I2-catalyzed reactions of Schiff base and alkyl aldehyde towards benzo[f]quinoline derivatives

Article abstract of DOI:10.1002/jhet.5570450412

(Chemical Equation Presented) A mild, efficient, and general method for the synthesis of benzo[f]quinoline derivatives via a molecular iodine-catalyzed reaction of Schiff base with alkyl aldehydes has been described. The structure of 3o was confirmed by X-ray diffraction study.

Full text of DOI:10.1002/jhet.5570450412

Jul-Aug 2008
1027
I2-Catalyzed Reactions of Schiff Base and Alkyl Aldehyde towards
Benzo[f]quinoline Derivatives
Xiang-Shan Wang*a,b, Qing Lia, Mei-Mei Zhangb, Chang-Sheng Yaoa, Shu-Jiang Tua,b
a School of Chemistry and Chemical Engineering, Xuzhou Normal University, Xuzhou, Jiangsu 221116 China
b The Key Laboratory of Biotechnology for Medical Plant of Jiangsu Province, Xuzhou, Jiangsu 221116 China
Received May 15, 2007
I2
N
CH Ar
R
RCH2CHO
+
THF
N
Ar
A mild, efficient, and general method for the synthesis of benzo[f]quinoline derivatives via a molecular
iodine-catalyzed reaction of Schiff base with alkyl aldehydes has been described. The structure of 3o was
confirmed by X-ray diffraction study.
J. Heterocyclic Chem., 45, 1027 (2008).
Scheme 1
INTRODUCTION
N
CH Ar
Quinoline and its derivatives represent an important
class of nitrogen-containing heterocycles as they
constitute useful intermediates in organic synthesis and
are useful dyes [1]. And they are well known in the
pharmaceutical industry and have been shown to possess
a broad spectrum of biological activities including such as
antiasthmatic, antiinflammatory and antimalarial activity
[2]. In addition, quinoline derivatives have been evaluated
as anticancer and antihelmintic agents [3]. A number of
synthetic strategies have been developed for the
preparation of substituted quinolines [4], except for the
classic methods for the synthesis of quinoline derivatives
include Skraup, Doebner–Von Miller, Conrad–Limbach,
Combes and Pfitzinger quinoline syntheses [5].
In recent years, the use of molecular iodine in organic
synthesis has received considerable attention as an
inexpensive, non-toxic, readily available mild Lewis acid
catalyst for organic transformations such as dehydration
of tertiary alcohols to alkenes [6], synthesis of benzyl
alkyl ethers [7], synthesis of mixed ethers under hydrogen
pressure [8], bis-indoles [9], deprotection of acetals [10],
esterification [11], transesterification [12] and Michael
addition [13]. Herein we would like to report 2-aryl-
benzo[f]quinoline derivatives in THF catalyzed by iodine
by the reaction of Schiff base and alkyl aldehydes.
I2
+
RCH2CHO
R
THF
N
Ar
1
2
3
condition (Table 1, entries 1 and 2). Similar reactions were
then attempted in the presence of 10, 20 and 30 mol% of I2.
The results from Table 1 (entries 5, 6 and 7) showed that 10
mol% I2 at reflux in THF was sufficient to push the reaction
forward. Higher loading of the catalyst did not improve the
reaction yield to a great extent. To find the optimum
reaction temperature, the reaction was carried out with 10
mol% of I2 at room temperature, 50° and reflux
temperature, resulting in the isolation of 3a in trace amount,
52 % and 73 % yields (Table 1, entries 3-6), respectively.
Thus, 10 mol% of I2 and a reaction temperature at reflux
were optimal conditions. In addition, CH3CN, benzene,
DMF and ClCH2CH2Cl (Table 1, entries 8~11) were also
tested as the solvents. In these cases, product 3a was
formed in slightly lower yield (Table 1, entries 8-11).
Table 1
Synthesis of 3a in THF under different reaction conditions [a].
Entry
Temp. / °C
I2/ mol %
Solvent
Yields
[b]/%
0
0
trace
52
73
72
73
72
70
70
69
RESULTS AND DISCUSSION
1
2
3
4
5
6
7
8
r.t.
0
0
THF
THF
THF
THF
THF
THF
THF
CH3CN
Benzene
DMF
Reflux
r.t.
50
Reflux
Reflux
Reflux
Reflux
Reflux
80
When the reaction of N-arylidenenaphthalen-2-amine 1
and alkyl aldehyde 2 was carried out in THF at refluxing
temperature in the presence of iodine (Scheme 1), the 2-
arylbenzo[f]quinoline derivatives were obtained as
expected in good yields.
In our initial study, the reaction of N-(4-chloro-phenyl-
idene)naphthalen-2-amine 1a and propylaldehyde 2 was
used as a model reaction to optimize the conditions. The
reaction was first carried out in THF in the absence of I2.
No reaction occurred at room temperature and reflux
10
10
10
20
30
10
30
20
20
9
10
11
Reflux
ClCH2CH2Cl
[a] Reagents and conditions: 1 (2 mmol), 2 (2 mmol), I2 (10 mol%),
solvent (10 mL). [b] Isolated yields.

1028
X.-S. Wang, Q. Li, M.-M. Zhang, C.-S. Yao, S.-J. Tu
Vol 45
followed by an intramolecular Friedel–Crafts cyclization
to give III. The subsequent dehydration of III results in
dihydroquinoline IV, which is further oxidized by air to
give an aromatized benzo[f]quinoline 3.
