Microwave-promoted alkynylation-cyclization of 2-aminoaryl ketones: A green strategy for the synthesis of 2,4-disubstituted quinolines

Article abstract of DOI:10.1055/s-0030-1259065

A series of 2,4-disubstituted quinolines were easily prepared through a one-pot reaction of structurally diverse 2-aminoaryl ketones with various arylacetylenes in the presence of K₅CoW₁₂O ₄₀3H₂O as a reusable a

Full text of DOI:10.1055/s-0030-1259065

3104
LETTER
Microwave-Promoted Alkynylation–Cyclization of 2-Aminoaryl Ketones:
A Green Strategy for the Synthesis of 2,4-Disubstituted Quinolines
S
ynthesi
r
s
of 2,4-
a
D
isubstitute
j
d
Q
uinoline
s
Mohammadpoor-Baltork,* Shahram Tangestaninejad,* Majid Moghadam, Valiollah Mirkhani, Salma Anvar,
Arsalan Mirjafari
Catalysis Division, Department of Chemistry, University of Isfahan, Isfahan 81746-73441, Iran
Fax +98(311)6689732; E-mail: imbaltork@sci.ui.ac.ir; E-mail: stanges@sci.ui.ac.ir
Received 19 July 2010
to the development of green processes. To the best of our
Abstract: A series of 2,4-disubstituted quinolines were easily pre-
pared through a one-pot reaction of structurally diverse 2-aminoaryl
ketones with various arylacetylenes in the presence of
K5CoW12O40·3H2O as a reusable and environmentally benign cata-
lyst under microwave irradiation and solvent-free conditions.
knowledge, there are no reports on the use of
K5CoW12O40·3H2O as a heterogeneous catalyst for the
synthesis of substituted quinolines.
Key words: 2,4-disubstituted quinolines, K5CoW12O40·3H2O,
microwave irradiation, 2-aminoaryl ketones, arylacetylenes
NEt2
HO
HN
N
H
MeO
Quinoline and, more specifically, substituted quinolines
exist in many natural products and have a wide spectrum
of biological activities.1 They have proven to be key com-
pounds for the synthesis of therapeutic agents e.g., antimi-
crobial, antibacterial, antiinflammatory, antiplatelet and
antimalarials.2 Known substituted quinoline drugs are
quinine I, which is used as an antipyretic (fever-reducing),
and chloroquine II, which is an antimalarial drug3
(Figure 1). Besides pharmacological activity, compounds
containing the 4-arylquinoline substructure have found
many applications, for example, as chemosensors for
fluoride ions,4 and as fluorescent sensors for the detection
of metal ions in aqueous solutions.5 Various cyclization
processes leading to these heterocycles, have been report-
ed in the literature, for example, Skraup,6 Doebner and
Miller,7 Friedländer,8 Combes,9 and others.10 Recently,
the synthesis of substituted quinolines has been reported
to take place by Meyer–Schuster rearrangement of 2-ami-
noaryl ketones and phenylacetylene in the presence of
In(OTf)3 and Zn(OTf)2/[hmim]PF6.11 However, in spite of
their potential utility, some of the reported methods in-
volve the use of Lewis or Brønsted acids. These tradition-
al acids are corrosive and produce significant amounts of
waste, which limit their usefulness and cause serious en-
vironmental and safety concerns. Furthermore, long reac-
tion times, low yields, tedious work-up, formation of by
products, and the use of expensive reagents and toxic or-
ganic solvents, are other disadvantages of some of these
methods. Due to their importance and useful properties,
the development of an efficient, general and environmen-
tally benign method for the preparation of these widely
used heterocyclic compounds is a major challenge in syn-
thetic organic chemistry. Consequently, a method that
uses K5CoW12O40·3H2O catalyst should greatly contribute
Cl
N
N
II
I
Figure 1 Structure of quinine (I) and chloroquine (II); two quinoline-
based drugs
The high catalytic activity of heteropoly compounds has
received significant interest in recent years.12 Because of
their weak super-acidic and redox properties, low toxicity,
ease of handling, low cost, stability, recoverability, and
reusability, heteropoly compounds have been used as ver-
satile heterogeneous and environmentally friendly cata-
lysts in different areas of organic synthesis. The
[CoIIIW12]5– anion is a well-defined outer-sphere electron-
transfer agent.13 During the intervening time, the potential
utility of numerous POM anions as electron-transfer
agents in the selective catalytic oxidations of inorganic
and organic substrates of practical importance has been
recognized.14 Due to the successful applications of
K5CoW12O40·3H2O as a catalyst, several synthetically
useful organic transformations using this salt have been
reported in the literature.15
As a part of our ongoing program to develop practical and
eco-friendly synthetic methodologies,16 we wish to report
a novel and straightforward synthesis of substituted quin-
olines via a one-pot reaction of 2-aminoaryl ketones and
arylacetylenes in the presence of K5CoW12O40·3H2O as a
reusable catalyst under microwave irradiation and sol-
vent-free conditions (Scheme 1).
