Molecular iodine-catalyzed and air-mediated tandem synthesis of quinolines via three-component reaction of amines, aldehydes, and alkynes

Article abstract of DOI:10.1016/j.tet.2011.03.087

A one-pot synthesis of quinolines via molecular iodine-catalyzed and air-mediated tandem condensation/imino-Diels-Alder/isomerization/oxidation of simple readily available amines, aldehydes, and alkynes has been developed. This methodology was extended to synthesize quinazolines from two molecules of amines and two molecules of glyoxalates.

Full text of DOI:10.1016/j.tet.2011.03.087

Tetrahedron 67 (2011) 3858e3862
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Tetrahedron
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Molecular iodine-catalyzed and air-mediated tandem synthesis of quinolines via
three-component reaction of amines, aldehydes, and alkynes
*
Xuejian Li, Zhenjun Mao, Yanguang Wang, Weixiang Chen, Xufeng Lin
Department of Chemistry, Zhejiang University, Zheda Road 38, Hangzhou 310027, China
a r t i c l e i n f o
a b s t r a c t
Article history:
A one-pot synthesis of quinolines via molecular iodine-catalyzed and air-mediated tandem condensa-
tion/imino-DielseAlder/isomerization/oxidation of simple readily available amines, aldehydes, and al-
kynes has been developed. This methodology was extended to synthesize quinazolines from two
molecules of amines and two molecules of glyoxalates.
Received 23 January 2011
Received in revised form 18 March 2011
Accepted 25 March 2011
Available online 31 March 2011
Ó 2011 Elsevier Ltd. All rights reserved.
Keywords:
Molecular iodine
Quinolines
Multicomponent reaction
Quinazolines
1. Introduction
derivatives in ionic liquid.5e All these methods are through strong
acid-catalyzed or metal-catalyzed sequential intermolecular addi-
Quinolines and their derivatives play an important role in or-
ganic chemistry, not only as key structural units in many natural
products and important pharmaceuticals but also as useful building
blocks for various biologically active molecules and functional ma-
terials.1 Consequently, synthesis of quinoline derivatives bearing
diverse substitution patterns has received much attention2 since
Skraup reported the classical method of quinoline synthesis in 1880
for the first time.3 Among these novel strategies for the synthesis of
quinolines, multicomponent reactions (MCRs) provides an easy
access to the preparation of quinoline derivatives, because multi-
component reactions (MCRs) have emerged as powerful and bond-
forming efficient tools in organic, combinatorial, and medicinal
chemistry.4 Recently, Tu developed the FeCl3-catalyzed three-
component coupling-/hydroarylation/dehydrogenation of alde-
hydes, alkynes, and amines for the synthesis of 2, 4-disubstituted
quinolines.5a Wang reported a sequential catalytic process for the
synthesis of quinolines by AuCl3/CuBr-catalyzed MCR strategy.5b Liu
synthesized the quinoline-2-carboxylates using Cu(OTf)2-catalyzed
tandem Grignard-type imine addition/FriedeleCrafts alkenylation
of arenes with alkynes.5c Guchhait described the synthesis of
polysubstituted quinolines via (HClO4)-modified montmorillonite-
catalyzed Povarov reaction.5d Nagarajan reported CuI/La(OTf)3 cat-
alyzed, one-pot three-component synthesis of isomeric ellipticine
tion of alkynes onto imines and subsequent intramolecular ring
closure by arylation. Considering the continued importance of the
quinoline core in both biological and chemical fields, new direct
approaches remain highly valuable to the contemporary collection
of synthetic methods.
Recently, molecular iodine has received considerable attention
as an inexpensive and readily available catalyst for various organic
transformations due to its moderate Lewis acidity and water-tol-
erance.6 Previously, we reported several molecular iodine-catalyzed
organic reactions.7 In continuation of our efforts to develop novel
MCRs and domino reaction strategy on heterocyclic synthesis,8
herein we report a metal-free and one-pot three-component syn-
thesis of quinolines under mild reaction conditions. This has been
done by assembling the quinoline core via molecular iodine-cata-
lyzed and air-mediated tandem condensation/imino-DielseAlder/
isomerization/oxidation of simple readily available amines, alde-
hydes, and alkynes.
2. Results and discussion
Exhaustive studies of the reaction conditions for the synthesis of
quinoline 4a from p-methoxyphenyl amine 1a with ethyl glyoxalate
2a and phenylacetylene 3a in the presence of molecular iodine
were conducted (Table 1). We examined several organic solvents,
which are commercially available and used without further puri-
fication or drying. We found that a remarkable solvent effect exis-
ted in 10 mol % iodine-catalyzed reaction at room temperature.