Under the optimized reaction conditions, a variety of
Schiff bases 1 and alkyl aldehydes 2 were tested. They all
gave the corresponding 3-arylbenzo[f]quinolines in
moderate to good yields (Table 2).
Table 3
Table 2
I2 catalyzed reaction of naphthalen-2-amine and alkyl aldehyde in THF
I2 catalyzed reaction of N-arylidenenaphthalen-2-amine and alkyl
aldehyde in THF [a].
Entry
R
CH3
CH2CH3
(CH2)4CH3
Products
Time / h
Yields [b]/ %
1
2
3
4a
4b
4c
4
4
4
59
68
73
Entry
Ar
R
Products Time
/ h
Yields
[b]/ %
73
72
78
70
68
77
79
1
2
3
4
5
6
7
8
4-ClC6H4
4-FC6H4
CH3
CH3
CH3
CH3
CH3
CH3
3a
3b
3c
3d
3e
3f
3
3
4
3
5
3
3
4
3
3
3
3
5
5
5
5
5
5
5
4
4
[a] Reagents and conditions: naphthalen-2-amine (2 mmol), 2 (4.2
mmol), I2 (10 mol%), THF (10 mL). [b]Isolated yields.
4-BrC6H4
2,4-Cl2C6H3
2-Thiophenyl
4-NO2C6H4
4-NO2C6H4
2-Thiophenyl
4-BrC6H4
4-FC6H4
Scheme 3
H
CH2CH3
CH2CH3
CH2CH3
CH2CH3
CH2CH3
CH2CH3
CH2CH3
Ph
Ph
Ph
Ph
Ph
3g
3h
3i
3j
3k
3l
3m
3n
3o
3p
3q
3r
3s
3t
I2
RCH2CHO
72
72
66
80
74
68
70
72
75
75
78
74
76
69
OH
R
I
9
10
11
12
13
14
15
16
17
18
19
20
21
H
I2
4-ClC6H4
N
CH Ar
3,4-Cl2C6H3
3-BrC6H4
4-NO2C6H4
4-BrC6H4
4-ClC6H4
N
CH Ar
OH
R
I2
I2
R
O
OH
4-FC6H4
R
H
-H2O
R
3-BrC6H4
2-Thiophenyl
4-BrC6H4
3-BrC6H4
Ph
(CH2)4CH3
(CH2)4CH3
N
H
Ar
N
H
Ar
N
H
Ar
3u
II
III
IV
air(O2)
[a]Reagents and conditions: 1 (2 mmol), 2 (2.1 mmol), I2 (10 mol%),
R
THF (10 mL). [b]Isolated yields.
N
Ar
We also try to examine the alkylimines, which are
difficult to purify by distillation, recrystallization, or
column chromatography. However, one-pot reactions of
naphthalen-2-amine (1.0 equiv) and alkyl aldehyde 2 (2.1
equiv) in the presence of iodine (1 mol %) in THF under
reflux and an air atmosphere were performed, the
resulting alkylimine further reacted with excess alkyl
aldehyde 2 to give the corresponding 2,3-dialkylbenzo-
[f]quinoline 4 in generate yields (Scheme 3, Table 3).
Scheme 2
NH2
I2
THF
+
2RCH2CHO
R
N
CH2R
4
Figure 1. Crystal structure of product 3o.
The products 3 and 4 were completely characterized by
IR, H NMR and elemental analyses, and the data was in
agreement with their structures. In order to further
confirm the structure, the X-ray diffraction analysis [15]
of the product 3o was carried out. The crystal structure of
3o was shown in Figure 1.
According to the literatures [14], we think that iodine
catalyzes the reaction as a mild Lewis acid. The
mechanism was proposed as shown in Scheme 2. In the
presence of iodine, alkyl aldehyde is in equilibrium with
the enol form I. The enol immediately reacts with the
iodine-activated Schiff base to form intermediate II,
1

Jul-Aug 2008
I2-Catalyzed Reactions of Schiff Base and Alkyl Aldehyde
1029
= 8.0 Hz, 1H, ArH), 9.20 (s, 1H, ArH). Anal. Calcd for
C20H13Cl2N: C, 71.02; H, 3.87; N, 4.14. Found: C, 71.20; H,
3.89; N, 4.05.
In summary, we have developed a general route to
benzo[f]quinolines from Schiff bases and alkyl aldehydes
catalyzed by iodine. The procedure offers several
advantages of mild and metal-free reaction conditions,
operational simplicity, and inexpensive reagents.
2-Methyl-3-(2-thiophenyl)-benzo[f]quinoline (3e). This
compound was obtained as pale yellow crystals, mp 125~126
°C. ir (KBr): ꢀmax 3080, 3062, 2962, 2925, 1006, 1589, 1562,
1531, 1478, 1438, 1423, 1393, 1384, 1308, 1269, 1242, 1220,
1200, 1159, 1039, 989, 949, 902, 851, 830, 752, 743, 722, 703,
676; 1H nmr (DMSO-d6): ꢁ 2.81 (s, 3H, CH3), 7.23-7.25 (m, 1H,
ArH), 7.66-7.77 (m, 4H, ArH), 7.84 (d, J = 8.8 Hz, 1H, ArH),
8.01-8.05 (m, 2H, ArH), 8.82 (d, J = 8.0 Hz, 1H, ArH), 9.11 (s,
1H, ArH). Anal. Calcd for C18H13NS: C, 78.51; H, 4.76; N, 5.09.
Found: C, 78.66; H, 4.63; N, 4.97.