Initially, 2-aminobenzophenone and phenylacetylene
were chosen as model substrates for optimization of the
reaction conditions (Table 1). The reaction of 2-ami-
nobenzophenone
(1 mmol)
and
phenylacetylene
(1 mmol) was first performed in the absence of the cata-
lyst under microwave irradiation17 (1000 W) at 110 °C in
order to establish the effectiveness of the catalyst. Under
SYNLETT 2010, No. 20, pp 3104–3112
Advanced online publication: 24.11.2010
DOI: 10.1055/s-0030-1259065; Art ID: D19310ST
x
x
.x
x
.2
0
1
0
© Georg Thieme Verlag Stuttgart · New York

LETTER
Synthesis of 2,4-Disubstituted Quinolines
3105
R1
Table 1 Optimization of the Reaction Conditions for the Synthesis
of 2,4-Diphenylquinoline (3a)a
R1
N
O
K5CoW12O40⋅3H2O
Ph
Ph
ArC CH
+
MW
R2
NH2
Ar
R2
Catalyst
O
PhC CH
+
1
3
2
N
Ph
NH2
Scheme 1 Microwave-promoted synthesis of 2,4-disubstituted qui-
nolines 3 by the reaction of 2-aminoaryl ketones 1 and arylacetylenes
2 catalyzed by K5CoW12O40·3H2O
Entry Catalyst
(mol%)
Temp
(°C)
Time
(min)
Yield
(%)b
1
2
no catalyst
110
110
110
110
110
110
110
120
110
110
100
110
110
110
110
15
15
15
15
15
15
15
15
15
20
15
15
10
15
180
0
65
46
43
32
40
95
95
95
95
80
70
81
70
15
these conditions, the reaction did not proceed and the
starting materials remained intact in the reaction mixture
(Table 1, entry 1). Then, the same reaction was examined
in the presence of different heteropoly compounds
(10 mol%) as catalysts for 15 minutes (Table 1, entries 2–
7). The results revealed that K5CoW12O40·3H2O was the
most effective catalyst in this reaction (Table 1, entry 7).
Next, we tested the effect of reaction time, the amount of
catalyst, the temperature and the MW power on the yield
of the product. Increasing either the temperature or the
amount of catalyst and/or prolonging the reaction time did
not improve the yield (Table 1, entries 8–10), while re-
ducing these parameters or reducing the microwave pow-
er led to a reduction in product yield (Table 1, entries 11–
14). In order to ascertain the effectiveness of microwave
heating, the reaction was also conducted using conven-
tional heating (110 °C) and the desired product was ob-
tained in only 15% yield after 3 hours (Table 1, entry 15).
Therefore, 1:1:0.01 molar ratios of 2-aminobenzophe-
none, phenylacetylene and K5CoW12O40·3H2O and a pow-
er of 1000 W at 110 °C were found to be the optimal
conditions.
H3PW12O40 (10)
3
H3PMo12O40 (10)
4
H4SiW12O40 (10)
5
AlPW12O40 (10)
6
AlPMo12O40 (10)
7
K5CoW12O40·3H2O (10)
K5CoW12O40·3H2O (10)
K5CoW12O40·3H2O (12)
K5CoW12O40·3H2O (10)
K5CoW12O40·3H2O (10)
K5CoW12O40·3H2O (8)
K5CoW12O40·3H2O (10)
K5CoW12O40·3H2O (10)
K5CoW12O40·3H2O (10)
8
9
10
11
12
13
14c
15d
a Reaction conditions: 2-aminobenzophenone (1 mmol), phenylacet-
A series of reactions were carried out to study the scope
and generality of the catalyst under the optimum condi- ylene (1 mmol), applied power of 1000 W.
b Isolated yield.
tions. A wide range of substituted and structurally diverse
2-aminoaryl ketones and arylacetylenes were used, and
c Reaction was performed with applied power of 800 W.
d Reaction was performed under thermal conditions.
the corresponding 2,4-diaryl quinolines were synthesized
in excellent yields (Table 2, entries 1–18).18 2-Aminoace-
der the same reaction conditions. These results indicate
tophenone as an alkyl substituted ketone was also convert-
that the present protocol is potentially applicable to the
ed efficiently into its corresponding quinoline in the
chemoselective conversion of arylacetylenes into their
presence of this catalyst (Table 2, entries 19 and 20). The
quinolines in the presence of alkylacetylenes. In this
reaction was generally clean and no side products, such as
manner, the reaction of an equimolar mixture of phenyl-
dihydroquinolines, were produced; in all cases, 2,4-disub-
acetylene and 1-hexyne with 2-amino-5-chloro-2′-fluo-
stituted quinolines were obtained as the sole products. As
robenzophenone (Table 1, entry 4) was performed under
shown in Table 2, the presence of electron-withdrawing
microwave irradiation. It was observed that only pheny-
or electron-donating substituents on the aromatic rings of
lacetylene reacted and that 1-hexyne remained intact in
starting materials had no significant effect on the yields of
the reaction mixture (Scheme 2).
the products. It is noteworthy that alkylacetylenes, such as
1-hexyne, did not afford the corresponding quinoline un-
F
F
F
O
PhC CH
Cl
Cl
Cl
catalyst
+
+
MW, 10 min
N
(CH2)3Me
Me(CH2)3C CH
N
Ph
H2N
90%
0%
Scheme 2 Selective conversion of arylacetylene into the corresponding quinoline in the presence of alkylacetylene catalyzed by
K5CoW12O40·3H2O
Synlett 2010, No. 20, 3104–3112 © Thieme Stuttgart · New York

