a
Rigaku Mercury CCD/AFC diffractometer.
General procedure for the synthesis of pyrrolo[2,3,4-kl]
acridin-1-ones (3). A mixture of isatin 1 (1.0 mmol), enaminone
2 (1.0 mmol), and 0.03 g of SSA was stirred in toluene (3mL) at
110ꢀC. The reaction was monitored by TLC. After the
completion, the reaction mixture was concentrated, filtered, the
precipitate was collected and purified by recrystallization
from 95% EtOH or EtOH/DMF (10:1) or by flash column
chromatography (petroleum ether/ethyl acetate = 3:1).
4,5-Dihydro-4,4-dimethyl-2-phenylpyrrolo[2,3,4-kl]acridin-1
(2H)-one (3a). Mp 172–174ꢀC; IR (KBr, cmꢂ1): 2957, 1705,
1646, 1507, 1343, 1146, 1088, 1011, 898, 832, 738, 631; 1H
NMR (400 MHz, DMSO-d6): d (ppm) 1.28 (s, 6H, 2 ꢁ CH3), 3.15
(s, 2H, CH2), 5.73 (s, 1H, CH), 7.44–7.61 (m, 5H, ArH), 7.70
(t, J = 7.2 Hz, 1H, ArH), 7.78 (t, J = 7.2 Hz, 1H, ArH), 8.11 (d,
J = 8.0 Hz, 1H, ArH), 8.53 (d, J = 7.6 Hz, 1H, ArH); HRMS
calcd. for C22H19N2O, [M+ H]: 327.1497, found: 327.1519.
2-(4-Chlorophenyl)-4,5-dihydro-4,4-dimethylpyrrolo[2,3,
4-kl]acridin-1(2H)-one (3b). Mp 178–180ꢀC; IR (KBr,
cmꢂ1): 2949, 1635, 1481, 1370, 1283, 1183, 1089, 1015,
954, 828, 726, 627; 1H NMR (400 MHz, DMSO-d6): d
(ppm) 1.29 (s, 6H, 2 ꢁ CH3), 3.16 (s, 2H, CH2), 5.80 (s,
1H, CH), 7.57–7.83 (m, 6H, ArH), 8.13 (d, J = 8.0 Hz, 1H,
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

Month 2014
An Efficient Synthesis of Pyrroline-Fused Acridine Derivatives Catalyzed by Silica
Sulfuric Acid
7.76 (m, 1H, ArH), 8.17–8.19 (m, 1H, ArH), 8.73–8.75 (m, 1H,
ArH); HRMS calcd. for C26H27N2O [M + H]: 383.2123, found:
9-Chloro-4,5-dihydro-2-(4-methoxyphenyl)-4,4-dimethylpyrrolo
[2,3,4-kl]acridin-1(2H)-one (3q). Mp 163–165ꢀC; IR (KBr, cmꢂ1):
2954, 1704, 1494, 1342, 1121, 1009, 819, 643; 1H NMR (400 MHz,
DMSO-d6): d (ppm) 1.27 (s, 6H, 2 ꢁ CH3), 3.11 (s, 2H, CH2), 3.85
(s, 3H, CH3O), 5.70 (s, 1H, CH), 7.12 (d, J=8.4 Hz, 2H, ArH), 7.41
(d, J=8.4 Hz, 2H, ArH), 7.75 (d, J=9.2 Hz, 1H, ArH), 8.06 (d,
J=8.8 Hz, 1H, ArH), 8.35–8.37 (m, 1H, ArH); HRMS calcd. for
C23H20ClN2O2 [M + H]: 391.1213, found: 391.1202.
383.2111.