EXPERIMENTAL
Melting points were determined in open capillaries and are
uncorrected. IR spectra were recorded on a TENSOR 27
1
spectrometer in KBr pellet. H NMR spectra were obtained in
DMSO-d6 solution with Me4Si as internal standard using a
Bruker-400 spectrometer. Elemental analyses were carried out
using Perkin-Elmer 240 II analyzer. X-ray diffraction was
measured on a Rigaku Mercury diffractometer.
Typical procedure for 3-arylbenzo[f]quinoline derivatives
3. A mixture of N-arylidenenaphthalen-2-amine (1, 2.0 mmol),
alkyl aldehyde (2, 2.1 mmol), iodine (0.051 g, 0.2 mmol) and
THF (10 mL) was stirred under reflux for several hours to
complete the reaction (monitored by TLC). The reaction mixture
was directly evaporated and 3-arylbenzo[f]quinoline derivatives
3 were obtained by silica gel column chromatography with
petroleum ether–acetone (10:1, v/v).
2-Methyl-3-(4-nitrophenyl)-benzo[f]quinoline (3f). This
compound was obtained as pale yellow crystals, mp 187~188
°C; ir (KBr): ꢀmax 3046, 2965, 1597, 1566, 1518, 1512, 1481,
1451, 1399, 1385, 1344, 1321, 1284, 1200, 1101, 1054, 1034,
1
1008, 898, 864, 854, 825, 746, 731, 714, 696; H nmr (DMSO-
d6): ꢁ 2.59 (s, 3H, CH3), 7.71-7.80 (m, 2H, ArH), 7.92 (d, J = 9.2
Hz, 1H, ArH), 7.99 (d, J = 8.4 Hz, 2H, ArH), 8.06-8.10 (m, 2H,
ArH), 8.38 (d, J = 8.0 Hz, 2H, ArH), 8.90 (d, J = 8.0 Hz, 1H,
ArH), 9.29 (s, 1H, ArH). Anal. Calcd for C20H14N2O2: C, 76.42;
H, 4.49; N, 8.91. Found: C, 76.46; H, 4.55; N, 8.77.
2-Ethyl-3-(4-nitrophenyl)-benzo[f]quinoline (3g). This
compound was obtained as pale yellow crystals, mp 152~153
°C; ir (KBr): ꢀmax 3080, 2961, 2920, 1603, 1597, 1568, 1517,
1477, 1444, 1347, 1319, 1281, 1103, 1034, 1013, 905, 864, 854,
836, 828, 748, 732, 718, 694; 1H nmr (DMSO-d6): ꢁ 1.22 (t, J =
7.2 Hz, 3H, CH3), 2.89 (q, J = 7.2 Hz, 2H, CH2), 7.74-7.79 (m,
2H, ArH), 7.91 (d, J = 8.4 Hz, 3H, ArH), 8.06-8.11 (m, 2H,
ArH), 8.38 (d, J = 8.0 Hz, 2H, ArH), 8.97 (d, J = 8.0 Hz, 1H,
ArH), 9.23 (s, 1H, ArH). Anal. Calcd for C21H16N2O2: C, 76.81;
H, 4.91; N, 8.53. Found: C, 76.70; H, 4.99; N, 8.50.
3-(4-Chlorophenyl)-2-methylbenzo[f]quinoline (3a). This
compound was obtained as pale yellow crystals, mp 168~170
°C; ir (KBr): ꢀmax 3048, 2969, 2929, 1594, 1561, 1478, 1449,
1401, 1373, 1276, 1236, 1219, 1168, 1108, 1086, 1035, 1012,
1
1003, 894, 830, 769, 757, 746, 727; H nmr (DMSO-d6): ꢁ 2.57
(s, 3H, CH3), 7.59 (d, J = 8.4 Hz, 2H, ArH), 7.72-7.79 (m, 4H,
ArH), 7.90 (d, J = 9.2 Hz, 1H, ArH), 8.05-8.08 (m, 2H, ArH),
8.88 (d, J = 8.0 Hz, 1H, ArH), 9.17 (s, 1H, ArH).Anal. Calcd for
C20H14ClN: C, 79.07; H, 4.65; N, 4.61. Found: C, 79.21; H, 4.59;
N, 4.70.
2-Ethyl-3-(2-thiophenyl)-benzo[f]quinoline (3h). This
compound was obtained as pale yellow crystals, mp 104~106
°C; ir (KBr): ꢀmax 3054, 2967, 2934, 2908, 2979, 1603, 1586,
1563, 1529, 1475, 1442, 1423, 1400, 1382, 1329, 1309, 1265,
1240, 1224, 1201, 1134, 1083, 1068, 998, 905, 850, 827, 748,
3-(4-Fluorophenyl)-2-methylbenzo[f]quinoline (3b). This
compound was obtained as pale yellow crystals, mp 157~158
°C; ir (KBr): ꢀmax 3065, 2984, 2966, 1599, 1562, 1506, 1477,
1450, 1440, 1397, 1384, 1299, 1276, 1157, 1094, 1038, 951,
1
1
735, 709, 673; H nmr (DMSO-d6): ꢁ 1.40 (t, J = 7.2 Hz, 3H,
903, 853, 837, 818, 796, 756, 702, 676; H nmr (DMSO-d6): ꢁ
CH3), 3.18 (q, J = 7.2 Hz, 2H, CH2), 7.23-7.26 (m, 1H, ArH),
7.70-7.76 (m, 4H, ArH), 7.86 (d, J = 8.4 Hz, 1H, ArH), 8.03-
8.07 (m, 2H, ArH), 8.88 (d, J = 8.4 Hz, 1H, ArH), 9.11 (s, 1H,
ArH).Anal. Calcd for C19H15NS: C, 78.86; H, 5.22; N, 4.84.
