Iodine-catalyzed synthesis of cyclopenta[c]quinoline derivatives via imino diels-alder reaction

Article abstract of DOI:10.1002/jhet.1670

A mild and efficient method for the synthesis of cyclopenta[c]naphtho[2,3- f]quinoline and cyclopenta[c]pyrazolo[4,3-f]quinoline derivatives via an imino Diels-Alder reaction of aromatic aldehyde, anthracen-2-amine, or 1H-indazol-5-amine and cyclopentanone catalyzed by iodine is described. This novel procedure has the advantages of mild reaction condition, high yields, and metal-free catalyst.

Full text of DOI:10.1002/jhet.1670

830
Iodine-Catalyzed Synthesis of Cyclopenta[c]quinoline Derivatives via
Imino Diels–Alder Reaction
Vol 51
a
b
b
a
*
Wei Wang, Hong Jiang, Mei-Mei Zhang, and Xiang-Shan Wang
aSchool of Chemistry and Chemical Engineering, Jiangsu Key Laboratory of Green Synthetic Chemistry for Functional
Materials, Jiangsu Normal University, Xuzhou, Jiangsu 221116, China
bThe Key Laboratory of Biotechnology on Medical Plant of Jiangsu Province, Jiangsu Normal University, Xuzhou,
Jiangsu 221116, China
*
E-mail: xswang1974@yahoo.com
Received November 11, 2011
DOI 10.1002/jhet.1670
Published online 22 November 2013 in Wiley Online Library (wileyonlinelibrary.com).
H2N
H2N
N
N
HN
O
N
H
+
ArCHO
I2, THF
I2, THF
N
Ar
N
Ar
A mild and efficient method for the synthesis of cyclopenta[c]naphtho[2,3-f]quinoline and cyclopenta[c]
pyrazolo[4,3-f ]quinoline derivatives via an imino Diels–Alder reaction of aromatic aldehyde, anthracen-2-
amine, or 1H-indazol-5-amine and cyclopentanone catalyzed by iodine is described. This novel procedure
has the advantages of mild reaction condition, high yields, and metal-free catalyst.
J. Heterocyclic., 51, 830 (2014).
INTRODUCTION
RESULTS AND DISCUSSION
Quinoline and its derivatives are privileged heterocyclic
scaffold because of their variety of medicinal properties,
such as antimicrobial [1], antiproliferative [2], antioxidant
[3], and antifungal activity [4], so the synthesis of quinolines
has been extensively researched in recent years [5]. Povarov
and coworkers [6] have explored an important methodology
that provided a convenient access to synthesis of quinoline
derivatives from an imino Diels–Alder reaction, which uses
Schiff base and electron-rich dienophile as reactants. This
reaction is also named as Povarov reaction and is usually
catalyzed by various Lewis acids, which is well documented
as a review by Kouznetsov in 2009 [7].
This methodology has been improved greatly by Wang
and coworkers in 2006 and catalyzed by iodine [8], using
aliphatic aldehyde as starting material. Iodine is a novel
metal-free Lewis acid, which is used to catalyze various
types of organic reactions in recent years [9]. In our previ-
ous work, using aromatic aldehyde and 2-naphthylamine
as starting materials to produce Schiff base, the dienophiles
were expanded to various ketones, such as aliphatic,
aromatic, and cyclicketone; they all gave the satisfied
results. In connection with our continued research on this
iodine-catalyzed Povarov reaction [10], in this article, we
would like to report an efficient synthesis of cyclopenta[c]
naphtho[2,3-f]quinoline and cyclopenta[c]pyrazolo[4,3-f ]
quinoline derivatives catalyzed by iodine. This novel
polycyclic ring skeleton containing both naphthalene
or pyrazole and quinoline rings may possess potential
bioactive for screening.
Treatment of aromatic aldehyde 1, 1H-indazol-5-amine
2, and cyclopentanone 3 in THF in the presence of 5 mol
% iodine at reflux condition afforded the corresponding
7-aryl-3,8,9,10-tetrahydrocyclopenta[c]pyrazolo[4,3-f ]
quinoline derivatives 4 in high yields (Scheme 1).
In our initial study, the amount of catalyst (I2) was iden-
tified firstly; therefore, the model reaction was conducted
using 4-chlorobenzaldehyde (1a), 1H-indazol-5-amine,
and cyclopentanone in the presence of various catalytic
amount of iodine. The screening results of the reaction
were summarized in Table 1. The 1, 5, and 10 mol% iodine
were used to mediate the reaction; 5 mol% I2 at reflux in
THF is sufficient to initiate the reaction (Table 1, entries
4–6). To find the optimum reaction temperature, the reac-
tion was carried out with 5 mol% of I2 at room temperature,
50ꢀC, and reflux temperature, resulting in the isolation of
4a in trace amount, 78%, and 86% yields (Table 1, entries
2, 3, and 5), respectively. In addition, CH3CN, benzene,
DMF, and CHCl3 (Table 1, entries 7–10) were also tested
as the solvents. In these cases, product 4a was formed in
slightly lower yields.
