A Cascade Reaction of Michael Addition and Truce-Smiles Rearrangement to Synthesize Trisubstituted 4-Quinolone Derivatives

Article abstract of DOI:10.1021/acs.joc.0c01662

A novel transition-metal-free cascade reaction to synthesize 4-quinolone derivatives has been demonstrated. Michael addition and Truce-Smiles rearrangement are included in this protocol, providing a broad scope of 4-quinolones in moderate-to-excellent yields. This work serves as an example of the use of sulfonamides through Truce-Smiles rearrangement to build heterocyclic compounds under mild conditions.

Full text of DOI:10.1021/acs.joc.0c01662

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A Cascade Reaction of Michael Addition and Truce-Smiles
Rearrangement to Synthesize Trisubstituted 4‑Quinolone
Derivatives
Caixia Xie, Di Yang, Xinfeng Wang, and Chen Ma*
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ABSTRACT: A novel transition-metal-free cascade reaction to
synthesize 4-quinolone derivatives has been demonstrated. Michael
addition and Truce-Smiles rearrangement are included in this protocol,
providing a broad scope of 4-quinolones in moderate-to-excellent
yields. This work serves as an example of the use of sulfonamides
through Truce−Smiles rearrangement to build heterocyclic compounds
under mild conditions.
to construct this skeleton was reported (Scheme 1c).5 In
addition, Canesi demonstrated a tandem Smiles−Michael
process using a nosyl group as a functional protecting group to
develop indole derivatives (Scheme 1d).6 In addition, they
have reported a Michael−Smiles ring-closure cascade process
to construct arylated cyclopropane.7
The 4-quinolone scaffold is a promising bioactive structure
and exhibits superior qualities in the treatment of human
disease.8 For example, dorfloxacin, ciprofloxacin, and ofloxacin
are widely used in varieties of acute and chronic bacterial
infections.9 In addition, 4-quinolone derivatives are very
important units of alkaloids, which exist in natural molecules
and have wide utility values.10−13 Furthermore, by means of
the modifications of the 4-quinolone skeleton, the specific
medicinal values were achieved, such as antibacterial,14
antitumor,15 antimalarial,16 and other activities.17
INTRODUCTION
■
The Smiles rearrangement reaction, as an intramolecular
nucleophilic aromatic substitution reaction, has been used to
construct a lot of heterocyclic compounds.1 However, a
vigorous revival of this reaction appeared in recent years, and it
is usually applied to cascade reactions.2 For example, Grimaud
reported a phenol Ugi−Smiles system for four-component
reaction (Scheme 1a).3 In 2012, a domino reaction to
construct dibenzoxazepinones via copper-catalyzed Ullmann
reaction, Smiles rearrangement, and ring-closing process was
reported (Scheme 1b).4 Recently, a cascade reaction of copper-
catalyzed C−H etherification and C−N Smiles rearrangement
Scheme 1. Examples of Applications of Smiles
Rearrangement in Recent Years
On account of these, many methods (Scheme 2) have been
reported to construct this skeleton catalyzed by transition-
metal catalysts such as Cu (a),18 Ni (b),19 Au (c),20 Rh (d),21
and Pd (e).22 A strategy without transition-metal catalysts was
reported; however, peroxide TBHP was involved in this report
(f).23 Hence, a simple and effective method for synthesizing 4-
quinolones is worthy of study. Based on our previous works1e1f
with the Smiles rearrangement applied on building heterocyclic
compounds, we envisaged that a cascade reaction of Michael-
addition and Smiles rearrangement between benzene sulfona-
mides and 1-(2-bromophenyl)-3-phenylprop-2-yn-1-ones
Received: July 13, 2020
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feed ratio was adjusted to 1:2, and the yield of the product was
improved to 78% (entry 2). Then, several bases were
investigated under the same conditions and K2CO3 was
proved to be the most effective base (entries 2−6). On this
basis, a screening of solvents was carried out, and the results
indicated that the most appropriate solvent was DMF (entries
7−9). No satisfactory yield of the desired product was
obtained whether increasing or decreasing the reaction
temperature (entries 10−11). However, when 2 equiv of
K2CO3 were used, the desired product with a yield of 95% was
obtained (entries 12−14). Therefore, the optimized reaction
conditions are summarized in entry 12.
Scheme 2. Synthetic Methods of 4-Quinolone Derivatives
With the optimized conditions in hand, the generality of the
methodology was further extended and the results are shown in
Table 2. First, the reaction underwent smoothly to give the
desired products in moderate-to-excellent yields when R2 was
phenyl with different substituents (3a−3g). A benzyl group
was also compatible, affording the corresponding products 3h,
with a lower yield of 48%. Surprisingly, naphthyl-substituted
benzene sulfonamide succeeded in giving the desired product
3i in a satisfactory yield. In addition, alkyl-substituted benzene
sulfonamides could also be subjected to this reaction to form
the products in moderate yields (3j−3l); it was a breakthrough
compared with the previous report.25 We then proceeded to
examine the scope of R1, and compounds 1 with strong
electron-withdrawing groups like −CF3 and −CN could also
be applied to this reaction (3m−3o). In addition, when −NO2
was positioned ortho to the sulfamide, the reaction took place
smoothly (3o).
would allow access to trisubstituted 4-quinolones with a loss of
sulfur dioxide.24
After getting these promising results, we turned to
investigate the substituent effects of 1-(2-bromophenyl)-3-
phenylprop-2-yn-1-ones. As for the R3 group, both electron-
donating groups and electron-withdrawing groups were
tolerated, and compounds bearing electron-withdrawing
groups (3r, 3s, 3nb) gave better yields than those bearing
electron-donating groups (3p, 3q, 3na). Also, electron effects
of R4 groups have no significant influence on the reaction and
the desired products were obtained in moderate-to-excellent
yields (3t−3x, 3oc, 3od). Surprisingly, a free alkyne or TMS-
protected alkyne (2ba and 2bc) both could work in this
procedure and gave the same product 3ba in acceptable yields.
Furthermore, compound 3bb could be obtained in a yield of
74% in this reaction with an aliphatic alkyne used as a reactant.
To confirm the structure of the product, an X-ray structure
of product 3a was obtained by X-ray crystallographic analysis
and is shown in Figure 1 (CCDC number: 2008744). In
addition, to examine the scalability of the present strategy, a
gram-scale reaction of compounds 1a and 2a was carried out
(Scheme 3). The corresponding product 3a was obtained in
77% isolated yield, which indicated a good practical utility of
the method.
RESULTS AND DISCUSSION
■
To confirm the feasibility of this approach, we used 4-
nitrobenzenesulfonamide and 1-(2-bromophenyl)-3-phenyl-
prop-2-yn-1-one as the model substrates to test our assumption
(Table 1). Our initial experiment was promoted by Cs2CO3 in
DMSO at 100 °C with a reactant ratio of 1:1. Also, the desired
product 3a was obtained in a yield of 39% (entry 1). Then, the
a
Table 1. Optimization of Reaction Conditions
b
entry
base
Cs2CO3
Cs2CO3
K2CO3
K3PO4
NaOH
t-BuOK
K2CO3
solvent
temperature
yield (%)
c
1
2
3
4
5
6
7
8
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
DMF
100
100
100
100
100
100
100
100
100
80
39
78
90
63
33
29
92
trace
43
68
45
95
65
88
From the overall results and previously published works,25,26
a possible mechanism is proposed (Scheme 4). First, the
intermediate 6 was obtained via Michael addition. Then,
Truce−Smiles rearrangement occurred driven by a loss of
sulfur dioxide, giving the intermediate 8. Also, its geometric
isomer 9 could be interconverted. Subsequently, an intra-
molecular nucleophilic substitution happened and the desired
products 4-quinolone derivatives 4 were obtained.