* Corresponding author. Tel.: þ86 571 87952759; fax: þ86 571 87953816; e-mail
address: lxfok@zju.edu.cn (X. Lin).
0040-4020/$ e see front matter Ó 2011 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2011.03.087

X. Li et al. / Tetrahedron 67 (2011) 3858e3862
3859
aldehydes 2, and alkynes 3, and the results were presented in
Table 2. First, we examined the scope of alkynes in this reaction,
and it was found that substituted phenylacetylenes 3aec were
suitable substrates for this transformation, and the expected
products were obtained in good yields (Table 2, entries 1e3). Then,
the versatility of this transformation was assessed by altering al-
dehydes 2 (Table 2, entries 1 and 6e12). Isolated yield was tuned by
the property of the substituted groups on compound 2. In case of
aromatic aldehydes, the reaction was carried out under reflux.
Except in case of 4-nitrobenzaldehyde, when the aromatic alde-
hyde carried an electron-donating group or an electro-
nwithdrawing group, isolated yields were comparable to those of
the ethyl glyoxalate case. It is noted that hydroxyl group on aro-
matic ring was well tolerated (Table 2, entries 10 and 14). When
aliphatic aldehyde 2h was used instead of aromatic ones, product 4l
was isolated with low yield (32%; Table 2, entry 12).
Subsequently, we investigated the scope of aromatic amines
(Table 2, entries 1, 4e5, 13, and 14). It can be seen that the reactions
proceeded smoothly to give the corresponding quinolines in
moderate to good yields when the aromatic amine carried an
electron-donating group or an electronwithdrawing group, except
that in cases of 4-nitroaniline, lower yield was obtained for 4e (45%;
Table 2, entry 5). Polycyclic aromatic amines, such as naphthalene-
2-amine 1f and 9-ethyl-carbazol-3-amine 1g produced benzo[f]
quinoline 4o (70% yield) and isomeric ellipticine 4p (68% yield),
respectively in the one-pot three-component reaction (Scheme 1).
Table 1
Optimization of reaction conditionsa
Entry
Iodine (mol %)
Solvent
T
t/h
Yieldb (%)
1
2
3
4
5
6
7
8
9
10
10
10
10
10
10
10
15
5
MeCN
PhMe
THF
DCM
EtOH
MeNO2
MeNO2
MeNO2
MeNO2
MeNO2
rt
rt
rt
rt
rt
rt
Reflux
rt
rt
12
24
24
24
24
12
6
7
24
24
75
65
68
53
44
82
74
83
65
0
10
0
rt
a
All the reactions were carried out using 1a (1 mmol), 2a (1 mmol), and 3a
(1.5 mmol) in 2 mL solvent.
b
Isolated yields.
These results showed that nitromethane was the most suitable
solvent for this transformation among others, such as acetonitrile,
toluene, THF, DCM, and EtOH (Table 1, entries 1e6). When the
model reaction was carried out under reflux, reduced yield was
observed (Table 1, entry 7). Furthermore, the reaction was accel-
erated when the amount of catalyst was increased to 15 mol %, but
the yield was not improved (Table 1, entry 8). When the reaction
was catalyzed by 5 mol % iodine, the reaction time was prolonged to
24 h and the desired product 4a was obtained with only 65% (Table
1, entry 9). While no quinoline product 4a was obtained in the
absence of molecular iodine (Table 1, entry 10). Thus, the most
suitable reaction conditions for the formation of 4a were estab-
lished (Table 1, entry 6). It is noteworthy that the metal-free re-
action proceeded smoothly without exclusion of moisture or air.
To reveal the generality of this method, we next explored the
protocol with a variety of simple readily available amines 1,
Table 2
Three-component synthesis of quinolinesa
Scheme 1.
To probe the reaction mechanism of the iodine-catalyzed tan-
dem synthesis of quinolines, propargylamine 5, which is identified
as the key intermediate in metal-catalyzed synthesis of quinolines,5
was treated with 20 mol % iodine in MeNO2 at room temperature or
under reflux for 12 h, but 4a was not observed and all of 5 was
recovered (Scheme 2). Furthermore, in case of disubstituted alkyne
3d, the 10 mol % iodine-catalyzed tandem reaction gave the desi-
red quinoline 4q with 83% yield at room temperature for 12 h
(Scheme 3). Thus the use of alkyne as a dienophile is suitable in this
reaction and the key-step of the mechanism may be an imino-
DielseAlder reaction.
