Metal-free intramolecular amination: One-pot tandem synthesis of 3-substituted 4-quinolones

Article abstract of DOI:10.1021/co1000103

3-Substituted 4-quinolones were synthesized using a one-pot metal-free strategy in moderate to quantitative yields. Carried out in dimethylsulfoxide (DMSO) via a sequential addition of materials, the methodology is tolerant of a wide range of functional groups and applicable to library synthesis.

Full text of DOI:10.1021/co1000103

RESEARCH ARTICLE
pubs.acs.org/acscombsci
Metal-Free Intramolecular Amination: One-Pot Tandem Synthesis of
3-Substituted 4-Quinolones
Qi-Lun Liu, Qiu-Lian Li, Xiang-Dong Fei, and Yong-Ming Zhu*
E01-1438, College of Pharmacy, Soochow University, Suzhou 215123, P.R. China
S Supporting Information
b
ABSTRACT: 3-Substituted 4-quinolones were synthesized using
a one-pot metal-free strategy in moderate to quantitative yields.
Carried out in dimethylsulfoxide (DMSO) via a sequential addition
of materials, the methodology is tolerant of a wide range of functional
groups and applicable to library synthesis.
KEYWORDS: quinolones, metal-free, one-pot, intramolecular amination
’ INTRODUCTION
procedure under mild conditions.12 Spectral data of chemset 1
showed typical aldehydic proton signals at about 9.5 ppm except
for 1{4} which exist solely in enolic form as evidenced by a
doublet (enolic hydroxyl signal) at 14.61 ppm in CDCl3 and a
broad singlet at 11.18 ppm in deuterated DMSO. Bernini
attempted to prepare 2-substituted 4-quinolones from enamine
formed in situ via a copper catalyzed one-pot strategy, but
evaporation of volatile materials was decisive and thus limited its
application.13 As Table 1 shows, our products could easily be
obtained from β-ketonaldehydes and amines in DMSO in the
presence of K2CO3 at 130 °C. DMSO was crucial for the present
study, when other solvents were employed, no or trivial amount
of product was observed (Table 1 Entries 5-8). The importance
of preheating of substrates before the addition of base suggested a
plausible reaction mechanism (Figure 1). And this was confirmed
by thin layer chromatography (TLC) analysis of the reaction.
Since chemset 1 and its Schiff base had the same Rf values, half an
equivalent of aniline was employed, the aniline spot disappeared,
and no product was detected before the addition of base.
Addition of base promoted the enamine-imine transformation
and further facilitated the dehydrobromination process to effect
the cyclization reaction. While weaker base failed to function in
either of the processes and stronger base triggered aldol con-
densation, K2CO3 proved to be the most suitable base (Table 1
Entries 9-10).
Since the finding of the antibacterial activities of Nalidixic
Acid,1 3-substituted 4-quinolone have been extensively studied
as a useful structural moiety for drug candidates. Apart from
the numerous marketed drugs such as Ciprofloxacin, Levoflox-
acin, and Moxifloxacin, scientists have found a wide range of
bioactive derivatives that exhibit antitumor,2 antibacterial,3 antiviral,4
antitrypanosomal,3f and selective M1 positive allosteric modulating
activities.5 All these justify the effort to develop new efficient
synthesis strategies for this structural moiety. However, existing
synthesis methods for 3-substituted 4-quinolones usually require
multi steps and laborious isolation of the intermediates,6 rare
substrates,7 or protective groups8 to furnish the reaction, and thus
find limited application in library synthesis. With recent advances
in chemistry, more efficient, mild, and diversity oriented reactions
such as metal-catalyzed couplings, multicomponent reactions
(MCRs), and combinatorial approaches have gained and will
continue to gain much progress.9 Numerous transition metal
catalyzed amination of aromatic rings have been reported.10 As part
of our continuing effort at the construction of heterocycles via
transition metal catalyzed reactions,11 we set out to develop an
efficient synthesis methodology for a quinolone library. Herein we
report a serendipitous finding, an efficient one-pot metal-free
combinatorial process (Figure 1) for the synthesis of 3-substituted
4-quinolones (chemset 3) using amines (chemset 2) and 3-(2-
bromophenyl)-3-oxopropanal derivatives (chemset 1).
