Selective reduction of nitroarenes by a Hantzsch 1,4-dihydropyridine: A facile and efficient approach to substituted quinolines

Article abstract of DOI:10.1055/s-0030-1260609

An efficient reductive cyclization of o-nitrocinnamoyl compounds was achieved by employing a Hantzsch 1,4-dihydropyridine ester as a biomimetic reducing agent in the presence of catalytic palladium on carbon. This approach was successfully applied to the synthesis of substituted quinolines. Georg Thieme Verlag Stuttgart ? New York.

Full text of DOI:10.1055/s-0030-1260609

2066
PAPER
Selective Reduction of Nitroarenes by a Hantzsch 1,4-Dihydropyridine:
A Facile and Efficient Approach to Substituted Quinolines
S
ubstituted Quin
u
i
Selecti
-
ve Redu
G
ction of
N
itroaren
u
a
State Key Laboratory of Applied Organic Chemistry, College of Chemistry and Chemical Engineering, Lanzhou University,
Lanzhou 730000, P. R. of China
b
Engineering Research Center for Eco-Dyeing & Finishing of Textiles, Ministry of Education, Zhejiang Sci-Tech University,
Hangzhou 310018, P. R. of China
Fax +86(931)8625657; E-mail: liuqiang@lzu.edu.cn
Received 16 March 2011; revised 21 April 2011
SnCl2,7 HCOONH4–Pd/C,7 Fe/AcOH8 and baker’s yeast9
have been used for the selective reductive cyclization of
2-nitrochalcones; however, some of these methods suffer
from relatively low yields, poor regioselectivity, tedious
reaction procedures, relatively expensive reagents and/or
rather lengthy synthetic sequences. Therefore, the devel-
opment of new strategies for the efficient reductive cy-
clization of o-nitrocinnamoyl compounds is urgently
needed.
Abstract: An efficient reductive cyclization of o-nitrocinnamoyl
compounds was achieved by employing a Hantzsch 1,4-dihydropy-
ridine ester as a biomimetic reducing agent in the presence of cata-
lytic palladium on carbon. This approach was successfully applied
to the synthesis of substituted quinolines.
Key words: quinolines, reductive cyclization, Hantzsch ester, bio-
mimetic reducing agent
The search for a more efficient chemoselective hydroge-
nation is one of the most intensely pursued challenges in
modern chemistry. In this regard, the selective transfor-
mation of nitroarenes bearing reducible functional groups
to functionalized anilines is an important research area
because of the relevance of these compounds to the phar-
maceutical and fine chemical industries. The functional-
ization of quinolines, thanks to the abundance of
quinolines in biologically and medicinally active com-
pounds,1 has received much attention to date. The reduc-
tion of o-nitrocinnamoyl compounds with reducing
agents, followed by cyclization to form quinolines, is one
of the major routes to access functionalized quinolines;
however, the process is somewhat difficult because of the
lack of selectivity in the reduction of a nitro group in the
presence of olefinic and carbonyl substituents. Reduction
systems such as CO,2 Sm–TiCl4,3 Zn–TiCl4,4 SmI2,5 In,6
Generally, the reduction of nitro compounds to amines is
approached using one of three methods. First is the cata-
lytic hydrogenation of the nitro compounds with molecu-
lar hydrogen by metal catalysts.10 The second is the
stoichiometric reduction of the corresponding aromatic
nitro compounds by using iron,11a tin,11b zinc11c and so on.
The third is the chemoselective hydrogenation of aromatic
nitro compounds catalyzed by metals in the presence of
organic reductants, such as silane/siloxane12 and ammoni-
um formate/copper nanoparticles.13 In contrast to the
chemical conversions described above, the biomimetic re-
duction of nitroarenes using nicotinamide adenine dinu-
cleotide (NADH) models has seldom been reported.14 The
Hantzsch 1,4-dihydropyridine HEH (diethyl 2,6-dimeth-
yl-1,4-dihydropyridine-3,5-dicarboxylate, see Scheme 1),
a model compound of coenzyme NAD(P)H, is one of the
most widely investigated biomimetic reductants. Recent
O
HEH, Pd/C, AcOH, 120 °C
(this work)
R
N
R
NO2
2
1
O
O
H
H
HEH
ammonium salt
THF, r.t.
HEH
phosphoric acid
solvent, heat
EtO
OEt
N
O
H
HEH
R
NO2
N
R
H
Scheme 1
SYNTHESIS 2011, No. 13, pp 2066–2072
x
x.
x
x
.
