Iodine-catalyzed Povarov reaction for synthesis of cyclobuta[c]quinoline derivatives

Article abstract of DOI:10.1007/s11164-013-1024-4

The iodine-catalyzed Povarov reaction of aromatic aldehydes, amines, and cyclobutanone in THF is described. The amines include naphthalen-2-amine and anthracen-2-amine. Cyclobuta[c]quinoline derivatives are obtained in high yields. This novel procedure ha

Full text of DOI:10.1007/s11164-013-1024-4

Res Chem Intermed
DOI 10.1007/s11164-013-1024-4
Iodine-catalyzed Povarov reaction for synthesis
of cyclobuta[c]quinoline derivatives
•
Jin-Ming Yang Lin Wu Dong Fang Jian Cao
•
•
•
•
Yu-Jing Zhou Xiang-Shan Wang
Received: 22 October 2012 / Accepted: 4 January 2013
Ó Springer Science+Business Media Dordrecht 2013
Abstract The iodine-catalyzed Povarov reaction of aromatic aldehydes, amines, and
cyclobutanone in THF is described. The amines include naphthalen-2-amine and
anthracen-2-amine. Cyclobuta[c]quinoline derivatives are obtained in high yields. This
novel procedure has the advantages of mild reaction condition, high yields, and metal-
free catalyst.
Keywords Quinoline Á Naphthalen-2-amine Á Anthracen-2-amine Á Iodine Á
Synthesis
Introduction
Quinolines are an important class of compounds. They are the main components of
many biologically active molecules and are widely used as key intermediates in the
synthesis of numerous natural products and medicinal reagents. Because their
derivatives have anti-microbial [1, 2], anti-proliferative [3], anti-oxidant [4], and
anti-fungal activity [5], synthesis of quinolines has been extensively researched in
recent years [6–12]. Imino Diels–Alder reactions of Schiff bases with electron-rich
dienophiles were investigated by Povarov and coworkers [13] in 1967. In recent
years this reaction, named the Povarov reaction, has been shown to be an important
method of synthesis of quinoline derivatives [14].
J.-M. Yang Á L. Wu Á D. Fang Á J. Cao
Key Laboratory of Coastal Wetland Bioresources and Environmental Protection of Jiangsu
Province, College of Chemistry and Chemical Engineering, Yancheng Teachers University,
Yancheng 224002, Jiangsu, People’s Republic of China
Y.-J. Zhou Á X.-S. Wang (&)
School of Chemistry and Chemical Engineering, Jiangsu Key Laboratory of Green Synthetic
Chemistry for Functional Materials, Jiangsu Normal University, Xuzhou 221116,
Jiangsu, People’s Republic of China
e-mail: xswang1974@yahoo.com
123

J.-M. Yang et al.
Iodine is a novel metal-free Lewis acid which has been used to catalyze various
types of organic reaction in recent years [15–17]. In our previous work, iodine was
found to be an efficient catalyst for promotion of the Povarov reaction of ketones
as dienophiles [17, 18]. In connection with our continued research on this iodine-
catalyzed Povarov reaction, herein we report an efficient synthesis of cyclobuta[c]
naphtho[2,3-f]quinoline and cyclobuta[c]benzo[4,3-f]quinoline derivatives catalyzed
by iodine.
Results and discussion
Treatment of aromatic aldehyde 1, naphthalen-2-amine 2, and cyclobutanone 3 with
5 mol% iodine in THF under reflux conditions afforded the corresponding 3-aryl-
1,2-dihydrocyclobuta[c]benzo[f]quinoline derivatives 4 in high yields (Scheme 1).
In our initial study, different reaction temperatures were examined, using 4-chlo-
robenzaldehyde (1a), naphthalen-2-amine (2), cyclobutanone (3), and 5 mol% I2 in
THFasmodelreaction. Useofroomtemperature,50 °C, andrefluxtemperatureresulted
in isolation of 4a in trace amounts and 83 and 90 % yield, respectively (Table 1, entries
2, 3, and 5). The screening results are summarized in Table 1. The reaction yield
remained unchanged when the amount of iodine was increased, but the yield decreased
O
H2N
I2, THF
+
+
ArCHO
N
Ar
3
4
1
2
Scheme 1 The reaction of 1, 3, and naphthalen-2-amine
Table 1 Yield optimization for 4a under different conditions
Entry
Temp. (°C)
I2 (mol%)
Solvent
Isolated yields (%)
1
2
Reflux
r.t.
0
5
THF
0
trace
83
84
90
90
85
80
78
80
THF
3
50
5
THF
4
Reflux
Reflux
Reflux
Reflux
Reflux
80
1
THF
5
5
THF
6
10
5
THF
7
CH3CN
Benzene
DMF
CHCl3
8
5
9
5
10
Reflux
5
Reagents and conditions: 4-chlorobenzaldehyde 1a (0.141 g, 1.0 mmol), 2 (0.143 g, 1.0 mmol),
3 (0.074 g, 1.05 mmol), solvent (10 mL)
123

Iodine-catalyzed Povarov synthesis of cyclobuta[c]quinolines
when the amount of iodine was reduced; 5 mol% I2 at reflux in THF is, therefore,
sufficient to initiate the reaction. In addition, a survey of solvents (Table 1, entries 7-10)
indicated THF is the best solvent when 5 mol% I2 was using as promoter.