With this protocol in hand we next studied the scope of the
reaction. R3 affected the reaction significantly, with electron rich
aromatics giving yields higher than its electron poor counterparts
(Table 2 Entries 1-10) and alkyl substituents (Table 2 Entries
11-12). Unlike R3, R1 and R2 did not have much impact on the
outcomes of the reaction. Good yields were obtained with both
electron donating and attracting substitutents (Table 2 Entries
13-21). Yields decreased as the steric hindrance grew larger
(Table 2 Entries 3, 16, 17). Unexpectedly, our attempt to expand
’ RESULTS AND DISCUSSION
In the light of preceding works, we envisioned that the target
molecule could be obtained via intramolecular cyclization/
amination of the enamines (i-2) formed in situ (Figure 1). To
study the proposed reaction, we first, on the basis of our previous
work in CuI catalyzed reactions, carried out a series of reaction
conditions screening and found that i-1 undergoes cyclization in
yields as good as reactions with no catalyst and ligand (Table 1
Entries 1-4). Chemset 1 could be obtained through a modified
Received: September 22, 2010
Published: November 9, 2010
r
2010 American Chemical Society
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dx.doi.org/10.1021/co1000103 ACS Comb. Sci. 2011, 13, 19–23
|

ACS Combinatorial Science
RESEARCH ARTICLE
Figure 1. Construction of quinolone structure moiety.
Table 1. Screening of Reaction Conditions
Table 2. Synthesis of 3-Substituted 4-Quinolones
entry catalyst
ligand
base
solvent
yielda (%)
95b
1
CuI 1,10-phenanthroline K2CO3 DMSO
2
CuI DMEDA
CuI L-proline
K2CO3 DMSO
K2CO3 DMSO
K2CO3 DMSO
K2CO3 toluene
96b
94b
3
4
95b/94.8c/85d
ndd,e
5
entry
R1
R2
R3
product yielda (%)
6
K2CO3 methanol ndd,e
K2CO3 dioxane ndd,e
1
H
H
H
H
H
H
H
H
H
H
H
H
H
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Ph
3{1,1}
3{1,2}
3{1,3}
3{1,4}
3{1,5}
3{1,6}
95
7
8
K2CO3 DMF
KOH DMSO
Na2CO3 DMSO
traced
40d,e
30d,e
2
4-OMeC6H4
2-MeC6H4
4-FC6H4
97.5
77
3
9
4
87.3
56
10
a Isolated yield. b 0.05 mmol Schiff base, 5% equiv CuI, 10% equiv ligand,
2 equiv base, 3 mL of DMSO, 130 °C. c 1 and 2 were heated in DMSO at
90 °C for 0.5 h before the addition of 1 equiv of base. d All components
were heated together. e Not detected.
5
2,4-Cl2C6H3
1-naphthyl
6
84
7
3,4-OCH2OC6H3 3{1,7}
95
8
4-MeC6H4
3{1,8}
3{1,9}
3{1,10}
3{1,11}
3{1,12}
3{2,1}
3{3,1}
3{4,1}
3{5,1}
3{6,1}
3{7,1}
3{8,1}
3{9,1}
3{10,1}
3{11,1}
82
9
3-NO2C6H4
52
the scope to the synthesis of 2-methyl-4-quinolone led to the
isolation of 2-methylchromone in 60% yield when 2-bromoben-
zoylacetone and aniline were employed as the starting materials
(Figure 2). This result was in good accordance with Bernini's
report that enamine of ketones could not be formed in DMSO
alone.13 Successful completion of the present protocol may be
accounted for by the stronger reactivity of aldehyde than ketones
and the activated bromine by adjacent carbonyl group.
10
11
12
13
2-pyridyl
40
cyclopropyl
63
benzyl
Ph
51.2
80.3
70
4-MeC6H4
14 4,5-OCH2O Ph
Ph
15
H
Me
Ph
97
16 3-Me
Ph
Ph
52
17
18
19
H
H
H
2-ClC6H4
4-FC6H4
4-ClC6H4
Ph
Ph
65
’ CONCLUSION
Ph
65.2
82
Ph
A copper-free tandem strategy using easily obtained β-keton-
aldehydes and amines as starting material for the synthesis of
3-substituted 4-quinolones is reported. The strategy gives 3-sub-
stituted quinolones in up to 97.5% yield without isolation of
intermediates, and is tolerant of a wide range of functional groups
and applicable to library synthesis.