According to the optimized conditions, various aromatic
aldehydes 1 were then subjected to react with 2 and 3 to
generate a library of cyclopenta[c]pyrazolo [4,3-f]
quinoline derivatives 4a–l (Table 2). For aldehyde 1, the
yields of 4 were not sensitive to the electronic properties of
the aromatic ring in the presence of electron-withdrawing
groups (such as halide) or electron-donating groups (such
as alkyl or alkoxy group, Table 2).
© 2013 HeteroCorporation

May 2014
Synthesis of Cyclopenta[c]quinolines
831
Scheme 1. The reaction of 1, 3, and 1H-indazol-5-amine.
O
N
HN
H2N
I2
N
+
+
ArCHO
N
THF
H
N
Ar
1
2
3
4
This optimized condition was also suitable for anthracen-
Table 1
Yield optimization for 4a under different conditions.a
2-amine 5, which was selected as a reactant to react with
aromatic aldehyde 1 and cyclopentanone 3 (Scheme 2). The
desired reactions carried out smoothly and gave cyclopenta
[c]naphtha[2,3-f]quinoline derivatives 6a–l in high yields
(Table 3). The structures of the products 4 and 6 were
Entry
Temp. (ꢀC)
I2 (mol %)
Solvent
Yields (%)b
1
2
3
4
5
6
7
8
9
10
Reflux
RT
50
0
5
5
THF
THF
THF
0
trace
78
1
characterized by H NMR, IR, and HRMS; their data are
all in good agreement with their structures.
Reflux
Reflux
Reflux
Reflux
Reflux
80
1
5
10
5
5
THF
THF
THF
CH3CN
Benzene
DMF
CHCl3
82
86
86
82
80
78
82
EXPERIMENTAL
Melting points were determined in open capillaries and are
uncorrected. IR spectra were recorded on a Tensor 27 spectrometer
(Bruker Corporation: Karlsruhe, DE.) in KBr pellet. 1H NMR spec-
tra were obtained from a solution in DMSO-d6 or CDCl3 with
Me4Si as internal standard using a Bruker-400 spectrometer
(Bruker Corporation: Karlsruhe, DE.). HRMS analyses were
5
5
Reflux
aReagents and conditions: 4-chlorobenzaldehyde 1a (0.281 g, 2.0 mmol),
2 (0.266 g, 2.0 mmol), 3 (0.168 g, 2.0 mmol), solvent (10 mL).
bIsolated yields.
Table 2
Table 3
Synthetic results of 4a–l catalyzed by iodine in THF.a
Synthetic results of 6a–l catalyzed by iodine in THF.a
Yields
Yields
Entry
Ar
Products
Time (h)
(%)b
Entry
Ar
Products
Time (h)
(%)b
1
2
3
4
5
6
7
8
4-ClC6H4
4-MeC6H4
4-FC6H4
4-MeOC6H4
3,4-Cl2C6H3
2-BrC6H4
3-MeOC6H4
3-BrC6H4
4a
4b
4c
4d
4e
4f
4g
4h
4i
10
14
8
14
8
10
10
12
14
10
12
8
86
84
90
82
92
86
88
90
90
82
86
91
1
2
3
4
5
6
7
8
4-MeC6H4
4-FC6H4
3-ClC6H4
6a
6b
6c
6d
6e
6f
6g
6h
6i
18
12
14
12
12
18
16
14
14
16
16
12
83
86
80
88
90
78
82
86
90
81
79
86
2-ClC6H4
3,4-Cl2C6H3
3,4-(MeO)2C6H3
4-BrC6H4
3-MeOC6H4
2-BrC6H4
4-MeOC6H4
3-BrC6H4
2,3-Cl2C6H3
9
Piperonyl
3,5-(MeO)2C6H3
3-ClC6H4
9
10
11
12
4j
4k
4l
10
11
12
6j
6k
6l
2-FC6H4
aReagents and conditions: 1 (2.0 mmol), 2 (0.266 g, 2.0 mmol), 3 (0.168 g,
2.0 mmol), I2 (0.1 mmol, 0.026 g), THF (10 mL).
bIsolated yields.
aReagents and conditions: 1 (1.0 mmol), 5 (0.193 g, 1.0 mmol), 3 (0.084 g,
1.0 mmol), I2 (0.05 mmol, 0.013 g), THF (10 mL).
bIsolated yields.
Scheme 2. The reaction of 1, 3, and anthracen-2-amine.
O
I2
H2N
+
+
ArCHO
THF
N
Ar
1
5
3
6
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

832
W. Wang, H. Jiang, M. M. Zhang, and X. S. Wang
Vol 51
carried out using a Bruker-micro-TOF-Q-MS analyzer (Bruker
Corporation: Karlsruhe, DE.).