We used these optimized reaction conditions to examine the range of suitable
aldehydes 1. When different aromatic aldehydes 1 were reacted with 2 and 3 under the
standard conditions, cyclobuta[c]benzo[f]quinoline derivatives 4a–k were obtained in
high yields (Table 2). For aldehyde 1, yields of 4 were not sensitive to the electronic
properties of the aromatic ring in the presence of electron-withdrawing groups (for
example halide) or electron-donating groups (for example alkoxy group, Table 2).
Because of the good results obtained from synthesis of these cyclobuta[c]benzo
[f]quinolines, we reasoned the reaction might be suitable for use with other amines. With
this working hypothesis, anthracen-2-amine 5 was examined in this reaction instead of
naphthalen-2-amine (Scheme 2). To our delight, the desired reactions occurred
smoothly, giving cyclobuta[c]naphtha[2,3-f]quinoline derivatives 6a–l in high yields
as expected (Table 3). The structures of the products 4 and 6 were characterized by use of
1H NMR and IR spectroscopy and HRMS; the results obtained were all in good
agreement with the expected structures. The structure of product 4d was further
confirmed by X-ray diffraction analysis; its crystal structure is shown in Fig 1.
Table 2 Results from synthesis of 4a–k catalyzed by iodine in THF
Entry
Ar
Product
Time (h)
Isolated yield (%)
1
2
4-ClC6H4
4a
4b
4c
4d
4e
4f
8
6
90
87
90
92
84
86
86
90
94
85
88
3-ClC6H4
3
2-ClC6H4
6
4
4-MeOC6H4
2,4-Cl2C6H3
3,4-(MeO)2C6H3
3-BrC6H4
10
6
5
6
12
8
7
4g
4h
4i
8
Piperonyl
10
8
9
2-Thienyl
10
11
2-FC6H4
4j
6
3-MeOC6H4
4k
8
Reagents and conditions: 1 (1.0 mmol), 2 (0.143 g, 1.0 mmol), 3 (0.074 g, 1.05 mmol), I2 (0.05 mmol,
0.013 g), THF (10 mL)
O
I2, THF
H2N
+
+
ArCHO
N
Ar
1
5
6
3
Scheme 2 Reaction of 1, 3, and anthracen-2-amine
123

J.-M. Yang et al.
Isolated yield (%)
Table 3 Results from synthesis of 6a–l catalyzed by iodine in THF
Entry
Ar
Product
Time (h)
1
2
4-ClC6H4
6a
6b
6c
6d
6e
6f
10
12
10
16
10
16
12
10
10
8
89
85
90
84
89
92
87
90
86
91
86
88
3-ClC6H4
3
2-ClC6H4
4
Piperonyl
5
3,4-Cl2C6H3
3,4-(MeO)2C6H3
3-BrC6H4
6
7
6g
6h
6i
8
3-MeOC6H4
2-FC6H4
9
10
11
12
2,3-Cl2C6H3
2-MeOC6H4
4-MeOC6H4
6j
6k
6l
10
16
Reagents and conditions: 1 (1.0 mmol), 5 (0.193 g, 1.0 mmol), 3 (0.074 g, 1.05 mmol), I2 (0.05 mmol,
0.013 g), THF (10 mL)
Fig. 1 The crystal structure of product 4d
X-ray diffraction analysis indicated that all the rings in 4d, i.e. the pyridine, four-
membered, naphthalene, and benzene rings, are coplanar. The central pyridine ring
is nearly parallel to the adjacent four-membered and naphthalene rings, forming
dihedral angles of 1.2(2)° and 1.4(1)8, respectively. It forms a dihedral angle of
10.6(2)8 with the benzene ring.
In accordance with the literature [18, 19], we believe iodine catalyzes the
reaction as a mild Lewis acid. The mechanism tentatively proposed is shown in
Scheme 3. In the presence of iodine, cyclobutanone is in equilibrium with its enol
form. The Schiff base I may be formed by initial reaction of the aromatic aldehyde
and amine. Imino Diels–Alder reaction between the iodine-activated Schiff base
II and the enol then occurs selectively to form the stable intermediate III.
Dehydration of III results in dihydroquinoline IV, which is further oxidized by air
to afford the aromatized final products 4 or 6.
123

Iodine-catalyzed Povarov synthesis of cyclobuta[c]quinolines
OH
O
I2
Ar
NH2
N
I2
-H2O
ArCHO
+
I
HO
OH
-H2O
Air
4 or 6
N
imino-Diels-Alder
Reaction
N
I2
N
Ar
Ar
IV
Ar
III
II
Scheme 3 Possible mechanism of formation of the products
Experimental
Melting points were determined in open capillaries and are uncorrected. IR spectra
1
were recorded on a Tensor 27 spectrometer as KBr pellets. H NMR spectra were
obtained from solutions in DMSO-d6 or CDCl3, with Me4Si as internal standard,
using a Bruker-400 spectrometer. HRMS analysis was performed with a Bruker-
micro-TOF-Q-MS analyzer.