20 5-MeO
21
Ph
68
H
3,5-Me2C6H3 Ph
Ph Ph
84
22 5-F
a Isolated yield.
85
’ EXPERIMENTAL SECTION
DMSO was dried over CaH2 and distilled. Melting points were
determined without correction on an XT5 digital melting-point
apparatus purchased from Beijing Keyi Elec-opti Instrument
Factory. 1H NMR and 13C NMR spectra were obtained from a
solution in CDCl3 or DMSO with tetramethylsilane (TMS) as
internal standard using a Varian Inova 400/101 MHz (1H/13C)
or 300/75 MHz (1H/13C) spectrometer, δ in parts per million
(ppm), and J in hertz (Hz). IR data were recorded on ProStar
LC240 using KBr tablets, wavenumbers in cm-1. HRMS analyses
were carried out using a time-of-flight mass spectrometry (TOF-
MS) or Saturan2200 (ESI) instrument.
Figure 2. Isolation of 2-methylchromone.
3 h, poured into water, basified with NaHCO3, heated at 80 °C
for 0.5 h, and then separated between EtOAc and water. The
organic layer was dried over Na2SO4, filtered, evaporated, and
run through column chromatography to give chemset 1.
General Procedure for the Synthesis of Chemset 3. A
mixture of chemset 1 (0.5 mmol) and chemset 2 (0.55 mmol)
were stirred at 90-100 °C for 0.5 h in DMSO under N2, then
General Procedure for the Synthesis of Chemset 1. A
solution of the ketone (2 mmol) in DMF (3 mL) was added to a
solution of POCl3 (3.5 equiv) in DMF (2 mL) at 0 °C under
nitrogen, and the mixture was stirred at room temperature for
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ACS Combinatorial Science
RESEARCH ARTICLE
K2CO3 (0.5 mmol) was added and stirred at 130 °C for another
8 h. The reaction mixture was separated between EtOAc (3ꢀ20
mL) and 30 mL of water. The organic layer was dried over
Na2SO4, filtered, evaporated under vacuum, and purified by
column chromatography to give chemset 3.
1,3-Diphenylquinolin-4(1H)-one (3{1,1}). White solid, mp
209-211 °C. 1H NMR (400 MHz, CDCl3): δ 8.59 (d, J = 8.1
Hz, 1H), 7.82 (s, 1H), 7.71 (d, J = 7.7 Hz, 2H), 7.59 (m, 3H),
7.43 (m, 6H), 7.30 (t, J = 7.3 Hz, 1H), 7.03 (d, J = 8.5 Hz, 1H);
13C NMR (101 MHz, CDCl3): δ175.97, 160.14, 142.02, 141.14,
135.36, 134.11, 131.71, 131.01, 128.80, 128.75, 128.35, 127.20,
126.80, 123.89, 121.92, 117.29, 116.45, 115.38, 114.78, 55.78; IR
(KBr): 3048, 3036, 2936, 1616, 1580, 1549, 1497, 1477, 1368,
1325, 1256, 756, 696. HRMS (EI): Mþ calcd for C21H15NO
297.1154. Found: 297.1154.
1-(4-Methoxyphenyl)-3-phenylquinolin-4(1H)-one (3{1,2}).
Pale yellow solid, mp 124-127 °C. 1H NMR (400 MHz, CDCl3):
δ 8.58 (d, J = 7.9 Hz, 1H), 7.81 (s, 1H), 7.71 (d, J = 7.6 Hz, 2H),
7.49 (t, J = 7.7 Hz, 1H), 7.43-7.33 (m, 5H), 7.30 (t, J = 7.3 Hz,
1H), 7.08 (d, J = 8.6 Hz, 2H), 7.02 (d, J = 8.5 Hz, 1H), 3.90 (s,
3H).13C NMR (101 MHz, CDCl3): δ 175.97, 160.14, 142.02,
141.14, 135.36, 134.11, 131.71, 128.80, 128.75, 128.35, 127.20,
126.80, 123.89, 121.92, 117.29, 115.38, 55.78. IR (KBr): 3063,
3048, 3009, 2970, 2932, 2833, 1624, 1609, 1585, 1508, 1325, 1246,
1024, 775. HRMS (EI): Mþ calcd for C22H17NO2 327.1259.
