Employing Arylacetylene as a Diene Precursor and Dienophile: Synthesis of Quinoline via the Povarov Reaction

Article abstract of DOI:10.1021/acs.joc.1c00793

A novel I2-mediated Povarov reaction of arylacetylenes and anilines for the synthesis of 2,4-substituted quinolines has been developed, in which arylacetylene first acts as both a diene precursor and dienophile. This work further develops the Povarov reaction to expand the types of diene precursors. Preliminary mechanistic studies indicate that the I2/DMSO system realized the oxidative carbonylation of C(sp)-H of arylacetylene and then undergoes a [4 + 2] cycloaddition reaction.

Full text of DOI:10.1021/acs.joc.1c00793

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Employing Arylacetylene as a Diene Precursor and Dienophile:
Synthesis of Quinoline via the Povarov Reaction
Xiao-Xiao Yu,† Peng Zhao,† You Zhou, Chun Huang, Li-Sheng Wang, Yan-Dong Wu,* and An-Xin Wu*
Cite This: J. Org. Chem. 2021, 86, 8381−8388
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ABSTRACT: A novel I2-mediated Povarov reaction of arylacety-
lenes and anilines for the synthesis of 2,4-substituted quinolines has
been developed, in which arylacetylene first acts as both a diene
precursor and dienophile. This work further develops the Povarov
reaction to expand the types of diene precursors. Preliminary
mechanistic studies indicate that the I2/DMSO system realized the
oxidative carbonylation of C(sp)−H of arylacetylene and then
undergoes a [4 + 2] cycloaddition reaction.
Scheme 1. Transformation of Arylacetylenes to Quinoline
by Povarov Reaction
uinoline and their derivatives are important scaffolds
Q widely found in natural products and pharmaceutical
molecules.1 In recent decades, numerous classic name
reactions have been developed for the synthesis of quinoline,
2
̈
such as the Skraup quinoline synthesis and the Friedlander
quinoline synthesis.3 Among them, the Povarov reaction, a
formal [4 + 2] cycloaddition reaction of 2-azadienes with
dienophiles, is a highly efficient strategy that has recently been
widely used in quinoline synthesis.4 Aromatic imines, used as
the dienes, are key reaction intermediates in the Povarov
reaction, and their generation has received considerable
research attention accordingly.5 However, strategies mainly
focused on aldehydes as their precursors6 (Scheme 1a). Only
one study has reported using a ketone carbonyl as the aromatic
imine precursor in the Povarov reaction7 (Scheme 1b). In
2014, our group has developed methyl ketones as aromatic
imines precursors to construct 2,4-substituted quinoline,8 via
the oxidation of methyl ketone C(sp3)−H bonds (Scheme 1c).
However, as aromatic imine precursors remain limited to
carbonyl compounds, the development of new precursors has
become a valuable research area. Arylacetylene is usually used
as a dienophile in the Povarov reaction,5e,6b,f,9 but to the best
of our knowledge, there have been no reports employing
arylacetylene as the diene precursor. Recently, we fortunately
found that quinoline can be synthesized in the I2/DMSO
system from simple and easily available starting materials
arylacetylene and aniline, showing that arylacetylene can first
play a dual role simultaneously and more importantly,
providing a completely new method for quinoline synthesis
via the Povarov reaction (Scheme 1d).
Cu(OTf)2 was added (entry 1). Considering the equivalents of
iodine has influence on the reaction yield, we next optimized
the iodine equivalent, and 1.0 equiv was chosen as the best
condition (entries 2−4). Next, we screened the different
temperatures, and 120 °C gave the best result (entries 5−9).
Received: April 6, 2021
Published: June 9, 2021
Based on the above experimental findings and our group’s
continued interest in the synthesis of nitrogen heterocycles,10
we first optimized conditions for the reaction between
phenylacetylene (1a) and p-toluidine (2a) (Table 1). Initially,
it was found that the reaction led to the desired 2,4-substituded
quinoline in 28% yield with 0.5 equiv of iodine in DMSO when
https://doi.org/10.1021/acs.joc.1c00793
© 2021 American Chemical Society
J. Org. Chem. 2021, 86, 8381−8388
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a
a b
,
Table 1. Optimization of the Reaction Conditions
Scheme 2. Substrate Scope for the Synthesis of 3
b
Entry
I2 (equiv)
Acid
Temp (°C)
Yield (%)
1
2
3
4
5
6
7
8
9
0.5
1.0
1.6
2.0
1.0
1.0
1.0
1.0
1.0
1.0
1.0
1.0
1.0
1.0
1.0
1.0
1.0
1.0
1.0
1.0
Cu(OTf)2
Cu(OTf)2
Cu(OTf)2
Cu(OTf)2
Cu(OTf)2
Cu(OTf)2
Cu(OTf)2
Cu(OTf)2
Cu(OTf)2
Cu(OTf)2
Cu(OTf)2
Cu(OTf)2
−
Fe(OTf)2
Fe(OTf)3
FeCl3
HCl(36%)
HI(40%)
TfOH
110
110
110
110
80
28
32
30
25
Trace
30
40
38
20
Trace
30
39
Trace
30
32
30
20
70
40
100
120
130
140
120
120
120
120
120
120
120
120
120
120
120
c
10
11
12
d
e
13
14
15
16
17
18
19
20
TFA
45
a
a
Reaction conditions: 1a (1.5 mmol), 2a (0.5 mmol), I2, acid (2.0
equiv), indicated temperature, DMSO 4 mL, 6 h, unless otherwise
Reaction conditions: 1 (3 mmol), 2a (1 mmol), I2 (2 mmol), and HI
b
(40% in water, 4 mmol) heated in 4 mL of DMSO. Products were
obtained in isolated yields.
b
c
noted. Products were obtained in isolated yields. 1a (0.5 mmol).
d
e
1a (1 mmol). 1a (2 mmol).
−i-Pr, −t-Bu, −OCH3, and −SCH3) and an electron-
withdrawing group (−Ph) were compatible with the reaction,
giving the product 4a−4f in good yields (51%−72%).
Furthermore, amines with a halogenated aromatic ring (−F,
−Cl, −Br, −OCF3) were readily transformed into halogenated
products 4g−4j in 50%−63% yields. A polysubstituted
aromatic amine substrate also afforded corresponding poly-
substituted quinoline product 4k in 31% yield. Fortunately,
large sterically hindered group naphthylamine was well
tolerated in the reaction (4l, 40%). Finally, the reactions of
p-OCH3-amine with p-Et-arylacetylene and p-Et-amine with m-
OCH3-arylacetylene were conducted, giving the corresponding
target compounds 4m and 4n in 68% and 67% yields,
respectively.