K2CO3
K2CO3
K2CO3
toluene
CH3CN
DMF
9
10
11
12
13
14
K2CO3
DMF
DMF
DMF
DMF
120
100
100
100
K2CO3 (2 equiv)
K2CO3 (1 equiv)
K2CO3 (4 equiv)
CONCLUSIONS
To conclude, we have described a transition metal-free cascade
reaction from benzene sulfonamides and 1-(2-bromophenyl)-
a
■
Reaction conditions: 1a (0.3 mmol), 2a (0.6 mmol), solvent (2 mL),
base (3 equiv), temperature, air, TLC monitored the end of the
b
c
reaction. Isolated yield. 1a (0.3 mmol), 2a (0.3 mmol)
B
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a b
,
Table 2. Substrate Scope
Figure 1. X-ray structure of compound 3a.
Scheme 3. Gram-Scale Reactions of 1a and 2a
Scheme 4. Proposed Reaction Mechanism
constructing heterocyclic compounds. Applications of this
cascade strategy to construct heterocyclic compounds with
bioactivities are under study in our laboratory.
EXPERIMENTAL SECTION
■
General Information. Benzenesulfonamides and 1-(2-bromo-
phenyl)-3-phenylprop-2-yn-1-ones were prepared according to
literature procedures.27−30 Other reagents were commercially
available and were used without further purification. All reactions
were monitored by thin-layer chromatography (TLC). H NMR, 13C
1
NMR, and 19F NMR spectra were recorded on a Bruker Avance 400
(400 MHz) spectrometer, using CDCl3 or DMSO-d6 as a solvent and
tetramethylsilane (TMS) as an internal standard. HRMS spectra were
determined on a Q-TOF 6510 spectrograph (Agilent). Melting points
were determined on an XD-4 digital micro melting-point apparatus.
General Experimental Procedures for the Synthesis of
Benzenesulfonamides 1.27 A solution of substituted aniline (5
mmol) and NaOAc (6 mmol) in CH2Cl2 (30 mL) was stirred at room
temperature. Substituted benzenesulfonyl chloride (5 mmol) was
diluted in CH2Cl2 and then added into the mixture dropwise. Then,
the mixture was stirred overnight and the white solid was separated
out. The solid was purified through filtration, washing, and
recrystallization to give the desired product 1.
a
Reaction conditions: 1 (0.3 mmol), 2 (0.6 mmol), DMF (2 mL),
K2CO3 (2 equiv), 100 °C, air, TLC monitored the end of the
b
reaction. Isolated yield.
3-phenylprop-2-yn-1-ones to construct 4-quinolone deriva-
tives. The cascade reaction includes Michael addition, Truce-
Smiles rearrangement, and intramolecular nucleophilic sub-
stitution under mild conditions. A wide range of densely
functionalized 4-quinolone derivatives could be obtained
through this process, which has potential applications in
biomedical research. The use of sulfonamides though
Michael−Smiles rearrangement sets up a novel method for
General Experimental Procedures for the Synthesis of 1-(2-
Bromophenyl)-3-phenylprop-2-yn-1-ones.28 A solution of al-
kyne (12 mmol) in anhydrous THF (30 mL) and n-BuLi (2.5 M, 10
mmol) was stirred at −78 °C under and an N2 atmosphere for 1 h.
C
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Then, the aldehyde (10 mmol) was added slowly and the mixture was
warmed to room temperature for 3 h, until the TLC monitored the
end of the reaction. The mixture was quenched with saturated
solution of NH4Cl and extracted with dichloromethane (30 mL × 3).
The combined organic layers were washed, dried over anhydrous
Na2SO4, and then concentrated under reduced pressure. The organic
layer was mixed with IBX (12 mmol) and DMSO (20 mL), and then
the mixture was stirred at room temperature for about 12 h until the
TLC monitored the end of the reaction. The mixture was quenched
with water (30 mL) and extracted with ethyl acetate (30 mL × 3).
The organic layers were combined, dried, filtered, and concentrated.
The product 2a−2od was purified by column chromatography with
petroleum ether/ethyl acetate = 10:1−20:1.
General Experimental Procedures for the Syntheses of 2ba
and 2bc.29 A solution of aldehyde (10 mmol) in anhydrous THF
(30 mL) was stirred at 0 °C under an N2 atmosphere. A solution of
ethynylmagnesium bromide or 1-propynylmagnesium bromide in
THF (0.5 M solution, 13 mmol) was added dropwise at 0 °C for
about 30 min, warmed to room temperature, and then stirred for
about 4 h. Saturated aqueous NH4Cl solution (30 mL) was added,
and the mixture was evaporated in vacuo, separated by EtOAc and
saturated aqueous NaCl solution. The organic layer was dried by
Na2SO4 and evaporated in vacuo to obtain the intermediate. Then,
the intermediate, NaBr (10 mmol), NaHCO3 (20 mmol), and
TEMPO (0.5 mmol) were stirred in CH2Cl2 (50 mL) at 0 °C. A
solution of NaOCl (12%, 30 mmol) was added slowly, and the
mixture were stirred at this temperature until TLC monitored the end
of the reaction. The mixture was separated by CH2Cl2 and saturated
aqueous NaCl solution. The organic layers were combined, dried,
filtered, and concentrated. The product 2ba or 2bc was purified by
column chromatography with petroleum ether/ethyl acetate = 100:1.
General Experimental Procedures for the Synthesis of
2bb.30 A solution of trimethylsilylacetylene (10.4 mmol) in
anhydrous THF (30 mL) was stirred at 0 °C under an N2
atmosphere. A solution of i-PrMgBr in THF (1.0 mol/L, 10.2 mL)
was added dropwise at 0 °C for about 40 min, and the mixtures were
stirred for another 15 min at this temperature. Then, the aldehyde (12
mL) was added slowly and the mixtures were stirred for 30 min, then
warmed to room temperature, and again stirred for about 4 h.
Saturated aqueous NH4Cl solution (30 mL) was added, and the
mixture was evaporated in vacuo, separated by EtOAc and saturated
aqueous NaCl solution. Next, the same procedure as compound 2ba
or 2bc was carried out to get the desired product 2bb.
2H), 6.89 (d, J = 8.4 Hz, 1H), 2.31 (s, 3H); 13C{1H} NMR (100
MHz, CDCl3): δ = 175.9, 152.0, 146.0, 143.4, 142.3, 139.1, 136.6,
134.0, 132.4, 132.2, 130.3, 130.2, 129.7, 128.3, 127.7, 125.9, 124.2,
122.6, 121.8, 118.4, 21.2. HRMS (ESI-TOF) m/z: [(M + H)+] Calcd
for C28H20N2O3 433.1547; found 433.1540.