Found: 327.1260.
134.62, 131.92, 130.41, 130.07, 128.73, 128.28, 128.18, 127.36,
127.18, 127.14, 126.69, 126.17, 125.83, 123.97, 122.18, 122.13,
117.41. IR (KBr): 3055, 3028, 1620, 1589, 1476, 1321, 762.
HRMS (EI): Mþ calcd for C25H17NO 347.1310. Found:
347.1309.
1-(Benzo[d][1,3]dioxol-5-yl)-3-phenylquinolin-4(1H)-one
1
(3{1,7}). White solid, mp 173-175 °C. H NMR (400 MHz,
CDCl3): δ 8.57 (d, J = 7.5 Hz, 1H), 7.80 (s, 1H), 7.70 (d, J = 7.5
Hz, 2H), 7.52 (m, 1H), 7.40 (m, 3H), 7.31 (t, J = 7.4 Hz, 1H),
7.08 (d, J = 8.5 Hz, 1H), 6.98 (d, J = 7.9 Hz, 1H), 6.96-6.89 (m,
2H), 6.13 (d, J = 4.7 Hz, 2H). 13C NMR (101 MHz, CDCl3):
176.03, 148.98, 148.55, 141.83, 141.07, 135.31, 135.18, 131.81,
128.79, 128.39, 127.30, 127.28, 126.81, 123.99, 122.09, 121.30,
117.24, 109.13, 108.64, 102.42. IR (KBr): 3044, 3032, 1618,
1603, 1576, 1487, 1229, 1036, 750. HRMS (EI): Mþ calcd for
C22H15NO3 341.1052. Found: 341.1069.
3-Phenyl-1-p-tolylquinolin-4(1H)-one (3{1,8}). Pale yellow
solid, mp 164-166 °C. 1H NMR (400 MHz, CDCl3): δ 8.58 (d,
J = 8.1 Hz, 1H), 7.80 (s, 1H), 7.75-7.64 (m, 2H), 7.54-7.43 (m,
1H), 7.44-7.27 (m, 8H), 7.03 (d, J = 8.5 Hz, 1H), 2.48 (s, 3H).13C
NMR (101 MHz, CDCl3): 176.00, 141.79, 140.89, 139.78, 138.90,
135.37, 131.69, 130.93, 128.77, 128.34, 127.37, 127.23, 127.19,
126.82, 123.92, 122.00, 117.28, 21.33. IR (KBr): 3057, 3028, 2957,
2922, 1622, 1603, 1584, 1514, 1479, 1327, 1254, 758. HRMS (EI):
Mþ calcd for C22H17NO 311.1310. Found: 311.1313.
1-(3-Nitrophenyl)-3-phenylquinolin-4(1H)-one (3{1,9}).
1
Pale yellow solid, mp 229-230 °C. H NMR (400 MHz,
3-Phenyl-1-o-tolylquinolin-4(1H)-one (3{1,3}). Pale yellow
1
CDCl3): δ 8.56 (dd, J = 8.1, 1.4 Hz, 1H), 8.46-8.40 (m,
1H), 8.37 (s, 1H), 7.89-7.83 (m, 2H), 7.76 (s, 1H), 7.66 (d, J =
7.3 Hz, 2H), 7.58-7.51 (m, 1H), 7.40 (dt, J = 11.1, 7.6 Hz, 3H),
7.31 (t, J = 7.3 Hz, 1H), 6.96 (d, J = 8.5 Hz, 1H). 13C NMR (101
MHz, CDCl3): 173.37, 146.70, 139.69, 137.97, 137.57, 132.01,
131.38, 129.63, 128.91, 126.13, 125.77, 125.02, 124.93, 124.06,
121.89, 121.77, 120.55, 120.42, 113.72. IR (KBr): 3078, 3026,
2957, 2924, 2855, 1626, 1609, 1587, 1528, 1477, 1350, 750.