To further understand the reaction mechanism of this novel
process, a series of control experiments were conducted
(Scheme 4). First, phenylacetylene reacted with iodine and
DMSO at 120 °C when HI was added, giving phenylglyoxal in
43% yield (Scheme 4a). Next, under the standard conditions,
we reacted α-iodophenone 1ab as a substrate with p-toluidine
2a and phenylacetylene 1a giving the corresponding product
3a in 72% yield (Scheme 4b). Furthermore, 2-hydroxyaceto-
phenone (1ac) was reacted with 2a and 1a under the optimal
conditions, affording 3a in 74% yield (Scheme 4c). 3a was also
obtained in 73% yield when the hydrated species 1ad was
treated with p-toluidine (2a) and phenylacetylene (1a) under
the optimal conditions (Scheme 4d). These results show that
α-iodophenone, 2-hydroxyacetophenone, and phenylglyoxal
were pivotal intermediates in this transformation. Finally,
under the optimal conditions preprepared C-acylimine
To further improve the reaction yield, we optimized the
equivalent ratio of phenylacetylene to aniline, and 3:1 was the
best ratio (entries 10−12). In addition, we also tried not to add
any acid additives in the reaction, but the yield was trace (entry
13). Finally, various acid additives were further screened,
including Fe(OTf)2, Fe(OTf)3, FeCl3, HCl, HI, TfOH, and
TFA (entries 14−20). To our delight, adding HI to the
reaction afforded 3a in a greatly improved yield of 70%.
With optimized conditions in hand, we next tested the effect
of different phenylacetylene substituents on this transformation
(Scheme 2). Phenylacetylene bearing electron-donating groups
(−Me, −Et, −n-Pr, −t-Bu, −OMe, −OEt) at the para-position
give the corresponding product in satisfactory yields (3b−3g,
68%−74%). Various halogen substituents, in either the para-
or meta-position, were also compatible with the reaction (3h−
3j, 40%−61%). The yields of products substituted by methyl
and methoxy groups at the meta-position can also reach 63%
and 68% (3k−3l) respectively. Long-chain substituents and
large hindered substituents, such as naphthalene, afforded the
desired compounds in moderate to good yields under the
optimal conditions (3m−3o, 60%−69%). Fortunately, a
heterocyclic thiophene-substituted alkyne was also compatible
with this reaction, giving product 3p in 66% yield. Finally, we
tried to use alkyl alkynes in the reaction; unfortunately, alkyl
alkynes were not compatible with the reaction under the
optimal conditions.
To further examine the reaction scopes, a brief screening of
other commercially available substituted aryl amines was
conducted (Scheme 3). Both electron-donating groups (−Et,
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a b
,
Furthermore, the 18O-labling experiment indicated that the
source of carbonyl oxygen was mainly from H2O (see the
Supporting Information for details).
Scheme 3. Substrate Scope for the Synthesis of 4
From the above control experiments and previous studies,
the possible mechanism10d,11 for the present reaction was
proposed (Scheme 5). First, iodine activates phenylacetylene
Scheme 5. Proposed Mechanism
a
1a to afford iodonium cation A with release of I−.10d Species A
is then attacked by H2O to give enol intermediate B. The enol
intermediate B is then isomerized to α-iodophenone 1ab. The
conversion of 1ab into 1aa has two paths. In path a, 1ab is
converted to 1aa by Kornblum oxidation, while, in path b, 1ab
reacts with H2O to generate 2-hydroxyacetophenone 1ac,
which is then oxidized to 1aa. Next, 1aa is attacked by p-
toluidine (2a) to afford C-acylimine C, which then reacts with
another molecule of phenylacetylene (1a) via the Povarov
reaction to obtain final product 3a.
Reaction conditions: 1a (3 mmol), 2 (1 mmol), I2 (2 mmol), and HI
b
(40% in water, 4 mmol) heated in 4 mL of DMSO. Products were
obtained in isolated yields.
Scheme 4. Control Experiments
CONCLUSION
■
In conclusion, we have developed a novel method to generate
quinolines using the Povarov reaction, in which arylacetylene
first acts as both a diene precursor and dienophile. The
C(sp)−H of arylacetylene is oxidized to an aldehyde by the I2/
DMSO system and then generates diene C-acylimine by
reacting with aniline in situ. This development of the Povarov
reaction greatly broadens the types of diene precursors
applicable and expands the substrate scopes beyond carbonyl
compounds. Further research of the new kind of diene
precursor in the Povarov reaction to construct more nitrogen-
containing heterocycles is underway in our laboratory.
EXPERIMENTAL SECTION
■
General Methods. All other substrates and reagents were
commercially available and used without further purification. All
new compounds were fully characterized. TLC analysis was
performed using precoated glass plates. Column chromatography
was performed using silica gel (200−300 mesh). H, 13C, and 19F
1
spectra were recorded in CDCl3 on 400 MHz NMR spectrometers,
1
and chemical shifts of H NMR are reported in ppm, relative to the
substrates 5 were reacted with 1a; when R = H, the yield of
5aa was 42%, and when R = OCH3, asymmetric product 5bb
can be obtained in 54% yield (Scheme 4e), which showed that
C-acylimine was a key intermediate in this reaction.
internal standard of tetramethylsilane (TMS, δ = 0.00 ppm).
Chemical shifts of 13C{1H} NMR were reported in ppm with the
solvent as the internal standard (CDCl3, δ = 77.0 ppm). Data are
reported as follows: chemical shift, multiplicity (s = singlet, d =
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doublet, t = triplet, m = multiplet), coupling constants (Hz), and
integration. 13C{1H} spectra were recorded in CDCl3 on 100 MHz
NMR spectrometers, and resonances (δ) are given in ppm. 19F spectra
were recorded in CDCl3 on 376 MHz NMR spectrometers, and
resonances (δ) are given in ppm. HRMS data were obtained on a
Bruker 7-T FT-ICR MS equipped with an electrospray source. The X-
ray crystal-structure determinations of 4a were obtained on a Bruker
SMART APEX CCD system. Melting points were determined using
an XT-4 apparatus and not corrected.
General Procedures for the Synthesis of Products 3 (3a as
an Example). A mixture of phenylacetylene 1a (3.0 mmol, 3 equiv),
2a (1.0 mmol, 1 equiv) and hydriodic acid (40% in water, 4.0 mmol, 4
equiv), and iodine (2.0 mmol, 2 equiv) in DMSO (4 mL) was stirred
at 120 °C in the metal heating block, until almost complete
conversion of the substrates by TLC analysis. The mixture was then
quenched with saturation Na2S2O3 solution (50 mL) and extracted
with EtOAc (3 × 50 mL). The combined organic layers were washed
with brine, dried over anhydrous Na2SO4, and concentrated under
reduced pressure. The crude product was purified by column
chromatography on silica gel (eluent: petroleum ether/EtOAc =
40:1) to afford the product 3a.
Analytical Data for Products 3a−4n. (6-Methyl-4-phenyl-
quinolin-2-yl)(phenyl)methanone (3a). Yield 70%; 226.5 mg; yellow
solid; column chromatography, silica gel (PE/EA, 40:1); mp 139−
141 °C. 1H NMR (400 MHz, CDCl3) δ 8.27−8.25 (m, 2H), 8.16 (d,
J = 8.4 Hz, 1H), 8.02 (s, 1H), 7.75 (s, 1H), 7.64−7.61 (m, 2H),
7.56−7.50 (m, 7H), 2.51 (s, 3H). 13C{1H} NMR (100 MHz, CDCl3)
δ 193.9, 153.3, 148.8, 145.9, 138.8, 137.8, 136.3, 132.9, 132.2, 131.4,
130.6, 129.5, 128.6, 128.5, 128.1, 127.4, 124.5, 121.1, 22.0. HRMS
(ESI-TOF): m/z [M + H]+ calcd for C23H18NO+, 324.1383; found,
324.1388.
