A highly selective method for the synthesis of 1,3-diarylbenzo[f]quinoline derivatives catalyzed by silver triflate

Article abstract of DOI:10.1007/s00706-011-0662-8

The three-component reactions of aromatic aldehydes, naphthalen-2-amine, and phenylacetylene catalyzed by AgOTf in toluene selectively gave 1,3-diarylbenzo[f]quinolines in high yields. This procedure provides an efficient method for the synthesis of benzo[f]quinolines under mild reaction conditions and with high yields, high selectivity, and operational simplicity. Springer-Verlag 2011.

Full text of DOI:10.1007/s00706-011-0662-8

Monatsh Chem (2012) 143:935–938
DOI 10.1007/s00706-011-0662-8
ORIGINAL PAPER
A highly selective method for the synthesis
of 1,3-diarylbenzo[f]quinoline derivatives catalyzed
by silver triflate
•
Xiang-Shan Wang Jie Zhou Mei-Mei Zhang
•
•
•
Wei Wang Yu-Ling Li
Received: 30 January 2011 / Accepted: 25 September 2011 / Published online: 17 November 2011
Ó Springer-Verlag 2011
Abstract The three-component reactions of aromatic alde-
hydes, naphthalen-2-amine, and phenylacetylene catalyzed by
AgOTf in toluene selectively gave 1,3-diarylbenzo[f]quino-
lines in high yields. This procedure provides an efficient
method for the synthesis of benzo[f]quinolines under mild
reaction conditions and with high yields, high selectivity, and
operational simplicity.
dienophiles is one of the most convenient methods for
quinoline preparation. This reaction is usually catalyzed by
various Lewis acids, which was well documented in a
review by Kouznetsov [29] in 2009. However, these
methodologies possess some drawbacks, such as long
reaction times, multiple synthesis steps, or poor yields.
Recently, we found that Yb(OTf)3 was an efficient
catalyst to promote this type of reaction with high yields
using symmetrical but-2-ynedioate as reactant, reacting
with naphthalen-2-amine and aromatic aldehyde in toluene
[30]. To address the challenge of regioselectivity in this
novel reaction, phenylacetylene was selected to react with
naphthalen-2-amine and aromatic aldehyde. In this paper,
we report the highly regioselective reaction of naphthalen-
2-amine, phenylacetylene, and aromatic aldehyde cata-
lyzed by AgOTf.
Keywords Phenylacetylene Á Benzo[f]quinoline Á
AgOTf Á Synthesis
Introduction
Benzoquinoline and its derivatives are very useful com-
pounds in various fields of chemistry. For example, some
benzoquinolines exhibit antibacterial activity [1, 2], uridine
diphosphate-glucuronosyl transferase activity [3, 4], anti-
microbial activity [5], antimalarial activity [6], agonistic
activity [7], and antipsychotic activity [8]. In view of the
importance of these compounds, several methods for the
synthesis of benzoquinolines were developed by Kozlov
[9–15] and other groups [2, 16–28]. Among these known
procedures, the imino-Diels–Alder reaction (or Povarov
reaction) of N-arylimines (Schiff bases) with electron-rich
Results and discussion
Treatment of aromatic aldehyde 1, naphthalen-2-amine (2),
and phenylacetylene (3) in toluene in the presence of
1 mol% AgOTf at 100 °C afforded the corresponding 1,3-
diarylbenzo[f]quinoline derivatives 4 rather than 1,2-di-
arylbenzo[f]quinolinesinhighyieldsandhighregioselectivity
(Scheme 1).
In our initial study, Yb(OTf)3 was used as a catalyst to
promote the model reaction of 4-bromobenzaldehyde,
naphthalen-2-amine, and phenylacetylene. To our surprise,
the model reaction did not occur in the presence of 1 mol%
Yb(OTf)3 in toluene at 100 °C. Subsequently, screening of
other Lewis acid catalysts (trifluoromethanesulfonates)
containing other metal ions as well as solvents and opti-
mum temperature was carried out in our lab. A summary of
the optimization experiments is provided in Table 1.
Electronic supplementary material The online version of this
article (doi:10.1007/s00706-011-0662-8) contains supplementary
material, which is available to authorized users.
X.-S. Wang (&) Á J. Zhou Á M.-M. Zhang Á W. Wang Á Y.-L. Li
School of Chemistry and Chemical Engineering, Jiangsu Key
Laboratory of Green Synthetic Chemistry for Functional
Materials, Xuzhou Normal University, Xuzhou Jiangsu 221116,
People’s Republic of China
e-mail: xswang1974@yahoo.com
123