2
0
1
1
Advanced online publication: 26.05.2011
DOI: 10.1055/s-0030-1260609; Art ID: H29111SS
© Georg Thieme Verlag Stuttgart · New York

PAPER
Substituted Quinolines by the Selective Reduction of Nitroarenes
2067
Table 2 Synthesis of Quinolinesa
studies in our laboratory have shown that the reducibility
of HEH is dramatically enhanced in the presence of palla-
dium on carbon (Pd/C).15 Moreover, high chemoselectiv-
ities have been observed by regulating reaction
conditions, such as the amount of HEH, reaction temper-
atures and solvents. We have examined the selective re-
duction of a nitro group with HEH and Pd/C in the
presence of epoxy, ester or amide substituents and have
successfully accomplished the synthesis of 2H-1,4-ben-
zoxazine,15c benzoxazole15e and benzimidazole15e deriva-
tives. In this paper, we report that substituted quinolines
can be efficiently synthesized by the highly chemoselec-
tive Pd/C-catalyzed reduction of o-nitrocinnamoyl com-
pounds by HEH (Scheme 1).
O
R
HEH, Pd/C
AcOH
N
R
NO2
1
2
Entry Substrate
Productb
2a
Yieldc (%)
1
2
1a R = Ph
95
85
83
96
82
87
72d
70d
80
78
86
79
1b R = 4-MeC6H4
1c R = 2-MeC6H4
1d R = 4-MeOC6H4
1e R = 3-MeOC6H4
1f R = 2-MeOC6H4
1g R = 4-ClC6H4
1h R = 4-BrC6H4
1i R = 4-F3CC6H4
1j R = 1-naphthyl
1k R = 3-pyridyl
1l R = Me
2b
2c
3
4
2d
2e
As a new direction in the research of enantioselective hy-
drogenation catalyzed by organocatalysts, considerable
progress has been made over the past decade in the use of
HEH to selectively reduce the electron-deficient carbon–
carbon double bond of a,b-unsaturated carbonyl com-
pounds.16 The steady transfer hydrogenation of a,b-unsat-
urated carbonyl compounds16a 1 (Scheme 1 left) and
quinolines17 2 (Scheme 1 right) has been reported to occur
using HEH in the presence of organocatalysts. These two
side reactions pose difficulties in obtaining the desired
quinolines efficiently. Our preliminary studies focused on
the reductive cyclization of 2-nitrochalcone (1a) with
HEH (Table 1). No reaction occurred at room temperature
using ethanol or acetic acid as a solvent (Table 1, entries
1 and 3). Initial success was obtained by refluxing an eth-
anolic solution of 1a and HEH in the presence of Pd/C
(Table 1, entry 2). To our delight, when the reaction was
performed in refluxing acetic acid, quinoline 2a was ob-
tained in excellent yield (Table 1, entry 4). Importantly,
no conversion was observed when the reaction was re-
fluxed in acetic acid in the absence of Pd/C or HEH
(Table 1, entries 5 and 6).
5
6
2f
7
2g
8
2h
2i
9
10
11
12
2j
2k
2l
O
13
14
82
N
NO2
2m
2n
1m
1n R = H
85e
a Reaction conditions: 1 (1.0 mmol), HEH (3.6 mmol), 10% Pd/C
(2 wt% of HEH), AcOH (20 mL), 120 °C, 15 h.
b All products are known compounds and were characterized by EI-MS
spectrometry, and IR, 1H NMR and 13C NMR spectroscopy.
c Isolated yields.
Under the optimized conditions, the scope of the reaction
was explored with a variety of o-nitrocinnamoyl com-
pounds. The results are summarized in Table 2. The reac-
d HEH (3.2 mmol) was used.
e Analysis by GC-MS.
Table 1 Optimization of Reaction Conditionsa
O
Ph
N
Ph
NO2
2a
1a
Entry
Conditionsa
Yield (%)
1
2
3
4
5
6
10% Pd/C (2 wt% of HEH), HEH (3.6 equiv), EtOH, r.t., 15 h
10% Pd/C (2 wt% of HEH), HEH (3.6 equiv), EtOH, reflux, 15 h
10% Pd/C (2 wt% of HEH), HEH (3.6 equiv), AcOH, r.t., 15 h
10% Pd/C (2 wt% of HEH), HEH (3.6 equiv), AcOH, reflux, 15 h
HEH (3.6 equiv), AcOH, reflux, 15 h
0
49
0
95
0
10% Pd/C (18 mg), AcOH, reflux, 15 h
0
a Reactions were performed with 1a (1.0 mmol) and solvent (0.05 M/[starting material]).
Synthesis 2011, No. 13, 2066–2072 © Thieme Stuttgart · New York

2068
R.-G. Xing et al.
PAPER
Table 3 Synthesis of 2,3-Disubstituted Quinolinesa
tion works well with an electron-donating group (R =
4-Tol, 2-Tol, 4-MeOC6H4, 3-MeOC6H4, 2-MeOC6H4;
Table 2, entries 2–6) or an electron-withdrawing group
(R = 4-F3CC6H4; Table 2, entry 9) located on the benzoyl
ring of the o-nitrocinnamoyl compounds. When the para
position of the benzoyl ring was substituted by chlorine or
bromine, a small amount of dehalogenated product was
produced. To avoid overhydrogenation, the amount of
O
O
O
R2
R1
R1
HEH, Pd/C
AcOH
N
R2
NO2
3
4
HEH was decreased from 3.6 to 3.2 equivalents. The cor- Entry Substrate R1
responding 2-(4-halophenyl)quinoline yields were 72%
R2
Productb
Yieldc (%)
1
2
3
4
3a
3b
3c
3d
Me
Me
Me
Ph
4a
4b
4c
4d
82
74
77
98
and 70%, respectively (Table 2, entries 7 and 8). Good
results were obtained using 1-(naphthalen-1-yl)-3-(2-
nitrophenyl)prop-2-en-1-one (1j; Table 2, entry 10) and
3-(2-nitrophenyl)-1-(pyridin-3-yl)prop-2-en-1-one (1k;
Table 2, entry 11) as the starting materials. Aliphatic ke-
tones were also suitable for the reductive cyclization pro-
cedure (Table 2, entries 12 and 13). In particular, 2-
nitrocinnamaldehyde (1n) was converted into quinoline
(Table 2, entry 14) in 85% yield, which indicates that this
biomimetic reduction is tolerant to aldehydes and the
present reductive cyclization is highly chemoselective.
Ph
Ph
EtO
Me
O
O
OEt
5
3e
EtO
EtO
74
N
H
4e
To further broaden the scope of application, the synthesis
of 2,3-disubstituted quinolines was carried out by employ-
a Reaction conditions: 3 (1.0 mmol), HEH (3.6 mmol), 10% Pd/C
(2 wt% of HEH), AcOH (20 mL), 120 °C, 15 h.
ing a range of functionalized 2-(2-nitrobenzylidene)-1,3- b All products are known compounds and were characterized by EI-MS
spectrometry, and IR, 1H NMR and 13C NMR spectroscopy.
dicarbonyl compounds 3 as reactants (Table 3). These
starting materials have a highly electron-deficient double
c Isolated yields.
bond which can be easily reduced by HEH.18 Again, good
alyzed by Pd/C. As shown in Scheme 2, the high
functional group tolerance was observed for the reductive
chemoselectivities of the hydrogenation may arise from
cyclization reaction and the corresponding 2,3-disubsti-
the strong absorption of HEH on the palladium surface.
tuted quinolines were obtained in moderate to excellent
Thus, HEH is not only the reductant of the reaction but
yields (Table 3, entries 1–5).
also the modifier for the palladium surface. The preferen-
We also observed hydrogen gas evolution during reflux-
ing in acetic acid containing HEH and catalytic Pd/C. The
generation of hydrogen gas from HEH is supported by
DFT calculations.15e These facts indicate that palladium
hydride is generated during the aromatization of HEH cat-
tial absorption of HEH hinders absorption and the selec-
tive hydrogenation of the less-reactive moiety, thereby
leading to the predominant hydrogenation of the nitro
group.
Scheme 2
Synthesis 2011, No. 13, 2066–2072 © Thieme Stuttgart · New York

PAPER
Substituted Quinolines by the Selective Reduction of Nitroarenes
Quinolines 2 and 4; General Procedure
2069
In summary, we have demonstrated that the Hantzsch 1,4-
dihydropyridine HEH, a model compound of coenzyme
NAD(P)H, is a mild and efficient reductant for the reduc-
tive cyclization of o-nitrocinnamoyl compounds. The
high chemoselectivities and good yields make this a
promising method for the synthesis of substituted quino-
lines from simple and readily available nitroarenes. The
chemical behavior of HEH in the presence of Pd/C is dif-
ferent from that reported in homogeneous systems. In
comparison to the boom of research for HEH in homoge-
neous catalytic systems during the past few decades, more
elegant applications of HEH in heterogeneous catalytic
systems are expected.
To a soln of the o-nitrocinnamoyl compound 1 or 3 (1.0 mmol) in
AcOH (20 mL) were added HEH (3.6 mmol) and 10% Pd/C (2 wt%
of HEH), and the mixture was refluxed under stirring and argon at-
mosphere for 15 h. After completion of the reaction, as monitored
by TLC, the mixture was filtered and the filtrate was concentrated
under reduced pressure. The corresponding quinoline 2 or 4 was
isolated by silica gel column chromatography (PE–acetone) and
identified by comparing its EI-MS and 1H NMR, 13C NMR and IR
spectroscopic data with those reported in the literature.
2-Phenylquinoline (2a)
Yield: 195 mg (95%); white solid; mp 83–85 °C.
IR (KBr): 3421, 3053, 1596, 1553, 1447, 1318, 1074, 829, 766
cm–1.
1H NMR (400 MHz, CDCl3): d = 7.47–7.57 (m, 4 H), 7.74 (dt,
J = 7.4, 1.2 Hz, 1 H), 7.82 (d, J = 8.0 Hz, 1 H), 7.87 (d, J = 8.8 Hz,
1 H), 8.19–8.23 (m, 4 H).
13C NMR (100 MHz, CDCl3): d = 118.9, 126.2, 127.1, 127.4, 127.5,
128.8, 129.3, 129.6, 129.7, 136.7, 139.6, 148.3, 157.3.
EI-MS: m/z (%) = 205 (100.0) [M+], 176 (8.4), 102 (21.5), 88 (7.5),
76 (5.4), 51 (2.4).
1H and 13C NMR spectra were recorded on a Varian Mercury Plus
instrument (at 400 MHz and 100 MHz, respectively) and internally
referenced to the tetramethylsilane signal or residual protic solvent
signals. 1H NMR data are given as follows: chemical shift (d, ppm),
multiplicity (s = singlet, d = doublet, t = triplet, q = quartet, quint =
quintet, m = multiplet or unresolved), coupling constant(s) in Hz,
integration. 13C NMR data are reported in terms of chemical shift (d,
ppm). Mass spectra were recorded by EI methods on a TRACE
DSQ mass spectrometer. IR spectra were recorded on a Nicolet
NEXUS 670 FT-IR spectrometer. All reactions under standard con-
ditions were monitored by thin-layer chromatography (TLC) on sil-
ica gel F254 plates. Silica gel (200–300 mesh) was used for column
chromatography. The employed solvents were dried using standard
procedures. Commercially obtained reagents were used without fur-
ther purification.
2-(4-Tolyl)quinoline (2b)
Yield: 186 mg (85%); white solid; mp 79–81 °C.
IR (KBr): 3420, 3058, 1927, 1702, 1595, 1575, 1498, 815, 788
cm–1.
1H NMR (400 MHz, CDCl3): d = 2.43 (s, 3 H), 7.33 (d, J = 8.0 Hz,
2 H), 7.50 (t, J = 7.2 Hz, 1 H), 7.71 (dt, J = 7.2, 1.2 Hz, 1 H), 7.79
(dd, J = 8.0, 0.8 Hz, 1 H), 7.85 (d, J = 8.8 Hz, 1 H), 8.07 (d, J = 8.0
Hz, 2 H), 8.17 (t, J = 8.4 Hz, 2 H).
13C NMR (100 MHz, CDCl3): d = 21.4, 118.9, 126.1, 126.9, 127.1,
127.5, 129.2, 129.6, 129.7, 136.7, 136.9, 139.4, 148.3, 157.3.
EI-MS: m/z (%) = 219 (100.0) [M+], 204 (23.6), 128 (3.7), 109
(13.8), 95 (6.1), 84 (4.7).
o-Nitrocinnamoyl Compounds 1a–k; General Procedure6b
Starting materials 1a–k were easily obtained via a modified
Claisen–Schmidt reaction using o-nitrobenzaldehyde (5 mmol), the
appropriate ketone (5 mmol), K2CO3 (3.5 g) and NaOH (200 mg);
these compounds were placed into a triturator and ground for about
10 min. After completion of the reaction, the mixture was extracted
with EtOAc (3 × 25 mL) and the extracts were washed with H2O
(3 × 25 mL) and concentrated. The product 1a–k was purified using
column chromatography (PE–acetone).
2-(2-Tolyl)quinoline (2c)
Yield: 182 mg (83%); white solid; mp 70–71 °C.
IR (KBr): 3423, 3057, 2958, 1952, 1726, 1598, 1456, 837, 760
cm–1.
2-(2-Nitrobenzylidene)cyclopentanone (1m)19
A soln of cyclopentanone (100 mmol) and morpholine (9 mL, 100
mmol) in toluene (100 mL) was heated under reflux in a Dean–Stark
apparatus until no further H2O was collected. o-Nitrobenzaldehyde
(100 mmol) was then added to the cooled solution and the mixture
was heated under reflux until no further H2O was collected. A 1:1
mixture of H2O and concd HCl (50 mL) was added dropwise to the
stirred, cooled solution which was left for a further hour. The solu-
tion was then washed with 10% aq Na2CO3 (100 mL), dried
(MgSO4), filtered and concentrated; the product was purified using
column chromatography (PE–acetone, 10:1).
