A multicomponent reaction of acetals for the preparation of quinolines

Article abstract of DOI:10.3184/174751913X13814036942713

A straightforward, mild, one-pot method has been found for the preparation of quinolines via a multi-component reaction using acetals or cyclic acetals, aromatic amines and alkynes catalysed by Bi(OTf)3. It gives good yields under mild conditions. This approach has been successfully applied for the synthesis of a range of quinolines with a variety of functional groups.

Full text of DOI:10.3184/174751913X13814036942713

JOURNAL OF CHEMICAL RESEARCH 2013
NOVEMBER, 677–680
RESEARCH PAPER 677
A multicomponent reaction of acetals for the preparation of quinolines
Xue-Lin Zhang, Qin-Pei Wu* and Qing-Shan Zhang
School of Chemical Engineering and Environment, Beijing Institute of Technology, Beijing 100081, P.R. China
A straightforward, mild, one-pot method has been found for the preparation of quinolines via a multi-component reaction using
acetals or cyclic acetals, aromatic amines and alkynes catalysed by Bi(OTf)3. It gives good yields under mild conditions. This
approach has been successfully applied for the synthesis of a range of quinolines with a variety of functional groups.
Keywords: quinolines, multicomponent reaction, acetals, amines, alkynes
Table 1 Results of screening solvents and Lewis acidsa
Quinolines are an important family of heterocyclic compounds
which include a number of biologically active compounds.1
Numerous synthetic methods have been developed for the
synthesis of the quinoline ring construction.1,2 Friedländer
annulation is the most simple, straightforward, and widely used
approach.3–5 Drawbacks associated with this type of reaction
are the low stability of 2-aminobenzaldehyde. Povarov reaction6
is another well-established protocol involving the coupling of
N-aryl aldimines with alkynes or alkenes catalysed by either
protic7 or Lewis acids.8 Although these approaches provide
efficient access to quinolines, many starting materials are not
readily available.
Entry
Catalyst
Solvent
Temp./°C
Time/h
Yield/%b
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
18
InCl3
Bi(OTf)3
FeCl3
BiCl3
AlCl3
SnCl2
CuCl
CuBr
CuI
CuOTf
I2
Bi(OTf)3
Bi(OTf)3
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
CH3NO2
EtOH
82
82
82
82
82
82
82
82
82
8
8
6
36
73
54
47
60
40
56
59
24
63
63
69
26
55
67
15
70
25
10
9
9
8
8
10
8
10
8
82
82
102
80
102
83
67
In view of the fact that imines can be formed in situ from
aldehydes and amines,9 a three-component Povarov reaction
involving aldehydes, amines, and alkynes has been established
for constructing quinoline nucleus.6,10 Compared to stepwise
procedures, multicomponent reactions (MCRs) exhibit
advantages since several bonds are formed in a one-pot
operation and the formation of waste is minimised.
9
8
9
9
8
9
Bi(OTf)3 1, 4-dioxane
Bi(OTf)3
Bi(OTf)3
Bi(OTf)3
Bi(OTf)3
DCE
THF
Toluene
CH2Cl2
110
40
aReaction conditions: phenylacetylene (1.5 mmol), benzaldehyde dimethyl
acetal (1.2 mmol), aniline (1.0 mmol), catalyst (0.30 mmol), solvent
(4.0 mL), reflux.
Acetals are extensively used as protecting groups11–13 and
prove to be a versatile function able to undergo a wide range
of reactions such as the displacement of one alkoxy group in
acetals by various nucleophiles.14–16 However, MCRs including
acetals are quite scarce. As part of our continuing effort on
extending the application of acetals as a function in the area
of organic synthesis, we report here the first reaction of acetals
with alkynes and anilines to furnish quinolines (Scheme 1).
This mild reaction of acetals was observed during our
investigation on an InCl3-catalysed A3-reaction of acetals
with alkynes and amines, via a one-pot process for preparing
propargylamines. Instead of the anticipated propargylamine
product, a quinoline derivative was formed in 38% isolated
yield when the reaction was conducted in toluene at 110 °C. The
valuable results prompted us to establish a mild protocol for the
construction of the quinoline ring starting from acetals.