138.5, 134.9, 133.6, 132.1, 131.5, 130.6, 129.3, 127.5, 125.6, 125.2,
124.7, 121.2, 35.1, 34.8, 31.4, 31.1, 22.0. HRMS (ESI-TOF): m/z [M
+ H]+ calcd for C31H34NO+, 436.2635; found, 436.2650.
(4-Methoxyphenyl)(4-(4-methoxyphenyl)-6-methylquinolin-2-
yl)methanone (3f). Yield 72%; 276.1 mg; yellow solid; column
chromatography, silica gel (PE/EA, 15:1); mp 177−179 °C. 1H NMR
(400 MHz, CDCl3) δ 8.30 (d, J = 8.8 Hz, 2H), 8.14 (d, J = 8.4 Hz,
1H), 7.95 (s, 1H), 7.79 (s, 1H), 7.59 (d, J = 8.4 Hz, 1H), 7.50 (d, J =
8.4 Hz, 2H), 7.07 (d, J = 8.4 Hz, 2H), 6.99 (d, J = 8.8 Hz, 2H), 3.89
(s, 3H), 3.88 (s, 3H), 2.50 (s, 3H). 13C{1H} NMR (100 MHz,
CDCl3) δ 192.4, 163.6, 159.8, 154.0, 148.4, 145.8, 138.3, 133.8, 132.0,
130.8, 130.4, 130.1, 129.0, 127.4, 124.5, 121.0, 114.0, 113.4, 55.4,
+
55.3, 21.9. HRMS (ESI-TOF): m/z [M + H]+ calcd for C25H22NO3 ,
384.1594; found, 384.1593.
(4-Ethoxyphenyl)(4-(4-ethoxyphenyl)-6-methylquinolin-2-yl)-
methanone (3g). Yield 74%; 304.5 mg; yellow solid; column
chromatography, silica gel (PE/EA, 15:1); mp 170−172 °C. 1H NMR
(400 MHz, CDCl3) δ 8.29 (d, J = 8.4 Hz, 2H), 8.15 (d, J = 8.4 Hz,
1H), 7.94 (s, 1H), 7.79 (s, 1H), 7.59 (d, J = 8.4 Hz, 1H), 7.48 (d, J =
8.4 Hz, 2H), 7.06 (d, J = 8.0 Hz, 2H), 6.97 (d, J = 8.4 Hz, 2H), 4.14
(d, J = 6.8 Hz, 2H), 4.11 (d, J = 6.8 Hz, 2H), 2.50 (s, 3H), 1.48 (t, J =
4.8 Hz, 3H), 1.45 (t, J = 4.8 Hz, 3H). 13C{1H} NMR (100 MHz,
CDCl3) δ 192.4, 163.0, 159.3, 154.1, 148.5, 145.8, 138.3, 133.9, 132.0,
130.8, 130.4, 130.0, 128.9, 127.4, 124.6, 121.0, 114.6, 113.9, 63.7,
63.5, 22.0, 14.8, 14.7. HRMS (ESI-TOF): m/z [M + Na]+ calcd for
C27H25NO3Na+, 434.1727; found, 434.1734.
(4-Fluorophenyl)(4-(4-fluorophenyl)-6-methylquinolin-2-yl)-
methanone (3h). Yield 40%; 143.8 mg; white solid; column
chromatography, silica gel (PE/EA, 40:1); mp 108−110 °C; 1H
NMR (400 MHz, CDCl3) δ 8.38−8.34 (m, 2H), 8.15 (d, J = 8.4 Hz,
1H), 8.01 (s, 1H), 7.70 (s, 1H), 7.65−7.62 (m, 1H), 7.55−7.51 (m,
2H), 7.28−7.17 (m, 4H), 2.52 (s, 3H). 13C{1H} NMR (100 MHz,
CDCl3) δ 192.0, 165.8 (d, J = 253.0 Hz, 1JCF), 163.0 (d, J = 247.0 Hz,
1JCF), 153.1, 147.9, 145.8, 139.2, 134.2 (d, J = 9.0 Hz, 3JCF), 133.7 (d,
(6-Methyl-4-(p-tolyl)quinolin-2-yl)(p-tolyl)methanone (3b). Yield
71%; 249.5 mg; yellow solid; column chromatography, silica gel (PE/
1
EA, 40:1); mp 137−139 °C. H NMR (400 MHz, CDCl3) δ 8.17−
8.15 (m, 3H), 7.97 (s, 1H), 7.78 (s, 1H), 7.62−7.60 (m, 1H), 7.46 (d,
J = 8.0 Hz, 2H), 7.36 (d, J = 8.0 Hz, 2H), 7.32 (d, J = 8.0 Hz, 2H),
2.51 (s, 3H), 2.48 (s, 3H), 2.46 (s, 3H). 13C{1H} NMR (100 MHz,
CDCl3) δ 193.7, 153.7, 148.9, 145.8, 143.9, 138.6, 138.5, 134.9, 133.7,
132.1, 131.6, 130.5, 129.5, 129.3, 128.9, 127.5, 124.6, 121.1, 22.0,
21.8, 21.3. HRMS (ESI-TOF): m/z [M + H]+ calcd for C25H22NO+,
352.1696; found, 352.1705.
4
J = 3.0 Hz, JCF), 132.5 (d, J = 3.0 Hz, 4JCF), 132.4, 131.2 (d, J = 8.0
3
2
Hz, JCF), 130.6, 127.4, 124.3, 121.1, 115.8 (d, J = 22.0 Hz, JCF),
115.2 (d, J = 21.0 Hz, JCF), 22.0. 19F NMR (376 MHz, CDCl3) δ
2
−105.17, −112.88. HRMS (ESI-TOF): m/z [M + H]+ calcd for
C23H16F2NO+, 360.1194; found, 360.1203.
(4-Chlorophenyl)(4-(4-chlorophenyl)-6-methylquinolin-2-yl)-
methanone (3i). Yield 61%; 239.3 mg; white solid; column
chromatography, silica gel (PE/EA, 40:1); mp 180−182 °C. 1H
NMR (400 MHz, CDCl3) δ 8.26 (d, J = 8.4 Hz, 2H), 8.14 (d, J = 8.4
Hz, 1H), 8.01 (s, 1H), 7.68 (s, 1H), 7.64 (d, J = 8.4 Hz, 1H), 7.55−
7.48 (m, 6H), 2.52 (s, 3H). 13C{1H} NMR (100 MHz, CDCl3) δ
192.3, 152.9, 147.6, 145.8, 139.5, 139.4, 136.2, 134.8, 134.6, 132.9,
132.4, 130.8, 130.7, 129.0, 128.4, 127.3, 124.2, 120.9, 22.1. HRMS
(ESI-TOF): m/z [M + H]+ calcd for C23H16Cl2NO+, 392.0603;
found, 392.0618.