2-(4-Chlorophenyl)-9-fluoro-4,5-dihydro-4,4-dimethylpyrrolo
[2,3,4-kl]acridin-1(2H)-one (3j).Mp 190–192ꢀC; IR (KBr, cmꢂ1):
2957, 1703, 1508, 1360, 1223, 1110, 825, 699; 1H NMR
(400 MHz, DMSO-d6): d (ppm) 1.33 (s, 6H, 2 ꢁ CH3), 3.19 (s,
2H, CH2), 5.63 (s, 1H, CH), 7.44–7.52 (m, 5H, ArH), 8.13–8.16
(m, 1H, ArH), 8.28–8.31 (m, 1H, ArH); HRMS calcd. for
C22H17FClN2O [M + H]: 379.1013, found: 379.0985.
9-Chloro-2-(4-chlorophenyl)-4,5-dihydro-4,4-dimethylpyrrolo
[2,3,4-kl]acridin-1(2H)-one (3r).Mp 180–182ꢀC; IR (KBr, cmꢂ1):
1
9-Fluoro-4,5-dihydro-4,4-dimethyl-2-p-tolylpyrrolo[2,3,4-kl]
2954, 1707, 1651, 1506, 1359, 1252, 1103, 826, 718; H NMR
acridin-1(2H)-one (3k). Mp 170–172ꢀC; IR (KBr, cmꢂ1): 3079,
(300 MHz, CDCl3): d (ppm) 1.31 (s, 6H, 2 ꢁ CH3), 3.16 (s, 2H,
CH2), 5.63 (s, 1H, CH), 7.43–7.47 (m, 4H, ArH), 7.60–7.63 (m,
1H, ArH), 8.00–8.02 (m, 1H, ArH), 8.56–8.58 (m, 1H, ArH);
HRMS calcd. for C22H17N2OCl2 [M + H]: 395.0718, found:
395.0697.
9-Chloro-4,5-dihydro-4,4-dimethyl-2-(3,5-dimethylphenyl)pyrrolo
[2,3,4-kl]acridin-1(2H)-one (3s). Mp 180–181ꢀC; IR (KBr, cmꢂ1):
2928, 1705, 1636, 1521, 1474, 1396, 1254, 1176, 1109, 1035, 803;
1H NMR (300 MHz, CDCl3): d (ppm) 1.32 (s, 6H, 2 ꢁ CH3), 2.39
(s, 6H, 2 ꢁ CH3), 3.17 (s, 2H, CH2), 5.63 (s, 1H, CH), 7.03–7.08
(m, 3H, ArH), 7.61–7.64 (m, 1H, ArH), 8.04 (d, J=9.0 Hz, 1H,
ArH), 8.64–8.65 (m, 1H, ArH); HRMS calcd. for C24H22ClN2O
[M + H]: 389.1421, found: 389.1401.
2-(4-Tert-butylphenyl)-9-chloro-4,5-dihydro-4,4-dimethylpyrrolo
[2,3,4-kl]acridin-1(2H)-one (3t). Mp 182–183ꢀC; IR (KBr, cmꢂ1):
2947, 1575, 1485, 1392, 1319, 1253, 1077, 989, 833, 717; 1H
NMR (300 MHz, CDCl3): d (ppm) 1.33 (s, 6H, 2 ꢁ CH3), 1.38
(s, 9H, C(CH3)3), 3.19 (s, 2H, CH2), 5.67 (s, 1H, CH), 7.40–
7.42 (m, 2H, ArH), 7.54–7.57 (m, 2H, ArH), 7.67 (d, J=9.0 Hz,
1H, ArH), 8.08 (d, J=9.0 Hz, 1H, ArH), 8.69–8.70 (m, 1H,
ArH); HRMS calcd. for C26H26ClN2O [M + H]: 417.1734, found:
1
1711, 1635, 1504, 1403, 1256, 1119, 1063, 775, 707; H NMR
(300 MHz, CDCl3): d (ppm) 1.30 (s, 6H, 2 ꢁ CH3), 2.41 (s, 3H,
CH3), 3.16 (s, 2H, CH2), 5.60 (s, 1H, CH), 7.33–7.34 (m, 4H,
ArH), 7.42–7.47 (m, 1H, ArH), 8.10–8.13 (m, 1H, ArH), 8.28
(d, J = 6.9 Hz, 1H, ArH); HRMS calcd. for C23H20N2OF
[M + H]: 359.1560, found: 359.1564.