1-(4-Methoxyphenyl)-3-(4-nitrophenyl)-2-phenylquinolin-4(1H)-
one (3c, 98 mg, 73%). Eluent in chromatography: petroleum ether/
EtOAc 3:1. Light yellow solid, mp 261−263 °C, 1H NMR (400 MHz,
CDCl3): δ = 8.56 (dd, J = 8.0 Hz, 1.2 Hz, 1H), 7.97 (dd, J = 6.8 Hz,
1.6 Hz, 2H), 7.54−7.49 (m, 1H), 7.43−7.38 (m, 1H), 7.30−7.27 (m,
2H), 7.08 (dd, J = 6.8 Hz, 2.4 Hz, 2H), 7.02−6.99 (m, 3H), 6.95−
6.89 (m, 3H), 6.83 (dd, J = 6.8 Hz, 2.0 Hz, 2H), 3.77 (s, 3H);
13C{1H} NMR (100 MHz, CDCl3): δ = 175. 9, 159.4, 152.3, 146.0,
143.4, 142.5, 134.0, 132.4, 132.3, 131.7, 130.9, 130.3, 128.3, 127.7,
126.7, 125.9, 124.2, 122.6, 121.8, 118.4, 114.6, 55.5. HRMS (ESI-
TOF) m/z: [(M + H)+] Calcd for C28H20N2O4 449.1496; found
449.1498.
1-(4-Bromophenyl)-3-(4-nitrophenyl)-2-phenylquinolin-4(1H)-
one (3d, 113 mg, 76%). Eluent in chromatography: petroleum ether/
EtOAc 3:1. Off-white solid, mp >300 °C, 1H NMR (400 MHz,
CDCl3): δ = 8.6 (dd, J = 1.6 Hz, 8.0 Hz, 1H), 8.0 (d, J = 8.4 Hz, 2H),
7.6−7.4 (m, 4H), 7.3 (s, 2H), 7.1−7.0 (m, 5H), 6.9−6.9 (m, 2H), 6.9
(d, J = 8.4 Hz, 1H); 13C{1H} NMR (100 MHz, CDCl3): δ = 75.9,
151.5, 146.2, 142.9, 142.0, 138.3, 133.6, 132.9, 132.5, 132.4, 131.7,
130.3, 128.7, 128.0, 127.0, 125.9, 124.5, 123.1, 122.7, 122.2, 118.0.
HRMS (ESI-TOF) m/z: [(M + H)+] Calcd for C27H17N2O3Br
497.0496; found 497.0492.
1-(4-Chlorophenyl)-3-(4-nitrophenyl)-2-phenylquinolin-4(1H)-
one (3e, 106 mg, 78%). Eluent in chromatography: petroleum ether/
EtOAc 3:1. Light yellow solid, mp 311−313 °C, 1H NMR (400 MHz,
CDCl3): δ = 8.56 (dd, J = 1.6 Hz, 8.0 Hz, 1H), 7.97 (d, J = 8.8 Hz,
2H), 7.55−7.51 (m, 1H), 7.44−7.40 (m, 1H), 7.34−7.27 (m, 4H),
7.14−7.11 (m, 2H), 7.08−7.00 (m, 3H), 6.94 (dd, J = 7.6 Hz, 1.6 Hz,
2H), 6.85 (d, J = 8.4 Hz, 1H); 13C{1H} NMR (100 MHz, CDCl3): δ
= 175.9, 151.6, 146.1, 143.0, 142.0, 137.7, 135.0, 133.6, 132.5, 132.4,
131.4, 130.2, 129.9, 128.7, 128.0, 126.9, 125.8, 124.4, 122.7, 122.1,
118.0. HRMS (ESI-TOF) m/z: [(M + H)+] Calcd for C27H17N2O3Cl
453.1000; found 453.1004.
1-(4-Fluorophenyl)-3-(4-nitrophenyl)-2-phenylquinolin-4(1H)-
one (3f, 114 mg, 87%). Eluent in chromatography: petroleum ether/
1
EtOAc 3:1. Light yellow solid, mp >300 °C, H NMR (400 MHz,
CDCl3) δ = 8.56 (dd, J = 8.0 Hz, 1.6 Hz, 1H), 7.97−7.94 (m, 2H),
7.56−7.51 (m, 1H), 7.44−7.40 (m, 1H), 7.29 (d, J = 8.0 Hz, 2H),
7.19−7.14 (m, 2H), 7.06−7.00 (m, 5H), 6.96−6.92 (m, 2H), 6.86 (d,
J = 7.4 Hz, 1H); 13C{1H} NMR (100 MHz, CDCl3): δ = 175.91,
163.3 (d, 1JC,F = 248.0 Hz, 1C), 151.9, 1456.1, 143.1, 142.2, 135.2 (d,
4JC,F = 3.4 Hz, 1C), 133.8, 132.5, 132.4, 131.9 (d, 3JC,F = 8.7 Hz, 1C),
130.3, 128.6, 127.9, 126.9, 125.8, 124.4, 122.7, 122.0, 118.1, 116.8 (d,
2JC,F = 23.0 Hz, 1C). 19F NMR (376 MHz, CDCl3): δ = −110.5 (s,
General Experimental Procedures for the Synthesis of 4-
Quinolones. A mixture of compound 1 (0.3 mmol), compound 2
(0.6 mmol), K2CO3 (0.6 mmol), and DMF was stirred in a sealed
tube, and the mixture was heated to 100 °C with an oil bath. TLC
monitored the end of the reaction. Then, the mixture was cooled to
room temperature and brine (50 mL) was poured into the solution.
The mixture was extracted with EtOAc (5 × 50 mL). The organic
layers were combined and dried using anhydrous Na2SO4. After that,
the product was purified by column chromatography with petroleum
ether/ethyl acetate = 3:1−1:1, and the desired product was obtained
after vacuum-rotary evaporation.
1F). HRMS (ESI-TOF) m/z: [(M + H)+] Calcd for C27H17N2O3F
437.1296; found 437.1297.
1-(4-Iodophenyl)-3-(4-nitrophenyl)-2-phenylquinolin-4(1H)-one
(3g, 121 mg, 74%). Eluent in chromatography: petroleum ether/
1
EtOAc 3:1. Light yellow solid, mp >300 °C, H NMR (400 MHz,
CDCl3): δ = 8.57 (d, J = 8.0 Hz, 1H), 7.98 (d, J = 8.4 Hz, 2H), 7.67
(d, J = 8.4 Hz, 2H), 7.55−7.51 (m, 1H), 7.45 (t, J = 8.0 Hz, 1H), 7.29
(d, J = 8.8 Hz, 2H), 7.09−7.01 (m, 3H), 6.93 (d, J = 8.4 Hz, 4H),
6.85 (d, J = 8.4 Hz, 1H); 13C{1H} NMR (100 MHz, CDCl3): δ =
175.9, 151.5, 146.2, 143.0, 141.9, 139.0, 138.9, 133.6, 132.5, 132.4,
131.9, 130.3, 128.8, 128.0, 127.0, 125.9, 124.5, 122.7, 118.0, 94.7.
HRMS (ESI-TOF) m/z: [(M + H)+] Calcd for C27H17N2O3I
545.0357; found 545.0355.
1-Benzyl-3-(4-nitrophenyl)-2-phenylquinolin-4(1H)-one (3h, 62
mg, 48%). Eluent in chromatography: petroleum ether/EtOAc 3:1.