J= 7.2 Hz, 2H, CH2), 7.41–7.48 (m, 2H, ArH), 7.53 (t, J=7.2Hz,
1H, ArH), 7.78 (d, J = 8.0 Hz, 1H, ArH), 7.90 (s, 2H, ArH),
8.50 (s, 1H, ArH), 13.67 (s, 1H, NH). IR (KBr): n 3210, 3160,
3125, 3052, 2906, 2849, 1665, 1573, 1540, 1476, 1461, 1431,
1385, 1349, 1307, 1290, 1176, 1162, 1099, 1044, 1018, 957,
910, 849, 820, 788, 756, 735 cmꢁ1. HRMS (ESI, m/z): Calcd
for C19H15BrN3 [M + H]+ 364.0449, found 364.0416.
7-(3-Methoxyphenyl)-3,8,9,10-tetrahydrocyclopenta[c]pyrazolo
[4,3-f]quinoline 4g. m.p. 221–223ꢀC; 1H NMR (DMSO-d6,
400 MHz): dH 2.24–2.31 (m, 2H, CH2), 3.28 (t, J = 7.2 Hz, 2H,
CH2), 3.49–3.52 (m, 2H, CH2), 3.85 (s, 3H, CH3O), 7.04–7.05
(m, 1H, ArH), 7.45 (d, J = 6.8 Hz, 3H, ArH), 7.88 (d, J = 9.2 Hz,
1H, ArH), 7.94 (d, J = 10.4Hz, 1H, ArH), 8.48 (s, 1H, ArH),
13.64 (s, 1H, NH). IR (KBr): n 3186, 3136, 3097, 3040, 2938,
1600, 1564, 1538, 1484, 1449, 1430, 1380, 1344, 1333, 1268,
1232, 1177, 1153, 1026, 956, 927, 856, 834, 788, 765, 734,
702 cmꢁ1. HRMS (ESI, m/z): Calcd for C20H18N3O [M + H]+
316.1450, found 316.1444.
7-(3-Bromophenyl)-3,8,9,10-tetrahydrocyclopenta[c]pyrazolo
[4,3-f]quinoline 4h. m.p. 282–284ꢀC; 1H NMR (DMSO-d6,
400 MHz): dH 2.34–2.40 (m, 2H, CH2), 3.28 (t, J = 7.6 Hz, 4H,
2CH2), 3.63–3.67 (m, 1H, NH), 7.61–7.64 (m, 1H, ArH), 7.86
(d, J = 8.0 Hz, 1H, ArH), 7.93 (d, J= 8.0 Hz, 1H, ArH), 8.06 (d,
J= 9.2 Hz, 1H, ArH), 8.15 (s, 1H, ArH), 8.19 (d, J= 9.2 Hz, 1H,
ArH), 8.70 (s, 1H, ArH). IR (KBr): n 3177, 3036, 3013, 2983, 2836,
1625, 1581, 1547, 1456, 1419, 1375, 1352, 1340, 1294, 1275, 1181,
1075, 956, 919, 875, 853, 792, 716, 704 cmꢁ1. HRMS (ESI, m/z):
Calcd for C19H15BrN3 [M + H]+ 364.0449, found 364.0443.
7-Piperonyl-3,8,9,10-tetrahydrocyclopenta[c]pyrazolo[4,3-f]
quinoline 4i. m.p. 259–261ꢀC; 1H NMR (DMSO-d6, 400 MHz):
dH 2.25–2.30 (m, 2H, CH2), 3.27 (t, J = 7.2 Hz, 2H, CH2), 3.49
(t, J = 7.6 Hz, 2H, CH2), 6.11 (s, 2H, CH2), 7.06 (d, J = 8.0 Hz,
1H, ArH), 7.40 (d, J = 8.4 Hz, 1H, ArH), 7.47 (s, 1H, ArH),
7.86 (d, J = 9.2 Hz, 1H, ArH), 7.91 (d, J = 9.2 Hz, 1H, ArH),
8.46 (s, 1H, ArH), 13.63 (s, 1H, NH). IR (KBr): n 3176, 3129,
3090, 3037, 2983, 2907, 2862, 2813, 1584, 1561, 1532, 1504,
1493, 1445, 1390, 1331, 1261, 1239, 1176, 1143, 1107, 1038,
956, 929, 863, 822, 785, 739 cmꢁ1. HRMS (ESI, m/z): Calcd
for C20H16N3O2 [M + H]+ 330.1243, found 330.1218.