HRMS (EI): Mþ calcd for C21H14N2O3 342.1004. Found:
342.1008.
solid, mp 138-140 °C. H NMR (400 MHz, CDCl3): δ 8.61
(d, J = 8.1 Hz, 1H), 7.78-7.70 (m, 3H), 7.54-7.28 (m, 9H), 6.80
(d, J = 8.5 Hz, 1H), 2.10 (s, 3H). 13C NMR (101 MHz, CDCl3):
176.09, 141.25, 140.47, 140.09, 136.18, 135.32, 132.05, 131.93,
130.11, 128.81, 128.38, 128.34, 128.03, 127.38, 127.26, 126.84,
123.99, 122.31, 116.85, 17.34. IR (KBr): 3053, 3024, 1624, 1587,
1479, 1327, 766. HRMS (EI): Mþ calcd for C22H17NO 311.1310.
Found: 311.1310.
1-(4-Fluorophenyl)-3-phenylquinolin-4(1H)-one (3{1,4}).
1
Pale yellow solid, mp 223-225 °C. H NMR (400 MHz,
CDCl3): δ 8.57 (d, J = 8.0 Hz, 1H), 7.77 (s, 1H), 7.69 (d, J =
7.5 Hz, 2H), 7.51 (t, J = 7.6 Hz, 1H), 7.48-7.25 (m, 8H), 6.98
(d, J = 8.5 Hz, 1H). 13C NMR (101 MHz, CDCl3): 176.00,
164.02, 161.53, 141.49, 140.85, 137.41, 135.13, 131.92, 129.73,
129.64, 128.77, 128.40, 127.35, 127.35, 126.78, 126.16, 124.11,
122.30, 117.59, 117.36, 116.96. IR (KBr): 3049, 3038, 1618,
1582, 1508, 1477, 1223, 756. HRMS (EI): Mþ calcd for C21H14-
FNO 315.1059. Found: 315.1059.
1-(2,4-Dichlorophenyl)-3-phenylquinolin-4(1H)-one (3{1,5}).
Pale yellow solid, mp 145-147 °C. 1H NMR (400 MHz, CDCl3): δ
8.56 (d, J = 8.0 Hz, 1H), 7.75-7.65 (m, 3H), 7.62 (s, 1H),
7.56-7.42 (m, 3H), 7.39 (t, J = 7.4 Hz, 3H), 7.30 (t, J = 7.3 Hz,
1H), 6.77 (d, J= 8.5 Hz, 1H). 13C NMR (101 MHz, CDCl3): 176.16,
140.76, 140.11, 137.00, 136.71, 134.88, 134.14, 132.21, 131.16,
131.06, 129.12, 128.81, 128.36, 127.43, 126.66, 124.25, 122.85,
116.29. IR (KBr): 3057, 3026, 2957, 2924, 1622, 1589, 1476, 1331,
760. HRMS (EI): Mþ calcd for C21H13Cl2NO 365.0374. Found:
365.0389.
3-Phenyl-1-(pyridin-2-yl)quinolin-4(1H)-one (3{1,10}).
Pale yellow solid, mp 210-211 °C. 1H NMR (400 MHz, CDCl3):
δ 8.00-7.91 (m, 1H), 7.81 (dd, J = 8.1, 1.5 Hz, 1H), 7.22 (td, J =
7.8, 1.9 Hz, 1H), 6.94 (dd, J = 8.2, 1.1 Hz, 2H), 6.81-6.69 (m, 3H),
6.64 (t, J = 7.6 Hz, 3H), 6.59-6.47 (m, 3H). 13C NMR (101 MHz,
CDCl3): 176.31, 153.45, 150.41, 140.45, 139.44, 135.16, 131.87,
128.92, 128.32, 127.43, 127.33, 126.68, 124.37, 124.29, 122.72,
121.60, 116.53. IR (KBr): 3051, 1618, 1607, 1580, 1553, 1481,
1470, 1437, 1317, 752. HRMS (EI): Mþ calcd for C22H14N2O
298.1106. Found: 298.1105.
1-Cyclopropyl-3-phenylquinolin-4(1H)-one (3{1,11}).
Pale yellow solid, mp 180-182 °C. 1H NMR (400 MHz, CDCl3):
δ 8.51 (d, J = 8.0 Hz, 1H), 7.90 (d, J = 8.6 Hz, 1H), 7.85 (s, 1H),
7.65 (t, J = 7.8 Hz, 3H), 7.39 (m, 3H), 7.29 (t, J = 7.4 Hz, 1H),
3.54-3.37 (m, 1H), 1.27 (q, J = 6.4 Hz, 2H), 1.12-1.01 (m, 2H).