Light yellow solid, mp 196−198 °C, 1H NMR (400 MHz, CDCl3): δ
= 8.59 (dd, J = 8.4 Hz, 1.6 Hz, 1H), 7.97 (d, J = 8.8 Hz, 2H), 7.61 (td,
J = 7.2 Hz, 1.6 Hz, 1H), 7.44 (t, J = 7.6 Hz, 2H), 7.34−7.27 (m, 4H),
7.25−7.22 (m, 2H), 7.18 (t, J = 7.6 Hz, 2H), 7.09−7.07 (m, 2H),
7.01−7.99 (m, 2H), 5.27 (s, 2H); 13C{1H} NMR (100 MHz,
CDCl3): δ = 175.7, 152.8, 146.1, 143.5, 140.7, 136.1, 132.8, 132.4,
3-(4-Nitrophenyl)-1,2-diphenylquinolin-4(1H)-one (3a, 119 mg,
95%). Eluent in chromatography: petroleum ether/EtOAc 3:1. Light
yellow solid, mp 279−281 °C, 1H NMR (400 MHz, CDCl3): δ = 8.58
(dd, J = 8.0 Hz, 1.6 Hz, 1H), 7.98 (d, J = 8.8 Hz, 2H), 7.54−7.49 (m,
1H), 7.44−7.40 (m, 1H), 7.37−7.28 (m, 5H), 7.18−7.16 (m, 2H),
7.00−6.92 (m, 5H), 6.9 (d, J = 8.8 Hz, 1H); 13C{1H} NMR (100
MHz, CDCl3): δ = 175.9, 151.9, 146.0, 143.3, 142.1, 139.1, 133.9,
132.4, 132.3, 130.3, 130.0, 129.6, 129.0, 128.4, 127.7, 126.7, 125.8,
124.2, 122.6, 121.8, 118.3. HRMS (ESI-TOF) m/z: [(M + H)+]
Calcd for C27H18N2O3 419.1390; found 419.1390.
3-(4-Nitrophenyl)-2-phenyl-1-(p-tolyl)quinolin-4(1H)-one (3b,
114 mg, 88%). Eluent in chromatography: petroleum ether/EtOAc
3:1. Off-white solid, mp 291−293 °C, 1H NMR (400 MHz, CDCl3):
δ = 8.57 (dd, J = 1.6 Hz, 8.0 Hz, 1H), 7.98 (d, J = 8.8 Hz, 2H), 7.53−
7.48 (m, 1H), 7.43 (t, J = 7.2 Hz, 1H), 7.30 (d, J = 8.8 Hz, 2H), 7.13
(d, J = 8.0 Hz, 2H), 7.04−6.97 (m, 5H), 6.94 (dd, J = 1.6 Hz, 7.2 Hz,
D
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129.5, 129.1, 129.1, 128.5, 127.7, 127.3, 126.8, 125.5, 124.3, 122.7,
122.5, 117.4, 52.7. HRMS (ESI-TOF) m/z: [(M + H)+] Calcd for
C28H20N2O3 433.1547; found 433.1549.
yellow solid, mp 254−256 °C, 1H NMR (400 MHz, CDCl3): δ = 8.53
(dd, J = 8.0 Hz, 0.8 Hz, 1H), 7.90 (dd, J = 6.8 Hz, 1.2 Hz, 1H), 7.49−
7.45 (m, 1H), 7.41−7.33 (m, 3H), 7.30−7.27 (m, 3H), 7.24−7.19
(m, 1H), 7.11−7.08 (m, 1H), 7.06−7.04 (m, 2H), 7.01−6.91 (m,
4H), 6.88 (d, J = 8.4 Hz 1H); 13C{1H} NMR (100 MHz, CDCl3): δ =
175.4, 150.4, 149.9, 142.3, 139.3, 134.2, 132.3, 132., 131.3, 130.2,
130.1, 129.9, 129.5, 129.2, 128.9, 128.3, 128.1, 127.7, 127.1, 126.8,
125.3, 124.0, 123.9, 121.5, 118.1. HRMS (ESI-TOF) m/z: [(M +
H)+] Calcd for C27H18N2O3 419.1390; found 419.1395.
7-Methyl-3-(4-nitrophenyl)-1,2-diphenylquinolin-4(1H)-one (3p,
115 mg, 89%). Eluent in chromatography: petroleum ether/EtOAc
3:1. Light yellow solid, mp 256−258 °C, 1H NMR (400 MHz,
CDCl3): δ = 8.48 (d, J = 8.4 Hz, 1H), 7.98 (d, J = 8.4 Hz, 2H), 7.36−
7.24 (m, 6H), 7.17 (d, J = 6.8 Hz, 2H), 6.99−6.92 (m, 5H), 6.62 (s,
1H), 2.35 (s, 3H); 13C{1H} NMR (100 MHz, CDCl3): δ = 175.7,
151.7, 146.1, 143.3, 142.3, 139.2, 134.0, 132.5, 130.4, 130.1, 129.6,
129.0, 128.4, 127.7, 126.8, 126.1, 123.8, 122.7, 121.7, 117.9, 22.2.
HRMS (ESI-TOF) m/z: [(M + H)+] Calcd for C28H20N2O3
433.1547; found 433.1544.
7-Methoxy-3-(4-nitrophenyl)-1,2-diphenylquinolin-4(1H)-one
(3q, 110 mg, 82%). Eluent in chromatography: petroleum ether/
EtOAc 3:1. Light yellow solid, mp 289−291 °C, 1H NMR (400 MHz,
CDCl3): δ = 8.50 (d, J = 8.8 Hz, 1H), 7.97 (d, J = 8.4 Hz, 2H), 7.34−
7.27 (m, 5H), 7.17 (d, J = 7.2 Hz, 2H), 7.03−6.91 (m, 6H), 6.21−
6.20 (d, J = 2.0 Hz, 1H), 3.69 (s, 3H); 13C{1H} NMR (100 MHz,
CDCl3): δ = 175.4, 162.8, 146.0, 143.9, 143.4, 139.3, 134.0, 132.5,
130.4, 130.0, 129.6, 129.0, 128.8, 128.3, 127.7, 122.6, 112.9, 101.1,
55.4. HRMS (ESI-TOF) m/z: [(M + H)+] Calcd for C28H20N2O4
449.1496; found 449.1498.
1-(Naphthalen-2-yl)-3-(4-nitrophenyl)-2-phenylquinolin-4(1H)-
one (3i, 115 mg, 82%). Eluent in chromatography: petroleum ether/
EtOAc 3:1. Off-white solid, mp >300 °C, 1H NMR (400 MHz,
CDCl3): δ = 8.62−8.60 (m, 1H), 7.97 (d, J = 8.8 Hz, 2H), 7.85−7.79
(m, 2H), 7.52−7.48 (m, 3H), 7.40−7.34 (m, 6H), 7.05 (d, J = 7.6 Hz,
1H), 6.96 (t, J = 7.6 Hz, 1H), 6.86 (t, J = 7.6 Hz, 1H), 6.69−6.59 (m,
3H); 13C{1H} NMR (100 MHz, CDCl3): δ = 176.1, 152.7, 146.1,
143.3, 142.2, 132.5, 132.5, 131.1, 130.3, 129.9, 128.8, 128.6, 128.6,
128.5, 127.9, 127.4, 127.2, 127.0, 126.8, 125.9, 125.2, 124.4, 122.6,
122.6, 122.13, 118.5. HRMS (ESI-TOF) m/z: [(M + H)+] Calcd for
C31H20N2O3 469.1547; found 469.1544.