Entry R1
R2
R3
Product Yieldb (%)
1
4-MeO (1a) CO2Et (2a)
1a
1a
Ph (3a)
3-BrPh (3b) 4b
4-MePh (3c) 4c
3a
3a
3a
3a
3a
3a
3a
4a
82
65
73
60
45
71
75
80
41
70
77
32
61
63
2c
3
2a
2a
2a
4
4-Cl (1b)
4d
4e
4f
5
4-NO2 (1c) 2a
6c
7c
8c
9c
10c
11c
1a
1a
1a
1a
1a
1a
Ph (2b)
4-MePh (2c)
4-BrPh (2d)
4-NO2Ph (2e)
2-OHPh (2f)
3,4-(eOCH2Oe)Ph (2g) 3a
H (2h)
2b
4g
4h
4i
4j
4k
4l
12c,d 1a
3a
3a
3a
13c
14c
H (1d)
4-Me (1e)
4m
4n
2f
a
All the reactions were carried out using 1 (1 mmol), 2 (1 mmol), 3 (1.5 mmol),
and iodine (0.1 mmol) in 2 mL MeNO2 at rt for 12 h.
b
Isolated yields.
Under reflux.
Using Paraformaldehyde (1.5 mmol).
c
d
Scheme 2.

3860
X. Li et al. / Tetrahedron 67 (2011) 3858e3862
3. Conclusion
In conclusion, we have developed a molecular iodine-catalyzed
and air-mediated tandem synthesis of quinolines starting from
simple readily available amines, aldehydes, and alkynes. This has
been done by assembling the quinoline core via one-pot and three-
component reaction from [3þ2þ1] atom fragments by formation of
three new bonds. This methodology is extended to the ready access
to quinazoline derivatives.
Scheme 3.
Based on the experimental results above and together with our
previous work,7 we think that molecular iodine catalyzes the re-
action as a mild Lewis acid. Thus, we propose a possible mechanism
as shown in Scheme 4. The first step is the formation of the in-
termediate identified by the experiment in the preceding course,
namely Schiff base A formed by the condensation of amine 1 with
aldehyde 2. And then imino-DielseAlder reaction between the io-
dine-activated Schiff base A and alkyne dienophile 3 proceeds to
afford intermediate B, followed by isomerization to dihy-
droquinoline C, which is subsequently oxidized by O2 in air to give
the final quinoline product 4.
4. Experimental section
4.1. General
Melting points were obtained on a microscopical instrument
and uncorrected. NMR spectra were recorded at 400 MHz spec-
trometer and TMS as internal standard. IR spectra were recorded on
an FT-IR spectrometer. Low-resolution MS was obtained using ESI
ionization. HRMS data were obtained using EI ionization. All re-
agents and solvents used were commercially available. Column
chromatography was carried out on silica gel (300e400 mesh) with
mixed solvents (hexane/ethyl acetate).
4.2. General procedure for the synthesis of quinoline 4
After amine 1 (1 mmol) and aldehyde 2 (1 mmol) were dissolved
in CH3NO2 (2 mL), alkyne 3 (1.5 mmol), and iodine (0.1 mmol) were
added, and the solution was stirred at room temperature or under
reflux for 12 h. Then the reaction mixture was diluted with ethyl
acetate and washed with a solution of sodium thiosulfate followed
by water. The organic phase was dried over anhydrous Na2SO4, and
evaporation of the solvent followed by purification on silica gel
afforded pure desired quinoline 4.
4.3. General procedure for the synthesis of quinazoline 6
Scheme 4.
After amine 1 (1 mmol) and ethyl glyoxylate 2a (1 mmol) were
dissolved in CH3NO2 (2 mL), iodine (0.1 mmol) were added, and the
solution was stirred at 50 ꢀC for 12 h. Then the reaction mixture was
diluted with ethyl acetate, and washed with a solution of sodium
thiosulfate followed by water. The organic phase was dried over
anhydrous Na2SO4, and evaporation of the solvent followed by
purification on silica gel afforded pure desired quinazoline 6.