Initially, the reaction of aniline, benzaldehyde dimethyl
acetal and phenylacetylene was first conducted with InCl3
(10 mol%) in CH3CN solution. It failed at room temperature
but the anticipated 2, 4-diphenylquinoline was obtained in 36%
yield after the solution was heated to reflux. To improve the
yield, a variety of reaction parameters were optimised. Catalyst
screening was first executed and disclosed that Bi(OTf)3 was
the most efficient one among InCl3, FeCl3, BiCl3, AlCl3, SnCl2,
CuCl, CuBr, CuI and I2 (Table 1, entries 1–9). Both CuOTf
and I2 had slightly lower activity to afford quinoline products
bIsolated yields after flash chromatography.
(Table 1, entries 10–11). Solvent selection showed that this
multicomponent process proceeded with high efficiency in
refluxing CH3CN solution (Table 1, entry 2, yield 73%). In
refluxing toluene solution, the yield was slightly lower (Table
1, entry 17, yield 70%). In the solution of THF or EtOH, the
yield was much lower (Table 1, entries 13 and 16, yield<26%).
Both proved to be unsuitable for this transformation. The much
lower yield in dichloromethane than in 1, 2-dichloroethane is
possibly due to the lower reaction temperature (Table 1, entries
15 and 18; 25% versus 67%). It is important to note that this
is an inexpensive, regioselective, and efficient approach to 2,
4-substituted quinolines from the simple and readily available
starting materials.
Using the optimal conditions, a range of acetals were
examined for this three component one-pot procedure. As
described in Table 2, all the acetals tested were smoothly
transformed to the corresponding 2,4-disubstituted quinolines
in good yields. Moreover, electronic variation in the aryl acetals
alters the efficiency of the reaction. Electron donating groups,
like the p-methoxy and p-methyl, led to lower yields (Table
2, entries 2 and 3 versus 1). A weak electron-withdrawing
substituents, such as p-F, p-Cl, p-Br, led to slightly lower
R2
O
R3
Bi(OTf)3 (30 mol%)
R3
R2
+
+
R1
O
CH CN Reflux
,
3
NH2
8 h
N
R1
Scheme 1 A multicomponent reaction of acetals for quinolines.
* Correspondent. E-mail: qpwu@bit.edu.cn
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678 JOURNAL OF CHEMICAL RESEARCH 2013
Table 2 Three-component reaction of acetals with phenylacetylene and
Table 3 Three-component reaction of acetals with alkynes and amines to
amines to form quinolinesa
form quinolinesa
Quinoline
Entry 2-substituent
(acetal)
Quinoline
4-substituent
(alkyne)
Quinoline
Quinoline
Quinoline
Entry
Yield/%b
6-sbustituent Yield/%b
(amine)
2-substituent(acetal)
6-substituent(amine)
1
2
3
4
5
6
7
8
C6H5
p-CH3OC6H4
p-CH3C6H4
p-FC6H4
p-ClC6H4
p-BrC6H4
p-NO2C6H4
m-NO2C6H4
O
H
H
H
H
H
H
H
H
73
55
59
67
72
64
56
52
1
2
3
C6H5
C6H5
C6H5
C6H5
C6H5
C6H5
C6H5
C6H5
CH3O
CH3
Cl
NO2
NO2
COOEt
CH3
H
H
H
H
H
63
66
74
61
67
61
35
35
70
65
59
0
4
C6H5
5
6
p-ClC6H4
C6H5
C6H5
7
C6H5
n-hexyl
COOMe
p-FC6H4
p-CH3C6H4
p-CH3OC6H4
Diphenylacetylene
8
C6H5
9
C6H5
9
10
11
12
13
14
15
16
17
H
H
59
57
68
64
61
55
63
59
0
O
10
11
12
C6H5
C6H5
C6H5
O
O
aReaction conditions: alkyne (1.5 mmol), acetal (1.2 mmol), amine
(1.0 mmol), Bi(OTf)3 (0.197 g, 0.30 mmol), acetonitrile (4.0 mL), reflux, 8 h.
bIsolated yields after flash chromatography.
O
l
C
H
O
O
transformation (Table 2, entries 3–5, 9 and 10). But in terms of
alkyl acetals, the yield was zero (Table 2, entry 17).