Found: C, 78.67; H, 5.35; N, 4.98.
2.56 (s, 3H, CH3), 7.35 (t, J = 8.8 Hz, 2H, ArH), 7.70-7.78 (m,
4H, ArH), 7.89 (d, J = 9.2 Hz, 1H, ArH), 8.04-8.07 (m, 2H,
ArH), 8.87 (d, J = 8.0 Hz, 1H, ArH), 9.14 (s, 1H, ArH).Anal.
Calcd for C20H14FN: C, 83.60; H, 4.91; N, 4.87. Found: C,
83.52; H, 4.90; N, 4.59.
3-(4-Bromophenyl)-2-ethylbenzo[f]quinoline (3i). This
compound was obtained as pale yellow crystals, mp 140~142
°C; ir (KBr): ꢀmax 3050, 2974, 2932, 2910, 2829, 1603, 1586,
1473, 1440, 1405, 1393, 1373, 1331, 1316, 1293, 1274, 1220,
1131, 1099, 1071, 1008, 1031, 903, 827, 791, 751, 739, 723; 1H
nmr (DMSO-d6): ꢁ 1.22 (t, J = 7.6 Hz, 3H, CH3), 2.89 (q, J = 7.6
Hz, 2H, CH2), 7.59 (d, J = 8.4 Hz, 2H, ArH), 7.71-7.78 (m, 4H,
ArH), 7.90 (d, J = 8.8 Hz, 1H, ArH), 8.05-8.09 (m, 2H, ArH),
8.95 (d, J = 8.0 Hz, 1H, ArH), 9.17 (s, 1H, ArH). Anal. Calcd
for C21H16BrN: C, 69.62; H, 4.45; N, 3.87. Found: C, 69.77; H,
4.40; N, 3.90.
3-(4-Bromophenyl)-2-methylbenzo[f]quinoline (3c). This
compound was obtained as pale yellow crystals, mp 167~169
°C; ir (KBr): ꢀmax 3051, 2981, 2957, 1602, 1585, 1559, 1477,
1453, 1440, 1393, 1381, 1282, 1219, 1167, 1101, 1072, 1003,
904, 831, 795, 763, 784, 717; 1H nmr (DMSO-d6): ꢁ 2.58 (s, 3H,
CH3), 7.66 (d, J = 8.4 Hz, 2H, ArH), 7.70-7.79 (m, 4H, ArH),
7.91 (d, J = 8.8 Hz, 1H, ArH), 8.05-8.09 (m, 2H, ArH), 8.89 (d, J
= 8.4 Hz, 1H, ArH), 9.18 (s, 1H, ArH). Anal. Calcd for
C20H14BrN: C, 68.98; H, 4.05; N, 4.02. Found: C, 68.77; H,
4.20; N, 4.08.
3-(2,4-Dichlorophenyl)-2-methylbenzo[f]quinoline (3d).
This compound was obtained as pale yellow crystals, mp
157~158 °C; ir (KBr): ꢀmax 3058, 2959, 2920, 1604, 1586, 1552,
1474, 1449, 1401, 1376, 1277, 1034, 1168, 1140, 1098, 1074,
1039, 1031, 1004, 889, 869, 854, 829, 809, 755, 744, 704, 669;
1H nmr (DMSO-d6): ꢁ 2.37 (s, 3H, CH3), 7.58 (d, J = 8.0 Hz, 1H,
ArH), 7.59 (d, J = 8.4 Hz, 1H, ArH), 7.71-7.81 (m, 3H, ArH),
7.88 (d, J = 9.2 Hz, 1H, ArH), 8.05-8.09 (m, 2H, ArH), 8.89 (d, J
2-Ethyl-3-(4-fluorophenyl)-benzo[f]quinoline (3j). This
compound was obtained as pale yellow crystals, mp 124~126
°C; ir (KBr): ꢀmax 3054, 2972, 1600, 1058, 1474, 1441, 1403,
1377, 1333, 1318, 1275, 1222, 1160, 1097, 1031, 903, 861, 827,
1
792, 750; H nmr (DMSO-d6): ꢁ 1.22 (t, J = 7.2 Hz, 3H, CH3),
2.90 (q, J = 7.2 Hz, 2H, CH2), 7.34-7.38 (m, 2H, ArH), 7.68-
7.78 (m, 4H, ArH), 7.90 (d, J = 9.2 Hz, 1H, ArH), 8.06-8.09 (m,

1030
X.-S. Wang, Q. Li, M.-M. Zhang, C.-S. Yao, S.-J. Tu
Vol 45
2H, ArH), 8.95 (d, J = 8.0 Hz, 1H, ArH), 9.17 (s, 1H,
ArH).Anal. Calcd for C21H16FN: C, 83.70; H, 5.35; N, 4.65.
Found: C, 68.77; H, 4.20; N, 4.08.
1H, ArH), 8.08 (d, J = 6.8 Hz, 1H, ArH), 8.15 (d, J = 9.2 Hz,
1H, ArH), 8.97 (d, J = 7.6 Hz, 1H, ArH), 9.19 (s, 1H, ArH).
Anal. Calcd for C25H16ClN: C, 82.07; H, 4.41; N, 3.83. Found:
C, 82.30; H, 4.19; N, 4.01.
