An efficient and highly selective method for the synthesis of 3-arylbenzo-quinoline derivatives catalyzed by iodine via three-component reactions

Article abstract of DOI:10.1055/s-2008-1067087

A mild, efficient and highly selective method for the synthesis of benzo[f]quinoline derivatives via three-component reactions of arylaldehydes, naphthalen-2-amine and ketones or β-keto esters using iodine as catalyst is described. It should be noted that only one product was obtained, with high selectivity, when ketones or β-keto esters with two different α-hydrogen atoms were chosen as reactants.

Full text of DOI:10.1055/s-2008-1067087

1902
PAPER
An Efficient and Highly Selective Method for the Synthesis of 3-Arylbenzo-
quinoline Derivatives Catalyzed by Iodine via Three-Component Reactions
S
ynthesis of 3-Ary
i
lbenzo
a
quinoline
D
n
e
rivatives g-Shan Wang,*a,b Qing Li,a Jian-Rong Wu,a Yu-Ling Li,a Chang-Sheng Yao,a Shu-Jiang Tua,b
a
School of Chemistry and Chemical Engineering, Xuzhou Normal University, Xuzhou, Jiangsu 221116, P. R. of China
The Key Laboratory of Biotechnology, Medical Plant, Xuzhou, Jiangsu 221116, P. R. of China
Fax +86(516)83500065; E-mail: xswang1974@yahoo.com
b
Received 12 February 2008; revised 26 March 2008
However, many of these reported methods suffer from
drawbacks such as harsh reaction conditions, unsatisfac-
tory yields, prolonged reaction times and cumbersome
product isolation procedures. Furthermore, in the original
Abstract: A mild, efficient and highly selective method for the syn-
thesis of benzo[f]quinoline derivatives via three-component reac-
tions of arylaldehydes, naphthalen-2-amine and ketones or b-keto
esters using iodine as catalyst is described. It should be noted that
only one product was obtained, with high selectivity, when ketones reaction of Schiff base with ketones reported by Kozlov et
or b-keto esters with two different a-hydrogen atoms were chosen
al., almost all the ketones were limited to acetone or ace-
tophenone. Thus, the development of efficient, mild, es-
pecially highly selective processes for the preparation of
biologically active 3-arylquinoline derivatives appeared
interesting.
as reactants.
Key words: benzo[f]quinoline, iodine, ketone, b-keto ester, synthe-
sis
Wang et al.12 recently reported that Schiff bases could re-
act with aliphatic aldehydes, under the influence of iodine,
to give 3-aryl-2-substituted quinolines, demonstrating
that iodine was an efficient catalyst for this reaction. How-
ever, no ketones were explored in this iodine-catalyzed re-
action, in particular, no attempt was made to investigate
ketones with a-hydrogen atoms in two different environ-
ments in order to study selectivity. In connection with our
previous research on multi-component reactions,13 the
procedure reported herein successfully realized a three-
component reaction of arylaldehyde, naphthalen-2-amine
and either ketones or b-keto esters, catalyzed by iodine,
without isolating or purifying the intermediates, to afford
benzo[f]quinolines in good to high yields. Importantly,
only one 3-aryl-1-substituted benzo[f] quinoline product
was isolated, with high selectivity, when ketones or b-
keto esters with a-hydrogen atoms in different environ-
ments were chosen as starting materials.
Multi-component reactions (MCRs), often involving
three or more reactants combined in a one-pot procedure,
generate complex organic molecules and have become in-
creasingly popular during the last decade.1 They are con-
sidered as a new type of green chemistry in economical
reaction steps, because ordinary multi-step syntheses pro-
duce considerable amounts of waste, mainly due to com-
plex isolation procedures often involving expensive,
toxic, and hazardous solvents after each step. Thus MCRs
offer a convenient strategy for the rapid and convergent
construction of complex organic molecules without the
need for isolating and purifying the intermediates – this
results in substantial minimization of waste, labor, time
and cost. They provide a powerful tool for the one-pot
synthesis of diverse and complex compounds as well as
small and drug-like heterocycles. Benzo[f]quinoline and
its derivatives are very useful compounds in various fields
of chemistry, biology and pharmacology. Some of these
compounds exhibit antibacterial,2 UGT,3 inhibitory,4 anti-
microbial,5 antimalarial,6 agonistic,7 antipsychotic,8 and
antagonist activity.9
Treatment of 4-fluorobenzaldehyde (1a), naphthalen-2-
amine (2) and 2-pentanone (3) in tetrahydrofuran, in the
presence of 5 mol% iodine at reflux, selectively afforded
the corresponding 3-(4-fluorophenyl)-1-(n-propyl)ben-
zo[f]quinoline (4a) in 89% yield (Scheme 1).
In view of the importance of benzoquinoline and its deriv-
atives, several methods for the synthesis of benzo[f]quin-
olines were developed by Kozlov10 and other groups.11
Initially, the above reaction was used as a model with
which to optimize the conditions. When the reaction was
CHO
n-Pr
O
NH2
I2
THF
Me
n-Pr
+
+
N
F
1a
2
3
4a
F
Scheme 1
SYNTHESIS 2008, No. 12, pp 1902–1910
x
x.
x
x
.
2
0
0
8
Advanced online publication: 16.05.2008
DOI: 10.1055/s-2008-1067087; Art ID: F03708SS
© Georg Thieme Verlag Stuttgart · New York

PAPER
Synthesis of 3-Arylbenzoquinoline Derivatives
1903
carried out in tetrahydrofuran in the absence of iodine, no sponding benzo[f]quinolines (Table 2, entries 1–22).
reaction occurred at either room temperature or under re- However, we failed to get the expected products when al-
flux (Table 1, entries 1 and 2). We also evaluated the iphatic aldehydes were used. We also tested the sterically
amount of catalyst required for this transformation. It was hindered 3-methylbutan-2-one, 4,4-dimethylpentan-2-
found that 5 mol% iodine in tetrahydrofuran at reflux was one, 3,3-dimethylbutan-2-one and acetophenone. The de-
sufficient to push the reaction forward. Larger amounts of sired products were obtained, though in poor yields, if 3-
catalyst did not improve yields. To find the optimum reac- methylbutan-2-one was used instead of pentan-2-one or
tion temperature, the reaction was carried out with 5 hexan-2-one (Table 2, entries 23 and 24). Perhaps the 3-
mol% iodine at room temperature, 50 °C and at reflux; methylbutan-2-one, because of its steric hindrance, was
these conditions resulted in the isolation of 4a in trace not easy to convert into the enol form in the presence of
amounts, 72% and 89% yields, respectively (Table 1, en-
tries 3, 4 and 5). Thus, 5 mol% iodine in refluxing THF Table 2 Iodine-Catalyzed Reaction of Benzaldehydes, Naphthalen-
2-amine and Ketones in THFa
were optimal conditions. The effect of solvent under re-
flux conditions was also investigated for this reaction. As
shown in Table 1, THF gave the most satisfactory result in
comparison with other solvents (Table 1, entries 8–11).
Entry Ar
R
Product Time (h) Yield (%)b
1
2
4-FC6H4
n-Pr
n-Pr
n-Pr
n-Pr
n-Pr
n-Pr
n-Pr
4a
4b
4c
4d
4e
4f
10
12
12
14
12
12
15
14
14
16
10
12
12
14
12
10
14
12
14
14
12
12
48
48
12
12
89
84
84
80
84
83
78
81
82
79
80
84
86
80
84
88
83
89
84
80
84
84
13c
18c
90
88
Table 1 Synthesis of 4a under Different Reaction Conditionsa
4-ClC6H4
4-BrC6H4
3-BrC6H4
3-ClC6H4
2,4-(Cl)2C6H3
2-thienyl
3
Entry
Temp
r.t.
I2 (mol%) Solvent
Yield (%)b
4
1
2
0
0
THF
0
0
5
reflux
r.t.
THF
6
3
5
THF
trace
72
89
88
89
54
72
76
78
7
4g
4h
4i
4
50 °C
reflux
reflux
reflux
reflux
reflux
80 °C
reflux
5
THF
8
3,4-(MeO)2C6H3 n-Pr
5
5
THF
THF
9
4-MeC6H4
4-MeOC6H4
4-O2NC6H4
2,4-(Cl)2C6H3
4-ClC6H4
n-Pr
n-Pr
n-Pr
n-Bu
n-Bu
n-Bu
n-Bu
n-Bu
n-Bu
n-Bu
n-Bu
n-Bu
n-Bu
n-Bu
i-Pr
6
10
20
5
10
11
12
13
14
15
16
17
18
19
20
21
22
23
4j
7
THF
4k
4l
8
MeCN
benzene
DMF
DCE
9
5
4m
4n
4o
4p
4q
4r
4s
10
11
5
2-thioenyl
3-BrC6H4
4-FC6H4
5
a Reagents and conditions: 1a (2 mmol), 2 (2 mmol), 3 (2.5 mmol),
solvent (10 mL), 10 h.
b Isolated yield.
3-O2NC6H4
4-O2NC6H4
4-MeC6H4
4-MeOC6H4
4-BrC6H4
3-ClC6H4
R
O
NH2
I2
+
+
ArCHO
Me
R
THF
4t
N
Ar
1
2
3
4
4u
4v
4w
4x
4y
4z
Scheme 2
3-ClC6H4
Similarly, various benzaldehydes reacted with naphtha-
len-2-amine (2) and straight chain ketones, such as pen- 24
4-FC6H4
i-Pr
tan-2-one
and
hexan-2-one,
giving
3-aryl-
25
26
3-BrC6H4
4-O2NC6H4
Ph
benzo[f]quinoline derivatives, in good to high yields and
high selectivity (Scheme 2). The results, summarized in
Table 2, show that the process tolerates both electron-
donating and electron-withdrawing substituents in the
benzaldehydes. In all cases, the reactions proceeded effi-
ciently at reflux under mild conditions to afford the corre-
Ph
a Reagents and conditions: 1 (2 mmol), 2 (2 mmol), 3 (2.5 mmol), I2
(5 mol%), THF (10 mL).
b Isolated yield.
c Separated by silica gel column chromatography.
Synthesis 2008, No. 12, 1902–1910 © Thieme Stuttgart · New York

1904
X.-S. Wang et al.
PAPER
iodine. In our continued tests, we failed to get the corre-
sponding benzo[f]quinolines using 4,4-dimethylpentan-2-
one or 3,3-dimethylbutan-2-one as reactants. To our de-
light, acetophenone, which lacks an a-methylene moiety,
successfully gave satisfactory yields (Table 2, entries 25
and 26). In order to show the general scope of this reac-
tion, we also performed the reaction with a substituted
aniline such as p-toluidine, instead of naphthalene-2-
amine. However, we could not get the expected ben-
za[f]quinoline derivatives, possibly because the activity of
p-toluidine is less than that of 2-aminonaphthalene. All
the products were characterized by 1H NMR, IR and ele-
mental analyses. The product 4c was further confirmed by
X-ray diffraction analysis,14 and the crystal structure is
shown in Figure 1.
According to the literature,15 we think that iodine cata-
lyzes the reaction as a mild Lewis acid. The proposed
mechanism is shown in Scheme 3. In the presence of io-
dine, the ketone is in equilibrium with the enol form I or
I¢. However, the enol I, not I¢ due its steric hindrance, im-
mediately reacts with the iodine-activated Schiff base to
form intermediate II, followed by an intramolecular
Friedel–Crafts cyclization to give III. Subsequent dehy-
dration of III results in dihydroquinoline IV, which is
further oxidized by air to give an aromatized ben-
zo[f]quinoline 4.
Figure 1 ORTEP diagram of 4c
2-{3-(4-chlorophenyl)benzo[f]quinolin-1-yl}acetate (6a;
Ar = 4-ClC6H4) which formed. The structure of this com-
pound was supported by 1H NMR since a singlet was ob-
served at d = 4.63 ppm due to a methylene rather than
1
methyl group. In total, eleven further H NMR signals
arising from aromatic protons were detected, which fur-
ther established the structure of the product as 6 rather
than 6¢. These results conformed to those obtained by
Kozlov et al., reported in 2000,16 which showed that the
reaction was catalyzed by HCl in propan-2-ol with poor
yields (15–55%).
In conclusion, we have found an efficient method for the
synthesis of 3-aryl-1-substituted benzo[f]quinoline deriv-
atives via three-component reactions of arylaldehydes,
naphthalen-2-amine and either ketones or b-keto esters,
using 5 mol% iodine as catalyst. It should be noted that
only one product was obtained, with high selectivity,
when ketones or b-keto esters with two a-hydrogen atoms
in different environments were chosen as reactants. The
features of this procedure are mild reaction conditions,
operational simplicity and high selectivity.
Wang et al.12 demonstrated by 1H NMR that an aliphatic
aldehyde could convert into the enol in the presence of io-
dine, thus we selected the b-keto esters as reactants due to
their higher enol content. In order to obtain the desired
3-aryl-1-methylbenzo[f]quinoline-2-carbonylate, we car-
ried out the above reaction under the same reaction condi-
tions (Scheme 4, Table 3). Interestingly, it was the
O
C
OH
CHR
OH
I2
I2
H3C
H3C
CH2R
CH2R
I'
I
NH2
N
C
H
Ar
ArCHO
+
OH
CH2R
I2
N
C
Ar
N
C
H
Ar
I2
H
I2
H2C
R
CH2R
HO
CH2R
O
– H2O
N
H
Ar
N
Ar
N
Ar
H
H
IV
II
III
CH2R
N
air
Ar
Scheme 3
Synthesis 2008, No. 12, 1902–1910 © Thieme Stuttgart · New York

PAPER
Synthesis of 3-Arylbenzoquinoline Derivatives
1905
Me
CO2R
NH2
N
Ar
I2
+
ArCHO
MeCOCH2CO2R
+
6'
THF
CH2CO2R
1
2
5
N
Ar
6
Scheme 4
3-(4-Fluorophenyl)-1-(n-propyl)benzo[f]quinoline (4a)
Mp 123–124 °C.
Table 3 Iodine-Catalyzed Reactions of Benzaldehydes, Naphtha-
len-2-amine and b-Keto Esters in THFa
IR (KBr): 3041, 2987, 2956, 2931, 2873, 1599, 1580, 1549, 1525,
1482, 1458, 1435, 1376, 1350, 1295, 1224, 1157, 1097, 989, 910,
863, 831, 747 cm–1.
1H NMR (DMSO-d6): d = 1.10 (t, J = 7.6 Hz, 3 H, CH3), 1.86–1.93
(m, 2 H, CH2), 3.48 (t, J = 7.6 Hz, 2 H, CH2), 7.39 (d, J = 8.8 Hz,
2 H, ArH), 7.69–7.78 (m, 2 H, ArH), 7.96 (d, J = 8.8 Hz, 1 H, ArH),
8.07–8.12 (m, 3 H, ArH), 8.39 (dd, J = 8.4, 1.6 Hz, 2 H, ArH), 8.69
(d, J = 8.4 Hz, 1 H, ArH).
Entry Ar
R
Product Time (h) Yield (%)b
1
2
4-ClC6H4
Me
Me
Me
Me
Me
Me
6a
6b
6c
6d
6e
6f
8
6
8
6
8
8
8
6
8
8
8
8
92
90
93
94
90
93
89
90
82
83
80
84
2,4-Cl2C6H3
2,3-Cl2C6H3
4-NO2C6H4
4-BrC6H4
3
4
Anal. Calcd for C22H18FN: C, 83.78; H, 5.75; N, 4.44. Found: C,
83.66; H, 5.90; N, 4.31.
5
6
4-CH3 °C6H4
3-(4-Chlorophenyl)-1-(n-propyl)benzo[f]quinoline (4b)
Mp 116–117 °C.
7
2,3-(CH3O)2C6H3 Me
6g
6h
6i
IR (KBr): 3047, 2963, 2932, 2873, 1592, 1579, 1548, 1528, 1482,
1447, 1403, 1377, 1346, 1330, 1167, 1099, 1087, 1014, 989, 861,
837, 822, 745, 723 cm–1.
1H NMR (DMSO-d6): d = 1.06 (t, J = 7.2 Hz, 3 H, CH3), 1.83–1.90
(m, 2 H, CH2), 3.45 (t, J = 7.6 Hz, 2 H, CH2), 7.58 (d, J = 8.4 Hz,
2 H, ArH), 7.65–7.75 (m, 2 H, ArH), 7.93 (d, J = 9.2 Hz, 1 H, ArH),
8.01–8.08 (m, 2 H, ArH), 8.12 (s, 1 H, ArH), 8.32 (d, J = 8.4 Hz,
2 H, ArH), 8.66 (d, J = 8.4 Hz, 1 H, ArH).
8
3-NO2C6H4
2,4-Cl2C6H3
4-BrC6H4
3-BrC6H4
4-ClC6H4
Me
Et
Et
Et
Et
9
10
11
12
6j
6k
6l
Anal. Calcd for C22H18ClN: C, 79.63; H, 5.47; N, 4.22. Found: C,
79.75; H, 5.40; N, 4.45.
a Reagents and conditions: 1 (2 mmol), 2 (2 mmol), 5 (2.5 mmol), I2
(5 mol%), THF (10 mL).
b Isolated yields.
3-(4-Bromophenyl)-1-(n-propyl)benzo[f]quinoline (4c)
Mp 109–111 °C.
IR (KBr): 3047, 2960, 2871, 1578, 1547, 1482, 1440, 1401, 1376,
1359, 1272, 1165, 1102, 1068, 1010, 989, 941, 900, 861, 834, 821,
797, 745, 719 cm–1.
1H NMR (DMSO-d6): d = 1.04 (t, J = 7.2 Hz, 3 H, CH3), 1.78–1.86
(m, 2 H, CH2), 3.40 (t, J = 7.6 Hz, 2 H, CH2), 7.65–7.71 (m, 4 H,
ArH), 7.90 (d, J = 8.8 Hz, 1 H, ArH), 8.01–8.06 (m, 3 H, ArH), 8.22
(d, J = 8.4 Hz, 2 H, ArH), 8.62 (d, J = 8.4 Hz, 1 H, ArH).
Melting points were determined in open capillaries and are uncor-
rected. IR spectra were recorded on a TENSOR 27 spectrometer in
KBr pellets. 1H NMR spectra were obtained from solution in
DMSO-d6 or CDCl3 with TMS as internal standard using an Inova-
400 spectrometer. Elemental analyses were carried out on a Perkin-
Elmer 2400 II analyzer.
Anal. Calcd for C22H18BrN: C, 70.22; H, 4.82; N, 3.72. Found: C,
70.26; H, 4.66; N, 3.88.
Syntheses of 3-Arylbenzo[f]quinoline Derivatives 4; General
Procedure
A dry 50 mL flask was charged with arylaldehyde (2.0 mmol),
naphthalen-2-amine (2.0 mmol, 0.286 g), ketone (2.5 mmol), I2 (0.1
mmol, 0.025 g) and THF (10 mL). The reaction mixture was stirred
at reflux for 10–16 h (48 h for 4w and 4x). After completion of the
reaction as indicated by TLC, the mixture was cooled to r.t. and the
generated crystals were collected by filtration to give 4a–v, 4y and
4z. The products 4w and 4x were purified by silica gel (200–300
mm) column chromatography (acetone–PE, 1:3).
3-(3-Bromophenyl)-1-(n-propyl)benzo[f]quinoline (4d)
Mp 140–142 °C.
IR (KBr): 3051, 2953, 2866, 1583, 1548, 1523, 1478, 1452, 1436,
1338, 1245, 1070, 1011, 898, 850, 831, 797, 776, 738, 709, 681
cm–1.
1H NMR (DMSO-d6): d = 1.11 (t, J = 7.2 Hz, 3 H, CH3), 1.87–1.95
(m, 2 H, CH2), 3.49 (t, J = 7.6 Hz, 2 H, CH2), 7.51–7.55 (m, 1 H,
ArH), 7.69–7.80 (m, 3 H, ArH), 7.98 (d, J = 9.2 Hz, 1 H, ArH),
Synthesis 2008, No. 12, 1902–1910 © Thieme Stuttgart · New York

1906
X.-S. Wang et al.
PAPER
8.08–8.12 (m, 2 H, ArH), 8.18 (s, 1 H, ArH), 8.34 (d, J = 8.0 Hz,
1 H, ArH), 8.53 (s, 1 H, ArH), 8.70 (d, J = 8.4 Hz, 1 H, ArH).
1H NMR (DMSO-d6): d = 1.11 (t, J = 7.2 Hz, 3 H, CH3), 1.88–1.94
(m, 2 H, CH2), 2.41 (s, 3 H, CH3), 3.49 (t, J = 7.6 Hz, 2 H, CH2),
7.39 (d, J = 8.0 Hz, 2 H, ArH), 7.68–7.72 (m, 1 H, ArH), 7.75–7.79
(m, 1 H, ArH), 7.97 (d, J = 9.2 Hz, 1 H, ArH), 8.08–8.10 (m, 3 H,
ArH), 8.24 (d, J = 8.0 Hz, 2 H, ArH), 8.70 (d, J = 8.4 Hz, 1 H, ArH).
Anal. Calcd for C22H18BrN: C, 70.22; H, 4.82; N, 3.72. Found: C,
70.34; H, 4.70; N, 3.89.
3-(3-Chlorophenyl)-1-(n-propyl)benzo[f]quinoline (4e)
Mp 117–118 °C.
Anal. Calcd for C23H21N: C, 88.71; H, 6.80; N, 4.50. Found: C,
88.89; H, 6.71; N, 4.55.
IR (KBr): 3054, 2954, 2926, 2867, 1584, 1550, 1527, 1483, 1452,
1438, 1421, 1379, 1339, 1259, 1245, 1079, 992, 899, 850, 831, 778,
740, 682 cm–1.
3-(4-Methoxyphenyl)-1-(n-propyl)benzo[f]quinoline (4j)
Mp 103–104 °C.
IR (KBr): 3056, 2964, 2934, 2872, 2842, 1605, 1583, 1547, 1510,
1480, 1457, 1435, 1353, 1294, 1254, 1173, 1113, 1026, 831, 793,
742 cm–1.
1H NMR (DMSO-d6): d = 1.10 (t, J = 7.2 Hz, 3 H, CH3), 1.88–1.93
(m, 2 H, CH2), 3.48 (t, J = 7.6 Hz, 2 H, CH2), 3.86 (s, 3 H, CH3O),
7.12 (d, J = 8.4 Hz, 2 H, ArH), 7.67–7.71 (m, 1 H, ArH), 7.75–7.78
(m, 1 H, ArH), 7.95 (d, J = 8.8 Hz, 1 H, ArH), 8.07–8.09 (m, 3 H,
ArH), 8.30 (d, J = 8.8 Hz, 2 H, ArH), 8.69 (d, J = 8.4 Hz, 1 H, ArH).
1H NMR (DMSO-d6): d = 1.11 (t, J = 7.2 Hz, 3 H, CH3), 1.87–1.95
(m, 2 H, CH2), 3.49 (t, J = 7.6 Hz, 2 H, CH2), 7.55–7.62 (m, 2 H,
ArH), 7.70–7.80 (m, 2 H, ArH), 7.99 (d, J = 8.8 Hz, 1 H, ArH),
8.09–8.12 (m, 2 H, ArH), 8.19 (s, 1 H, ArH), 8.30 (d, J = 7.6 Hz,
1 H, ArH), 8.39 (d, J = 1.6 Hz, 1 H, ArH), 8.70 (d, J = 8.4 Hz, 1 H,
ArH).
Anal. Calcd for C22H18ClN: C, 79.63; H, 5.47; N, 4.22. Found: C,
79.73; H, 5.33; N, 4.34.
Anal. Calcd for C23H21NO: C, 84.37; H, 6.46; N, 4.28. Found: C,
84.50; H, 6.37; N, 4.33.
3-(2,4-Dichlorophenyl)-1-(n-propyl)benzo[f]quinoline (4f)
Mp 131–133 °C.
3-(4-Nitrophenyl)-1-(n-propyl)benzo[f]quinoline (4k)
Mp 146–147 °C.
IR (KBr): 3064, 2958, 2932, 2873, 1590, 1556, 1527, 1477, 1454,
1439, 1379, 1348, 1251, 1145, 1100, 1044, 989, 910, 891, 855, 833,
823, 794, 740, 731 cm–1.
1H NMR (DMSO-d6): d = 1.10 (t, J = 7.2 Hz, 3 H, CH3), 1.87–1.94
(m, 2 H, CH2), 3.50 (t, J = 7.6 Hz, 2 H, CH2), 7.63 (dd, J = 8.4, 2.0
Hz, 1 H, ArH), 7.74–7.84 (m, 5 H, ArH), 7.95 (d, J = 9.2 Hz, 1 H,
ArH), 8.12–8.15 (m, 2 H, ArH), 8.77 (d, J = 8.4 Hz, 1 H, ArH).
IR (KBr): 2955, 2886, 2864, 1597, 1581, 1552, 1511, 1481, 1450,
1339, 1196, 1164, 1108, 1090, 869, 848, 834, 801, 747 cm–1.
1H NMR (DMSO-d6): d = 1.12 (t, J = 7.2 Hz, 3 H, CH3), 1.90–1.96
(m, 2 H, CH2), 3.52 (t, J = 7.6 Hz, 2 H, CH2), 7.73–7.82 (m, 2 H,
ArH), 8.00 (d, J = 9.2 Hz, 1 H, ArH), 8.10–8.15 (m, 2 H, ArH), 8.29
(s, 1 H, ArH), 8.40 (d, J = 8.8 Hz, 2 H, ArH), 8.60 (d, J = 8.8 Hz,
2 H, ArH), 8.73 (d, J = 8.4 Hz, 1 H, ArH).
Anal. Calcd for C22H17Cl2N: C, 72.14; H, 4.68; N, 3.82. Found: C,
72.30; H, 4.42; N, 3.78.
Anal. Calcd for C22H18N2O2: C, 77.17; H, 5.30; N, 8.18. Found: C,
77.29; H, 5.16; N, 8.26.
1-(n-Propyl)-3-(2-thienyl)benzo[f]quinoline (4g)
Mp 117–118 °C.
1-(n-Butyl)-3-(2,4-dichlorophenyl)benzo[f]quinoline (4l)
Mp 84–85 °C.
IR (KBr): 3072, 2957, 2928, 2868, 1581, 1548, 1522, 1480, 1454,
1439, 1421, 1378, 1349, 1250, 1226, 1067, 1035, 989, 866, 833,
751, 732 cm–1.
1H NMR (DMSO-d6): d = 1.11 (t, J = 7.2 Hz, 3 H, CH3), 1.86–1.93
(m, 2 H, CH2), 3.47 (t, J = 7.6 Hz, 2 H, CH2), 7.24–7.26 (m, 1 H,
ArH), 7.68–7.79 (m, 3 H, ArH), 7.87 (d, J = 8.8 Hz, 1 H, ArH),
8.02–8.10 (m, 4 H, ArH), 8.68 (d, J = 8.4 Hz, 1 H, ArH).
IR (KBr): 3055, 2960, 2927, 2860, 1590, 1556, 1525, 1509, 1476,
1459, 1450, 1438, 1380, 1348, 1249, 1186, 1145, 1099, 1043, 893,
857, 834, 815, 794, 740 cm–1.
1H NMR (DMSO-d6): d = 0.98 (t, J = 7.2 Hz, 3 H, CH3), 1.49–1.57
(m, 2 H, CH2), 1.83–1.89 (m, 2 H, CH2), 3.52 (t, J = 7.0 Hz, 2 H,
CH2), 7.63 (dd, J = 8.4, 2.0 Hz, 1 H, ArH), 7.75–7.83 (m, 5 H,
ArH), 7.95 (d, J = 8.8 Hz, 1 H, ArH), 8.12–8.15 (m, 2 H, ArH), 8.78
(d, J = 8.4 Hz, 1 H, ArH).
Anal. Calcd for C20H17NS: C, 79.17; H, 5.65; N, 4.62. Found: C,
79.28; H, 5.49; N, 4.75.
3-(3,4-Dimethoxyphenyl)-1-(n-propyl)benzo[f]quinoline (4h)
Mp 135–136 °C.
Anal. Calcd for C23H19Cl2N: C, 72.64; H, 5.04; N, 3.68. Found: C,
72.77; H, 5.18; N, 3.57.
IR (KBr): 3057, 2988, 2957, 2866, 2834, 1601, 1581, 1547, 1511,
1482, 1457, 1416, 1337, 1317, 1252, 1227, 1172, 1148, 1107, 1029,
851, 849, 833, 811, 761 cm–1.
1-(n-Butyl)-3-(4-chlorophenyl)benzo[f]quinoline (4m)
Mp 99–100 °C.
IR (KBr): 3057, 2940, 2868, 1579, 1547, 1527, 1479, 1452, 1429,
1407, 1388, 1347, 1275, 1175, 1090, 1011, 992, 970, 942, 887, 871,
835, 812, 756, 740, 712 cm–1.
1H NMR (DMSO-d6): d = 0.97 (t, J = 7.2 Hz, 3 H, CH3), 1.48–1.55
(m, 2 H, CH2), 1.79–1.87 (m, 2 H, CH2), 3.47 (t, J = 7.6 Hz, 2 H,
CH2), 7.60 (d, J = 8.4 Hz, 2 H, ArH), 7.68–7.77 (m, 2 H, ArH), 7.95
(d, J = 8.8 Hz, 1 H, ArH), 8.06–8.11 (m, 3 H, ArH), 8.34 (d, J = 8.4
Hz, 2 H, ArH), 8.69 (d, J = 8.4 Hz, 1 H, ArH).
1H NMR (DMSO-d6): d = 1.12 (t, J = 7.2 Hz, 3 H, CH3), 1.88–1.94
(m, 2 H, CH2), 3.50 (t, J = 7.6 Hz, 2 H, CH2), 3.86 (s, 3 H, CH3O),
3.93 (s, 3 H, CH3O), 7.13 (d, J = 8.4 Hz, 1 H, ArH), 7.68–7.71 (m,
1 H, ArH), 7.75–7.79 (m, 1 H, ArH), 7.90 (dd, J = 8.4, 2.0 Hz, 1 H,
ArH), 7.95–7.98 (m, 2 H, ArH), 8.03–8.11 (m, 3 H, ArH), 8.70 (d,
J = 8.4 Hz, 1 H, ArH).
Anal. Calcd for C24H23NO2: C, 80.64; H, 6.49; N, 3.92. Found: C,
80.55; H, 6.30; N, 4.05.
Anal. Calcd for C23H20ClN: C, 79.87; H, 5.83; N, 4.05. Found: C,
79.72; H, 5.65; N, 4.11.
3-(4-Methylphenyl)-1-(n-propyl)benzo[f]quinoline (4i)
Mp 101–102 °C.
1-(n-Butyl)-3-(2-thienyl)benzo[f]quinoline (4n)
Mp 86–87 °C.
IR (KBr): 3057, 2958, 2868, 1604, 1581, 1546, 1525, 1479, 1454,
1434, 1374, 1348, 1259, 1180, 1113, 1017, 988, 833, 821, 745 cm–1.
Synthesis 2008, No. 12, 1902–1910 © Thieme Stuttgart · New York

PAPER
Synthesis of 3-Arylbenzoquinoline Derivatives
1907
IR (KBr): 3063, 2949, 2923, 2867, 1579, 1549, 1523, 1481, 1455,
1430, 1349, 1248, 1225, 868, 833, 754, 724 cm–1.
Anal. Calcd for C23H20N2O2: C, 77.51; H, 5.66; N, 7.86. Found: C,
77.43; H, 5.55; N, 7.80.
1H NMR (CDCl3): d = 1.08 (t, J = 7.2 Hz, 3 H, CH3), 1.61–1.68 (m,
2 H, CH2), 1.92–2.00 (m, 2 H, CH2), 3.49 (t, J = 8.0 Hz, 2 H, CH2),
7.19–7.21 (m, 1 H, ArH), 7.48–7.50 (m, 1 H, ArH), 7.62–7.71 (m,
2 H, ArH), 7.78–7.80 (m, 2 H, ArH), 7.94–7.97 (m, 2 H, ArH), 8.02
(d, J = 9.2 Hz, 1 H, ArH), 8.69 (d, J = 8.4 Hz, 1 H, ArH).
1-(n-Butyl)-3-(4-methylphenyl)benzo[f]quinoline (4s)
Mp 124–125 °C.
IR (KBr): 3055, 3030, 2960, 2947, 2923, 2867, 1579, 1547, 1525,
1509, 1479, 1464, 1429, 1392, 1350, 1255, 1180, 1018, 872, 835,
821, 811, 751, 733, 714 cm–1.
1H NMR (CDCl3): d = 1.05 (t, J = 7.2 Hz, 3 H, CH3), 1.56–1.67 (m,
2 H, CH2), 1.91–1.99 (m, 2 H, CH2), 2.44 (s, 3 H, CH3), 3.49 (t,
J = 7.6 Hz, 2 H, CH2), 7.34 (d, J = 8.0 Hz, 2 H, ArH), 7.60–7.68 (m,
2 H, ArH), 7.81 (s, 1 H, ArH), 7.93–7.95 (m, 2 H, ArH), 8.06 (d,
J = 8.8 Hz, 1 H, ArH), 8.11 (d, J = 8.0 Hz, 2 H, ArH), 8.69 (d,
J = 8.4 Hz, 1 H, ArH).
Anal. Calcd for C21H19NS: C, 79.45; H, 6.03; N, 4.41. Found: C,
79.52; H, 5.92; N, 4.54.
3-(3-Bromophenyl)-1-(n-butyl)benzo[f]quinoline (4o)
Mp 106–107 °C.
IR (KBr): 3054, 2959, 2930, 2872, 2858, 1584, 1568, 1549, 1487,
1478, 1456, 1436, 1419, 1340, 1260, 1242, 1091, 1070, 903, 866,
833, 816, 773, 742, 710, 682 cm–1.
1H NMR (CDCl3): d = 1.06 (t, J = 7.2 Hz, 3 H, CH3), 1.59–1.65 (m,
2 H, CH2), 1.91–1.99 (m, 2 H, CH2), 3.50 (t, J = 8.0 Hz, 2 H, CH2),
7.40 (t, J = 8.0 Hz, 1 H, ArH), 7.57 (dd, J = 2.0, 1.2 Hz, 1 H, ArH),
7.59–7.70 (m, 2 H, ArH), 7.79 (s, 1 H, ArH), 7.96 (d, J = 8.4 Hz,
2 H, ArH), 8.05 (d, J = 9.2 Hz, 1 H, ArH), 8.12–8.14 (m, 1 H, ArH),
8.38–8.39 (m, 1 H, ArH), 8.69 (d, J = 8.0 Hz, 1 H, ArH).
Anal. Calcd for C24H23N: C, 88.57; H, 7.12; N, 4.30. Found: C,
88.66; H, 7.18; N, 4.17.
1-(n-Butyl)-3-(4-methoxyphenyl)benzo[f]quinoline (4t)
Mp 117–118 °C.
IR (KBr): 3055, 2951, 2935, 2868, 2840, 1609, 1581, 1548, 1510,
1479, 1465, 1452, 1355, 1293, 1253, 1169, 1029, 872, 836, 811,
754 cm–1.
1H NMR (CDCl3): d = 1.05 (t, J = 7.2 Hz, 3 H, CH3), 1.58–1.66 (m,
2 H, CH2), 1.91–1.98 (m, 2 H, CH2), 3.48 (t, J = 8.0 Hz, 2 H, CH2),
3.89 (s, 3 H, CH3O), 7.04–7.08 (m, 2 H, ArH), 7.59–7.68 (m, 2 H,
ArH), 7.78 (s, 1 H, ArH), 7.92–7.95 (m, 2 H, ArH), 8.05 (d, J = 9.2
Hz, 1 H, ArH), 8.16–8.20 (m, 2 H, ArH), 8.68 (d, J = 8.4 Hz, 1 H,
ArH).
Anal. Calcd for C23H20BrN: C, 70.78; H, 5.16; N, 3.59. Found: C,
70.67; H, 5.22; N, 3.50.
1-(n-Butyl)-3-(4-fluorophenyl)benzo[f]quinoline (4p)
Mp 95–96 °C.
IR (KBr): 3055, 2950, 2925, 2865, 1600, 1580, 1549, 1528, 1481,
1450, 1388, 1353, 1330, 1295, 1219, 1156, 1100, 1012, 865, 851,
838, 809, 753, 735, 717 cm–1.
1H NMR (CDCl3): d = 1.06 (t, J = 7.2 Hz, 3 H, CH3), 1.59–1.65 (m,
2 H, CH2), 1.91–1.99 (m, 2 H, CH2), 3.50 (t, J = 8.0 Hz, 2 H, CH2),
7.20–7.24 (m, 2 H, ArH), 7.62–7.69 (m, 2 H, ArH), 7.79 (s, 1 H,
ArH), 7.94–7.97 (m, 2 H, ArH), 8.05 (d, J = 9.2 Hz, 1 H, ArH),
8.19–8.22 (m, 2 H, ArH), 8.69 (d, J = 8.4 Hz, 1 H, ArH).
Anal. Calcd for C24H23NO: C, 84.42; H, 6.79; N, 4.10. Found: C,
84.56; H, 6.70; N, 4.22.
3-(4-Bromophenyl)-1-(n-butyl)benzo[f]quinoline (4u)
Mp 113–114 °C.
IR (KBr): 3055, 2947, 2924, 2867, 2851, 1579, 1546, 1478, 1450,
1429, 1386, 1346, 1276, 1176, 1101, 1009, 993, 942, 886, 872, 829,
753, 712 cm–1.
1H NMR (DMSO-d6): d = 1.00 (t, J = 7.2 Hz, 3 H, CH3), 1.52–1.58
(m, 2 H, CH2), 1.83–1.90 (m, 2 H, CH2), 3.52 (t, J = 7.6 Hz, 2 H,
CH2), 7.70–7.79 (m, 4 H, ArH), 7.97 (d, J = 9.2 Hz, 1 H, ArH),
8.08–8.12 (m, 2 H, ArH), 8.31 (s, 1 H, ArH), 8.30 (d, J = 8.0 Hz,
2 H, ArH), 8.72 (d, J = 8.4 Hz, 1 H, ArH).
Anal. Calcd for C23H20FN: C, 83.86; H, 6.12; N, 4.25. Found: C,
83.98; H, 6.03; N, 4.37.
1-(n-Butyl)-3-(3-nitrophenyl)benzo[f]quinoline (4q)
Mp 128–129 °C.
IR (KBr): 3084, 3052, 2959, 2931, 2862, 1583, 1534, 1486, 1456,
1435, 1343, 1308, 1259, 1244, 1165, 1074, 926, 872, 857, 850, 834,
815, 799 cm–1.
1H NMR (CDCl3): d = 1.07 (t, J = 7.2 Hz, 3 H, CH3), 1.59–1.68 (m,
2 H, CH2), 1.93–2.00 (m, 2 H, CH2), 3.51 (t, J = 8.0 Hz, 2 H, CH2),
7.64–7.72 (m, 3 H, ArH), 7.87 (s, 1 H, ArH), 7.96–7.99 (m, 2 H,
ArH), 8.06 (d, J = 7.2 Hz, 1 H, ArH), 8.28–8.31 (m, 1 H, ArH), 8.59
(d, J = 7.6 Hz, 1 H, ArH), 8.69 (d, J = 8.0 Hz, 1 H, ArH), 9.06 (s,
1 H, ArH).
Anal. Calcd for C23H20BrN: C, 70.78; H, 5.16; N, 3.59. Found: C,
70.66; H, 5.30; N, 3.55.
1-(n-Butyl)-3-(3-chlorophenyl)benzo[f]quinoline (4v)
Mp 96–97 °C.
IR (KBr): 3055, 2960, 2932, 2859, 1585, 1550, 1525, 1484, 1456,
1436, 1420, 1340, 1260, 1241, 1166, 1094, 1076, 902, 868, 833,
815, 774, 742, 730 cm–1.
1H NMR (DMSO-d6): d = 1.00 (t, J = 7.2 Hz, 3 H, CH3), 1.52–1.58
(m, 2 H, CH2), 1.83–1.89 (m, 2 H, CH2), 3.52 (t, J = 7.6 Hz, 2 H,
CH2), 7.56–7.63 (m, 2 H, ArH), 7.70–7.80 (m, 2 H, ArH), 7.99 (d,
J = 9.2 Hz, 1 H, ArH), 8.09–8.12 (m, 2 H, ArH), 8.20 (s, 1 H, ArH),
8.29–8.32 (m, 1 H, ArH), 8.39–8.40 (m, 1 H, ArH), 8.73 (d, J = 8.4
Hz, 1 H, ArH).
Anal. Calcd for C23H20N2O2: C, 77.51; H, 5.66; N, 7.86. Found: C,
77.64; H, 5.52; N, 7.95.
1-(n-Butyl)-3-(4-nitrophenyl)benzo[f]quinoline (4r)
Mp 150–151 °C.
IR (KBr): 3056, 2952, 2929, 2882, 2868, 1597, 1580, 1551, 1531,
1508, 1481, 1453, 1430, 1337, 1258, 1163, 1108, 857, 850, 835,
799, 746 cm–1.
1H NMR (CDCl3): d = 1.07 (t, J = 7.2 Hz, 3 H, CH3), 1.59–1.67 (m,
2 H, CH2), 1.94–2.01 (m, 2 H, CH2), 3.53 (t, J = 8.0 Hz, 2 H, CH2),
7.66–7.73 (m, 2 H, ArH), 7.89 (s, 1 H, ArH), 7.97–8.01 (m, 2 H,
ArH), 8.07 (d, J = 8.8 Hz, 1 H, ArH), 8.37–8.42 (m, 4 H, ArH), 8.71
(d, J = 8.0 Hz, 1 H, ArH).
Anal. Calcd for C23H20ClN: C, 79.87; H, 5.83; N, 4.05. Found: C,
79.76; H, 5.93; N, 4.05.
3-(3-Chlorophenyl)-1-(isopropyl)benzo[f]quinoline (4w)
Mp 150–151 °C.
Synthesis 2008, No. 12, 1902–1910 © Thieme Stuttgart · New York

1908
X.-S. Wang et al.
PAPER
IR (KBr): 3050, 2962, 2928, 2869, 1597, 1581, 1547, 1480, 1451,
1420, 1394, 1333, 1294, 1249, 1162, 1078, 1068, 876, 829, 791,
755, 736, 698 cm–1.
1H NMR (DMSO-d6): d = 1.57 (d, J = 6.8 Hz, 6 H, 2 × CH3), 4.22–
4.28 (m, 1 H, CH), 7.58–7.63 (m, 2 H, ArH), 7.72–7.76 (m, 2 H,
ArH), 7.95 (d, J = 8.8 Hz, 1 H, ArH), 8.10 (d, J = 8.8 Hz, 2 H, ArH),
8.31 (s, 1 H, ArH), 8.35 (d, J = 9.2 Hz, 1 H, ArH), 8.43 (s, 1 H,
ArH), 8.60 (d, J = 8.0 Hz, 1 H, ArH).
1H NMR (CDCl3): d = 3.77 (s, 3 H, CH3O), 4.49 (s, 2 H, CH2), 7.50
(d, J = 8.4 Hz, 2 H, ArH), 7.64–7.67 (m, 2 H, ArH), 7.82 (s, 1 H,
ArH), 7.82–7.98 (m, 2 H, ArH), 8.05 (d, J = 8.8 Hz, 1 H, ArH), 8.16
(d, J = 8.4 Hz, 2 H, ArH), 8.48–8.51 (m, 1 H, ArH).
Anal. Calcd for C22H16ClNO2: C, 73.03; H, 4.46; N, 3.87. Found: C,
72.89; H, 4.57; N, 3.80.
Methyl 2-{3-(2,4-Dichlorophenyl)benzo[f]quinolin-1-yl}acetate
(6b)
Mp 155–156 °C.
Anal. Calcd for C22H18ClN: C, 79.63; H, 5.47; N, 4.22. Found: C,
79.85; H, 5.40; N, 4.10.
IR (KBr): 3058, 2955, 2843, 1732, 1591, 1557, 1477, 1448, 1434,
1382, 1356, 1337, 1222, 1200, 1158, 1098, 1046, 984, 899, 853,
833, 826, 796, 744 cm–1.
3-(4-Fluorophenyl)-1-(isopropyl)benzo[f]quinoline (4x)
Mp 162–163 °C.
IR (KBr): 3053, 2977, 2962, 2928, 2870, 1599, 1581, 1547, 1527,
1508, 1480, 1452, 1392, 1366, 1343, 1233, 1214, 1158, 844, 831,
801, 753, 719 cm–1.
1H NMR (DMSO-d6): d = 1.56 (d, J = 6.8 Hz, 6 H, 2 × CH3), 4.21–
4.28 (m, 1 H, CH), 7.38–7.42 (m, 2 H, ArH), 7.69–7.77 (m, 2 H,
ArH), 7.93 (d, J = 8.8 Hz, 1 H, ArH), 8.07–8.10 (m, 2 H, ArH), 8.24
(s, 1 H, ArH), 8.40–8.46 (m, 2 H, ArH), 8.60 (d, J = 8.0 Hz, 1 H,
ArH).
1H NMR (DMSO-d6): d = 3.65 (s, 3 H, CH3O), 4.72 (s, 2 H, CH2),
7.64 (dd, J = 8.4, 2.0 Hz, 1 H, ArH), 7.74–7.76 (m, 2 H, ArH),
7.81–7.84 (m, 2 H, ArH), 7.92 (s, 1 H, ArH), 7.98 (d, J = 8.8 Hz,
1 H, ArH), 8.13–8.15 (m, 1 H, ArH), 8.17 (d, J = 9.2 Hz, 1 H, ArH),
8.55–8.58 (m, 1 H, ArH).
Anal. Calcd for C22H15Cl2NO2: C, 66.68; H, 3.82; N, 3.53. Found:
C, 66.70; H, 3.77; N, 3.67.
Methyl 2-{3-(2,3-Dichlorophenyl)benzo[f]quinolin-1-yl}acetate
(6c)
Mp 158–159 °C.
Anal. Calcd for C22H18FN: C, 83.78; H, 5.75; N, 4.44. Found: C,
83.70; H, 5.57; N, 4.52.
3-(3-Bromophenyl)-1-phenylbenzo[f]quinoline (4y)
Mp 208–210 °C.
IR (KBr): 3053, 2955, 1733, 1591, 1579, 1551, 1485, 1447, 1435,
1413, 1389, 1360, 1334, 1229, 1194, 1156, 1046, 988, 924, 905,
833, 802, 791, 746, 733, 708 cm–1.
1H NMR (DMSO-d6): d = 3.65 (s, 3 H, CH3O), 4.73 (s, 2 H, CH2),
7.54–7.58 (m, 1 H, ArH), 7.71 (dd, J = 7.6, 1.2 Hz, 1 H, ArH),
7.75–7.79 (m, 2 H, ArH), 7.82 (dd, J = 8.0, 1.6 Hz, 1 H, ArH), 7.90
(s, 1 H, ArH), 7.98 (d, J = 9.2 Hz, 1 H, ArH), 8.13–8.15 (m, 1 H,
ArH), 8.18 (d, J = 9.2 Hz, 1 H, ArH), 8.56–8.58 (m, 1 H, ArH).
IR (KBr): 3054, 1601, 1576, 1543, 1477, 1419, 1389, 1345, 1328,
1275, 1252, 1231, 1150, 1083, 1069, 996, 943, 870, 838, 781, 756,
702, 689 cm–1.
1H NMR (CDCl3): d = 7.19–7.23 (m, 1 H, ArH), 7.50–7.62 (m, 8 H,
ArH), 7.70–7.72 (m, 1 H, ArH), 8.03–8.09 (m, 3 H, ArH), 8.18 (d,
J = 8.8 Hz, 1 H, ArH), 8.37 (d, J = 7.6 Hz, 1 H, ArH), 8.58–8.59 (m,
1 H, ArH).
Anal. Calcd for C22H15Cl2NO2: C, 66.68; H, 3.82; N, 3.53. Found:
C, 66.51; H, 3.67; N, 3.70.
Anal. Calcd for C25H16BrN: C, 73.18; H, 3.93; N, 3.41. Found: C,
73.03; H, 3.94; N, 3.55.
Methyl 2-{3-(4-Nitrophenyl)benzo[f]quinolin-1-yl}acetate (6d)
Mp 185–186 °C.
3-(4-Nitrophenyl)-1-phenylbenzo[f]quinoline (4z)
Mp 255–257 °C.
IR (KBr): 3054, 3008, 2954, 2844, 1732, 1595, 1583, 1553, 1516,
1483, 1454, 1438, 1364, 1333, 1259, 1216, 1201, 1163, 1108, 1088,
1023, 1011, 987, 950, 899, 871, 857, 849, 834, 802, 758, 744, 717,
690 cm–1.
1H NMR (DMSO-d6): d = 3.67 (s, 3 H, CH3O), 4.75 (s, 2 H, CH2),
7.73–7.75 (m, 2 H, ArH), 8.03 (d, J = 9.2 Hz, 1 H, ArH), 8.11–8.13
(m, 1 H, ArH), 8.17 (d, J = 8.8 Hz, 1 H, ArH), 8.40 (s, 1 H, ArH),
8.42 (d, J = 8.8 Hz, 2 H, ArH), 8.51–8.53 (m, 1 H, ArH), 8.56 (d,
J = 8.8 Hz, 2 H, ArH).
IR (KBr): 3053, 1599, 1578, 1547, 1509, 1475, 1397, 1340, 1259,
1153, 1106, 1078, 1008, 860, 849, 832, 801, 774, 755, 699 cm–1.
1H NMR (DMSO-d6): d = 7.21–7.25 (m, 1 H, ArH), 7.55–7.62 (m,
7 H, ArH), 8.09–8.12 (m, 2 H, ArH), 8.17 (s, 1 H, ArH), 8.22 (d,
J = 8.8 Hz, 1 H, ArH), 8.40 (d, J = 8.8 Hz, 2 H, ArH), 8.67 (d,
J = 8.8 Hz, 2 H, ArH).
Anal. Calcd for C25H16N2O2: C, 79.77; H, 4.28; N, 7.44. Found: C,
79.89; H, 4.10; N, 7.50.
Anal. Calcd for C22H16N2O4: C, 70.96; H, 4.33; N, 7.52. Found: C,
70.85; H, 4.21; N, 7.68.
Syntheses of 2-(3-Arylbenzo[f]quinolin-1-yl)acetate Derivatives
6; General Procedure
Methyl 2-{3-(4-Bromophenyl)benzo[f]quinolin-1-yl}acetate
(6e)
Mp 143–144 °C.
A dry 50 mL flask was charged with arylaldehyde (2.0 mmol),
naphthalen-2-amine (2.0 mmol, 0.286 g), b-keto ester (2.5 mmol),
I2 (0.1 mmol, 0.025 g) and THF (10 mL). The reaction mixture was
stirred at reflux for 6–8 h. After completion of the reaction as indi-
cated by TLC, a little DMF was added to the mixture until all the
yellow solid was dissolved. After the mixture was cooled to r.t., the
generated crystals were collected by filtration to give 6.
IR (KBr): 3019, 2992, 2943, 1742, 1582, 1550, 1525, 1478, 1454,
1431, 1423, 1366, 1326, 1301, 1271, 1215, 1198, 1154, 1084, 1071,
1007, 991, 875, 830, 753, 742, 730 cm–1.
1H NMR (CDCl3): d = 3.78 (s, 3 H, CH3O), 4.49 (s, 2 H, CH2),
7.63–7.69 (m, 4 H, ArH), 7.82 (s, 1 H, ArH), 7.95–7.99 (m, 2 H,
ArH), 8.05 (d, J = 9.2 Hz, 1 H, ArH), 8.10 (d, J = 8.4 Hz, 2 H, ArH),
8.48–8.51 (m, 1 H, ArH).
Methyl 2-{3-(4-Chlorophenyl)benzo[f]quinolin-1-yl}acetate
(6a)
Mp 138–139 °C.
Anal. Calcd for C22H16BrNO2: C, 65.04; H, 3.97; N, 3.45. Found: C,
64.90; H, 4.10; N, 3.55.
IR (KBr): 3024, 2994, 2944, 2841, 1743, 1582, 1551, 1528, 1479,
1454, 1433, 1424, 1368, 1326, 1300, 1271, 1215, 1198, 1154, 1106,
1090, 1012, 991, 945, 898, 890, 875, 833, 803, 753, 742, 732 cm–1.
Synthesis 2008, No. 12, 1902–1910 © Thieme Stuttgart · New York

PAPER
Synthesis of 3-Arylbenzoquinoline Derivatives
1909
Methyl 2-{3-(4-Methoxyphenyl)benzo[f]quinolin-1-yl}acetate
(6f)
1 H, ArH), 7.93–7.97 (m, 2 H, ArH), 8.04 (d, J = 8.8 Hz, 1 H, ArH),
8.09 (d, J = 8.4 Hz, 2 H, ArH), 8.50–8.82 (m, 1 H, ArH).
Mp 168–169 °C.
Ethyl 2-{3-(3-Bromophenyl)benzo[f]quinolin-1-yl}acetate (6k)
Mp 125–126 °C.
IR (KBr): 3001, 2957, 2935, 2836, 1737, 1605, 1580, 1549, 1531,
1509, 1481, 1454, 1436, 1393, 1355, 1336, 1308, 1292, 1202, 1182,
1113, 1029, 981, 936, 903, 866, 844, 816, 799, 747 cm–1.
1H NMR (DMSO-d6): d = 3.66 (s, 3 H, CH3O), 3.86 (s, 3 H, CH3O),
4.70 (s, 2 H, CH2), 7.14 (d, J = 8.8 Hz, 2 H, ArH), 7.69–7.71 (m,
2 H, ArH), 7.99 (d, J = 9.2 Hz, 1 H, ArH), 8.08–8.12 (m, 2 H, ArH),
8.19 (s, 1 H, ArH), 8.29 (d, J = 8.8 Hz, 2 H, ArH), 8.48–8.50 (m,
1 H, ArH).
IR (KBr): 3061, 2975, 2936, 2901, 1733, 1588, 1551, 1479, 1455,
1444, 1428, 1373, 1326, 1268, 1214, 1199, 1172, 1158, 1067, 1032,
995, 946, 903, 881, 837, 783, 751, 708, 683 cm–1.
1H NMR (CDCl3): d = 1.24 (t, J = 7.2 Hz, 3 H, CH3), 4.25 (q, J = 7.2
Hz, 2 H, CH2), 4.49 (s, 2 H, CH2), 7.38–7.42 (m, 1 H, ArH), 7.58–
7.60 (m, 1 H, ArH), 7.65–7.68 (m, 2 H, ArH), 7.83 (s, 1 H, ArH),
7.95–7.99 (m, 2 H, ArH), 8.06 (d, J = 8.4 Hz, 1 H, ArH), 8.13 (d,
J = 8.0 Hz, 1 H, ArH), 8.40–8.41 (m, 1 H, ArH), 8.52–8.54 (m, 1 H,
ArH).
Anal. Calcd for C23H19NO3: C, 77.29; H, 5.36; N, 3.92. Found: C,
77.18; H, 5.50; N, 3.89.
Methyl 2-{3-(2,3-Dimethoxyphenyl)benzo[f]quinolin-1-yl}ace-
tate (6g)
Anal. Calcd for C23H18BrNO2: C, 65.73; H, 4.32; N, 3.33. Found: C,
65.87; H, 4.15; N, 3.38.
Mp 180–182 °C.
Ethyl 2-{3-(4-Chlorophenyl)benzo[f]quinolin-1-yl}acetate (6l)
Mp 140–141 °C.
IR (KBr): 3041, 3009, 2938, 2837, 1732, 1622, 1580, 1497, 1468,
1436, 1405, 1358, 1330, 1272, 1194, 1156, 1093, 1055, 1022, 998,
957, 904, 833, 765, 747 cm–1.
1H NMR (DMSO-d6): d = 3.68 (s, 3 H, CH3O), 3.75 (s, 3 H, CH3O),
3.92 (s, 3 H, CH3O), 4.81 (s, 2 H, CH2), 7.30–7.32 (m, 2 H, ArH),
7.44–7.46 (m, 1 H, ArH), 7.80–7.82 (m, 2 H, ArH), 8.08 (d, J = 9.2
Hz, 1 H, ArH), 8.13 (s, 1 H, ArH), 8.18–8.21 (m, 1 H, ArH), 8.29
(d, J = 8.8 Hz, 1 H, ArH), 8.59–8.62 (m, 1 H, ArH).
IR (KBr): 3052, 2982, 2728, 1590, 1552, 1531, 1482, 1446, 1390,
1371, 1329, 1295, 1214, 1201, 1158, 1093, 1030, 1012, 862, 835,
824, 744 cm–1.
1H NMR (DMSO-d6): d = 1.14 (t, J = 7.2 Hz, 3 H, CH3), 4.13 (q,
J = 7.2 Hz, 2 H, CH2), 4.72 (s, 2 H, CH2), 7.67 (d, J = 8.8 Hz, 2 H,
ArH), 7.71–7.74 (m, 2 H, ArH), 8.02 (d, J = 8.8 Hz, 1 H, ArH),
8.10–8.13 (m, 1 H, ArH), 8.15 (d, J = 8.8 Hz, 1 H, ArH), 8.29 (s,
1 H, ArH), 8.36 (d, J = 8.4 Hz, 2 H, ArH), 8.53–8.55 (m, 1 H, ArH).
Anal. Calcd for C24H21NO4: C, 74.40; H, 5.46; N, 3.62. Found: C,
74.55; H, 5.37; N, 3.80.
Anal. Calcd for C23H18ClNO2: C, 73.50; H, 4.83; N, 3.73. Found: C,
73.65; H, 4.90; N, 3.67.
Methyl 2-{3-(3-Nitrophenyl)benzo[f]quinolin-1-yl}acetate (6h)
Mp 183–185 °C.
IR (KBr): 3092, 3075, 3053, 3007, 2958, 1733, 1587, 1553, 1520,
1491, 1446, 1436, 1346, 1276, 1261, 1200, 1156, 1109, 1065, 1017,
986, 943, 905, 853, 833, 809, 800, 745, 712, 681 cm–1.
1H NMR (CDCl3): d = 3.80 (s, 3 H, CH3O), 4.52 (s, 2 H, CH2),
7.67–7.72 (m, 3 H, ArH), 7.91 (s, 1 H, ArH), 7.96–8.01 (m, 2 H,
ArH), 8.07 (d, J = 8.8 Hz, 1 H, ArH), 8.29–8.32 (m, 1 H, ArH),
8.49–8.52 (m, 1 H, ArH), 8.59 (d, J = 7.6 Hz, 1 H, ArH), 9.06–9.07
(m, 1 H, ArH).
Acknowledgment
We are grateful to the Natural Science Foundation (06AXL10,
06PYL04) of Xuzhou Normal University and the Natural Science
Foundation (No. 04KJB150139) of the Education Committee of
Jiangsu Province for financial support.
References
Anal. Calcd for C22H16N2O4: C, 70.96; H, 4.33; N, 7.52. Found: C,
70.89; H, 4.28; N, 7.69.
(1) (a) Vijjay, N. C.; Rajesh, A. U.; Vinod, S.; Bindu, A. R.;
Sreekanth, J. S.; Lakshmi, B. Acc. Chem. Res. 2003, 36,
899. (b) Padwa, A.; Bur, S. K. Tetrahedron 2007, 63, 5341.
(c) Shin-Ichi, I. Acc. Chem. Res. 2000, 33, 511. (d) Tietze,
L. F. Chem. Rev. 1996, 96, 115. (e) Bunce, R. A.
Tetrahedron 1995, 51, 13103. (f) Nicolaou, K. C.;
Edmonds, D. J.; Bulger, P. G. Angew. Chem. Int. Ed. 2006,
45, 7134.
(2) (a) Selvi, G.; Rajendran, S. P. Asian J. Chem. 2004, 16,
1017. (b) Bahuguna, R. P.; Joshi, B. C. Indian J. Heterocycl.
Chem. 1994, 3, 265.
(3) (a) Carr, B. A.; Franklin, M. R. Xenobiotica 1998, 28, 949.
(b) Le, H. T.; Lamb, J. G.; Franklin, M. R. J. Biochem.
Toxicol. 1996, 11, 297.
(4) Abell, A. D.; Erhard, K. F.; Yen, H. K.; Yamashita, D. S.;
Brandt, M.; Mohammed, H.; Levy, M. A.; Holt, D. A.
Bioorg. Med. Chem. Lett. 1994, 4, 1365.
(5) Bahuguna, R. P.; Joshi, B. C.; Mangal, H. N. J. Indian Chem.
Soc. 1992, 69, 401.
(6) Mikhailitsyn, F. S.; Kozyreva, N. P.; Rabinovich, S. A.;
Maksakovskaya, Ye. V.; Kulikovskaya, I. M.; Dadasheva,
N. R.; Lebedeva, M. N.; Bekhli, A. F.; Lychko, N. D.;
Uvarova, N. A. Med. Parazitol. Parazit. Bolezni 1992, 50;
Chem. Abstr. 1992, 117, 251317.
Ethyl 2-{3-(2,4-Dichlorophenyl)benzo[f]quinolin-1-yl}acetate
(6i)
Mp 126–128 °C.
IR (KBr): 3057, 3030, 2973, 2930, 1731, 1590, 1556, 1529, 1476,
1450, 1383, 1368, 1353, 1332, 1229, 1201, 1156, 1099, 1045, 1029,
884, 858, 833, 825, 796, 741 cm–1.
1H NMR (CDCl3): d = 1.24 (t, J = 6.8 Hz, 3 H, CH3), 4.24 (q, J = 6.8
Hz, 2 H, CH2), 4.48 (s, 2 H, CH2), 7.42 (d, J = 8.0 Hz, 1 H, ArH),
7.55 (s, 1 H, ArH), 7.67–7.69 (m, 2 H, ArH), 7.77–7.80 (m, 2 H,
ArH), 7.97–8.05 (m, 3 H, ArH), 8.58 (d, J = 8.4 Hz, 1 H, ArH).
Anal. Calcd for C23H17Cl2NO2: C, 67.33; H, 4.18; N, 3.41. Found:
C, 67.50; H, 4.09; N, 3.53.
Ethyl 2-{3-(4-Bromophenyl)benzo[f]quinolin-1-yl}acetate (6j)
Mp 143–144 °C (Lit.16 143–144 °C).
IR (KBr): 3051, 2981, 2935, 1729, 1589, 1551, 1531, 1481, 1445,
1371, 1328, 1275, 1213, 1201, 1159, 1089, 1073, 1029, 1008, 947,
863, 834, 823, 744, 729 cm–1.
1H NMR (CDCl3): d = 1.23 (t, J = 7.2 Hz, 3 H, CH3), 4.24 (q, J = 7.2
Hz, 2 H, CH2), 4.46 (s, 2 H, CH2), 7.62–7.67 (m, 4 H, ArH), 7.81 (s,
Synthesis 2008, No. 12, 1902–1910 © Thieme Stuttgart · New York

1910
X.-S. Wang et al.
PAPER
(7) Nozulak, J.; Vigouret, J. M.; Jaton, A. L.; Hofmann, A.;
Dravid, A. R.; Weber, H. P.; Kalkman, H. O.; Walkinshaw,
M. D. J. Med. Chem. 1992, 35, 480.
(8) Szmuszkovicz, J.; Darlington, W. H.; Von Voigtlander, P. F.
WO 8804292 A1, 1988; Chem. Abstr. 1988, 110, 75335.
(9) Cannon, J. G.; Walker, K. A.; Montanari, A.; Long, J. P.;
Flynn, J. R. J. Med. Chem. 1990, 33, 2000.
J. Chem. 1988, 31, 89. (f) Tagmatarchis, N.;
Katerinopoulos, H. E. J. Heterocycl. Chem. 1996, 33, 983.
(g) Bahuguna, R. P.; Joshi, B. C. Indian J. Heterocycl.
Chem. 1994, 3, 265. (h) Beller, N. R.; Neckers, D. C.;
Papadopoulos, E. P. J. Org. Chem. 1977, 42, 3514.
(12) Lin, X. F.; Cui, S. L.; Wang, Y. G. Tetrahedron Lett. 2006,
47, 3127.
(10) (a) Kozlov, N. S.; Zhikhareva, O. D. Dokl. Akad. Nauk BSSR
1989, 33, 903; Chem. Abstr. 1989, 112, 198097.
(13) (a) Wang, X. S.; Zhang, M. M.; Jiang, H.; Shi, D. Q.; Tu, S.
J.; Wei, X. Y.; Zong, Z. M. Synthesis 2006, 4187.
(b) Wang, X. S.; Zhang, M. M.; Li, Q.; Yao, C. S.; Tu, S. J.
Synlett 2007, 3141.
(b) Kozlov, N. S.; Mikhalevskaya, S. V.; Serzhanina, V. A.
Khim. Geterotsikl. Soedin. 1989, 351; Chem. Abstr. 1989,
111, 173954. (c) Kozlov, N. S.; Zhikhareva, O. D. Vestsi
Akad. Navuk BSSR, Ser. Khim. Navuk 1987, 66; Chem.
Abstr. 1987, 109, 110224. (d) Kozlov, N. S.; Shmanai, G.
S.; Dang, N. T. Khim. Geterotsikl. Soedin. 1986, 1102;
Chem. Abstr. 1986, 106, 176147. (e) Kozlov, N. S.;
Mikhalevskaya, S. V.; Serzhanina, V. A.; Sauts, R. D. Dokl.
Akad. Nauk BSSR 1984, 28, 810; Chem. Abstr. 1984, 101,
210947. (f) Kozlov, N. S.; Zhikhareva, O. D.; Stremok, I. P.
Dokl. Akad. Nauk BSSR 1977, 21, 425; Chem. Abstr. 1977,
87, 69719. (g) Kozlov, N. S.; Zhikhareva, O. D.;
Gladchenko, L. F. Vestsi Akad. Navuk BSSR, Ser. Khim.
Navuk 1979, 72; Chem. Abstr. 1979, 92, 75415. (h)Kozlov,
N. S.; Gladchenko, L. F.; Sauts, R. D.; Serzhanina, V. A.
Khim. Geterotsikl. Soedin. 1978, 1646; Chem. Abstr. 1978,
90, 87223.
(14) X-ray crystal data for 4c. Empirical formula: C22H18BrN;
Formula weight: 376.28; Colorless block crystals; Crystal
size: 0.46 × 0.45 × 0.17 mm; Crystal system: triclinic; Space
group: P1; Unit cell dimensions: a = 9.203 (2) Å, b = 10.173
(2) Å, c = 10.582 (2) Å, a = 97.868 (3)°, b = 107.038 (3)°,
g = 112.235 (3)°; V = 841.7 (3) Å3; Z = 2; D(calcd) = 1.485
g/cm3; F(000) = 384, m(MoKa) = 2.444 mm–1. Intensity data
were collected on a Rigaku Mercury diffractometer with
graphite monochromated MoKa radiation (l = 0.71070 Å)
using w scan mode with 3.09° < q < 25.35°. Unique
reflections collected 3062; 2625 reflections with I > 2s (I)
were used in the refinement. The structure was solved by
direct methods and expanded using Fourier techniques. The
final cycle of full-matrix least squares technique gave
R = 0.0374 and wR = 0.0877.
(11) (a) Grachek, V. I. Russ. J. Gen. Chem. (Engl. Transl.) 2004,
74, 1748. (b) Kozlov, N. G.; Basalaeva, L. I. Russ. J. Org.
Chem. (Engl. Transl.) 2003, 39, 718. (c) Ripa, L.; Hallberg,
A. J. Org. Chem. 1998, 63, 84. (d) Stetsenko, A. V.; Fursii,
F. A. Ukr. Khim. Zh. (Russ. Ed.) 1986, 52, 755; Chem. Abstr.
1986, 107, 154204. (e) Bahuguna, R. P.; Joshi, B. C. Egypt.
(15) (a) Ji, S. J.; Wang, S. Y.; Zhang, Y.; Loh, T. P. Tetrahedron
2004, 60, 2051. (b) Ke, B. W.; Qin, Y.; He, Q. F.; Huang, Z.
Y.; Wang, F. P. Tetrahedron Lett. 2005, 46, 1751.
(16) Kozlov, N. G.; Sauts, R. D.; Gusak, K. N. Russ. J. Org.
Chem. (Engl. Transl.) 2000, 36, 531.
Synthesis 2008, No. 12, 1902–1910 © Thieme Stuttgart · New York