Facile one-pot synthesis of polysubstituted quinolines under solvent-free conditions using sulfamic acid as a reusable catalyst

Article abstract of DOI:10.1007/s00706-011-0590-7

A facile one-pot synthesis of polysubstituted quinoline derivatives has been demonstrated by using sulfamic acid as a reusable catalyst under solvent-free conditions. The synthetic method provides the basis and advantages of a simple experimental procedure and easy recovery and reuse of catalyst, which makes it a highly practical and environmentally benign pathway for the synthesis of polysubstituted quinolines. Interestingly, this one-pot synthesis could produce the products regioselectively in the presence of dis-symmetrical arylamines.

Full text of DOI:10.1007/s00706-011-0590-7

Monatsh Chem (2012) 143:471–478
DOI 10.1007/s00706-011-0590-7
ORIGINAL PAPER
Facile one-pot synthesis of polysubstituted quinolines
under solvent-free conditions using sulfamic acid
as a reusable catalyst
•
Min Zhang Biao Xiong Wei Yang
•
•
•
D. N. T. Kumar Yu-Qiang Ding
Received: 14 July 2010 / Accepted: 15 July 2011 / Published online: 19 August 2011
Ó Springer-Verlag 2011
Abstract A facile one-pot synthesis of polysubstituted
quinoline derivatives has been demonstrated by using sul-
famic acid as a reusable catalyst under solvent-free
conditions. The synthetic method provides the basis and
advantages of a simple experimental procedure and easy
recovery and reuse of catalyst, which makes it a highly
practical and environmentally benign pathway for the
synthesis of polysubstituted quinolines. Interestingly, this
one-pot synthesis could produce the products regioselec-
tively in the presence of dis-symmetrical arylamines.
chemosensors [13]. Considering these significant properties
and functions, the development of effective methods to
construct functionalized quinolines has been attracting
great attention. Further, the classical reactions, such as
Skraup [14], Friedlander [15], Combes [16], and Doebner-
Von Miller reactions [17], were reported over a century
ago, and additionally remarkable new protocols were also
extensively studied by providing new access to function-
alized quinolines in recent years, for example, involving
the cyclization reactions from ortho-nitrogen-containing
substrates [18, 19], cascade multicomponent reactions [20,
21], imino Diels-Alder reactions (Povarov-type reaction)
[22], and condensation-cyclization reactions from o-halo-
acetophenones [23]. However, many of these synthetic
methodologies still suffer from various drawbacks such as
complicated reaction conditions, lack of readily available
starting materials, requirement of multi-step processes, or
excessive use of reagents leading to tedious laboratory
procedures.
Keywords Multicomponent reaction ꢀ Heterocylces ꢀ
Reusable sulfamic acid catalyst ꢀ Solvent-free conditions ꢀ
Eliminations and oxidations
Introduction
Quinoline and its analogues represent a very important
class of nitrogen-containing heterocycles because of their
wide spectrum of biological and pharmaceutical activities
such as anti-malaria [1], anti-leishmania [2], anti-bacteria
[3], anti-asthma [4], anti-inflammation [5], anti-hyperten-
sion [6], tyrokinase inhibitor [7], histamine H3 receptor
inverse agonists [8], and therapeutic agents for estrogen-
dependent diseases [9]. In addition, quinoline derivatives
were widely employed as key intermediates for the man-
ufacturing of functionalized materials [10–12] and
It was noteworthy that the cross-coupling reactions
between aliphatic aldehydes and imines provided easier
pathways for the synthesis of quinoline derivatives; how-
ever, a key pretreatment step was required to form the
imines originally [24, 25]. However, the condensation
reaction of two molecules of aldehydes and one molecule
of arylamine showed a direct approach in achieving this
goal [26, 27], but the employed catalysts were generally
destroyed during the workup procedures and could not be
recovered or reused.