3-(4-Chlorophenyl)-2-ethylbenzo[f]quinoline (3k). This
compound was obtained as white powder, mp 142~143 °C, ir
(KBr): ꢀmax 3051, 2974, 2939, 1600, 1055, 1484, 1441, 1275,
1133, 1092, 1032, 1013, 903, 872, 827, 768, 751; 1H nmr
(DMSO-d6): ꢁ 1.23 (t, J = 7.6 Hz, 3H, CH3), 2.90 (q, J = 7.6 Hz,
2H, CH2), 7.60 (d, J = 8.4 Hz, 2H, ArH), 7.67 (d, J = 8.4 Hz, 2H,
ArH), 7.71-7.80 (m, 2H, ArH), 7.91 (d, J = 8.8 Hz, 1H, ArH),
8.06-8.10 (m, 2H, ArH), 8.96 (d, J = 8.0 Hz, 1H, ArH), 9.18 (s,
1H, ArH). Anal. Calcd for C21H16ClN: C, 79.36; H, 5.07; N,
4.41. Found: C, 79.50; H, 5.00; N, 4.48.
3-(3,4-Dichlorophenyl)-2-ethylbenzo[f]quinoline (3l). This
compound was obtained as pale yellow crystals, mp 105~107
°C; ir (KBr): ꢀmax 3059, 2957, 2932, 2877, 1584, 1553, 1466,
1444, 1406, 1388, 1373, 1337, 1311, 1281, 1248, 1219, 1134,
1069, 1028, 905, 880, 870, 837, 806, 750, 700; 1H nmr (DMSO-
d6): ꢁ 1.23 (t, J = 7.6 Hz, 3H, CH3), 2.89 (q, J = 7.6 Hz, 2H,
CH2), 7.63 (d, J = 8.4 Hz, 1H, ArH), 7.71-7.80 (m, 3H, ArH),
7.91 (d, J = 9.2 Hz, 2H, ArH), 8.05-8.10 (m, 2H, ArH), 8.95 (d, J
= 8.0 Hz, 1H, ArH), 9.18 (s, 1H, ArH). Anal. Calcd for
C21H15Cl2N: C, 71.60; H, 4.29; N, 3.98. Found: C, 68.77; H,
4.20; N, 4.08.
3-(4-Fluorophenyl)-2-phenylbenzo[f]quinoline (3q). This
compound was obtained as pale yellow crystals, mp 145~147
°C; ir (KBr): ꢀmax 3045, 1602, 1559, 1518, 1508, 1475, 1454,
1432, 1401, 1383, 1276, 1234, 1156, 1081, 1005, 909, 830, 814,
1
779, 753, 705; H nmr (DMSO-d6): ꢁ 7.15 (d, J = 8.8 Hz, 2H,
ArH), 7.36-7.42 (m, 5H, ArH), 7.45-7.49 (m, 2H, ArH), 7.72-
7.78 (m, 2H, ArH), 7.99 (d, J = 8.8 Hz, 1H, ArH), 8.08-8.10 (m,
1H, ArH), 8.17 (d, J = 8.8 Hz, 1H, ArH), 8.98 (d, J = 7.6 Hz,
1H, ArH), 9.19 (s, 1H, ArH). Anal. Calcd for C25H16FN: C,
85.94; H, 4.62; N, 4.01. Found: C, 85.90; H, 4.55; N, 4.13.
3-(3-Bromophenyl)-2-phenylbenzo[f]quinoline (3r). This
compound was obtained as pale yellow crystals, mp 144~145
°C; ir (KBr): ꢀmax 3054, 3027, 1599, 1558, 1471, 1451, 1440,
1431, 1415, 1392, 1309, 1278, 1246, 1222, 1075, 1062, 1004,
1
925, 908, 879, 830, 796, 767, 754, 703, 686; H nmr (DMSO-
d6): ꢁ 7.23-7.27 (m, 1H, ArH), 7.33-7.40 (m, 6H, ArH), 7.53 (d,
J = 8.0 Hz, 1H, ArH), 7.67 (s, 1H, ArH), 7.72-7.78 (m, 2H,
ArH), 8.01 (d, J = 9.2 Hz, 1H, ArH), 8.10 (d, J = 8.0 Hz, 1H,
ArH), 8.18 (d, J = 9.2 Hz, 1H, ArH), 8.99 (d, J = 7.2 Hz, 1H,
ArH), 9.20 (s, 1H, ArH). Anal. Calcd for C25H16BrN: C, 73.18;
H, 3.93; N, 3.41. Found: C, 73.27; H, 3.89; N, 3.29.
3-(3-Bromophenyl)-2-ethylbenzo[f]quinoline (3m). This
compound was obtained as white powder, mp 88~90 °C; ir
(KBr): ꢀmax 3059, 2970, 2926, 2869, 1589, 1558, 1474, 1445,
1407, 1379, 1294, 1276, 1195, 1164, 1061, 908, 875, 830, 793,
2-Phenyl-3-(2-thiophenyl)-benzo[f]quinoline (3s). This
compound was obtained as yellow crystals, mp 184~186 °C; ir
(KBr): ꢀmax 3050, 1604, 1580, 1561, 1526, 1473, 1437, 1422,
1392, 1305, 1273, 1248, 1228, 1097, 1058, 1003, 912, 866, 848,
1
769, 750, 719, 690; H nmr (DMSO-d6): ꢁ 1.23 (t, J = 7.2 Hz,
1
3H, CH3), 2.90 (q, J = 7.2 Hz, 2H, CH2), 7.49~7.52 (m, 1H,
ArH), 7.64 (d, J = 8.4 Hz, 1H, ArH), 7.70-7.81 (m, 4H, ArH),
7.91 (d, J = 9.2 Hz, 1H, ArH), 8.06-8.10 (m, 2H, ArH), 8.96 (d, J
= 8.4 Hz, 1H, ArH), 9.18 (s, 1H, ArH). Anal. Calcd for
C21H16BrN: C, 69.62; H, 4.45; N, 3.87. Found: C, 69.51; H,
4.62; N, 3.98.