3106
I. Mohammadpoor-Baltork et al.
LETTER
Table 2 Microwave-Promoted Synthesis of 2,4-Disubstituted Quinolines Catalyzed by K5CoW12O40·3H2Oa
Entry 2-Aminoaryl ketone
Acetylene
Quinoline
Time (min) Yield (%)b
Ph
O
1
15
15
95
95
CH
CH
N
Ph
H2N
3a
Ph
O
Cl
Cl
Cl
2
N
N
N
Ph
H2N
3b
Cl
O
Cl
3
4
10
10
96
90
Cl
CH
H2N
Ph
3c
F
O
F
Cl
Cl
CH
CH
H2N
O
Ph
3d
Ph
N
O2N
NO2
5
6
10
15
90
84
Ph
H2N
O
3e
Ph
N
CH
OMe
H2N
OMe
3f
Ph
N
CH
O
Cl
Cl
7
8
20
10
84
89
OMe
H2N
OMe
3g
CH
Cl
Cl
O
Cl
Cl
OMe
N
H2N
OMe
3h
Synlett 2010, No. 20, 3104–3112 © Thieme Stuttgart · New York

LETTER
Synthesis of 2,4-Disubstituted Quinolines
3107
Table 2 Microwave-Promoted Synthesis of 2,4-Disubstituted Quinolines Catalyzed by K5CoW12O40·3H2Oa (continued)
Entry 2-Aminoaryl ketone
Acetylene
Quinoline
Time (min) Yield (%)b
CH
F
F
O
Cl
Cl
9
10
90
OMe
N
H2N
OMe
3i
Ph
N
CH
O2N
O
NO2
10
11
15
90
90
OMe
H2N
OMe
3j
Ph
N
O
Cl
CH
Cl
5
H2N
3k
Cl
Cl
O
CH
Cl
Cl
12
15
93
N
H2N
3l
F
F
O
CH
Cl
Cl
13
5
96
N
H2N
3m
Ph
O2N
O
CH
NO2
14
15
5
95
96
N
H2N
3n
Ph
Cl
O
CH
Cl
10
N
MeO
H2N
OMe
3o
Synlett 2010, No. 20, 3104–3112 © Thieme Stuttgart · New York

3108
I. Mohammadpoor-Baltork et al.
LETTER
Table 2 Microwave-Promoted Synthesis of 2,4-Disubstituted Quinolines Catalyzed by K5CoW12O40·3H2Oa (continued)
Entry 2-Aminoaryl ketone
Acetylene
Quinoline
Time (min) Yield (%)b
Cl
Cl
O
CH
Cl
Cl
16
15
84
N
MeO
H2N
OMe
3p
F
F
O
CH
Cl
Cl
17
15
86
N
MeO
H2N
OMe
3q
Ph
O2N
O
CH
NO2
18
10
90
N
MeO
H2N
O
OMe
3r
19
20
20
20
75
82
CH
N
Ph
NH2
3s
O
CH
N
NH2
3t
a Reaction conditions: 2-Aminoaryl ketone (1 mmol), arylacetylene (1 mmol), catalyst (10 mol%) and 1000 W microwave power at 110 °C.
b Isolated yield.
The structure of the products was deduced from their IR, amide was added to the reaction mixture. Under these
1
mass, H and 13C NMR spectra and by their elemental conditions, after exposing the mixture to MW irradiation,
analysis. Furthermore, the structure of 3h was confirmed no progress was observed in the reaction, which is a good
by X-ray crystallographic analysis (CCDC 781894, indication of the presence of radical species in the reac-
Figure 2).
tion. Another reasonable explanation for the mechanism is
that the water reacts with radical cation 4 and produces the
acetophenone, which then reacts with 2-aminoaryl ketone
1 to afford the desired product. On the basis of this reason-
ing, the reaction can occur via two paths and therefore the
reaction must be accelerated. In this manner, the reaction
of phenylacetylene with catalyst was investigated in the
absence of 2-aminoaryl ketone 1 and it was found that, un-
der these conditions, less than 5% of acetophene was pro-
duced. When the model reaction was carried out in the
presence of water, only 30% of 2,4-disubstituted quino-
line was obtained. Therefore, the addition of water deacti-
vates the catalyst and decreases the yield. All these
The actual mechanism of the reaction is not clear at
present. However, according to published results,13,14 the
mechanism can be explained on the basis of an electron-
transfer phenomenon, in which the arylacetylene 2 is first
oxidized to a radical-cation intermediate 4 by transferring
an electron to Co(III) to produce Co(II). Nucleophilic at-
tack of 2-aminoaryl ketone 1 on 4 affords 5. One electron
transfer from Co(II) to 5 gives 6 and regenerates the
Co(III) species, which enters the next catalytic cycle. Fi-
nally, cyclization of 6 followed by elimination of water af-
fords the desired product 3 (Scheme 3). To validate the
suggested mechanism, a radical scavenger such as acryl-
Synlett 2010, No. 20, 3104–3112 © Thieme Stuttgart · New York

LETTER
Synthesis of 2,4-Disubstituted Quinolines
3109
Co (III)
ArC CH
ArC CH2
+ Co(II)
2
4
R1
R1
OH
O
Co(II)
R1
O
CH
CH
+
ArC CH2
+
Co(III)
NH2
NH
Ar
Ar
N
R2
R2
R2
H2
5
1
4
6
R1
N
R1 OH
– H2O
R2
Ar
N
H
Ar
R2
3
Scheme 3 Proposed mechanism for K5CoW12O40·3H2O catalyzed synthesis of 2,4-disubstituted quinolines
Table 3 Reuse of K5CoW12O40·3H2O Catalyst for the Synthesis of
3aa
Run
1
Cycle
Yield (%)b
0
1
2
3
4
5
95
95
92
90
87
85
2
3
4
5
6
a Reaction conditions: 2-Aminobenzophenone (1 mmol), phenylacet-
ylene (1 mmol), catalyst (10 mol%), 1000 W microwave power at
110 °C, 15 min.
b Isolated yield.
arylacetylenes using a sub-stoichiometric amount of
K5CoW12O40·3H2O under solvent-free conditions. The
notable features of this method are simple operation, en-
vironmentally friendly experimental conditions, short re-
action times and high yields of isolated products. In
addition, easy recovery and reuse of the catalyst and the
avoidance of toxic organic solvents make this procedure
an economical and green process for the synthesis of quin-
oline derivatives.