1-Methyl-3-(4-nirophenyl)-2-phenylquinolin-4(1H)-one (3j, 46
mg, 43%). Eluent in chromatography: petroleum ether/EtOAc 3:1.
1
Light yellow solid, mp >300 °C, H NMR (400 MHz. CDCl3): δ =
8.58 (dd, J = 8.0 Hz, 1.6 Hz, 1H), 7.98−7.95 (m, 2H), 7.79−7.75 (m,
1H), 7.63 (d, J = 8.8 Hz, 1H), 7.50−7.46 (m, 1H), 7.35−7.30 (m,
3H), 7.24−7.20 (m, 2H), 7.19−7.15 (m, 2H), 3.59 (s, 3H); 13C{1H}
NMR (100 MHz, CDCl3): δ = 175.5, 152.4, 146.0, 143.5, 141.4,
134.2, 132.8, 132.4, 129.5, 128.8, 127.3, 126.6, 124.2, 122.6, 122.1,
116.1, 37.8. HRMS (ESI-TOF) m/z: [(M + H)+] Calcd for
C22H16N2O3 357.1234; found 357.1232.
1-Ethyl-3-(4-nitrophenyl)-2-phenylquinolin-4(1H)-one (3k, 41
mg, 37%). Eluent in chromatography:petroleum ether/EtOAc 3:1.
Light yellow solid, mp 151−153 °C, 1H NMR (400 MHz, CDCl3): δ
= 8.59 (dd, J = 8.0 Hz, 1.6 Hz, 1H), 7.96 (d, J = 8.8 Hz, 2H), 7.77−
7.73 (m, 1H), 7.65 (d, J = 8.4 Hz, 1H), 7.48−7.44 (m, 1H), 7.33−
7.30 (m, 3H), 7.23−7.19 (m, 4H), 4.13 (q, J = 3.2 Hz, 2H), 1.33 (t, J
= 6.8 Hz, 3H); 13C{1H} NMR (100 MHz, CDCl3): δ = 175.4, 152.1,
146.0, 143.7, 139.9, 134.1, 132.7, 132.4, 129.4, 139.1, 128.7, 127.6,
127.1, 124.1, 122.3, 122.4, 116.3, 43.8, 14.4. HRMS (ESI-TOF) m/z:
[(M + H)+] Calcd for C23H18N2O3 371.1390; found 371.1390.
3-(4-Nitrophenyl)-2-phenyl-1-propylquinolin-4(1H)-one (3l, 55
mg, 48%). Eluent in chromatography: petroleum ether/EtOAc 3:1.
Light yellow solid, mp 169−171 °C, 1H NMR (400 MHz, CDCl3): δ
= 8.59 (dd, J = 8.0 Hz, 1.6 Hz, 1H), 7.96 (d, J = 8.8 Hz, 2H), 7.77−
7.73 (m, 1H), 7.60 (d, J = 8.8 Hz, 1H), 7.47 (t, J = 7.2 Hz, 1H),
7.33−7.30 (m, 3H), 7.22−7.17 (m, 4H), 3.97 (t, J = 8.0 Hz, 2H),
1.81−1.72 (m, 2H), 0.80 (t, J = 7.2 Hz, 3H); 13C{1H} NMR (100
MHz, CDCl3): δ = 175.4, 152.3, 146.0, 143.6, 140.2, 134.1, 132.7,
132.4, 129.4, 129.3, 128.7, 127.5, 127.0, 124.1, 122.6, 122.3, 116.4,
50.4, 22.3, 10.9. HRMS (ESI-TOF) m/z: [(M + H)+] Calcd for
C24H20N2O3 385.1547; found 385.1544.
7-Chloro-3-(4-nitrophenyl)-1,2-diphenylquinolin-4(1H)-one (3r,
128 mg, 94%). Eluent in chromatography: petroleum ether/EtOAc
1
3:1. Off-white solid, mp 275−277 °C, H NMR (400 MHz, CDCl3):
δ = 8.50 (d, J = 8.8 Hz, 1H), 7.99 (d, J = 8.4 Hz, 2H), 7.38−7.32 (m,
4H), 7.29−7.27 (m, 2H), 7.17 (d, J = 6.8 Hz, 2H), 7.01−6.96 (m,
3H), 6.92−6.90 (m, 2H), 6.85 (d, J = 1.6 Hz, 1H); 13C{1H} NMR
(100 MHz, CDCl3): δ = 175.4, 152.3, 146.2, 142.8, 142.8, 138.8,
138.7, 133.6, 132.4, 130.3, 129.9, 129.4, 128.6, 128.6, 127.8, 125.0,
124.2, 122.8, 122.4, 117.9, HRMS (ESI-TOF) m/z: [(M + H)+]
Calcd for C27H17N2O3Cl 453.1000; found 453.0999.
7-Fluoro-3-(4-nitrophenyl)-1,2-diphenylquinolin-4(1H)-one (3s,
126 mg, 96%). Eluent in chromatography: petroleum ether/EtOAc
1
3:1. Off-white solid, mp 311−313 °C, H NMR (400 MHz, CDCl3):
δ = 8.59 (t, J = 7.2 Hz, 1H), 7.99 (d, J = 7.6 Hz, 2H), 7.38−7.26 (m,
5H), 7.18−7.12 (m, 3H), 7.00−6.92 (m, 5H), 6.53 (d, J = 10.8 Hz,
1H); 13C{1H} NMR (100 MHz, CDCl3): δ = 175.3, 166.3 (d, 1JC,F
=
3
250 Hz, 1H), 152.3, 146.2, 143.7, (d, JC,F = 11.3 Hz, 1C), 142.8,
1,2-Diphenyl-3-(4-(trifluoromethyl)phenyl)quinolin-4(1H)-one
(3m, 48 mg, 36%). Eluent in chromatography: petroleum ether/
EtOAc 3:1. White solid, mp 289−290 °C, 1H NMR (400 MHz,
CDCl3): δ = 8.59 (dd, J = 8.0 Hz, 1.6 Hz, 1H), 7.51−7.46 (m, 1H),
7.41−7.27 (m, 6H), 7.26−7.23 (m, 2H), 7.17−7.14 (m, 2H), 6.98−
6.91 (m, 5H), 6.87 (d, J = 8.8 Hz, 1H); 13C{1H} NMR (100 MHz,
CDCl3): δ = 176.3, 151.7, 142.2, 139.6, 139.4, 134.2, 132.1, 131.8,
3
138.9, 133.7, 132.4, 130.3, 130.0 (d, JC,F = 10.6 Hz, 1C), 129.8 (d,
4JC,F = 1.6 Hz, 1C), 129.4, 128.6, 127.8, 122.7, 122.6, 122.2, 113.3 (d,
2
2JC,F = 23.1 Hz, 1C), 104.5 (d, JC,F = 27.0 Hz, 1C); 19F NMR (376
MHz, CDCl3): δ = −104.2 (m, 1F). HRMS (ESI-TOF) m/z: [(M +
H)+] Calcd C27H17N2O3F 437.1296; found 437.1295.
3-(4-Nitrophenyl)-1-phenyl-2-(p-tolyl)quinolin-4(1H)-one (3t, 96
mg, 74%). Eluent in chromatography: petroleum ether/EtOAc 3:1.