829, 756, 710; H nmr (DMSO-d6): ꢁ 6.51-6.52 (m, 1H, ArH),
6.83-6.91 (m, 1H, ArH), 7.52-7.54 (m, 5H, ArH), 7.62 (d, J =
9.2 Hz, 1H, ArH), 7.70-7.72 (m, 2H, ArH), 7.93 (d, J = 8.8 Hz,
1H, ArH), 8.06-8.07 (m, 1H, ArH), 8.14 (d, J = 9.2 Hz, 1H,
ArH), 8.87~8.89 (m, 1H, ArH), 9.02 (s, 1H, ArH). Anal. Calcd
for C23H15NS: C, 81.87; H, 4.48; N, 4.15. Found: C, 81.80; H,
4.59; N, 4.07.
3-(4-Nitrophenyl)-2-phenylbenzo[f]quinoline (3n). This
compound was obtained as Pale yellow crystals, mp 224~226
°C; ir (KBr): ꢀmax 3050, 1668, 1596, 1562, 1512, 1473, 1432,
1396, 1382, 1342, 1311, 1277, 1246, 1179, 1138, 1105, 1063,
2-(n-Amyl)-3-(4-bromophenyl)-benzo[f]quinoline (3t). This
compound was obtained as yellow crystals, mp 93~95 °C; ir
(KBr): ꢀmax 3054, 2955, 2926, 2854, 1624, 1592, 1516, 1476,
1446, 1407, 1307, 1237, 1102, 1072, 1032, 1010, 905, 869, 838,
1
1011, 909, 864, 852, 837, 759, 747, 701; H nmr (DMSO-d6): ꢁ
1
7.40 (s, 5H, ArH), 7.69 (d, J = 8.4 Hz, 2H, ArH), 7.76-7.78 (m,
2H, ArH), 8.02 (d, J = 8.8 Hz, 1H, ArH), 8.18 (d, J = 8.4 Hz,
2H, ArH), 8.20 (d, J = 8.0 Hz, 2H, ArH), 9.03 (d, J = 7.6 Hz,
1H, ArH), 9.29 (s, 1H, ArH). Anal. Calcd for C25H16N2O2: C,
79.77; H, 4.28; N, 7.44. Found: C, 79.85; H, 4.13; N, 7.54.
3-(4-Bromophenyl)-2-phenylbenzo[f]quinoline (3o). This
compound was obtained as pale yellow crystals, mp 205~207
°C; ir (KBr): ꢀmax 3056, 1678, 1603, 1584, 1566, 1487, 1472,
1431, 1402, 1393, 1277, 1247, 1178, 1104, 1072, 1008, 947,
812, 765, 750, 741, 727; H nmr (DMSO-d6): ꢁ 0.78 (t, J = 6.8
Hz, 3H, CH3), 1.20~1.23 (m, 4H, 2CH2), 1.55~1.58 (m, 2H,
CH2), 2.89 (t, J = 7.2 Hz, 2H, CH2), 7.58 (d, J = 8.4 Hz, 2H,
ArH), 7.72-7.78 (m, 4H, ArH), 7.90 (d, J = 8.8 Hz, 1H, ArH),
8.06-8.09 (m, 2H, ArH), 8.95 (d, J = 8.0 Hz, 1H, ArH), 9.18 (s,
1H, ArH). Anal. Calcd for C24H22BrN: C, 71.29; H, 5.48; N,
3.46. Found: C, 71.25; H, 5.58; N, 3.27.
2-(n-Amyl)-3-(3-bromophenyl)-benzo[f]quinoline (3u).
This compound was obtained as yellow crystals, mp 79~81 °C;
ir (KBr): ꢀmax 3052, 2953, 2924, 2857, 1624, 1591, 1560, 1478,
1448, 1405, 1377, 1273, 1056, 906, 887, 836, 810, 782, 752,
695; 1H nmr (DMSO-d6): ꢁ 0.80 (t, J = 6.8 Hz, 3H, CH3),
1.20~1.24 (m, 4H, 2CH2), 1.57~1.60 (m, 2H, CH2), 2.87 (t, J =
7.6 Hz, 2H, CH2), 7.48-7.52 (m, 1H, ArH), 7.62 (d, J = 7.6 Hz,
1H, ArH), 7.69-7.79 (m, 4H, ArH), 7.90 (d, J = 9.2 Hz, 1H,
ArH), 8.06-8.09 (m, 2H, ArH), 8.95 (d, J = 8.0 Hz, 1H, ArH),
9.18 (s, 1H, ArH). Anal. Calcd for C24H22BrN: C, 71.29; H, 5.48;
N, 3.46. Found: C, 71.33; H, 5.56; N, 3.40.
1
910, 864, 833, 776, 760, 748, 716, 700; H nmr (DMSO-d6): ꢁ
7.38 (d, J = 8.4 Hz, 2H, ArH), 7.39 (s, 5H, ArH), 7.52 (d, J = 8.4
Hz, 2H, ArH), 7.74-7.76 (m, 2H, ArH), 7.99 (d, J = 8.8 Hz, 1H,
ArH), 8.09-8.11 (m, 1H, ArH), 8.17 (d, J = 8.8 Hz, 1H, ArH),
9.19 (d, J = 7.6 Hz, 1H, ArH), 9.21 (s, 1H, ArH). Anal. Calcd
for C25H16BrN: C, 73.18; H, 3.93; N, 3.41. Found: C, 73.25; H,
3.88; N, 3.20.
3-(4-Chlorophenyl)-2-phenylbenzo[f]quinoline (3p). This
compound was obtained as pale yellow crystals, mp 186~188
°C; ir (KBr): ꢀmax 3083, 3048, 1603, 1588, 1568, 1493, 1472,
1431, 1395, 1383, 1277, 1246, 1177, 1086, 1012, 948, 910, 864,
Typical procedure for 2,3-dialkylbenzo[f]quinoline
derivatives 4. A mixture of naphthalen-2-amine (2.0 mmol),
alkyl aldehyde (2, 4.2 mmol), iodine (0.051 g, 0.2 mmol) and
THF (10 mL) was stirred under reflux for several hours to
1
833, 776, 764, 749, 723, 700, 676; H nmr (DMSO-d6): ꢁ 7.36-
7.44 (m, 9H, ArH), 7.73-7.76 (m, 2H, ArH), 7.98 (d, J = 9.2 Hz,

Jul-Aug 2008
I2-Catalyzed Reactions of Schiff Base and Alkyl Aldehyde
1031
Pharm. Bull. 2002, 50, 413-414. [f] Fossa, P.; Mosti, L.; Menozzi, G.;
marzano, C.; Baccichetti, F.; Bordin, F. Bioorg. Med. Chem. 2002, 10,
743-751. [g] Ryckebusch, A.; Derprez-Poulain, R.; Maes, L.; Debreu-
Fontaine, M. A.; Mouray, E.; Grellier, P.; Sergheraert, C.; J. Med. Chem.
2003, 46, 542-557. [h] Morgan, L. R.; Jursic, B. S.; Hooper, C. L.;
Neumann, D. M.; Thangaraj, K.; Leblanc, B. Bioorg. Med. Chem. Lett.
2002, 12, 3407-3411.
complete the reaction (monitored by TLC). The reaction mixture
was directly evaporated and 2,3-dialkylbenzo[f]quinoline
derivatives 4 were obtained by silica gel column chromatog-
raphy with petroleum ether–acetone (10:1, v/v).
3-Ethyl-2-methylbenzo[f]quinoline (4a). This compound
was obtained as pale yellow crystals, mp 215-217 °C; ir (KBr):
ꢀmax 3030, 2979, 2920, 2846, 2822, 1584, 1570, 1560, 1516,
1473, 1459, 1391, 1355, 1304, 1271, 1229, 1060, 1035, 894,
[3] Sakata, G.; Makino, K.; Karasawa, Y. Heterocycles 1988, 27,
2481–2515,
1
881, 818, 763, 714; H nmr (DMSO-d6): ꢁ 1.38 (t, J = 7.6 Hz,
[4a] Demeunynck, M.; Moucheron, C.; Mesmaeker, A. K.-D.
Tetrahedron Lett. 2002, 43, 261–264; [b] Baraznenok, I. L.;
Nenajdenko, V. G.; Balenkova, E. S. Eur. J. Org. Chem. 1999, 937–
941; [c] Ali, M. M.; Tasneem, K. C.; Rajanna, P. K.; Prakash, S.
Synlett 2001, 251–253; [d] Palacios, F.; Ochoa de Retana, A. M.;
Oyarzabal, J. Tetrahedron 1999, 55, 5947–5964; [e] Charpentier, P.;
Lobregat, V.; Levacher, V.; Dupas, G.; Queguiner, G.; Bourguignon,
J. Tetrahedron Lett. 1998, 39, 4013–4016; [f] Cho, C. S.; Kim, B. T.;
Kim, T. J.; Shim, S. C. Chem. Commun. 2001, 2576–2577; [g]
Uchiyama, K.; Hayashi, Y.; Narasaka, K. Synlett 1997, 445–447; [h]
Crousse, B.; Begue, J.-P.; Bonnet-Delpon, D. J. Org. Chem. 2000,
65, 5009–5013; [i] Lin, X. F.; Cui, S. L.; Wang, Y. G. Tetrahedron
Lett. 2006, 47, 4509-4512. [j] Lin, X. F.; Cui, S. L.; Wang, Y. G.
Tetrahedron Lett. 2006, 47, 3127-3130.
[5a] Skraup, H. Chem. Ber. 1880, 13, 2086–2087; [b] Mansake,
R. H.; Kulka, M. Org. React. 1953, 7, 59–61; [c] Doebner, O.; Miller, V.
W. Chem. Ber. 1881, 14, 2812–2813; [d] Conrad, M.; Limbach, L.
Chem. Ber. 1887, 20, 944–945; [e] Combes, A. Compt. Rend. 1888, 106,
142–143; [f] Pfitzinger, W. J. Prakt. Chem. 1886, 33, 100.
[6] Whitmore, F. C.; Rothrock, H. S. J. Am. Chem. Soc. 1933,
55, 1106–1109.
[7] Rutherford, K. G.; Mamer, O. A.; Prokipcak, J. M.; Jobin, R.
A. Can. J. Chem. 1966, 44, 2337–2339.
[8] Jenner, G. Tetrahedron Lett. 1988, 29, 2445–2448. 15.
Hessian, K. O.; Flynn, B. L. Org. Lett. 2003, 5, 4377–4380.
[9] Bandgar, B. P.; Shaikh, K. A. Tetrahedron Lett. 2003, 44,
1959–1961.
[10] Sun, J.; Dong, Y.; Cao, L.; Wang, X.; Wang, S.; Hu, Y. J.
Org. Chem. 2004, 69, 8932–8934.