7-(3,5-Dimethoxyphenyl)-3,8,9,10-tetrahydrocyclopenta[c]
pyrazolo[4,3-f ]quinoline 4j. m.p. 270–272ꢀC; 1H NMR
(DMSO-d6, 400 MHz): dH 2.27 (t, J = 7.2 Hz, 2H, CH2), 3.26–
3.29 (m, 2H, CH2), 3.48–3.51 (m, 2H, CH2), 3.83 (s, 6H, 2CH3O),
6.60 (s, 1H, ArH), 7.01 (s, 2H, ArH), 7.87 (d, J= 9.2 Hz, 1H, ArH),
7.94 (d, J= 10.0 Hz, 1H, ArH), 8.47 (s, 1H, ArH), 13.64 (s, 1H,
NH). IR (KBr): n 3196, 3144, 3102, 2995, 2933, 2844, 1673, 1591,
1538, 1457, 1427, 1380, 1361, 1327, 1284, 1205, 1157, 1095,
1066, 1051, 978, 940, 830, 791, 739, 706 cmꢁ1. HRMS (ESI, m/z):
Calcd for C21H20N3O2 [M+ H]+ 346.1556, found 346.1544.
7-(3-Chlorophenyl)-3,8,9,10-tetrahydrocyclopenta[c]pyrazolo
[4,3-f ]quinoline 4k. m.p. 200–201ꢀC; 1H NMR (DMSO-d6,
400 MHz): dH 2.25–2.29 (m, 2H, CH2), 3.27 (t, J = 7.2 Hz, 2H,
CH2), 3.48 (s, 2H, CH2), 7.52–7.58 (m, 2H, ArH), 7.84–7.93
(m, 4H, ArH), 8.48 (s, 1H, ArH), 13.67 (s, 1H, NH). IR
(KBr): n 3346, 3193, 3146, 3105, 2966, 2940, 2843, 1597,
1562, 1538, 1431, 1379, 1346, 1333, 1262, 1090, 961, 927,
879, 854, 816, 788, 779, 737, 720 cmꢁ1. HRMS (ESI, m/z):
Calcd for C19H15ClN3 [M + H]+ 320.0955, found 320.0947.
7-(2-Fluorophenyl)-3,8,9,10-tetrahydrocyclopenta[c]pyrazolo
[4,3-f ]quinoline 4l. m.p. 133–134ꢀC; 1H NMR (DMSO-d6,
400 MHz): dH 2.27 (t, J = 7.2Hz, 2H, CH2), 2.98–3.02 (m, 2H,
CH2), 3.52 (s, 2H, CH2), 7.37 (t, J = 8.4 Hz, 2H, ArH), 7.54
General procedure for the syntheses of cyclopenta[c]
pyrazolo[4,3-f]quinoline derivatives 4a–l. A dry 50 mL flask
was charged with aromatic aldehyde (2.0 mmol), 1H-indazol-5-
amine (0.266 g, 2.0 mmol), cyclopentanone (0.168 g, 2.0 mmol),
I2 (0.026 g, 0.1 mmol), and THF (10 mL). The reaction mixture
was stirred at reflux for 8–14 h. After completion of the reaction
as indicated by TLC, a little DMF was added to the mixture
until all the yellow solid was dissolved. The generated powder
was collected by filtration to give 4 when the mixture was
cooled to room temperature.
7-(4-Chlorophenyl)-3,8,9,10-tetrahydrocyclopenta[c]pyrazolo
[4,3-f]quinoline 4a. m.p. 283–285ꢀC; 1H NMR (DMSO-d6,
400 MHz): dH 2.26–2.30 (m, 2H, CH2), 3.26–3.31 (m, 2H, CH2),
3.49–3.52 (m, 2H, CH2), 7.59 (d, J = 8.4 Hz, 2H, ArH), 7.88 (d,
J = 9.2 Hz, 1H, ArH), 7.94 (d, J = 8.4 Hz, 3H, ArH), 8.48 (s, 1H,
ArH), 13.63 (s, 1H, NH). IR (KBr): n 3192, 3053, 2949, 2918,
1589, 1563, 1536, 1492, 1436, 1401, 1376, 1349, 1303, 1292,
1092, 1016, 959, 850, 818, 786, 736cmꢁ1. HRMS (ESI, m/z):
Calcd for C19H15ClN3 [M+ H]+ 320.0955, found 320.0956.
7-(p-Tolyl)-3,8,9,10-tetrahydrocyclopenta[c]pyrazolo[4,3-f]
quinoline 4b. m.p. 287–289ꢀC; 1H NMR (DMSO-d6, 400 MHz):
dH 2.24–2.28 (m, 2H, CH2), 2.39 (s, 3H, CH3), 3.26 (t, J=7.2Hz,
2H, CH2), 3.47–3.51 (m, 2H, CH2), 7.33 (d, J= 7.6 Hz, 2H, ArH),
7.74–7.81 (m, 2H, ArH), 7.86 (d, J= 8.8 Hz, 1H, ArH), 7.91–7.96
(m, 1H, ArH), 8.47 (s, 1H, ArH), 13.62 (s, 1H, NH). IR (KBr): n
3186, 3135, 3095, 3035, 2981, 2921, 2867, 1666, 1610, 1561,
1536, 1510, 1432, 1408, 1379, 1346, 1313, 1181, 1161, 1091, 953,
905, 822, 787, 738 cmꢁ1
. HRMS (ESI, m/z): Calcd for
C20H17N3Na [M + Na]+ 300.1501, found 300.1533.
