Triflic Anhydride Promoted Intramolecular Cyclization of N -Aryl Cinnamides: Access to Polysubstituted Quinolin-2(1 H)-ones

Article abstract of DOI:10.1055/s-0036-1590821

A facile and efficient synthesis of polysubstituted quinolin-2(1 H)-ones is developed via intramolecular cyclization of readily available N -aryl cinnamides promoted by triflic anhydride in N, N -dimethyl trifluoroacetamide (DTA) under mild conditions.

Full text of DOI:10.1055/s-0036-1590821

SYNTHESIS
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© Georg Thieme Verlag Stuttgart · New York
2017, 49, A–G
paper
A
en
Q. Zhang et al.
Paper
Synthesis
Triflic Anhydride Promoted Intramolecular Cyclization of N-Aryl
Cinnamides: Access to Polysubstituted Quinolin-2(1H)-ones
Qian Zhang
Jingwen Yuan
Mangfei Yu
O
O
O
O
R1
R1
Tf2O, DTA, 80 °C
DDQ
N
N
R
R
Ar
Ar
R2
R2
Rui Zhang*
Yongjiu Liang
Peng Huang
Dewen Dong*
14 examples, 68–85% yield
Jilin Province Key Laboratory of Green Chemistry and
Process, Changchun Institute of Applied Chemistry,
Chinese Academy of Sciences, 5625 Renmin Street,
Changchun 130022, P. R. of China
ariel@ciac.ac.cn
dwdong@ciac.ac.cn
Received: 24.04.2017
Accepted after revision: 05.06.2017
Published online: 02.08.2017
diated by triflic acid,11 and substituted quinolin-2(1H)-ones
from penta-2,4-dienamides mediated by concentrated
aqueous H2SO4.12 More recently, we achieved a facile syn-
thesis of indeno[2,1-c]quinolin-6(7H)-ones from α-acetyl
N-aryl cinnamides in the presence of polyphosphoric acid.13
In connection with these previous investigations and our
continued efforts on the synthesis of heterocycles through
acid-mediated processes, we decided to examine the reac-
tivity of α-acyl N-aryl cinnamides bearing different substit-
uents toward triflic acid and various anhydrides. As a result
of these studies, we developed a facile and efficient synthe-
sis of substituted quinolin-2(1H)-ones and dihydroquino-
lin-2(1H)-ones in the presence of triflic anhydride under
mild conditions. Herein, we report our experimental re-
sults.
The substrates, N-aryl cinnamides 1, were prepared by
Knoevenagel condensation of commercially available β-oxo
amides with aryl aldehydes in the presence of piperidine in
acetic acid according to a reported procedure.13 Next, we se-
lected 2-benzylidene-3-oxo-N-phenylbutanamide (1a) as a
model compound to investigate its reactivity under acidic
conditions. Thus, the reaction of 1a was first attempted in
the presence of triflic acid (1.0 equiv) in N,N-dimethyl tri-
fluoroacetamide (DTA) (5.0 mL) at 50 °C, but no reaction oc-
curred as indicated by TLC (Table 1, entry 1). On treatment
of 1a with triflic anhydride (1.0 equiv) at 50 °C in DTA, the
reaction proceeded to furnish a major product (45% yield)
after work-up and purification by silica gel column chroma-
tography, which was characterized as 3-acetyl-4-
phenylquinolin-2(1H)-one (2a) (entry 2) on the basis of
spectral and analytical data.
DOI: 10.1055/s-0036-1590821; Art ID: ss-2017-h0271-op
Abstract A facile and efficient synthesis of polysubstituted quinolin-
2(1H)-ones is developed via intramolecular cyclization of readily avail-
able N-aryl cinnamides promoted by triflic anhydride in N,N-dimethyl
trifluoroacetamide (DTA) under mild conditions.
Key words C–C bond formation, cyclization reaction, heterocycles,
quinolin-2(1H)-ones, triflic anhydride
Quinolin-2(1H)-ones and their analogues have drawn
considerable interest from researchers as a result of their
presence in numerous natural products and synthetic or-
ganic compounds, and due to their diverse and useful bio-
activities.1,2 For instance, some substituted quinolin-2(1H)-
ones have been identified as angiotensin II receptor antago-
nists, antibiotics, antiplatelet agents and antitumor agents.3
In addition, the utility of quinolin-2(1H)-ones as versatile
building blocks for the synthesis of a wide variety of aza-
heterocycles has directed extensive research toward the
construction of the framework of such compounds.4 To
date, many synthetic approaches are available to access
quinolin-2(1H)-ones and their derivatives, which include
the classical acid-catalyzed Knorr synthesis,5 the base-cata-
lyzed Friedländer synthesis6 and the metal-catalyzed het-
eroannulation of acyclic precursors.7 Recently, some im-
proved synthetic methods associated with microwaves8 or
irradiation9 have also been reported. Nevertheless, the de-
velopment of efficient and convenient synthetic approaches
for such aza-heterocycles, in particular those with flexible
substituent patterns, is still in demand.
The optimization of the reaction conditions, including
the reaction temperature, the solvent, the additive, and
acidic reagents, was then investigated as shown in Table 1.
When 1a and Tf2O (1.0 equiv) reacted in the presence of
DTA at 80 °C, the yield of 2a reached 79% (Table 1, entry 3).
During the course of our studies on the synthesis of
highly valuable heterocycles based on β-oxo amide deriva-
tives,10 we successfully developed efficient syntheses of
substituted pyrano[2,3-b]quinolines from enaminones me-
© Georg Thieme Verlag Stuttgart · New York — Synthesis 2017, 49, A–G

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Q. Zhang et al.
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Synthesis
Increasing the reaction temperature or the amount of Tf2O
had no significant influence on the yield of 2a or the reac-
tion time (entries 4 and 5). However, a decrease in the
amount of Tf2O to 0.8 equivalents resulted in a lower yield
of 2a (entry 6). A complex mixture was formed when triflu-
oroacetic anhydride (TFAA) or acetic anhydride (Ac2O) was
employed (entries 7 and 8). Interestingly, the reaction of 1a
and Tf2O (1.0 equiv) proceeded smoothly in DTA under ni-
trogen at 80 °C, as indicated by TLC results, to furnish, in-
stead of 2a, a pair of inseparable products, which were
characterized as 3-acetyl-4-phenyl-3,4-dihydroquinolin-
2(1H)-one (3a) and 3-(1-hydroxyethylidene)-4-phenyl-3,4-
dihydroquinolin-2(1H)-one (4a) on the basis of the NMR
and mass spectra (entry 9) (see the Supporting Informa-
tion). In the 1H NMR spectrum, 3a displays two characteris-
tic doublets at 3.94 and 4.72 ppm, which might be assigned
to the adjacent 3-H and 4-H of the quinolin-2(1H)-one ring,
respectively, and the resonance signal of the amide N–H ap-
pears at 8.21 ppm. By contrast, 4a displays a characteristic
singlet at 4.90 ppm assigned to 4-H of the quinolin-2(1H)-
one ring, the resonance signal of hydroxy O–H appears at
14.54 ppm due to the formation of a hydrogen bond, and
that for the amide N–H is shifted to 7.69 ppm. With the es-
tablishment of the structures of 3a and 4a, it is not difficult
to conclude that quinolin-2(1H)-one 2a is derived from di-
hydroquinolin-2(1H)-ones 3a and 4a via an oxidation pro-
cess. Considering all the above results, and in particular
that no reaction was observed in the presence of triflic acid
(as shown in Table 1, entry 1), triflic anhydride acts as a
promoter for the intramolecular cyclization of N-aryl cin-
namides 1 and the subsequent oxidation.14
It is worth noting that when the reaction of 1a with tri-
flic anhydride was conducted in the absence of DTA in tolu-
ene at 80 °C, only a mixture of 3a and 4a was obtained, even
on prolonging the reaction time (Table 1, entry 10). Next,
two separate experiments were performed involving treat-
ment of 1a with triflic anhydride (1.0 equiv) and DTA (1.0
equiv) in toluene at 80 °C (entries 11 and 12). These experi-
ments revealed that the reaction formed a mixture of com-
pounds 2a, 3a and 4a within 12 hours, and that both 3a and
4a could be completely converted into compound 2a when
the reaction time was extended to 24 hours. These results
suggest that DTA plays an important role in assisting the
oxidation of 3,4-dihydroquinolin-2(1H)-ones 3a and 4a to
the corresponding quinolin-2(1H)-one 2a, which is beyond
that of a solvent. To further promote this transformation,
Table 1 Reaction of 1a under Different Conditionsa
H
O
O
O
O
O
O
O
O
NH
NH
NH
conditions
NH
+
+
1a
3a
2a
4a
Entry
Reagent (equiv)
Additive (equiv)
Solvent
Temp (°C)
Time (h)
Yield (%)b
2a
3a + 4a
1
2
TfOH (1.0)
Tf2O (1.0)
Tf2O (1.0)
Tf2O (1.0)
Tf2O (1.2)
Tf2O (0.8)
TFAA (1.0)
Ac2O (1.0)
Tf2O (1.0)
Tf2O (1.0)
Tf2O (1.0)
Tf2O (1.0)
Tf2O (1.0)
Tf2O (1.0)
–
DTA
DTA
DTA
DTA
DTA
DTA
DTA
DTA
DTA
50
50
80
100
80
80
80
80
80
80
80
80
80
80
24
24
19
17
16
24
24
24
7
no reaction
–
45
–
–
–
–
–
3
–
79
4
–
76
5
–
74
6
–
68
7
–
mixture
mixture
0
8
–
9
–
85 (1:2)c
10
11
12
13
14
–
toluene
toluene
toluene
DTA
12
12
24
4
0
82 (1:2)
DTA (1.0)
DTA (1.0)
DDQ (1.0)
DDQ (1.0)
29
54 (1:3)
76
0
0
0
81
toluene
6
75
a Reaction conditions: 1a (1.0 mmol), additive (1.0 mmol), solvent (5.0 mL), under air.
b Yield of isolated product. Data in parentheses refers to the ratio of 3a/4a determined by 1H NMR spectroscopy.
c Reaction under N2.
© Georg Thieme Verlag Stuttgart · New York — Synthesis 2017, 49, A–G

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Synthesis
we investigated the reaction of 1a with triflic anhydride in
the presence of DDQ (1.0 equiv) in DTA or toluene at 80 °C
(entries 13 and 14). It was observed that the reaction time
could be dramatically reduced to several hours in both cas-
es.
Using the optimized conditions (see Table 1, entry 13), a
series of reactions of α-acetyl N-aryl cinnamides 1 was car-
ried out and some of the results are listed in Table 2. It was
found that the reactions of α-acetyl N-aryl cinnamides 1b–
g bearing different electron-donating groups R2 and R3 pro-
ceeded efficiently to afford the corresponding quinolin-
2(1H)-ones 2b–g in good to high yields (Table 2, entries 2–
7). The investigation revealed that α-acetyl N-aryl cin-
namides 1h and 1i bearing electron-withdrawing R3 groups
(Cl and NO2) could be converted into the corresponding
quinolin-2(1H)-ones 2h and 2i under identical reaction
conditions (entries 8 and 9). The validity of this quinolin-
2(1H)-one synthesis was evaluated by employing α-acetyl
N-aryl tertiary cinnamides 1j,k and α-benzoyl N-aryl sec-
ondary cinnamides 1l–n as the substrates (entries 10–14).
It should be mentioned that the structure of 2a was further
confirmed by single-crystal X-ray analysis and from its
spectral and analytical data (Figure 1).
Figure 1 ORTEP drawing of 2a
To gain insight into the mechanism of this transforma-
tion, a separate experiment was carried out by treatment of
an isolated mixture of 3a and 4a with DDQ in DTA at 80 °C,
and quinolin-2(1H)-one 2a was exclusively obtained in 87%
yield. On the basis of all the obtained experimental results,
a plausible mechanism for the reaction of N-aryl cinnamide
1 with Tf2O/DTA is proposed as depicted in Scheme 1. The
substrate N-aryl cinnamide 1 reacts with Tf2O in DTA to
generate a very reactive iminium triflate A,15,16 followed by
an intramolecular nucleophilic addition reaction to form
intermediates B and B′.17 The hydrolysis of intermediates B
and B′ gives rise to a mixture of 3 and 4, which can be
oxidized to give quinolin-2(1H)-one 2. In the presence of
Table 2 Synthesis of Substituted Quinolin-2(1H)-ones 2 from N-Aryl Cinnamides 1a
O
O
O
O
R1
R1
N
N
R
R
Tf2O, DDQ
DTA, 80 °C
R3
R2
R3
R2
1
2
Entry
Substrate
R
R1
R2
R3
Product
Time (h)
Yield (%)b
1
1a
1b
1c
1d
1e
1f
Me
Me
Me
Me
Me
Me
Me
Me
Me
Me
Me
Ph
H
H
H
2a
2b
2c
2d
2e
2f
4.0
3.5
3.5
4.0
4.5
3.5
4.0
3.5
3.0
4.0
5.0
4.0
7.0
4.0
81
77
83
85
68
75
80
76
77
84
82
80
74
83
2
H
2-Me
4-Me
4-Me
2-Me
H
H
H
3
H
4
H
4-Me
4-Me
2-Me
4-MeO
4-Cl
3-O2N
H
5
H
6
H
7
1g
1h
1i
H
H
2g
2h
2i
8
H
H
9
H
H
10
11
12
13
14
1j
Me
Me
H
H
2j
1k
1l
H
4-Cl
H
2k
2l
H
1m
1n
Ph
H
Me
H
H
2m
2n
Ph
H
4-MeO
a Reaction conditions: 1 (1.0 mmol), Tf2O (1.0 mmol), DDQ (1.0 mmol), DTA (5.0 mL), 80 °C.
b Yield of isolated product.
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Synthesis
DDQ, intermediates B and B′ quickly undergo oxidation to
form triflate C, which is hydrolyzed during the work-up
process to afford the final product 2.
sulting mixture was poured into saturated aqueous NaCl solution (30
mL) and extracted with CH2Cl2 (3 × 20 mL). The combined organic
phases were washed with H2O, dried over anhydrous MgSO4, filtered,
and evaporated in vacuo. The crude product was purified by flash sili-
ca gel chromatography (PE–EtOAc, 3:1) to give product 2a.
O
O
O
OTf
OTf
R1
Yield: 213 mg (81%); white solid; mp 242–245 °C.
R1
Tf2O
N
R
N
R
IR (KBr): 2997, 2881, 2847, 1709, 1657, 1595, 1481, 1431, 1374, 1344,
761, 700, 659 cm–1
.
Ar
Ar
R2
R2
A
1H NMR (300 MHz, CDCl3): δ = 2.23 (s, 3 H), 7.14 (t, J = 7.2 Hz, 1 H),
1
7.28–7.37 (m, 4 H), 7.48–7.54 (m, 4 H), 11.19 (s, 1 H).
13C NMR (100 MHz, CDCl3): δ = 30.7, 115.6, 118.8, 121.9, 126.6, 127.5,
127.9, 128.0, 130.4, 131.8, 133.3, 137.3, 148.0, 160.6, 200.9.
MS (MALDI-TOF): m/z = 286.1 [M + Na]+.
O
OTf
O
OTf
O
OTf
R1
R1
R1
O
N
R
- H+
H+
N
R
N
R
Ar
Ar
Ar
Colorless crystal, M = 263.28, monoclinic, P21/c, a = 12.6491(18) Å, b =
7.0985(10) Å, c = 15.060(2) Å, α = 90.00°, β = 97.09°, γ = 90.00°, V =
1341.9(3) Å3, Z = 4, T = 273 K, F000 = 552.0, F000′ = 552.25, R = 0.0461
(2211), wR2 = 0.1262 (2647). CCDC 1033852 contains the supplemen-
tary crystallographic data for this paper. The data can be obtained
free of charge from the Cambridge Crystallographic Data Centre via
www.ccdc.cam.ac.uk/getstructures.
R2
R2
R2
C
B'
B
H2O
H2O
O
H
O
O
O
O
O
R1
R1
O
R1
N
N
R
R
N
R
+
3-Acetyl-8-methyl-4-phenylquinolin-2(1H)-one (2b)
Yield: 213 mg (77%); white solid; mp 244–246 °C.
Ar
Ar
Ar
R2
R2
R2
3
4
2
IR (KBr): 3156, 3108, 3021, 1712, 1632, 1593, 1472, 1444, 1371, 770,
755, 705 cm–1
.
Scheme 1 A plausible mechanism for the cyclization reaction of N-aryl
cinnamides 1
1H NMR (300 MHz, CDCl3): δ = 2.26 (s, 3 H), 2.53 (s, 3 H), 7.04 (t,
J = 7.8 Hz, 1 H), 7.12 (d, J = 7.8 Hz, 1 H), 7.29–7.32 (m, 2 H), 7.38 (d,
J = 6.9 Hz, 1 H), 7.46–7.48 (m, 3 H), 9.74 (s, 1 H).
13C NMR (100 MHz, CDCl3): δ = 16.3, 30.5, 118.9, 121.3, 123.1, 125.0,
127.4, 127.7, 127.9, 131.6, 131.8, 133.7, 135.8, 148.3, 159.9, 200.7.
In summary, a facile and efficient synthesis of polysub-
stituted quinolin-2(1H)-ones 2 is developed via triflic anhy-
dride promoted intramolecular cyclization of readily avail-
able N-aryl cinnamides 1. The ready availability of the sub-
strates, mild reaction conditions, metal-catalyst-free,
simple procedure, good to high yields and synthetic poten-
tial of the products makes this novel protocol very attrac-
tive. Further work on the mechanism of the reaction and
the utilization and extension of the scope of the methodol-
ogy is currently under investigation in our laboratory.
MS (MALDI-TOF): m/z = 300.3 [M + Na]+.
3-Acetyl-6-methyl-4-phenylquinolin-2(1H)-one (2c)6f
Yield: 230 mg (83%); yellow solid; mp 260–262 °C.
IR (KBr): 2970, 2911, 2824, 1711, 1645, 1498, 1473, 1416, 1376, 818,
783, 705 cm–1
.
1H NMR (300 MHz, CDCl3): δ = 2.29 (s, 6 H), 7.01 (s, 1 H), 7.31–7.35
(m, 4 H), 7.48–7.51 (m, 3 H), 12.16 (s, 1 H).
13C NMR (100 MHz, CDCl3): δ = 20.1, 30.7, 115.5, 118.8, 126.0, 127.5,
127.8, 128.0, 131.6, 131.8, 131.9, 133.5, 135.3, 147.7, 160.4, 201.1.
MS (MALDI-TOF): m/z = 300.2 [M + Na]+.
All reagents were purchased from commercial sources and used with-
out purification, unless otherwise indicated. The products were puri-
fied by column chromatography over Haiyang silica gel (200–400
mesh). Compounds 2a,c,g,h,j are known and were identified by 1H
NMR, 13C NMR, IR spectroscopy and mass spectrometry. The data are
in good agreement with those reported in the literature. Melting
points were determined using a Perkin-Elmer PE-2400 instrument
and are uncorrected. IR spectra (KBr) were recorded on a Shimadzu
3-Acetyl-6-methyl-4-(p-tolyl)quinolin-2(1H)-one (2d)
Yield: 247 mg (85%); yellow solid; mp 262–264 °C.
IR (KBr): 2973, 2918, 2848, 1705, 1648, 1598, 1472, 1375, 1351, 825
cm–1
.
FTIR-8400S FTIR spectrophotometer in the range of 400–4000 cm–1
.
1H NMR (300 MHz, CDCl3): δ = 2.28 (s, 3 H), 2.29 (s, 3 H), 2.44 (s, 3 H),
7.06 (s, 1 H), 7.20 (d, J = 8.1 Hz, 2 H), 7.28–7.37 (m, 4 H), 11.77 (s, 1 H).
13C NMR (100 MHz, CDCl3): δ = 20.1, 20.4, 30.8, 115.5, 118.9, 126.0,
127.9, 128.2, 130.4, 131.5, 131.8, 135.3, 137.8, 147.9, 150.4, 201.3.
MS (MALDI-TOF): m/z = 314.2 [M + Na]+.
1H NMR and 13C NMR spectra were recorded on Bruker-300 (or Varian
Inova-400) spectrometers at 25 °C at 300 MHz (or 400 MHz) and 100
MHz, respectively, with TMS as the internal standard. Mass spectra
were recorded on a Bruker Daltonics-Autoflex III Smartbeam MALDI
TOF mass spectrometer.
3-Acetyl-4-phenylquinolin-2(1H)-one (2a);6e,8d Typical Procedure
3-Acetyl-8-methyl-4-(p-tolyl)quinolin-2(1H)-one (2e)
Yield: 197 mg (68%); white solid; mp 273–276 °C.
To a solution of Tf2O (282 mg, 1.0 mmol) in DTA (5.0 mL) was added
1a (265 mg, 1.0 mmol) and DDQ (227 mg, 1.0 mmol) with stirring at
0 °C for 30 min. The mixture was then heated at 80 °C for 4 h. The re-
© Georg Thieme Verlag Stuttgart · New York — Synthesis 2017, 49, A–G

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Synthesis
IR (KBr): 3151, 3093, 2992, 1710, 1628, 1567, 1472, 1445, 1370, 857,
794, 764 cm–1
3-Acetyl-1-methyl-4-phenylquinolin-2(1H)-one (2j)7i
.
Yield: 232 mg (84%); light yellow solid; mp 179–180 °C.
1H NMR (300 MHz, CDCl3): δ = 2.24 (s, 3 H), 2.43 (s, 3 H), 2.50 (s, 3 H),
7.04 (t, J = 7.5 Hz, 1 H), 7.14–7.20 (m, 4 H), 7.29 (s, 1 H), 7.36 (d, J = 7.2
Hz, 1 H), 9.32 (s, 1 H).
13C NMR (100 MHz, CDCl3): δ = 16.2, 20.3, 30.6, 119.0, 121.3, 122.8,
125.1, 127.9, 128.2, 130.6, 131.5, 131.8, 135.8, 137.7, 148.4, 159.8,
200.8.
IR (KBr): 2983, 2940, 1710, 1632, 1371, 767, 706 cm–1
.