Considering the drawbacks arising from the usage of the
above-mentioned methods, the search for an effective
catalytic process along with eco-compatible preparation of
quinolines from readily available starting materials is of
great importance. In the past decade, the application of
sulfamic acid (NH2SO3H, SA) in catalysis has attracted
M. Zhang (&) ꢀ B. Xiong ꢀ W. Yang ꢀ
D. N. T. Kumar ꢀ Y.-Q. Ding
School of Chemical and Materials Engineering,
Jiangnan University, 1800 Lihu Road, 214122 Wuxi,
Jiangsu, People’s Republic of China
e-mail: zm31289@yahoo.com.cn
123

472
M. Zhang et al.
considerable attention because of its notable advantages
such as being a cost-effective, non-volatile, non-hygro-
scopic, odorless, non-corrosive, and crystalline solid acid
with outstanding physical stability [28]. We were therefore
motivated to investigate its new catalytic application to the
synthesis of quinoline derivatives since the construction of
heterocyclic compounds is one of our major research
interests [29, 30]. Hereby, we report an effective method
for the synthesis of polysubstituted quinolines via a one-pot
synthesis from readily available aliphatic aldehydes 1 and
arylamines 2 in the presence of catalytic amounts of
reusable SA catalyst under solvent-free conditions.
Obviously, the use of 10 mol% of catalyst is considered to
be sufficient to promote the reaction. The reaction under
catalyst-free conditions failed to yield the expected product
even after a prolonged reaction time spanning 24 h
(Table 1, entry 4). Subsequently, we investigated the
effects of several organic solvents including 1,4-dioxane,
acetonitrile, ethanol, and 1,2-dichloroethane on the reac-
tions, and 87, 72, 84, and 71% GC yield was detected
respectively by employing 10 mol% of SA catalyst
(Table 1, entries 5–8) at 80 °C for 3 h. The results indicate
that the reaction efficiency and yields in solution are lower
than those obtained under solvent-free conditions
(Table 2). Thus, the optimized reaction conditions can be
summarized as: 10 mol% of SA catalyst, solvent-free
conditions, and 80 °C.
Results and discussion
With the availability of the best reaction conditions in
hand, we tried to recover and reuse the SA catalyst. After
completion of the reaction for the first run, diethyl ether
was added to the resulting mixture to separate the product.
The remaining solid catalyst was recovered by filtration
and reused in the next run without further purification
under the optimized reaction conditions. This procedure
was repeated six times, and the results are outlined in
Table 1 (entry 9). The detected yields were observed to be
close in proximity to the initial value in the previous four
cycles, and subsequently a slight gradual decrease in the
yields was observed in the two latter cycles. Hence, the
catalyst could be effectively recycled for at least four times
without any loss of activity.
In order to formulate a highly effective conversion system,
the synthesis of 3-benzyl-2-phenethylquinoline (3c) from
3-phenylpropanal (1a, 2 mmol) and aniline (2c, 1 mmol)
was chosen as a model reaction to evaluate the influence of
different catalyst loadings and solvents. Initially, we car-
ried out the reaction at 80 °C for 3 h under solvent-free
conditions in the presence of 10 mol% of sulfamic acid
catalyst, and 91% GC yield was detected (Table 1, entry 1).
The usage of 9, 8, and 5 mol% of catalyst resulted in 85,
85, and 72% yield, respectively, which indicates that the
decreased catalyst loadings lead to reduced yields (Table 1,
entry 2). Further, an increase of catalyst loading (11 mol%)
did not improve the yield significantly (Table 1, entry 3).
Table 1 Screening optimized reaction conditions for the synthesis of 3c and investigation for the reuse of catalyst
Ph
O
+
2 Ph
NH2
N
Ph
1a
3c
2c
Entry
Catalyst loading/mol%
Solvent
Yields/%a
1
2
3
4
5
6
7
8
9
10
–
91
9, 8, 5
11
–
85, 85, 72
90
–
b
–
–
–
10
1,4-Dioxane
MeCN
87
10
72
10
EtOH
84
10
ClCH2CH2Cl
–
71
91, 89, 88, 90, 85, 79c
10
Reaction conditions: unless otherwise stated, 268 mg 1a (2 mmol) and 93 mg aniline (2c, 1 mmol) along with 0.1 mmol of SA were stirred in an
open Schlenk tube equipped with circulating cooling water at 80 °C for 3 h
a
GC yields with tetradecane as internal standard
b
The reaction was carried out for 24 h
c
GC yields as the SA catalyst was reused for 6 cycles
123

Facile one-pot synthesis of polysubstituted quinolines
473
Table 2 Facile one-pot synthesis of polyfunctional quinoline derivatives catalyzed by sulfamic acid under solvent-free conditions
R2
R2
R1
NH2SO3H (10 mol%)
80 °C, solvent-free
O
+
R1
2
NH2
N
R1
2
1
3
1a: R1 = PhCH2
2a: R2 = OMe
1
2
1b
: R = Ph
2b
: R = Me
1
2
1c
: R = 4-Br-C6H4
2c
: R = H
1
2
1d
: R = Et
2d
: R = Br
2e: R2 = Cl
CHO
1e =
8
Entry
1
1
2
Reaction
time/h
Product 3a
Yield/%b
73
1a
2a
3
MeO
Ph
N
Ph
3a [26]
2
3
4
1a
1a
1a
2b
2c
2d
3
3
3
86
83
76
Ph
N
Ph
3b
Ph
N
Ph
3c [18]
Br
Ph
N
Ph
3d
5
6
7
1b
1b
1b
2a
2b
2e
3
5
5
80
78
73
MeO
Ph
Ph
N
3e [21]
Ph
Ph
N
3f [21]
Cl
Ph
Ph 3g
N
123