(3-Bromophenyl)(4-(3-bromophenyl)-6-methylquinolin-2-yl)-
methanone (3j). Yield 55%; 264.7 mg; yellow solid; column
chromatography, silica gel (PE/EA, 40:1); mp 151−153 °C. 1H
NMR (400 MHz, CDCl3) δ 8.44 (s, 1H), 8.21 (d, J = 8.0 Hz, 1H),
8.16 (d, J = 8.4 Hz, 1H), 8.02 (s, 1H), 7.75 (d, J = 8.0 Hz, 1H), 7.70−
7.64 (m, 4H), 7.47−7.38 (m, 3H), 2.53 (s, 3H). 13C{1H} NMR (100
MHz, CDCl3) δ 192.0, 152.5, 147.3, 145.8, 139.7, 139.6, 138.0, 135.7,
134.3, 132.6, 132.3, 131.7, 130.8, 130.2, 130.0, 129.6, 128.2, 127.3,
124.1, 122.8, 122.3, 120.9, 22.1. HRMS (ESI-TOF): m/z [M + H]+
calcd for C23H16Br2NO+, 479.9593; found, 479.9603.
(4-Ethylphenyl)(4-(4-ethylphenyl)-6-methylquinolin-2-yl)-
methanone (3c). Yield 69%; 261.9 mg; white solid; column
chromatography, silica gel (PE/EA, 40:1); mp 105−107 °C. 1H
NMR (400 MHz, CDCl3) δ 8.20−8.15 (m, 3H), 7.98 (s, 1H), 7.79 (s,
1H), 7.61 (d, J = 8.8 Hz, 1H), 7.49 (d, J = 8.0 Hz, 2H), 7.38 (d, J =
8.0 Hz, 2H), 7.34 (d, J = 8.0 Hz, 2H), 2.78 (q, J = 7.6 Hz, 2H), 2.75
(q, J = 7.6 Hz, 2H), 2.51 (s, 3H), 1.34 (t, J = 7.6 Hz, 3H), 1.29 (t, J =
7.6 Hz, 3H). 13C{1H} NMR (100 MHz, CDCl3) δ 193.7, 153.7,
150.0, 148.9, 145.9, 144.7, 138.5, 135.2, 133.9, 132.1, 131.7, 130.5,
129.5, 128.1, 127.7, 127.5, 124.6, 121.1, 29.1, 28.7, 22.0, 15.4, 15.2.
HRMS (ESI-TOF): m/z [M + H]+ calcd for C27H26NO+, 380.2009;
found, 380.2014.
(6-Methyl-4-(4-propylphenyl)quinolin-2-yl)(4-propylphenyl)-
methanone (3d). Yield 73%; 297.5 mg; yellow solid; column
1
chromatography, silica gel (PE/EA, 40:1); mp 92−94 °C. H NMR
(400 MHz, CDCl3) δ 8.20−8.15 (m, 3H), 7.98 (s, 1H), 7.80 (s, 1H),
7.60 (d, J = 8.8 Hz, 1H), 7.47 (d, J = 8.0 Hz, 2H), 7.37−7.31 (m,
4H), 2.73−2.66 (m, 4H), 2.51 (s, 3H), 1.77−1.67 (m, 4H), 1.03 (t, J
= 7.2 Hz, 3H), 0.98 (t, J = 7.6 Hz, 3H). 13C{1H} NMR (100 MHz,
CDCl3) δ 193.6, 153.7, 148.9, 148.5, 145.8, 143.2, 138.5, 135.2, 133.9,
132.1, 131.6, 130.5, 129.4, 128.7, 128.3, 127.5, 124.6, 121.1, 38.2,
37.8, 24.5, 24.2, 22.0, 13.9, 13.8. HRMS (ESI-TOF): m/z [M + H]+
calcd for C29H30NO+, 408.2322; found, 408.2335.
(6-Methyl-4-(m-tolyl)quinolin-2-yl)(m-tolyl)methanone (3k).
Yield 63%; 221.4 mg; yellow solid; column chromatography, silica
1
gel (PE/EA, 40:1); mp 99−101 °C. H NMR (400 MHz, CDCl3) δ
8.15 (d, J = 8.4 Hz, 1H), 8.04 (s, 2H), 7.98 (s, 1H), 7.76 (s, 1H),
7.62−7.59 (m, 1H), 7.45−7.31 (m, 6H), 2.50 (s, 3H), 2.47 (s, 3H),
2.44 (s, 3H). 13C{1H} NMR (100 MHz, CDCl3) δ 194.3, 153.5,
148.9, 145.9, 138.6, 138.4, 137.8, 136.3, 135.1, 133.7, 132.1, 131.6,
130.6, 130.1, 129.2, 128.8, 128.4, 127.9, 127.5, 126.6, 124.5, 121.0,
22.0, 21.5, 21.4. HRMS (ESI-TOF): m/z [M + H]+ calcd for
C25H22NO+, 352.1696; found, 352.1706.
(4-(tert-Butyl)phenyl)(4-(4-(tert-butyl)phenyl)-6-methylquinolin-
2-yl)methanone (3e). Yield 68%; 296.2 mg; column chromatography,
1
silica gel (PE/EA, 40:1); yellow solid; mp 153−155 °C. H NMR
(400 MHz, CDCl3) δ 8.22−8.16 (m, 3H), 7.99 (s, 1H), 7.83 (s, 1H),
7.63−7.50 (m, 7H), 2.53 (s, 3H), 1.43 (s, 9H), 1.38 (s, 9H). 13C{1H}
NMR (100 MHz, CDCl3) δ 193.6, 156.7, 153.7, 151.6, 148.8, 145.9,
8384
https://doi.org/10.1021/acs.joc.1c00793
J. Org. Chem. 2021, 86, 8381−8388

The Journal of Organic Chemistry
pubs.acs.org/joc
Article
(3-Methoxyphenyl)(4-(3-methoxyphenyl)-6-methylquinolin-2-
yl)methanone (3l). Yield 68%; 260.7 mg; yellow solid; column
chromatography, silica gel (PE/EA, 15:1); mp 127−129 °C. 1H NMR
(400 MHz, CDCl3) δ 8.15 (d, J = 8.4 Hz, 1H), 8.01 (s, 1H), 7.84 (d, J
= 8.0 Hz, 2H), 7.77 (s, 1H), 7.62−7.59 (m, 1H), 7.48−7.39 (m, 2H),
7.18−7.04 (m, 4H), 3.87 (s, 3H), 3.87 (s, 3H), 2.50 (s, 3H). 13C{1H}
NMR (100 MHz, CDCl3) δ 193.6, 159.7, 159.3, 153.3, 148.6, 145.8,
139.1, 138.8, 137.4, 132.2, 130.6, 129.6, 129.0, 127.4, 124.5, 124.4,
121.9, 120.9, 119.7, 115.3, 115.1, 114.0, 55.40, 55.35, 22.0. HRMS
(6-Isopropyl-4-(4-methoxyphenyl)quinolin-2-yl)(4-methoxy-
phenyl)methanone (4b). Yield 72%; 296.3 mg; yellow solid; column
chromatography, silica gel (PE/EA, 15:1); mp 108−110 °C. 1H NMR
(400 MHz, CDCl3) δ 8.30 (d, J = 8.4 Hz, 2H), 8.20 (d, J = 8.8 Hz,
1H), 7.96 (s, 1H), 7.85 (s, 1H), 7.70 (d, J = 8.8 Hz, 1H), 7.53 (d, J =
8.4 Hz, 2H), 7.09 (d, J = 8.4 Hz, 2H), 6.99 (d, J = 8.8 Hz, 2H), 3.91
(s, 3H), 3.89 (s, 3H), 3.08−3.05 (m, 1H), 1.30 (d, J = 6.8 Hz, 6H),
1.29 (s, 3H). 13C{1H} NMR (100 MHz, CDCl3) δ 192.5, 163.6,
159.9, 154.1, 149.0, 148.7, 146.2, 133.8, 130.8, 130.7, 130.2, 129.3,
129.1, 127.4, 122.0, 121.0, 114.1, 113.4, 55.4, 55.3, 34.4, 23.8. HRMS
+
(ESI-TOF): m/z [M + H]+ calcd for C25H22NO3 , 384.1594; found,
+
(ESI-TOF): m/z [M + H]+ calcd for C27H26NO3 , 412.1907; found,
384.1605.