Figure 2 X-ray crystal structure of 3h
observations showed that the proposed mechanism
(Scheme 3) is more reasonable.
The reusability and recycling of the K5CoW12O40·3H2O
catalyst, which is one of the key advantages of this proce-
dure, was tested in the reaction of 2-aminobenzophenone
and phenylacetylene as a model. After completion of the
reaction, the mixture was cooled to room temperature; the
catalyst was separated by simple filtration by diluting with
cold ethanol and dried at 100 °C. The recovered catalyst
could be reused at least five additional times in subse-
quent reactions without significant loss of activity
(Table 3).
Acknowledgment
The authors are grateful to the Center of Excellence of Chemistry
and the Research Council of the University of Isfahan for financial
support of this work.
References and Notes
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promoted, one-pot synthesis of 2,4-disubstituted quino-
lines via cyclocondensation of 2-aminoaryl ketones and
Synlett 2010, No. 20, 3104–3112 © Thieme Stuttgart · New York

3110
I. Mohammadpoor-Baltork et al.
LETTER
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(18) Synthesis of 2,4-Disubstituted Quinolines; General
Procedure
A mixture of 2-aminoaryl ketone 1 (1 mmol), arylacetylene
2 (1 mmol) and K5WCo12O40·3H2O (10 mol%) was
irradiated under solvent-free conditions for the appropriate
time (Table 2). The progress of the reaction was monitored
by TLC (n-hexane–EtOAc, 9:1). After completion of the
reaction, the mixture was cooled to r.t. and cold EtOH (20
mL) was added. The residue was filtered, the filtrate was
evaporated, and the crude product was purified by recrystal-
lization from EtOH to afford the pure product in 75–96%
yields.
2,4-Diphenylquinoline (3a)
Mp 107–109 °C (Lit.11b 107 °C). IR (KBr): 3062, 2922,
1616, 1475, 1317, 1274, 960, 767 cm–1. 1H NMR (500 MHz,
CDCl3): d = 7.40–7.45 (m, 2 H), 7.47–7.55 (m, 7 H), 7.70 (t,
J = 7.5 Hz, 1 H), 7.77 (s, 1 H), 7.88 (d, J = 3.2 Hz, 1 H), 8.15
(d, J = 8.1 Hz, 2 H), 8.21 (d, J = 8.8 Hz, 1 H). MS: m/z =
281.09 (7.07) [M]+, 254.15 (91.45), 179.41 (21.88), 103.16
(35.60), 77.18 (100.00), 51.23 (33.55).
6-Chloro-2,4-diphenylquinoline (3b)
Mp 98–99 °C (Lit.10g 98 °C). IR (KBr): 2922, 2852, 1587,
1543, 1481, 887, 823, 779, 700 cm–1. 1H NMR (500 MHz,
CDCl3): d = 7.47–7.50 (m, 1 H), 7.53–7.60 (m, 7 H), 7.68
(dd, 1J = 9.0 Hz, 2J = 2.2 Hz, 1 H), 7.85 (s, 1 H), 7.87 (d, J =
2.0 Hz, 1 H), 8.17–8.20 (m, 3 H). MS: m/z = 317.08 (2.15)
[M + 2]+, 315.03 (8.10) [M]+, 280.11 (6.22), 238.08 (2.63),
103.05 (20.24), 77.05 (100.00), 51.09 (57.09).
6-Chloro-4-(2-chlorophenyl)-2-phenylquinoline (3c)
Mp 112–114 °C (Lit.11b 112 °C). IR (KBr): 2951, 1643,
1469, 1365, 1228, 1022, 829 cm–1. 1H NMR (500 MHz,
CDCl3): d = 7.39–7.41 (m, 1 H), 7.44–7.50 (m, 4 H), 7.53–
7.56 (m, 2 H), 7.62 (d, J = 7.9 Hz, 1 H), 7.67 (dd, 1J =
9.0 Hz, 2J = 2.1 Hz, 1 H), 7.84 (s, 1 H), 8.19–8.21 (m, 3 H).
MS: m/z = 351.02 (11.13) [M + 2]+, 349.00 (17.97) [M]+,
314.06 (5.91), 279.12 (13.09), 278.13 (38.28), 201.10
(22.46), 102.96 (38.87), 76.96 (81.25), 74.97 (50.78), 50.98
(100.00).
6-Chloro-4-(2¢-fluorophenyl)-2-phenylquinoline (3d)
Mp 124–126 °C (Lit.11b 125 °C). IR (KBr): 3055, 2922,
2850, 1593, 1544, 1481, 1354, 885, 835, 802, 756 cm–1. 1H
NMR (500 MHz, CDCl3): d = 7.27–7.37 (m, 2 H), 7.44–7.56
(m, 5 H), 7.66–7.70 (m, 2 H), 7.88 (s, 1 H), 8.19 (d, J =
8.2 Hz, 3 H). MS: m/z = 334.02 (8.59) [M + 2]+, 331.98
(14) (a) Saha, S. K.; Ali, M.; Banerjee, P. Coord. Chem. Rev.
1993, 122, 41. (b) Weinstock, I. A. Chem. Rev. 1998, 98,
113.
(15) (a) Habibi, M. H.; Tangestaninejad, S.; Mohammadpoor-
Baltork, I.; Mirkhani, V.; Yadollahi, B. Tetrahedron Lett.
2001, 42, 2851. (b) Firouzabadi, H.; Jafari, A. A. J. Iran.
