Triple zirconocene/br?nsted acid/CuO cooperative and relay catalysis system for tandem Mannich addition/C-C formative cyclization/oxidation

Article abstract of DOI:10.1039/c7ra00870h

A new triple cooperative and relay catalysis system featuring the Mannich addition followed by C-C construction and oxydehydrogenation is described. The zirconocene dichloride and trimellitic acid synergic catalysis triggered the Mannich addition and C-C bond construction reactions, while CuO allowed relay catalysis for oxydehydrogenation. This novel strategy demonstrated superior activity for the synthesis of substituted quinolines from commercially available anilines, aldehydes and ketones. The corresponding substituted quinolines were synthesized with 32 examples in 90-96% yields under mild reaction conditions. A novel zirconocene-Br?nsted acid complex, generated in situ and acting as an active catalyst, was validated from the mechanistic studies.

Full text of DOI:10.1039/c7ra00870h

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Triple zirconocene/brønsted acid/CuO cooperative
and relay catalysis system for tandem Mannich
addition/C–C formative cyclization/oxidation†
Cite this: RSC Adv., 2017, 7, 28616
*
Yanlong Luo, Huaming Sun, Weiqiang Zhang, Xiu Wang, Shan Xu, Guofang Zhang,
*
Yajun Jian and Ziwei Gao
A new triple cooperative and relay catalysis system featuring the Mannich addition followed by C–C
construction and oxydehydrogenation is described. The zirconocene dichloride and trimellitic acid
synergic catalysis triggered the Mannich addition and C–C bond construction reactions, while CuO
allowed relay catalysis for oxydehydrogenation. This novel strategy demonstrated superior activity for the
synthesis of substituted quinolines from commercially available anilines, aldehydes and ketones. The
corresponding substituted quinolines were synthesized with 32 examples in 90–96% yields under mild
reaction conditions. A novel zirconocene–Brønsted acid complex, generated in situ and acting as an
active catalyst, was validated from the mechanistic studies.
Received 20th January 2017
Accepted 18th May 2017
DOI: 10.1039/c7ra00870h
rsc.li/rsc-advances
(Scheme 1). This is because such kind of reactions could
construct these fundamental bonds of organic molecules in
Introduction
a single step. In literature, two divergent synthetic procedures
with such cascade reaction were available. In 2010, Shin13
discovered an one pot redox-pinacol-Mannich–Michael cascade
reaction leading to the synthesis of 1-aminoindanes and 5,6-
Relay catalysis reactions are the one-pot multi-catalysis cascade
reactions in which each catalytic system promotes one type of
transformation in a consecutive fashion. The strategy of relay
catalysis obviates the requirement of isolation and purication
of products resulting from the each independent trans-
formation. More importantly, the advent of one-pot orthogonal
relay catalysis reactions made intricate organic syntheses
feasible, which were inaccessible and inefficient by the classical
step-wise catalysis. However, establishing such processes need
to overcome a number of challenging issues, such as the chemo
selectivity and the compatibility between the catalytic systems.
The combined metal/metal and metal/organo catalyst dual
catalysis are potential kinds of relay catalysis that has stimu-
lated intensive interest in recent years. A number of signicant
reactions have been developed using metal/metal relay catalysis
including Au/Ni,1 Au/Ag,2 Au/Yb,3 Au/Sc,4 Ru/Pd/Cu5 and Pd/Ag/
Bi6 catalyst systems. Regarding to the metal/organo relay catal-
ysis, the metal-Brønsted acid based systems have contributed
largely.7–12 The metal catalysts such as Au, Rh, Pd, Ag and Ru are
used in combination with a variety of Brønsted acids. In this
context, the development of divergent relay catalysis
approaches employing new catalysts is highly desirable.
The cascade reactions for the Mannich reaction followed by
the C–C or C–N bond formation are of highly appealing
Key Laboratory of Applied Surface and Colloid Chemistry, MOE School of Chemistry
and Chemical Engineering, Shaanxi Normal University, Xi'an 710062, P. R. China.
E-mail: hmsun@snnu.edu.cn; zwgao@snnu.edu.cn
Scheme 1 The reactions involving the Mannich reaction followed by
C–C/C–N bond formation.
† Electronic supplementary information (ESI) available. See DOI:
10.1039/c7ra00870h
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Table 1 Catalyst and Brønsted acid screening for three-component
fused azacycles (Scheme 1, eq. a). In this reaction, the gold
catalyst rendered the Mannich reaction followed by C–N
formation in an intramolecular manner. Very recently, HCl,14
iodine,15 CuCl2,16 FeCl3 (ref. 17) and AgOTf18 catalyzed three
components tandem reactions of anilines, aldehydes and
ketones for the construction of multi-functionalized quinoline
had been reported (Scheme 1, eq. b). This approach undergone
intermolecular Mannich reaction followed by intramolecular
C–C bond formation and oxydehydrogenation.
sequence reactiona
Entry
Catalyst
Brønsted acid
Yieldb (%)
In this paper, combination with the advantages of cascade
reaction integrating the Mannich addition and C–C/C–N bond
construction, the development of new catalytic systems is highly
desirable in organic synthesis. Herein, we report an unprece-
dented cooperative and relay catalysis by zirconocene dichlor-
ide, trimellitic acid and CuO triple catalytic system for the
Mannich addition/C–C bond formation/oxydehydrogenation
sequence (Scheme 1, eq. c). This triple cooperative and relay
catalytic system demonstrated superior activity for synthesis of
polysubstituted quinoline from arylamines, aldehydes and
ketones under mild condition.