7-(4-Fluorophenyl)-3,8,9,10-tetrahydrocyclopenta[c]pyrazolo
[4,3-f]quinoline 4c. m.p. 258–259ꢀC; 1H NMR (DMSO-d6,
400 MHz): dH 2.24–2.34 (m, 2H, CH2), 3.25–3.29 (m, 2H, CH2),
3.48–3.52 (m, 2H, CH2), 7.33–7.38 (m, 2H, ArH), 7.87 (d,
J = 8.8 Hz, 1H, ArH), 7.92–7.97 (m, 3H, ArH), 8.48 (s, 1H,
ArH), 13.64 (s, 1H, NH). IR (KBr): n 3193, 3146, 3111, 2934,
1669, 1602, 1567, 1537, 1509, 1434, 1411, 1385, 1346, 1218,
1157, 1093, 956, 842, 740 cmꢁ1. HRMS (ESI, m/z): Calcd for
C19H15FN3 [M+ H]+ 304.1250, found 304.1291.
7-(4-Methoxyphenyl)-3,8,9,10-tetrahydrocyclopenta[c]pyrazolo
[4,3-f]quinoline 4d. m.p. 279–281ꢀC; 1H NMR (DMSO-d6,
400 MHz): dH 2.25–2.29 (m, 2H, CH2), 3.27 (t, J = 7.2 Hz, 2H,
CH2), 3.47–3.51 (m, 2H, CH2), 3.84 (s, 3H, CH3O), 7.08 (d,
J = 8.8 Hz, 2H, ArH), 7.84–7.93 (m, 4H, ArH), 8.46 (s, 1H,
ArH), 13.60 (s, 1H, NH). IR (KBr): n 3178, 3093, 2980, 2915,
1605, 1560, 1536, 1509, 1461, 1418, 1380, 1347, 1307, 1255,
1174, 1095, 1032, 950, 838, 819, 784, 746 cmꢁ1. HRMS (ESI,
m/z): Calcd for C20H18N3O [M+ H]+ 316.1450, found 316.1491.
7-(3,4-Dichlorophenyl)-3,8,9,10-tetrahydrocyclopenta[c]pyrazolo
[4,3-f ]quinoline 4e. m.p. >300ꢀC; 1H NMR (DMSO-d6,
400 MHz): dH 2.25–2.29 (m, 2H, CH2), 3.26–3.30 (m, 2H, CH2),
3.47 (s, 2H, CH2), 7.78 (d, J = 8.4 Hz, 1H, ArH), 7.88–7.96
(m, 3H, ArH), 8.13 (d, J = 1.6 Hz, 1H, ArH), 8.47 (s, 1H, ArH),
13.67 (s, 1H, NH). IR (KBr): n 3186, 2968, 2911, 2848, 1588,
1536, 1471, 1438, 1397, 1350, 1294, 1133, 1097, 1032, 965,
931, 846, 818, 749, 728 cmꢁ1. HRMS (ESI, m/z): Calcd for
C19H14Cl2N3 [M + H]+ 354.0565, found 354.0555.
7-(2-Bromophenyl)-3,8,9,10-tetrahydrocyclopenta[c]pyrazolo
[4,3-f ]quinoline 4f. m.p. 246–248ꢀC; 1H NMR (DMSO-d6,
400 MHz): dH 2.25–2.31 (m, 2H, CH2), 2.89 (s, 2H, CH2), 3.53 (d,
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

May 2014
Synthesis of Cyclopenta[c]quinolines
833
(d, J = 5.6 Hz, 1H, ArH), 7.61 (t, J = 7.2 Hz, 1H, ArH), 7.90
(s, 2H, ArH), 8.50 (s, 1H, ArH), 13.66 (s, 1H, NH). IR (KBr): n
3194, 3147, 3106, 2926, 1665, 1616, 1571, 1555, 1538, 1493,
1450, 1379, 1348, 1297, 1271, 1254, 1217, 1191, 1105, 1084,
957, 914, 856, 819, 769 cmꢁ1. HRMS (ESI, m/z): Calcd for
C19H15FN3 [M + H]+ 304.1250, found 304.1256.
General procedure for the syntheses of cyclopenta[c]
naphtho[2,3-f]quinoline derivatives 6a–l. A dry 50 mL flask
was charged with aromatic aldehyde (1.0 mmol), anthracen-2-
amine (0.193g, 1.0 mmol), cyclopentanone (0.084 g, 1.0 mmol),
I2 (0.013g, 0.05mmol), and THF (10 mL). The reaction mixture
was stirred at reflux for 12–18h. After completion of the reaction
as indicated by TLC, a little DMF was added to the mixture until
all the yellow solid was dissolved. The generated powder was
collected by filtration to give 6 when the mixture was cooled to
room temperature.