2
130.4, 130.1, 129.6, 128.9, 128.6 (q, JC,F = 32.0 Hz, 1C), 128.37 (q,
1
1JC,F = 270 Hz, 1C), 128.1, 128.0, 127.6, 126.8, 125.9, 124.5 (q, 3JC,F
=
Light yellow solid, mp >300 °C, H NMR (400 MHz, CDCl3): δ =
3.6 Hz), 124.0, 122.7, 118.3; 19F NMR (376 MHz, CDCl3): δ =
−62.5 (s, 3F). HRMS (ESI-TOF) m/z: [(M + H)+] Calcd for
C28H18NOF3 442.1413; found 442.1418.
8.57 (d, J = 7.6 Hz, 1H), 8.00 (d, J = 8.8 Hz, 2H), 7.52 (t, J = 7.2 Hz,
1H), 7.43 (t, J = 7.6 Hz, 1H), 7.36−7.28 (m, 5H), 7.17 (d, J = 6.8 Hz,
2H), 6.86 (d, J = 8.8 Hz, 1H), 6.80 (t, J = 8.8 Hz, 4H), 2.13 (s, 3H);
13C{1H} NMR (100 MHz, CDCl3): δ = 176.0, 152.1, 146.0, 143.4,
4-(4-Oxo-1,2-diphenyl-1,4-dihydroquinolin-3-yl)benzonitrile (3n,
111 mg, 93%). Eluent in chromatography: petroleum ether/EtOAc
3:1. Light yellow solid, mp 249−250 °C, 1H NMR (400 MHz,
CDCl3): δ = 8.57 (dd, J = 8.0 Hz, 1.2 Hz, 1H), 7.53−7.48 (m, 1H),
7.43−7.38 (m, 3H), 7.36−7.37 (m, 3H), 7.24 (d, J = 8.4 Hz, 2H),
7.17 (d, J = 6.8 Hz, 2H), 7.00−6.96 (m, 3H), 6.92−6.90 (m, 2H),
6.87 (d, J = 8.4 Hz, 1H); 13C{1H} NMR (100 MHz, CDCl3): δ =
176.0, 151.8, 142.2, 141.1, 139.2, 134.0, 132.3, 132.3, 131.3, 130.4,
130.1, 129.6, 129.0, 128.3, 127.7, 126.8, 125.9, 124.2, 119.2, 118.3,
109.8. HRMS (ESI-TOF) m/z: [(M + H)+] Calcd for C28H18N2O
399.1492; found 399.1496.
142.2, 139.3, 138.3, 132.4, 132.2, 130.9, 130.2, 130.0, 129.6, 128.9,
128.4, 126.8, 125.8, 124.2, 122.7, 122.0, 118.3, 21.2; HRMS (ESI-
TOF) m/z: [(M + H)+] Calcd for C28H20N2O3 433.1547; found
433.1541.
2-(4-Methoxyphenyl)-3-(4-nitrophenyl)-1-phenylquinolin-4(1H)-
one (3u, 97 mg, 72%). Eluent in chromatography: petroleum ether/
EtOAc 3:1. Light yellow solid, mp 274−276 °C, 1H NMR (400 MHz,
CDCl3): δ = 8.57 (d, J = 8.0 Hz, 1H), 8.01 (d, J = 8.4 Hz, 2H), 7.52−
7.49 (m, 1H), 7.43−7.29 (m, 6H), 7.17 (d, J = 7.2 Hz, 2H), 6.87−
6.81 (m, 3H), 6.51 (d, J = 8.0 Hz, 2H), 3.63 (s, 3H); 13C{1H} NMR
(100 MHz, CDCl3): δ = 175.9, 159.1, 151.9, 146.0, 143.5, 142.2,
139.4, 132.4, 132.3, 131.7, 130.0, 129.7, 129.0, 126.8, 126.1, 125.8,
3-(2-Nitrophenyl)-1,2-diphenylquinolin-4(1H)-one (3o, 122 mg,
97%). Eluent in chromatography: petroleum ether/EtOAc 3:1. Light
E
https://dx.doi.org/10.1021/acs.joc.0c01662
J. Org. Chem. XXXX, XXX, XXX−XXX

The Journal of Organic Chemistry
pubs.acs.org/joc
Article
1
124.2, 122.7, 122.1, 118.3, 113.1, 55.0. HRMS (ESI-TOF) m/z: [(M
+ H)+] Calcd for C28H20N2O4 449.1496; found 449.1499.
NMR (100 MHz, CDCl3): δ = 174.84, 166.21 (d, JC,F = 250 Hz,
1C), 150.77, 149.89, 143.86 (d, 3JC,F = 11.3 Hz, 1C), 134.06, 133.95,
132.41, 130.99, 130.14 (d, 3JC,F = 4.9 Hz, 1C), 130.06, 129.95, 129.49
2-(4-Chlorophenyl)-3-(4-nitrophenyl)-1-phenylquinolin-4(1H)-
4
one (3v, 111 mg, 82%). Eluent in chromatography: petroleum ether/
(d, JC,F = 3.0 Hz, 1C), 129.21, 128.44, 128.20, 127.90, 127.20,
1
2
EtOAc 3:1. Light yellow solid, mp >300 °C, H NMR (400 MHz,
124.05, 122.05, 121.87, 112.88 (d, JC,F = 23.1 Hz, 1C), 104.23 (d,
2JC,F = 27.0 Hz, 1C); 19F NMR (376 MHz, CDCl3): δ = −104.5 (s,
CDCl3): δ = 8.56 (d, J = 6.8 Hz, 1H), 8.03 (d, J = 8.8 Hz, 2H), 7.54−
7.50 (m, 1H), 7.45−7.33 (m, 4H), 7.21 (d, J = 8.8 Hz, 2H), 7.17 (m,
2H), 6.99 (d, J = 8.4 Hz, 2H), 6.89−6.85 (m, 3H); 13C{1H} NMR
(100 MHz, CDCl3): δ = 175.9, 150.5, 146.3, 142.8, 142.2, 139.0,
134.6, 132.5, 132.4, 131.6, 1230.0, 129.9, 129.3, 128.1, 126.8, 125.8,
124.4, 122.9, 122.1, 118.3; HRMS (ESI-TOF) m/z: [(M + H)+]
Calcd for C27H17N2O3Cl 453.1000; found 453.1008.
1F). HRMS (ESI-TOF) m/z: [(M + H)+] Calcd for C27H17N2O3F
437.1296; found 437.1296.
7-Chloro-3-(2-nitrophenyl)-1,2-diphenylquinolin-4(1H)-one
(3ob, 123 mg, 91%). Eluent in chromatography: petroleum ether/
EtOAc 3:1. Light yellow solid, mp >300 °C, H NMR (400 MHz,
CDCl3): δ = 8.49 (d, J = 8.8 Hz, 1H), 7.95 (dd, J = 8.0 Hz, 6.4 Hz,
1H), 7.46−7.42 (m, 1H), 7.31−7.37 (m, 5H), 7.30−7.25 (m, 1H),
7.11−7.06 (m, 3H), 7.02−6.96 (m, 4H), 6.88 (d, J = 1.6 Hz, 1H);
13C{1H} NMR (100 MHz, CDCl3): δ = 174.9, 150.7, 149.8, 143.0,
1
2-(4-Fluorophenyl)-3-(4-nitrophenyl)-1-phenylquinolin-4(1H)-
one (3w, 106 mg, 81%). Eluent in chromatography: petroleum
1
ether/EtOAc 3:1. Light yellow solid, mp >300 °C, H NMR (400
MHz, CDCl3): δ = 8.57 (dd, J = 8.0 Hz, 1H), 8.02 (d, J = 8.4 Hz,
2H), 7.54−7.52 (m, 1H), 7.45−7.41 (m, 1H), 7.39−7.34 (m, 3H),
7.30 (d, J = 8.8 Hz, 2H); 7.17−7.15 (m, 2H), 6.94−6.90 (m, 2H),
6.87 (d, J = 8.8 Hz, 1H), 6.72 (t, J = 8.4 Hz, 2H); 13C{1H} NMR
(100 MHz, CDCl3): δ = 175. 9, 163.2 (d, 1JC,F = 249 Hz, 1C), 150.8,
146.2, 143.0, 142.2, 139.1, 132.4, 132.4, 132.3 (d, 3JC,F = 8.5 Hz, 1C),
130.1 (d, 4JC,F = 3.8 Hz, 1C), 130.0, 129.8, 129.2, 126.8, 125.8, 124.4,
138.9, 138.6, 134.0, 133.9, 132.4, 130.1, 130.1, 130.1, 130.0, 129.5,
129.5, 129.3, 128.7, 128.4, 128.2, 127.9, 127.2, 124.7, 124.1, 123.7,
122.1. HRMS (ESI-TOF) m/z: [(M + H)+] Calcd for C27H17N2O3Cl
[(M + H)+]: 453.1000; found 453.1004.
2-(4-Fluorophenyl)-3-(2-nitrophenyl)-1-phenylquinolin-4(1H)-
one (3oc, 102 mg, 78%). Eluent in chromatography: petroleum
ether/EtOAc 3:1. Light yellow solid, mp 210−212 °C, 1H NMR (400
MHz, CDCl3): δ = 8.54 (dd, J = 8.0 Hz, 1.2 Hz, 1H), 7.94 (dd, J = 8.0
Hz, 1.6 Hz, 1H), 7.53−7.48 (m, 1H), 7.44−7.28 (m, 7H), 7.15−7.11
(m, 1H), 7.08−7.04 (m, 2H), 7.03−6.99 (m, 1H), 6.89 (d, J = 8.8 Hz,
1H), 6.73−6.64 (m, 2H); 13C{1H} NMR (100 MHz, CDCl3): δ =
175.4, 163.3 (d, 1JC,F = 248 Hz, 1C), 150.0, 149.4, 142.3, 139.3. 134.1,
2
122.8, 122.2, 118.3, 115.2 (d, JC,F = 21.7 Hz, 1C); 19F NMR (376
MHz, CDCl3): δ = −110.8 (m, 1F). HRMS (ESI-TOF) m/z: [(M +
H)+] Calcd for C27H17N2O3F 437.1296; found 437.1298.
2-(3-Fluorophenyl)-3-(4-nitrophenyl)-1-phenylquinolin-4(1H)-
one (3x, 106 mg, 81%). Eluent in chromatography: petroleum ether/
1
3
3
EtOAc 3:1. Off-white solid, mp 273−274 °C, H NMR (400 MHz,
132.5, 132.2, 132.1 (d, JC,F = 8.3 Hz, 1C), 131.7 (d, JC,F = 8.5 Hz,
CDCl3): δ = 8.56 (d, J = 7.2 Hz, 1H), 8.01 (d, J = 8.4 Hz, 2H), 7.55−
7.51 (m, 1H), 7.45−7.29 (m, 6H), 7.22−7.16 (m, 2H), 7.01 (dd, J =
13.6 Hz, 7.6 Hz, 1H), 6.88 (d, J = 8.8 Hz, 1H), 6.76−6.67 (m, 3H);
1C), 131. 1, 130.4 (d, 4JC,F = 3.6 Hz, 1C), 130.2, 130.1, 130.1, 129.4,
129.1, 127.9, 126.9, 125.3, 124.1, 124.0, 121.8, 118.1, 115.5 (d, 2JC,F
=
21.6 Hz, 1C), 114.6 (d, JC,F = 21.8 Hz, 1C); 19F NMR (376 MHz,
CDCl3): δ = −111.4 (m, 1F). HRMS (ESI-TOF) m/z: [(M + H)+]
Calcd for C27H17N2O3F 437.1296; found 437.1290.
2
13C{1H} NMR (100 MHz, CDCl3): δ = 175.9, 162.9 (d, 1J C,F = 247
3
Hz, 1C), 150.2, 146.3, 142.8, 142.2, 138.9, 135.8 (d, J
= 7.7 Hz,
C,F
4
3-(2-Nitrophenyl)-1-phenyl-2-(p-tolyl)quinolin-4(1H)-one (3od,
106 mg, 82%). Eluent in chromatography: petroleum ether/EtOAc
3:1. Yellow solid, mp 234−236 °C, 1H NMR (400 MHz, CDCl3): δ =
8.54 (dd, J = 8.0 Hz, 1.6 Hz, 1H), 7.93 (dd, J = 8.0 Hz, 1.2 Hz, 1H),
7.50−7.46 (m, 1H), 7.44−7.22 (m, 7H), 7.08−7.05 (m, 2H), 7.00−
6.98 (m, 1H), 6.89−6.86 (m, 2H), 6.79−6.64 (m, 2H), 2.11 (s, 3H);
13C{1H} NMR (100 MHz, CDCl3): δ = 175.5, 150.7, 150.0, 142.4,
139.5, 138.1, 134.2, 132.3, 132.0, 130.2, 130.2, 130.1, 129.5, 128.8,
128.8, 127.8, 127.6, 126.9, 125.3, 124.0, 123.8, 121.6, 118.1, 21.2.
HRMS (ESI-TOF) m/z: [(M + H)+] Calcd for C28H20N2O3
433.1547; found 433.1543.
3-(4-Nitrophenyl)-1-(p-tolyl)quinolin-4(1H)-one (3ba, 70 mg,
66%; 3bb, 61 mg, 57%). Eluent in chromatography: petroleum
ether/EtOAc 3:1. Yellow solid, mp 201−202 °C, 1H NMR (400
MHz, CDCl3): δ = 8.57 (d, J = 8.0 Hz, 1H), 8.24 (d, J = 8.0 Hz, 2H),
7.94 (d, J = 8.0 Hz, 3H), 7.56−7.52 (m, 1H), 7.45−7.41 (m, 3H),
7.37 (d, J = 8.0 Hz, 2H), 7.08 (d, J = 8.0 Hz, 1H), 2.51 (s, 3H);
13C{1H} NMR (100 MHz, CDCl3): δ = 175.5, 146.5, 142.5, 142.4,
140.9, 140.2, 138.5, 132.2, 131.1, 129.0, 127.3, 127.2, 124.6, 123.6,
119.4, 117.6, 21.3. HRMS (ESI-TOF) m/z: [(M + H)+] Calcd for
C22H16N2O3 357.1234; found 357.1234.
2-Methyl-3-(4-nitrophenyl)-1-(p-tolyl)quinolin-4(1H)-one (3bc,
82 mg, 74%). Eluent in chromatography: petroleum ether/EtOAc
3:1−1:1. Off-white solid, mp 272−273 °C, 1H NMR (400 MHz,
CDCl3): δ = 8.49 (d, J = 8.0 Hz, 1H), 8.29 (d, J = 8.0 Hz, 2H), 7.54
(d, J = 8.0 Hz, 2H), 7.48−7.44 (m, 3H), 7.38−7.34 (m, 1H), 7.24 (d,
J = 8.0 Hz, 2H), 6.76 (d, J = 8.0 Hz, 1H); 13C{1H} NMR (100 MHz,
CDCl3): δ = 175.5, 148.5, 146.9, 144.0, 142.5, 140.2, 136.6, 132.2,
132.0, 131.3, 128.6, 126.6, 125.3, 123.9, 123.5, 121.6, 117.9, 21.3,
20.7. HRMS (ESI-TOF) m/z: [(M + H)+] Calcd for C23H18N2O3
371.1390; found 371.1390.
1C), 132.5, 132. 4, 1230.0, 129.8 (d, JC,F = 4.1 Hz, 1C), 129.6 (d,
3JC,F = 8.2 Hz, 1C), 129.3, 126. 8, 126.4, 126.4, 125.8, 124.5, 122.8,
121.9, 118.4, 117.7 (d, 2JC,F = 22.6 Hz, 1C), 115.7 (d, 2JC,F = 20.7 Hz,
1C); 19F NMR (376 MHz, CDCl3): δ = −112.0 (m, 1F). HRMS
(ESI-TOF) m/z: [(M + H)+] Calcd for C27H17N2O3F 437.1296;
found 437.1295.
4-(7-Methyl-4-oxo-1,2-diphenyl-1,4-dihydroquinolin-3-yl)-
benzonitrile (3na, 95 mg, 77%). Eluent in chromatography:
petroleum ether/EtOAc 3:1. White solid, mp 268−270 °C, 1H
NMR (400 MHz, CDCl3): δ = 8.45 (d, J = 8.0 Hz, 1H), 7.39 (d, J =
8.4 Hz, 2H), 7.36−7.27 (m, 3H), 7.23 (d, J = 8.4 Hz, 3H), 7.16−7.14
(m, 2H), 6.99−6.94 (m, 3H), 6.91−6.88 (m, 2H), 6.61 (s, 1H), 2.33
(s, 3H); 13C NMR (100 MHz, CDCl3): δ = 175.8, 151.5, 143.1,
142.3, 141.2, 139.3, 134.1, 132.3, 131.2, 130.4, 130.1, 129.5, 128.9,
128.2, 127.6, 126.7, 125.9, 123.8, 122.1, 119.2, 117.8. HRMS (ESI-
TOF) m/z: [(M + H)+] Calcd for C29H20N2O 413.1648; found
413.1642.
4-(7-Fluoro-4-oxo-1,2-diphenyl-1,4-dihydroquinolin-3-yl)-
benzonitrile (3nb, 116 mg, 93%). Eluent in chromatography:
petroleum ether/EtOAc 3:1. White solid, mp 269−271 °C, 1H
NMR (400 MHz, CDCl3): δ = 8.56 (dd, J = 8.8 Hz, 6.4 Hz, 1H), 7.41
(d, J = 8.0 Hz, 2H), 7.37−7.29 (m, 3H), 7.23−7.21 (m, 2H), 7.17−
7.15 (m, 2H), 7.14−7.09 (m, 1H), 7.03−6.96 (m, 3H), 6.94−6.90
(m, 2H), 6.52 (dd, J = 10.8 Hz, 2.0 Hz, 1H); 13C{1H} NMR (100
MHz, CDCl3): δ = 175.3, 166.2 (d, 1JC,F = 250 Hz, 1C), 152.2, 143.7
3
(d, JC,F = 11.3 Hz, 1C), 140.7, 138.9, 133.7, 132.2, 131.3, 130.3,
129.9, 129.8, 129.3, 128.4, 127.7, 122.6 (d, 4JC,F = 1.2 Hz, 1C), 122.5,
2
2
119.1, 113.1 (d, JC,F = 23.0 Hz, 1C), 104.4 (d, JC,F = 27.0 Hz, 1C),
110.0; 19F NMR (376 MHz, CDCl3): δ = −104.5 (m, 1F). HRMS
(ESI-TOF) m/z: [(M + H)+] Calcd for C28H17N2OF 417.1398;
found 417.1396.
7-Fluoro-3-(2-nitrophenyl)-1,2-diphenylquinolin-4(1H)-one
(3oa, 124 mg, 95%). Eluent in chromatography: petroleum ether/
EtOAc 3:1. Light yellow solid, mp 254−256 °C, 1H NMR (400 MHz,
CDCl3): δ = 8.55 (dd, J = 8.8 Hz, 6.4 Hz, 1H), 7.93 (d, J = 8.0 Hz,
1H), 7.45−7.41 (m, 1H), 7.37−7.26 (m, 5H), 7.13−7.05 (m, 4H),
7.01−6.94 (m, 4H), 6.55 (dd, J = 11.2 Hz, 2.4 Hz, 1H); 13C{1H}
ASSOCIATED CONTENT
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sı
* Supporting Information
The Supporting Information is available free of charge at
https://pubs.acs.org/doi/10.1021/acs.joc.0c01662.
F
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Article
1H and 13C NMR spectra for products and X-ray data for
3a in CIF format (PDF)
Difunctionalization of Indolenines with α-(Benzothiazol-2-ylsulfonyl)
Carbonyl Compounds. Adv. Synth. Catal. 2017, 359, 2549−2556.
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CCDC 2008744 contains the supplementary crystallographic
data for this paper. These data can be obtained free of charge
via www.ccdc.cam.ac.uk/data_request/cif, or by emailing
data_request@ccdc.cam.ac.uk, or by contacting The Cam-
bridge Crystallographic Data Centre, 12 Union Road,
Cambridge CB2 1EZ, UK; fax: +44 1223 336033.
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AUTHOR INFORMATION
Corresponding Author
Chen Ma − School of Chemistry and Chemical Engineering,
Shandong University, Jinan 250100, P. R. China; orcid.org/
0000-0001-8908-4658; Email: chenma@sdu.edu.cn
■
Authors
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Caixia Xie − School of Chemistry and Chemical Engineering,
Shandong University of Technology, Zibo 255049, P. R. China;
School of Chemistry and Chemical Engineering, Shandong
University, Jinan 250100, P. R. China
Di Yang − School of Chemistry and Chemical Engineering,
Shandong University, Jinan 250100, P. R. China
Xinfeng Wang − School of Chemistry and Chemical Engineering,
Shandong University, Jinan 250100, P. R. China
Complete contact information is available at:
https://pubs.acs.org/10.1021/acs.joc.0c01662
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Development and Use. J. Antimicrob. Chemother. 2003, 51, 13−20.
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Acad. Sci. 2006, 103, 19484−19489. (d) Zackrisson, G.; Brorson, J.-
Notes
The authors declare no competing financial interest.
ACKNOWLEDGMENTS
■
We are grateful to the National Science Foundation of China
(no. 21572117) and State Key Laboratory of Bioactive
Substance and Function of Natural Medicines, Institute of
Materia Medica, Chinese Academy of Medical Sciences and
Peking Union Medical College (no. GTZK201707) for
financial support of this research.
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