1
2
3
4
5
6
7
8
Cp2TiCl2/CuCl2
Cp2TiCl2/CuBr2
Cp2TiCl2/Cu(acac)2
Cp2TiCl2/Cu(OAc)2
Cp2TiCl2/CuSO4$5H2O
Cp2TiCl2/CuO
Cp2TiCl2/Cu(OTf)2
Cp2TiCl2/Cu(ClO4)2
Cp*TiCl3/CuO
Cp2ZrCl2/CuO
Cp2ZrCl2/CuO
Cp2ZrCl2/CuO
Cp2ZrCl2/CuO
Cp2ZrCl2/CuO
Cp2ZrCl2/CuO
Cp2ZrCl2/CuO
Cp2ZrCl2/CuO
Cp2ZrCl2/CuO
PhCOOH
PhCOOH
PhCOOH
PhCOOH
PhCOOH
PhCOOH
PhCOOH
PhCOOH
PhCOOH
PhCOOH
PhOH
PhSO3H
Ph (COOH)NH2
Ph (COOH)OH
Ph (COOH)2
(CH2)3(COOH)2
HNC4H7COOH
H2NPh (SO3H)2
5-SO3HPhCOOH (OH)
Ph (COOH)3
Ph (COOH)3
30
28
25
22
24
31
26
27
29
34
20
26
41
42
47
29
28
45
48
54
88c
9
10
11
12
13
14
15
16
17
18
19
20
21
Results and discussion
We choose aniline, benzaldehyde and methyl pyruvate as
substrates to optimize the conditions of cascade Mannich
addition, C–C bond construction and oxydehydrogenation
reaction (Table 1). At rst, simple copper salts such as CuCl2,
CuBr2, Cu(acac)2, Cu(OAc)2, CuSO4$5H2O, CuO, Cu(OTf)2 and
Cu(ClO4)2 were used as catalysts in the presence of both Cp2-
TiCl2 and PhCOOH (Table 1, entries 1–8). Among these metal
salts, CuO was found to be the most effective catalyst and the
desired product 4aa was obtained in 31% yield (Table 1, entry 6).
Other commercially available metallocene complexes such as
Cp*TiCl3 and Cp2ZrCl2 were also used as Lewis acid catalysts for
the three-component sequence reactions, which demonstrated
that Cp2ZrCl2 was the best catalyst for this transformation
(Table 1, entries 9 and 10). In light of our previous ndings that
salicylato–titanocene complexes and phenols–titanocene
complexes function as organometallic Lewis acids,19 a selection
of oxygen donor ligands such as phenol and benzenesulfonic
acid were evaluated in the reaction of aniline, benzaldehyde and
methyl pyruvate (Table 1, entries 11 and 12). None of them
provide satisfactory results, which suggested that mono-
functional acids were unsuitable for this three-component
cascade reaction. With the assistance of o-aminobenzoic acid,
salicylic acid and phthalic acid, the Zr catalyst was slightly
activated and the tandem reaction afforded desired product
with 41%, 42% and 47% yields, respectively (Table 1, entries 13–
15). When glutaric acid and proline were introduced into this
triple catalytic system, the desired products were obtained in
29% and 28% yields (Table 1, entries 16 and 17). The above
results indicated that the aromatic diacids show up higher
activity than the aliphatic diacids and amino acids. We
hypothesized that higher activity of this catalytic system could
be achieved by employing multifunctional acids such as 2-
aminobenzene-1,4-disulfonic acid, trimellitic acid and 5-sulfo-
salicylic acid (Table 1, entries 18–20). To our pleased, trimellitic
Cp2ZrCl2/CuO
Cp2ZrCl2/CuO
Cp2ZrCl2/CuO
a
All reactions were conducted using the aniline (1.0 mmol),
benzaldehyde (1.0 mmol), methyl pyruvate (1.0 mmol), catalyst
(0.05 mmol, 5 mol%), Brønsted acid (0.05 mmol, 5 mol%), 50 ꢀC, 1 h.
b
Isolated yields. c 50 ꢀC, 2 h.
acid is the most potent catalyst among the three multifunc-
tional aromatic acids, which promotes the reaction to afford the
desired product in 54% yield, higher than 5-sulfosalicylic acid
and 2-aminobenzene-1,4-disulfonic acid. When the reaction
time extended to 2 h, the yield increases to 88%, but the yield
increased slightly with further extension of the reaction time
(Table 1, entry 21). Aer an extensive screening of the reaction
parameters (see the ESI†), the best yield of 4aa was obtained
when reaction was performed in i-propanol/water (3 : 1) at
ꢀ
60 C.
With the optimal reaction conditions in hand, we set out to
expand the generality and scope of Cp2ZrCl2, trimellitic acid
and CuO catalyzed three-component cascade reaction. 1 mmol
aldehyde, 1.1 mmol of anilines and 1.5 mmol of ketones with 5
moꢀl% of Cp2ZrCl2, 5 mol% of trimellitic acid, 5 mol% of CuO at
60 C for 2 h were operated as the typical selection. It is found
that the reaction proceeded smoothly with aldehydes and
aromatic amines bearing either electron-withdrawing or
donating groups (Table 2). The substituents with different
electron properties has little impact on this transformation,
such as anilines containing methyl (4ab), methoxyl (4ac) or
uorous (4ai) group, benzaldehydes with methyl (4ak), i-propyl
(4al), t-butyl (4am) or methoxyl (4ad) group and pyruvate with
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Table 2 Zirconocene dichloride/trimellitic acid/copper oxide cata-
lyzed three components tandem reaction of aldehydes, arylamines
and pyruvatesa,b
provided a convenient route for the construction of tricyclic–
quinolines.