Chem. Soc. 2005, 2, 85. (c) Kantevari, V. C.; Chary, M. V.;
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LETTER
(21.56) [M]+, 298.08 (6.33), 194.07 (14.61), 102.96 (49.38),
Synthesis of 2,4-Disubstituted Quinolines
3111
(93.39) [M]+, 362.15 (100.00), 334.14 (52.69), 333.14
76.96 (100.00), 74.95 (65.63), 50.97 (96.25).
2,4-Diphenyl-6-nitroquinoline (3e)
(60.33), 332.12 (44.01), 296.13 (16.53), 283.13 (15.91),
141.59 (23.35), 99.04 (8.01), 51.10 (5.58). Anal. Calcd for
C22H15ClFN (347.09): C, 72.63; H, 4.16; N, 3.85. Found: C,
72.51; H, 4.21; N, 3.78.
Mp 265–266 °C (Lit.10h 264 °C). IR (KBr): 2922, 2852,
1595, 1440, 1382, 1338, 883, 846, 771, 752 cm–1. 1H NMR
(500 MHz, CDCl3): d = 7.54–7.64 (m, 8 H), 7.99 (s, 1 H),
8.26 (d, J = 7.0 Hz, 2 H), 8.35 (d, J = 9.2 Hz, 1 H), 8.50 (dd,
1J = 9.2 Hz, 2J = 2.4 Hz, 1 H), 8.87 (d, J = 2.4 Hz, 1 H).
MS: m/z = 326.11 (3.20) [M]+, 244.02 (13.24), 203.06
(10.96), 146.58 (27.40), 100.66 (25.11), 78.08 (29.68),
77.04 (81.28), 55.10 (100.00).
2-(3-Methoxyphenyl)-6-nitro-4-phenylquinoline (3j)
Mp 194–195 °C. IR (KBr): 2922, 2852, 1620, 1597, 1554,
1340, 1267, 1035, 875, 810, 702 cm–1. 1H NMR (500 MHz,
CDCl3): d = 3.95 (s, 3 H), 7.08 (dd, 1J = 8.17 Hz, 2J = 2.0 Hz,
1 H), 7.47 (t, J = 8.0 Hz, 1 H), 7.57–7.64 (m, 5 H), 7.79 (d,
J = 7.7 Hz, 1 H), 7.85 (s, 1 H), 7.97 (s, 1 H), 8.34 (d, J =
9.3 Hz, 1 H), 8.50 (dd, 1J = 8.8 Hz, 2J = 1.8 Hz, 1 H), 8.86
(d, J = 2.1 Hz, 1 H). 13C NMR (125 MHz, CDCl3): d = 55.51,
113.07, 116.47, 120.27, 120.83, 122.91, 123.08, 124.93,
129.16, 129.35, 129.47, 130.04, 131.82, 136.92, 139.98,
145.49, 151.02, 151.27, 159.83, 160.33. MS: m/z = 356.13
(85.19) [M]+, 355.11 (100.00), 326.08 (14.89), 241.16
(19.52), 201.16 (25.31), 176.20 (29.32), 139.27 (32.10),
132.61 (31.48), 78.11 (26.85), 77.10 (91.36), 51.13 (51.23).
Anal. Calcd for C22H16N2O (324.13): C, 74.15; H, 4.53; N,
7.86. Found: C, 73.97; H, 4.57; N, 7.92.
2-(3-Methoxyphenyl)-4-phenylquinoline (3f)
Mp 170 °C. IR (KBr): 2922, 2852, 1625, 1544, 1462,
1097 cm–1. 1H NMR (500 MHz, CDCl3): d = 3.94 (s, 3 H),
7.04 (d, J = 7.1 Hz, 1 H), 7.44 (t, J = 8.3 Hz, 1 H), 7.49–7.58
(m, 6 H), 7.73–7.78 (m, 2 H), 7.80–7.82 (m, 2 H), 7.92 (d,
J = 8.5 Hz, 1 H), 8.28 (s, 1 H). MS: m/z = 311.06 (26.34)
[M]+, 310.03 (35.61), 281.06 (15.85), 267.10 (4.70), 241.04
(5.03), 204.08 (9.88), 176.04 (21.59), 140.08 (16.95), 57.05
(92.20), 55.05 (100.00).
6-Chloro-2-(3-methoxyphenyl)-4-phenylquinoline (3g)
Mp 129–130 °C. IR (KBr): 2924, 2831, 1600, 1543, 1485,
1344, 1041, 877, 823, 769 cm–1. 1H NMR (500 MHz,
CDCl3): d = 3.94 (s, 3 H, OMe), 7.04 (dd, 1J = 8.2 Hz, 2J =
2.4 Hz, 1 H), 7.44 (t, J = 8.0 Hz, 1 H), 7.54–7.60 (m, 5 H),
7.67 (dd, 1J = 8.2 Hz, 2J = 2.3 Hz, 1 H), 7.73 (d, J = 7.6 Hz,
1 H), 7.79 (s, 1 H), 7.83 (s, 1 H), 7.87 (d, J = 1.7 Hz, 1 H),
8.18 (d, J = 8.9 Hz, 1 H). 13C NMR (125 MHz, CDCl3): d =
55.47, 112.72, 115.70, 120.01, 120.14, 124.51, 126.60,
128.75, 128.86, 129.49, 129.90, 130.47, 131.78, 132.29,
137.77, 140.68, 147.19, 148.44, 156.86, 160.23. MS: m/z =
347.98 (5.99) [M + 2]+, 345.99 (48.98) [M]+, 343.98
(100.00), 317.99 (6.51), 314.99 (27.87), 203.11 (14.34),
155.01 (21.52), 139.04 (23.57), 132.55 (27.66), 77.13
(7.68). Anal. Calcd for C22H16ClNO (345.09): C, 76.41; H,
4.66; N, 4.05. Found: C, 76.28; H, 4.71; N, 3.97.