General procedure for synthesis of 4a–k and 6a–l
To amixture of aromatic aldehyde (1.0 mmol), amine (0.143 g, 1.0 mmol naphthalen-
2-amine for 4; 0.193 g, 1.0 mmol anthracen-2-amine for 6), and cyclobutanone
(0.074 g, 1.0 mmol)in THF (10 mL) was added I2 (0.013 g, 0.05 mmol). The reaction
mixture was stirred at reflux for the required time (indicated in the tables). After
completion of the reaction, as indicated by TLC, DMF was immediately added to the
mixture in small amounts until all the yellow solid had dissolved. The mixture was then
cooled to room temperature and the powder obtained was collected by filtration to give
4 or 6.
3-(4-Chlorophenyl)-1,2-dihydrobenzo[f]cyclobuta[c]quinoline 4a
1
mp 203–204 °C; H NMR (CDCl3, 400 MHz): dH 3.78 (t, J = 3.6 Hz, 2H, CH2),
3.90 (t, J = 3.6 Hz, 2H, CH2), 7.50 (d, J = 8.4 Hz, 2H, ArH), 7.62–7.69 (m, 2H,
123

J.-M. Yang et al.
ArH), 7.94 (d, J = 9.2 Hz, 2H, ArH), 8.09 (d, J = 9.2 Hz, 1H, ArH), 8.20
(d, J = 8.4 Hz, 2H, ArH), 8.35 (d, J = 8.0 Hz, 1H, ArH). IR (KBr, cm-1): m 3044,
2968, 2919, 1605, 1583, 1557, 1482, 1445, 1424, 1412, 1384, 1369, 1277, 1264,
1244, 1172, 1104, 1089, 1011, 989, 862, 829, 744, 734, 709. HRMS (ESI, m/z):
Calcd. for C21H15ClN [M ? H]? 316.0893, found 316.0910.
3-(3-Chlorophenyl)-1,2-dihydrocyclobuta[c]benzo[f]quinoline 4b
1
mp 176–178 °C; H NMR (CDCl3, 400 MHz): dH 3.77 (t, J = 3.2 Hz, 2H, CH2),
3.86–3.87 (m, 2H, CH2), 7.40-7.46 (m, 2H, ArH), 7.61–7.67 (m, 2H, ArH), 7.92
(d, J = 8.8 Hz, 2H, ArH), 8.03 (d, J = 9.2 Hz, 1H, ArH), 8.08 (d, J = 7.2 Hz, 1H,
ArH), 8.28 (s, 1H, ArH), 8.34 (d, J = 7.2 Hz, 1H, ArH). IR (KBr, cm-1): m 3048,
2960, 2920, 1606, 1585, 1558, 1490, 1478, 1449, 1428, 1392, 1364, 1269, 1259,
1241, 1218, 1174, 1077, 958, 894, 825, 787, 772, 750, 723. HRMS (ESI, m/z):
Calcd. for C21H15ClN [M ? H]? 316.0893, found 316.0900.
3-(2-Chlorophenyl)-1,2-dihydrocyclobuta[c]benzo[f]quinoline 4c
1
mp 199–201 °C; H NMR (CDCl3, 400 MHz): dH 3.61 (t, J = 3.6 Hz, 2H, CH2),
3.88 (t, J = 4.0 Hz, 2H, CH2), 7.38–7.44 (m, 2H, ArH), 7.52 (d, J = 7.6 Hz, 1H,
ArH), 7.64–7.72 (m, 3H, ArH), 7.95 (d, J = 8.0 Hz, 2H, ArH), 8.05 (d, J = 9.2 Hz,
1H, ArH), 8.43 (d, J = 7.2 Hz, 1H, ArH). IR (KBr, cm-1): m 3046, 2960, 2920,
1594, 1581, 1568, 1487, 1474, 1451, 1426, 1377, 1265, 1244, 1184, 1081, 1048,
1035, 989, 825, 754, 737, 706. HRMS (ESI, m/z): Calcd. for C21H15ClN [M ? H]?
316.0893, found 316.0902.
3-(4-Methoxyphenyl)-1,2-dihydrocyclobuta[c]benzo[f]quinoline 4d
1
mp 177–180 °C; H NMR (CDCl3, 400 MHz): dH 3.77 (s, 2H, CH2), 3.87 (s, 2H,
CH2), 3.92 (s, 3H, OCH3), 7.08 (d, J = 8.8 Hz, 2H, ArH), 7.63–7.66 (m, 2H,
ArH), 7.94 (s, 2H, ArH), 8.05 (d, J = 8.8 Hz, 1H, ArH), 8.23 (d, J = 8.4 Hz, 2H,
ArH), 8.36 (d, J = 7.2 Hz, 1H, ArH). IR (KBr, cm-1): m 3046, 2998, 2925, 2833,
1603, 1582, 1510, 1485, 1464, 1445, 1372, 1249, 1177, 1163, 1037, 1030, 832,
739. HRMS (ESI, m/z): Calcd. for C22H18NO [M ? H]? 312.1388, found
312.1406.