1H NMR (400 MHz, CDCl3): d = 2.42 (s, 3 H), 7.29–7.36 (m, 3 H),
7.49–7.58 (m, 3 H), 7.74 (dt, J = 8.4, 1.2 Hz, 1 H), 7.85 (d, J = 7.6
Hz, 1 H), 8.18 (d, J = 8.8 Hz, 1 H), 8.20 (d, J = 8.8 Hz, 1 H).
13C NMR (100 MHz, CDCl3): d = 20.3, 122.3, 126.0, 126.4, 126.7,
127.5, 128.5, 129.5, 129.6, 129.7, 130.8, 136.0, 136.1, 140.6, 147.8,
160.2.
EI-MS: m/z (%) = 219 (38.1) [M+], 218 (100) [M – 1]+, 109 (33.0),
75 (11.4), 63 (15.5), 51 (17.4), 39 (23.1).
2-(4-Methoxyphenyl)quinoline (2d)
Yield: 226 mg (96%); white solid; mp 123–125 °C.
2-(2-Nitrobenzylidene)-1,3-dicarbonyl Compounds 3a–e;
General Procedure20
IR (KBr): 3412, 2960, 1718, 1598, 1498, 1430, 1251, 818, 750
cm–1.
1H NMR (400 MHz, CDCl3): d = 3.88 (s, 3 H), 7.04 (d, J = 8.8 Hz,
2 H), 7.49 (dt, J = 7.6, 0.8 Hz, 1 H), 7.70 (dt, J = 7.8, 1.2 Hz, 1 H),
7.78–7.83 (m, 2 H), 8.12–8.17 (m, 4 H).
13C NMR (100 MHz, CDCl3): d = 55.4, 114.2, 118.5, 125.9, 126.9,
127.4, 128.9, 129.5, 129.6, 132.2, 136.6, 148.2, 156.9, 160.8.
A soln of o-nitrobenzaldehyde (1.0 mmol), the appropriate 1,3-di-
carbonyl compound (1.1 mmol), piperidine (0.1 mmol) and glacial
AcOH (0.5 mmol) in reagent grade benzene (0.2 M) was heated to
reflux using a Dean–Stark apparatus for 5 h or until the reaction
went to completion. The reaction mixture was cooled to r.t. and di-
luted with EtOAc (80 mL). This mixture was washed with 1 M aq
HCl (2 × 15 mL), 1 M aq NaOH (2 × 15 mL) and brine (2 × 15 mL).
The organic layer was dried (Na2SO4), filtered and concentrated un-
der reduced pressure. The crude residue was purified by silica gel
flash chromatography (PE–acetone) to afford the product 3a–e.
EI-MS: m/z (%) = 235 (100.0) [M+], 220 (39.6), 192 (37.6), 149
(18.0), 95 (7.0), 44 (6.1).
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R.-G. Xing et al.
PAPER
2-(3-Methoxyphenyl)quinoline (2e)
Yield: 193 mg (82%); colorless oil.
EI-MS: m/z (%) = 273 (100.0) [M+], 204 (60.0), 101 (17.5), 76
(22.2), 69 (27.6), 50 (29.1).
IR (KBr): 3059, 2929, 1724, 1599, 1557, 1289, 1041, 830, 781 cm–1.
2-(Naphthalen-1-yl)quinoline (2j)
Yield: 199 mg (78%); white solid; mp 95–97 °C.
1H NMR (400 MHz, CDCl3): d = 3.92 (s, 3 H), 7.01 (dd, J = 8.2, 2.4
Hz, 1 H), 7.42 (t, J = 8.0 Hz, 1 H), 7.51 (t, J = 8.0 Hz, 1 H), 7.69–
7.73 (m, 2 H), 7.77–7.85 (m, 3 H), 8.18 (d, J = 8.4 Hz, 2 H).
13C NMR (100 MHz, CDCl3): d = 55.4, 112.7, 115.4, 119.0, 120.0,
126.3, 127.2, 127.4, 129.6, 129.7, 129.8, 136.7, 141.1, 148.2, 157.1,
160.1.
IR (KBr): 3422, 3055, 1709, 1596, 1503, 1423, 1301, 837, 782
cm–1.
1H NMR (400 MHz, CDCl3): d = 7.45–7.53 (m, 2 H), 7.60 (t,
J = 7.6 Hz, 2 H), 7.70–7.73 (m, 2 H), 7.78 (t, J = 7.2 Hz, 1 H), 7.90–
7.96 (m, 3 H), 8.12 (d, J = 8.0 Hz, 1 H), 8.23 (d, J = 8.4 Hz, 1 H),
8.28 (d, J = 8.4 Hz, 1 H).
13C NMR (100 MHz, CDCl3): d = 123.3, 125.4, 125.7, 126.0, 126.6,
126.6, 127.0, 127.6, 127.8, 128.3, 129.1, 129.7, 129.8, 131.3, 134.0,
136.3, 138.7, 148.1, 159.4.
EI-MS: m/z (%) = 235 (83.5) [M+], 204 (100.0), 130 (97.1), 102
(53.5), 75 (38.1), 39 (49.0).
2-(2-Methoxyphenyl)quinoline (2f)
Yield: 204 mg (87%); colorless oil.
EI-MS: m/z (%) = 255 (47.9) [M+], 254 (100.0) [M – 1]+, 127
(36.0), 113 (10.7), 75 (13.0), 63 (10.4), 51 (14.4), 39 (10.6).
IR (KBr): 3059, 2933, 1714, 1599, 1497, 1253, 1023, 833, 757
cm–1.
1H NMR (400 MHz, CDCl3): d = 3.87 (s, 3 H), 7.04 (d, J = 8.4 Hz,
1 H), 7.13 (dt, J = 7.6, 0.8 Hz, 1 H), 7.42 (dt, J = 8.4, 2.0 Hz, 1 H),
7.53 (dt, J = 8.0, 1.2 Hz, 1 H), 7.70 (dt, J = 6.8, 1.6 Hz, 1 H), 7.82–
7.90 (m, 3 H), 8.14 (d, J = 8.4 Hz, 1 H), 8.17 (d, J = 8.4 Hz, 1 H).
13C NMR (100 MHz, CDCl3): d = 55.5, 111.3, 121.1, 123.3, 126.0,
126.9, 127.3, 129.0, 129.5, 129.6, 130.2, 131.4, 134.9, 148.2, 157.0,
157.1.
EI-MS: m/z (%) = 235 (84.8) [M+], 204 (100.0), 191 (13.3), 130
(98.8), 102 (53.4), 89 (20.5), 75 (37.4), 63 (41.8), 51 (43.6), 39
(47.8).
2-(Pyridin-3-yl)quinoline (2k)
Yield: 177 mg (86%); yellow solid; mp 69–72 °C.
IR (KBr): 3499, 3004, 1710, 1598, 1507, 1362, 1224, 839, 788
cm–1.
1H NMR (400 MHz, CDCl3): d = 7.46 (ddd, J = 8.0, 4.8, 0.4 Hz, 1
H), 7.57 (td, J = 8.0, 1.2 Hz, 1 H), 7.76 (dt, J = 6.8, 1.6 Hz, 1 H),
7.85 (d, J = 8.4 Hz, 1 H), 7.89 (d, J = 8.4 Hz, 1 H), 8.18 (d, J = 8.4
Hz, 1 H), 8.27 (d, J = 8.4 Hz, 1 H), 8.50 (td, J = 8.0, 2.0 Hz, 1 H),
8.70 (dd, J = 4.8, 1.6 Hz, 1 H), 9.36 (d, J = 2.0 Hz, 1 H).
13C NMR (100 MHz, CDCl3): d = 118.5, 123.7, 126.8, 127.4, 127.5,
129.7, 130.0, 135.0, 135.2, 137.2, 148.4, 148.7, 150.1, 154.6.
EI-MS: m/z (%) = 206 (100.0) [M+], 180 (35.5), 154 (10.5), 128
(31.2), 101 (16.8), 89 (24.5), 76 (33.2), 63 (21.9), 51 (62.1), 39
(21.0).
2-(4-Chlorophenyl)quinoline (2g)
Yield: 172 mg (72%); light yellow crystals; mp 108–110 °C.
IR (KBr): 3394, 3061, 1938, 1710, 1594, 1428, 1286, 816, 786
cm–1.
1H NMR (400 MHz, CDCl3): d = 7.48–7.55 (m, 3 H), 7.73 (t,
J = 8.0 Hz, 1 H), 7.82 (d, J = 8.4 Hz, 2 H), 8.10–8.22 (m, 4 H).
13C NMR (100 MHz, CDCl3): d = 118.5, 126.5, 127.2, 127.5, 128.8,
129.0, 129.7, 129.8, 135.5, 137.0, 138.0, 148.2, 156.0.
EI-MS: m/z (%) = 239 (86.4) [M+], 204 (100.0), 176 (11.3), 102
(17.4), 88 (11.3), 75 (8.1), 40 (5.2).
2-Methylquinoline (2l)
Yield: 113 mg (79%); colorless oil.
IR (KBr): 3390, 3055, 1716, 1658, 1602, 1504, 1425, 821, 783
cm–1.
1H NMR (400 MHz, CDCl3): d = 2.74 (s, 3 H), 7.25 (d, J = 8.4 Hz,
1 H), 7.46 (t, J = 7.4 Hz, 1 H), 7.67 (t, J = 7.2 Hz, 1 H), 7.74 (d,
J = 8.0 Hz, 1 H), 8.00–8.04 (m, 2 H).
13C NMR (100 MHz, CDCl3): d = 25.3, 121.9, 125.6, 126.4, 127.4,
128.5, 129.3, 136.1, 147.7, 158.9.
2-(4-Bromophenyl)quinoline (2h)
Yield: 198 mg (70%); white solid; mp 119–121 °C.
IR (KBr): 3417, 3059, 1712, 1596, 1552, 1362, 1221, 818, 768
cm–1.
1H NMR (400 MHz, CDCl3): d = 7.54 (dt, J = 7.4, 1.2 Hz, 1 H),
7.65 (dd, J = 6.8, 2.0 Hz, 2 H), 7.73 (dt, J = 6.8, 1.2 Hz, 1 H), 7.83
(dd, J = 7.6, 1.2 Hz, 2 H), 8.05 (dd, J = 6.8, 2.0 Hz, 2 H), 8.16 (d,
J = 8.4 Hz, 1 H), 8.22 (d, J = 8.4 Hz, 1 H).
13C NMR (100 MHz, CDCl3): d = 118.5, 123.9, 126.5, 127.2, 127.5,
129.1, 129.7, 129.9, 132.0, 137.0, 138.5, 148.2, 156.0.
EI-MS: m/z (%) = 283 (64.9) [M+], 204 (100.0), 176 (20.0), 149
(57.4), 102 (72.4), 75 (45.3), 50 (43.0).
EI-MS: m/z (%) = 143 (100.0) [M+], 128 (17.6), 115 (25.7), 101
(10.1), 89 (11.1), 75 (16.5), 63 (16.2), 51 (21.7).
2,3-Dihydro-1H-cyclopenta[b]quinoline (2m)
Yield: 139 mg (82%); white solid; mp 59–60 °C.
IR (KBr): 3393, 3056, 1724, 1702, 1621, 1497, 1404, 862, 782
cm–1.
1H NMR (400 MHz, CDCl3): d = 2.20 (quint, J = 7.6 Hz, 2 H), 3.08
(dt, J = 7.6, 1.2 Hz, 2 H), 3.16 (t, J = 7.6 Hz, 2 H), 7.45 (dt, J = 7.6,
0.8 Hz, 1 H), 7.61 (dt, J = 8.4, 1.2 Hz, 1 H), 7.72 (d, J = 7.6 Hz, 1
H), 7.87 (s, 1 H), 8.02 (d, J = 8.4 Hz, 1 H).
13C NMR (100 MHz, CDCl3): d = 23.6, 30.5, 34.5, 125.5, 127.4,
127.4, 128.3, 128.5, 130.4, 135.6, 147.4, 167.9.
EI-MS: m/z (%) = 168 (100.0) [M – 1]+, 140 (11.2), 115 (13.4), 89
(11.0), 84 (28.2), 63 (26.2), 51 (20.3), 39 (32.3).
2-[4-(Trifluoromethyl)phenyl]quinoline (2i)
Yield: 218 mg (80%); white solid; mp 141–142 °C.
IR (KBr): 3393, 2923, 1720, 1592, 1324, 1119, 1071, 816, 789 cm–1.
1H NMR (400 MHz, CDCl3): d = 7.57 (t, J = 8.0 Hz, 1 H), 7.74–
7.79 (m, 3 H), 7.84–7.90 (m, 2 H), 8.18 (d, J = 8.4 Hz, 1 H), 8.25–
8.29 (m, 3 H).
1-(2-Methylquinolin-3-yl)ethanone (4a)
13C NMR (100 MHz, CDCl3): d = 118.6, 124.2 (q, J = 271.0 Hz),
125.6 (q, J = 4.0 Hz), 126.8, 127.4, 127.5, 127.7, 129.8, 129.9,
131.0 (q, J = 30.0 Hz), 137.0, 142.8, 148.2, 155.5.
Yield: 152 mg (82%); yellow solid; mp 72–74 °C.
IR (KBr): 3057, 2965, 1708, 1679, 1562, 1420, 1196, 812, 780
cm–1.
Synthesis 2011, No. 13, 2066–2072 © Thieme Stuttgart · New York

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Substituted Quinolines by the Selective Reduction of Nitroarenes
2071
1H NMR (400 MHz, CDCl3): d = 2.72 (s, 3 H), 2.92 (s, 3 H), 7.56
(dt, J = 7.4, 1.2 Hz, 1 H), 7.79 (dt, J = 8.0, 1.2 Hz, 1 H), 7.86 (d,
J = 8.0 Hz, 1 H), 8.04 (d, J = 8.8 Hz, 1 H), 8.48 (s, 1 H).
Supporting Information for this article is available online at
http://www.thieme-connect.com/ejournals/toc/synthesis.
13C NMR (100 MHz, CDCl3): d = 25.6, 29.2, 125.6, 126.6, 128.3,
128.6, 131.1, 131.7, 138.1, 148.3, 157.6, 199.9.
Acknowledgment
We thank the National Natural Science Foundation of China (Grant
No. 20702023) and Zhejiang Provincial Top Academic Discipline
of Applied Chemistry and Eco-Dyeing & Finishing Engineering
(Grant No. YR2010007) for financial support.
EI-MS: m/z (%) = 185 (62.2) [M+], 170 (91.7), 142 (100), 115
(31.8), 101 (13.1), 75 (10.2), 43 (11.2).
(2-Methylquinolin-3-yl)(phenyl)methanone (4b)
Yield: 183 mg (74%); white solid; mp 60–62 °C.
IR (KBr): 3421, 3059, 1718, 1617, 1591, 1553, 1222, 865, 771 cm–1.
References
1H NMR (400 MHz, CDCl3): d = 2.16 (s, 3 H), 7.50–7.52 (m, 3 H),
7.60 (m, 1 H), 7.67–7.70 (m, 2 H), 7.79–7.81 (m, 1 H), 7.92 (d,
J = 8.1 Hz, 1 H), 8.19 (d, J = 8.4 Hz, 1 H), 8.38 (s, 1 H).
13C NMR (100 MHz, CDCl3): d = 30.4, 126.1, 127.2, 128.4, 128.8,
129.1, 129.3, 129.5, 134.8, 140.2, 140.9, 148.3, 156.8, 203.0.
EI-MS: m/z (%) = 247 (57.9) [M+], 232 (100.0), 204 (35.8), 176
(17.6), 101 (17.2), 88 (12.0), 75 (37.6), 51 (44.0), 43 (79.3).
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Phenyl(2-phenylquinolin-3-yl)methanone (4c)
Yield: 238 mg (77%); white solid; mp 134–136 °C.
IR (KBr): 3408, 3059, 1718, 1664, 1593, 1554, 1234, 871, 770
cm–1.
1H NMR (400 MHz, CDCl3): d = 7.26–7.34 (m, 5 H), 7.47 (t,
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EI-MS: m/z (%) = 309 (12.3) [M+], 280 (32.1), 232 (17.4), 105
(32.5), 77 (100), 51 (59.7).
Ethyl 2-Methylquinoline-3-carboxylate (4d)
Yield: 211 mg (98%); brown solid; mp 65–66 °C.
IR (KBr): 3407, 3050, 1718, 1620, 1560, 1278, 1064, 870, 782
cm–1.
1H NMR (400 MHz, CDCl3): d = 1.45 (t, J = 7.2 Hz, 3 H), 3.00 (s,
3 H), 4.44 (q, J = 7.2 Hz, 2 H), 7.53 (t, J = 7.6 Hz, 1 H), 7.77 (t,
J = 7.6 Hz, 1 H), 7.85 (d, J = 8.0 Hz, 1 H), 8.04 (d, J = 8.4 Hz, 1 H),
8.72 (s, 1 H).
13C NMR (100 MHz, CDCl3): d = 14.3, 25.6, 61.3, 123.9, 125.7,
126.4, 128.4, 128.5, 131.6, 139.8, 148.5, 158.4, 166.5.
EI-MS: m/z (%) = 215 (95.9) [M+], 187 (16.4), 169 (100.0), 142
(65.3), 115 (29.4), 101 (15.6), 75 (11.0).
Ethyl 2-Oxo-1,2-dihydroquinoline-3-carboxylate (4e)
Yield: 161 mg (74%); yellow solid; mp 162–164 °C.
IR (KBr): 3446, 3009, 1729, 1620, 1565, 1483, 1210, 874, 797
cm–1.
1H NMR (400 MHz, DMSO): d = 1.29 (t, J = 6.8 Hz, 3 H), 4.26 (q,
J = 6.8 Hz, 2 H), 7.21 (dt, J = 8.0, 1.2 Hz, 1 H), 7.31 (d, J = 8.4 Hz,
1 H), 7.59 (dt, J = 8.0, 1.2 Hz, 1 H), 7.80 (dd, J = 8.0, 0.8 Hz, 1 H),
8.47 (s, 1 H), 12.02 (s, 1 H).
13C NMR (100 MHz, DMSO): d = 14.1, 60.7, 115.0, 117.7, 122.2,
123.4, 129.4, 132.6, 140.1, 143.5, 158.5, 164.4.
EI-MS: m/z (%) = 217 (37) [M+], 172 (36.7), 145 (100.0), 116
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R.-G. Xing et al.
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Synthesis 2011, No. 13, 2066–2072 © Thieme Stuttgart · New York