6-Chloro-4-phenyl-2-p-tolylquinoline (3k)
Mp 123–124 °C (Lit.10i 132 °C). IR (KBr): 2922, 2852,
1589, 1539, 1352, 1153, 887, 835 cm–1. 1H NMR (500 MHz,
CDCl3): d = 2.45 (s, 3 H), 7.34 (d, J = 8.0 Hz, 2 H), 7.53–
7.59 (m, 5 H), 7.66 (dd, 1J = 8.9 Hz, 2J = 1.9 Hz, 1 H), 7.83
(s, 1 H), 7.85 (d, J = 1.9 Hz, 1 H), 8.09 (d, J = 8.0 Hz, 2 H),
8.16 (d, J = 8.9 Hz, 1 H). MS: m/z = 331.04 (34.88) [M + 2]+,
329.05 (100.00) [M]+, 294.10 (22.84), 201.12 (10.96),
176.12 (12.89), 146.89 (32.10), 91.16 (2.91), 51.13 (4.40).
6-Chloro-4-(2-chlorophenyl)-2-p-tolylquinoline (3l)
Mp 125–126 °C. IR (KBr): 2922, 2852, 1581, 1350, 1153,
1053, 881, 813 cm–1. 1H NMR (500 MHz, CDCl3): d = 2.45
(s, 3 H), 7.34 (d, J = 7.9 Hz, 2 H), 7.38–7.40 (m, 1 H), 7.45–
7.49 (m, 3 H), 7.61 (d, J = 7.8 Hz, 1 H), 7.66 (dd, 1J =
9.0 Hz, 2J = 2.2 Hz, 1 H), 7.81 (s, 1 H), 8.10 (d, J = 8.0 Hz,
2 H), 8.17 (d, J = 8.9 Hz, 1 H). 13C NMR (125 M Hz,
CDCl3): d = 22.69, 120.41, 124.34, 126.41, 127.44, 129.63,
129.72, 130.01, 130.07, 130.50, 131.35, 131.67, 135.47,
136.28, 139.81, 142.47, 147.05, 157.02, 160.73. MS: m/z =
366.96 (12.71) [M + 4]+, 364.96 (65.56) [M + 2]+, 362.97
(100.00) [M]+, 361.96 (53.06), 327.99 (37.78), 293.05
(3.00), 146.34 (65.83), 145.49 (95.56), 144.50 (33.06),
132.44 (17.78), 91.10 (3.59), 51.06 (4.24). Anal. Calcd for
C22H15Cl2N (363.06): C, 72.54; H, 4.15; N, 3.85. Found: C,
72.43; H, 4.20; N, 3.79.
6-Chloro-4-(2-chlorophenyl)-2-(3-methoxyphenyl)-
quinoline (3h)
Mp 168–169 °C. IR (KBr): 2922, 2850, 1604, 1583, 1544,
1471, 1433, 1282, 1174, 1043, 887, 839, 763, 705 cm–1. 1H
NMR (500 MHz, CDCl3): d = 3.94 (s, 3 H), 7.04 (dd, 1J =
8.2 Hz, 2J = 2.5 Hz, 1 H), 7.39 (dd, 1J = 7.4 Hz, 2J = 1.7 Hz,
1 H), 7.42–7.51 (m, 4 H), 7.61 (d, J = 9.0 Hz, 1 H), 7.67 (dd,
1J = 7.8 Hz, 2J = 2.2 Hz, 1 H), 7.72 (d, J = 7.6 Hz, 1 H),
7.79–7.81 (m, 2 H), 8.18 (d, J = 9.0 Hz, 1 H). 13C NMR (125
MHz, CDCl3): d = 55.48, 112.73, 115.81, 120.03, 120.70,
124.41, 126.65, 127.04, 129.91, 130.12, 130.17, 130.65,
131.37, 131.76, 132.45, 133.34, 136.34, 140.51, 145.78,
146.90, 156.81, 160.26. MS: m/z = 383.12 (8.09) [M + 4]+,
381.14 (4.30) [M + 2]+, 379.00 (72.32) [M]+, 378.14
(100.00), 350.11 (27.90), 237.12 (15.63), 132.85 (22.99),
75.06 (20.09). Anal. Calcd for C22H15Cl2NO (379.05): C,
69.49; H, 3.98; N, 3.68. Found: C, 69.32; H, 4.03; N, 3.75.