Aliphatic
aldehydes
such
as
cyclo-
hexanecarbaldehyde was also readily introduced into this
reaction, reacted with 1-naphthylamine or 4-methoxy aniline
and methyl pyruvate afforded the desired products (4an, 4ao) in
91% and 90% yields, respectively. Heterocyclic furfuraldehyde
afforded the desired product in 91% yield (4ap). 1-Naph-
thaldehyde reacted with aniline and methyl pyruvate or ethyl
pyruvate under standard conditions afforded the multiply
substituted quinolines in 92% and 91% yield (4aq and 4ar). As
expected, m-substituted aniline and aldehyde (4as) produced
desired quinoline in 92% yield. Gratifyingly, the sterically
hindered ortho-substituted anilines (4at) still furnished the
desired product in more than 90% yield.
The zirconocene dichloride/trimellitic acid/CuO cooperative
and relay catalytic system was successfully applied in the three-
component coupling sequence reaction of aliphatic ketones
and aromatic ketones under the optimized conditions (Table 3).
The reaction results had not signicantly effected by aliphatic
ketones. The catalytic sequence reaction of 2-butanone with
benzaldehyde and 1-naphthylamine afforded the products (4bb)
in 93% yields, whereas other chain ketones including 2-pen-
tone, 2-hexanone and 2-heptanone afforded 2,4-substituted
quinolines in 91–93% yield (4bd), (4be), (4bf). Cyclic ketones
such as cyclohexanone (4bg) was also readily introduced into
this reaction, the desired product being formed with yield of
96%. Various halogens, such as uorine, chlorine, bromine,
iodine and electron-donating groups such as methyl were all
tolerated in this reaction, afforded the products with 91–94%
yields (4bh, 4bi, 4bj, 4bk and 4be). This triple cooperative and
relay catalytic system were also applied in the three-component
cascade reaction of aromatic ketone, such as anilines, benzal-
dehyde reacted with acetophenone afforded 2,4-diphenylqui-
noline in 90% and 91% yield(4bl and 4bm), albeit with longer
reaction time (12 h). To our pleased, chain aldehyde can also be
used as substrate for this reaction afforded 6-methoxy-4-ethyl-2-
propylquinoline in 90% yield with 12 h(4bn). More importantly,
this cooperative and relay catalytic system for synthesis of
substituted quinoline could be easily scaled up and the desired
disubstituted quinoline was obtained in 92% yield (Scheme 2).
To get more information about the reaction mechanism,
several control experiments (Table 4) and parallel experiment
(Scheme 3) were set up under the standard conditions. The
three components cascade reaction of aniline, benzaldehyde
and methyl pyruvate without catalyst or with 5 mol% CuO did
a
All reactions were conducted using aldehyde (1.0 mmol); arylamine
(1.1 mmol); pyruvate (1.5 mmol); Cp2ZrCl2 (0.05 mmol, 5 mol%); CuO
(0.05 mmol, 5 mol%); trimellitic acid (0.05 mmol,
5 mol%); i-
PrOH : H2O (3 : 1, 0.5 mL); all reactions were carried out at 60 ꢀC for
2 h. b Isolated yield.
methyl or ethyl group. Aniline with methyl (4ab) and methoxyl
(4ac) substituents led to the excellent results (90–91%), when
benzaldehyde and methyl pyruvate were used. The p-substitu-
ents of anilines were changed from methyl (4ae), i-propyl (4af),
t-butyl (4ag) to methoxyl (4ah) reacted with 4-methox-
ybenzaldehyde and methyl pyruvate, the yields of the conden-
sation reaction were 93–95%. Under the similar condition,
treating 4-uroaniline and benzaldehyde with methyl pyruvate
afforded the substituted quinoline (4ai) in 90% yield. Benzal-
dehydes with methoxyl (4aj), methyl (4ak), i-propyl (4al) or t-
butyl (4am) substituents obtained 92–94% yields when they
reacted with 1-naphthylamine and methyl pyruvate, which
ꢀ
not get the desired product at 60 C for 2 h (Table 4, entries 1
and 2). In the presence of 5 mol% trimellitic acid, three-
component sequence reaction afforded the desired quinoline
in 14% yield (Table 4, entry 3). With addition of 5 mol% Cp2-
ZrCl2 in the reaction only obtained 17% yield of quinoline
(Table 4, entry 4), which eliminated the possibility that i-prop-
anol or water coordination with zirconocene dichloride released
HCl promotes this reaction. With the assistance of 5 mol%
Cp2ZrCl2 and 5 mol% trimellitic acid, the desired product was
isolated in 44% yield (Table 4, entries 5). Adding 5 mol% CuO
into this catalytic system, the yield of 4-methoxycarbonyl-2-
phenylquinoline was up to 92% (Table 4, entry 6). It is clear
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Table 3 Zirconocene dichloride/trimellitic acid/copper oxide cata- Table 4 Control experimenta
lyzed three components tandem reaction of aldehydes, arylamines
and ketonesa,b
Trimellitic acid
(mol%)
Cp2ZrCl2
(mol%)
Entry
CuO (mol%)
Yieldb (%)
1
2
3
4
5
6
—
5
—
—
—
5
—
—
5
—
5
—
—
—
5
5
5
ND
ND
14
17
44
5
92
a
Reaction conditions: a mixture of aldehyde (1.0 mmol); aniline (1.1
mmol); methyl pyruvate (1.5 mmol); i-PrOH : H2O (3 : 1, 0.5 mL); all
reactions were carried out at 60 ꢀC for 2 h, ND ¼ no detected.
b
Isolated yield.