13C NMR (75 MHz, CDCl3): 175.87, 141.42, 140.88, 135.63,
131.81, 128.73, 128.29, 127.30, 127.05, 126.90, 123.80, 121.76,
116.07, 33.86, 8.36. IR (KBr): 3069, 3017, 1620, 1609, 1578, 1483,
1329, 754. HRMS (EI): Mþ calcd for C18H15NO 261.1154. Found:
261.1155.
1-(Naphthalen-1-yl)-3-phenylquinolin-4(1H)-one (3{1,6}).
Pale yellow solid, mp 115-118 °C. 1H NMR (400 MHz,
CDCl3): δ 8.64 (dd, J = 6.2, 3.3 Hz, 1H), 8.07 (d, J = 8.1 Hz,
1H), 8.00 (d, J = 8.3 Hz, 1H), 7.85 (s, 1H), 7.72 (d, J = 7.3 Hz,
2H), 7.60 (m, 3H), 7.44 (t, J = 7.6 Hz, 1H), 7.41-7.31 (m, 5H),
7.25 (dd, J = 12.9, 5.3 Hz, 1H), 6.70 (dd, J = 6.1, 3.3 Hz, 1H). 13C
NMR (75 MHz, CDCl3): 176.15, 142.06, 141.28, 137.45, 135.14,
1-Benzyl-3-phenylquinolin-4(1H)-one (3{1,12}). White solid,
mp 169-171 °C. 1H NMR (400 MHz, CDCl3): δ 8.59 (dd, J = 8.1,
1.3 Hz, 1H), 7.86 (s, 1H), 7.76-7.67 (m, 2H), 7.61-7.51 (m, 1H),
7.43 (t, J = 7.5 Hz, 2H), 7.35 (m, 6H), 7.19 (d, J = 7.0 Hz, 2H), 5.40
(s, 2H). 13C NMR (75 MHz, CDCl3): 175.98, 142.61, 139.47,
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RESEARCH ARTICLE
135.39, 135.25, 132.06, 129.26, 128.76, 128.35, 128.30, 127.61,
127.53, 127.17, 126.08, 123.80, 122.15, 116.03, 56.62. IR (KBr):
3049, 3028, 1626, 1611, 1580, 1555, 1491, 756. HRMS (EI): Mþ
calcd for C22H17NO 311.1310. Found: 311.1310.
7.03 (d, J = 8.5 Hz, 1H). 13C NMR (101 MHz, CDCl3): 175.82,
141.44, 141.32, 140.75, 133.75, 132.96, 131.94, 130.48, 130.01,
129.74, 128.46, 127.66, 127.22, 126.71, 124.20, 120.84, 117.28.
IR (KBr): 3063, 3034, 3009, 2956, 2924, 2855, 1622, 1611, 1584,
1555, 1493, 11090, 864, 829, 760, 704. HRMS (EI): Mþ calcd for
C21H14ClNO 331.0764. Found: 331.0766.
6-Methoxy-1,3-diphenylquinolin-4(1H)-one (3{9,1}). Pale
yellow solid, mp 157-169 °C. 1H NMR (400 MHz, CDCl3): δ
7.98 (d, J = 2.9 Hz, 1H), 7.79 (s, 1H), 7.72 (d, J = 7.7 Hz, 2H),
7.64-7.52 (m, 3H), 7.48-7.35 (m, 4H), 7.29 (t, J = 6.9 Hz, 1H),
7.12 (dd, J = 9.3, 2.9 Hz, 1H), 6.98 (d, J = 9.3 Hz, 1H), 3.93 (s,
3H). 13C NMR (101 MHz, CDCl3): 175.32, 156.57, 141.55,
140.84, 135.53, 135.40, 130.35, 129.56, 128.79, 128.33, 127.96,
127.61, 127.13, 122.56, 121.07, 118.91, 106.05, 55.87. IR (KBr):