6-Chloro-4-(2-fluorophenyl)-2-(3-methoxyphenyl)-
quinoline (3i)
Mp 114–115 °C. IR (KBr): 3035, 2935, 2835, 1589, 1544,
1483, 1280, 1043, 887, 761 cm–1. 1H NMR (500 MHz,
CDCl3): d = 3.94 (s, 3 H), 7.04 (dd, 1J = 8.1 Hz, 2J = 2.4 Hz,
1 H), 7.30 (t, J = 9.0 Hz, 1 H), 7.35 (t, J = 7.5 Hz, 1 H), 7.42–
7.47 (m, 2 H), 7.53–755 (m, 1 H), 7.65 (s, 1 H), 7.68 (dd,
1J = 8.9 Hz, 2J = 2.2 Hz, 1 H), 7.72 (d, J = 7.7 Hz, 1 H), 7.79
(s, 1 H), 7.86 (s, 1 H), 8.19 (d, J = 8.9 Hz, 1 H). 13C NMR
(125 MHz, CDCl3): d = 55.47, 112.74, 115.75, 116.20,
116.37, 120.01, 121.06, 124.37, 124.59, 125.08, 125.21,
126.72, 129.89, 130.62, 130.85, 130.91, 131.63, 131.65,
131.77, 132.48, 140.54, 142.53, 146.97, 156.84, 158.67,
160.25, 160.65. MS: m/z = 365.15 (44.01) [M + 2]+, 363.15
6-Chloro-4-(2-fluorophenyl)-2-p-tolylquinoline (3m)
Mp 162 °C. IR (KBr): 3032, 2922, 2852, 1614, 1543, 1479,
1352, 1211, 1151, 887, 754 cm–1. 1H NMR (500 MHz,
CDCl3): d = 2.44 (s, 3 H), 7.27–7.35 (m, 4 H), 7.44 (s, 1 H),
7.53 (s, 1 H), 7.63–7.67 (m, 2 H), 7.85 (s, 1 H), 8.09 (d, J =
6.9 Hz, 2 H), 8.16 (d, J = 10.3 Hz, 1 H). 13C NMR (125
MHz, CDCl3): d = 22.69, 116.16, 116.34, 120.77, 124.33,
124.54, 126.54, 127.43, 129.64, 130.50, 130.76, 130.82,
131.67, 132.17, 136.28, 139.81, 142.47, 147.04, 157.02,
160.72. MS: m/z = 349.02 (35.04) [M + 2]+, 347.04 (100.00)
[M]+, 346.03 (78.57), 312.07 (21.21), 155.85 (21.88),
145.49 (19.42), 91.12 (6.92). Anal. Calcd for C22H15ClFN
(347.09): C, 75.97; H, 4.35; N, 4.03. Found: C, 75.85; H,
4.41; N, 3.95.
6-Nitro-4-phenyl-2-p-tolylquinoline (3n)
Mp 202–203 °C. IR (KBr): 2922, 2850, 1593, 1548, 1483,
1336, 1180, 819, 746 cm–1. 1H NMR (500 MHz, CDCl3):
d = 2.46 (s, 3 H), 7.37 (d, J = 8.0 Hz, 2 H), 7.56–7.64 (m,
5 H), 7.97 (s, 1 H), 8.16 (d, J = 8.0 Hz, 2 H), 8.32 (d, J =
9.2 Hz, 1 H), 8.48 (dd, 1J = 9.2 Hz, 2J = 2.5 Hz, 1 H), 8.85
(d, J = 2.5 Hz, 1 H). 13C NMR (125 MHz, CDCl3): d = 22.70,
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I. Mohammadpoor-Baltork et al.
LETTER
120.53, 122.91, 123.03, 124.74, 127.77, 129.13, 129.29,
129.48, 129.82, 131.67, 135.72, 137.02, 140.87, 145.30,
151.14, 159.99. MS: m/z = 340.07 (100.00) [M]+, 310.09
(7.43), 294.10 (25.54), 293.10 (60.75), 202.05 (24.60),
176.02 (45.16), 145.72 (38.17), 139.18 (19.35), 91.04
(11.96), 77.03 (8.60), 57.01 (50.54). Anal. Calcd for
C22H16N2O2 (340.12): C, 77.63; H, 4.74; N, 3.23. Found: C,
77.50; H, 4.80; N, 8.14.
8.9 Hz, 2J = 2.2 Hz, 1 H), 7.82 (s, 1 H), 8.15 (t, J = 9.0 Hz,
3 H). 13C NMR (125 MHz, CDCl3): d = 55.42, 114.32,
116.17, 116.34, 120.47, 124.33, 124.51, 124.54, 126.36,
126.54, 128.93, 130.49, 130.75, 130.82, 131.53, 131.62,
131.65, 131.97, 142.35, 156.61, 160.67, 161.13. MS:
m/z = 365.01 (25.00) [M + 2]+, 363.04 (96.00) [M]+, 362.02
(30.25), 319.00 (35.50), 285.09 (50.50), 149.12 (67.00),
141.42 (55.75), 99.00 (26.50), 95.20 (65.00), 85.21 (70.00),
83.19 (95.00), 81.19 (87.00), 77.15 (27.00), 57.21 (95.00),
55.17 (100.00). Anal. Calcd for C22H15ClFNO (363.08): C,
72.63; H, 4.16; N, 3.85. Found: C, 72.50; H, 4.21; N, 3.77.
2-(4-Methoxyphenyl)-6-nitro-4-phenylquinoline (3r)
Mp 221 °C. IR (KBr): 2922, 2852, 1643, 1593, 1479, 1253,
1095, 954, 796, 761 cm–1. 1H NMR (500 MHz, CDCl3): d =
3.91 (s, 3 H), 7.07 (d, J = 8.8, 2 H), 7.56–7.64 (m, 5 H), 7.94
(s, 1 H), 8.24 (d, J = 8.8 Hz, 2 H), 8.29 (d, J = 9.3 Hz, 1 H),
8.47 (dd, 1 H, 1J = 9.3 Hz, 2J = 2.5 Hz, 1 H), 8.80 (d, J =
2.5 Hz, 1 H). 13C NMR (125 MHz, CDCl3): d = 55.48,
114.48, 120.19, 122.92, 123.04, 124.54, 129.12, 129.26,
129.37, 129.45, 131.01, 131.48, 137.07, 145.15, 151.02,
151.20, 159.53, 161.81. MS: m/z = MS: 356.06 (100.00)
[M]+, 326.06 (2.85), 309.09 (25.00), 267.11 (6.84), 241.11
(5.38), 202.09 (8.29), 176.08 (12.95), 169.68 (8.10), 132.79
(16.58), 120.54 (9.20), 63.03 (8.00), 57.11 (4.81). Anal.