9-Fluoro-4,5-dihydro-2-(4-methoxyphenyl)-4,4-dimethylpyrrolo
[2,3,4-kl]acridin-1(2H)-one (3l). Mp 167–169ꢀC; IR (KBr, cmꢂ1):
2949, 1699, 1514, 1353, 1196, 1098, 1017, 943, 843, 785, 634; 1H
NMR (400 MHz, DMSO-d6): d (ppm) 1.23 (s, 6H, 2 ꢁ CH3), 3.07
(s, 2H, CH2), 3.82 (s, 3H, OCH3), 5.66 (s, 1H, CH), 7.10 (d,
J=8.8 Hz, 2H, ArH), 7.39 (d, J= 8.8 Hz, 2H, ArH), 7.62
(t, J=8.8 Hz, 1H, ArH), 7.95 (d, J=8.8 Hz, 1H, ArH), 8.08 (t,
J=4.0 Hz, 1H, ArH); HRMS calcd. for C23H20FN2O2 [M + H]:
375.1509, found: 375.1518.
2-(4-Tert-butylphenyl)-9-fluoro-4,5-dihydro-4,4-dimethylpyrrolo
[2,3,4-kl]acridin-1(2H)-one (3m). Mp 199–200ꢀC; IR (KBr, cmꢂ1):
1
2950, 1707, 1639, 1493, 1348, 1201, 1086, 1017, 955, 833; H
NMR (300 MHz, CDCl3): d (ppm) 1.30 (s, 6H, 2 ꢁ CH3), 1.35 (s,
9H, C(CH3)3), 3.16 (s, 2H, CH), 5.65 (s, 1H, CH), 7.38–7.44 (m,
3H, ArH), 7.51–7.54 (m, 2H, ArH), 8.09–8.11 (m, 1H, ArH), 8.27–
8.30 (m, 1H, ArH). HRMS calcd. for C26H26FN2O [M+H]:
401.2029, found: 401.2008.
9-Fluoro-4,5-dihydro-4,4-dimethyl-2-(3,5-dimethylphenyl)
pyrrolo[2,3,4-kl]acridin-1(2H)-one (3n). Mp 148–150ꢀC; IR
(KBr, cmꢂ1): 2940, 1697, 1602, 1454, 1354, 1251, 1096,
970, 896, 834, 707, 634; 1H NMR (400 MHz, DMSO-d6): d
(ppm) 1.24 (s, 6H, 2 ꢁ CH3), 2.34 (s, 6H, 2 ꢁ CH3), 3.07
(s, 2H, CH2), 5.71 (s, 1H, CH), 7.05–7.07 (m, 3H, ArH),
7.63 (t, J = 8.4 Hz, 1H, ArH), 7.98 (d, J = 7.2 Hz, 1H,
ArH), 8.09 (d, J = 7.2 Hz, 1H, ArH); HRMS calcd. for
C24H22N2OF [M + H]: 373.1716, found: 373.1726.
2-Butyl-9-fluoro-4,5-dihydro-4,4-dimethylpyrrolo[2,3,4-kl]
acridin-1(2H)-one (3o). Mp 143–145ꢀC; IR (KBr, cmꢂ1):
2938, 1699, 1510, 1450, 1356, 1245, 1126, 1028, 831, 789;
1H NMR (400 MHz, DMSO-d6,): d (ppm) 0.90–0.92 (m, 3H,
CH3), 1.27–1.32 (m, 8H, CH2 + 2 ꢁ CH3), 1.60–161 (m, 2H,
CH2), 3.03–3.04 (m, 2H, CH2), 3.70–3.72 (m, 2H, CH2),
5.89 (s, 1H, CH), 7.59 (d, J = 5.2 Hz, 1H, ArH), 7.95–7.96
(m, 1H, ArH), 8.05–8.06 (m, 1H, ArH); HRMS calcd. for
C20H22N2OF [M + H]: 325.1717, found: 325.1739.