3049, 2965, 2938, 2837, 1607, 1578, 1553, 1491, 1368, 1325, 1036,
808, 779, 698, 579. HRMS (EI): Mþ calcd for C22H17NO2
327.1259. Found: 327.1254.
1-Phenyl-3-p-tolylquinolin-4(1H)-one (3{2,1}). Pale yellow
solid, mp 173-174 °C. 1H NMR (400 MHz, CDCl3): δ 8.59 (d,
J = 8.0 Hz, 1H), 7.81 (s, 1H), 7.60 (m, 5H), 7.47 (m, 3H), 7.38 (t,
J = 7.5 Hz, 1H), 7.22 (d, J = 7.7 Hz, 2H), 7.03 (d, J = 8.5 Hz, 1H),
2.37 (s, 3H). 13C NMR (101 MHz, CDCl3): 176.11, 141.50,
141.30, 140.72, 136.96, 132.31, 131.69, 130.41, 129.57, 129.08,
128.62, 127.69, 127.29, 126.73, 123.91, 122.10, 117.14, 21.32. IR
(KBr): 3057, 3044, 1626, 1612, 1597, 1477, 1329, 1258, 758.
HRMS (EI): Mþ calcd for C22H17NO 311.1310. Found: 311.1312.
5,7-Diphenyl-[1,3]dioxolo[4,5-g]quinolin-8(5H)-one (3{3,1}).
Pale yellow solid, mp 274-276 °C. 1H NMR (400 MHz, CDCl3): δ
7.92 (s, 1H), 7.71 (s, 2H), 7.69 (s, 1H), 7.66-7.53 (m, 3H),
7.47-7.34 (m, 4H), 7.33-7.24 (m, 1H), 6.39 (s, 1H), 6.02 (s, 2H).
13C NMR (101 MHz, CDCl3): 174.74, 151.63, 145.84, 141.74,
140.40, 137.97, 135.38, 130.48, 129.72, 128.84, 128.33, 127.61,
127.19, 122.68, 121.49, 104.20, 102.08, 96.51. IR (KBr): 3075,
3057, 2909, 1634, 1584, 1493, 1468, 1236, 1030, 694. HRMS (EI):
Mþ calcd for C22H15NO3 341.1052. Found: 341.1049.
3-(3,5-Dimethylphenyl)-1-phenylquinolin-4(1H)-one
(3{10,1}). White solid, mp 218-220 °C. 1H NMR (400 MHz,
CDCl3): δ 8.59 (d, J = 8.0 Hz, 1H), 7.81 (s, 1H), 7.60 (m, 3H),
7.48 (m, 3H), 7.38 (t, J = 7.5 Hz, 1H), 7.33 (s, 2H), 7.03 (d, J = 8.5
Hz, 1H), 6.96 (s, 1H), 2.35 (s, 6H). 13C NMR (101 MHz,
CDCl3): 176.10, 141.58, 141.52, 140.75, 137.82, 135.12, 131.70,
130.43, 129.58, 129.04, 127.73, 127.35, 126.81, 126.61, 123.94,
122.44, 117.14, 77.48, 77.16, 76.84, 21.50. IR (KBr): 3044, 3013,
3001, 2916, 1622, 1586, 1553, 1479, 1339, 754. HRMS (EI): Mþ
calcd for C23H19NO 325.1467. Found: 325.1468.
3-Methyl-1-phenylquinolin-4(1H)-one (3{4,1}). White solid,
1
mp 169-170 °C. H NMR (400 MHz, CDCl3): δ 8.46 (d, J =
8.1 Hz, 1H), 7.63-7.47 (m, 4H), 7.47-7.34 (m, 3H), 7.29 (t, J =
7.5 Hz, 1H), 6.96 (d, J = 8.6 Hz, 1H), 2.13 (s, 3H). 13C NMR (101
MHz, CDCl3): 178.12, 141.55, 141.05, 140.49, 131.31, 130.27,
129.34, 127.68, 126.54, 123.32, 118.45, 116.99, 13.86. IR (KBr):
3048, 3011, 1628, 1589, 1553, 1483, 1371, 1308, 762, 694. HRMS
(EI): Mþ calcd for C16H13NO 235.0997. Found: 235.0995.