[11] Ramalinga, K.; Vijayalakshimi, P.; Kaimal, T. N. B.
Tetrahedron Lett. 2002, 43, 879–882.
3H, CH3), 2.71 (s, 3H, CH3), 3.19 (q, J = 7.0 Hz, 2H, CH3), 7.85-
7.95 (m, 2H, ArH), 8.05 (d, J = 9.2 Hz, 1H, ArH), 8.21 (d, J =
8.0 Hz, 1H, ArH), 8.41 (d, J = 8.8 Hz, 1H, ArH), 8.99 (d, J = 8.0
Hz, 1H, ArH), 9.73 (s, 1H, ArH). Anal. Calcd for C16H15N: C,
86.84; H, 6.83; N, 6.33. Found: C, 86.97; H, 6.68; N, 6.30.
2-Ethyl-3-(n-proyl)-benzo[f]quinoline (4b). This compound
was obtained as Pale yellow crystals, mp 208~210 °C; ir (KBr):
ꢀmax 2960, 2928, 2869, 1634, 1602, 1582, 1514, 1468, 1453,
1430, 1360, 1318, 1287, 1258, 1223, 1205, 1081, 934, 895, 825,
1
755, 713; H nmr (DMSO-d6): ꢁ 0.87 (t, J = 7.2 Hz, 3H, CH3),
1.07 (t, J = 7.2 Hz, 3H, CH3), 1.39-1.43 (m, 2H, CH3), 3.05 (q, J
= 7.2 Hz, 2H, CH3), 3.19 (t, J = 7.8 Hz, 2H, CH3), 7.87-7.96 (m,
2H, ArH), 8.07 (d, J = 9.2 Hz, 1H, ArH), 8.23 (d, J = 8.8 Hz,
1H, ArH), 8.45 (d, J = 9.2 Hz, 1H, ArH), 9.10 (d, J = 8.0 Hz,
1H, ArH), 9.75 (s, 1H, ArH). Anal. Calcd for C18H19N: C, 86.70;
H, 7.68; N, 5.62. Found: C, 86.79; H, 7.60; N, 5.55.
2-(n-Amyl)-3-(n-hexyl)-benzo[f]quinoline (4c). This
compound was obtained as pale yellow crystals, mp 51~52 °C. ir
(KBr): ꢀmax 3051, 2952, 2923, 2857, 1610, 1569, 1479, 1467,
1432, 1406, 1381, 1353, 1305, 1231, 1207, 1185, 1126, 1031,
1
906, 897, 830, 749, 728; H nmr (DMSO-d6): ꢁ 0.84~0.90(m,
6H, 2CH3), 1.30~1.38 (m, 10H, 5CH2), 1.66~1.78 (m, 4H,
2CH2), 2.84 (t, J = 7.6 Hz, 2H, CH2), 2.92 (t, J = 7.6 Hz, 2H,
CH2), 7.63-7.73 (m, 2H, ArH), 7.83 (d, J = 9.2 Hz, 1H, ArH),
7.98-8.01 (m, 2H, ArH), 8.82 (d, J = 8.0 Hz, 1H, ArH), 8.90 (s,
1H, ArH). Anal. Calcd for C24H31N: C, 86.43; H, 9.37; N, 4.20.
Found: C, 86.30; H, 9.52; N, 4.11.
[12] Chavan, S. P.; Kale, R. R.; Shivasankar, K.; Chandake, S. I.;
Benjamin, S. B. Synthesis 2003, 2695–2698.
[13a] Yadav, J. S.; Reddy, B. V. S.; Sadasiv, K.; Satheesh, G.
Tetrahedron Lett. 2002, 43, 9695–9697; [b] Wang, S. Y.; Ji, S. J.; Loh,
T. P. Synlett 2003, 2377–2379.
Acknowledgement. We are grateful to the Natural Science
Foundation (04KJB150139) of Jiangsu Education Committee
and Natural Science Foundation (06XLA010, 06PYL04) of
Xuzhou Normal University for financial support.
[14a] Ji, S. J.; Wang, S. Y.; Zhang, Y.; Loh, T. P. Tetrahedron
2004, 60, 2051–2055; [b] Ke, B. W.; Qin, Y.; He, Q. F.; Huang, Z. Y.;
Wang, F. P. Tetrahedron Lett. 2005, 46, 1751–1753.
REFERENCES AND NOTES
[15] Crystal data for 3o: C25H16BrN; M = 410.30, Pale yellow
block crystals, 0.78 ꢀ 0.55 ꢀ 0.17 mm, Monoclinic, space group P 21/c,
a = 12.704 (2), b = 9.4917 (14), c = 15.142 (3) Å, ꢀ = 94.612 (4) °, V =
1819.9 (5) 3, Z = 4, Dc = 1.497 g.cm-3. F(000) = 832, μ(MoKꢁ) = 2.268
mm-1. Intensity data were collected on Rigaku Mercury diffractometer
with graphite monochromated MoKꢁ radiation (ꢂ = 0.71070 Å) using ꢃ
scan mode with 3.03 ° < ꢄ < 25.35 °. 3336 unique reflections were
measured and 3034 reflections with I>2ꢅ(I) were used in the refinement.
Structure solved by direct methods and expanded using Fourier
techniques. The final cycle of full-matrix least squares technique to R =
0.0423 and wR = 0.0814.
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Asano, M.; Hatori, C.; Aramori, I.; Oku, T.; Tanaka, H. J. Med. Chem.
2004, 47, 2853-2863. [c] Ma, Z.; Hano, Y.; Nomura, T.; Chen, Y.
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