9-Chloro-4,5-dihydro-4,4-dimethyl-2-p-tolylpyrrolo[2,3,
4-kl]acridin-1(2H)-one (3p). Mp 172–174ꢀC; IR (KBr, cmꢂ1):
2958, 1915, 1612, 1550, 1445, 1318, 1229, 1101, 984, 823,
715; 1H NMR (400 MHz, DMSO-d6): d (ppm) 1.26 (s, 6H,
2 ꢁ CH3), 2.39 (s, 3H, CH3), 3.11 (s, 2H, CH2), 5.74 (s,
1H, CH), 7.36–7.37 (m, 4H, ArH), 7.74 (d, J = 7.6 Hz, 1H,
ArH), 8.02 (d, J = 8.8 Hz, 1H, ArH), 8.35–8.36 (m, 1H,
ArH); HRMS calcd. for C23H20N2OCl [M + H]: 375.1264,
found: 375.1285.
417.1714.
2-Butyl-9-chloro-4,5-dihydro-4,4-dimethylpyrrolo[2,3,4-kl]acridin-
1(2H)-one (3u). Mp 141–143ꢀC; IR (KBr, cmꢂ1): 2950, 1706, 1500,
1346, 1240, 1091, 956, 890, 824, 697; 1H NMR (300 MHz, CDCl3):
d
(ppm) 0.92–0.94 (m, 3H, CH3), 1.29–1.37 (m, 8H,
2 ꢁ CH3 + CH2), 1.65–1.66 (s, 2H, CH2), 3.09–3.10 (m, 2H, CH2),
3.72–3.74 (m, 2H, CH2), 5.51 (s, 1H, CH), 7.57–7.58 (m, 1H,
ArH), 7.96–7.98 (m, 1H, ArH), 8.56–8.57 (m, 1H, ArH); HRMS
calcd. for C20H22N2OCl [M + H]: 341.1421, found: 341.1412.
2-(4-Tert-butylphenyl)-4,5-dihydro-4,4,9-trimethylpyrrolo[2,3,
4-kl]acridin-1(2H)-one (3v). Mp 173–175ꢀC; IR (KBr, cmꢂ1):
2962, 1716, 1570, 1376, 1240, 1092, 956, 930, 897, 824, 697,
621; 1H NMR (300MHz, DMSO-d6): d (ppm) 1.22 (s, 6H,
2 ꢁ CH3), 1.31 (s, 9H, C(CH3)3), 3.07 (s, 2H, CH2), 5.67 (s,
1H, CH), 7.39–7.40 (m, 2H, ArH), 7.55–7.57 (m, 3H, ArH),
7.95–7.99 (m, 1H, ArH), 8.26–8.27 (m, 1H, ArH); HRMS
calcd. for C26H26BrN2O [M+ H]: 461.1229, found: 461.1251.
8-Bromo-4,5-dihydro-4,4-dimethyl-2-p-tolylpyrrolo[2,3,4-kl]
acridin-1(2H)-one (3w). Mp 172–174ꢀC; IR (KBr, cm–1): 2949,
1705, 1499, 1351, 1102, 961, 826, 740, 635; 1H NMR
(400 MHz, DMSO-d6): d (ppm) 1.20 (s, 6H, 2 ꢁ CH3), 2.34
(s, 3H, CH3), 3.05 (s, 2H, CH2), 5.65 (s, 1H, CH), 7.30–7.32
(m, 4H, ArH), 7.71–7.72 (m, 1H, ArH), 8.17–8.18 (m, 1H,
ArH), 8.29–8.30 (m, 1H, ArH); HRMS calcd. for C23H20BrN2O
[M + H]: 419.0759, found: 419.0776.