Scheme 3 The paralleled experiment.
catalytic species (Scheme 3a). This control experiments and
parallel experiment indicated that zirconocene dichloride and
trimellitic acid demonstrated good compatibility with CuO in
three components cascade reaction, which presented a new
cooperative and relay catalysis system for synthesis of multiply
substituted quinolines from anilines, aldehydes and ketones. N-
Arylimines and methyl pyruvate under the standard condition
also afforded the desired product in 92% yield (Scheme 3b),
which indicated that the imine was rstly formed in this reac-
tion, followed by Mannich addition and cyclization.
a
Reaction conditions: a mixture of aldehyde (1.0 mmol); arylamine (1.1
The interaction of zirconocene dichloride and trimellitic
acid in three-component coupling sequence reaction for
synthesis of substituted quinolines were investigated by 1H
NMR and HRMS analyses. 1H NMR experiments, which were
conducted using Cp2ZrCl2 in D2O (Fig. 1), showed that no
coordination occurred and only one Cp singlet of Cp2ZrCl2 at
d ¼ 6.49 ppm ( ) was detected. When adding 1 equiv. trimellitic
acid, a new zirconocene complex species II formed, which
resonated at d ¼ 6.57 ppm ( ). Intensity of the Cp singlet at d ¼
6.57 didn't increase as the time went on. Adding 2 equiv. aniline
into this transformation, zirconocene dichloride (I) was
consumed gradually in D2O and transformed to a new zirco-
nocene species Cp2Zr(OOC)2PhCOOH (II).20 The above conclu-
sion was also certied by HRMS analysis, corresponding to the
[II + H]+ signal at m/z 428.9921 (Fig. S3–S6†). These observations
clearly demonstrated that during the reaction, zirconocene
dichloride readily converted into zirconocene complexes II, and
presumably it was the organometallic binary acid catalyst.
mmol); ketone (1.5 mmol); Cp2ZrCl2 (0.05 mmol, 5 mol%); CuO
(0.05 mmol, 5 mol%); trimellitic acid (0.05 mmol,
5 mol%); i-
PrOH : H2O (3 : 1,0.5 mL), 60 ꢀC for 8 h. b Isolated yield. c 12 h.
Scheme 2 Scaled up for the gram scale.
that the high efficiency of the coupling sequence reaction
should not be attributed to zirconocene dichloride, trimellitic
acid or CuO individually. We proposed that the cooperation of
zirconocene dichloride, trimellitic acid and the relay of CuO,
resulted in the efficient cooperative and relay catalysis. The
control experiments using 10 mol% HCl afforded the
substituted quinolines in 10% yield, indicating HCl was not
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than Cu(0) due to its coordination with H2O. Active Cu(0)$H2O
is facilely oxidized by oxygen in the air to restore CuO, which
enters next catalytic cycle.
Conclusions
In summary, we have developed a triple cooperative and relay
catalysis system that the combination of organometallic Lewis
acids and Brønsted acids with metal were developed for three-
component cascade Mannich addition/C–C formative
cyclization/oxidation reaction. The green syntheses of
substituted quinolines were achieved from readily available
anilines, aldehydes and aromatic or aliphatic ketones in good to
excellent yields. 1H NMR and HRMS analysis unveiled that
Cp2Zr(OOC)2PhCOOH was catalytic specis, which signicantly
accelerated the condensation of aldehydes, anilines and
ketones into dihydroquinolines with i-propanol and water as
solvent. Meanwhile, CuO catalyzed oxydehydrogenation of
dihydroquinolines to generate quinolines.
Fig. 1 Partial 400 MHz 1H NMR spectra (D2O) of a mixture of Cp2ZrCl2
(1.0 equiv.) and trimellitic acid (1.0 equiv.) with PhNH2 (2.0 equiv).
6.49 ppm I [Cp2ZrCl2]; 6.57 ppm II Cp2Zr(OOC)2PhCOOH.
1
Taken HNMR, HRMS, control experiments and paralleled
experiments together, a plausible catalytic cycle of zirconocene
dichloride/trimellitic acid/CuO triple cooperative and relay
catalytic system in three-component sequence reaction was
illustrated in Scheme 4. Zirconocene dichloride I pre-catalyst
activated by trimellitic acid and transformed to binary acid
catalyst II in the presence of aniline. The incoming ketone
coordinated to Zr center of II. In transition state A, enolation
was accelerated as the carbonyl coordinated to oxytropic Zr and
methyl formed hydrogen bond with the carboxyl oxygen of tri-
mellitic acid. The carbon–carbon bond formation is illustrated
in transition state A. The coordinated enolate then undergoes
addition to the aldimine, which is activated by H+ from the
other carboxyl group of trimellitic acid. This transition state
show cases the cooperative nature of this binary acid catalytic
system. In transition state B, the electron-rich benzene ring
attacked the keto-carbonyl group to formed the intermediate
dihydroquinoline. Aer the dihydroquinoline was released, the
zirconocene catalyst II was regenerated from the transition state
B by coordination of the carboxyl group again. The coordination
of the dihydroquinoline and CuO may induce a combination of
electron transfer and intramolecular rearrangement to give the
desired product21 and Cu(0)$H2O, which should be more stable
Experimental
General methods and materials
All manipulations were performed in an atmosphere of air. All
reagents were purchased from the commercial approaches and
used without further purication unless specied otherwise. 1H
and 13C NMR spectra were recorded on a Bruker EQUINX55 (400
1
1
MHz for H; 101 MHz for 13C) spectrometer in CDCl3. For H
NMR, tetramethylsilane (TMS) served as internal standard (d ¼
0) and 1H NMR chemical shis are reported in ppm downeld
of tetramethylsilane and referenced to residual solvent peak
(CDCl3 at 7.26 ppm) unless otherwise noted. The data are re-
ported as follows: chemical shi, integration, multiplicity (s ¼
singlet, d ¼ doublet, t ¼ triplet, q ¼ quartet and m ¼ multiplet),
and coupling constant in Hz. For 13C NMR, CDCl3 was used as
internal standard (d ¼ 77.0) and spectra were obtained with
complete proton decoupling. HRMS (ESI) analysis was per-
formed and (HRMS) data were reported with sodium mass/
charge (m/z) ratios as values in atomic mass units. Column
chromatography was performed on silica gel (230–400 mesh)
and analytical thin layer chromatography was carried out using
250 mm commercial silica gel plates. Visualization of the
developed chromatogram was performed by UV absorbance and
stained with an iodine vapor.