3.89 (t, J = 7.2 Hz, 2H, CH2), 7.58–7.61 (m, 3H, ArH), 7.76
(d, J = 8.0 Hz, 1H, ArH), 7.91 (d, J = 9.2 Hz, 1H, ArH), 7.99
(d, J = 9.2 Hz, 1H, ArH), 8.07–8.13 (m, 3H, ArH), 8.40 (s,
1H, ArH), 9.12 (s, 1H, ArH). IR (KBr): n 3047, 2960, 2931,
2892, 2843, 1546, 1469, 1436, 1421, 1381, 1357, 1302, 1281,
1265, 1246, 1130, 1059, 1028, 934, 895, 877, 824, 751 cmꢁ1
.
HRMS (ESI, m/z): Calcd for C26H18Cl2N [M + H]+ 414.0816,
found 414.0801.
4-(3,4-Dimethoxyphenyl)-2,3-dihydro-1H-cyclopenta[c]
1
naphtho[2,3-f]quinoline 6f. m.p: 213–214ꢀC; H NMR (CDCl3,
400 MHz): dH 2.29–2.36 (m, 2H, CH2), 3.33 (t, J = 7.2 Hz, 2H,
CH2), 3.91 (t, J = 7.2Hz, 2H, CH2), 3.97 (s, 3H, CH3O), 4.03
(s, 3H, CH3O), 7.01 (d, J = 8.4 Hz, 1H, ArH), 7.46 (dd,
J = 7.6Hz, J0 = 1.6 Hz, 1H, ArH), 7.57–7.60 (m, 3H, ArH), 7.98
(s, 2H, ArH), 8.06–8.14 (m, 2H, ArH), 8.41 (s, 1H, ArH), 9.14
(s, 1H, ArH). IR (KBr): n 3086, 3044, 2991, 2951, 2930, 2867,
2833, 1599, 1586, 1551, 1512, 1481, 1461, 1415, 1389, 1330,
1287, 1231, 1178, 1140, 1114, 1026, 956, 888, 829, 807,
757 cmꢁ1. HRMS (ESI, m/z): Calcd for C28H33NO2Na [M+ Na]+
428.1626, found 428.1683.
4-(p-Tolyl)-2,3-dihydro-1H-cyclopenta[c]naphtho[2,3-f ]
1
quinoline 6a. m.p: 274–276ꢀC; H NMR (CDCl3, 400 MHz): dH
2.29–2.36 (m, 2H, CH2), 2.45 (s, 3H, CH3), 3.30–3.34 (m, 2H,
CH2), 3.91–3.95 (m, 2H, CH2), 7.34 (d, J = 8.0 Hz, 2H, ArH),
7.57–7.61 (m, 2H, ArH), 7.83 (d, J = 8.0 Hz, 2H, ArH), 7.97
(d, J = 2.4 Hz, 2H, ArH), 8.06–8.09 (m, 1H, ArH), 8.12–8.15
(m, 1H, ArH), 8.41 (s, 1H, ArH), 9.17 (s, 1H, ArH). IR (KBr): n
2977, 2933, 2913, 2844, 1551, 1482, 1433, 1384, 1346, 1320,
1262, 1182, 1016, 889, 833, 818, 750, 639 cmꢁ1. HRMS (ESI, m/
z): Calcd for C27H21NNa [M+ Na]+ 382.1572, found 382.1580.
4-(4-Fluorophenyl)-2,3-dihydro-1H-cyclopenta[c]naphtho
[2,3-f]quinoline 6b. m.p: 237–238ꢀC; 1H NMR (CDCl3,
400 MHz): dH 2.29–2.36 (m, 2H, CH2), 3.26–3.30 (s, 2H, CH2),
3.89–3.93 (m, 2H, CH2), 7.19–7.24 (m, 2H, ArH), 7.58–7.60 (m,
2H, ArH), 7.90–8.00 (m, 4H, ArH), 8.06–8.08 (m, 1H, ArH),
8.11–8.14 (m, 1H, ArH), 8.41 (s, 1H, ArH), 9.14 (s, 1H, ArH). IR
(KBr): n 3049, 2954, 2916, 1600, 1553, 1506, 1481, 1432, 1421,
1385, 1344, 1320, 1297, 1263, 1222, 1155, 1098, 1011, 889, 847,
4-(4-Bromophenyl)-2,3-dihydro-1H-cyclopenta[c]naphtho
[2,3-f]quinoline 6g. m.p: 268–269ꢀC; 1H NMR (CDCl3,
400 MHz): dH 2.35 (t, J = 7.2 Hz, 2H, CH2), 3.30 (t, J = 7.6 Hz,
2H, CH2), 3.92–3.96 (m, 2H, CH2), 7.59–7.62 (m, 2H, ArH),
7.66 (d, J = 8.4 Hz, 2H, ArH), 7.82 (d, J = 8.0Hz, 2H, ArH), 7.96–
8.02 (m, 2H, ArH), 8.07–8.10 (m, 1H, ArH), 8.13–8.15 (m, 1H,
ArH), 8.42 (s, 1H, ArH), 9.17 (s, 1H, ArH). IR (KBr): n 2944,
2916, 2878, 1583, 1549, 1478, 1432, 1420, 1384, 1319, 1260,
1070, 1008, 959, 890, 837, 822, 752 cmꢁ1. HRMS (ESI, m/z):
Calcd for C26H19BrN [M + H]+ 424.0701, found 424.0682.