8-Methyl-1,3-diphenylquinolin-4(1H)-one (3{5,1}). Pale
6-Fluoro-1,3-diphenylquinolin-4(1H)-one (3{11,1}). Pale
1
yellow solid, mp 121-123 °C. H NMR (400 MHz, CDCl3):
δ 8.18 (dd, J = 9.1, 2.7 Hz, 1H), 7.81 (s, 1H), 7.67 (d, J = 7.4 Hz,
2H), 7.59 (dq, J = 13.3, 6.5 Hz, 3H), 7.44 (d, J = 7.0 Hz, 2H), 7.38
(t, J = 7.5 Hz, 2H), 7.29 (d, J = 7.4 Hz, 1H), 7.25-7.17 (m, 1H),
7.03 (m, 1H). 13C NMR (101 MHz, CDCl3): 175.09, 160.58,
158.14, 141.63, 141.19, 137.24, 134.90, 130.50, 129.80, 128.70,
128.34, 128.12, 127.51, 127.38, 127.32, 126.72, 121.38, 120.53,
120.28, 119.57, 119.50, 111.73, 111.50. IR (KBr): 3061, 3040,
2961, 2924, 1692, 1614, 1580, 1562, 1487, 1325, 1254, 820, 698,
579. HRMS (EI): Mþ calcd for C21H14FNO 315.1059. Found:
315.1062.
1
yellow solid, mp 189-191 °C. H NMR (400 MHz, CDCl3):
δ 8.51 (d, J = 7.7 Hz, 1H), 7.78 (s, 1H), 7.70 (d, J = 8.0 Hz, 2H),
7.55-7.42 (m, 3H), 7.42-7.26 (m, 7H), 1.78 (s, 3H). 13C NMR
(101 MHz, CDCl3): 176.33, 145.55, 144.64, 139.89, 136.24,
135.12, 129.90, 128.74, 128.34, 127.26, 127.09, 126.93, 125.79,
124.35, 121.48, 22.41. IR (KBr): 3061, 3022, 1618, 1578, 1562,
1479, 1308, 770, 696. HRMS (EI): Mþ calcd for C22H17NO
311.1310. Found: 311.1310.
Spectral data for 2-methyl-4-chromone, see ref 14.
3-(2-Chlorophenyl)-1-phenylquinolin-4(1H)-one (3{6,1}).
Pale yellow solid, mp 164-166 °C. 1H NMR (400 MHz, CDCl3):
δ 8.57 (d, J = 8.0 Hz, 1H), 7.79 (s, 1H), 7.65-7.37 (m, 9H),
7.32-7.23 (m, 2H), 7.08 (d, J = 8.5 Hz, 1H). 13C NMR (101
MHz, CDCl3): 175.61, 143.22, 141.30, 140.99, 134.15, 133.92,
132.74, 131.99, 130.43, 129.83, 129.66, 129.05, 127.67, 127.31,
126.71, 124.23, 120.44, 120.02, 117.37. IR (KBr): 3051, 3030,
3013, 1630, 1601, 1587, 1557, 1479, 1331, 764, 745, 704. HRMS
(EI): Mþ calcd for C21H14ClNO 331.0764. Found: 331.0764.
3-(4-Fluorophenyl)-1-phenylquinolin-4(1H)-one (3{7,1}).
Pale yellow solid, mp 199-201 °C. 1H NMR (400 MHz,
CDCl3): δ 8.56 (d, J = 8.0 Hz, 1H), 7.79 (s, 1H), 7.71-7.55
(m, 5H), 7.53-7.43 (m, 3H), 7.39 (t, J = 7.5 Hz, 1H), 7.08 (t, J =
8.7 Hz, 2H), 7.03 (d, J = 8.6 Hz, 1H).13C NMR (75 MHz,
CDCl3): 176.31, 164.48, 161.20, 156.30, 153.04, 133.86, 130.84,
130.73, 127.87, 126.48, 125.46, 124.59, 124.53, 118.19, 115.75,
115.46. IR (KBr): 3048, 1620, 1576, 1555, 1510, 1479, 1327,
1225, 835, 756, 694, 532. HRMS (EI): Mþ calcd for C21H14NO
315.1059. Found: 315.1058.
’ ASSOCIATED CONTENT
S
Supporting Information. Spectral data of all compounds.
b
This material is available free of charge via the Internet at
http://pubs.acs.org.
’ AUTHOR INFORMATION
Corresponding Author
*E-mail: zhuyongming@suda.edu.cn.
’ ACKNOWLEDGMENT
This work was partially supported by the National Natural
Science Foundation of China (Grants 20472062 and 20672079)
and the Natural Science Foundation of Jiangsu Province (No.
BK2006048).
3-(4-Chlorophenyl)-1-phenylquinolin-4(1H)-one (3{8,1}).
1
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