General procedure for the synthesis of 4,5-dihydropyrrolo
[2,3,4-kl]acridin-1-ones (5). A mixture of isatin 1 (1.0 mmol),
enaminone 4 (1.0 mmol), and 0.03g of SSA was stirred in toluene
(3mL) at 110ꢀC. The reaction was monitored by TLC. After the
completion, the reaction mixture was filtered, concentrated. The
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

M.-H. Hua, W. Lin, C.-P. Cao, Z.-B. Huang, and D.-Q. Shi
Vol 000
crude product was purified by flash column chromatography
2-(2-Chlorophenyl)-9-methylpyrrolo[2,3,4-kl]acridin-1(2H)-
one (5i). Mp 258–260ꢀC; IR (KBr, cmꢂ1): 2957, 1713,
1626, 1472, 1386, 1321, 1126, 890, 827, 728; 1H NMR
(300 MHz, CDCl3): d (ppm) 2.66 (s, 3H, CH3), 5.59–5.62 (m, 1H,
ArH), 6.83–6.89 (m, 2H, ArH), 6.98–7.01 (m, 1H, ArH) 7.37–7.39
(m, 1H, ArH), 7.47–7.49 (m, 3H, ArH), 7.64–7.72 (m, 2H, ArH);
HRMS calcd. for C21H14ClN2O [M + H]: 345.0795, found: 345.0779.
9-Bromo-2-(3,5-dimethylphenyl)-2H-pyrrolo[2,3,4-kl]acridin-
1-one (5j). Mp 198–200ꢀC; IR (KBr, cmꢂ1): 2949, 1635, 1481,
1370, 1283, 1183, 1089, 1015, 954, 828, 726, 627; 1H NMR
(300 MHz, CDCl3): d (ppm) 2.43 (s, 6H, 2 ꢁ CH3), 6.98–7.00 (m,
1H, ArH), 7.09–7.10 (m, 1H, ArH), 7.21–7.22 (m, 2H, ArH),
7.69–7.71 (m, 1H, ArH), 7.81–7.84 (m, 1H, ArH), 7.93–7.97 (m,
1H, ArH), 8.24–8.27 (m, 1H, ArH), 9.05–9.06 (m, 1H, ArH); HRMS
calcd. for C22H15BrN2ONa [M + Na]: 425.0265, found: 425.0236.
2,4-Diphenylpyrrolo[2,3,4-kl]acridin-1(2H)-one (5k). Mp 237–
239ꢀC;. IR (KBr, cmꢂ1): 2980, 1707, 1641, 1518, 1383, 1179,
1096, 807; 1H NMR (400 MHz, CDCl3): d (ppm) 7.23–7.24
(m, 1H, ArH), 7.45–7.49 (m, 4H, ArH), 7.61–7.78 (m, 7H, ArH),
7.90–7.91 (m, 1H, ArH), 8.02–8.03 (m, 1H, ArH), 8.40–8.41 (m,
1H, ArH), 8.85–8.87 (m, 1H, ArH); HRMS calcd. for
C26H16N2ONa [M+ Na]: 395.1160, found, 395.1171.
(petroleum ether/ethyl acetate= 3:1).
2-Phenylpyrrolo[2,3,4-kl]acridin-1(2H)-one (5a). Mp 298–
300ꢀC; IR (KBr, cmꢂ1): 3070, 1711, 1635, 1263, 1174, 1066,
1
813; H NMR (300 MHz, CDCl3): d (ppm) 7.00–7.03 (m, 1H,
ArH), 7.46–7.48 (m, 1H, ArH), 7.61–7.72 (m, 5H, ArH), 7.79–
7.93 (m, 3H, ArH), 8.44 (d, J = 8.4 Hz 1H, ArH), 8.92 (d,
J = 8.7 Hz 1H, ArH); HRMS calcd. for C20H12N2ONa [M + Na]:
319.0847, found: 319.0839.