One interesting extension of this methodology is the ready ac-
cess to quinazoline derivatives. We investigated the possibility of
iodine-catalyzed intermolecular annulation of
a-iminoester gen-
erated in situ by condensation of aniline and ethyl glyoxalate, as
shown in Scheme 5. When anilines 1a and 1e were treated with 2a
in the presence of 10 mol % iodine in MeNO2 at 50 ꢀC for 12 h,
quinazolines 6a and 6b were obtained in 78% yield and 70% yield,
respectively. The tandem reaction involves iodine-catalyzed imino-
DielseAlder cyclization and air-mediated oxidation reaction. This
one-step and metal-free strategy for access substituted quinazo-
line, which is potentially useful scaffold for the synthesis of bi-
ologically active compounds,9 is concise and efficient.
4.4. Characterization data
4.4.1. Ethyl 6-methoxy-4-phenylquinoline-2-carboxylate (4a)5c. Yellow
solid, mp 146e147 ꢀC; IR (KBr)
n
1730, 1619, 1492, 1473, 1366, 1224,
1107, 1027, 841, 763, 708 cmꢁ1; 1H NMR (400 MHz, CDCl3)
d
8.20 (d,
J¼9.2 Hz, 1H), 8.02 (s, 1H), 7.42e7.51 (m, 5H), 7.36 (dd, J¼3.2 Hz,
J¼2.4 Hz, 1H), 7.14 (d, J¼2.4 Hz, 1H), 4.48 (q, J¼7.2 Hz, 2H), 3.74 (s,
3H), 1.41 (t, J¼7.2 Hz, 3H) ppm; 13C NMR (100 MHz, CDCl3)
d 165.59,
159.49, 147.99, 145.38, 144.32, 137.90, 132.68, 129.27, 129.15, 128.72,
128.58, 122.72, 121.75, 103.30, 62.02, 55.46, 14.37 ppm; MS (ESI): m/
z ([MþH]þ): 308.
4.4.2. Ethyl 4-(3-bromophenyl)-6-methoxyquinoline-2-carboxyl-ate
(4b). Yellow solid, mp 156e157 ꢀC; IR (KBr)
n
1715,1620,1586,1547,
1481, 1438, 1222, 1127, 1107, 1022, 834 cmꢁ1 1H NMR (400 MHz,
CDCl3)
;
d
8.28 (d, J¼9.2 Hz, 1H), 8.07 (s, 1H), 7.70e7.71 (m, 1H),
7.63e7.66 (m, 1H), 7.41e7.49 (m, 3H), 7.14 (d, J¼2.8 Hz, 1H), 4.56 (q,
J¼6.8 Hz, 2H), 3.83 (s, 3H), 1.49 (t, J¼6.8 Hz, 3H) ppm; 13C NMR
(100 MHz, CDCl3)
d 165.39, 159.71, 146.19, 145.33, 144.27, 139.87,
132.80, 132.21, 131.66, 130.24, 128.79, 127.89, 122.89, 122.85, 121.67,
102.89, 62.10, 55.52, 14.36 ppm; MS (ESI): m/z ([MþH]þ): 386;
HRMS (EI): m/z calcd for (C19H16BrNO3): 385.0314; found: 385.0304.
Scheme 5.

X. Li et al. / Tetrahedron 67 (2011) 3858e3862
3861
4.4.3. Ethyl 6-methoxy-4-p-tolylquinoline-2-carboxylate (4c)5c. Yellow
solid, mp 145e146 ꢀC; IR (KBr)
1712, 1621, 1508, 1473, 1374, 1245,
1178,1026, 827 cmꢁ1; 1H NMR (400 MHz, CDCl3)
7.42e7.45 (m, 1H), 7.20(d, J¼2.4 Hz, 1H), 3.82 (s, 3H); 13C NMR
n
(100 MHz, CDCl3) d 158.54, 151.64, 148.33, 148.08, 145.57, 144.95,
d
8.26 (d, J¼9.2 Hz,
138.27, 131.82, 129.26, 128.81, 128.62, 127.92, 127.26, 123.98, 122.56,
119.38, 103.59, 55.48 ppm; MS (ESI): m/z ([MþH]þ): 357; HRMS
(EI): m/z calcd for (C22H16N2O3): 356.1161; found: 356.1146.
1H), 8.08 (s, 1H), 7.41e7.46 (m, 3H), 7.34e7.37 (m, 2H), 7.25
(d, J¼2.4 Hz,1H), 4.55 (q, J¼6.8 Hz, 2H), 3.82 (s, 3H), 2.48 (s, 3H),1.48
(t, J¼6.8 Hz, 3H) ppm; 13C NMR (100 MHz, CDCl3)
d 165.56, 159.35,
147.98, 145.34, 144.27, 138.44, 134.89, 132.59, 129.37, 129.16, 129.17,
122.59, 121.65, 103.28, 61.89, 55.39, 21.19, 14.30 ppm; MS (ESI): m/z
([MþH]þ): 322.