412.1923.
(4-Butylphenyl)(4-(4-butylphenyl)-6-methylquinolin-2-yl)-
methanone (3m). Yield 69%; 300.6 mg; yellow solid; column
(6-(tert-Butyl)-4-(4-methoxyphenyl)quinolin-2-yl)(4-methoxy-
phenyl)methanone (4c). Yield 66%; 280.8 mg; orange solid; column
chromatography, silica gel (PE/EA, 15:1); mp 124−126 °C. 1H NMR
(400 MHz, CDCl3) δ 8.30 (d, J = 8.8 Hz, 2H), 8.20 (d, J = 8.8 Hz,
1H), 8.03 (s, 1H), 7.97 (s, 1H), 7.88 (d, J = 8.8 Hz, 1H), 7.54 (d, J =
8.4 Hz, 2H), 7.08 (d, J = 8.4 Hz, 2H), 6.99 (d, J = 8.8 Hz, 2H), 3.89
(s, 3H), 3.88 (s, 3H), 1.37 (s, 9H). 13C{1H} NMR (100 MHz,
CDCl3) δ 192.4, 163.5, 159.8, 154.2, 151.1, 148.9, 145.7, 133.8, 130.7,
130.2, 130.1, 129.0, 128.6, 126.9, 120.9, 120.6, 114.0, 113.4, 55.4,
55.2, 35.1, 31.0. HRMS (ESI-TOF): m/z [M + H]+ calcd for
1
chromatography, silica gel (PE/EA, 40:1); mp 88−90 °C. H NMR
(400 MHz, CDCl3) δ 8.20−8.14 (m, 3H), 7.98 (s, 1H), 7.80 (s, 1H),
7.59 (d, J = 8.8 Hz, 1H), 7.47 (d, J = 8.0 Hz, 2H), 7.37−7.30 (m,
4H), 2.78−2.71 (m, 2H), 2.70−2.68 (m, 2H), 2.50 (s, 3H), 1.74−
1.68 (m, 2H), 1.67−1.61(m, 2H), 1.46−1.43 (m, 2H), 1.40−1.36 (m,
2H), 0.99 (d, J = 7.2 Hz, 3H), 0.94 (d, J = 7.2 Hz, 3H). 13C{1H}
NMR (100 MHz, CDCl3) δ 193.6, 153.7, 148.8, 148.7, 145.9, 143.4,
138.4, 135.1, 133.8, 132.0, 131.6, 130.5, 129.4, 128.6, 128.2, 127.4,
124.6, 121.1, 35.8, 35.4, 33.5, 33.2, 22.4, 22.3, 22.0, 14.0, 13.9. HRMS
(ESI-TOF): m/z [M + H]+ calcd for C31H34NO+, 436.2635; found,
436.2651.
+
C28H28NO3 , 426.2064; found, 426.2069.
(6-Methoxy-4-(4-methoxyphenyl)quinolin-2-yl)(4-methoxy-
phenyl)methanone (4d). Yield 68%; 271.6 mg; white solid; column
chromatography, silica gel (PE/EA, 15:1); mp 142−144 °C. 1H NMR
(400 MHz, CDCl3) δ 8.31 (d, J = 8.8 Hz, 2H), 8.14 (d, J = 9.2 Hz,
1H), 7.97 (s, 1H), 7.51 (d, J = 8.4 Hz, 2H), 7.42−7.39 (m, 1H), 7.30
(d, J = 2.4 Hz, 1H), 7.07 (d, J = 8.4 Hz, 2H), 6.99 (d, J = 8.8 Hz, 2H),
3.89 (s, 3H), 3.88 (s, 3H), 3.82 (s, 3H). 13C{1H} NMR (100 MHz,
CDCl3) δ 192.2, 163.5, 159.8, 159.2, 152.5, 147.5, 143.2, 133.8, 132.3,
130.5, 130.2, 129.2, 128.7, 122.3, 121.4, 114.1, 113.3, 103.5, 55.5,
(6-Methyl-4-(4-pentylphenyl)quinolin-2-yl)(4-pentylphenyl)-
methanone (3n). Yield 67%; 310.7 mg; yellow solid; column
1
chromatography, silica gel (PE/EA, 40:1); mp 90−92 °C. H NMR
(400 MHz, CDCl3) δ 8.20−8.14 (m, 3H), 7.98 (s, 1H), 7.80 (s, 1H),
7.60 (d, J = 8.4 Hz, 1H), 7.47 (d, J = 8.0 Hz, 2H), 7.37−7.31 (m,
4H), 2.73 (d, J = 9.6 Hz, 2H), 2.69 (d, J = 9.6 Hz, 2H), 2.51 (s, 3H),
1.74−1.70 (m, 2H), 1.69−1.65 (m, 2H), 1.40−1.38 (m, 4H), 1.37−
1.33 (m, 4H), 0.94 (t, J = 6.0 Hz, 3H), 0.90 (t, J = 6.8 Hz, 3H).
13C{1H} NMR (100 MHz, CDCl3) δ 193.7, 153.8, 148.81, 148.77,
+
55.4, 55.3. HRMS (ESI-TOF): m/z [M + H]+ calcd for C25H22NO4 ,
400.1543; found, 400.1544.
145.9, 143.5, 138.5, 135.1, 133.8, 132.0, 131.6, 130.6, 129.5, 128.6,
128.2, 127.4, 124.6, 121.1, 36.1, 35.7, 31.6, 31.4, 31.1, 30.8, 22.6, 22.5,
22.0, 14.04, 13.99. HRMS (ESI-TOF): m/z [M + H]+ calcd for
C33H38NO+, 464.2948; found, 464.2966.
(4-Methoxyphenyl)(4-(4-methoxyphenyl)-6-(methylthio)-
quinolin-2-yl)methanone (4e). Yield 65%; 270.1 mg; yellow solid;
column chromatography, silica gel (PE/EA, 15:1); mp 133−135 °C.