2-(3,5-Dimethylphenyl)-2H-pyrrolo[2,3,4-kl]acridin-1-one
(5b). Mp 208–210ꢀC; IR (KBr, cmꢂ1): 2946, 1711, 1650, 1465,
1350, 1218, 1050, 855, 781; 1H NMR (300 MHz, CDCl3): d
(ppm) 2.43 (s, 6H, 2ꢁ CH3), 6.97–6.98 (m, 1H, ArH), 7.09 (s, 1H,
ArH), 7.23–7.24 (m, 2H, ArH), 7.67–7.68 (m, 1H, ArH), 7.81–7.92
(m, 3H, ArH), 7.42–7.45 (m, 1H, ArH), 8.91–8.93 (m, 1H, ArH);
HRMS calcd. for C22H16N2ONa [M + Na]: 347.1160, found:
347.1171.
2-(3-Chloro-4-fluorophenyl)pyrrolo[2,3,4-kl]acridin-1(2H)-one
(5c). Mp 238–240ꢀC; IR (KBr, cmꢂ1): 2949, 1711, 1516, 1353,
1254, 1124, 1032, 832, 646; 1H NMR (300 MHz, CDCl3): d
(ppm) 6.99–7.01 (m, 1H, ArH), 7.35–7.40 (m, 1H, ArH), 7.53–
7.54 (m, 1H, ArH), 7.72–7.74 (m, 2H, ArH), 7.83–7.94 (m, 3H,
ArH), 8.44 (d, J= 8.4 Hz, 1H, ArH), 8.89 (d, J= 7.2 Hz 1H, ArH);
HRMS calcd. for C20H11FClN2O [M + H]: 349.0544, found:
349.0529.
2-(4-Tert-butylphenyl)-9-fluoro-4-phenylpyrrolo[2,3,4-kl]acridin-
1(2H)-one (5l). Mp 226–228ꢀC; IR (KBr, cmꢂ1): 2978, 1706, 1632,
1503, 1130, 1118 1096, 854; 1H NMR (400 MHz, CDCl3): d (ppm)
1.35 (s, 9H, (CH3)3), 7.18 (d, J = 6 8 Hz, 1H, ArH), 7.37–7.63
(m, 10H, ArH), 7.92 (s, 1H, ArH), 8.31–8.36 (m, 2H, ArH);
HRMS calcd. for C30H23N2OFNa [M+ Na]: 469.1692, found:
469.1696.
2-(2-Chlorophenyl)pyrrolo[2,3,4-kl]acridin-1(2H)-one
(5d). Mp 234–236ꢀC; IR (KBr, cmꢂ1): 3055, 1709, 1629, 1484,
1117, 1066, 765; 1H NMR (300 MHz, CDCl3): d (ppm) 6.69
(d, J = 5.1 Hz 1H, ArH), 7.50–7.51 (m, 2H, ArH), 7.57–7.58 (m,
1H, ArH), 7.67–7.68 (m, 2H, ArH), 7.81–7.84 (m, 1H, ArH),
7.89–7.94 (m, 2H, ArH), 8.45 (d, J = 6.6 Hz 1H, ArH), 6.92
(d, J = 6.3 Hz 1H, ArH); HRMS calcd. for C20H11N2OClNa
[M+ Na]: 353.0458, found: 353.0468.
2-(4-Chlorophenyl)-4-phenylpyrrolo[2,3,4-kl]acridin-1(2H)-
one (5m). Mp 216–218ꢀC; IR (KBr, cmꢂ1): 2920, 1717, 1635,
1
1384, 1110, 1079, 779; H NMR (400 MHz, CDCl3): d (ppm)
7.29 (s, 1H, ArH), 7.46–7.49 (m, 1H, ArH), 7.52–7.57 (m,
2H, ArH), 7.59–7.64 (m, 4H, ArH), 7.74–7.76 (m, 2H,
ArH), 7.80–7.84 (m, 1H, ArH), 7.93–7.97 (m, 1H, ArH), 8.09
(s, 1H, ArH), 8.44 (d, J = 8.4 Hz, 1H, ArH), 8.88 (d, J = 8.4 Hz,
1H, ArH); HRMS calcd. for C26H16N2OCl [M + H]: 407.0951,
found: 407.0940.