4.4.10. 2-(6-Methoxy-4-phenylquinolin-2-yl)phenol (4j). Yellow solid,
mp 158e159 ꢀC; IR (KBr)
n
1621, 1586, 1509, 1494, 1429, 1270, 1218,
1122, 1035, 756, 701 cmꢁ1
;
1H NMR (400 MHz, CDCl3)
d
15.13 (s,
1H), 7.99 (d, J¼9.2 Hz, 1H), 7.92e7.93 (m, 2H), 7.56e758 (m, 5H),
7.33e7.41 (m, 2H), 7.17 (d, J¼2.4 Hz, 1H), 7.10 (d, J¼8 Hz, 1H), 6.93 (t,
4.4.4. Ethyl 6-chloro-4-phenylquinoline-2-carboxylate (4d). White
J¼7.2 Hz, 1H), 3.80(s, 3H) ppm; 13C NMR (100 MHz, CDCl3)
d 157.78,
solid, mp 179e180 ꢀC; IR (KBr)
n
1736, 1604, 1484, 1451, 1387, 1234,
1143, 1114, 1020, 840, 705 cmꢁ1
;
1H NMR (400 MHz, CDCl3)
d
8.31
154.60, 147.77, 144.87, 139.72, 138.72, 138.71, 131.57, 131.56, 129.32,
128.93, 128.74, 128.65, 128.30, 127.27, 126.63, 121.76, 119.60, 103.71,
55.40 ppm; MS (ESI): m/z ([MþH]þ): 328; HRMS (EI): m/z calcd for
(C22H17NO2): 327.1259; found: 327.1263.
(m, 1H), 8.14 (d, J¼5.2 Hz, 1H), 7.92 (d, J¼4.4 Hz, 1H), 7.69e7.74 (m,
1H), 7.51e7.57 (m, 5H), 4.53e4.60 (q, J¼7.2 Hz, 2H), 1.46e1.51
(t, J¼7.2 Hz, 3H) ppm; 13C NMR (100 MHz, CDCl3)
d 165.09, 149.01,
147.94, 146.51, 136.83, 134.76, 132.65, 131.00, 129.37, 128.95, 128.83,
128.38, 124.48, 121.96, 62.29, 14.30 ppm; MS (ESI): m/z ([MþH]þ):
312; HRMS (EI): m/z calcd for (C18H14ClNO2): 311.0713; found:
311.0712.
4.4.11. 2-(Benzo[d][1,3]dioxol-5-yl)-6-methoxy-4-phenylquinoline
(4k). Yellow solid, mp 135e136 ꢀC; IR (KBr)
n
1626, 1603, 1491,
1454, 1335, 1249, 1104, 1033, 968, 922, 815 cmꢁ1 1H NMR
(400 MHz, CDCl3)
;
d
8.09 (d, J¼9.2 Hz, 1H), 7.73 (s, 1H), 7.68 (s, 1H),
7.63 (q, J¼1.6 Hz, 1H), 7.51e7.55(m, 5H), 7.37 (q, J¼2.8 Hz, 1H), 7.16
(d, J¼2.8 Hz, 1H), 6.91 (d, J¼8 Hz, 1H), 6.02 (s, 2H), 3.78(s, 3H) ppm;
4.4.5. Ethyl 6-nitro-4-phenylquinoline-2-carboxylate (4e). Yellow
solid, mp 204e205 ꢀC; IR (KBr) v 1716, 1619, 1534, 1502, 1344, 1257,
13C NMR (100 MHz, CDCl3)
d 157.63, 154.01, 148.52, 148.35, 147.71,
1140, 1110, 848, 785, 707 cmꢁ1 1H NMR (400 MHz, CDCl3)
; d 8.92
144.77, 138.73, 134.24, 131.40, 129.32, 128.66, 128.30, 126.43, 121.71,
121.33, 119.24, 108.41, 107.70, 103.76, 101.27, 55.42 ppm; MS (ESI):
m/z ([MþH]þ): 356; HRMS (EI): m/z calcd for (C23H17NO3):
355.1208; found: 355.1197.