1H NMR (400 MHz, CDCl3) δ 8.30 (d, J = 8.8 Hz, 2H), 8.12 (d, J =
9.2 Hz, 1H), 7.97 (s, 1H), 7.75 (s, 1H), 7.64−7.61 (m, 1H), 7.51 (d, J
= 8.4 Hz, 2H), 7.07 (d, J = 8.4 Hz, 2H), 7.00 (d, J = 8.8 Hz, 2H), 3.90
(s, 3H), 3.89 (s, 3H), 2.49 (s, 3H). 13C{1H} NMR (100 MHz,
CDCl3) δ 192.2, 163.6, 159.9, 153.8, 147.6, 145.4, 139.8, 133.8, 130.8,
130.7, 129.8, 129.0, 128.8, 127.8, 121.6, 120.1, 114.1, 113.4, 55.4,
55.3, 15.3. HRMS (ESI-TOF): m/z [M + H]+ calcd for
C25H22NO3S+, 416.1315; found, 416.1330.
(4-Methoxyphenyl)(4-(4-methoxyphenyl)-6-phenylquinolin-2-
yl)methanone (4f). Yield 51%; 227.2 mg; orange solid; column
chromatography, silica gel (PE/EA, 15:1); mp 154−156 °C; 1H NMR
(400 MHz, CDCl3) δ 8.32 (d, J = 8.4 Hz, 3H), 8.23 (d, J = 1.2 Hz,
1H), 8.05−8.00 (m, 2H), 7.64 (d, J = 7.2 Hz, 2H), 7.55 (d, J = 8.4
Hz, 2H), 7.48−7.44 (m, 2H), 7.39 (d, J = 7.2 Hz, 1H), 7.09 (d, J =
8.4 Hz, 2H), 7.01 (d, J = 8.8 Hz, 2H), 3.90 (s, 3H), 3.86 (s, 3H).
13C{1H} NMR (100 MHz, CDCl3) δ 192.3, 163.7, 160.0, 154.7,
(6-Methyl-4-(naphthalen-2-yl)quinolin-2-yl)(naphthalen-2-yl)-
methanone (3o). Yield 60%; 254.1 mg; white solid; column
chromatography, silica gel (PE/EA, 40:1); mp 178−180 °C. 1H
NMR (400 MHz, CDCl3) δ 8.88 (s, 1H), 8.32−8.29 (m, 1H), 8.21−
8.16 (m, 2H), 8.05−8.01 (m, 2H), 7.98−7.89 (m, 5H), 7.80 (s, 1H),
7.69−7.67 (m, 1H), 7.64−7.51 (m, 5H), 2.49 (s, 3H). 13C{1H} NMR
(100 MHz, CDCl3) δ 193.8, 153.7, 148.8, 145.9, 138.9, 135.6, 135.3,
134.1, 133.6, 133.2, 133.0, 132.4, 132.3, 130.7, 129.9, 128.8, 128.5,
128.3, 128.2, 127.9, 127.8, 127.7, 127.6, 127.3, 126.74, 126.68, 126.5,
124.6, 121.4, 22.0. HRMS (ESI-TOF): m/z [M + H]+ calcd for
C31H22NO+, 424.1696; found, 424.1705.
(6-Methyl-4-(thiophen-3-yl)quinolin-2-yl)(thiophen-3-yl)-
methanone (3p). Yield 66%; 221.4 mg; yellow solid; column
chromatography, silica gel (PE/EA, 40:1); mp 150−152 °C. 1H NMR
(400 MHz, CDCl3) δ 9.05 (d, J = 1.6 Hz, 1H), 8.16−8.13 (m, 2H),
7.97 (d, J = 5.2 Hz, 1H), 7.88 (s, 1H), 7.61−7.56 (m, 2H), 7.52−7.50
(m, 1H), 7.37−7.33 (m, 2H), 2.52 (s, 3H). 13C{1H} NMR (100
MHz, CDCl3) δ 185.8, 153.4, 146.0, 143.3, 139.8, 138.9, 138.3, 137.3,
132.1, 130.6, 129.5, 128.8, 127.5, 126.3, 125.2, 125.0, 124.4, 120.4,
149.4, 146.6, 140.8, 140.2, 133.9, 132.3, 131.2, 130.9, 129.9, 129.5,
128.9, 127.9, 127.6, 127.5, 123.5, 121.4, 114.2, 113.5, 55.5, 55.4.
+
HRMS (ESI-TOF): m/z [M + H]+ calcd for C30H24NO3 , 446.1751;
+
22.0. HRMS (ESI-TOF): m/z [M + H]+ calcd for C19H14NOS2 ,
found, 446.1769.
(6-Ffluoro-4-(4-methoxyphenyl)quinolin-2-yl)(4-methoxy-
phenyl)methanone (4g). Yield 63%; 244.1 mg; yellow solid; column
chromatography, silica gel (PE/EA, 15:1); mp 178−180 °C. 1H NMR
(400 MHz, CDCl3) δ 8.29 (d, J = 8.8 Hz, 2H), 8.26−8.23 (m, 1H),
8.00 (s, 1H), 7.67−7.64 (m, 1H), 7.55−7.47 (m, 3H), 7.08 (d, J = 8.8
Hz, 2H), 7.00 (d, J = 8.8 Hz, 2H), 3.90 (s, 3H). 13C{1H} NMR (100
336.0511; found, 336.0522.
(6-Ethyl-4-(4-methoxyphenyl)quinolin-2-yl)(4-methoxyphenyl)-
methanone (4a). Yield 70%; 278.2 mg; yellow solid; column
chromatography, silica gel (PE/EA, 15:1); mp 117−119 °C. 1H
NMR (400 MHz, CDCl3) δ 8.30 (d, J = 8.8 Hz, 2H), 8.18 (d, J = 8.4
Hz, 1H), 7.95 (s, 1H), 7.81 (s, 1H), 7.65−7.63 (m, 1H), 7.51 (d, J =
8.8 Hz, 2H), 7.08 (d, J = 8.8 Hz, 2H), 6.99 (d, J = 8.8 Hz, 2H), 3.90
(s, 3H), 3.89 (s, 3H), 2.83−2.77 (m, 2H), 1.30−1.26 (t, J = 7.6 Hz,
3H)). 13C{1H} NMR (100 MHz, CDCl3) δ 192.4, 163.6, 159.8,
154.0, 148.6, 146.0, 144.5, 133.8, 130.84, 130.77, 130.6, 130.1, 129.0,
127.4, 123.3, 121.0, 114.0, 113.4, 55.4, 55.3, 29.2, 15.4. HRMS (ESI-
1
MHz, CDCl3) δ 192.0, 163.7, 161.6 (d, J = 249.0 Hz, JCF), 160.1,
4
4
154.3 (d, J = 2.0 Hz, JCF), 148.8 (d, J = 6.0 Hz, JCF), 144.3, 133.8,
133.3 (d, J = 9.0 Hz, 3JCF), 130.6, 129.4, 128.8, 128.4 (d, J = 10.0 Hz,
3JCF), 121.4, 120.0 (d, J = 26.0 Hz, JCF), 114.3, 113.5, 109.3 (d, J =
2
23.0 Hz, 2JCF), 55.44, 55.35. 19F NMR (376 MHz, CDCl3) δ −104.02.
+
+
TOF): m/z [M + H]+ calcd for C26H24NO3 , 398.1751; found,
HRMS (ESI-TOF): m/z [M + H]+ calcd for C24H19FNO3 ,
398.1762.