3-(2,4-Dichlorophenyl)-1,2-dihydrocyclobuta[c]benzo[f]quinoline 4e
1
mp 204–207 °C; H NMR (CDCl3, 400 MHz): dH 3.60 (t, J = 4.0 Hz, 2H, CH2),
3.88 (t, J = 4.0 Hz, 2H, CH2), 7.40–7.42 (m, 1H, ArH), 7.54 (d, J = 2.0 Hz, 1H,
ArH), 7.65 (d, J = 5.6 Hz, 1H, ArH), 7.68–7.71 (m, 2H, ArH), 7.95 (d, J = 8.8 Hz,
2H, ArH), 8.03 (d, J = 9.2 Hz, 1H, ArH), 8.42 (d, J = 7.2 Hz, 1H, ArH). IR (KBr,
cm-1): m 3043, 2978, 2933, 1579, 1552, 1470, 1446, 1425, 1401, 1383, 1365, 1270,
1243, 1215, 1182, 1173, 1138, 1099, 1080, 1045, 1032, 989, 946, 866, 831, 813,
123

Iodine-catalyzed Povarov synthesis of cyclobuta[c]quinolines
793, 750. HRMS (ESI, m/z): Calcd. for C21H14Cl2N [M ? H]? 350.0503, found
350.0501.
3-(3,4-Dimethoxyphenyl)-1,2-dihydrocyclobuta[c]benzo[f]quinoline 4f
1
mp 185–188 °C; H NMR (CDCl3, 400 MHz): dH 3.77 (t, J = 3.6 Hz, 2H, CH2),
3.86–3.88 (m, 2H, CH2), 3.97 (s, 3H, CH3O), 4.07 (s, 3H, CH3O), 7.00
(d, J = 8.4 Hz, 1H, ArH), 7.59–7.66 (m, 2H, ArH), 7.68–7.70 (m, 1H, ArH),
7.90–7.91 (m, 1H, ArH), 7.93 (s, 1H, ArH), 7.99–8.00 (m, 1H, ArH), 8.04
(d, J = 9.2 Hz, 1H, ArH), 8.34 (d, J = 7.6 Hz, 1H, ArH). IR (KBr, cm-1): m 3011,
2964, 2932, 2919, 2836, 1600, 1581, 1560, 1529, 1513, 1484, 1468, 1455, 1441, 1416,
1379, 1322, 1273, 1257, 1228, 1185, 1159, 1128, 1026, 972, 868, 852, 835, 822, 769, 753,
737. HRMS (ESI, m/z): Calcd. for C23H20NO2 [M ? H]? 342.1494, found 342.1529.
3-(3-Bromophenyl)-1,2-dihydrocyclobuta[c]benzo[f]quinoline 4g
1
mp 191–192 °C; H NMR (CDCl3, 400 MHz): dH 3.77 * 3.79 (m, 2H, CH2),
3.87–3.89 (m, 2H, CH2), 7.38 (t, J = 8.0 Hz, 1H, ArH), 7.56 (d, J = 8.0 Hz, 1H,
ArH), 7.62–7.68 (m, 2H, ArH), 7.93 (d, J = 9.2 Hz, 2H, ArH), 8.03 (d, J = 9.2 Hz,
1H, ArH), 8.12 (d, J = 8.0 Hz,1H, ArH), 8.34 (d, J = 7.2 Hz, 1H, ArH), 8.44
(s, 1H, ArH). IR (KBr, cm-1): m 3044, 3020, 2969, 2916, 1606, 1583, 1555, 1523,
1490, 1473, 1446, 1423, 1389, 1363, 1318, 1271, 1257, 1238, 1217, 1172, 1067,
994, 954, 904, 864, 833, 789, 767, 748, 728, 705. HRMS (ESI, m/z): Calcd. for
C21H15BrN [M ? H]? 360.0388, found 360.0389.
3-Piperonyl-1,2-dihydrocyclobuta[c]benzo[f]quinoline 4h
mp 183–186 °C; 1H NMR (CDCl3, 400 MHz): dH 3.70–3.71 (m, 2H, CH2),
3.80–3.82 (m, 2H, CH2), 6.04 (s, 2H, CH2), 6.94 (d, J = 8.4 Hz, 1H, ArH),
7.58–7.64 (m, 2H, ArH), 7.70 (dd, J = 8.0 Hz, J’ = 1.6 Hz, 1H, ArH), 7.81
(d, J = 1.6 Hz, 1H, ArH), 7.88–7.91 (m, 2H, ArH), 8.00 (d, J = 8.8 Hz, 1H, ArH),
8.29–8,31 (m, 1H, ArH). IR (KBr, cm-1): m 3046, 3026, 2964, 2921, 2884, 1604,
1585, 1502, 1483, 1451, 1395, 1369, 1347, 1324, 1260, 1243, 1226, 1184, 1103,
1040, 932, 867, 832, 809, 752, 735. HRMS (ESI, m/z): Calcd. for C22H16NO
[M ? H]? 326.1181, found 326.1189.