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X.-S. Wang et al.
According to the optimized conditions, various aro-
matic aldehydes 1 were then subjected to react with 2
and 3 to generate a library of 1,3-diarylbenzo[f]quino-
lines 4 (Table 2). For aldehyde 1, the yields of 4 were
not sensitive to the electronic properties of the aromatic
ring. In the presence of both electron-withdrawing groups
(such as halide and nitro) and electron-donating groups
(such as alkyl or alkoxyl groups) (Table 2), they all
give 1,3-diarylbenzo[f]quinoline derivatives 4 in high
yields.
Scheme 1
According to the literature [31], we think that AgOTf
catalyzes the reaction as a mild Lewis acid, another
important role is reacting with phenylacetylene to form
(phenylethynyl)silver. A proposed mechanism is given in
Scheme 2. The Schiff base I may be formed by the
reaction of aromatic aldehyde and naphthalene-2-amine.
Then the imino-Diels–Alder reaction between the AgOTf-
activated Schiff base II and (phenylethynyl)silver takes place
to form intermediate III regioselectively, followed by isom-
erization to give 3,4-dihydrobenzo[f]quinoline IV, which
is further oxidized by air to afford the final aromatized
1,3-diarylbenzo[f]quinoline 4.
Table 1 Synthesis of 4a under different reaction conditions
Entry
T/°C
Solvent
Cat. (mol%)
Isolated
yield/%
1
100
100
100
100
RT
Toluene
Toluene
Toluene
Toluene
Toluene
Toluene
Toluene
Toluene
Toluene
Toluene
Toluene
Toluene
Toluene
THF
Yb(OTf)3 (1)
AgOTf (1)
AgOTf (5)
AgOTf (10)
AgOTf (1)
AgOTf (1)
AgOTf (1)
AgOTf (1)
Sc(OTf)3 (1)
Cu(OTf)2 (1)
Zn(OTf)2 (1)
Ca(OTf)2 (1)
Y(OTf)3 (1)
AgOTf (1)
AgOTf (1)
AgOTf (1)
0
2
92
90
92
Trace
62
76
90
0
3
4
5
6
50
In conclusion, we found a mild and highly regioselective
method for the synthesis of 1,3-diarylbenzo[f]quinoline
derivatives via three-component reactions of aromatic
aldehydes, naphthalen-2-amine, and phenylacetylene cata-
lyzed by AgOTf. The features of this procedure are mild
reaction conditions, high yields, high regioselectivity, and
operational simplicity.
7
80
8
Reflux
100
100
100
100
100
Reflux
Reflux
100
9
10
11
12
13
14
15
16
0
0
0
0
72
78
68
Benzene
DMF
Experimental
Reaction conditions: 0.370 g 4-bromobenzaldehyde (2.0 mmol),
0.286 g naphthalen-2-amine (2.0 mmol), 0.204 g phenylacetylene
(2.0 mmol), 10 cm3 solvent
Melting points were determined in open capillaries. IR
spectra were recorded on a TENSOR 27 spectrometer in
KBr pellets. NMR spectra were obtained from solutions in
DMSO-d6 with Me4Si as internal standard using a Bruker
400 MHz spectrometer. HRMS analyses were carried out
using a Bruker-micro TOF-Q-MS analyzer.
RT room temperature, THF tetrahydrofuran, DMF N,N-dimethyl-
formamide
Finally it was found that only AgOTf was an efficient
catalyst for this reaction (4a in 92% yield; Table 1, entry
2). The results showed that at room temperature trace
amounts of products were observed by thin-layer chroma-
tograpy (TLC; Table 1, entry 5). To our delight, at 100 °C
in toluene the reaction proceeded smoothly in 92% yield.
Similar reactions were then carried out in the presence of 1,
5, and 10 mol% of AgOTf. The results from Table 1
(entries 3, 4, and 5) showed that 1 mol% of AgOTf at
100 °C is enough to promote the reaction in high yield
(92%). Higher loading of the catalyst did not improve the
reaction condition to a great extent. Thus, the optimal
reaction temperature and catalyst amount is 100 °C and
1 mol% AgOTf, respectively.
General procedure for the synthesis of 1,3-
diarylbenzo[f]quinoline derivatives 4
A dry 50-cm3 flask was charged with aromatic aldehyde
(2.0 mmol), 0.286 g naphthalen-2-amine (2.0 mmol), 0.204 g
phenylacetylene (2.0 mmol), 0.026 g AgOTf (0.1 mmol),
and 10 cm3 toluene. The reaction mixture was stirred at
100 °C for 10–14 h. A small amount of DMF (5 cm3) was
added to the mixture, and then the undissolved material was
removed by hot filtration. The desired products 4 were
obtained as crystals when the filtrate was cooled to room
temperature.
123

Synthesis of 1,3-diarylbenzo[f]quinoline derivatives
Table 2 Synthetic results of 4
catalyzed by AgOTf in toluene
937
Entry
Ar
Product
Time/h
Yield/%a
M.p. (Lit. m.p.)/°C
1
4-BrC6H4
4-ClC6H4
2-FC6H4
4a
4b
4c
4d
4e
4f
12
10
10
10
11
14
14
10
10
14
10
92
87
90
86
88
89
86
84
90
93
87
182–183 (183–184 [32])
171–172 (164–165 [33])
154–155
2
3
4
4-FC6H4
170–172 (171–172 [34])
189–190
5
3-ClC6H4
4-CH3C6H4
4-MeOC6H4
3-NO2C6H4
4-NO2C6H4
2-Thienyl
3,4-Cl2C6H3
6
149–150
7
4g
4h
4i
154–155 (154–155 [35])
232–233 (231 [35])
256–258 (254 [35])
177–178 (181–182 [36])
232–234
Reaction conditions: 1
8
(2 mmol), 0.286 g 2 (2 mmol),
0.204 g 3 (2 mmol), 0.026 g
AgOTf (0.1 mmol), 10 cm3
toluene, 100 °C
9
10
11
4j
4k
a
Isolated yields
Ar
142.0, 140.0, 133.9, 132.6, 131.9, 130.7, 129.4, 129.3,
128.92, 128.87, 128.5, 128.4, 128.2, 127.3, 127.0, 126.8,
NH2
N
AgOTf
+
RCHO
ꢀ
125.8, 122.5, 121.3 ppm; IR (KBr): m = 3,055, 1,574,
1,543, 1,523, 1,476, 1,448, 1,346, 1,252, 1,232, 1,150,
1,084, 947, 871, 839, 783, 756, 703, 691 cm-1; HRMS
(ESI): calcd for C25H17ClN (M ? H?) 366.1050, found
306.1065.
I
Ph
+C
Ph
+
Ph
C
N
+
Air
4
Ag
TfOAg
N
3-(4-Methylphenyl)-1-phenylbenzo[f]quinoline
N
Ar
Ar
H
(4f, C26H19N)
Ar
M.p.: 149–150 °C; 1H NMR (400 MHz, DMSO-d6):
d = 2.40 (s, 3H, CH3), 7.18–7.22 (m, 1H, ArH), 7.37 (d,
J = 8.0 Hz, 2H, ArH), 7.51–7.62 (m, 7H, ArH), 7.95 (s,
1H, ArH), 8.02–8.06 (m, 2H, ArH), 8.16 (d, J = 9.2 Hz,
1H, ArH), 8.26 (d, J = 8.4 Hz, 2H, ArH) ppm; 13C NMR
(100 MHz, DMSO-d6): d = 150.4, 148.9, 148.8, 144.0,
142.0, 132.4, 131.9, 129.5, 129.3, 129.1, 128.9, 128.6,
128.4, 128.1, 128.0, 127.0, 126.7, 126.7, 122.0, 119.9,
IV
III
II
AgOTf
Ph
C
CH
Ph
C
C Ag
Scheme 2
3-(2-Fluorophenyl)-1-phenylbenzo[f]quinoline
(4c, C25H17FN)
M.p.: 154–155 °C; 1H NMR (400 MHz, DMSO-d6):
d = 7.21–7.25 (m, 1H, ArH), 7.37–7.45 (m, 2H, ArH),
7.49–7.52 (m, 2H, ArH), 7.55–7.62 (m, 6H, ArH), 7.80 (d,
J = 2.0 Hz, 1H, ArH), 8.05–8.08 (m, 2H, ArH), 8.18–8.23
(m, 2H, ArH) ppm; 13C NMR (100 MHz, DMSO-d6):
d = 155.4, 151.7, 149.3, 148.9, 141.9, 138.5, 136.2, 135.7,
132.7, 132.0, 131.9, 131.0, 129.3, 128.9, 128.8, 128.4,
128.2, 127.3, 127.2, 127.0, 125.8, 122.6, 121.2, 112.7 ppm;
ꢀ
35.8 ppm; IR (KBr): m = 3,056, 3,024, 2,913, 1,603, 1,578,
1,542, 1,477, 1,441, 1,357, 1,284, 1,257, 1,181, 1,017, 873,
839, 822, 769, 753, 700 cm-1; HRMS (ESI): calcd for
C26H20N (M ? H?) 346.1596, found 346.1592.
3-(3,4-Dichlorophenyl)-1-phenylbenzo[f]quinoline
(4k, C25H16Cl2N)
M.p.: 232–234 °C; 1H NMR (400 MHz, DMSO-d6):
d = 7.18–7.22 (m, 1H, ArH), 7.50–7.61 (m, 7H, ArH),
7.79 (d, J = 8.8 Hz, 1H, ArH), 8.01–8.09 (m, 3H, ArH),
8.16 (d, J = 9.2 Hz, 1H, ArH), 8.36 (dd, J = 8.4, 2.0 Hz,
1H, ArH), 8.62 (d, J = 2.0 Hz, 1H, ArH) ppm; 13C NMR
(100 MHz, DMSO-d6): d = 152.7, 148.9, 146.3, 144.3,
142.0, 140.0, 133.9, 132.6, 131.9, 130.7, 129.4, 129.3,
128.9, 128.5, 128.4, 128.2, 127.3, 127.0, 126.8, 125.8,
ꢀ
IR (KBr): m = 3,054, 3,029, 1,579, 1,545, 1,485, 1,477,
1,451, 1,359, 1,213, 1,081, 1,032, 896, 872, 833, 773, 765,
748, 702 cm-1; HRMS (ESI): calcd for C25H17FN
(M ? H?) 350.1345, found 350.1331.
3-(3-Chlorophenyl)-1-phenylbenzo[f]quinoline
(4e, C25H16ClN)
M.p.: 189–190 °C; 1H NMR (400 MHz, DMSO-d6):
d = 7.19–7.23 (m, 1H, ArH), 7.51–7.62 (m, 9H, ArH),
8.03–8.09 (m, 3H, ArH), 8.18 (d, J = 8.8 Hz, 1H, ArH),
ꢀ
122.5, 121.3, 117.6 ppm; IR (KBr): m = 3,051, 3,029,
1,577, 1,540, 1,524, 1,473, 1,449, 1,382, 1,343, 1,326,
1,251, 1,223, 1,155, 1,130, 1,025, 946, 875, 835, 815, 766,
748, 704 cm-1; HRMS (ESI): calcd for C25H16Cl2N
(M ? H?) 400.0660, found 400.0661.
8.32–8.35 (m, 1H, ArH), 8.44–8.45 (m, 1H, ArH) ppm; 13
NMR (100 MHz, DMSO-d6): d = 152.7, 149.2, 148.9,
C
123

938
X.-S. Wang et al.
Acknowledgments We are grateful to the National Natural Science
Foundation of China (20802061), a project funded by the Priority
Academic Program Development of Jiangsu Higher Education Insti-
tutions, the Natural Science Foundation (08KJD150019) and Qing
Lan Project (08QLT001, 10QLD008) of Jiangsu Education Com-
mittee for financial support.
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