388.1343; found, 388.1353.
8385
https://doi.org/10.1021/acs.joc.1c00793
J. Org. Chem. 2021, 86, 8381−8388

The Journal of Organic Chemistry
pubs.acs.org/joc
Article
(6-Chloro-4-(4-methoxyphenyl)quinolin-2-yl)(4-methoxy-
phenyl)methanone (4h). Yield 60%; 242.3 mg; yellow soild; column
chromatography, silica gel (PE/EA, 15:1); mp 167−169 °C. 1H NMR
(400 MHz, CDCl3) δ 8.29 (d, J = 8.8 Hz, 2H), 8.18 (d, J = 8.8 Hz,
1H), 8.02−7.99 (m, 2H), 7.72−7.69 (m, 1H), 7.49 (d, J = 8.4 Hz,
2H), 7.09 (d, J = 8.4 Hz, 2H), 7.00 (d, J = 8.8 Hz, 2H), 3.92 (s, 3H),
3.91 (s, 3H). 13C{1H} NMR (100 MHz, CDCl3) δ 192.0, 163.8,
160.2, 155.1, 148.6, 145.7, 134.2, 133.9, 132.3, 130.8, 129.3, 128.8,
128.2, 124.7, 121.7, 114.3, 113.5, 55.5, 55.4. HRMS (ESI-TOF): m/z
193.6, 159.7, 159.4, 153.3, 149.0, 145.9, 145.1, 139.1, 137.4, 131.2,
130.6, 129.7, 129.1, 127.4, 124.5, 123.4, 122.0, 121.0, 119.9, 115.2,
115.0, 114.2, 55.5, 55.4, 29.3, 15.5; HRMS (ESI-TOF): m/z [M +
+
H]+ calcd for C26H24NO3 , 398.1751; found, 398.1762.
(6-Methoxy-4-phenylquinolin-2-yl)(phenyl)methanone (5aa).
Yield 42%; 142.5 mg; white solid; column chromatography, silica
gel (PE/EA, 20:1); mp 206−208 °C. 1H NMR (400 MHz, CDCl3) δ
8.26 (d, J = 7.2 Hz, 2H), 8.13 (d, J = 9.2 Hz, 1H), 8.04 (s, 1H), 7.60−
7.47 (m, 9H), 7.41−7.38 (m, 1H), 3.77 (s, 3H). 13C{1H} NMR (100
MHz, CDCl3) δ 193.6, 159.4, 151.8, 147.8, 143.2, 137.9, 136.4, 132.7,
132.3, 131.3, 129.2, 128.6, 128.5, 127.9, 122.4, 121.4, 103.4, 55.4.
+
[M + H]+ calcd for C24H19ClNO3 , 404.1048; found, 404.1047.
(6-Bromo-4-(4-methoxyphenyl)quinolin-2-yl)(4-methoxy-
phenyl)methanone (4i). Yield 52%; 233.1 mg; orange soild; column
chromatography, silica gel (PE/EA, 15:1); mp 168−170 °C. 1H NMR
(400 MHz, CDCl3) δ 8.28 (d, J = 8.8 Hz, 2H), 8.18 (d, J = 1.6 Hz,
1H), 8.09 (d, J = 8.8 Hz, 1H), 7.98 (s, 1H), 7.83−7.80 (m, 1H), 7.47
(d, J = 8.4 Hz, 2H), 7.08 (d, J = 8.4 Hz, 2H), 6.99 (d, J = 8.8 Hz, 2H),
3.90 (s, 3H), 3.89 (s, 3H). 13C{1H} NMR (100 MHz, CDCl3) δ
191.9, 163.7, 160.1, 155.1, 148.4, 145.8, 133.8, 133.2, 132.3, 130.7,
129.1, 128.7, 128.5, 127.9, 122.5, 121.6, 114.3, 113.5, 55.4, 55.3.
+
HRMS (ESI-TOF): m/z [M + H]+ calcd for C23H18NO2 , 340.1332;
found, 340.1331.
(6-Methoxy-4-phenylquinolin-2-yl)(4-methoxyphenyl)-
methanone (5bb). Yield 54%; 199.3 mg; yellow solid; column
chromatography, silica gel (PE/EA, 12:1); mp 165−167 °C. 1H NMR
(400 MHz, CDCl3) 8.32 (d, J = 8.8 Hz, 2H), 8.15 (d, J = 8.8 Hz, 1H),
8.00 (s, 1H), 7.56−7.49 (m, 6H), 7.42 (d, J = 8.8 Hz, 1H), 6.99 (d, J
= 8.4 Hz, 2H), 3.89 (s, 3H), 3.81 (s, 3H). 13C{1H} NMR (100 MHz,
CDCl3) δ 192.1, 163.5, 159.3, 152.5, 147.8, 143.2, 138.0, 133.8, 132.3,
129.3, 129.2, 128.7, 128.6, 128.5, 122.4, 121.5, 113.4, 103.5, 55.5,
+
HRMS (ESI-TOF): m/z [M + H]+ calcd for C24H19BrNO3 ,
448.0543; found, 448.0545.
+
55.4. HRMS (ESI-TOF): m/z [M + H]+ calcd for C24H20NO3 ,
(4-Methoxyphenyl)(4-(4-methoxyphenyl)-6-(trifluoromethoxy)-
quinolin-2-yl)methanone (4j). Yield 50%; 226.7 mg; yellow soild;
column chromatography, silica gel (PE/EA, 15:1); mp 126−128 °C.
1H NMR (400 MHz, CDCl3) δ 8.32−8.28 (m, 3H), 8.03 (s, 1H),
370.1438; found, 370.1436.
2-Oxo-2-phenylacetaldehyde (1aa).12 Yield 43%; 57.7 mg; white
solid; column chromatography, silica gel (PE/EA, 5:1);1H NMR (400
MHz, CDCl3) δ 8.12 (d, J = 7.6 Hz, 2H), 7.60−7.57 (t, J = 7.6 Hz,
1H), 7.50−7.43 (t, J = 7.6 Hz, 2H), 6.39 (d, J = 8.8 Hz, 1H), 5.13 (d,
J = 9.6 Hz, 1H). 13C{1H} NMR (100 MHz, CDCl3) δ 192.7, 134.6,
132.1, 129.9, 128.7, 88.6.
7.88 (s, 1H), 7.65 (d, J = 8.8 Hz, 1H), 7.50 (d, J = 8.4 Hz, 2H), 7.10
(d, J = 8.0 Hz, 2H), 7.01 (d, J = 8.4 Hz, 2H), 3.92 (s, 3H), 3.91 (s,
3H). 13C{1H} NMR (100 MHz, CDCl3) δ 191.9, 163.9, 160.3, 155.4,
149.4, 148.2, 145.5, 133.9, 133.0, 130.7, 129.1, 128.7, 127.9, 123.7,
1
121.7, 120.5 (q, J = 256.0 Hz, JCF), 116.4, 114.4, 113.6, 55.5, 55.4.