3-(2-Thienyl)-1,2-dihydrocyclobuta[c]benzo[f]quinoline 4i
1
mp 155–157 °C; H NMR (CDCl3, 400 MHz): dH 3.69 * 3.71 (m, 2H, CH2),
3.87–3.89 (m, 2H, CH2), 7.18–7.20 (m, 1H, ArH), 7.48 (d, J = 4.8 Hz, 1H, ArH),
7.61–7.65 (m, 2H, ArH), 7.66–7.70 (m, 1H, ArH), 7.89–7.92 (m, 2H, ArH), 7.99
(d, J = 9.2 Hz, 1H, ArH), 8.33 (d, J = 7.6 Hz, 1H, ArH). IR (KBr, cm-1): m 3049,
2973, 2929, 1622, 1603, 1581, 1517, 1486, 1448, 1400, 1373, 1342, 1303, 1232,
1064, 1042, 833, 810, 748, 726, 701. HRMS (ESI, m/z): Calcd. for C19H14NS
[M ? H]? 288.0847, found 288.0874.
123

J.-M. Yang et al.
3-(2-Fluorophenyl)-1,2-dihydrocyclobuta[c]benzo[f]quinoline 4j
mp 127–130 °C; 1H NMR (CDCl3, 400 MHz): dH 3.66–3.68 (m, 2H, CH2),
3.81–3.83 (m, 2H, CH2), 7.18–7.22 (m, 1H, ArH), 7.32–7.36 (m, 1H, ArH),
7.41–7.47 (m, 1H, ArH), 7.63–7.69 (m, 2H, ArH), 7.92–7.94 (m, 2H, ArH), 8.05
(d, J = 9.2 Hz, 1H, ArH), 8.17–8.21 (m, 1H, ArH), 8.41 (d, J = 7.6 Hz, 1H, ArH).
IR (KBr, cm-1): m 3047, 2966, 2925, 1616, 1582, 1487, 1452, 1427, 1413, 1381,
1267, 1244, 1211, 1181, 1101, 1070, 1027, 988, 942, 869, 824, 792, 753. HRMS
(ESI, m/z): Calcd. for C21H15FN [M ? H]? 300.1189, found 300.1194.
3-(3-Methoxyphenyl)-1,2-dihydrocyclobuta[c]benzo[f]quinoline 4k
1
mp 140–142 °C; H NMR (CDCl3, 400 MHz): dH 3.79 (t, J = 3.6 Hz, 2H, CH2),
3.86–3.88 (m, 2H, CH2), 3.95 (s, 3H, CH3O), 6.99–7.02 (m, 1H, ArH), 7.44
(t, J = 8.0 Hz, 1H, ArH), 7.60–7.67 (m, 2H, ArH), 7.78 (d, J = 8.0 Hz, 1H, ArH),
7.88 (s, 1H, ArH), 7.91–7.93 (m, 2H, ArH), 8.05 (d, J = 8.8 Hz, 1H, ArH), 8.35
(d, J = 7.2 Hz, 1H, ArH). IR (KBr, cm-1): m 3048, 3001, 2961, 2918, 2834, 1610,
1583, 1563, 1526, 1491, 1452, 1425, 1408, 1390, 1367, 1322, 1283, 1249, 1221,
1185, 1148, 1092, 1068, 1048, 990, 883, 825, 803, 787, 751, 730. HRMS (ESI, m/z):
Calcd. for C22H18NO [M ? H]? 312.1388, found 312.1393.
3-(4-Chlorophenyl)-1,2-dihydrocyclobuta[c]naphtho[2,3-f]quinoline 6a
1
mp 261–264 °C; H NMR (CDCl3, 400 MHz): dH 3.80 (s, 2H, CH2), 3.99 (s, 2H,
CH2), 7.51 (d, J = 7.2 Hz, 2H, ArH), 7.60–7.61 (m, 2H, ArH), 7.91 (d, J = 9.2 Hz,
1H, ArH), 7.99 (d, J = 9.2 Hz, 1H, ArH), 8.10 (s, 2H, ArH), 8.20 (d, J = 7.2 Hz,
2H, ArH), 8.39 (s, 1H, ArH), 8.77 (s, 1H, ArH). IR (KBr, cm-1): m 3051, 2970,
2925, 1619, 1597, 1556, 1474, 1445, 1420, 1390, 1366, 1349, 1329, 1269, 1243,
1215, 1169, 1145, 1074, 997, 946, 907, 879, 784, 735, 717. HRMS (ESI, m/z):
Calcd. for C25H17ClN [M ? H]? 366.1050, found 366.1064.
3-(3-Chlorophenyl)-1,2-dihydrocyclobuta[c]naphtho[2,3-f]quinoline 6b
1
mp 205–208 °C; H NMR (CDCl3, 400 MHz): dH 3.75 (s, 2H, CH2), 3.92 (s, 2H,
CH2), 7.40–7.47 (m, 2H, ArH), 7.57–7.59 (m, 2H, ArH), 7.89 (d, J = 9.2 Hz, 1H,
ArH), 7.96 (d, J = 9.2 Hz, 1H, ArH), 8.05–8.06 (m, 3H, ArH), 8.26 (s, 1H, ArH),
8.35 (s, 1H, ArH), 8.70 (s, 1H, ArH). IR (KBr, cm-1): m 3047, 2968, 2922, 1619,
1591, 1572, 1481, 1430, 1409, 1390, 1348, 1331, 1280, 1213, 1168, 1134, 1088,
1052, 1012, 946, 879, 839, 742, 728. HRMS (ESI, m/z): Calcd. for C25H17ClN
[M ? H]? 366.1050, found 366.1053.