Typical procedures for synthesis of substituted quinolones
A 10 mL test tube equipped with a magnetic stirrer and
a septum, was charged with aldehyde (1.0 mmol), amine (1.1
mmol), and the ketone (1.5 mmol) in one portion. Cp2ZrCl2
(0.05 mmol, 5 mol%), CuO (0.05 mmol, 5 mol%) and trimellitic
acid (0.05 mmol, 5 mol%) were stirred in i-PrOH : H2O (3 : 1) 0.5
mL. The reaction mixture was heated to 60 ꢀC and stirred until
the reaction was completed as indicated by TLC, then the
reaction mixture was quenched with distilled water (5.0 mL).
The aqueous phase was extracted with dichloride methane (3–5
mL), dried over Na2SO4 and concentrated in vacuo to give the
Scheme 4 Proposed mechanism of zirconocene dichloride/trimellitic
acid/CuO cooperative and relay catalysis for synthesis of substituted
quinolines.
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crude product. The crude product was puried by ash column (petroleum ether/ethyl acetate ¼ 10 : 1); IR (KBr): 1732, 1595,
chromatography on neutral silica gel (ethyl acetate:petroleum 1349, 1251, 1205, 1152, 774, 698 cmꢁ1 1H NMR (400 MHz,
ether). Full experimental details and characterization data for CDCl3) d 8.54 (d, J ¼ 1.4 Hz, 1H), 8.33 (s, 1H), 8.15 (s, 3H), 7.66
;
all quinolines product are included in the ESI.†
(d, J ¼ 1.8 Hz, 1H), 7.05 (d, J ¼ 8.8 Hz, 2H), 4.07 (s, 3H), 3.89 (s,
4-Methoxycarbonyl-2-phenylquinoline (4aa). Yield, 92%; 3H), 3.14 (d, J ¼ 13.6, 6.8 Hz, 1H), 1.37 (d, J ¼ 6.9 Hz, 6H). 13
C
primrose yellow solid; mp 217–218 ꢀC; Rf 0.51 (petroleum ether/ NMR (101 MHz, CDCl3) d 167.11, 160.97, 155.45, 148.29, 148.21,
ethyl acetate ¼ 10 : 1); IR (KBr): 1728, 1593, 1346, 1250, 1203, 134.92, 131.60, 130.00, 129.50, 128.72, 123.75, 121.70, 119.84,
1
1149, 771, 694 cmꢁ1; H NMR (400 MHz, CDCl3) d 8.75 (d, J ¼ 114.29, 55.41, 52.60, 34.56, 23.88. HRMS (ESI): m/z called for
8.5 Hz, 1H), 8.41 (s, 1H), 8.22 (s, 3H), 7.77 (s, 1H), 7.63 (s, 1H), C21H21NO3 [M + H]+, 336.1594; found, 336.1589.
7.55 (s, 2H), 7.50 (d, J ¼ 7.1 Hz, 1H), 4.07 (s, 3H). 13C NMR (101
6-t-Butyl-4-methoxycarbonyl-2-[4-methoxyl]phenylquinoline
ꢀ
MHz, CDCl3) d 166.85, 156.71, 149.29, 138.81, 135.61, 130.35, (4ag). Yield, 95%; yellow solid; mp 207–208 C; Rf 0.50 (petro-
129.91, 129.74, 128.94, 127.81, 127.48, 125.43, 124.00, 120.34, leum ether/ethyl acetate ¼ 10 : 1); IR (KBr): 1733, 1596, 1349,
52.72. HRMS (ESI): m/z called for C17H13NO2 [M + H]+, 264.1019; 1252, 1205, 1143, 774, 698 cmꢁ1 1H NMR (400 MHz, CDCl3)
;
found, 264.1026.
d 8.72 (d, J ¼ 2.0 Hz, 1H), 8.34 (s, 1H), 8.15 (dd, J ¼ 15.5, 8.8 Hz,
6-Methyl-4-methoxycarbonyl-2-phenylquinoline (4ab). Yield, 3H), 7.85 (dd, J ¼ 8.9, 2.1 Hz, 1H), 7.05 (d, J ¼ 8.8 Hz, 2H), 4.08
93%; primrose yellow solid; mp 212–213 ꢀC; Rf 0.45 (petroleum (s, 3H), 3.89 (s, 3H), 1.46 (s, 9H). 13C NMR (101 MHz, CDCl3)
ether/ethyl acetate ¼ 10 : 1); IR (KBr): 1730, 1608, 1352, 1254, d 167.12, 160.97, 155.62, 150.36, 147.90, 135.08, 131.62, 129.59,
1209, 1153, 775, 698 cmꢁ1; 1H NMR (400 MHz, CDCl3) d 8.51 (s, 128.73, 123.44, 120.40, 119.88, 114.29, 55.41, 52.61, 35.29,
1H), 8.35 (s, 1H), 8.19 (d, J ¼ 7.3 Hz, 2H), 8.12 (d, J ¼ 8.6 Hz, 1H), 31.22. HRMS (ESI): m/z called for C21H21NO3 [M + H]+, 350.1751;
7.61–7.57 (m, 1H), 7.54 (s, 2H), 7.47 (s, 1H), 4.06 (s, 3H), 2.58 (s, found, 350.1756.
