An efficient method for synthesis of 3-arylbenzo[f]quinoline-1,2-dicarboxylates catalyzed by SnCl2

Article abstract of DOI:10.1007/s11164-014-1791-6

A wide variety of 3-arylbenzo[f]quinoline-1,2-dicarboxylates and their dehydro derivatives have been synthesized by one-pot, three-component reaction of an aromatic aldehyde, naphthalene-2-amine, and dimethyl but-2-ynedioate in the presence of SnCl_2<

Full text of DOI:10.1007/s11164-014-1791-6

Res Chem Intermed
DOI 10.1007/s11164-014-1791-6
An efficient method for synthesis of 3-arylbenzo[f]
quinoline-1,2-dicarboxylates catalyzed by SnCl2
•
Qing Yan Hongjun Zang Jiaxuan Feng
•
•
•
•
Mingguang Li Danni Yang Hai Lu Bowen Cheng
•
Received: 12 June 2014 / Accepted: 14 August 2014
Ó Springer Science+Business Media Dordrecht 2014
Abstract A wide variety of 3-arylbenzo[f]quinoline-1,2-dicarboxylates and their
dehydro derivatives have been synthesized by one-pot, three-component reaction of
an aromatic aldehyde, naphthalene-2-amine, and dimethyl but-2-ynedioate in the
presence of SnCl2 under reflux in acetonitrile. This procedure has several advan-
tages, for example high yield, short reaction time, easy work-up, little pollution, and
low price of the catalyst.
Keywords SnCl2 Á Imino Diels–Alder Á Aromatic aldehyde Á
Dimethyl but-2-ynedioate Á Synthesis
Introduction
Multicomponent reactions (MCRs) are very important in organic synthesis because
of the formation of carbon–carbon and carbon–hetero atom bonds [1–6]. Compared
with classical stepwise synthesis, MCRs have the advantages of high atom-
economy, selectivity, and fewer byproducts, so these reactions are becoming
increasingly attractive.
Benzoquinoline and its derivatives are famous for their diverse biological
activity, for example antibacterial activity [7, 8], uridine diphosphate-glucuronosyl
transferase activity [9, 10], antimicrobial activity [11], antimalarial activity [12],
agonistic activity [13], and antipsychotic activity [14]. In recent years, much effort
has been directed toward activating imine systems for cycloadditions by increasing
their electron-deficient character, and many applications have been discovered [15,
16]. These applications have attracted the attention of organic chemists wishing to
Q. Yan Á H. Zang (&) Á J. Feng Á M. Li Á D. Yang Á H. Lu Á B. Cheng
State Key Laboratory of Hollow Fiber Membrane Materials and Processes, Department of
Environmental and Chemistry Engineering, Tianjin Polytechnic University, Tianjin, China
e-mail: chemhong@126.com
123

Q. Yan et al.
H
C O
H
COOC
3
H
COOC
3
NH2
+
n
mmo
10
S Cl2
l
H
COOC
3
+
e
re ux
N2
fl
M
N
C
R
2
N
H
COOC
3
3
R
a
1
4
Scheme 1 Synthesis of 3-arylbenzo[f]quinolone-1,2-dicarboxylates
develop efficient synthetic routes for highly functionalized benzoquinoline deriv-
atives [17].
The imino Diels–Alder reaction enables easy preparation of six-membered
nitrogen heterocycles and related fused ring heterocycles [18–22]. Lewis acid and
Brønsted acid-catalyzed imino Diels–Alder reactions have been reported [23–31],
and have been developed into convenient methods for synthesis of a wide variety of
benzoquinoline derivatives. This method still has huge potential. Very recently,
Wang [5] and Maiti et al. [6], reported one-pot synthesis of 3-arylbenzo[f]quinoline-
1,2-dicarboxylate derivatives via an imino Diels–Alder reaction catalyzed by
Yb(OTf)3 or SbCl3. As far as we are aware, there is no report of the use of SnCl2, a
nontoxic and inexpensive catalyst, for synthesis of 3-arylbenzo[f]quinoline-1,2-
dicarboxylate derivatives. Our recent success in effective use of this catalyst for
three-component coupling of aromatic aldehydes, 1-naphthylamine, and 5,5-
dimethylcyclohexane-1,3-dione and our continuing efforts in the synthesis of
bioactive heterocyclic compounds [32] encouraged us to study three-component
reaction of naphthylamines, aromatic aldehydes, and dialkyl acetylene dicarbox-
ylates. A crucial aspect of this study was discovery of an efficient synthetic route to
3-arylbenzo[f]quinoline-1,2-dicarboxylate derivatives via an imino Diels–Alder
reaction; we also found that SnCl2 has highly catalytic activity in imino Diels–Alder
reactions, with the advantages of low price and ready availability. In the work
discussed in this report, we investigated reaction temperature, reaction time,
different solvents, and the scope of this reaction with different aromatic aldehydes,
aromatic amines, and dimethyl but-2-ynedioate.
We report a facile method of preparation of 3-arylbenzo[f]quinolone-1,2-
dicarboxylate derivatives in the presence of SnCl2 as an efficient catalyst in
acetonitrile under reflux (Scheme 1).
Results and discussion
In the first set of experiments we investigated heating of 2-naphthylamine (1a,
1 mmol), 4-chlorobenzaldehyde (2, 1 mmol), and dimethyl but-2-ynedioate (3,
1.2 mmol) under reflux in a variety of solvents and with different catalysts as model
reaction (Table 1). In the absence of catalyst only a trace of the expected product,
3-arylbenzo[f]quinolone-1,2-dicarboxylate (4), was obtained after 24 h (Table 1,
entry 1). Obviously, the catalyst was an essential component of the reaction. Use of
123

Synthesis of 3-arylbenzo[f]quinoline-1,2-dicarboxylates
Table 1 Optimization of the reaction conditions
H
C O
H
COOC
3
H
COOC
3
NH2
+
ata st
H
3
COOC
C
l
y
+
e
re ux
N2
fl
M
N
C
N
H
COOC
3
3
Cl
Cl
a
2
a
4
a
1
Entry
Catalyst/%
Solvent
Time (h)
Yield (%)a
1
–
MeCN
MeCN
MeCN
MeCN
MeCN
MeCN
MeCN
Toluene
DMF
24
24
24
24
8
Trace
Trace
Trace
87
2
NH2SO3H/10
ZnCl2/10
SnCl2/10
SnCl2/10
SnCl2/10
SnCl2/10
SnCl2/10
SnCl2/10
SnCl2/10
SnCl2/1
3
4
5
55
6
16
32
24
24
24
24
24
24
24
65
7
88
8
Trace
62
9
10
11
12
13
14
THF
59
MeCN
MeCN
MeCN
MeCN
Trace
64
SnCl2/5
SnCl2/15
SnCl2/20
72
69
Reaction conditions: 10 mL MeCN, 1.0 mmol 4-chlorobenzaldehyde, 1.0 mmol 2-naphthylamine,
1.1 mmol dimethyl but-2-ynedioate, and 0.1 mmol SnCl2
a
Isolated yields
ZnCl2 or NH2SO3H as catalyst also led to negative results (Table 1, entries 2, 3).
We found SnCl2 was an effective catalyst for the imino Diels–Alder reaction
(Table 1, entry 4). These findings demonstrated SnCl2 was important in the Diels–
Alder reaction. A catalytic amount (0.1 equiv) of SnCl2 was therefore used for
synthesis of the 3-arylbenzo[f]quinolone-1,2-dicarboxylate derivatives. Reaction
under reflux for 8, 16, 24, and 32 h gave 4 in 55, 65, 87, and 88 % yield,
respectively (Table 1, entries 4–7), clearly showing that 24 h was the optimum
reaction time. When different solvents (MeCN, THF, DMF, and toluene) were
investigated (Table 1, entries 4, 8–10) it was found that MeCN was the best reaction
medium, providing 3-arylbenzo[f]quinolone-1,2-dicarboxylate in 87 % yield
(Table 1, entry 4); the nonpolar solvent toluene failed to afford the desired product
(Table 1, entry 8). To determine the optimum amount of catalyst, the one-pot
reaction was conducted with different amounts of SnCl2 (Table 1, entries 4, 11–14).
Reaction with 10 mol% SnCl2 as catalyst resulted in a good yield.
Encouraged by these results, we investigated the scope of the method by reaction
of different aromatic aldehydes, 2-naphthylamine, and dimethyl but-2-ynedioate
under the aforementioned optimized reaction conditions; the results are listed in
123

Q. Yan et al.
Table 2 SnCl2-catalyzed reaction of aromatic aldehydes, 2-naphthylamine. and dimethyl but-2-yne-
dioate
H
C O
H
COOC
3
H
COOC
3
NH2
+
n
mmo
S Cl2 10
l
H
COOC
3
+
e
re ux
N2
fl
M
N
C
R
N
H
COOC
3
3
R
a
a-
k
1
2
a-
4 k
Entry
R
Product 4
Time (h)
Yield (%)a
m.p. (°C)
Found
Reported
1
4-Chloro
3-Chloro
4a
4b
4c
4d
4e
4f
24
24
24
24
24
24
24
24
24
24
24
87
83
80
73
70
79
70
61
82
60
64
173–174
142–143
210–212
171–173
163–165
159–160
143–145
160–161
181–182
128–130
183–185
175–176 [5]
2
143–144 [5]
3
2,4-Dichloro
2-Chloro
4-Fluoro
209–210 [5]
4
–
5
165–167 [5]
6
2-Bromo
3-Nitro
–
7
4g
4h
4i
142–143 [6]
8
4-Nitro
162 [6]
9
2-Methoxy
4-Methoxy
4-Hydroxy
–
10
11
4j
128–129 [6]
–
4k
Reaction conditions: 10 mL MeCN, 1.0 mmol aromatic aldehyde, 1.0 mmol 2-naphthylamine, 1.1 mmol
dimethyl but-2-ynedioate, and 0.1 mmol SnCl2
a
Isolated yields
Table 2 (entries 1–11). It was apparent our procedure provided an opportunity for
further chemical elaboration for synthesis of a variety of 3-arylbenzo[f]quinolone-
1,2-dicarboxylate derivatives. A variety of aromatic aldehydes containing electron-
donating and-electron withdrawing substituents reacted with 2-naphthylamine in
good yields (Table 2, entries 1–11). The scope was then extended to reaction of
aromatic aldehydes with 1-naphthylamine but the yield of the corresponding
3-arylbenzo[f]quinolone-1,2-dicarboxylate derivatives was moderate (Table 3,
entries 1–3). Although transformation times and yields were different, the catalyst
SnCl2 was convincingly an essential component of the reaction.
According to the literature [5, 33], a probable mechanism for the synthesis of
3-arylbenzo[f]quinolone-1,2-dicarboxylate may be postulated as shown in
Scheme 2. First, reaction may occur between the aromatic aldehyde and naphtha-
lene-2-amine to form the Schiff base a. Imino Diels–Alder reaction between the
SnCl2-activated Schiff base b and dimethyl but-2-ynedioate then occurs to form
intermediate c, followed by isomerization to form 3,4-dihydrobenzo[f]quinolines, d,
which will be further oxidized by air to afford the final aromatized 3-aryl-
benzo[f]quinoline-1,2-dicarboxylate, 4.
123

Synthesis of 3-arylbenzo[f]quinoline-1,2-dicarboxylates
Table 3 SnCl2-catalyzed reaction of aromatic aldehydes, 1-naphthylamine, and dimethyl but-2-yne-
dioate
NH2
H
C O
H
COOC
3
R1
n
mmo
S Cl2 10
l
N
+
+
e
re ux
N2
fl
M
N
C
R1
H
COOC
3
H
COOC
3
3
H
COOC
3
1
b
-n
2
l
m-o
4
Entry
R1
Product 4
Time
Yield (%)a
m.p. (°C)
Found
Reported
1
2
3
3-Nitro
4l
20
22
22
73
75
60
143–145
163–164
119–120
146 [6]
164 [6]
–
4-Methyl
4-Fluoro
4m
4n
Reaction condition: 10 mL MeCN, 1.0 mmol aromatic aldehyde, 1.0 mmol 1-naphthylamine, 1.1 mmol
dimethyl but-2-ynedioate and 0.1 mmol SnCl2
a
Isolated yields
R
NH2
N
n
S Cl2
+
H
CO
R
N
C
Sn
l2
a
b
R
H
H
COOC
3
H
COOC
H
COOC
3
3
COOC
N
3
HN
4
H
COOC
H
COOC
3
3
R
R
c
d
Scheme 2 Possible mechanism for the reaction
Experimental
All chemicals were commercially available and used as received. Reactions were
monitored by TLC. All yields refer to isolated products. Melting points were
measured on an X-4 digital microscopic melting-point apparatus and are
uncorrected. 1H NMR spectra were measured on a Bruker Avance 300 spectrometer
with TMS as internal standard. Infrared spectra were recorded on a Thermo
Scientific Nicolet 6700 FT-IR spectrometer using KBr optics. Elemental analysis
was performed with a Perkin–Elmer auto-analyzer.
123

Q. Yan et al.
The structures of the new 3-arylbenzo[f]quinolone-1,2-dicarboxylate derivatives
(4d, 4f, 4i, 4k, and 4n) were completely characterized on the basis of their IR and
1H NMR spectra and by elemental analysis. Known compounds were identified by
comparison of their melting points with values reported in the literature.
General procedure for synthesis of 3-arylbenzo[f]quinolone-1,2-dicarboxylate
derivatives
A mixture of 2-naphthylamine (1 mmol), aromatic aldehyde (1 mmol), and
dimethyl but-2-ynedioate (1.2 mmol) was dissolved in MeCN (10 ml). The mixture
was stirred at reflux in a 100-ml round-bottomed flask in the presence of SnCl2
(1 mmol, 20 %) under an N2 atmosphere at 80 °C. These results obtained are listed
in Table 1. After completion of the reaction, as indicated by TLC, the MeCN was
evaporated under reduced pressure, and water (20 ml) was added. The resulting
solution was extracted with EtOAc (3 9 10 mL). The combined organic layers
were dried over Na2SO4 and concentrated. Products were purified by column
chromatography on silica gel with ethyl acetate–petroleum (1:5 to 1:10) as eluent to
afford the pure product.
Compound 4d: Yellow solid; mp: 171–173 °C; IR (KBr): 2,935, 1,750, 1,721,
1
1,552, 1,436, 1,238, 1,136, 1,011, 952, 887, 835, 769, 738, 534 cm-1. H NMR
(400 MHz, CDCl3) d 7.95 (d, J = 8.6 Hz, 1H), 7.58 (dd, J = 12.5, 8.4 Hz, 2H),
7.46 (dd, J = 7.2, 2.2 Hz, 1H), 7.41 (dd, J = 9.3, 6.3 Hz, 1H), 7.38–7.34 (m, 1H),
7.24–7.21 (m, 1H), 7.14 (pd, J = 7.4, 1.8 Hz, 2H), 6.74 (d, J = 8.8 Hz, 1H), 4.00
(s, 3H), 3.74 (s, 3H). Anal. Calcd for C23H16ClNO4: C 68.07, H 3.97, N 3.45; found:
C 68.05, H 3.94, N 3.47.
Compound 4f: Yellow solid; mp: 159–160 °C; IR (KBr): 2,955, 1,728, 1,555,
1,483, 1,439, 1,372, 1,242, 1,119, 1,076, 997, 832, 800, 747 cm-1 1H NMR
.
(400 MHz, CDCl3) d 7.95 (d, J = 8.8 Hz, 1H), 7.65–7.51 (m, 3H), 7.49–7.45 (m,
1H), 7.41 (dd, J = 12.1, 3.4 Hz, 1H), 7.23 (d, J = 7.8 Hz, 1H), 7.18 (t, J = 8.1 Hz,
1H), 7.12–7.05 (m, 1H), 6.74 (d, J = 8.8 Hz, 1H), 4.00 (s, 3H), 3.74 (s, 3H). Anal.
Calcd for C23H16BrNO4: C 61.35, H 3.58, N 3.11; found: C 61.36, H 3.59, N 3.14.
Compound 4i: White solid; mp: 181–182 °C; IR (KBr): 2,955, 1,738, 1,718,
1,702, 1,599, 1,546, 1,430, 1,237, 1,119, 1,064, 1,026, 1,011, 833, 812, 737 cm-1
.
1H NMR (400 MHz, CDCl3) d 8.37–8.27 (m, 1H), 8.06 (s, 2H), 8.01–7.91 (m, 1H),
7.67 (pd, J = 7.1, 1.4 Hz, 2H), 7.58 (dd, J = 7.5, 1.7 Hz, 1H), 7.46–7.39 (m, 1H),
7.13 (t, J = 7.5 Hz, 1H), 6.95 (d, J = 8.3 Hz, 1H), 4.10 (s, 3H), 3.75 (s, 3H), 3.68
(s, 3H). Anal. Calcd for C24H19NO5: C 71.81, H 4.77, N 3.49; found: C 71.80, H
4.74, N 3.53.
Compound 4k: White solid; mp: 183–185 °C; IR (KBr): 3,610, 2,945, 1,750,
1
1,721, 1,552, 1,436, 1,238, 1,136, 1,011, 952, 887, 835, 769, 738, 534 cm-1. H
NMR (400 MHz, CDCl3) d 8.36–8.29 (m, 1H), 8.09 (dd, J = 19.8, 9.0 Hz, 2H),
8.00–7.94 (m, 1H), 7.67 (tt, J = 8.7, 3.7 Hz, 2H), 7.59 (dd, J = 7.5, 1.6 Hz, 1H),
7.48–7.39 (m, 1H), 7.14 (t, J = 7.5 Hz, 1H), 6.95 (d, J = 8.1 Hz, 1H), 4.11 (s, 3H),
3.68 (s, 3H). Anal. Calcd for C23H17NO5: C 71.31, H 4.42, N 3.62; found: C 71.33,
H 4.41, N 3.64.
123

Synthesis of 3-arylbenzo[f]quinoline-1,2-dicarboxylates
Compound 4n: Yellow solid; mp: 119–120 °C; IR (KBr): 2,953, 1,752, 1,557,
1
1,526, 1,430, 1,332, 1,232, 1,128, 996, 831, 747, 732, 694, 687 cm-1. H NMR
(400 MHz, CDCl3) d 7.94 (d, J = 8.9 Hz, 1H), 7.72 (d, J = 8.2 Hz, 1H), 7.67 (d,
J = 8.0 Hz, 1H), 7.50 (dd, J = 9.0, 4.6 Hz, 1H), 7.39 (ddd, J = 11.8, 10.1, 7.0 Hz,
2H), 7.23–7.19 (m, 1H), 7.14 (d, J = 8.6 Hz, 1H), 7.07 (d, J = 8.6 Hz, 1H), 6.92 (t,
J = 7.8 Hz, 1H), 4.08 (s, 2H), 3.77 (s, 3H). Anal. Calcd for C23H16FNO4: C 70.95,
H 4.14, N 3.60; found: C 70.94, H 4.16, N 3.61.
Conclusions
In conclusion, we report a one-pot, three-component reaction for synthesis of
3-arylbenzo[f]quinolone-1,2-dicarboxylate derivatives by imino Diels–Alder reac-
tion of aromatic aldehydes, 2-naphthylamine, and dimethyl but-2-ynedioate in
MeCN using 10 mol% SnCl2 as catalyst. Compared with reactions reported in the
literature, the main advantages of this procedure are milder conditions, economical
steps, and inexpensive catalyst.
Acknowledgments The project was supported by the National Natural Science Foundation of China
(No. 21346001, 21406166) and the Tianjin National Natural Science Foundation (No. 11JCZDJC21300).
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