3-(2-Chlorophenyl)-1,2-dihydrocyclobuta[c]naphtho[2,3-f]quinoline 6c
1
mp 208–210 °C; H NMR (CDCl3, 400 MHz): dH 3.65 (t, J = 4.0 Hz, 2H, CH2),
3.96 (t, J = 4.0 Hz, 2H, CH2), 7.38–7.45 (m, 2H, ArH), 7.53 (d, J = 7.6 Hz, 1H,
ArH), 7.58–7.60 (m, 2H, ArH), 7.72–7.74 (m, 1H, ArH), 7.92 (d, J = 9.2 Hz, 1H,
123

Iodine-catalyzed Povarov synthesis of cyclobuta[c]quinolines
ArH), 7.98 (d, J = 9.2 Hz, 1H, ArH), 8.07–8.09 (m, 1H, ArH), 8.11–8.14 (m, 1H,
ArH), 8.40 (s, 1H, ArH), 8.84 (s, 1H, ArH). IR (KBr, cm-1): m 3046, 2945, 2907,
1593, 1568, 1476, 1434, 1415, 1388, 1329, 1268, 1214, 1176, 1155, 1124, 1072,
1039, 942, 877, 822, 743, 729. HRMS (ESI, m/z): Calcd. for C25H16ClNNa
[M ? Na]? 388.0869, found 388.0871.
3-Piperonyl-1,2-dihydrocyclobuta[c]naphtho[2,3-f]quinoline 6d
mp 238–240 °C; 1H NMR (CDCl3, 400 MHz): dH 3.69–3.70 (m, 2H, CH2),
3.86–3.88 (m, 2H, CH2), 6.03 (s, 2H, CH2), 6.93 (d, J = 8.0 Hz, 1H, ArH),
7.53–7.55 (m, 2H, ArH), 7.68 (d, J = 8.4 Hz, 1H, ArH), 7.78 (d, J = 1.2 Hz, 1H,
ArH), 7.86 (d, J = 9.2 Hz, 1H, ArH), 7.92 (d, J = 9.2 Hz, 1H, ArH), 8.01–8.05
(m, 2H, ArH), 8.32 (s, 1H, ArH), 8.67 (s, 1H, ArH). IR (KBr, cm-1): m 3050, 2974,
2921, 2885, 1595, 1574, 1561, 1502, 1482, 1446, 1425, 1412, 1400, 1342, 1246,
1229, 1175, 1114, 1098, 1041, 937, 890, 878, 851, 827, 799, 744, 727. HRMS (ESI,
m/z): Calcd. for C26H18NO2 [M ? H]? 376.1338, found 376.1343.
3-(3,4-Dichlorophenyl)-1,2-dihydrocyclobuta[c]naphtho[2,3-f]quinoline 6e
1
mp 253–255 °C; H NMR (CDCl3, 400 MHz): dH 3.78 (s, 2H, CH2), 3.98 (s, 2H,
CH2), 7.55–7.59 (m, 3H, ArH), 7.88 (d, J = 9.2 Hz, 1H, ArH), 7.98 (d, J = 9.2 Hz,
1H, ArH), 8.01–8.03 (m, 1H, ArH), 8.05–8.10 (m, 2H, ArH), 8.36–8.38 (m, 2H,
ArH), 8.75 (s, 1H, ArH). IR (KBr, cm-1): m 3038, 2970, 2920, 1617, 1595, 1565,
1552, 1470, 1423, 1408, 1385, 1359, 1280, 1269, 1216, 1183, 1170, 1136, 1056,
1027, 953, 879, 824, 743, 723. HRMS (ESI, m/z): Calcd. for C25H16Cl2N [M ? H]?
400.0660, found 400.0686.
3-(3,4-Dimethoxyphenyl)-1,2-dihydrocyclobuta[c]naphtho[2,3-f]quinoline 6f
mp 221–222 °C; dH 3.78 (s, 2H, CH2), 3.95 (s, 2H, CH2), 3.99 (s, 3H, CH3O), 4.10
(s, 3H, CH3O), 7.01 (d, J = 8.4 Hz, 1H, ArH), 7.57–7.59 (m, 2H, ArH), 7.69
(d, J = 8.4 Hz, 1H, ArH), 7.95–7.99 (m, 3H, ArH), 8.04–8.10 (m, 2H, ArH), 8.38
(s, 1H, ArH), 8.75 (s, 1H, ArH). IR (KBr, cm-1): m 3050, 3002, 2956, 2930, 2834,
1591, 1574, 1511, 1487, 1462, 1440, 1421, 1388, 1334, 1253, 1228, 1180, 1144,
1111, 1096, 1027, 974, 881, 851, 823, 808, 743. HRMS (ESI, m/z): Calcd. for
C27H22NO2 [M ? H]? 392.1651, found 392.1657.