3H). 13C NMR (101 MHz, CDCl3) d 166.97, 155.72, 147.94,
6-Methoxy-4-methoxycarbonyl-2-[4-methoxyl]phenylquinoline
ꢀ
138.90, 138.01, 134.81, 132.18, 129.99, 129.53, 128.90, 127.36, (4ah). Yield, 95%; yellow solid; mp 210–211 C; Rf 0.48 (petro-
124.24, 124.02, 120.23, 52.65, 22.13. HRMS (ESI): m/z called for leum ether/ethyl acetate ¼ 10 : 1); IR (KBr): 1725, 1591, 1343,
C
18H15NO2 [M + H]+, 278.1176; found, 278.1177.
1247, 1201, 1146, 767, 691 cmꢁ1 1H NMR (400 MHz, CDCl3)
;
6-Methoxy-4-methoxycarbonyl-2-phenylquinoline
(4ac). d 8.38 (s, 1H), 8.20 (d, J ¼ 2.3 Hz, 1H), 8.14 (d, J ¼ 8.6 Hz, 2H), 8.08
Yield, 95%; primrose yellow solid; mp 215–219 ꢀC; Rf (d, J ¼ 9.2 Hz, 1H), 7.41 (d, J ¼ 9.2 Hz, 1H), 7.05 (d, J ¼ 8.6 Hz,
0.47(petroleum ether/ethyl acetate ¼ 10 : 1); IR (KBr): 1726, 2H), 4.06 (s, 3H), 3.98 (s, 3H), 3.89 (s, 3H). 13C NMR (101 MHz,
1591, 1344, 1253, 1206, 1152, 774, 697 cmꢁ1; 1H NMR (400 MHz, CDCl3) d 167.06, 160.79, 158.78, 153.78, 145.70, 133.23, 131.59,
CDCl3) d 8.40 (s, 1H), 8.21 (d, J ¼ 2.7 Hz, 1H), 8.16 (d, J ¼ 7.5 Hz, 131.52, 128.47, 125.15, 122.65, 120.32, 114.28, 103.32, 55.57,
2H), 8.10 (d, J ¼ 9.2 Hz, 1H), 7.52 (s, 2H), 7.42 (d, J ¼ 2.6 Hz, 2H), 55.40, 52.55. HRMS (ESI): m/z called for C19H17NO4 [M + H]+,
4.04 (s, 3H), 3.97 (s, 3H). 13C NMR (101 MHz, CDCl3) d 166.91, 324.1230; found, 324.1234.
159.05, 154.03, 145.70, 138.92, 133.17, 131.72, 129.29, 128.88,
6-Fluoro-4-methoxycarbonyl-2-[4-methoxyl]phenylquinoline
ꢀ
127.14, 125.55, 122.79, 120.69, 103.22, 55.57, 52.56. HRMS (ESI): (4ai). Yield, 90%; yellow solid; mp 230–231 C; Rf 0.46 (petro-
m/z called for C17H13NO2 [M + H]+, 294.1130; found, 294.1125. leum ether/ethyl acetate ¼ 10 : 1); IR (KBr): 1723, 1585, 1342,
4-Methoxycarbonyl-2-[4-methoxyl]phenylquinoline
(4ad). 1245, 1200, 1144, 767, 691 cmꢁ1 1H NMR (400 MHz, CDCl3)
;
Yield, 92%; primrose yellow solid; mp 220–221 ꢀC; Rf 0.49 d 8.87 (d, J ¼ 8.5 Hz, 1H), 8.57 (s, 1H), 8.43 (s, 3H), 7.92 (s, 1H),
(petroleum ether/ethyl acetate ¼ 10 : 1); IR (KBr): 1731, 1596, 7.89 (s, 1H), 7.74 (s, 2H), 7.70 (d, J ¼ 7.1 Hz, 1H), 4.11 (s, 3H). 13
C
1349, 1253, 1206, 1152, 778, 698 cmꢁ1 1H NMR (400 MHz, NMR (101 MHz, CDCl3) d 176.91, 164.83, 158.21, 148.78, 144.31,
;
CDCl3) d 8.71 (d, J ¼ 8.3 Hz, 1H), 8.36 (s, 1H), 8.18 (d, J ¼ 8.9 Hz, 140.25, 138.90, 138.60, 137.94, 138.83, 138.45, 134.39, 133.05,
3H), 7.75 (d, J ¼ 1.2 Hz, 1H), 7.59 (s, 1H), 7.06 (d, J ¼ 8.8 Hz, 2H), 129.33, 51.65. HRMS (ESI): m/z called for C17H12FNO2 [M + H]+,
4.07 (s, 3H), 3.89 (s, 3H). 13C NMR (101 MHz, CDCl3) d 166.96, 282.1019; found, 282.1012.