9-Fluoro-2-(4-methoxyphenyl)pyrrolo[2,3,4-kl]acridin-1(2H)-
one (5e). Mp 240–242ꢀC; IR (KBr, cmꢂ1): 2956, 1703, 1636,
1512, 1386, 1256, 1181, 1118, 783, 612; 1H NMR (300 MHz,
CDCl3):
d (ppm) 3.91 (s, 3H, CH3O), 6.95–6.96 (m,
1H, ArH), 7.11 (d, J = 7.5 Hz, 2H, ArH), 7.51–7.53
(m, 2H, ArH), 7.68–7.71 (m, 2H, ArH), 7.85–7.89 (m, 1H, ArH)
8.43–8.47 (m, 2H, ArH); HRMS calcd. for C21H13FN2O2Na
[M + Na]: 367.0859, found: 367.0852.
2-(4-Chlorophenyl)-9-fluoropyrrolo[2,3,4-kl]acridin-1(2H)-
one (5f). Mp 236–238ꢀC; IR (KBr, cmꢂ1): 3022, 1716, 1635,
1498, 1399, 1323, 1253, 1109, 867, 776, 692; 1H
NMR (300 MHz, CDCl3): d (ppm) 7.02–7.03 (m, 1H, ArH),
7.56–7.58 (m, 4H, ArH), 7.70–7.71 (m, 2H, ArH), 7.88 (d,
J = 7.2 Hz, 1H, ArH), 8.44–8.45 (m, 2H, ArH); HRMS calcd.
2-(4-Bromophenyl)-9-fluoro-4-phenylpyrrolo[2,3,4-kl]acridin-
1(2H)-one (5n). Mp 246–247ꢀC; IR (KBr, cmꢂ1): 2923, 1715,
1641, 1183, 1080, 1069, 859; 1H NMR (400MHz, CDCl3): d
(ppm) 7.47–7.53 (m, 6H, ArH), 7.65–7.71 (m, 5H, ArH), 8.01 (s,
1H, ArH), 8.39–8.41 (m, 2H, ArH); HRMS calcd. for
C26H14N2OFBrNa [M + Na]: 491.0171, found: 491.0187.
9-Chloro-2-(2,4-dimethylphenyl)-4-phenylpyrrolo[2,3,4-kl]
acridin-1(2H)-one (5o). Mp 226–227ꢀC; IR (KBr, cmꢂ1):
2927, 2354, 1706, 1635, 1499, 1380, 1315, 1109, 845; 1H
NMR (400 MHz, CDCl3): d (ppm) 1.98 (s, 3H, CH3), 2.15
(s, 3H, CH3), 6.61 (s, 1H, ArH), 6.80–7.17 (m, 6H, ArH),
7.36–7.37 (m, 2H, ArH), 7.49–7.52 (m, 1H, ArH), 7.69
(s, 1H, ArH), 8.02 (d, J = 9.2 Hz, 1H, ArH), 8.52–8.53
(m, 1H, ArH); HRMS calcd. for C28H20N2OCl [M + H]:
435.1264, found: 435.1240.
for C20H11ClFN2O [M + H]: 349.0544, found: 349.0518.
2-(3-Chloro-4-fluorophenyl)-9-fluoropyrrolo[2,3,4-kl]acridin-
1(2H)-one (5g). Mp 230–232ꢀC; IR (KBr, cmꢂ1): 2987,
1713, 1626, 1472, 1386, 1125, 999, 826, 728, 615; 1H NMR
(300 MHz, CDCl3): d (ppm) 7.03–7.04 (m, 1H, ArH), 7.35–7.41
(m, 1H, ArH), 7.54–7.56 (m, 1H, ArH), 7.72–7.73 (m, 3H,
ArH), 7.90–7.93 (m, 1H, ArH), 8.44–8.47 (m, 2H, ArH); HRMS
2-(2,4-Dimethylphenyl)-4-phenylpyrrolo[2,3,4-kl]acridin-1
(2H)-one (5p). Mp 200–201ꢀC; IR (KBr, cmꢂ1): 3040, 2920,
2354, 1707, 1684, 1498, 1376, 1227, 1096, 856; 1H NMR
(400 MHz, CDCl3): d (ppm) 1.97 (s, 3H, CH3), 2.14 (s,
3H, CH3), 6.59 (s, 1H, ArH), 6.90–7.18 (m, 7H, ArH),
7.37–7.39 (m, 2H, ArH), 7.45–7.49 (m, 1H, ArH), 7.58–7.62
(m, 1H, ArH), 8.12 (d, J = 8.8 Hz, 1H, ArH), 8.57 (d,
J = 8.4 Hz, 1H, ArH); HRMS calcd. for C28H20N2ONa
[M + Na]: 423.1473, found: 423.1441.