Calcd for C22H16N2O3 (356.12): C, 74.15; H, 4.53; N, 7.86.
Found: C, 74.29; H, 4.48; N, 7.78.
6-Chloro-2-(4-methoxyphenyl)-4-phenylquinoline (3o)
Mp 135–136 °C (Lit.10j 135 °C). IR (KBr): 2916, 2850,
1587, 1516, 1026, 825, 777, 704 cm–1. 1H NMR (500 MHz,
CDCl3): d = 3.89 (s, 3 H), 7.04 (d, J = 8.7 Hz, 2 H), 7.54–
7.57 (m, 5 H), 7.65 (dd, 1J = 9.1 Hz, 2J = 2.1 Hz, 1 H), 7.79
(s, 1 H), 7.84 (d, J = 2.2 Hz, 1 H), 8.14–8.18 (m, 3 H). 13
C
NMR (125 MHz, CDCl3): d = 55.42, 114.32, 119.55, 124.48,
126.26, 128.67, 128.81, 128.92, 129.46, 130.36, 131.50,
131.72, 131.80, 137.89, 147.22, 148.32, 156.60, 161.10.
MS: m/z = 347.02 (35.27) [M + 2]+, 345.03 (100.00) [M]+,
344.02 (52.05), 310.06 (9.08), 301.06 (7.79), 155.21
(21.32), 132.71 (33.22), 120.50 (8.82), 99.17 (2.70).
6-Chloro-4-(2-chlorophenyl)-2-(4-methoxyphenyl)
quinoline (3p)
Mp 140–141 °C. IR (KBr): 2958, 2852, 1602, 1541, 1469,
1373, 1247, 1157, 1022, 889, 771 cm–1. 1H NMR (500 MHz,
CDCl3): d = 3.89 (s, 3 H), 7.05 (d, J = 8.8 Hz, 2 H), 7.39 (dd,
1J = 7.3 Hz, 2J = 2.2 Hz, 1 H), 7.44–7.50 (m, 3 H), 7.61 (dd,
1J = 7.5 Hz, 2J = 1.4 Hz, 1 H), 7.65 (dd, 1J = 9.6 Hz, 2J =
2.2 Hz, 1 H), 7.78 (s, 1 H), 8.13–8.17 (m, 3 H).13C NMR
(125 MHz, CDCl3): d = 55.42, 120.10, 124.36, 126.27,
126.99, 128.94, 130.08, 130.50, 131.36, 131.52, 131.66,
131.92, 133.35, 136.49, 145.59, 146.99, 156.58, 161.14.
MS: m/z = 381.93 (17.57) [M + 2]+, 379.92 (39.53) [M]+,
378.93 (100.00), 343.96 (10.35), 265.02 (12.67), 176.09
(8.70), 154.29 (9.97), 132.51 (10.43), 99.14 (7.77), 57.12
(43.92), 55.13 (47.97). Anal. Calcd for C22H15Cl2NO
(379.05): C, 69.49; H, 3.98; N, 3.68. Found: C, 69.31; H,
4.05; N, 3.60.
4-Methyl-2-phenylquinoline (3s)
Mp 63–65 °C (Lit.10k 65–67 °C). IR (KBr): 2924, 2854,
1648, 1553, 1458, 1242, 1161, 950, 748 cm–1. 1H NMR (500
MHz, CDCl3): d = 2.72 (s, 3 H), 7.37–7.40 (m, 1 H), 7.44–
7.51 (m, 3 H), 7.65–7.72 (m, 2 H), 7.95 (d, J = 8.3 Hz, 1 H),
8.08–8.14 (m, 3 H). MS: m/z = 219.00(100) [M]+, 203.98
(12.68), 134.90 (48.59), 119.87 (67.61), 91.86 (80.28),
88.85 (78.87), 76.82 (85.21), 64.83 (83.80).
4-Methyl-2-p-tolylquinoline (3t)
Mp 53–54 °C (Lit.10l 51–53 °C). IR (KBr): 2925, 2854,
1658, 1615, 1462, 1245, 1162, 1112, 874, 754 cm–1. 1H
NMR (500 MHz, CDCl3): d = 2.44 (s, 3 H), 2.70 (s, 3 H),
7.30–733 (m, 2 H), 7.48–7.52 (m, 1 H), 7.69–7.74 (m, 2 H),
7.97 (d, J = 8.3 Hz, 1 H), 8.07–8.10 (m, 2 H), 8.15–8.18 (m,
1 H). MS: m/z = 233.00 (62.28) [M]+, 218.98 (60.53),
217.97 (35.53), 134.88 (30.26), 119.82 (53.95), 90.84
(75.00), 88.81 (84.65), 76.80 (67.54), 64.81 (100.00).
6-Chloro-4-(2-fluorophenyl)-2-(4-methoxyphenyl)
quinoline (3q)
Mp 121 °C. IR (KBr): 2924, 2852, 1608, 1463, 1355, 1253,
1174, 1022, 825, 761 cm–1. 1H NMR (500 MHz, CDCl3):
d = 3.90 (s, 3 H), 7.05 (d, J = 8.7, 2 H), 7.28–7.32 (m, 1 H),
7.35 (t, J = 7.3, 1 H), 7.44 (dt, 1J = 7.3 Hz, 2J = 1.7 Hz, 1 H),
7.51–7.56 (m, 1 H), 7.61 (d, J = 1.9 Hz, 1 H), 7.65 (dd, 1J =
Synlett 2010, No. 20, 3104–3112 © Thieme Stuttgart · New York

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