19F NMR (376 MHz, CDCl3) δ −57.66. HRMS (ESI-TOF): m/z [M
ASSOCIATED CONTENT
■
+
+ H]+ calcd for C25H19F3NO4 , 454.1261; found, 454.1270.
sı
* Supporting Information
(4-Methoxyphenyl)(5,6,7-trimethoxy-4-(4-methoxyphenyl)-
quinolin-2-yl)methanone (4k). Yield 31%; 142.4 mg; orange soild;
column chromatography, silica gel (PE/EA, 12:1); mp 140−142 °C.
1H NMR (400 MHz, CDCl3) δ 8.24 (d, J = 8.8 Hz, 2H), 7.70 (s, 1H),
The Supporting Information is available free of charge at
https://pubs.acs.org/doi/10.1021/acs.joc.1c00793.
Crystallographic data and copies of the 1H and 13C{1H}
NMR spectra (PDF)
7.45 (s, 1H), 7.37 (d, J = 8.8 Hz, 2H), 7.01−6.95 (m, 4H), 4.04 (s,
3H), 3.97 (s, 3H), 3.90 (s, 3H), 3.89 (s, 3H), 3.31 (s, 3H). 13C{1H}
NMR (100 MHz, CDCl3) δ 192.4, 163.6, 158.9, 155.8, 153.7, 148.6,
147.7, 145.7, 143.7, 133.7, 133.6, 129.8, 129.0, 121.9, 118.5, 113.5,
112.6, 106.0, 61.3, 60.9, 56.1, 55.5, 55.3. HRMS (ESI-TOF): m/z [M
Accession Codes
CCDC 2056325 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.
+
+ H]+ calcd for C27H26NO6 , 460.1755; found, 460.1749.
(4-Methoxyphenyl)(1-(4-methoxyphenyl)benzo[f]quinolin-3-yl)-
methanone (4l). Yield 40%; 167.8 mg; yellow solid; column
chromatography, silica gel (PE/EA, 15:1); mp 197−199 °C. 1H
NMR (400 MHz, CDCl3) δ 8.34 (d, J = 8.4 Hz, 2H), 8.10 (d, J = 9.2
Hz, 1H), 8.01 (d, J = 6.0 Hz, 2H), 7.90−7.87 (m, 2H), 7.55−7.22 (m,
1H), 7.39 (d, J = 8.4 Hz, 2H), 7.26−7.21 (m, 1H), 7.06−7.00 (m,
4H), 3.92 (s, 3H), 3.91 (s, 3H). 13C{1H} NMR (100 MHz, CDCl3) δ
192.0, 163.7, 159.7, 153.4, 149.3, 148.4, 134.5, 133.9, 133.5, 131.8,
129.6, 129.5, 129.1, 128.9, 128.6, 128.5, 127.4, 125.7, 125.3, 124.5,
114.7, 113.5, 55.5, 55.4. HRMS (ESI-TOF): m/z [M + H]+ calcd for
AUTHOR INFORMATION
■
Corresponding Authors
An-Xin Wu − Key Laboratory of Pesticide & Chemical
Biology, Ministry of Education, College of Chemistry, Central
China Normal University, Wuhan 430079, P. R. China;
orcid.org/0000-0001-7673-210X; Email: chwuax@
mail.ccnu.edu.cn
Yan-Dong Wu − Key Laboratory of Pesticide & Chemical
Biology, Ministry of Education, College of Chemistry, Central
China Normal University, Wuhan 430079, P. R. China;
Email: chwuyd@mail.ccnu.edu.cn
+
C28H22NO3 , 420.1594; found, 420.1611.
(4-Ethylphenyl)(4-(4-ethylphenyl)-6-methoxyquinolin-2-yl)-
methanone (4m). Yield 68%; 268.9 mg; yellow solid; column
chromatography, silica gel (PE/EA, 30:1); mp 144−146 °C. 1H NMR
(400 MHz, CDCl3) δ 8.21−8.14 (m, 3H), 8.01 (s, 1H), 7.50 (d, J =
7.6 Hz, 2H), 7.43−7.32 (m, 6H), 3.82 (s, 3H), 2.79−2.71 (m, 4H),
1.33 (t, J = 7.6 Hz, 3H), 1.29 (t, J = 7.6 Hz, 3H). 13C{1H} NMR (100
MHz, CDCl3) δ 193.5, 159.3, 152.2, 149.8, 147.9, 144.7, 143.3, 135.3,
134.0, 132.4, 131.7, 129.3, 128.8, 128.2, 127.6, 122.3, 121.5, 103.6,
55.5, 29.0, 28.6, 15.4, 15.2. HRMS (ESI-TOF): m/z [M + H]+ calcd
+
for C27H26NO2 , 396.1958; found, 396.1969.
Authors
(6-Ethyl-4-(3-methoxyphenyl)quinolin-2-yl)(3-methoxyphenyl)-
methanone (4n). Yield 67%; 266.1 mg; yellow solid; column
chromatography, silica gel (PE/EA, 15:1); mp 104−106 °C. 1H NMR
(400 MHz, CDCl3) δ 8.20 (d, J = 8.8 Hz, 1H), 8.01 (s, 1H), 7.84−
7.80 (m, 3H), 7.68−7.66 (m, 1H), 7.49−7.40 (m, 2H), 7.20−7.14
(m, 2H), 7.10−7.05 (m, 2H), 3.89 (s, 3H), 3.89 (s, 3H), 2.84−2.78
(m, 2H), 1.31−1.27 (m, 3H). 13C{1H} NMR (100 MHz, CDCl3) δ
Xiao-Xiao Yu − Key Laboratory of Pesticide & Chemical
Biology, Ministry of Education, College of Chemistry, Central
China Normal University, Wuhan 430079, P. R. China
Peng Zhao − Key Laboratory of Pesticide & Chemical Biology,
Ministry of Education, College of Chemistry, Central China
Normal University, Wuhan 430079, P. R. China
8386
https://doi.org/10.1021/acs.joc.1c00793
J. Org. Chem. 2021, 86, 8381−8388

The Journal of Organic Chemistry
pubs.acs.org/joc
Article
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You Zhou − Key Laboratory of Pesticide & Chemical Biology,
Ministry of Education, College of Chemistry, Central China
Normal University, Wuhan 430079, P. R. China
Chun Huang − Key Laboratory of Pesticide & Chemical
Biology, Ministry of Education, College of Chemistry, Central
China Normal University, Wuhan 430079, P. R. China
Li-Sheng Wang − Key Laboratory of Pesticide & Chemical
Biology, Ministry of Education, College of Chemistry, Central
China Normal University, Wuhan 430079, P. R. China
Complete contact information is available at:
https://pubs.acs.org/10.1021/acs.joc.1c00793
Author Contributions
†X.-X.Y. and P.Z. contributed equally to this work.
Notes
The authors declare no competing financial interest.
ACKNOWLEDGMENTS
■
We are grateful to the National Natural Science Foundation of
China (Grants 21971079, 21971080, and 21772051). It was
also supported by the 111 Project B17019.
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