4-(3-Methoxyphenyl)-2,3-dihydro-1H-cyclopenta[c]naphtho
[2,3-f]quinoline 6h. m.p: 150–152ꢀC; 1H NMR (CDCl3,
400 MHz): dH 2.30–2.33 (m, 2H, CH2), 3.29–3.33 (m, 2H,
CH2), 3.90 (d, J = 7.2 Hz, 2H, CH2), 3.92 (s, 3H, CH3O), 7.01
(d, J = 8.0 Hz, 1H, ArH), 7.42–7.49 (m, 3H, ArH), 7.58–7.60
(m, 2H, ArH), 7.97 (s, 2H, ArH), 8.05–8.08 (m, 1H, ArH),
8.11–8.13 (m, 1H, ArH), 8.40 (s, 1H, ArH), 9.14 (s, 1H,
ArH). IR (KBr): n 3051, 2949, 2834, 1580, 1554, 1539,
1486, 1462, 1436, 1420, 1388, 1365, 1320, 1265, 1234,
818, 747, 635, 611 cmꢁ1
. HRMS (ESI, m/z): Calcd for
C26H18FNNa [M+ Na]+ 386.1321, found 386.1324.
4-(3-Chlorophenyl)-2,3-dihydro-1H-cyclopenta[c]naphtho
[2,3-f]quinoline 6c. m.p: 194–195ꢀC; 1H NMR (CDCl3,
400 MHz): dH 2.29–2.37 (m, 2H, CH2), 3.27–3.31 (s, 2H, CH2),
3.89–3.92 (m, 2H, CH2), 7.42–7.48 (m, 2H, ArH), 7.58–7.61
(m, 2H, ArH), 7.78 (d, J = 7.2 Hz, 1H, ArH), 7.92–8.00 (m, 3H,
ArH), 8.06–8.08 (m, 1H, ArH), 8.11–8.13 (m, 1H, ArH), 8.40
(s, 1H, ArH), 9.14 (s, 1H, ArH). IR (KBr): n 3045, 2956, 1593,
1540, 1473, 1438, 1418, 1387, 1366, 1331, 1321, 1299, 1266,
1257, 1232, 1163, 1079, 996, 956, 903, 884, 819, 803, 789,
744, 732 cmꢁ1. HRMS (ESI, m/z): Calcd for C26H19ClN
[M + H]+ 380.1206, found 380.1195.
4-(2-Chlorophenyl)-2,3-dihydro-1H-cyclopenta[c]naphtho
[2,3-f]quinoline 6d. m.p: 216–217ꢀC; 1H NMR (CDCl3,
400 MHz): dH 2.35 (t, J = 7.6 Hz, 2H, CH2), 3.04 (s, 2H, CH2),
3.96 (t, J=7.2Hz, 2H, CH2), 7.40–7.44 (m, 2H, ArH), 7.52
(d, J = 6.4 Hz, 2H, ArH), 7.59–7.62 (m, 2H, ArH), 7.98 (dd,
J = 9.2 Hz, J0 = 2.4 Hz, 2H, ArH), 8.07–8.10 (m, 1H, ArH),
8.14–8.16 (m, 1H, ArH), 8.43 (s, 1H, ArH), 9.20 (s, 1H, ArH).
IR (KBr): n 3049, 2966, 2847, 1619, 1556, 1475, 1433, 1376,
1323, 1299, 1280, 1253, 1173, 1142, 952, 937, 892, 877, 820,
744 cmꢁ1. HRMS (ESI, m/z): Calcd for C26H19ClN [M + H]+
380.1206, found 380.1204.
1147, 1091, 1043, 994, 953, 884, 820, 791, 743, 693 cmꢁ1
.
HRMS (ESI, m/z): Calcd for C27H22NO [M + H]+ 376.1701,
found 376.1721.
4-(2-Bromophenyl)-2,3-dihydro-1H-cyclopenta[c]naphtho
[2,3-f ]quinoline 6i. m.p: 206–208ꢀC; 1H NMR (CDCl3,
400 MHz): dH 2.32–2.39 (m, 2H, CH2), 2.88–3.02 (m, 2H,
CH2), 3.94–3.98 (m, 2H, CH2), 7.30–7.34 (m, 1H, ArH),
7.46–7.50 (m, 2H, ArH), 7.59–7.62 (m, 2H, ArH), 7.71
(d, J = 8.4 Hz, 1H, ArH), 7.94–8.02 (m, 2H, ArH), 8.07–8.10
(m, 1H, ArH), 8.14–8.16 (m, 1H, ArH), 8.43 (s, 1H, ArH),
9.20 (s, 1H, ArH). IR (KBr): n 3051, 2964, 2846, 1619, 1596,
1557, 1473, 1424, 1375, 1323, 1300, 1172, 1142, 1069, 1027,
952, 893, 877, 820, 744 cmꢁ1. HRMS (ESI, m/z): Calcd for
C26H19BrN [M + H]+ 424.0701, found 424.0705.