calcd. for C20H10ClF2N2O [M + H]: 367.0450, found: 367.0450.
2-(2,6-Dichlorophenyl)-9-methylpyrrolo[2,3,4-kl]acridin-1
(2H)-one (5h).Mp 268-269ꢀC; IR (KBr, cmꢂ1): 2947, 1635, 1370,
1283, 1183, 1090, 1015, 958, 829, 726; 1H NMR (300 MHz,
CDCl3): d (ppm) 2.67 (s, 3H, CH3), 6.62–6.64 (m, 1H, ArH),
7.44–7.47 (m, 1H, ArH), 7.56–7.68 (m, 3H, ArH), 7.77 (d,
J = 8.4 Hz, 1H, ArH) 7.91 (d, J = 8.7 Hz, 1H, ArH), 8.35 (d,
J = 8.4 Hz, 1H, ArH), 8.69–8.70 (m, 1H, ArH); HRMS calcd. for
C21H13Cl2N2O [M+ H]: 379.0405, found: 379.0390.
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

Month 2014
An Efficient Synthesis of Pyrroline-Fused Acridine Derivatives Catalyzed by Silica
Sulfuric Acid
REFERENCES AND NOTES
9-Chloro-2,4-diphenylpyrrolo[2,3,4-kl]acridin-1(2H)-one
(5q). Mp 268–270ꢀC; IR (KBr, cmꢂ1): 2920, 1705, 1633, 1384,
1130, 1096, 854; 1H NMR (400MHz, CDCl3): d (ppm) 7.32–
7.35 (m, 1H, ArH), 7.48–7.56 (m, 4H, ArH), 7.63–7.76 (m, 6H,
ArH), 7.86–7.89 (m, 1H, ArH), 8.06–8.07 (m, 1H, ArH), 8.38–
8.40 (m, 1H, ArH), 8.90–8.91 (m, 1H, ArH); HRMS calcd. for
C26H16N2OCl [M+ H]: 407.0951, found: 407.0954.
4-Methyl-2-phenylpyrrolo[2,3,4-kl]acridin-1(2H)-one (5r).Mp 200–
202ꢀC; IR (KBr, cmꢂ1): 2989, 1718, 1637, 1384, 1153, 1031, 778;
1H NMR (400MHz, CDCl3): d (ppm) 2.54 (s, 3H, CH3), 6.76 (s,
1H, ArH), 7.44 (t, J = 6.4 Hz, 1H, ArH), 7.55–7.63 (m, 5H,
ArH), 7.72 (t, J = 7.6 Hz, 1H, ArH), 7.85 (t, J = 7.2 Hz,
1H, ArH), 8.33 (d, J = 8.8 Hz, 1H, ArH), 8.79 (d, J = 8.4 Hz,
1H, ArH); HRMS calcd. for C21H14N2ONa [M + Na]:
333.1004, found: 333.1008.
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Acknowledgment. This work was partially supported by the
Major Basic Research Project of the Natural Science Foundation of
the Jiangsu Higher Education Institutions (No. 10KJA150049), A
Project Funded by the Priority Academic Project Development of
Jiangsu Higher Education Institutions and the Natural Science
Foundation of the Jiangsu Higher Education Institutions (No.
11KJB150014).
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet