An efficient synthesis of 1,3-diarylbenzo[f]quinolines from 2-halogenated acetophenone, aromatic aldehyde, and naphthalen-2-amine catalyzed by iodine

Article abstract of DOI:10.1002/jhet.211

(Chemical Equation Presented) The three-component reaction of aromatic aldehyde, naphthalen-2-amine and 2-halogenated acetophenone in THF catalyzed by 5 mol % iodine at reflux unexpectedly gave 1,3-diarylbenzo[f]quinolines, with halogen losing in the form

Full text of DOI:10.1002/jhet.211

1222
An Efficient Synthesis of 1,3-Diarylbenzo[f]quinolines from
2-Halogenated Acetophenone, Aromatic Aldehyde, and
Naphthalen-2-Amine Catalyzed by Iodine
Vol 46
Xiang-Shan Wang,a,b* Qing Li,a Jie Zhou,a and Shu-Jiang Tua,b
aSchool of Chemistry and Chemical Engineering, Xuzhou Normal University, Xuzhou,
Jiangsu 221116, China
bThe Key Laboratory of Biotechnology for Medical Plant of Jiangsu Province, Xuzhou,
Jiangsu 221116, China
*E-mail: xswang1974@yahoo.com
Received December 8, 2008
DOI 10.1002/jhet.211
Published online 5 November 2009 in Wiley InterScience (www.interscience.wiley.com).
The three-component reaction of aromatic aldehyde, naphthalen-2-amine and 2-halogenated acetophe-
none in THF catalyzed by 5 mol % iodine at reflux unexpectedly gave 1,3-diarylbenzo[f]quinolines,
with halogen losing in the formation of the products. The formation of unexpected 1,3-diarylbenzo[f]-
quinolines was tentatively explained by Cram’s rule to one of the steps in the mechanism.
J. Heterocyclic Chem., 46, 1222 (2009).
INTRODUCTION
In view of the importance of the benzoquinoline and
its derivatives, several methods for the synthesis of ben-
zo[f]quinoline and its derivatives were developed by
Kozlov [9] and other groups [10]. However, many of
these reported methods suffer from drawbacks such as
harsh reaction conditions, unsatisfactory yields, pro-
longed reaction time or cumbersome product isolation
procedure. In our previous paper, we have reported the
1,3-substituented benzoquinolines via three component
reaction of aromatic aldehyde, naphthalen-2-amine and
ketones [11]. Our interest in synthesis of heterocyclic
compounds [12] by multicomponent reaction stimulates
us to find some new and more substituented benzoquino-
lines, such as 1,3-diaryl-2-halogenated benzoquinoline
derivatives, so we perform the 2-halogenated acetophe-
none in the aforementioned reaction instead of acetophe-
none. To our surprised, the desired products 1,3-diaryl-
2-halogenated benzoquinolines were not observed, with
1,3-diarylbenzoquinoline derivatives being obtained. It
should be noted that the halogen lose in these I2-cata-
lyzed three-component reactions.
There has been tremendous interest in developing
highly efficient transformations for the preparation of or-
ganic compounds, as well as, biologically active materi-
als. There is also a need for synthetic chemists to find
new, efficient, and strategically important processes,
which are environmentally benign and lead to greater
structural variation in short period of times with high
yields and simple work-up procedures. Multicomponent
reactions are useful and efficient methods in organic syn-
thesis. The major advantages of these reactions are a sin-
gle purification step, higher yields than stepwise assem-
bly, the use of simple and diverse precursors to construct
complex molecules, and the use of only a single promoter
or catalyst. Thus, the development of new multicompo-
nent reactions is a popular area of research in current or-
ganic chemistry and is also acceptable from a ‘‘Green
Chemistry" point of view [1]. They provide a powerful
tool toward the one-pot synthesis of diverse and complex
compounds as well as small and drug-like heterocycles
[2]. Such as benzo[f]quinoline and its derivatives, are
very useful compounds in the various fields of chemistry
including biological and pharmacological viewpoints.
Some of which exhibit antibacterial activity [3], UDP
(Uridine diphosphate)-glucuronosyl transferase activity
[4], antimicrobial activity [5], antimalarial activity [6],
agonistic activity [7], and antipsychotic activity [8].
RESULTS AND DISCUSSION
Initially, the reaction of 4-chlorobenzaldehyde 1a,
naphthalen-2-amine
2 and 2-bromo-1-(4-nitrophenyl)
ethanone 3a was used as a model reaction to optimize the
C
V
2009 HeteroCorporation

November 2009
An Efficient Synthesis of 1,3-Diarylbenzo[f]quinolines from 2-Halogenated
Acetophenone, Aromatic Aldehyde, and Naphthalen-2-amine Catalyzed by Iodine
1223
Table 1
Synthesis of 4a under different reaction conditions.a
zation were proposed to form the quinoline or benzoqui-
noline derivatives (Scheme 2). However, no stereoselec-
tivity was put forward in the Friedel–Crafts cyclization
of the addition product. It is a Friedel–Crafts cyclization
as well as an intra-molecular nucleophilic addition reac-
tion with benzene as nucleophilic reagent attacking car-
boxyl group, with a chiral centre being connected with
this carboxyl group. The stereochemistry of the Friedel–
Crafts cyclization should be in agreement with Cram’s
rule, so the hydroxyl group and the hydrogen atom lie
on syn periplanar geometry with halogen on the anti
periplanar geometry. Subsequent elimination reaction of
HX for their anti periplanar rather than H2O results in
oxirenoquinoline. The oxirane ring is opened to give 2-
hydroxybenzoquinoline induced by iodine, which is fur-
ther dehydrated to afford final 1,3-diaryl benzoquinoline
(Scheme 2). The reason why the halogens lose is per-
haps best explained by Cram’s rule in the formation of
the benzoquinolines.
Entry Temperature(ꢀC) I2 (mol %)
Solvent
THF
THF
Yieldsb(%)
1
2
3
4
5
6
7
8
9
RT
0
0
0
0
Reflux
RT
50
5
5
THF
THF
Trace
76
90
Reflux
Reflux
Reflux
Reflux
Reflux
5
THF
THF
THF
10
20
5
86
89
CH3CN
Benzene
DMF
82
78
5
10 80
11 Reflux
5
5
84
79
ClCH2CH2Cl
a Reagents and conditions: 1a (2 mmol, 0.281 g), 2 (2 mmol, 0.286 g),
3a (2 mmol, 0.488 g), solvent (10 mL), 12 h.
b Isolated yields.
conditions. The reaction was first carried out in THF in
the absence of I2. No reaction occurred at room tempera-
ture and reflux condition (Table 1, entries 1 and 2). We
also evaluated the amount of catalyst required for this
transformation. It was found that 5 mol % of I2 at reflux
in THF was sufficient to push the reaction forward. More
amounts of the catalyst did not improve yields. To find
the optimum reaction temperature, the reaction was car-
ried out with 5 mol % of I2 at room temperature, 50 and
refluxing temperature, resulting in the isolation of 4a in
trace amount, 76% and 90% yields (Table 1, entries 3, 4,
and 5), respectively. Thus, 5 mol % of I2 and a reaction
temperature at reflux were optimal conditions. In addition,
we also looked into the solvent effect at reflux condition
for this reaction. As showed in Table 1, THF gave the
most satisfactory result in comparison with other solvents.
(Table 1, entries 8–11).
In conclusion, we found an efficient method for the
synthesis of benzo[f]quinoline derivatives via three-com-
ponent reaction of aromatic aldehyde, naphthalen-2-
amine and 2-halogenated acetophenone using 5 mol %
of iodine as catalyst, with halogen losing in the forma-
tion of the products. A Cram’s rule in the I2-catalyzed
Friedel–Crafts reaction was proposed to occur in the for-
mation of the products.
EXPERIMENTAL
Melting points were determined in open capillaries and are
uncorrected. IR spectra were recorded on a TENSOR 27 spec-
trometer in KBr pellet. 1H NMR spectra were obtained from
solution in DMSO-d6 with Me4Si as internal standard using a
Bruker-400 spectrometer. HRMS analyses were carried out
using a Bruker-micro-TOF-Q-MS analyzer.
In our initial study, we think it was an unexpected
product. Subsequently, we repeated the reactions under
the same reaction conditions with various kinds of ben-
zaldehydes bearing either electron-withdrawing groups
(such as halide, nitro) or electron-donating groups (such
as alkyl group, or alkoxyl group) or a-halogenated ace-
tophenones (Scheme 1). However, the designed reac-
tions all gave the products of 1,3-diarylbenzoquinoline
derivatives rather than 1,3-diaryl-2-halogenated benzo-
quinolines in good to high yields (Table 2). Further-
more, in order to confirm the structure of product, the
X-ray diffraction of 4a was carried out [13]. The crystal
structure of 4a was shown in Figure 1, which made fur-
ther confirmation of structure 4. This raises an interest-
ing question: why do the halogens lose in the formation
of the benzoquinolines?
Typical procedure for 1,3-diarylbenzo[f]quinoline deriva-
tives 4. A dry 50 mL flask was charged with aromatic alde-
hyde (2.0 mmol), naphthalen-2-amine (2.0 mmol, 0.286 g),
2-halogenated acetophenone (2.0 mmol), I2 (0.1 mmol, 0.026
g) and THF (10 mL). The reaction mixture was stirred at
reflux for 11–15 h. After completion of the reaction as indi-
cated by TLC, a little DMF was added to the mixture until the
all yellow solid was dissolved. The generated crystals were
collected by filtration to give 4 when the mixture was cooled
to room temperature.
Scheme 1
According to the literatures [14], in these I2-catalyzed
reactions, the subsequent reactions including condensa-
tion, addition, Friedel–Crafts, dehydration and aromati-
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

1224
X.-S. Wang, Q. Li, J. Zhou, and S.-J. Tu
Vol 46
Table 2
I2-catalyzed reactions of benzaldehyde, naphthalen-2-amine, and a-halogenated acetophenones in THF.a
Entry
Ar
Ar0
X
Products
Time (h)
Yieldsb (%)
1
2
4-ClC6H4
4-NO2C6H4
4-NO2C6H4
4-NO2C6H4
4-NO2C6H4
4-NO2C6H4
4-NO2C6H4
4-FC6H4
4-FC6H4
4-FC6H4
4-FC6H4
4-FC6H4
4-FC6H4
4-ClC6H4
4-ClC6H4
3-ClC6H4
3-ClC6H4
3-ClC6H4
3-ClC6H4
3-ClC6H4
C6H5
Br
Br
Br
Br
Br
Br
Br
Br
Br
Br
Br
Br
Br
Br
Br
Br
Br
Br
Br
Cl
Cl
Cl
Cl
Br
Br
Br
4a
4b
4c
4d
4e
4f
4g
4h
4i
4j
4k
4l
4m
4n
4o
4p
4q
4r
4s
12
14
11
12
13
14
15
12
13
15
13
13
15
12
13
15
14
15
15
12
12
14
15
15
13
15
90
86
91
82
81
84
88
79
80
82
89
84
78
83
82
78
80
81
86
82
79
87
84
89
86
86
2,3-(CH3O)2C6H3
4-NO2C6H4
2,3-Cl2C6H3
2,4-Cl2C6H3
3,4-(CH3)2C6H3
2,4-Cl2C6H3
3-BrC6H4
4-ClC6H4
3,5-(CH3O)2C6H3
4-BrC6H4
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
3-NO2C6H4
3-BrC6H4
2,4-Cl2C6H3
2-Thiophenyl
3-BrC6H4
4-BrC6H4
3-NO2C6H4
3,4-(CH3)2C6H3
4-NO2C6H4
4-ClC6H4
4t
C6H5
C6H5
C6H5
4u
4v
4w
4x
4y
4z
4-BrC6H4
3-BrC6H4
2-Thiophenyl
4-ClC6H4
4-BrC6H4
3-NO2C6H4
3-NO2C6H4
3-NO2C6H4
a Reagents and conditions: 1 (2 mmol), 2 (2 mmol, 0.286g), 3 (2 mmol), I2 (0.1 mmol, 0.026 g), and THF (10 mL).
b Isolated yields.
J ¼ 8.4 Hz, 2H, ArH), 8.08 (d, J ¼ 8.4 Hz, 2H, ArH), 8.09 (s,
1H, ArH), 8.21–8.23 (m, 1H, ArH), 8.41–8.47 (m, 4H, ArH).
HRMS (ESI, m/z): calcd. for C25H16N2O2 (MþHþ) 411.0900,
found 411.0915.
3-(4-Chlorophenyl)-1-(4-nitrophenyl)benzo[f]
quinoline
(4a). This compound was obtained as pale yellow crystals, mp
286–288ꢀC; ir (KBr): mmax 3101, 3074, 3048, 1596, 1580,
1544, 1514, 1493, 1476, 1449, 1408, 1388, 1344, 1305, 1282,
1177, 1152, 1107, 1091, 1010, 851, 832, 797, 758, 744, 717,
704, 692; 1H NMR (DMSO-d6): d 7.28–7.32 (m, 1H, ArH),
7.48–7.50 (m, 1H, ArH), 7.57–7.64 (m, 3H, ArH), 7.85 (d,
3-(2,3-Dimethoxyphenyl)-1-(4-nitrophenyl)benzo[f] quino-
line (4b). This compound was obtained as pale yellow crys-
tals, mp 140–141ꢀC; ir (KBr): mmax 3073, 3006, 2970, 2937,
2838, 1598, 1578, 1519, 1465, 1430, 1302, 1263, 1227, 1167,
1179, 1167, 1107, 1085, 1040, 1001, 856, 837, 805, 781, 746,
703; 1H NMR (DMSO-d6): d 3.75 (s, 3H, CH3), 3.84 (s, 3H,
CH3), 7.05 (dd, J ¼ 8.0 Hz, J0 ¼ 1.2 Hz, 1H, ArH), 7.19–7.26
(m, 2H, ArH), 7.51–7.61 (m, 3H, ArH), 7.68 (d, J ¼ 8.8 Hz,
2H, ArH), 7.91–7.93 (m, 2H, ArH), 8.03 (d, J ¼ 8.8 Hz, 1H,
ArH), 8.14 (d, J ¼ 8.8 Hz, 1H, ArH), 8.39 (d, J ¼ 8.8 Hz,
2H, ArH). HRMS (ESI, m/z): calcd. for C27H21N2O4 (MþHþ)
437.1501, found 437.1498.
3-(4-Nitrophenyl)-1-(4-nitrophenyl)benzo[f]quinoline (4c). This
compound was obtainedꢀ as pale yellow crystals, mp 235–
237ꢀC, Lit.[15] 231–232 C; ir (KBr): mmax 3083, 1598, 1578,
1545, 1514, 1450, 1343, 1257, 1163, 1106, 1084, 1041, 1015,
993, 850, 816, 750, 694; 1H NMR (DMSO-d6): d 7.22–7.24
(m, 1H, ArH), 7.54–7.59 (m, 2H, ArH), 7.70 (d, J ¼ 8.4 Hz,
2H, ArH), 7.82 (s, 1H, ArH), 7.95 (d, J ¼ 7.6 Hz, 1H, ArH),
8.09 (d, J ¼ 9.2 Hz, 1H, ArH), 8.15 (d, J ¼ 8.8 Hz, 1H,
ArH), 8.38–8.46 (m, 6H, ArH). HRMS (ESI, m/z): calcd. for
C25H16N3O4 (MþHþ) 422.1141, found 422.1145.
3-(2,3-Dichlorophenyl)-1-(4-nitrophenyl)benzo[f]quinoline
(4d). This compound was obtained as pale yellow crystals, mp
196–197ꢀC; ir (KBr): mmax 3099, 3056, 1597, 1575, 1545,
Figure 1. The crystal structure of product 4a.
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

November 2009
An Efficient Synthesis of 1,3-Diarylbenzo[f]quinolines from 2-Halogenated
Acetophenone, Aromatic Aldehyde, and Naphthalen-2-amine Catalyzed by Iodine
1225
Scheme 2
1515, 1478, 1446, 1412, 1341, 1286, 1251, 1192, 1156, 1124,
1104, 1049, 875, 859, 844, 789, 767, 723, 705; 1H NMR
(DMSO-d6): d 7.21–7.25 (m, 1H, ArH), 7.36–7.40 (m, 1H,
ArH), 7.53–7.59 (m, 3H, ArH), 7.65–7.71 (m, 4H, ArH), 7.94
(d, J ¼ 7.6 Hz, 1H, ArH), 8.06 (d, J ¼ 9.2 Hz, 1H, ArH),
8.11 (d, J ¼ 9.2 Hz, 1H, ArH), 8.40 (d, J ¼ 8.8 Hz, 2H,
ArH). HRMS (ESI, m/z): calcd. for C25H15N2Cl2O2 (MþHþ)
445.0511, found 445.0508.
ArH), 8.45 (d, J ¼ 8.4 Hz, 2H, ArH). HRMS (ESI, m/z): calcd.
for C27H21N2O2 (MþHþ) 405.1603, found 405.1593.
3-(2,4-Dichlorophenyl)-1-(4-fluorophenyl)benzo[f]quinoline
(4g). This compound was obtained as pale yellow crystals, mp
172–174ꢀC; ir (KBr): mmax 3069, 1601, 1586, 1555, 1507, 1475,
1448, 1378, 1347, 1332, 1246, 1217, 1158, 1139, 1100, 1048,
1038, 1016, 952, 896, 873, 859, 849, 825, 805, 775, 752; 1H
NMR (DMSO-d6): d 7.28–7.30 (m, 1H, ArH), 7.32–7.45 (m,
2H, ArH), 7.53–7.63 (m, 5H, ArH), 7.71 (s, 1H, ArH), 7.81 (d,
J ¼ 2.0 Hz, 1H, ArH), 7.85 (d, J ¼ 8.4 Hz, 1H, ArH), 8.02
(d, J ¼ 8.8 Hz, 1H, ArH), 8.07 (d, J ¼ 7.6 Hz, 1H, ArH), 8.20
(d, J ¼ 8.8 Hz, 1H, ArH). HRMS (ESI, m/z): calcd. for
C25H15Cl2NF (MþHþ) 418.0566, found 418.0550.
3-(2,4-Dichlorophenyl)-1-(4-nitrophenyl)benzo[f]quinoline
(4e). This compound was obtained as pale yellow crystals, mp
202–203ꢀC. ir (KBr): mmax 3104, 3077, 1589, 1579, 1556,
1545, 1516, 1473, 1448, 1381, 1348, 1249, 1162, 1142, 1102,
1
1048, 1038, 991, 860, 838, 824, 803, 789, 758, 707; H NMR
(DMSO-d6): d 7.30–7.34 (m, 1H, ArH), 7.54 (d, J ¼ 8.4 Hz,
1H, ArH), 7.60–7.66 (m, 2H, ArH), 7.78 (s, 1H, ArH), 7.82–
7.89 (m, 4H, ArH), 8.06 (d, J ¼ 8.8 Hz, 1H, ArH), 8.11 (d,
J ¼ 8.0 Hz, 1H, ArH), 8.25 (d, J ¼ 9.2 Hz, 1H, ArH), 8.44
(d, J ¼ 8.8 Hz, 2H, ArH). HRMS (ESI, m/z): calcd. for
C25H15N2Cl2O2 (MþHþ) 445.0511, found 445.0493.
3-(3-Bromophenyl)-1-(4-fluorophenyl)benzo[f]quinoline
(4h). This compound was obtained as pale yellow crystals, mp
221–222ꢀC; ir (KBr): mmax 3058, 1601, 157 2, 1542, 1506,
1477, 1446, 1386, 1344, 1328, 1252, 1230, 1154, 1088, 1069,
1
994, 873, 834, 796, 782, 756, 709, 689; H NMR (DMSO-d6):
d 7.26–7.30 (m, 1H, ArH), 7.42–7.46 (m, 2H, ArH), 7.50–7.59
(m, 5H, ArH), 7.69–7.72 (m, 1H, ArH), 8.03–8.07 (m, 3H,
ArH, 8.17 (d, J ¼ 9.2 Hz, 1H, ArH), 8.36 (d, J ¼ 8.0 Hz, 1H,
ArH ), 8.56–8.57 (m, 1H, ArH). HRMS (ESI, m/z): calcd. for
C25H16BrFN (MþHþ) 428.0450, found 428.0468.
3-(3,4-Dimethylphenyl)-1-(4-nitrophenyl)benzo[f]quinoline
(4f). This compound was obtained as pale yellow crystals, mp
234–236ꢀC; ir (KBr): mmax 3068, 2974, 2917, 2858, 1595,
1579, 1544, 1452, 1477, 1451, 1339, 1283, 1260, 1126, 1103,
1015, 1005, 885, 860, 851, 831, 802, 759, 742, 714, 705; 1H
NMR (DMSO-d6): d 2.31 (s, 3H, CH3), 2.36 (s, 3H, CH3),
7.29–7.34 (m, 2H, ArH), 7.48 (d, J ¼ 8.8 Hz, 1H, ArH), 7.55–
7.59 (m, 1H, ArH), 7.85 (d, J ¼ 8.4 Hz, 2H, ArH), 8.02
(s, 1H, ArH), 8.06–8.12 (m, 3H, ArH), 8.17–8.21 (m, 2H,
3-(4-Chlorophenyl)-1-(4-fluorophenyl)benzo[f]quinoline
(4i). This compound was obtained as pale yellow crystals, mp
173–174ꢀC; ir (KBr): mmax 3054, 1602, 1579, 1544, 1505,
1 478, 1449, 1406, 1385, 1356, 1330, 1215, 1155, 1090, 1010,
866, 830, 799, 745, 714; 1H NMR (DMSO-d6): d 7.25–7.30
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

1226
X.-S. Wang, Q. Li, J. Zhou, and S.-J. Tu
Vol 46
(m, 1H, ArH), 7.42–7.46 (m, 2H, ArH), 7.54–7.63 (m, 6H,
ArH), 8.01 (s, 1H, ArH), 8.04 (d, J ¼ 8.8 Hz, 2H, ArH), 8.16
(d, J ¼ 9.2 Hz, 1H, ArH), 8.36 (d, J ¼ 8.4 Hz, 1H, ArH),
8.39 (d, J ¼ 8.8 Hz, 2H, ArH). HRMS (ESI, m/z): calcd. for
C25H16ClFN (MþHþ) 384.0955, found 384.0966.
7.21–7.23 (m, 1H, ArH), 7.24–7.28 (m, 1H, ArH), 7.43–7.67
(m, 6H, ArH), 7.76 (dd, J ¼ 8.0 Hz, J0 ¼ 1.2 Hz, 1H, ArH),
7.95 (d, J ¼ 8.8 Hz, 1H, ArH), 8.02 (s, 1H, ArH), 8.03 (d, J
¼ 8.8 Hz, 1H, ArH), 8.09 (dd, J ¼ 8.0 Hz, J0 ¼ 1.2 Hz, 1H,
ArH), 8.15 (d, J ¼ 8.8 Hz, 1H, ArH). HRMS (ESI, m/z): calcd.
for C23H15ClNS (MþHþ) 372.0614, found 372.0625.
3-(3,5-Dimethoxyphenyl)-1-(4-fluorophenyl)benzo[f]quino-
line (4j). This compound was obtained as pale yellow crystals,
mp 119–120ꢀC; ir (KBr): mmax 3051, 2984, 2952, 2935, 2830,
1592, 1549, 1528, 1508, 1488, 1451, 1357, 1301, 1216, 1201,
1157, 1061, 1047, 941, 862, 833, 807, 752, 698; 1H NMR
(DMSO-d6): d 3.87 (s, 6H, 2CH3O), 6.64–6.66 (m, 1H, ArH),
7.27–7.29 (m, 1H, ArH), 7.42–7.46 (m, 2H, ArH), 7.50 (d,
J ¼ 2.4 Hz, 2H, ArH), 7.54–7.59 (m, 4H, ArH), 8.01–8.05 (m,
3H, ArH), 8.16 (d, J ¼ 9.2 Hz, 1H, ArH). HRMS (ESI, m/z):
calcd. for C27H21FNO2 (MþHþ) 410.1556, found 410.1558.
3-(4-Bromophenyl)-1-(4-fluorophenyl)benzo[f]quinoline
(4k). This compound was obtained as white powder, mp 167–
169ꢀC, ir (KBr): mmax 3050, 1603, 1579, 1544, 1505, 1475, 1448,
1354, 1227, 1153, 1089, 1073, 1007, 865, 830, 756; 1H NMR
(DMSO-d6): d 7.26–7.30 (m, 1H, ArH), 7.42–7.47 (m, 2H, ArH),
7.55–7.59 (m, 4H, ArH), 7.25 (d, J ¼ 8.8 Hz, 2H, ArH), 8.02 (s,
1H, ArH), 8.04 (d, J ¼ 8.8 Hz, 2H, ArH), 8.17 (d, J ¼ 8.8 Hz, 1H,
ArH), 8.33 (d, J ¼ 8.4 Hz, 2H, ArH). HRMS (ESI, m/z): calcd. for
C25H16FBrN (MþHþ) 428.0450, found 428.0435.
3-(3-Bromophenyl)-1-(3-chlorophenyl)benzo[f]quinoline
(4p). This compound was obtained as pale yellow crystals, mp
195–196ꢀC; ir (KBr): mmax 3052, 1592, 1578, 1544, 1529, 1467,
1451, 1407, 1382, 1358, 1327, 1262, 1239, 1161, 1098, 1078,
1066, 951, 881, 872, 834, 793, 770, 745, 718, 702, 692; 1H
NMR (DMSO-d6): d 7.27–7.32 (m, 1H, ArH), 7.46 (dd, J ¼ 7.6
Hz, J0 ¼ 1.2 Hz, 1H, ArH), 7.51–7.73 (m, 7H, ArH), 8.05–8.11
(m, 3H, ArH), 8.20 (d, J ¼ 8.8 Hz, 1H, ArH), 8.39 (d, J ¼ 8.0
Hz, 1H, ArH), 8.59–8.60 (m, 1H, ArH). HRMS (ESI, m/z):
calcd. for C25H16BrClN(MþHþ) 444.0155, found 444.0163.
3-(4-Bromophenyl)-1-(3-chlorophenyl)benzo[f]quinoline
(4q). This compound was obtained as pale yellow crystals, mp
216–218ꢀC; ir (KBr): mmax 3047, 1578, 1562, 1543, 1527,
1472, 1451, 1417, 1384, 1355, 1329, 1101, 1074, 1008, 871,
1
862, 834, 825, 806, 784, 745, 718, 706; H NMR (DMSO-d6):
d 7.28–7.32 (m, 1H, ArH), 7.47 (d, J ¼ 7.2 Hz, 1H, ArH),
7.56–7.69 (m, 5H, ArH), 7.76 (d, J ¼ 8.4 Hz, 2H, ArH), 8.05–
8.08 (m, 3H, ArH), 8.19 (d, J ¼ 9.2 Hz, 1H, ArH), 8.35 (d,
1-(4-Fluorophenyl)-3-(3-nitrophenyl)benzo[f]quinoline
(4l). This compound was obtained as pale yellow crystals, mp
222–224ꢀC; ir (KBr): mmax 3055, 1605, 1580, 1527, 1481,
1450, 1434, 1345, 1256, 1225, 1163, 1109, 1072, 896, 873,
849, 834, 801, 791, 746, 712; 1H NMR (DMSO-d6): d 7.21–
7.29 (m, 3H, ArH), 7.45–7.55 (m, 3H, ArH), 7.67–7.73 (m,
2H, ArH), 7.82 (s, 1H, ArH), 7.91 (d, J ¼ 7.6 Hz, 1H, ArH),
8.04 (d, J ¼ 8.8 Hz, 2H, ArH), 8.13 (d, J ¼ 8.8 Hz, 1H,
ArH), 8.30–8.33 (m, 1H, ArH), 8.61–8.63 (m, 1H, ArH), 9.08–
9.09 (m, 1H, ArH). HRMS (ESI, m/z): calcd. for C25H16FN2O2
(MþHþ) 395.1196, found 395.1196.
J
¼ 8.4 Hz, 2H, ArH). HRMS (ESI, m/z): calcd. for
C25H16BrClN (MþHþ) 444.0155, found 444.0157.
1-(3-Chlorophenyl)-3-(3-nitrophenyl)benzo[f]quinoline
(4r). This compound was obtained as pale yellow crystals, mp
221–222ꢀC; ir (KBr): mmax 3052, 1580, 1563, 1531, 1484, 1472,
1450, 1408, 1347, 1297, 1278, 1256, 1237, 1164, 1113, 1098,
1074, 909, 871, 833, 801, 745, 717, 704; 1H NMR (DMSO-d6): d
7.28–7.32 (m, 1H, ArH), 7.47 (d, J ¼ 7.2 Hz, 1H, ArH), 7.56–
7.70 (m, 5H, ArH), 7.82–7.86 (m, 1H, ArH), 8.06–8.11 (m, 2H,
ArH), 8.20– 8.22 (m, 2H, ArH), 8.35 (d, J ¼ 7.6 Hz, 1H, ArH),
8.81 (d, J ¼ 7.6 Hz, 1H, ArH), 9.17 (s, 1H, ArH). HRMS (ESI,
m/z): calcd. for C25H16N2O2 (MþHþ) 411.0900, found 411.0899.
1-(3-Chlorophenyl)-3-(3,4-dimethylphenyl)benzo[f]quino-
line (4s). This compound was obtained as yellow crystals, mp
182–184ꢀC; ir (KBr): mmax 3053, 2963, 2939, 2916, 1580,
1561, 1544, 1505, 1471, 1451, 1416, 1390, 1345, 1327, 1258,
1246, 1163, 1133, 1097, 1073, 998, 890, 873, 832, 812, 790,
745, 716, 705; 1H NMR (DMSO-d6): d 2.31 (s, 3H, CH3),
2.35 (s, 3H, CH3), 7.25–7.32 (m, 2H, ArH), 7.44–7.47 (m, 1H,
ArH), 7.53–7.67 (m, 5H, ArH), 7.98 (s, 1H, ArH), 8.03–8.10
(m, 3H, ArH), 8.15– 8.17 (m, 2H, ArH). HRMS (ESI, m/z):
calcd. for C27H21NCl (MþHþ) 394.1363, found 394.1366.
3-(4-Nitrophenyl)-1-phenylbenzo[f]quinoline (4t). This com-
pound was obtained as yellow crystals, mp 200-201 ꢀC,
3-(3-Bromophenyl)-1-(4-chlorophenyl)benzo[f]quinoline
(4m). This compound was obtained as white powder, mp 218–
220ꢀC; ir (KBr): mmax 3049, 1595, 1577, 1564, 1547, 1524,
1491, 1477, 1449, 1394, 1350, 1330, 1255, 1236, 1084, 1067,
1015, 993, 890, 870, 837, 804, 755, 710, 699; 1H NMR
(DMSO-d6): d 7.29–7.32 (m, 1H, ArH), 7.50–7.72 (m, 8H,
ArH), 8.04–8.08 (m, 3H, ArH), 8.18 (d, J ¼ 9.2 Hz, 1H,
ArH), 8.37 (d, J ¼ 8.0 Hz, 1H, ArH), 8.51–8.58 (m, 1H,
ArH). HRMS (ESI, m/z): calcd. for C25H16BrClN (MþHþ)
444.0155, found 444.0155.
3-(2,4-Dichlorophenyl)-1-(4-chlorophenyl)benzo[f]quinoline
(4n). This compound was obtained as pale yellow crystals, mp
172–174ꢀC; ir (KBr): mmax 3086, 3049, 1585, 1552, 1524, 1490,
1474, 1448, 1392, 1378, 1347, 1332, 1247, 1138, 1100, 1090,
1047, 1037, 1013, 952, 871, 861, 834, 822, 802, 791, 751, 716;
1H NMR (DMSO-d6): d 7.30–7.35 (m, 1H, ArH), 7.54 (d, J ¼
8.4 Hz, 1H, ArH), 7.59–7.66 (m, 5H, ArH), 7.71 (m, 1H, ArH),
7.82 (d, J ¼ 2.4 Hz, 1H, ArH), 7.86 (d, J ¼ 8.4 Hz, 1H, ArH),
8.03 (d, J ¼ 9.2 Hz, 1H, ArH), 8.08 (d, J ¼ 7.6 Hz, 1H, ArH),
8.21 (d, J ¼ 9.2 Hz, 1H, ArH). HRMS (ESI, m/z): calcd. for
C25H15Cl3N (MþHþ) 434.0270, found 434.0264.
ꢀ
Lit.[15] 192 C; ir (KBr): mmax 3053, 1599, 1578, 1547, 1509,
1475, 1397, 1340, 1259, 1153, 1106, 1078, 1008, 860, 849,
832, 774, 755, 699; 1H NMR (DMSO-d6): d 7.22–7.25 (m,
1H, ArH), 7.55–7.63 (m, 7H, ArH), 8.07 (d, J ¼ 7.0 Hz, 1H,
ArH), 8.11 (d, J ¼ 9.2 Hz, 1H, ArH), 8.17 (s, 1H, ArH), 8.22
(d, J ¼ 8.8 Hz, 1H, ArH), 8.40 (d, J ¼ 8.8 Hz, 2H, ArH),
8.67 (d, J ¼ 8.8 Hz, 2H, ArH). HRMS (ESI, m/z): calcd. for
C25H17N2O2 (MþHþ) 377.1290, found 377.1274.
1-(3-Chlorophenyl)-3-(2-thiophenyl)benzo[f]quinoline (4o). This
compound was obtained as pale yellow crystals, mp 211–
213ꢀC; ir (KBr): mmax 3097, 3067, 1580, 1562, 1469, 1453,
1421, 1352, 1321, 1255, 1242, 1166, 1154, 1098, 1068, 1027,
860, 851, 829, 794, 779, 744, 716; 1H NMR (DMSO-d6): d
3-(4-Chlorophenyl)-1-phenylbenzo[f]quinoline (4u). This com-
pound was obtained as yellow crystals, mp 164–165ꢀC; ir
(KBr): mmax 3051, 1576, 1545, 1527, 1491, 1474, 1449, 1354,
1279, 1255.1167, 1088, 1009, 834, 722, 753, 700; 1H NMR
(DMSO-d6): d 7.19–7.23 (m, 1H, ArH), 7.51–7.62 (m, 9H,
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

November 2009
An Efficient Synthesis of 1,3-Diarylbenzo[f]quinolines from 2-Halogenated
Acetophenone, Aromatic Aldehyde, and Naphthalen-2-amine Catalyzed by Iodine
1227
REFERENCES AND NOTES
ArH), 8.01–8.07 (m, 3H, ArH), 8.17 (d, J ¼ 8.8 Hz, 1H,
ArH), 8.41 (d, J ¼ 8.4 Hz, 2H, ArH). HRMS (ESI, m/z): calcd.
for C25H17ClN (MþHþ) 366.1050, found 366.1057.
[1] (a) Dcmling, A.; Ugi, I. Angew Chem 2000, 112, 3300; (b)
Ramon, D. J.; Yus, M. Angew Chem 2005, 117, 1628; (c) Ulaczyk-Le-
sankom, A.; Hall, D. G. Curr Opin Chem Biol 2005, 9, 266.
[2] (a) Vijay, N. C.; Rajesh, A. U.; Vinod, S.; Bindu, A. R.;
Sreekanth, J. S.; Lakshmi, B. Acc Chem Res 2003, 36, 899; (b) Albert,
P.; Scott, K. B. Tetrahedron 2006, 63, 5341; (c) Umkehrer, M.; Kolb,
J.; Burdack, C.; Hiller, W. Synlett 2005, 79.; (d) Tietze, L. F. Chem
Rev 1996, 96, 115; (e) Habib-Zahmani, H.; Hacini, S.; Bories, C.;
Faure, R.; Rodriguez, J. Synthesis 2005,2151; (f) Nicolaou, K. C.;
Edmonds, D. J.; Bulger, P. G. Angew Chem Int Ed 2006, 45, 7134;
(g) Wang, Z.; Zhou, L.; El-Boubbou, K.; Ye, X.-S.; Huang, X. J Org
Chem 2007, 72, 6409.
3-(4-Bromophenyl)-1-phenylbenzo[f]quinoline (4v). This com-
pound was obtained as yellow crystals, mp 171–172ꢀC; ir
(KBr): mmax 3051, 3028, 1575, 1544, 1527, 1474, 1448, 1353,
1329, 1278, 1256, 1073, 1006, 833, 814, 771, 753, 700; 1H
NMR (DMSO-d6): d 7.19–7.23 (m, 1H, ArH), 7.51–7.61 (m,
7H, ArH), 7.75 (d, J ¼ 8.4 Hz, 2H, ArH). 8.01–8.07 (m, 3H,
ArH), 8.17 (d, J ¼ 8.8 Hz, 1H, ArH), 8.33 (d, J ¼ 8.4 Hz,
2H, ArH). HRMS (ESI, m/z): calcd. for C25H17BrN (MþHþ)
410.0544, found 410.0544.
3-(3-Bromophenyl)-1-phenylbenzo[f]quinoline (4w). This
compound was obtained as yellow crystals, mp 207–209ꢀC; ir
(KBr): mmax 3054, 1576, 1542, 1522, 1476, 1447, 1388, 1345,
1328, 1252, 1231, 1083, 1069, 995, 943, 869, 838, 781, 756,
702, 689; 1H NMR (DMSO-d6): d 7.15–7.19 (m, 1H, ArH),
7.37–7.41 (m, 1H, ArH), 7.47–7.59 (m, 7H, ArH), 7.67 (d,
J ¼ 8.4 Hz, 1H, ArH), 7.77 (s, 1H, ArH), 7.89 (d, J ¼ 8.0 Hz,
1H, ArH), 8.02 (d, J ¼ 9.2 Hz, 1H, ArH), 8.10–8.16 (m, 2H,
ArH), 8.41 (s, 1H, ArH). HRMS (ESI, m/z): calcd. for
C25H17BrN (MþHþ) 410.0544, found 410.0556.
[3] (a) Selvi, G.; Rajendran, S. P. J Asian Chem 2004, 16,
1017; (b) Bahuguna, R. P.; Joshi, B. C. Indian J Heterocycl Chem
1994, 3, 265.
[4] (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.
[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, 1, 50; Chem Abstr 1992, 117,
251317.
1-(3-Nitrophenyl)-3-(2-thiophenyl) benzo[f]quinoline (4x). This
compound was obtained as yellow crystals, mp 278–280ꢀC; ir
(KBr): mmax 3050, 1584, 1845, 1525, 1484, 1454, 1420, 1347,
1
1259, 1042, 1092, 1083, 883, 870, 835, 799, 753, 743, 696; H
[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.
NMR (DMSO-d6): d 7.23–7.27 (m, 2H, ArH), 7.46 (d, J ¼ 8.4
Hz, 1H, ArH), 7.54–7.58(m, 1H, ArH), 7.78 (dd, J ¼ 5.2 Hz;J0
¼ 1.2 Hz, 1H, ArH), 7.85–7.90 (m, 1H, ArH), 7.94–7.97 (m,
2H, ArH), 8.05 (d, J ¼ 8.8 Hz, 1H, ArH), 8.09–8.10 (m, 2H,
ArH), 8.18 (d, J ¼ 8. 8 Hz, 1H, ArH), 8.45–8.47 (m, 2H,
ArH). HRMS (ESI, m/z): calcd. for C23H15N2O2S (MþHþ)
383.0854, found 383.0841.
[8] Szmuszkovicz, J.; Darlington, W. H.; Von Voigtlander, P.
F.1988,WO 8804292 A1; Chem Abstr 1988, 110, 75335.
[9] (a) Kozlov, N. S.; Zhikhareva, O. D. Dokl Akad Nauk
BSSR 1989, 33, 903; Chem Abstr 1989, 112, 198097. (b) Kozlov, N.
S.; Zhikhareva, O. D. Vestsi Akad Navuk BSSR, Ser Khim Navuk
1987, 66; (c) Kozlov, N. S.; Gladchenko, L. F.; Sauts, R. D.; Serzha-
nina, V. A. Khim Geterotsikl Soedin 1978, 1646; Chem Abstr 1978,
90, 87223; (d) Kozlov, N. G.; Popova, L. A. Russ J Org Chem 1999,
35, 603; (e) Kozlov, N. G.; Basalaeva, L. I. Russ J Org Chem 2003,
39, 718; (f) Kozlov, N. G.; Basalaeva, L. I. Russ J Gen Chem 2006,
76, 1810; (g) Kozlov, N. G.; Gusak, K. N.; Bezborodov, V. S. Russ J
Org Chem 2000, 36, 88.
3-(4-Chlorophenyl)-1-(3-nitrophenyl)benzo[f]
quinoline
(4y). This compound was obtained as yellow crystals, mp 258–
259ꢀC; ir (KBr): mmax 3083, 3058, 1582, 1527, 1489, 1451,
1407, 1351, 1303, 1258, 1209, 1164, 1092, 1047, 1009, 892,
862, 832, 813, 745, 715; 1H NMR (DMSO-d6): d 7.24–7.28 (m,
1H, ArH), 7.51 (d, J ¼ 8.4 Hz, 1H, ArH), 7.56–7.60 (m, 1H,
ArH), 7.62 (d, J ¼ 8.4 Hz, 2H, ArH), 7.85–7.88 (m, 1H, ArH),
7.95 (d, J ¼ 7.6 Hz, 1H, ArH), 8.06–8.08 (m, 2H, ArH), 8.13 (s,
1H, ArH), 8.20 (d, J ¼ 9.2 Hz, 1H, ArH), 8.42 (d, J ¼ 8.4 Hz,
2H, ArH), 8.45–8.47 (m, 2H, ArH). HRMS (ESI, m/z): calcd. for
C25H16ClN2O2 (MþHþ) 411.0900, found 411.0894.
[10] (a) Grachek, V. I. Russ J Gen Chem 2004, 74, 1748; (b)
Kozlov, N. G.; Basalaeva, L. I. Russ J Org Chem 2003, 39, 718; (c)
Ripa, L.; Hallberg, A. J Org Chem 1998, 63, 84; (d) Stetsenko, A.
V.; Fursii, F. A. Ukr Khim Zh 1986, 52, 755; Chem Abstr 1986,
107, 154204; (e) Bahuguna, R. P.; Joshi, B. C. Egypt 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 Het-
erocycl Chem 1994, 3, 265; (h) Beller, N. R.; Neckers, D. C.; Papa-
dopoulos, E. P. J Org Chem 1977, 42, 3514.
3-(4-Bromophenyl)-1-(3-nitrophenyl)benzo[f] quinoline
(4z). This compound was obtained as yellow crystals, mp 263–
264ꢀC; ir (KBr): mmax 3056, 1581, 1527, 1486, 1451, 1384,
1351, 1304, 1258, 1210, 1179, 1163, 1075, 1006, 891, 861, 831,
814, 744, 705; 1H NMR (DMSO-d6): d 7.25–7.29 (m, 1H, ArH),
7.52 (d, J ¼ 8.4 Hz, 1H, ArH), 7.57–7.61(m, 1H, ArH), 7.77 (d,
J ¼ 8.4 Hz, 2H, ArH), 7.88 (d, J ¼ 8.0 Hz, 1H, ArH), 7.95–7.97
(m, 1H, ArH), 8.04–8.10 (m, 2H, ArH), 8.15 (m, 1H, ArH), 8.27
(d, J ¼ 9.2 Hz, 1H, ArH), 8.37 (d, J ¼ 8.4 Hz, 2H, ArH), 8.45–
8.48 (m, 2H, ArH). HRMS (ESI, m/z): calcd. for C25H16BrN2O2
(MþHþ) 455.0395, found 455.0399.
[11] Wang, X. S.; Li, Q.; Wu, J. R.; Li, Y. L.; Yao, C. S.; Tu,
S. J. Synthesis 2008, 1902.
[12] (a) Wang, X. S.; Li, Q.; Yao, C. S.; Tu, S. J. Eur J Org
Chem 2008, 3513; (b) Wang, X. S.; Zhang, M. M.; Li, Q.; Yao, C. S.;
Tu, S. J Synlett 2007, 3141; (c) Wang, X. S.; Zhang, M. M.; Jiang,
H.; Yao, C. S.; Tu, S. J. Tetrahedron 2007, 63, 4439.
[13] Crystal data for 4a: C25H15ClN2O2; M ¼ 410.84, color-
less block crystals, 0.34
ꢁ
0.32
ꢁ
0.22 mm3, Triclinic, space
group P-1, a ¼ 9.1390 (12), b ¼ 9.5350 (11), c ¼ 11.9668 (17)
ꢀ
Acknowledgment. The authors are grateful to the National Nat-
ural Science foundation of China (20802061), the Natural
Science foundation (08KJD150019), and Qing Lan Project
(08QLT001) of Jiangsu Education Committee for financial
support.
˚
A, a ¼ 108.182 (4), b ¼ 105.366 (4), c ¼ 92.739 (3) , V ¼
945.6 (2) 3, Z ¼ 2, Dc ¼ 1.443 g cmꢂ3. F(000) ¼ 424, l(MoKa)
¼ 0.228 mmꢂ1. Intensity data were collected on Rigaku Mercury
diffractometer with graphite monochromated MoKa radiation (k ¼
0.71070 A) using x scan mode with 2.27 < y < 27.87 ꢀ. 4467
ꢀ
˚
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

1228
X.-S. Wang, Q. Li, J. Zhou, and S.-J. Tu
Vol 46
unique reflections were measured and 3779 reflections with I >
2r (I) were used in the refinement. Structure solved by direct
methods and expanded using Fourier techniques. The final cycle of
L.; Wang, Y. G. Tetrahedron Lett 2006, 47, 3217; (d) Lin, X. F.; Cui,
S. L.; Wang, Y. G. Tetrahedron Lett 2006, 47, 4509; (e) Iranpoor, N.;
Tamami, B.; Niknam, K. Can J Chem 1997, 75, 1913; (f) Tamami, B.;
Iranpoor, N.; Mahdavi, H. Synth Commun 2002, 32, 1251; (g) Phukan,
P. J Org Chem 2004, 69, 4005; (h) Gerus, I. I.; Kruchok, I. S.;
Kukhar, V. P. Tetrahedron Lett 1999, 40, 5923.
full-matrix least squares technique to
0.1209.
R
¼
0.0493 and wR
¼
[14] (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; (c) Lin, X. F.; Cui, S.
[15] Kozlov, N. S.; Korobchenko, L. V.; Shmanai, G. S.;
Tsvirko, M. P. Chem Heterocycl Compd 1976, 12, 106.
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet