The synthesis of 3,4-disubstituted dihydroquinolin-2(1H)-one under metal-free conditions in aqueous solution

Article abstract of DOI:10.3184/174751914X14099310712383

A novel route toward 3,4-disubstituted dihydroquinolin-2(1H )-ones via radical process has been developed in aqueous solution without metals. This method offers a new and simple route for the synthesis of skeleton of dihydroquinolin-2(1H )-one in one step

Full text of DOI:10.3184/174751914X14099310712383

542 RESEARCH PAPER
VOL. 38 SEPTEMBER, 542–545
JOURNAL OF CHEMICAL RESEARCH 2014
The synthesis of 3,4-disubstituted dihydroquinolin-2(1H)-one under metal-
free conditions in aqueous solution
Hongyan Wang, Bin Sun, Jun Yang, Jitao Wang, Pu Mao, Liangru Yang and Wenpeng Mai*
Chemistry and Chemical Engineering School, Henan University of Technology, Henan Province, Zhengzhou 450001, P.R. China
A novel route toward 3,4-disubstituted dihydroquinolin-2(1H)-ones via radical process has been developed in aqueous solution
without metals. This method offers a new and simple route for the synthesis of skeleton of dihydroquinolin-2(1H)-one in one step.
Keywords: dihydroquinolin-2(1H)-one, metal-free conditions, aqueous solution
have also been developed.11–14 Despite their efficiencies,
The 3,4-disubstituted dihydroquinolin-2(1H)-one unit is an
important component of pharmacologically and biologically
active compounds, and its derivatives are found in many natural
products and pharmaceuticals which have cardiovascular, anti-
inflammatory and phosphodiesterase inhibitory activities
(Scheme 1).1–3 Moreover, the 3,4-dihydroquinolin-2(1H)-one
unit is not only very important in pharmaceuticals, but is also
a good synthetic block for 1,2,3,4-tetrahydroquinolines and
quinolin-2(1H)-ones (Scheme 2).4 As a result, the development
of a simple and highly efficient method for construction
of 3,4-dihydroquinolin-2(1H)-one is desirable. Generally,
the preparation of a 3,4-dihydroquinolin-2(1H)-one system
involves the Friedel–Crafts cyclisation5–7, and palladium8–9 or
rhodium10 catalysed reactions. Recently, other methods such
as Ugi/acrylanilide [6π]-photocyclisations, intermolecular
tandem reactions and Mn-mediated intramolecular cyclisations
most of them are catalysed by metals, or require harsh
reaction conditions involving strong acid or base, or the use
of complicated compounds as substrates. Radical reactions
have been widely applied in organic synthesis, especially in
cyclisation reactions.15,16 However, radical tandem cyclisation
for constructing 3,4-disubstituted dihydroquinolin-2(1H)-ones
remains rare. Recently, we have reported a silver-catalysed
approach for the synthesis of 3,4-dihydroquinolin-2(1H)-ones.17
As a logical extension of the catalytic method, we now report a
new approach to the 3,4-disubstituted dihydroquinolin-2(1H)-
ones under metal-free condition.
We first selected N-methyl-N-phenylcinnamamide (1a) and
pentane-2,4-dione (2) as substrates to investigate the reaction
conditions. The results were summarised in Table 1. Based
on our previous work, the AgNO3–K2S2O8 catalytic system
was firstly examined at 100 °C in CH3CN/H2O solution and
product 3 was isolated in 65% yield (Table 1, entry 1). Ag2O as
catalyst gave a similar result under the same condition (Table 1,
entry 2). Unexpectedly, the reaction still proceeded well when
changing the silver metal to copper metal (Table 1, entries 3 and
4). This did not happen in our previous work on the synthesis
of 3,4-dihydroquinolin-2(1H)-ones. So we considered that
the metal does not play a key role in this transformation. We
were pleased to find that K2S2O8 itself displayed catalytic
effect in this transformation with 56% product yield (Table 1,
entry 5). We next examined (NH4)2S2O8 as oxidant under the
same conditions, it still showed a catalytic effect but the yield
decreased to 39% (Table 1, entry 6). No reaction occurred
in the absence of oxidant (Table 1, entry 7). When other
oxidants such as BOP, TBHP and H2O2 were tested under the
same conditions, no reaction occurred (Table 1, entries 8–10).
Improving the amount of K2S2O8, the yield increased slightly
(Table 1, entry 13). However, the product was not obtained in
acetone/H2O or EtOAc/H2O using K2S2O8 as oxidant which
demonstrated solvent also played an important role (Table 1,
entries 11 and 12).
N
NO2
l
C
N
O
H
N
O
NMDA antagonist
H
Meloscine
OMe
N
CF3
O
O
HO
Cl
OMe
O
N
O
H
N
H
HIV-1 reverse
transcriptase inhibitor
Insecticidal antibiotic
Scheme 1 Some drugs containing 3,4-dihydroquinolin-2-one structure.
Ar
Ar
N
Ar
R
O
R
R
[O]
[H]
(a)
(b)
N
O
N
quinolin-2(1H)-ones
1,2,3,4-tetrahydroquinolines
Scheme 2 Utility of 3,4-dihydroquinolin-2(1H)-ones.
* Correspondent. E-mail: maiwp@yahoo.com

JOURNAL OF CHEMICAL RESEARCH 2014 543
Table 1 Effect of solvents, catalysts and oxidants in the new reactiona
Table 2 Direct synthesis of 3,4-disubstituted dihydroquinoline-2(1H)-one
without metala
O
O
O
O
R2
Catalyst
O
O
+
O
O
R1
N
Oxidant
Solvent
K2S2O8, 2.0eq
CH3CN/H2O
R2
+
X
N
O
1a
2
。
R1
R3
2
N
O
100 C
O
X
N
O
3
1a-1m
R3
3-15
Entry
Catalyst
Oxidant
Solvent
Yield /%b
1
2
3
4
5
6
7
8
9
10
11
12
13c
14d
AgNO3
Ag2O
CuCl
CuI
–
K2S2O8
K2S2O8
K2S2O8
K2S2O8
K2S2O8
(NH4)2S2O8
–
BPO
TBHP
H2O2
CH3CN/H2O
CH3CN/H2O
CH3CN/H2O
CH3CN/H2O
CH3CN/H2O
CH3CN/H2O
CH3CN/H2O
CH3CN/H2O
CH3CN/H2O
CH3CN/H2O
65
58
44
51
56
39
0
0
0
0
Entry
X, R1, R2, R3
Products Yield/%b
1
2
3
4
5
6
7
8
9
10
11
12
13
X=C, R1 =H, R2 =H, R3 =Me
X=C, R1 =H, R2 =m-OMe, R3 =Me
X=C, R1 =H, R2 =o-Me, R3 =Me
X=C, R1 =H, R2 =o-Br, R3 =Me
X=C, R1 =H, R2 =o-Cl, R3 =Me
X=C, R1 =H, R2 =p-F, R3 =Me
X=C, R1 =H, R2 =p-Br, R3 =Me
X=C, R1 =H, R2 =p-Cl, R3 =Me
X=N, R1 =H, R2 =H, R3 =Bz
3
4
70
73
56
69
58
43
50
57
46
72
51
75
64
5
6
7
8
–
–
–
–
–
–
–
–
9
10
11
12
13
14
15
K2S2O8
K2S2O8
K2S2O8
K2S2O8
Acetone/H2O
EtOAc/H2O
CH3CN/H2O
CH3CN/H2O
trace
0
70
63
X=C, R1 =p-Cl, R2 =H, R3 =Me
X=C, R1 =p-F, R2 =H, R3 =Me
X=C, R1 =H, R2 =H, R3 =Et
–
X=C, R1 =H, R2 =H, R3 =CH2CH2CN
aCatalyst (20 mol%), 1a (1.0 mmol), 2 (2.0 mmol) and oxidant (1.0 equiv.) in
3 mL of the indicated solvent/H2O (1:1) at 100 °C for 15 h. TBHP, tert-butyl-
hydroperoxide; DTBP, tert-butyl-peroxide; BPO, benzoyl peroxide.
bIsolated yields.
aReaction conditions: N-methyl-N-phenylcinnamamide (1.0 mmol),
pentane-2,4-dione (2.0 mmol), AgNO3 (0.2 mmol) and K2S2O8 (2.0 mmol),
heating to 100 °C for 15 h, CH3CN/H2O (V:V=3:3 mL).
bIsolated yield.
cK2S2O8 (2.0 equiv.).
dK2S2O8 (3.0 equiv.).
The novel reactions were carried out under the optimised
reaction conditions, and the results summarised in Table 2.
As shown in Table 2, many 3,4-dihydroquinolin-2(1H)-ones
could be obtained cleanly under metal-free condition. MeO,
Cl, Br, F, and pyridine substituents in substrates 1 were
compatible with the current condition. Electron-withdrawing
and donating substituted groups, such as o-Cl(Br), p-Br(Cl,
F), m-OMe and o-Me on the phenyl ring (2) of cinnamic acid
do not influence the reactivity. The products were obtained in
moderate yields (Table 2, 3–10). For example, (E)-N-methyl-
N-phenyl-3-(o-tolyl)acrylamide reacted with 2 to form the
3,4-dihydroquinoline-2(1H)-one 5 in 56% yield. Electron-
withdrawing group on phenyl ring of substrate 1 also worked
well in this transformation. For example, N-(4-fluorophenyl)-N-
methylcinnamamide reacted with 2 to produce the product 13 in
51% yield. On changing the N-protecting group from Me to Et,
Bz and CH3CH2CN, the reaction still proceeded well (Table 2,
11, 14 and 15). Unfortunately, the reaction did not work well
under the optimised conditions when using 1-phenylbutane-
1,3-dione and ethyl 3-oxobutanoate as substrate 2 (Table 1, 16
and 17). The reason for this is not clear at present.
TCI companies and used directly. Reactions were monitored by
TLC (Qingdao Haiyang Chemical Co. Ltd. Silica gel 60 F254).
Products were detected using a UV-Vis lamp (254 nm). Column
chromatography was performed on Qingdao Haiyang Chemical Co.
Ltd. Gel 60 (200–300 mesh). The 1H and 13C NMR spectras were
obtained on a Bruker 400 MHz NMR Fourier transform spectrometer.
1H NMR data were reported as: chemical shift (δ ppm), multiplicity,
coupling constant (Hz), and integration. 13C NMR data were reported
in terms of chemical shift (δ ppm) multiplicity, and coupling constant
(Hz). The spectra are referenced against the internal solvent (CDCl3,
δ
1H=7.26 ppm, 13C=77.0 ppm; DMSO-d6,
δ
1H=2.50 ppm,
13C=40.0 ppm). Data are reported as follows: s=singlet, d=doublet,
t=triplet, q=quartet and m=multiplet. ESI-MS spectra were recorded
on a Bruker Esquire 3000.
Synthesis of substrate 1; general procedure
A 50 mL anhydrous flask was fitted with a magnetic stirrer bar, and
cinnamic acid (5 mmol, 0.74 g) and SOCl2 (5 mL) were added. After
stirring at 60 °C for 3 h, the redundant SOCl2 was evaporated under
reduced pressure and the liquid was added dropwise into another flask
containing N-methylaniline (10 mmol, 1.07 g) dissolved in anhydrous
CH2Cl2 (20 mL). The mixture was stirred for 1 h at room temperature.
The organic phase was then washed by HCl aqueous solution and
K2CO3 aqueous solution, then dried by anhydrous Na2SO4. After
evaporating the CH2Cl2, the N-methyl-N-phenylcinnamamide was
obtained in 97% yield and used in the next step directly.
In summary, we have developed a radical tandem cyclisation
to synthesise 3,4-disubstituted dihydroquinoline-2(1H)-ones
that have very important place in pharmaceutical field. Method
worked in aqueous solution without a metal which eliminated
the worries of metal contamination in the preparation of drugs.
Further investigations of this method are ongoing in our
laboratory.
Synthesis of 3–15; general procedure
1 (1.0 mmol), 2 (2.0 mmol), K2S2O8 (540 mg, 2.0 mmol) and a stirrer
were added to a 50 mL tube and then CH3CN (3 mL) and H2O (3 mL)
were added. The mixture was stirred at 100 °C for 15 h (monitored
by TLC). The solution was then diluted by ethyl acetate (20 mL) and
washed with a solution of K2CO3 and water, then dried by anhydrous
Na2SO4. The crude mixture was purified by column chromatography
on silica gel (petroleum ether/ethyl acetate=15:1–6:1, v/v) to give the
products 3–15.
Experimental
All experiments were carried out using a conical flask in the air.
Cinnamic acids, thionyl chloride, aromatic secondary amines and
pentane-2,4-dione were purchased from commercial suppliers and
used as received unless otherwise noted. All solvents and other
commercially available reagents were purchased from Acros or

544 JOURNAL OF CHEMICAL RESEARCH 2014
3-(1-Methyl-2-oxo-4-phenyl-1,2,3,4-tetrahydroquinolin-3-yl)
pentane-2,4-dione (3): Yellow solid; m.p. 144–148 °C, 1H NMR
(400 MHz, CDCl3) δ 7.39–7.31 (m, 4H), 7.14–7.09 (m, 3H), 7.04 (dd,
J=7.6 Hz,0.8 Hz,1H), 6.83 (d, J=7.2 Hz, 1H), 4.22 (d, J=8.4 Hz,
1H), 3.79 (t, J=7.6 Hz, 1H), 3.53 (d, J=7.2 Hz, 1H), 3.41 (s, 3H), 2.18
(s, 3H), 2.14 (s, 3H); 13C NMR (100 MHz, CDCl3) δ 203.13, 202.87,
168.76, 139.69, 139.60, 129.16, 128.60, 128.44, 128.44, 128.33, 127.74,
127.25, 123.46, 114.90, 66.87, 48.87, 45.03, 30.14, 30.08, 29.95, 29.71.
FT-IR ν/cm–1 (KBr): 1720, 1666, 1593, 1466, 1377, 1250, 744, 702.
HRMS (ESI) calcd for C21H21NO3 [M + H]+:336.1594; found:336.1592.
3-(4-(3-Methoxyphenyl)-1-methyl-2-oxo-1,2,3,4-tetrahydroquinolin-
3-yl)pentane-2,4-dione (4): Yellow liquid: 1H NMR (400 MHz,CDCl3)
δ 7.36–7.26 (m, 1H),7.10 (d, J=8.4 Hz, 1H), 7.39 (t, J=7.2 Hz, 1H), 6.86
(dd, J=7.8 Hz, 2.4 Hz, 2H), 6.74 (d, J=8.0 Hz, 1H), 6.66 (s, 1H), 4.19 (d,
J=8.8 Hz, 1H), 3.80 (s, 3H), 3.77 (t, J=7.2 Hz, 1H), 3.54 (t, J=7.2 Hz,
1H), 3.41 (s, 3H), 2.19 (s, 3H), 2.15 (s, 3H); 13C NMR (100 MHz,
CDCl3) δ 203.15, 202.84, 168.75, 160.13, 141.32, 139.57, 130.20,
128.58, 128.32, 127.14, 123.46, 120.68, 114.87, 114.36, 112.80, 66.70,
55.22, 48.77, 45.03, 30.07, 29.70. FT-IR ν/cm–1 (KBr): 1703, 1670, 1601,
1458, 1369, 1263, 1130, 1041, 762. HRMS (ESI) calcd for C22H23NO4
[M + H]+:366.1700; found:366.1697.
3-(1-Methyl-2-oxo-4-(o-tolyl)-1,2,3,4-tetrahydroquinolin-3-yl)
pentane-2,4-dione (5): Yellow solid m.p. 142–145 °C: 1H NMR
(400 MHz, CDCl3) δ 7.34–7.30 (m, 1H), 7.27–7.17 (m, 3H), 7.10 (dd,
J=8.0 Hz,1H), 6.98–6.95 (m, 2H), 6.62 (d, J=7.6 Hz, 1H), 4.56 (d,
J=6.4 Hz, 1H), 3.78 (dd, J=10.4 Hz, 6.4 Hz, 1H), 3.57 (d, J=6.4 Hz,
1H), 3.44 (s, 3H), 2.33 (s, 3H), 2.15 (s, 3H), 2.12 (s, 3H); 13C NMR
(100 MHz, CDCl3) δ 203.48, 203.04, 169.27, 139.85, 137.55, 137.00,
131.35, 128.16, 128.07, 127.92, 127.83, 127.68, 126.91, 123.43, 114.79,
66.09, 47.72, 40.89, 30.38, 30.18, 29.92, 19.65. FT-IR ν/cm–1 (KBr): 1705,
1668, 1595, 1369, 1136, 752, 723. HRMS (ESI) calcd for C22H23 NO3
[M + H]+:350.1751; found: 350.1748.
3-(4-(2-Bromophenyl)-1-methyl-2-oxo-1,2,3,4-tetrahydroquinolin-
3-yl)pentane-2,4-dione (6): White solid m.p. 181–184 °C:
1H NMR (400 MHz, CDCl3) δ 7.61 (dd, J=8.0 Hz, 1.2 Hz, 1H), 7.46
(dd, J=7.6 Hz, 1.6 Hz, 1H), 7.33–7.28 (m, 1H), 7.22 (m, 1H), 7.12–6.99
(m, 4H), 4.98 (d, J=7.2 Hz, 1H), 4.28 (dd, J=11 Hz, 6.8 Hz, 1H), 3.93
(d, J=10.4 Hz, 1H), 3.47 (s, 3H), 2.35 (s, 3H), 2.16 (s, 3H); 13C NMR
(100 MHz, CDCl3) δ 201.20, 200.72, 169.38, 139.50, 138.62, 133.74,
129.22, 129.01, 128.72, 128.63, 128.47, 127.89, 123.99, 123.79, 115.75,
67.63, 46.54, 41.28, 30.41, 30.18, 29.75. FT-IRν/cm–1 (KBr): 1709,
1668, 1595, 1469, 1371, 1020, 750. HRMS (ESI) calcd for C21H20BrNO3
[M + H]+:414.0699; found: 414.0695.
3-(4-(2-Chlorophenyl)-1-methyl-2-oxo-1,2,3,4-tetrahydroquinolin-
3-yl)pentane-2,4-dione (7): White solid m.p. 178–182 °C: 1H NMR
(400 MHz, CDCl3) δ 7.49 (dd, J=7.6 Hz, 2.0 Hz, 1H), 7.36–7.24 (m,
4H), 7.11 (d, J=7.6 Hz, 1H), 7.04–6.98 (m, 2H), 6.71 (d, J=7.6 Hz, 1H),
4.80 (d, J=10.0 Hz, 1H), 3.93 (dd, J=6.4 Hz, 2.0 Hz, 1H), 3.52 (d,
J=6.4 Hz, 1H), 3.43 (s, 3H), 2.21 (s, 3H), 2.17 (s, 3H); 13C NMR
(100 MHz, CDCl3) δ 203.09, 202.50, 168.75, 13 9.74, 136.80, 134.82,
130.52, 130.29, 129.23, 128.39, 127.95, 127.74, 126.55, 123.46, 114.92,
66.27, 47.21, 42.13, 30.43, 30.14, 29.89; FT-IR ν/cm–1 (KBr): 1705, 1676,
150 9, 1471, 1369, 1259, 1041, 752. HRMS (ESI) calcd for C21H20ClNO3
[M + H]+:370.1204; found:370.1214.
1H), 2.15 (s, 1H); 13C NMR (100 MHz, CDCl3) δ 202.74, 202.58, 168.30,
139.52, 138.98, 132.23, 129.95, 128.70, 128.67, 126.19, 123.67, 121.60,
115.10, 67.13, 48.69, 44.47, 30.35, 30.04, 29.62. FT-IR ν/cm–1 (KBr):
1703, 1670, 1603, 1489, 1371, 1138, 1074, 1012, 810, 760. HRMS (ESI)
calcd for C21H20BrNO3 [M + H]+:414.0699; found:414.0695.
3-(4-(4-Chlorophenyl)-1-methyl-2-oxo-1,2,3,4-tetrahydroquinolin-
1
3-yl)pentane-2,4-dione (10): Yellow solid m.p. 139–142 °C: H NMR
(400 MHz, CDCl3) δ 7.39–7.34 (m, 1H), 7.33–7.30 (m, 2H), 7.12 (d,
J=8.0 Hz, 1H), 7.07–7.02 (m, 3H), 6.85 (m, J=7.6 Hz, 1H), 4.18 (d,
J=7.6 Hz, 1H), 3.75 (t, J=7.6 Hz, 1H), 3.55 (d, J=8.0 Hz, 1H), 3.39
(s, 1H), 2.20 (s, 3H), 2.15 (s, 3H); 13C NMR (100 Hz, CDCl3) δ 202.74,
202.59, 168.33, 139.52, 138.45, 133.50, 129.60, 128.70, 128.65, 126.28,
123.66, 115.10, 67.14, 48.76, 44.40, 30.33, 30.03, 29.59. FT-IR ν/cm–1
(KBr): 1703, 1670, 1603, 1493, 1371, 1138, 1095, 1016, 760. HRMS
(ESI) calcd for C21H20ClNO3 [M + H]+:370.1204; found:370.1202.
3-(1-Benzyl-2-oxo-4-phenyl-1,2,3,4-tetrahydro-1,8-naphthyridin-
1
3-yl)pentane-2,4-dione (11): White solid m.p. 143–148 °C: H NMR
(400 MHz, CDCl3) δ 8.30 (d, J=3.6 Hz, 1H), 7.47 (d, J=7.6 Hz, 2H),
7.36–7.23 (m, 7H), 7.10–7.04 (m, 3H), 6.91 (dd, J=12.4 Hz, 4.8 Hz, 1H),
5.51 (q, J=14.0 Hz, 1H), 4.28 (d, J=10.0 Hz, 1H), 3.84 (dd, J=6.8H
z,5.8 Hz,1H), 3.58 (d, J=5.6 Hz, 1H), 2.15 (s, 6H); 13C NMR (100 MHz,
CDCl3) δ 202.89, 202.69, 169.16, 150.62, 146.84, 138.93, 137.77,
136.67, 129.37, 128.59, 128.49, 128.21, 128.10, 127. 03, 122.69, 118.91,
66.40, 48.63, 43.93, 43.86, 30.30, 29.93. FT-IR ν/cm–1 (KBr):1705,
1658, 1587, 1442, 1209, 766, 704. HRMS (ESI) calcd for C24H24N2O3
[M + H]+:370.1204; found:370.1202.
3-(6-Chloro-1-methyl-2-oxo-4-phenyl-1,2,3,4-tetrahydroquinolin-
3-yl)pentane-2,4-dione (12): White solid m.p. 173–175 °C:
1H NMR (400 MHz, CDCl3) δ 7.42–7.35 (m, 3H), 7.33 (m, 1H), 7.14
(dd, J=7.6 Hz, 1.6 Hz, 2H), 7.02 (d, J=8.8 Hz, 1H), 6.76 (dd, J=1.8 Hz,
0.8 Hz, 1H), 4.22 (d, J=9.6 Hz, 1H), 3.75 (dd, J=9.4 Hz, 6.8 Hz, 1H),
3.49 (t, J=7.6 Hz, 1H), 3.39 (s, 3H), 2.17 (d, J=5.2 Hz, 6H); 13C NMR
(100 MHz, CDCl3) δ 203.10, 202.66, 168.54, 13 8.81, 138.31, 129.42,
128.67, 128.45, 128.34, 128.14, 128.12, 116.08, 66.39, 48.53, 44.87,
30.22, 29.97. FT-IR ν/cm–1 (KBr): 1707, 1672, 1493, 1410, 1371, 1246,
1136, 818, 710. HRMS (ESI) calcd for C21H20ClNO3 [M + H]+:370.1204;
found:370.1202.
3-(6-Fluoro-1-methyl-2-oxo-4-phenyl-1,2,3,4-tetrahydroquinolin-
1
3-yl)pentane-2,4-dione (13): White solid m.p. 155–159 °C: H NMR
(400 MHz, CDCl3) δ 7.42–7.33 (m, 3H), 7.15 (dd, J=7.6 Hz, 1.6 Hz,
2H), 7.04 (d, J=4.8 Hz, 2H), 6.51 (dd, J=9.2 Hz, 1.2 Hz, 1H), 4.24 (d,
J=10.0 Hz, 1H), 3.75 (dd, J=9.6 Hz, 7.8 Hz, 1H), 3.50 (t, J=6.8 Hz,
1H), 3.40 (s, 3H), 2.16 (s, 6H); 13C NMR (100 MHz, CDCl3) δ 203.14,
202.75, 168.50, 159.99, 157.57, 138.85, 135.87, 129.38, 128.52, 128.10,
116.07, 115.99, 115.66, 115.42, 114.66, 11 4.44, 66.40, 48.54, 44.97,
30.36, 30.22, 29.97. FT-IR ν/cm–1 (KBr): 1705, 1670, 1504, 1360,
1157, 814. HRMS (ESI) calcd for C21H20FNO3 [M + H]+:354.1500;
found:354.1497.
3-(1-Ethyl-2-oxo-4-phenyl-1,2,3,4-tetrahydroquinolin-3-yl)pentane-
2,4-dione (14): White solid m.p. 128–131 °C: 1H NMR (400 MHz,
CDCl3) δ 7.37–7.26 (m, 4H), 7.15–7.10 (m, 3H), 7.05 (dd, J=7.6 Hz,
0.8 Hz, 1H), 6.90 (d, J=7.2 Hz, 1H), 4.14 (d, J=6.8 Hz, 1H), 4.04
(dd, J=9.4 Hz, 2.8 Hz, 2H), 3.80 (dd, J=8.6 Hz, 2.8 Hz, 1H), 3.60
(d, J=8.8 Hz, 1H), 2.20 (s, 3H), 2.13 (s, 3H), 1.28 (t, J=7.2 Hz, 3H).
13C NMR (100 MHz, CDCl3) δ 202.72, 202.69, 167.89, 139.93, 138.51,
129.25, 129.00, 128.45, 128.24, 127.57, 126.86, 123.42, 114.91, 67.71,
48.85, 45.17, 37.72, 30.44, 29.25, 12.63. FT-IR ν/cm–1 (KBr): 1707, 1655,
1603, 1496, 1466, 1388, 769, 704. HRMS (ESI) calcd for C22H23NO3
[M + H]+:350.1751; found:350.1748.
3-(4-(4-fluorophenyl)-1-methyl-2-oxo-1,2,3,4-tetrahydroquinolin-
1
3-yl)pentane-2,4-dione (8): Yellow solid m.p. 144–148 °C: H NMR
(400 MHz, CDCl3) δ 7.39–7.34 (m, 1H), 7.12–7.02 (m, 6H), 6.85 (d,
J=7.2 Hz, 1H), 4.19 (d, J=7.6 Hz, 1H), 3.76 (t, J=8.0 Hz, 1H), 3.56
(t, J=8.oHz, 1H), 3.39 (s, 3H), 2.19 (s, 3H), 2.14 (s, 3H); 13C NMR
(100 MHz, CDCl3) δ 202.77, 202.65, 168.44, 163.34, 160.89, 139.53,
135.59, 135.55, 129.91, 129.83, 128.69, 128.56, 126.67, 123.61, 116.11,
115.90, 115.06, 67.23, 48.97, 44.31, 30.33, 30.04, 29.54. FT-IR ν/cm–1
(KBr): 1707, 1664, 1504, 1375, 1225, 762, 667. HRMS (ESI) calcd for
C21H20FNO3 [M + H]+:354.1500; found:354.1498.
3-(4-(4-Bromophenyl)-1-methyl-2-oxo-1,2,3,4-tetrahydroquinolin-3-
yl)pentane-2,4-dione (9): Yellow liquid: 1H NMR (400 MHz, CDCl3) δ
7.49–7.46 (m, 2H), 7.39–7.35 (m, 1H), 7.12 (d, J=8.4 Hz, 1H), 7.06–6.99
(m, 3H), 6.85 (m, J=7.2 Hz, 1H), 4.16 (d, J=7.6 Hz, 1H), 3.75 (t,
J=7.6 Hz, 1H), 3.55 (d, J=8.0 Hz, 1H), 3.43 (s, 1H), 3.39 (s, 3H), 2.20 (s,
3-(2,4-Dioxopentan-3-yl)-2-oxo-4-phenyl-3,4-dihydroquinolin-
1
1(2H)-yl)propanenitrile (15): White solid m.p. 126–128 °C: H NMR
(400 MHz, CDCl3) δ 7.41–7.31 (m, 4H), 7.17–7.05 (m, 4H), 6.90 (d,
J=7.6 Hz, 1H), 4.33–4.11 (m, 3H), 3.81 (t, J=0.8 Hz, 1H), 3.53 (d,
J=0.8 Hz, 1H), 2.76 (t, J=7.2 Hz, 2H), 2.18 (s, 3H), 2.15 (s, 3H);
13C NMR (100 MHz, CDCl3) δ 202.75, 202.49, 16 8.88, 139.28,
137.86, 129.49, 129.23, 128.76, 128.27, 127.89, 127.26, 124.29, 117.35,
114.53, 66.98, 48.59, 45.03, 39.08, 30.30, 29.63, 15.94. FT-IR ν/cm–1
(KBr): 1701, 1668, 1599, 1462, 1367, 1169, 748. HRMS (ESI) calcd for
C23H22N2O3 [M + H]+:375.1703; found:375.1700.

JOURNAL OF CHEMICAL RESEARCH 2014 545
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We gratefully acknowledge National Natural Science
Foundation of China (Nos. 21302042 and 21172055),
Program for Innovative Research Team from Zhengzhou
(131PCXTD605) and Plan for Scientific Innovation Talent of
Henan University of Technology (171147).
10 A.L. Roschchin, N.A. Bumagin and I.P. Beletskaya, Tetrahedron Lett.,
1995, 36, 125.
11 B.E. Ali, K. Okuro, G. Vasapollo and H. Alper, J. Am. Chem. Soc., 1996,
118, 4264.
12 K. Fujita, Y. Takahashi, M. Owaki, K. Yamamoto and R. Yamaguchi, Org.
Lett., 2004, 6, 2785.
Received 2 July 2014; accepted 2 August 2014
Paper 1402747 doi: 10.3184/174751914X14099310712383
Published online: 25 September 2014
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