161.15, 156.27, 149.28, 135.50, 131.38, 130.10, 129.83, 128.85,
4-Methoxycarbonyl-2-[4-methoxylphenyl]benzoquinoline
ꢀ
127.39, 125.40, 123.67, 119.93, 114.33, 55.42, 52.70. HRMS (ESI): (4aj). Yield, 94%; yellow solid; mp 213–214 C; Rf 0.49 (petro-
m/z called for C18H15NO3 [M + H]+, 294.1125; found, 294.1130. leum ether/ethyl acetate ¼ 10 : 1); IR (KBr): 1733, 1597, 1351,
6-Methyl-4-methoxycarbonyl-2-[4-methoxyl]phenylquinoline 1255, 1209, 1154, 778, 697 cmꢁ1
;
1H NMR (400 MHz, CDCl3)
ꢀ
(4ae). Yield, 93%; yellow solid; mp 224–225 C; Rf 0.52 (petro- d 9.48 (d, J ¼ 7.8 Hz, 1H), 8.59 (d, J ¼ 9.2 Hz, 1H), 8.42 (s, 1H),
leum ether/ethyl acetate ¼ 10 : 1); IR (KBr): 1729, 1596, 1348, 8.33 (d, J ¼ 8.6 Hz, 2H), 7.90 (d, J ¼ 7.5 Hz, 1H), 7.85 (d, J ¼
1254, 1207, 1151, 773, 696 cmꢁ1
;
1H NMR (400 MHz, CDCl3) 9.2 Hz, 1H), 7.73 (s, 2H), 7.09 (d, J ¼ 8.6 Hz, 2H), 4.09 (s, 3H),
d 8.48 (s, 1H), 8.32 (s, 1H), 8.16 (d, J ¼ 8.8 Hz, 2H), 8.08 (d, J ¼ 3.91 (s, 3H). 13C NMR (101 MHz, CDCl3) d 167.19, 161.03,
8.6 Hz, 1H), 7.59 (dd, J ¼ 8.6, 1.6 Hz, 1H), 7.26 (s, 2H), 7.05 (d, J 154.45, 147.28, 135.39, 133.48, 131.59, 131.52, 128.69, 128.52,
¼ 8.8 Hz, 2H), 4.07 (s, 3H), 3.90 (s, 3H), 2.58 (s, 3H). 13C NMR 127.59, 126.97, 125.14, 122.37, 122.07, 119.02, 114.25, 55.40,
(101 MHz, CDCl3) d 190.81, 167.07, 160.97, 155.31, 147.91, 52.70. HRMS (ESI): m/z called for C22H17NO3 [M + H]+, 344.1281;
137.53, 134.73, 132.07, 131.98, 131.48, 129.76, 128.69, 124.22, found, 344.1286.
123.67, 119.81, 114.31, 114.28, 55.39, 52.62, 22.08. HRMS (ESI):
4-Methoxycarbonyl-2-[4-methylphenyl]benzoquinoline (4ak).
m/z called for C19H17NO3 [M + H]+, 308.1281; found, 308.1289. Yield, 93%; yellow solid; mp 225–226 ꢀC; Rf 0.53 (petroleum
6-i-Propyl-4-methoxycarbonyl-2-[4-methoxyl]phenylquinoline ether/ethyl acetate ¼ 10 : 1); IR (KBr): 1736, 1598, 1352, 1254,
(4af). Yield, 93%; yellow solid; mp 210–211 ꢀC; Rf 0.51 1208, 1155, 778, 697 cmꢁ1; 1H NMR (400 MHz, CDCl3) d 9.50 (d, J
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¼ 7.8 Hz, 1H), 8.60 (d, J ¼ 9.2 Hz, 1H), 8.45 (s, 1H), 8.27 (d, J ¼ J ¼ 2.6 Hz, 1H), 8.06 (d, J ¼ 9.3 Hz, 1H), 7.62 (s, 1H), 7.40 (dd, J ¼
7.8 Hz, 2H), 7.86 (d, J ¼ 9.2 Hz, 2H), 7.74 (s, 2H), 7.38 (d, J ¼ 9.2, 2.6 Hz, 1H), 7.19 (d, J ¼ 3.3 Hz, 1H), 6.98 (s, 1H), 4.05 (s, 3H),
7.7 Hz, 2H), 4.09 (s, 3H), 2.47 (s, 3H). 13C NMR (101 MHz, CDCl3) 3.97 (s, 3H). 13C NMR (101 MHz, CDCl3) d 169.16, 168.26,
d 167.22, 154.89, 147.37, 139.75, 136.16, 135.51, 133.48, 131.66, 166.72, 159.03, 153.30, 146.21, 145.46, 143.92, 133.20, 131.35,
129.65, 128.80, 128.54, 127.61, 127.25, 127.06, 125.19, 122.36, 125.50, 122.95, 119.44, 112.27, 109.55, 103.47, 55.59, 52.60.
119.38, 52.73, 21.40. HRMS (ESI): m/z called for C22H17NO3 [M + HRMS (ESI): m/z called for C16H13NO4 [M + H]+, 284.0917;
H]+, 328.1332; found, 328.1342.
found, 284.0922.
4-Methoxycarbonyl-2-[4-i-propylphenyl]benzoquinoline (4al).