3-(3-Bromophenyl)-1,2-dihydrocyclobuta[c]naphtho[2,3-f]quinoline 6g
1
mp 211–212 °C; H NMR (CDCl3, 400 MHz): dH 3.75 (t, J = 3.6 Hz, 2H, CH2),
3.92 (t, J = 4.0 Hz, 2H, CH2), 7.35–7.38 (m, 1H, ArH), 7.54–7.58 (m, 3H, ArH),
7.88 (d, J = 9.2 Hz, 1H, ArH), 7.95 (d, J = 9.2 Hz, 1H, ArH), 8.03–8.09 (m, 3H,
ArH), 8.34 (s, 1H, ArH), 8.41 (s, 1H, ArH), 8.70 (s, 1H, ArH). IR (KBr, cm-1):
m 3051, 2969, 2925, 1616, 1596, 1556, 1474, 1444, 1419, 1376, 1347, 1331, 1269,
1243, 1216, 1168, 1145, 1067, 996, 946, 909, 879, 783, 735, 710. HRMS (ESI, m/z):
Calcd. for C25H17BrN [M ? H]? 410.0544, found 410.0554.
123

J.-M. Yang et al.
3-(3-Methoxyphenyl)-1,2-dihydrocyclobuta[c]naphtho[2,3-f]quinoline 6h
mp 209–211 °C; dH 3.81 (s, 2H, CH2), 3.98 (s, 5H, CH2 ? CH3O), 7.03
(d, J = 6.0 Hz, 1H, ArH), 7.44–7.48 (m, 1H, ArH), 7.58–7.60 (m, 2H, ArH), 7.79
(d, J = 8.0 Hz, 1H, ArH), 7.89 (s, 1H, ArH), 7.93–7.99 (m, 2H, ArH), 8.06–8.12 (m,
2H, ArH), 8.38 (s, 1H, ArH), 8.77 (s, 1H, ArH). IR (KBr, cm-1): m 3047, 3014, 2962,
2947, 2923, 2825, 1596, 1570, 1557, 1494, 1481, 1460, 1428, 1374, 1345, 1322,
1274, 1241, 1184, 1157, 1080, 1040, 1009, 996, 882, 850, 819, 792, 773, 744, 723.
HRMS (ESI, m/z): Calcd. for C26H20NO [M ? H]? 362.1545, found 362.1547.
3-(2-Fluorophenyl)-1,2-dihydrocyclobuta[c]naphtho[2,3-f]quinoline 6i
1
mp 174–176 °C; H NMR (CDCl3, 400 MHz): dH 3.71 (s, 2H, CH2), 3.91–3.92
(m, 2H, CH2), 7.18–7.23 (m, 1H, ArH), 7.33–7.36 (m, 1H, ArH), 7.42–7.46 (m, 1H,
ArH), 7.57–7.60 (m, 2H, ArH), 7.92 (d, J = 9.2 Hz, 1H, ArH), 7.98 (d, J = 9.2 Hz,
1H, ArH), 8.06–8.08 (m, 1H, ArH), 8.11–8.13 (m, 1H, ArH), 8.19–8.23 (m, 1H,
ArH), 8.40 (s, 1H, ArH), 8.83 (s, 1H, ArH). IR (KBr, cm-1): m 3057, 2975, 2952,
2918, 1611, 1596, 1575, 1544, 1484, 1449, 1428, 1407, 1388, 1349, 1330, 1267,
1247, 1217, 1205, 1184, 1149, 1101, 1051, 1032, 999, 944, 896, 875, 819, 783, 767,
750, 736. HRMS (ESI, m/z): Calcd. for C25H17FN [M ? H]? 350.1345, found
350.1362.
3-(2,3-Dichlorophenyl)-1,2-dihydrocyclobuta[c]naphtho[2,3-f]quinoline 6j
1
mp 278–280 °C; H NMR (CDCl3, 400 MHz): dH 3.62 (s, 2H, CH2), 3.98 (s, 2H,
CH2), 7.34–7.38 (m, 1H, ArH), 7.56–7.61 (m, 4H, ArH), 7.90 (d, J = 9.2 Hz, 1H,
ArH), 8.00 (d, J = 9.2 Hz, 1H, ArH), 8.08–8.10 (m, 1H, ArH), 8.12–8.15 (m, 1H,
ArH), 8.42 (s, 1H, ArH), 8.75 (s, 1H, ArH). IR (KBr, cm-1): m 3052, 2993, 2945,
2909, 1617, 1593, 1560, 1487, 1412, 1385, 1347, 1329, 1312, 1267, 1219, 1207,
1169, 1155, 1119, 1107, 1062, 1044, 997, 948, 875, 819, 784, 765, 740, 722, 705.
HRMS (ESI, m/z): Calcd. for C25H16Cl2N [M ? H]? 400.0660, found 400.0661.
3-(2-Methoxyphenyl)-1,2-dihydrocyclobuta[c]naphtho[2,3-f]quinoline 6k
mp 202–205 °C; dH 3.61 (s, 2H, CH2), 3.91 (s, 2H, CH2), 3.94 (s, 3H, CH3O), 7.04
(d, J = 8.4 Hz, 1H, ArH), 7.14–7.17 (m, 1H, ArH), 7.42–7.46 (m, 1H, ArH),
7.56–7.59 (m, 2H, ArH), 7.95 (s, 3H, ArH), 8.06–8.08 (m,1H, ArH), 8.11–8.13 (m,
1H, ArH), 8.39 (s, 1H, ArH), 8.84 (s, 1H, ArH). IR (KBr, cm-1): m 3048, 2997,
2959, 2920, 2835, 1616, 1594, 1487, 1463, 1435, 1410, 1381, 1345, 1277, 1248,
1167, 1119, 1060, 1044, 1032, 894, 883, 821, 747. HRMS (ESI, m/z): Calcd. for
C26H20NO [M ? H]? 362.1545, found 362.1557.
3-(4-Methoxyphenyl)-1,2-dihydrocyclobuta[c]naphtho[2,3-f]quinoline 6l
mp 222–223 °C; dH 3.77 (t, J = 4.0 Hz, 2H, CH2), 3.90 (s, 3H, CH3O), 3.94
(t, J = 4.0 Hz, 2H, CH2), 7.05 (d, J = 8.8 Hz, 2H, ArH), 7.55–7.57 (m, 2H, ArH),
123

Iodine-catalyzed Povarov synthesis of cyclobuta[c]quinolines
7.90 (d, J = 9.2 Hz, 1H, ArH), 7.95 (d, J = 9.2 Hz, 1H, ArH), 8.04–8.09 (m, 2H,
ArH), 8.19 (d, J = 8.8 Hz, 2H, ArH), 8.36 (s, 1H, ArH), 8.74 (s, 1H, ArH). IR (KBr,
cm-1): m 3042, 2999, 2961, 2923, 2835, 1592, 1570, 1509, 1483, 1438, 1390, 1347,
1331, 1318, 1304, 1275, 1248, 1163, 1107, 1031, 898, 879, 841, 744. HRMS (ESI,
m/z): Calcd. for C26H20NO [M ? H]? 362.1545, found 362.1547.
Conclusion
In summary, we report a facile method for synthesis of cyclobuta[c]benzo[f]quinoline
and cyclobuta[c]naphtho[2,3-f]quinoline derivatives by three-component reaction of
aromatic aldehyde, naphthalen-2-amine or anthracen-2-amine, and cyclobutanone,
catalyzed by iodine. The features of this procedure are mild reaction conditions, high
yields, operational simplicity, and metal-free catalyst.
Acknowledgments The work was partially supported by the Natural Science Foundation of Jiangsu
Province (grant no. BK2011422), the Nature Science Key Basic Research of Jiangsu Province for Higher
Education (no. 05KJD150251), the Key Laboratory of Organic Synthesis of Jiangsu Province (KJS1112),
and the Jiangsu Provincial Key Laboratory of Coastal Wetland Bioresources and Environmental
Protection (JLCBE06008).
References
1. S. Eswaran, A.V. Adhikari, N.S. Shetty, Eur. J. Med. Chem. 44, 4637 (2009)
2. H.G. Bhatt, Y.K. Agrawal, Med. Chem. Res. 19, 392 (2010)
3. M. Mor, F. Bordi, C. Carmi, S. Vezzosi, A. Lodola, P.G. Petronini, R. Alfieri, A. Cavazzoni, Chem.
Abstr. 153, 145526 (2010)
4. V.A. Kuzmin, L.I. Mazaletskaya, T.D. Nekipelova, E.N. Khodot, Russ. Chem. Bull. 57, 2405 (2008)
5. P. Manivel, S.M. Roopan, R.S. Kumar, F.N. Khan, J. Chilean Chem, Soc. 54, 183 (2009)
6. X.F. Lin, S.L. Cui, Y.G. Wang, Tetrahedron Lett. 47, 3127 (2006)
7. D.Q. Shi, L.H. Niu, H. Yao, H. Jiang, J. Heterocycl. Chem. 46, 237 (2009)
8. M. Li, Y.L. Hou, L.R. Wen, F.M. Gong, J. Org. Chem. 75, 8522 (2010)
9. X.S. Wang, Q. Li, J. Zhou, S.J. Tu, J. Heterocycl. Chem. 46, 1222 (2009)
10. Y. Luo, X.L. Pan, J. Wu, Org. Lett. 13, 1150 (2011)
11. Y. Chen, S.J. Tu, B. Jiang, F. Shi, J. Heterocycl. Chem. 44, 1201 (2007)
12. B.W. Michel, L.D. Steffens, M.S. Sigman, J. Am. Chem. Soc. 133, 8317 (2011)
13. L.S. Povarov, Russ. Chem. Rev. 36, 656 (1967)
14. V.V. Kouznetsov, Tetrahedron 65, 2721 (2009)
15. S.S. Shen, X.P. Xu, S.J. Ji, Chinese. J. Org. Chem. 29, 806 (2009)
16. H.S. Wang, J.Y. Miao, L.F. Zhao, Chinese. J. Org. Chem. 25, 615 (2005)
17. Z.H. Zhang, Q.B. Liu, Prog. Chem. 18, 271 (2006)
18. X.S. Wang, Q. Li, C.S. Yao, S.J. Tu, Eur. J. Org. Chem. 20, 3513 (2008)
19. X.S. Wang, Q. Li, J.R. Wu, S.J. Tu, J. Comb. Chem. 11, 433 (2009)
123