474
M. Zhang et al.
Table 2 continued
Entry
1
2
Reaction
time/h
Product 3a
Yield/%b
63
8
1c
2b
3
Br
N
Br
3h
9
1d
1e
2d
2a
5
3
66
86
Br
N
3i
10
MeO
7
8
N
3j
11
12
1e
1e
2c
3
3
86
83
7
8
N
3k
2d
Br
7
8
N
3l
Reaction conditions: aldehyde 1 (2 mmol) and aniline derivatives 2 (1 mmol) along with 0.1 mmol of SA were stirred in an open Schlenk tube
equipped with circulating cooling water at 80 °C for appropriate time
a
1
Known compounds were marked with related references; the IR, H NMR spectra were found to be identical with the ones described in the
reference
b
Isolated yield after flash chromatography
To investigate the generality of this synthetic method
under optimized reaction conditions, various aliphatic
aldehydes 1 and arylamines 2 bearing weak electron with-
drawing groups (such as halide) or electron releasing groups
(such as CH3, CH3O) were employed for the quinoline
synthesis. As shown in Table 2, all reactions proceeded
smoothly and yielded the expected products in good to
excellent isolated yields. It was found that the influence of
substituents on the benzene ring of arylamines was quite
effective on the reactions. The arylamines possessing elec-
tron-donating groups showed faster reactions and completed
the conversion of starting materials in 3 h (Table 2, entries 1,
2, 5, 8, 10), which might be attributable to the more easy
formation of imines and electrophilic attack of C(2) of
arylimines to another imines (or enamines) (see the proposed
mechanism, Scheme 3). As the products tolerate halides
(Table 2, entries 4, 7–9, 12), they have the potential for the
synthesis of molecular materials via further classical cross-
coupling reactions (Table 2, entries 4, 7, 8, 10). The products
3j, 3k, 3l containing two terminal vinyl groups provide the
potentials in preparation of macrocyclic compounds or long
chain polymers via intra- or intermolecular olefin metathesis
(Table 2, entries 10, 11, 12) [31], and their arising substrate
undec-10-enal (1e) was found to be a renewable natural
resource from castor oil. Interestingly, different functional
groups could be introduced into the quinoline skeleton by
mediating appropriate starting materials with the current SA
catalysis method (Table 2).
123

Facile one-pot synthesis of polysubstituted quinolines
475
R1
Scheme 1
R1
N
4
+
O
NH2SO3H (10 mol%)
80 °C, solvent-free
2 R1
+
R1
NH2
1a 1b
,
2f
R1
N
4'
Not found
Ph
Ph
Ph
N
N
Ph
4b
4a, yield 83%
, yield 78%
Scheme 2
NH2SO3H (10 mol%)
80 °C, solvent-free
R1
O
2 R1
1a, 1b
+
R1
NH2
N
5
2g
Ph
Ph
Ph
N
Ph
N
5b, yield 70%
5a
, yield 76%
The substrate 3,4-dimethylbenzenamine (2f) was
employed to investigate the regioselectivity of the reaction,
which could lead to two possible regioisomers 4, 40
(Scheme 1); however, the results showed that only one
regioisomer 4 was obtained, and 2,3,6,7-tetrasubstituted
quinoline products 4a, 4b were obtained in 83% and 78%
isolated yields, respectively.
aldehyde leading to the formation of quinoline could also
explain the outcome of the reaction [24].