4-(4-Methoxyphenyl)-2,3-dihydro-1H-cyclopenta[c]naphtho
[2,3-f]quinoline 6j. m.p: 235–236ꢀC; 1H NMR (CDCl3,
400 MHz): dH 2.30–2.34 (m, 2H, CH2), 3.29–3.33 (m, 2H,
CH2), 3.90–3.93 (m, 5H, CH2 + CH3O), 7.06 (d, J = 8.4 Hz, 2H,
ArH), 7.57–7.59 (m, 2H, ArH), 7.90 (d, J = 8.8 Hz, 2H, ArH),
7.96 (d, J = 4.0 Hz, 2H, ArH), 8.06–8.08 (m, 1H, ArH), 8.11–
8.14 (m, 1H, ArH), 8.40 (s, 1H, ArH), 9.15 (s, 1H, ArH). IR
(KBr): n 3054, 3007, 2956, 2926, 2836, 1605, 1549, 1509,
1480, 1437, 1417, 1388, 1370, 1320, 1307, 1250, 1174, 1111,
4-(3,4-Dichlorophenyl)-2,3-dihydro-1H-cyclopenta[c]naphtho
[2,3-f]quinoline 6e. m.p: 233–235ꢀC; 1H NMR (CDCl3,
400 MHz): dH 2.30–2.37 (m, 2H, CH2), 3.26–3.29 (m, 2H, CH2),
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

834
W. Wang, H. Jiang, M. M. Zhang, and X. S. Wang
Vol 51
1032, 886, 832, 742 cmꢁ1. HRMS (ESI, m/z): Calcd for
C27H22NO [M + H]+ 376.1701, found 376.1694.
Acknowledgments. We are grateful to the National Natural Sci-
ence foundation of China (20802061), the Priority Academic
Program Development of Jiangsu Higher Education Institutions,
Qing Lan Project (08QLT001, 10QLD008) and Graduate
Foundation (CXLX12_0984) of Jiangsu Education Committee
for financial support.
4-(3-Bromophenyl)-2,3-dihydro-1H-cyclopenta[c]naphtho
[2,3-f]quinoline 6k. m.p: 198–200ꢀC; 1H NMR (CDCl3,
400 MHz): dH 2.29–2.36 (m, 2H, CH2), 3.27–3.30 (m, 2H,
CH2), 3.88–3.91 (m, 2H, CH2), 7.37–7.41 (m, 1H, ArH), 7.57–
7.60 (m, 3H, ArH), 7.83 (d, J = 7.6 Hz, 1H, ArH), 7.96 (dd,
J = 9.2 Hz, J0 = 1.6 Hz, 2H, ArH), 8.05–8.08 (m, 1H, ArH),
8.10–8.13 (m, 2H, ArH), 8.40 (s, 1H, ArH), 9.13 (s, 1H, ArH).
IR (KBr): n 3046, 2942, 1590, 1552, 1539, 1471, 1438, 1419,
1387, 1365, 1345, 1332, 1321, 1296, 1267, 1258, 1164, 1070,
995, 955, 884, 820, 789, 738, 707 cmꢁ1. HRMS (ESI, m/z):
Calcd for C26H19BrN [M + H]+ 424.0701, found 424.0696.
4-(2,3-Dichlorophenyl)-2,3-dihydro-1H-cyclopenta[C]naphtho
[2,3-f]quinoline 6l. m.p: 263–264ꢀC; 1H NMR (CDCl3,
400 MHz): dH 2.35 (t, J = 7.2 Hz, 2H, CH2), 2.88–3.00 (m, 2H,
CH2), 3.93–3.97 (m, 2H, CH2), 7.36 (t, J = 7.6 Hz, 1H, ArH),
7.42 (d, J = 7.6 Hz, 1H, ArH), 7.57 (d, J = 7.6 Hz, 1H, ArH),
7.59–7.62 (m, 3H, ArH), 7.92 (d, J = 9.2 Hz, 1H, ArH), 8.00 (d,
J = 9.2 Hz, 1H, ArH), 8.07–8.09 (m, 1H, ArH), 8.42 (s, 1H,
ArH), 9.19 (s, 1H, ArH). IR (KBr): n 3044, 2950, 2845, 1621,
1556, 1485, 1457, 1409, 1377, 1330, 1324, 1258, 1212, 1173,
1158, 1145, 1063, 1042, 879, 779, 741, 701 cmꢁ1. HRMS (ESI,
m/z): Calcd for C26H18Cl2N [M+ H]+ 414.0816, found 414.0821.
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Journal of Heterocyclic Chemistry
DOI 10.1002/jhet