(s,1H), 8.53 (s, 2H), 8.27 (s,1H), 7.56e7.62 (m, 5H), 4.59 (q, J¼5.2 Hz,
2H), 1.51(t, J¼5.2 Hz, 3H) ppm; 13C NMR (100 MHz, CDCl3)
d 164.71,
152.32, 150.80, 150.17, 146.87, 136.02, 133.02, 129.70, 129.49, 129.25,
126.88, 123.42, 122.76, 122.65, 62.78, 14.33 ppm; MS (ESI): m/z
([MþH]þ): 323; HRMS (EI): m/z calcd for (C18H14N2O4): 322.0954;
found: 322.0946.
4.4.12. 6-Methoxy-4-phenylquinoline (4l)2o. Yellow liquid; IR (neat)
n
3058, 2925, 1619, 1584, 1493, 1428, 1256, 1032, 1030,853 cmꢁ1; 1H
4.4.6. 6-Methoxy-2,4-diphenylquinoline (4f)5. Yellow solid, mp
NMR (400 MHz, CDCl3)
1H), 7.46e7.55 (m, 5H), 7.38 (d, J¼8.8 Hz, 1H), 7.27 (d, J¼4.4 Hz, 1H),
7.19 (s, 1H), 3.77 (s, 3H) ppm; 13C NMR (100 MHz, CDCl3)
157.80,
d
8.78 (d, J¼4.8 Hz, 1H), 8.07 (d, J¼9.2 Hz,
119e120 ꢀC; IR (KBr)
n
2362, 2341,1616,1588,1545,1487,1357,1221,
1025, 836, 695 cmꢁ1
;
1H NMR (400 MHz, CDCl3)
d
8.13e8.16 (m,
d
3H), 7.76 (s, 1H), 7.48e7.58 (m, 7H), 7.37e7.44 (m, 2H), 7.18 (d,
147.41, 147.01, 144.71, 138.25, 131.15, 129.20, 128.57, 128.26, 127.61,
J¼2.8 Hz, 1H), 3.78 (s, 3H); 13C NMR (100 MHz, CDCl3)
d
158.07,
121.65, 121.57, 103.63, 55.30 ppm; MS (ESI): m/z ([MþH]þ): 236.
155.13, 148.79, 141.09, 138.22, 131.47, 129.39, 129.22, 128.77, 128.65,
126.58, 122.32, 119.15, 118.46, 118.48, 117.87, 104.19, 55.46 ppm; MS
(ESI): m/z ([MþH]þ): 312.
4.4.13. 2,4-Diphenylquinoline (4m)5a. Light yellow liquid; IR (neat)
n
1634, 1588, 1519, 1489, 1446, 1343, 1260, 967, 768, 701, 590 cmꢁ1
;
1H NMR (400 MHz, CDCl3)
2H), 7.90 (d, J¼8.0 Hz, 1H), 7.82 (s, 1H), 7.70e7.75 (m, 1H), 7.45e7.56
(m, 9H) ppm; 13C NMR (100 MHz, CDCl3)
156.89, 149.18, 148.82,
d
8.24(d, J¼8.4 Hz, 1H), 8.19 (d, J¼6.8 Hz,
4.4.7. 6-Methoxy-4-phenyl-2-p-tolylquinoline (4g). Yellow solid;
mp 136e137 ꢀC; IR (KBr)
n
1617, 1590, 1546, 1488, 1394, 1222, 1113,
1027, 834, 781, 706 cmꢁ1 1H NMR (400 MHz, CDCl3)
8.05e8.25(m, 3H), 7.74 (s, 1H), 7.46e7.59 (m, 5H), 7.28e7.37 (m,
3H), 7.17 (s, 1H), 3.76 (s, 3H), 2.40 (s, 3H) ppm; 13C NMR (100 MHz,
CDCl3) 157.59, 154.52, 147.59, 144.83, 138.88, 138.74, 138.86,
d
;
139.66, 138.41, 130.12, 129.55, 129.50, 129.33, 128.81, 128.58, 128.39,
127.59, 126.31, 125.78, 125.63, 119.35 ppm; MS (ESI): m/z ([MþH]þ):
282.
d
d
136.45, 131.45, 129.44, 129.29, 128.59, 128.22, 127.09, 121.60, 119.38,
103.68, 55.32, 21.23 ppm; MS (ESI): m/z ([MþH]þ): 326; HRMS (EI):
m/z calcd for (C23H19NO): 325.1467; found: 325.1456.
4.4.14. 2-(6-Methyl-4-phenylquinolin-2-yl)phenol (4n). Yellow solid,
mp 190e191 ꢀC; IR (neat)
n
1587, 1546, 1492, 1418, 1355, 1295, 1246,
877, 853, 754, 708 cmꢁ1; 1H NMR (400 MHz, CDCl3)
d¼15.26 (s, 1H),
7.95 (d, J¼8.8 Hz, 1H), 7.89e7.91 (m, 2H), 7.60 (s, 1H), 7.50e7.57 (m,
6H), 7.30e7.34 (m, 1H), 7.06e7.09 (m, 1H), 6.90 (t, J¼8 Hz, 1H), 2.44
4.4.8. 2-(4-Bromophenyl)-6-methoxy-4-phenylquinoline
(4h). Yellow solid; mp 135e136 ꢀC; IR (KBr)
n
1617, 1589, 1544,
1488,1356,1224,1071,1027, 827, 767, 704 cmꢁ1; 1H NMR (400 MHz,
CDCl3)
(s, 3H) ppm; 13C NMR (100 MHz, CDCl3)
d 160.98, 156.49, 149.41,
143.68, 138.10, 136.69, 132.38, 131.71, 129.38, 128.63, 128.57, 127.63,
126.76, 125.24, 124.59, 119.03, 118.58, 118.51, 117.51, 21.72 ppm; MS
(ESI): m/z ([MþH]þ): 312; HRMS (EI): m/z calcd for (C22H17NO):
311.1310; found: 311.1306.
d
8.07 (d, J¼9.2 Hz, 1H), 7.99 (d, J¼8.8 Hz, 2H), 7.66 (s, 1H),
7.56 (d, J¼8.8 Hz, 2H), 7.43e7.57 (m, 5H), 7.34 (q, J¼6.8 Hz, 1H),
7.13(d, J¼2.8 Hz, 1H), 3.74(s, 3H) ppm; 13C NMR (100 MHz, CDCl3)
d
151.94, 153.16, 147.93, 144.85, 138.55, 131.85, 131.56, 130.28,
4.4.15. 1,3-Diphenylbenzo[f]quinoline (4o)2p
148e149 ꢀC; IR (KBr)
1579, 1544, 1447, 1359, 1256, 1159, 1072,
1026, 834, 748, 694 cmꢁ1; 1H NMR (400 MHz, CDCl3)
8.03 (s, 1H),
8.00 (s, 1H), 7.60 (s, 1H), 7.43e7.57 (m, 13H), 7.26 (d, J¼1.2 Hz, 1H)
ppm; 13C NMR (100 MHz, CDCl3)
155.39, 149.78, 149.15, 143.01,
139.00, 132.90, 131.47, 129.72, 129.29, 129.21, 129.10, 128.82, 128.60,
128.37, 128.11, 128.02, 127.38, 126.43, 125.51, 122.77, 121.80 ppm;
MS (ESI): m/z ([MþH]þ): 332.
.
Yellow solid, mp
129.30, 128.77, 128.70,128.41, 126.75, 123.44,122.00, 119.05, 103.68,
55.42 ppm; MS (ESI): m/z ([MþH]þ): 390; HRMS (EI): m/z calcd for
(C22H16BrNO): 389.0415; found: 389.0421.
n
d
4.4.9. 6-Methoxy-2-(4-nitrophenyl)-4-phenylquinoline (4i)3. Light
d
yellow solid, mp 100e101 ꢀC; IR(KBr)
n
1707, 1602, 1512, 1342, 1244,
1196, 1105, 1034, 851, 819, 740 cmꢁ1
;
1H NMR (400 MHz, CDCl3)
d
8.35 (s, 4H), 8.16 (d, J¼9.2 Hz, 1H), 7.81 (s, 1H), 7.51e7.58 (m, 5H),

3862
X. Li et al. / Tetrahedron 67 (2011) 3858e3862
4.4.16. 7-Ethyl-1,3-diphenyl-7H-pyrido[2,3-c]carbazole
(4p)2q. Yellow solid, mp 197e198 ꢀC; IR (KBr)
1613, 1555, 1515,
1488,1407,1329,1145,1097, 794, 741, 687 cmꢁ1; 1H NMR (400 MHz,
CDCl3)
Supplementary data
n
Copies of the 1H, 13C NMR spectra. Supplementary data associ-
ated with this article can be found in the online version at
doi:10.1016/j.tet.2011.03.087.
d
8.29 (d, J¼8.8 Hz, 1H), 8.24 (d, J¼7.6 Hz, 2H), 7.90(s, 1H),
7.85 (d, J¼8.8 Hz, 1H), 7.48e7.56 (m, 4H), 7.33e7.43 (m, 4H), 7.34 (d,
J¼7.6 Hz, 1H), 7.20 (q, J¼7.6 Hz, 1H), 6.64 (t, J¼8.0 Hz, 1H), 6.06 (d,
J¼8 Hz, 1H), 4.40 (q, J¼7.2 Hz, 2H), 1.43 (t, J¼7.2 Hz, 3H) ppm; 13C
References and notes
NMR (100 MHz, CDCl3)
d 152.72, 146.55, 146.37, 142.78, 139.57,
138.83, 138.40, 129.46, 129.40, 129.06,128.72,128.08, 127.18, 124.95,
123.72, 123.25, 122.25, 121.12, 118.53, 114.39, 114.04, 108.26, 37.54,
14.17 ppm; MS (ESI): m/z ([MþH]þ): 399.
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4.4.17. Triethyl 6-methoxyquinoline-2,3,4-tricarboxylate (4q). Light
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yellow liquid; IR (neat)
n
2983, 1733, 1620, 1561, 1498, 1420,
1302, 1062, 1024, 836 cmꢁ1
;
1H NMR (400 MHz, CDCl3)
d
8.16
(d, J¼7.6 Hz, 1H), 7.50 (m, 1H), 7.34 (s, 1H), 4.52e4.56 (m, 4H),
4.43 (q, J¼7.2 Hz, 2H), 3.94 (s, 3H), 1.38e1.46 (m, 9H) ppm; 13C
NMR (100 MHz, CDCl3)
d 165.83, 165.57, 165.27, 160.35, 145.08,
143.80, 137.55, 131.95, 125.43, 124.88, 124.27, 102.69, 62.39,
62.36, 62.21, 55.59, 14.03, 13.92, 13.80 ppm; MS (ESI): m/z
([MþH]þ): 376; HRMS (EI): m/z calcd for (C19H21NO7): 375.1318;
found: 375.1324.
4.4.18. Diethyl 6-methoxy-3-(4-methoxyphenyl)-3,4-dihydroquinaz-
oline-2,4-dicarboxylate (6a)9c. Red liquid; IR (neat)
n
2991, 1754,
1719, 1618, 1560, 1508, 1244, 1177, 1027, 832 cmꢁ1 1H NMR
(400 MHz, CDCl3)
;
d
7.36 (d, J¼8.0 Hz, 1H), 7.06e7.09 (m, 2H),
6.85e6.90 (m, 3H), 6.74 (d, J¼2.4 Hz, 1H), 5.31 (s, 1H), 4.11e4.24 (m,
4H), 3.80 (s, 3H), 3.79 (s, 3H), 1.24 (t, J¼6.8 Hz, 3H), 1.06 (t, J¼6.8 Hz,
3H) ppm; 13C NMR (100 MHz, CDCl3)
d 169.69,162.37,158.61,158.11,
145.68, 136.59, 133.49, 127.14, 125.16, 121.12, 114.90, 114.43, 111.36,
63.84, 61.85, 61.78, 55.43, 55.38, 13.92, 13.59 ppm; MS (ESI): m/z
([MþH]þ): 413.
4.4.19. Diethyl
carboxylate (6b)9c. Yellow liquid; IR (neat)
1585, 1513, 1381, 1291, 1257, 1189, 1022, 827 cmꢁ1
(400 MHz, CDCl3)
6-methyl-3-p-tolyl-3,4-dihydroquinazoline-2,4-di-
2981, 1740, 1619,
1H NMR
n
;
d
7.32 (d, J¼8.0 Hz, 1H), 7.14 (m, 3H), 7.03 (s,
1H), 6.99 (d, J¼7.6 Hz, 2H), 5.32 (s, 1H), 4.12e4.27 (m, 4H), 2.33
(s, 3H), 2.31 (s, 3H), 1.23 (t, J¼7.2 Hz, 3H), 1.06 (t, J¼7.2 Hz, 3H)
ppm; 13C NMR (100 MHz, CDCl3)
d 169.94, 162.45, 146.53, 141.10,
137.55, 137.16, 136.18, 130.19, 129.88, 126.77, 125.79, 122.92,
120.28, 63.44, 61.93, 61.88, 21.06, 20.85, 13.94, 13.57 ppm; MS
(ESI): m/z ([MþH]þ): 381.
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Acknowledgements
The authors thank the National Natural Science Foundation
of China (No. 20702047 and 21032005) and Zhejiang Provincial
Natural Science Foundation of China (Y4090028 and R407106) for
financial support of this research.