1H NMR (300 MHz, CDCl3): δ = 2.24 (s, 3 H), 3.80 (s, 3 H), 7.16 (t, J =
6.0 Hz, 1 H), 7.28–7.32 (m, 3 H), 7.43–7.48 (m, 4 H), 7.61 (t, J = 6.0 Hz,
1 H).
13C NMR (100 MHz, CDCl3): δ = 28.4, 30.4, 113.2, 119.6, 121.3, 127.5,
127.6, 127.8, 128.1, 130.3, 132.0, 133.1, 138.6, 145.3, 158.3, 200.7.
MS (MALDI-TOF): m/z = 292.3 [M + H]+.
MS (MALDI-TOF): m/z = 278.1 [M + H]+.
3-Acetyl-4-(o-tolyl)quinolin-2(1H)-one (2f)
3-Acetyl-4-(4-chlorophenyl)-1-methylquinolin-2(1H)-one (2k)
Yield: 207 mg (75%); yellow solid; mp 212–215 °C.
Yield: 255 mg (82%); yellow solid; mp 172–174 °C.
IR (KBr): 3083, 3000, 2938, 1710, 1640, 1373, 1316, 822, 767 cm–1
1H NMR (300 MHz, CDCl3): δ = 2.29 (s, 3 H), 3.80 (s, 3 H), 7.18 (t, J =
6.0 Hz, 1 H), 7.23–7.26 (m, 3 H), 7.44–7.47 (m, 3 H), 7.63 (t, J = 6.0 Hz,
1 H).
13C NMR (100 MHz, CDCl3): δ = 28.5, 30.4, 113.4, 119.4, 121.5, 127.4,
127.8, 129.5, 130.6, 131.6, 134.1, 138.7, 144.3, 158.3, 200.5.
MS (MALDI-TOF): m/z = 312.1 [M + H]+.
IR (KBr): 2990, 2878, 2839, 1711, 1642, 1597, 1479, 1430, 1357, 755
.
cm–1
.
1H NMR (300 MHz, CDCl3): δ = 2.12 (s, 3 H), 2.35 (s, 3 H), 7.03 (d,
J = 7.8 Hz, 1 H), 7.12 (t, J = 6.9 Hz, 2 H), 7.28–7.44 (m, 4 H), 7.54 (t, J =
8.1 Hz, 1 H), 12.08 (s, 1 H).
13C NMR (100 MHz, CDCl3): δ = 18.8, 30.4, 115.5, 118.7, 122.1, 124.9,
126.3, 127.5, 128.0, 129.2, 130.5, 131.5, 133.0, 135.2, 137.2, 148.3,
160.6, 200.3.
MS (MALDI-TOF): m/z = 300.2 [M + Na]+.
3-Benzoyl-4-phenylquinolin-2(1H)-one (2l)
Yield: 260 mg (80%); white solid; mp 251–252 °C.
IR (KBr): 3019, 2999, 1673, 1635, 1591, 1471, 1374, 839, 749, 690 cm–1
3-Acetyl-4-(4-methoxyphenyl)quinolin-2(1H)-one (2g)8e
Yield: 234 mg (80%); white solid; mp 257–259 °C.
.
1H NMR (300 MHz, CDCl3): δ = 7.13 (t, J = 7.2 Hz, 2 H), 7.28–7.33 (m, 6
H), 7.36 (d, J = 7.5 Hz, 2 H), 7.49 (t, J = 7.5 Hz, 2 H), 7.84 (d, J = 7.2 Hz, 2
H), 11.64 (s, 1 H).
13C NMR (100 MHz, CDCl3): δ = 115.8, 118.9, 121.9, 126.4, 127.2,
127.4, 127.7, 128.2 (2 C), 129.8, 130.3, 132.3, 133.0, 136.2, 137.5,
149.4, 161.0, 193.5.
IR (KBr): 2965, 2882, 2834, 1705, 1653, 1608, 1498, 1429, 1377, 818,
766 cm–1
.
1H NMR (400 MHz, CDCl3): δ = 2.29 (s, 3 H), 3.88 (s, 3 H), 7.01 (d, J =
8.0 Hz, 2 H), 7.14 (t, J = 7.2 Hz, 1 H), 7.27 (d, J = 8.4 Hz, 2 H), 7.34 (d, J =
8.0 Hz, 1 H), 7.47 (d, J = 8.0 Hz, 1 H), 7.53 (t, J = 7.2 Hz, 1 H), 12.80 (s, 1
H).
MS (MALDI-TOF): m/z = 348.2 [M + Na]+.
13C NMR (100 MHz, CDCl3): δ = 31.9, 55.6, 114.4, 116.1, 119.7, 122.7,
126.6, 127.5, 130.7, 131.6, 133.9, 138.9, 147.3, 159.8, 159.9, 202.2.
3-Benzoyl-6-methyl-4-phenylquinolin-2(1H)-one (2m)
MS (MALDI-TOF): m/z = 316.2 [M + Na]+.
Yield: 251 mg (74%); white solid; mp 255–257 °C.
3-Acetyl-4-(4-chlorophenyl)quinolin-2(1H)-one (2h)6f,8e
IR (KBr): 2997, 2915, 1676, 1641, 1593, 1500, 1373, 818, 766, 697 cm–1
.
1H NMR (300 MHz, CDCl3): δ = 2.28 (s, 3 H), 7.03 (s, 1 H), 7.18–7.24
(m, 3 H), 7.29–7.35 (m, 6 H), 7.49 (t, J = 7.2 Hz, 1 H), 7.81 (d, J = 7.2 Hz,
2 H), 12.52 (s, 1 H).
13C NMR (100 MHz, CDCl3): δ = 20.0, 115.7, 118.8, 125.7, 127.2, 127.4,
127.6, 128.2 (2 C), 129.7, 131.5, 131.8, 132.2, 133.1, 135.6, 136.3,
149.2, 160.8, 193.7.
Yield: 226 mg (76%); white solid; mp 260–262 °C.
IR (KBr): 2994, 2884, 2847, 1707, 1652, 1486, 1378, 817, 760 cm–1
1H NMR (400 MHz, CDCl3): δ = 2.34 (s, 3 H), 7.13 (t, J = 8.0 Hz, 1 H),
7.19 (d, J = 8.0 Hz, 1 H), 7.23 (d, J = 8.0 Hz, 2 H), 7.41–7.43 (m, 2 H),
7.46 (s, 1 H), 7.53 (t, J = 8.0 Hz, 1 H), 12.53 (s, 1 H).
.
13C NMR (100 MHz, DMSO-d6): δ = 32.0, 116.2, 119.2, 122.9, 127.5,
129.0, 131.2, 131.8, 133.6, 133.9, 134.0, 139.0, 146.5, 159.7, 202.1.
MS (MALDI-TOF): m/z = 362.2 [M + Na]+.
MS (MALDI-TOF): m/z = 320.2 [M + Na]+.
3-Benzoyl-4-(4-methoxyphenyl)quinolin-2(1H)-one (2n)
Yield: 295 mg (83%); light yellow solid; mp 264–266 °C.
IR (KBr): 2955, 2934, 1676, 1625, 1504, 1476, 1377, 833, 753 cm–1
3-Acetyl-4-(3-nitrophenyl)quinolin-2(1H)-one (2i)
.
Yield: 237 mg (77%); white solid; mp 233–236 °C.
1H NMR (300 MHz, CDCl3): δ = 3.77 (s, 3 H), 6.82 (d, J = 6.0 Hz, 2 H),
7.11–7.19 (m, 3 H), 7.28 (s, 1 H), 7.36 (t, J = 7.2 Hz, 3 H), 7.44–7.52 (m,
2 H), 7.83 (d, J = 6.0 Hz, 2 H), 11.96 (s, 1 H).
13C NMR (100 MHz, CDCl3): δ = 54.2, 112.7, 115.8, 119.2, 121.8, 125.1,
126.4, 127.4, 128.2, 129.6, 129.8, 130.2, 132.3, 136.2, 137.5, 149.3,
158.8, 161.0, 193.7.
IR (KBr): 2997, 2885, 2853, 1700, 1673, 1530, 1481, 1351, 765 cm–1
.
1H NMR (300 MHz, CDCl3): δ = 2.47 (s, 3 H), 7.10 (d, J = 6.0 Hz, 1 H),
7.19 (t, J = 9.0 Hz, 1 H), 7.42 (d, J = 9.0 Hz, 1 H), 7.60 (t, J = 6.0 Hz, 1 H),
7.69–7.74 (m, 2 H), 8.20 (s, 1 H), 8.35–8.37 (m, 1 H), 11.62 (s, 1 H).
13C NMR (100 MHz, DMSO-d6): δ = 31.9, 116.2, 119.0, 123.1, 124.0 (2
C), 127.5, 130.7, 132.0, 134.1, 136.0, 136.4, 139.1, 145.7, 148.2, 159.7,
202.1.
MS (MALDI-TOF): m/z = 356.3 [M + H]+.
MS (MALDI-TOF): m/z = 331.2 [M + Na]+.
© Georg Thieme Verlag Stuttgart · New York — Synthesis 2017, 49, A–G

F
Q. Zhang et al.
Paper
Synthesis
3-Acetyl-4-phenyl-3,4-dihydroquinolin-2(1H)-one (3a) and 3-(1-
Hydroxyethylidene)-4-phenyl-3,4-dihydroquinolin-2(1H)-one (4a)
J.-D.; Messaoudi, S.; Alami, M. Adv. Synth. Catal. 2013, 355, 2044.
(f) Wu, Y.-L.; Chuang, C.-P.; Lin, P.-Y. Tetrahedron 2000, 56, 6029.
(g) Battistuzzi, G.; Bernini, R.; Cacchi, S.; Salve, I. D.; Fabrizi, G.
Adv. Synth. Catal. 2007, 349, 297.
Yield: 225 mg (85%); yellow solid.
IR (KBr): 3202, 3040, 3022, 1642, 1597, 1488, 1434, 1314, 895, 757
(5) (a) Kulkarni, B. A.; Ganesan, A. Chem. Commun. 1998, 785. (b) Li,
K.; Foresee, L. N.; Tunge, J. A. J. Org. Chem. 2005, 70, 2881.
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(d) Inglis, S. R.; Stojkoski, C.; Branson, K. M.; Cawthray, J. F.;
Fritz, D.; Wiadrowski, E.; Ryke, M. S.; Booker, G. W. J. Med. Chem.
2004, 47, 5405. (e) Fourquez, J. M.; Godard, A.; Marsais, F.;
Quéguiner, G. J. Heterocycl. Chem. 1995, 32, 1165. (f) Coppolar,
G. M.; Hardtmann, G. E. J. Heterocycl. Chem. 1979, 16, 1605.
(g) Iyobe, A.; Uchida, M.; Kamata, K.; Hotei, Y.; Kusama, H.;
Harada, H. Chem. Pharm. Bull. 2001, 49, 822.
(6) (a) Hewawasam, P.; Fan, W.; Knipe, J.; Moon, S. L.; Boissard, C.
G.; Gribkoff, V. K.; Starrett, J. E. Jr. Bioorg. Med. Chem. Lett. 2002,
12, 1779. (b) Ismaili, L.; Nadaradjane, A.; Nicod, L.; Guyon, C.;
Xicluna, A.; Robert, J.; Refouvelet, B. Eur. J. Med. Chem. 2008, 43,
1270. (c) Marcaccini, S.; Pepino, R.; Pozo, M. C.; Basurto, S.;
García-Valverde, M.; Torrobab, T. Tetrahedron Lett. 2004, 45,
3999. (d) Grzegożek, M. J. Heterocycl. Chem. 2008, 45, 1879.
(e) Schejn, A.; Balan, L.; Falk, V.; Aranda, L.; Medjahdi, G.;
Schneider, R. CrystEngComm 2014, 16, 4493. (f) Vijayalakshmi,
S.; Ragunath, L.; Rajendran, S. P. Heterocycl. Commun. 2001, 7,
177.
cm–1
.
1H NMR (400 MHz, CDCl3): δ (3a + 4a) = 1.99 (s, 3 H), 2.25 (s, 3 H),
3.94 (d, J = 7.4 Hz, 1 H), 4.72 (d, J = 7.4 Hz, 1 H), 4.90 (s, 1 H), 6.74 (d,
J = 8.0 Hz, 1 H), 6.81 (d, J = 8.0 Hz, 1 H), 6.94–6.96 (m, 1 H), 6.97–6.99
(m, 1 H), 7.10–7.19 (m, 3 H), 7.10–7.26 (m, 6 H), 7.25–7.26 (m, 4 H),
7.31–7.33 (m, 1 H), 7.69 (s, 1 H), 8.21 (s, 1 H), 14.54 (s, 1 H).
13C NMR (100 MHz, CDCl3): δ (3a + 4a) = 18.3, 29.1, 43.1, 43.7, 60.3,
97.8, 114.4, 114.7, 122.4, 122.9, 124.4, 124.7, 125.6, 125.8, 126.4,
126.6, 127.0, 127.2, 127.8, 127.9, 128.0, 133.7, 134.8, 139.2, 145.3,
167.0, 169.4, 174.2, 201.4.
MS (MALDI-TOF): m/z = 288.2 [M + Na]+.
Funding Information
Financial support of this research by the National Natural Science
Foundation of China (21502185, 21172211 and 21542006) is grate-
fully acknowledged.
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(7) (a) Cortese, N. A.; Ziegler, C. B. Jr.; Hrnjez, B. J.; Heck, R. F. J. Org.
Chem. 1978, 43, 2952. (b) Kadnikov, D. V.; Larock, R. C. J. Org.
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Supporting Information
Supporting information for this article is available online at
https://doi.org/10.1055/s-0036-1590821.
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© Georg Thieme Verlag Stuttgart · New York — Synthesis 2017, 49, A–G