Cl
H
O
In term of aniline substrates, as shown in Table 3, both
electron-deficient and electron-sufficient aryl amines, such
as p-methoxy, acyl and p-nitro anilines, exhibited similar
efficiency and gave the corresponding products with good
yields (Table 3, entries 1–6). Aryl alkynes gave the products
in higher yields than alkyl alkenes (Table 3, entries 7–11).
When 1-octyne or methyl propiolate was employed in this
process, the desired quinoline product was formed in a much
lower yield (Table 3, entries 7 and 8). The yield associated
with 4-fluorophenylacetylene was quite good (70%) and
higher than those with p-methoxy or p-methylphenylacetylene
(Table 3, entry 9 versus 10 and 11). A strong electron-donating
p-methoxy group led to a lower yield than the weak electron-
donating group of p-methyl (Table 3, entries 10 and 11). But in
terms of diphenylacetylene, the yield was zero (Table 3, entry
12). Aldehydes gave the quinoline product in yield and a [4+2]
pathway was proposed for the coupling of aldehyde, alkyne and
amines. Probably a different mechanism takes place as acetals
are used in this reaction.
To elucidate the reaction pathway, we hoped to intercept
the reaction intermediate. Yang and coworkers19 demonstrated
that [In–H] generated in the InCl3/Et3SiH/MeOH system is
an active agent for reductive amination of aldehydes with
various amines. Accordingly, we introduced Et3SiH into this
reaction system in an attempt to trap an iminium ion. Under our
standard reaction conditions, Et3SiH (2.0 equiv.) was added to
the reaction solution of benzaldehyde dimethyl acetal, aniline,
and phenylacetylene. Indeed, only N-benzyl-4-methylaniline
(the reductive amination product) was obtained in 91% yield
(Scheme 2). The formation of N-benzyl-4-methylaniline showed
that benzaldehyde dimethyl acetal was first transformed into an
iminium ion with aniline and subsequently reduced by Et3SiH
in situ. The direct reductive amination of acetals with amines
could occur in situ in the presence of Bi(OTf)3–Et3SiH. These
experimental findings provided corroborative evidence that
this acetal protocol proceeds via the formation of an iminium
ion as an intermediate.20,21
O
H
O
O
H
O
Br
O
O
O
O
H
Br
CH3
H
O
O
aReaction conditions: phenylacetylene (1.5 mmol), acetals (1.2 mmol),
amines (1.0 mmol), Bi(OTf)3 (0.197 g, 0.30 mmol), acetonitrile (4.0 mL),
reflux, 8 h.
bIsolated yields after flash chromatography.
yields (Table 2, entries 4–6 versus 1), but higher than those
for electron donating groups (Table 2, entries 4–6 versus 2
and 3). With strong electron-withdrawing groups like m-NO2
and p-NO2 the yields were also good, but less than in those
associated with weak electron-withdrawing groups (Table 2,
entries 7 and 8 versus 4–6). Compared to the trace amount of
quinoline product given by m-nitrobenzaldehyde,17 our process
gave the expected product at quite good yield (Table 2, entry 8,
yield 52%). Thus these results validate an efficient procedure
from acetals to build 2, 4-diarylquinoline nucleus.2,10,17
The substrate versatility of this mild protocol was further
demonstrated by cyclic acetals, which are more stable than
their acyclic acetals. As shown in Table 2, both five- and six-
membered-ring acetals showed similar reactivity to acyclic
acetals undergoing this mild MCR to give the corresponding
quinolines with good yields (Table 2, entries 9–15). In some
cases, the yields given by acetals were nearly the same as
those associated with the corresponding aldehydes.10,18 Halogen
substituents in acetals show slight reduction in yield in this
O
NH2
Bi(OTf)3 (30 mol%)
O
+
Ph
+
+
Et iH
3S
NH
CH3CN, Reflux
8 h
Scheme 2 The reductive amination product.
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JOURNAL OF CHEMICAL RESEARCH 2013 679
1H), 7.76 (s, 1H), 7.72–7.66 (m, 1H), 7.52–7.41 (m, 6H). 13C NMR
(100 MHz, CDCl3) δ 153.01, 148.83, 147.76, 147.29, 144.40, 136.87,
129.29, 129.02, 128.47, 127.69, 127.27, 126.27, 125.13, 124.74, 122.96,
118.04.