In conclusion, we have demonstrated a facile SA cata-
lyzed method for the synthesis of polysubstituted quinoline
derivatives via one-pot reactions. The method allows
assembling a wide range of expected products and intro-
ducing different functional groups into the quinoline
skeleton by simply mediating with the reactants. Interest-
ingly, this one-pot synthesis could produce the products
regioselectively in the presence of dis-symmetrical
arylamines such as 3,4-dimethylbenzenamine and b-naph-
thylamine. The obtained products containing halides or
vinyl groups have the potential for further chemical
transformations. The represented simple experimental
procedure along with the advantages of easy recovery and
reuse of SA catalyst and solvent-free conditions makes it a
highly practical and environmentally benign pathway for
the synthesis of polysubstituted quinolines.
Similarly, the reactions of 1a, 1b with b-naphthylamine
(2g) gave only one regioisomer 5a, 5b in 76 and 70%
isolated yield, respectively. The results are well in agree-
ment with the fact that the reactivity at the a-position is
much higher than that of the b-position in the naphthalene
moiety [32] (Scheme 2).
The proposed mechanism for this cyclization reaction is
illustrated in Scheme 1 based on the published information
[24–27, 33]. The imine A or its tautomer enamine A0 is
formed initially via dehydration of aliphatic aldehyde and
arylamine catalyzed by the SA catalyst, then the Schiff
base dimerisation and ortho-carbon nucleophilic addition
to the enamine moiety results in tetrahydroquinoline
intermediate B, and the final quinoline product is formed
by aniline elimination and air oxidative aromatization
promoted by the SA catalyst (Scheme 3). Alternatively, a
Povarov reaction between imine and enol formed from
Experimental
All obtained products were characterized by melting
points, 1H NMR, 13C NMR, infrared spectra, and low- and
123

476
M. Zhang et al.
R2
R3
Scheme 3
R2
R1
NH2SO3H (10 mol%)
80 °C, solvent-free
O
+
R1
2
R3
R3
N
NH2
R1
2
1
3
R2
Air oxidative
aromatization
NH2
SA
H2O
R3
SA
R2
R2
R3
HN
R1
N
R2
R3
NH
R1
R1
A
N
H
R3
R1
R2
B
A'
high-resolution mass spectra (MS and HRMS). Melting
points were measured on an Electrothermal SGW-X4
microscopy digital melting point apparatus. IR spectra
were recorded on a FTLA2000 spectrometer. 1H NMR and
13C NMR spectra were obtained on Bruker-200 and
Avance 300, chemical shifts were reported in parts per
million (ppm, d) downfield from tetramethylsilane. Proton
coupling patterns are described as singlet (s), doublet (d),
triplet (t), quartet (q), multiplet (m), and broad (br). LRMS
and HRMS were measured on a Finnigan MAT 95 spec-
trometer. TLC was performed using commercially
prepared 100–400 mesh silica gel plates (GF254), and
visualization was effected at 254 nm. All the chemical
reagents were purchased from commercial sources (Alfa,
Acros, Aldrich) and used without further purification.
silica eluting with petroleum ether-ethyl acetate (30:1) to
provide desired quinoline products.
3-Benzyl-6-methoxy-2-(2-phenylethyl)quinoline
(3a) [26]
Yield 73%; white solid; m.p.: 136–137 °C (Ref. [26]
142–144 °C).
3-Benzyl-6-methyl-2-(2-phenylethyl)quinoline
(3b, C25H23N)
Yield 86%; white solid; m.p.: 124–126 °C; 1H NMR
(200 MHz, CDCl3): d = 8.01 (d, J = 8.4 Hz, 1H), 7.70 (s,
1H), 7.51–7.55 (m, 2H), 7.11–7.36 (m, 10H), 4.08 (s, 2H),
3.19–3.28 (m, 2H), 3.03–3.13 (m, 2H), 2.54 (s, 3H) ppm;
13C NMR (50 MHz, CDCl3): d = 158.9, 140.7, 138.1,
134.6, 134.4, 131.1, 129.8, 127.6, 127.3, 127.2, 126.8,
125.8, 125.1, 124.7, 124.6, 37.4, 36.3, 34.1, 20.2 ppm; IR
(KBr): vꢀ = 3,021, 2,928, 1,601, 1,493, 1,451, 1,355, 1,132,
1,031, 938 cm-1; MS (EI): m/z = 337 [M]?; HRMS (EI):
338.1902 [M ? H]?.