In conclusion, we have described the first MCR of acetals via
activating both C–O and C–H bonds. Both alkyloxy groups of
acetals were displaced with amines and alkynes in situ to give
quinolines. Besides the advantages of MCR, our protocol also
provides methods to reduce waste and synthetic steps due to
eliminating deprotection procedure with regards to protecting
groups. The first MCR of acetals might broadly expand the
role of acetals apart from use as a masking group. The scope,
mechanism, stereoselectivity, and synthetic applications of this
reaction are under investigation.
2-(3-Nitrophenyl)-4-phenylquinoline: Yellow solid, m.p. 153–154 °C;
1
yield 52% (Table 2, entry 8); H NMR (400 MHz, CDCl3) δ 9.00 (t,
J=1.9 Hz, 1H), 8.52 (d, J=7.8 Hz, 1H), 8.24 (dd, J=8.2, 2.2 Hz, 1H),
8.19 (d, J=8.4 Hz, 1H), 7.87 (d, J=8.4 Hz, 1H), 7.79 (s, 1H), 7.72 (dd,
J=11.1, 4.2 Hz, 1H), 7.63 (t, J=8.0 Hz, 1H), 7.52–7.44 (m, 6H). 13C NMR
(100 MHz, CDCl3) δ 152.92, 148.95, 147.82, 147.73, 140.25, 136.92,
132.32, 129.21, 129.00, 128.76, 128.50, 127.70, 127.67, 126.09, 125.12,
124.76, 122.89, 121.40, 117.64. HRMS (ESI) calcd for C21H15N2O2
[M+H+]: 327.11280, found 327.11273.
Experimental
Reactions were performed under air. The materials were used as
purchased. Unless otherwise stated, all solvents and reagents were
commercially available and used as purchased without further
purification. Reactions were monitored by thin-layer chromatography
using gel F 254 plates. The silica gel (300–400 meshes) was used for
column chromatography, and the distillation range of petroleum ether
was 60–90 °C. NMR spectra was recorded in CDCl3 on either a Varian
400 MHz or a Bruker 400 MHz Fourier-transform spectrometer.
Chemical shifts were reported in ppm referenced to TMS or the CHCl3
solvent residual peak at 7.26 ppm for 1H and 77.23 ppm for 13C.
2-(3-Bromophenyl)-4-phenylquinoline2: White solid, m.p. 91–92 °C;
yield 63% (Table 2, entry 15); 1H NMR (400 MHz, CDCl3) δ 8.30 (s, 1H),
8.15 (d, J=8.4 Hz, 1H), 8.03 (d, J=7.9 Hz, 1H), 7.83 (d, J=8.4 Hz, 1H),
7.69–7.63 (m, 2H), 7.52–7.38 (m, 7H), 7.31 (d, J=9.1 Hz, 1H).
2-(3-Bromophenyl)-6-methyl-4-phenylquinoline2: Yellow solid, m.p.
94–95 °C; yield 59% (Table 2, entry 16); 1H NMR (400 MHz, CDCl3) δ
8.27 (s, 1H), 8.01 (dd, J=16.8, 8.2 Hz, 2H), 7.62 (s, 1H), 7.55 (s, 1H), 7.49–
7.41 (m, 7H), 7.28–7.24 (m, 1H), 2.37 (s, 3H).
6-Methoxy-2, 4-diphenylquinoline: Yellow solid, m.p. 119–120 °C
1
(lit.24 108–110 °C); yield 63% (Table 3, entry 1); H NMR (400 MHz,
CDCl3) δ 8.11–8.05 (m, 3H), 7.69 (s, 1H), 7.47 (m, 7H), 7.38–7.29 (m, 2H),
7.11 (d, J=2.6 Hz, 1H), 3.72 (s, 3H).
Preparation of quinolines
The acetal (1.2 mmol), aromatic amine (1.0 mmol), alkyne (1.5 mmol),
and Bi(OTf)3 (0.197 g, 0.3 mmol) were added to a flask (25 mL),
followed by the addition of acetonitrile (4.0 mL) under air. The mixture
was stirred under reflux and monitored by TLC. The solution was then
cooled to room temperature, diluted with dichloromethane (5 mL),
and washed with brine. The aqueous layer was extracted with CH2Cl2
(3×10 mL). The combined organic layer was dried over MgSO4,
filtered, and evaporated under vacuum. The residue was purified by
column chromatography on silica gel (petroleum ether) to afford the
desired product.
6-Methyl-2, 4-diphenylquinoline: White solid, m.p. 128–129 °C (lit.25
1
111 °C); yield 66% (Table 3, entry 2); H NMR (400 MHz, CDCl3) δ
8.25–8.17 (m, 3H), 7.82 (s, 1H), 7.69 (s, 1H), 7.63–7.53 (m, 8H), 7.49 (t,
J=6.6 Hz, 1H), 2.51 (s, 3H).
6-Chloro-2, 4-diphenylquinoline: White solid, m.p. 129–130°C (lit.22
130–132 °C); yield 74% (Table 3, entry 3); 1H NMR (400 MHz, CDCl3)
δ 8.23 (t, J=8.9 Hz, 3H), 7.91–7.86 (m, 2H), 7.70 (dd, J=9.0, 2.3 Hz, 1H),
7.62–7.49 (m, 8H).
6-Nitro-2, 4-diphenylquinoline: Yellow solid, m.p. 200–201 °C (lit.26
264 °C); yield 61% (Table 3, entry 4); 1H NMR (400 MHz, CDCl3) δ 8.78
(d, J=2.4 Hz, 1H), 8.41 (dd, J=9.2, 2.4 Hz, 1H), 8.25 (d, J=9.2 Hz, 1H),
8.17 (dd, J=7.9, 1.5 Hz, 2H), 7.90 (s, 1H), 7.56–7.44 (m, 8H). 13C NMR
(100 MHz, CDCl3) δ 159.01, 150.24, 150.01, 144.36, 137.46, 135.85,
130.73, 129.42, 128.42, 128.30, 128.11, 128.02, 126.81, 123.78, 122.05,
121.89, 119.70.
2,4-Diphenylquinoline: White solid, m.p. 113–114 °C (lit.22 111–
112 °C); yield 73% (Table 2, entry 1), 61% (Table 2, entry 13) and 55
1
(Table 2, entry 14); H NMR (400 MHz, CDCl3) δ 8.25 (d, J=8.5 Hz,
1H), 8.20 (d, J=8.2 Hz, 2H), 7.91 (d, J=8.4 Hz, 1H), 7.83 (s, 1H), 7.74 (t,
J=8.3 Hz, 1H), 7.60–7.44 (m, 9H).
2-(4-Methoxyphenyl)-4-phenylquinoline: White solid, m.p. 77–78 °C
(lit.23 78–79 °C); yield 55% (Table 2, entry 2); H NMR (400 MHz,
CDCl3) δ 8.13 (d, J=8.4 Hz, 1H), 8.09 (d, J=8.9 Hz, 2H), 7.80 (d,
J=8.4 Hz, 1H), 7.69 (s, 1H), 7.66–7.61 (m, 1H), 7.50–7.41 (m, 5H), 7.39–
7.33 (m, 1H), 6.96 (d, J=10.7 Hz, 2H), 3.80 (s, 3H).
2-(4-Chlorophenyl)-6-nitro-4-phenylquinoline18: Yellow solid, m.p.
1
1
118–119 °C; yield 67% (Table 3, entry 5); H NMR (400 MHz, CDCl3)
δ 8.77 (s, 1H), 8.41 (d, J=9.2 Hz, 1H), 8.23 (d, J=9.2 Hz, 1H), 8.13 (d,
J=8.5 Hz, 2H), 7.86 (s, 1H), 7.49 (dt, J=22.6, 7.5 Hz, 7H).
4-Phenyl-2-(p-tolyl)-quinoline: White solid, m.p. 104–105 °C (lit.23
95–96 °C); yield 59% (Table 2, entry 3), 59% (Table 2, entry 9) and 57%
(Table 2, entry 10); 1H NMR (400 MHz, CDCl3) δ 8.23 (d, J=8.5 Hz, 1H),
8.10 (d, J=7.4 Hz, 2H), 7.89 (d, J=8.4 Hz, 1H), 7.81 (s, 1H), 7.76–7.69 (m,
1H), 7.60–7.43 (m, 6H), 7.33 (d, J=7.8 Hz, 2H), 2.44 (s, 3H).
Ethyl-2, 4-diphenylquinoline-6-carboxylate: White solid, m.p.
133–134 °C; yield 61% (Table 3, entry 6); 1H NMR (400 MHz, CDCl3) δ
8.69 (s, 1H), 8.32 (t, J=8.2 Hz, 2H), 8.23 (d, J=7.0 Hz, 2H), 7.89 (s, 1H),
7.65–7.47 (m, 7H), 4.40 (q, J=7.1 Hz, 2H), 1.40 (t, J=7.1 Hz, 3H). 13C
NMR (100 MHz, CDCl3) δ 166.47, 158.80, 150.79, 137.81, 130.33, 130.05,
129.70, 129.25, 129.06, 128.95, 128.26, 127.88, 125.13, 120.12, 109.89,
61.40, 14.45. HRMS (ESI) calcd forC24H20NO2 [M+H+]: 354.14886,
found 354.14886.
4-Hexyl-6-methyl-2-phenylquinoline: White solid, m.p. 67–68 °C;
yield 35% (Table 3, entry 7); 1H NMR (400 MHz, CDCl3) δ 8.10–8.03 (m,
2H), 7.99 (d, J=8.6 Hz, 1H), 7.70 (s, 1H), 7.59 (s, 1H), 7.44 (dd, J= 11.9,
8.2 Hz, 3H), 7.36 (t, J=7.3 Hz, 1H), 3.07–2.95 (m, 2H), 2.50 (s, 3H),
1.73 (m, 2H), 1.40 (dd, J=14.8, 7.1 Hz, 2H), 1.28 (t, J=6.8 Hz, 4H), 0.83
(t, J=7.1 Hz, 3H). 13C NMR (100 MHz, CDCl3) δ 155.19, 147.50, 145.99,
139.08, 134.67, 130.32, 129.15, 127.92, 127.70, 126.43, 125.46, 121.33,
117.66, 31.48, 30.66, 29.05, 28.41, 21.59, 20.95, 13.07. HRMS (ESI) calcd
forC22H26N [M+H+]: 304.20598, found 304.20596.
2-(4-Fluorophenyl)-4-phenylquinoline: White solid, m.p. 64–65 °C
1
(lit.23 63–64 °C); yield 67% (Table 2, entry 4); H NMR (400 MHz,
CDCl3) δ 8.16–8.08 (m, 3H), 7.82 (d, J=8.4 Hz, 1H), 7.70–7.63 (m, 2H),
7.53–7.33 (m, 6H), 7.13 (t, J=8.7 Hz, 2H). 13C NMR (100 MHz, CDCl3)
δ 164.02, 161.54, 154.73, 148.31, 147.72, 137.27, 134.77, 134.74, 128.98,
128.61, 128.50, 128.43, 128.35, 127.58, 127.44, 125.36, 124.64, 117.94,
114.84, 114.62.
2-(4-Chlorophenyl)-4-phenylquinoline: White solid, m.p. 104–105 °C
(lit.23 104–105 °C); yield 72% (Table 2, entry 5), 68% (Table 2, entry
11) and 64% (Table 2, entry 12). 1H NMR (400 MHz, CDCl3) δ 8.27 (d,
J=8.3 Hz, 1H), 8.19 (d, J=8.6 Hz, 2H), 7.94 (d, J=8.4 Hz, 1H), 7.81–7.75
(m, 2H), 7.61–7.56 (m, 5H), 7.52 (dd, J=11.0, 4.3 Hz, 3H).
2-(4-Bromophenyl)-4-phenylquinoline: White solid, m.p. 121–122 °C
Methyl-2-phenylquinoline-4-carboxylate: White solid, m.p. 57–58 °C;
yield 35% (Table 3, entry 8); 1H NMR (400 MHz, CDCl3) δ 8.67 (s, 1H),
8.22 (d, J=8.3 Hz, 1H), 7.93 (d, J=7.8 Hz, 1H), 7.88–7.79 (m, 1H), 7.65
1
(lit.23 111–112 °C); yield 64% (Table 2, entry 6); H NMR (400 MHz,
CDCl3) δ 8.15 (d, J=8.4 Hz, 1H), 8.01 (d, J=8.6 Hz, 2H), 7.83 (d,
J=8.0 Hz, 1H), 7.71–7.64 (m, 2H), 7.60–7.55 (m, 2H), 7.49–7.39 (m, 6H).
2-(4-Nitrophenyl)-4-phenylquinoline: Yellow solid, m.p. 160–161 °C
(d, J=6.9 Hz, 2H), 7.48 (d, J=7.3 Hz, 3H), 7.26 (s, 1H), 3.75 (s, 3H). 13
C
NMR (101 MHz, CDCl3) δ 168.41, 158.08, 148.42, 139.38, 131.77, 129.56,
128.79, 128.63, 128.31, 127.39, 125.88, 125.12, 52.53. HRMS (ESI) calcd
forC17H14NO2 [M+H+]: 264.10191, found 264.10165.
1
(lit.23 156–157 °C); yield 56% (Table 2, entry 7); H NMR (400 MHz,
CDCl3) δ 8.32–8.24 (m, 4H), 8.17 (d, J=8.5 Hz, 1H), 7.85 (d, J=8.4 Hz,
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680 JOURNAL OF CHEMICAL RESEARCH 2013
4
5
W. Luo, Q. Mu, W. Qiu, T. Liu, F. Yang, X. Liu and J. Tang, Tetrahedron,
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4-(4-Fluorophenyl)-2-phenylquinoline: Light yellow solid, m.p. 82–
83 °C (lit.27 82–84 °C); yield 70% (Table 3, entry 9); 1H NMR (400 MHz,
CDCl3) δ 8.16 (d, J=8.8 Hz, 1H), 8.10 (dd, J=8.3, 1.2 Hz, 2H), 7.77 (d,
J=8.4 Hz, 1H), 7.70 (s, 1H), 7.68–7.62 (m, 1H), 7.47–7.35 (m, 6H), 7.16
(dd, J=9.9, 7.4 Hz, 2H). 13C NMR (100 MHz, CDCl3) δ 163.10, 160.63,
155.85, 147.78, 147.03, 138.50, 133.32, 133.28, 130.26, 130.18, 129.18,
128.58, 128.37, 127.82, 126.53, 125.43, 124.69, 124.31, 118.35, 114.74,
114.52. HRMS (ESI) calcd forC21H15FN [M+H+]: 300.11830, found
300.11816.
2-Phenyl-4-(p-tolyl)quinoline: Light yellow oily liquid; yield 65%
(Table 3, entry 10); 1H NMR (400 MHz, CDCl3) δ 8.15 (d, J=8.5 Hz, 1H),
8.10 (d, J=7.2 Hz, 2H), 7.85 (d, J=8.3 Hz, 1H), 7.72 (s, 1H), 7.66–7.61 (m,
1H), 7.43 (t, J=7.3 Hz, 2H), 7.37 (d, J=8.1 Hz, 4H), 7.27 (d, J=7.9 Hz,
2H), 2.39 (s, 3H). 13C NMR (100 MHz, CDCl3) δ 155.86, 148.16, 147.79,
138.70, 137.28, 134.43, 129.06, 128.44, 128.40, 128.25, 127.78, 126.54,
125.18, 124.84, 124.66, 118.29, 20.28. HRMS (ESI) calcd for C22H18N
[M+H+]: 296.14338, found 296.14307.
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86 °C (lit.28 101.4–102.0 °C); yield 59% (Table 3, entry 11); H NMR
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(400 MHz, CDCl3) δ 8.15 (d, J=8.4 Hz, 1H), 8.10 (d, J=7.1 Hz, 2H), 7.86
(d, J=8.4 Hz, 1H), 7.70 (s, 1H), 7.65–7.60 (m, 1H), 7.40 (m, 6H), 6.99 (d,
J=8.7 Hz, 2H), 3.81 (s, 3H).
N-Benzyl-4-methylaniline29: Light yellow oily liquid; yield 91%
(Scheme 2); 1H NMR (400 MHz, CDCl3) δ 7.47–7.35 (m, 4H), 7.34–7.24
(m, 1H), 7.03 (d, J=7.9 Hz, 2H), 6.61 (d, J=8.3 Hz, 2H), 4.34 (s, 2H), 3.97
(br s, 1H), 2.28 (s, 3H).
Financial support of this work from the National Natural
Science Foundation of China (21172019) is appreciated.
Received 17 July 2013; accepted 23 August 2013
Paper 1302076 doi: 10.3184/174751913X13814036942713
Published online: 11 November 23013
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