General procedure for synthesis of the quinolines
3a–3l, 4a, 4b, 5a, 5b
A Schlenk tube equipped with a magnetic stirrer bar and a
provision of circulating cool water was used in the exper-
imentation. The catalyst SA (10 mg, 0.1 mmol), arylamine
(1 mmol), and aldehyde (2 mmol) were introduced suc-
cessively, and the resulting mixture was stirred in an open
system at 80 °C for a duration of 3–5 h. TLC was used to
detect the completion of the reaction. After cooling to room
temperature, the reaction mixture was washed and extrac-
ted with diethyl ether (5 9 15 cm3). The residues of the
solid sulfamic acid catalyst could be recycled for the next
run after removal of the solvent. The combined organic
solvent was evaporated to afford the crude product, which
was purified by using flash column chromatography on
3-Benzyl-2-(2-phenylethyl)quinoline (3c) [18]
Yield 83%; white solid; m.p.: 94–97 °C.
3-Benzyl-6-bromo-2-(2-phenylethyl)quinoline
(3d, C24H19BrN)
Yield 76%; white solid; m.p.: 89–91 °C; 1H NMR
(200 MHz, CDCl3): d = 7.98 (d, J = 9.0 Hz, 1H), 7.89
(d, J = 1.8 Hz, 1H), 7.75 (dd, J = 2.2 Hz, 1H), 7.65 (s,
1H), 7.10–7.39 (m, 10H), 4.08 (s, 2H), 3.21–3.30 (m, 2H),
3.06–3.14 (m, 2H) ppm; 13C NMR (50 MHz, CDCl3):
d = 161.7, 145.4, 141.8, 138.8, 135.2, 133.7, 132.2, 130.4,
129.2, 129.0, 128.8, 128.6, 128.4, 128.3, 126.7, 126.0,
119.6, 38.6, 37.6, 35.1 ppm; IR (KBr): vꢀ = 3,025, 2,927,
123

Facile one-pot synthesis of polysubstituted quinolines
477
1,595, 1,494, 1,477, 1,453, 1,397, 1,059, 918 cm-1; MS
30.6, 30.5, 30.2, 30.0, 29.9, 29.8, 29.6, 29.3, 29.2, 29.1,
27.6 ppm; IR (KBr): vꢀ = 3,074, 2,925, 1,624, 1,513, 1,493,
1,381, 1,229, 1,165, 1,034, 909 cm-1; MS (EI): m/z = 421
[M]?; HRMS (EI): 422.3417 [M ? H]?.
(EI): m/z = 401 [M]?; HRMS (EI): 402.0842 [M ? H]?.
2-Benzyl-6-methoxy-3-phenylquinoline (3e) [21]
Yield 80%; light yellow oil.
2-(Dec-9-enyl)-3-(non-8-enyl)quinoline (3k, C28H41N)
Yield 86%; colorless oil; 1H NMR (200 MHz, CDCl3):
d = 8.03 (d, J = 8.0 Hz, 1H), 7.86 (s, 1H), 7.72 (d,
J = 8.2 Hz, 1H), 7.64 (dd, J = 7.2 Hz, J = 8.4 Hz, 1H),
7.64 (dd, J = 7.2 Hz, J = 8.2 Hz, 1H), 6.62 (d,
J = 7.6 Hz, 1H), 5.73–5.94 (m, 3H), 4.93–5.06 (m, 6H),
2.99 (t, J = 8.0 Hz, 2H), 2.80 (d, J = 8.0 Hz, 2H), 2.07
(m, 4H),1.34–1.58 (m, 18H) ppm; 13C NMR (50 MHz,
CDCl3): d = 162.7, 139.7, 139.5, 135.3, 134.5, 129.6,
128.8, 128.7, 127.3, 126.0, 117.5, 114.6, 114.5, 113.1,
50.2, 44.4, 36.3, 34.2, 32.8, 30.9, 30.3, 30.2, 30.1, 30.0,
29.9, 29.8, 29.7, 29.5, 29.4, 29.3, 27.6 ppm; IR (KBr):
vꢀ = 2,925, 1,640, 1,603, 1,505, 1,491, 1,319, 992,
909 cm-1; MS (EI): m/z = 391 [M]?; HRMS (EI):
392.3316 [M ? H]?.
2-Benzyl-3-phenylquinoline (3f) [21]
Yield 78%; colorless oil.
2-Benzyl-6-chloro-3-phenylquinoline (3g, C22H16ClN)
Yield 73%; colorless oil; 1H NMR (200 MHz, CDCl3):
d = 8.11 (d, J = 8.8 Hz, 1H), 7.89 (s, 1H), 7.66–7.80 (m,
2H), 7.13–7.44 (m, 8H), 6.94–6.98 (m, 2H), 4.34 (s, 2H)
ppm; 13C NMR (50 MHz, CDCl3): d = 160.0, 139.5,
139.4, 137.4, 136.3, 132.4, 131.0, 130.7, 129.8, 129.5,
129.4, 129.3, 129.2, 129.1, 129.0, 128.9, 128.8, 128.7,
128.6, 128.5, 128.2, 127.9, 127.4, 126.5, 118.5, 114.4,
43.2 ppm; IR (KBr): vꢀ = 3,033, 2,982, 1,601, 1,498, 1,467,
1,377, 1,029, 932 cm-1; MS (EI): m/z = 329 [M]?; HRMS
(EI): 330.1048 [M ? H]?.
2,3-Bis(4-bromobenzyl)-6-methylquinoline
(3h, C23H17Br2N)
6-Bromo-2-(dec-9-enyl)-3-(non-8-enyl)quinoline
Yield 63%; white solid; m.p.: 121–123 °C; 1H NMR
(200 MHz, CDCl3): d = 8.05 (d, J = 8.4 Hz, 1H), 7.86 (s,
1H), 7.61–7.52 (m, 4H), 7.27 (m, 2H), 7.06 (d, J = 8.4 Hz,
2H), 6.83 (d, J = 8.4 Hz, 2H), 4.23 (s, 2H), 2.57(s, 3H)
ppm; 13C NMR (50 MHz, CDCl3): d = 157.3, 146.3,
138.9, 138.7, 137.0, 136.9, 135.1, 132.5, 131.8, 131.6,
131.3, 130.9, 130.8, 129.1, 127.2, 126.7, 122.5, 122.5,
120.4, 42.6, 22.1 ppm; IR (KBr): vꢀ = 3,021, 2,981, 1,605,
1,499, 1,427, 1,376, 1,033, 933 cm-1; MS (EI): m/z = 466
[M ? 1]?; HRMS (EI): 465.9804 [M ? H]?.
(3l, C28H40BrN)
Yield 83%; colorless oil; 1H NMR (200 MHz, CDCl3):
d = 7.89 (d, J = 8.0 Hz, 1H), 7.71–7.76 (m, 1H), 7.25 (d,
J = 8.4 Hz, 2H), 6.50 (d, J = 8.8 Hz, 2H), 5.73–5.90 (m,
3H), 4.93–5.06 (m, 6H), 3.07 (t, J = 7.2 Hz, 2H), 2.96 (t,
J = 8.0 Hz, 1H), 2.82 (t, J = 6.8 Hz, 1H), 2.06 (m, 4H),
1.33–1.65 (m, 17H) ppm; 13C NMR (50 MHz, CDCl3):
d = 163.6, 140.3, 139.6, 135.3, 134.5, 130.2, 128.8, 128.2,
127.6, 127.3, 126.0, 119.8, 117.5, 114.6, 50.2, 44.4, 36.3,
34.2, 32.8, 30.9, 30.3, 30.2, 30.2, 30.0, 29.9, 29.8, 29.7, 29.5,
29.4, 29.3, 27.6 ppm; IR (KBr): vꢀ = 2,925, 1,640, 1,596,
1,497, 1,317, 1,260, 1,177, 1,072, 995, 909 cm-1; MS (EI):
m/z = 472 [M ? 2]?; HRMS (EI): 470.2418 [M ? 1]?.
6-Bromo-3-ethyl-2-propylquinoline (3i, C14H16BrN)
Yield 66%; colorless oil; 1H NMR (200 MHz, CDCl3):
d = 7.87–7.91 (m, 2H), 7.77 (s, 1H), 7.64–7.70 (m, 1H),
2.79–3.00 (m, 4H), 1.84 (q, J = 8.0 Hz, 2H), 1.34 (t,
J = 7.4 Hz, 3H), 1.08 (t, J = 7.4 Hz, 3H) ppm; 13C NMR
(50 MHz, CDCl3): d = 162.6, 145.0, 136.4, 132.7, 131.9,
131.7, 130.3, 128.9, 128.5, 119.2, 114.2, 37.7, 25.2, 22.6,
14.3, 14.2 ppm; IR (KBr): vꢀ = 2,963, 1,594, 1,477, 1,377,
1,345, 1,184, 911 cm-1; MS (EI): m/z = 279 [M ? 1]?;
HRMS (EI): 278.0539 [M ? H]?.
3-Benzyl-6,7-dimethyl-2-(2-phenylethyl)quinoline
(4a, C26H25N)
Yield 83%; white solid; m.p.: 97–100 °C; 1H NMR
(200 MHz, CDCl3): d = 7.89 (s, 1H), 7.67 (s, 1H), 7.48
(s, 1H), 7.11–7.36 (m, 10H), 4.07 (s, 2H), 3.17–3.26 (m,
2H), 3.08 (t, J = 5.2 Hz, 2H), 2.50 (s, 3H), 2.45 (s, 3H)
ppm; 13C NMR (50 MHz, CDCl3): d = 160.2, 146.0,
142.1, 139.6, 139.0, 135.7, 135.5, 131.5, 128.9, 128.7,
128.6, 128.5, 128.4, 128.3, 128.0, 126.4, 126.3, 126.0,
125.8, 38.7, 37.7, 35.5, 20.4, 20.0 ppm; IR (KBr):
2-(Dec-9-enyl)-6-methoxy-3-(non-8-enyl)quinoline
(3j, C29H43NO)
Yield 86%; colorless oil; 1H NMR (200 MHz, CDCl3):
d = 7.93 (d, J = 9.0 Hz, 1H), 7.77 (s, 1H), 7.26 (d,
J = 9.0 Hz, 1H), 7.01 (s, 1H), 6.80 (d, J = 9.2 Hz, 1H),
6.61 (d, J = 8.8 Hz, 1H), 5.76–5.91 (m, 3H), 4.93–5.06
(m, 6H), 3.93 (s, 3H), 2.95 (t, J = 8.0 Hz, 2H), 2.78 (t,
J = 8.0 Hz, 2H), 2.06 (m, 4H), 1.19–1.78 (m, 17H) ppm;
13C NMR (50 MHz, CDCl3): d = 162.6, 139.9, 139.7,
135.4, 134.7, 129.3, 128.8, 127.6, 127.2, 126.3, 117.6,
114.6, 114.3, 113.2, 59.3, 50.3, 44.6, 36.4, 34.3, 32.5, 30.7,
vꢀ = 3,025, 2,916, 1,602, 1,493, 1,453, 1,074, 1,028 cm-1
MS (EI): m/z = 351 [M]?; HRMS (EI): 352.2062
[M ? H]?.
;
2-Benzyl-6,7-dimethyl-3-phenylquinoline (4b, C24H21N)
1
Yield 78%; light yellow oil; H NMR (200 MHz, CDCl3):
d = 7.96 (s, 1H), 7.86 (s, 1H), 7.55 (s, 1H), 7.41–7.11 (m,
8H), 6.98–6.94 (m, 2H), 4.33 (s, 2H), 2.52 (s, 3H), 2.48 (s,
3H) ppm; 13C NMR (50 MHz, CDCl3): d = 158.4, 146.8,
123

478
M. Zhang et al.
4. Dube D, Blouin M, Brideau C, Chan CC, Desmarais S, Ethier D,
Falgueyret JP, Friesen RW, Girard M, Girard Y, Guay J, Rien-
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8:1255
5. Roma G, Braccio MD, Grossi G, Mattioli F, Ghia M (2000) Eur J
Med Chem 35:1021
140.4, 140.1, 140.0, 136.6, 136.3, 135.7, 129.9, 129.2,
128.7, 128.6, 128.4, 127.8, 127.0, 126.2, 43.1, 20.9,
20.5 ppm; IR (KBr): vꢀ = 3,037, 2,912, 1,601, 1,478,
1,453, 1,074, 948 cm-1; MS (EI): m/z = 323 [M]?; HRMS
(EI): 324.1746 [M ? H]?.
6. Ebisu H, Nishikawa M, Tanaka M, Okazoe T, Morizawa Y,
Shinyama H, Nakamura N (1999) J Cardiovasc Pharmacol 34:526
7. Maguire MP, Sheets KR, Mcvety K, Spada AP, Zilberstein A
(1994) J Med Chem 37:2129
2-Benzyl-3-(2-phenylethyl)benzo[f]quinoline
(5a, C28H23N)
1
Yield 70%; light yellow oil; H NMR (200 MHz, CDCl3):
8. Altenbach RJ, Liu H, Banfor PN, Browman KE, Fox GB, Fryer
RM, Komater VA, Krueger KM, Marsh K, Miller TR, Pan J, Pan
L, Sun M, Thiffault C, Wetter J, Zhao C, Zhou D, Esbenshade
TA, Hancock AA, Cowart MD (2007) J Med Chem 50:5439
9. Frotscher M, Ziegler E, Marchais-Oberwinkler S, Kruchten P,
Neugebauer A, Fetzer L, Scherer C, Mu¨ller-Vieira U, Messinger
J, Thole H, Hartmann RW (2008) J Med Chem 51:2158
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11. Jenekhe SA, Lu L, Alam MM (2001) Macromolecules 34:7315
12. Espinosa LM, Ronda JC, Galia M, Cadiz V (2010) J Polym Sci
Polym Chem 48:869
d = 9.57 (d, J = 7.6 Hz, 1H), 8.01 (d, J = 7.4 Hz, 1H),
7.78–8.00 (m, 4H), 7.21–7.56 (m, 11H), 4.20 (s, 2H),
3.36–3.42 (m, 4H) ppm; 13C NMR (50 MHz, CDCl3):
d = 157.8, 140.4, 140.3, 137.2, 136.6, 134.1, 131.9, 130.0,
129.7, 129.6, 129.3, 129.1, 128.9, 128.8, 128.6, 128.5,
128.4, 128.3, 128.2, 128.0, 127.9, 127.4, 126.4, 125.5,
125.1, 124.8, 43.2, 41.2, 39.4 ppm; MS (EI): m/z = 373
[M]?; HRMS (EI): 374.1908 [M ? H]?.
13. Ou S, Lin Z, Duan C, Zhang H, Bai Z (2006) Chem Commun
42:4392
14. Skraup ZH (1880) Ber Dtsch Chem Ges 13:2086
15. Friedlander P (1882) Ber Dtsch Chem Ges 15:2572
16. Combes A (1888) Bull Soc Chim Fr 49:89
17. Doebner O, Miller WV (1881) Ber Dtsch Chem Ges 14:2812
18. Jacob J, Jones WD (2003) J Org Chem 68:3563
19. Huo ZB, Gridnev ID, Yamamoto Y (2010) J Org Chem 75:1266
20. Majumder S, Gipson KR, Odom AL (2009) Org Lett 11:4720
21. Beller M, Thiel OR, Trauthwein H, Hartung CG (2000) Chem
Eur J 6:2513
22. Dobbelaar PH, Marzabadi CH (2010) Tetrahedron Lett 51:201
23. Qi CM, Zheng QW, Hua RM (2009) Tetrahedron 65:1316
24. Tanaka SY, Yasuda M, Baba A (2006) J Org Chem 71:800
25. Lin XF, Cui SL, Wang YG (2006) Tetrahedron Lett 47:3127
26. Bian XQ, Liu LH, Geng X, Xie ZY, Li SS, Wang CD (2009)
J Chem Res (S) 81
3-Benzyl-2-phenylbenzo[f]quinoline (5b, C26H19N)
1
Yield 70%; light yellow oil; H NMR (200 MHz, CDCl3):
d = 9.48 (d, J = 8.0 Hz, 1H), 7.95–8.03 (m, 2H),
7.68–7.86 (m, 4H), 7.24–7.51 (m, 10H), 4.49 (s, 2H)
ppm; 13C NMR (50 MHz, CDCl3): d = 157.9, 140.2,
140.1, 137.2, 136.6, 134.1, 131.7, 130.3, 129.6, 129.6,
129.3, 129.1, 128.9, 128.8, 128.6, 128.5, 128.4, 128.3,
128.2, 128.1, 127.9, 127.4, 126.4, 125.6, 125.3, 125.0,
43.0 ppm; MS (EI): m/z = 345 [M]?; HRMS (EI): 346.15
[M ? H]?.
Acknowledgments The authors thank ‘‘the Fundamental Research
Funds for the Central Universities’’ (JUSRP10905), the ‘‘Start-up grant
of Jiangnan University’’ (1045210372090460) for financial support.
27. Bulgakov RG, Kuleshov SP, Vafin RR, Dzhemilev UM (2009)
Russ J Org Chem 45:944
28. Wang B (2005) Synlett 8:1342
29. Zhang M, Jiang HF, Neumann H, Beller M, Dixneuf PH (2009)
Angew Chem Int Ed 48:1681
30. Zhang M, Jiang HF, Liu HL, Zhu QH (2007) Org Lett 9:4111
31. Vougioukalakis GC, Grubbs RH (2010) Chem Rev 110:1746
32. Wang XS, Li Q, Zhang MM, Yao CS, Tu SJ (2008) J Heterocycl
Chem 45:1027
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123