4-Methoxycarbonyl-2-naphthylquinoline (4aq). Yield, 92%;
Yield, 92%; yellow solid; mp 229–230 ꢀC; Rf 0.52 (petroleum ether/ primrose yellow solid; mp 233–234 ꢀC; Rf 0.47 (petroleum ether/
ethyl acetate ¼ 10 : 1); IR (KBr): 1721, 1583, 1340, 1244, 1197, 1141, ethyl acetate ¼ 10 : 1); IR (KBr): 1717, 1585, 1340, 1242, 1195,
1
1
762, 683 cmꢁ1; H NMR (400 MHz, CDCl3) d 9.50 (d, J ¼ 8.0 Hz, 1141, 763, 685 cmꢁ1; H NMR (400 MHz, CDCl3) d 8.88 (d, J ¼
1H), 8.61 (d, J ¼ 9.2 Hz, 1H), 8.46 (s, 1H), 8.30 (d, J ¼ 8.2 Hz, 2H), 8.5 Hz, 1H), 8.32 (d, J ¼ 8.4 Hz, 1H), 8.27 (s, 1H), 8.16 (d, J ¼
7.91–7.83 (m, 2H), 7.77–7.68 (m, 2H), 7.45 (d, J ¼ 8.2 Hz, 2H), 4.08 8.1 Hz, 1H), 8.02–7.96 (m, 2H), 7.85 (t, J ¼ 7.6 Hz, 1H), 7.79–7.71
(s, 3H), 3.04 (dt, J ¼ 13.8, 6.9 Hz, 1H), 1.36 (d, J ¼ 7.0 Hz, 6H). 13
C
(m, 2H), 7.64 (t, J ¼ 7.7 Hz, 1H), 7.54 (dt, J ¼ 13.4, 6.6 Hz, 2H),
NMR (101 MHz, CDCl3) d 167.20, 154.99, 150.66, 147.39, 4.07 (s, 3H). 13C NMR (101 MHz, CDCl3) d 166.73, 158.97,
136.64, 135.47, 133.48, 131.68, 128.80, 128.53, 127.60, 127.43, 149.15, 137.87, 135.19, 134.05, 131.14, 130.33, 130.07, 129.55,
127.04, 125.22, 122.39, 122.37, 119.50, 52.71, 34.07, 23.97. 128.52, 127.99, 126.87, 126.13, 125.53, 124.50, 123.87, 52.76.
HRMS (ESI): m/z called for C24H21NO3 [M + H]+, 356.1645; HRMS (ESI): m/z called for C21H15NO3 [M + H]+, 314.1176;
found, 356.1650.
found, 314.1180.
4-Methoxycarbonyl-2-[4-t-butylphenyl]benzoquinoline (4am).
4-Ethoxycarbonyl-2-naphthylquinoline (4ar). Yield, 91%;
Yield, 94%; primrose yellow solid; mp 215–216 ꢀC; Rf 0.48 yellow solid; mp 235–236 ꢀC; Rf 0.46 (petroleum ether/ethyl
(petroleum ether/ethyl acetate ¼ 10 : 1); IR (KBr): 1721, 1585, 1342, acetate ¼ 10 : 1); IR (KBr): 1726, 1589, 1343, 1247, 1201, 1145,
1245, 1294, 1140, 765, 685 cmꢁ1; 1H NMR (400 MHz, CDCl3) d 9.51 763, 688 cmꢁ1; 1H NMR (400 MHz, CDCl3) d 8.85 (d, J ¼ 8.6 Hz,
(d, J ¼ 7.9 Hz, 1H), 8.61 (d, J ¼ 9.2 Hz, 1H), 8.47 (s, 1H), 8.30 (d, J ¼ 1H), 8.29 (d, J ¼ 8.3 Hz, 1H), 8.23 (s, 1H), 8.13 (d, J ¼ 8.2 Hz, 1H),
8.4 Hz, 2H), 7.88 (s, 2H), 7.78–7.71 (m, 2H), 7.62 (d, J ¼ 8.4 Hz, 2H), 8.01–7.94 (m, 2H), 7.83 (s, 1H), 7.75 (d, J ¼ 0.9 Hz, 2H), 7.65–7.60
4.09 (s, 3H), 1.43 (s, 9H). 13C NMR (101 MHz, CDCl3) d 167.22, (m, 1H), 7.53 (d, J ¼ 1.8 Hz, 2H), 4.54 (s, 2H), 1.46 (s, 3H). 13C
154.97, 152.90, 147.42, 136.24, 135.51, 133.49, 131.69, 128.82, NMR (101 MHz, CDCl3) d 166.34, 158.98, 149.12, 137.94, 135.69,
128.54, 127.60, 127.16, 125.90, 125.22, 122.40, 122.37, 119.54, 134.04, 131.17, 130.32, 130.02, 129.51, 128.50, 127.94, 126.85,
52.73, 34.82, 31.33. HRMS (ESI): m/z called for C25H23NO3 [M + H]+, 126.13, 125.39, 124.30, 123.90, 61.93, 14.31. HRMS (ESI): m/z
370.1802; found, 370.1805.
called for C21H21NO3 [M + H]+, 328.1332; found, 328.1335.
7-Methoxy-4-methoxycarbonyl-2-phenylquinoline (4as).
4-Methoxycarbonyl-2-cyclohexylbenzoquinoline (4an). Yield,
91%; primrose yellow solid; mp 213–214 ꢀC; Rf 0.47 (petroleum Yield, 92%; primrose yellow solid; mp 215–216 ꢀC; Rf 0.52
ether/ethyl acetate ¼ 10 : 1); IR (KBr): 1729, 1595, 1345, 1253, (petroleum ether/ethyl acetate ¼ 10 : 1); IR (KBr): 1726, 1589,
1204, 1151, 774, 698 cmꢁ1; 1H NMR (400 MHz, CDCl3) d 9.42 (d, J 1345, 1248, 1186, 1146, 769, 682 cmꢁ1 1H NMR (400 MHz,
;
¼ 7.7 Hz, 1H), 8.57 (d, J ¼ 9.2 Hz, 1H), 7.89 (s, 2H), 7.85 (d, J ¼ CDCl3) d 8.67 (d, J ¼ 9.3 Hz, 1H), 8.27 (s, 1H), 8.21–8.17 (m, 2H),
9.3 Hz, 1H), 7.71 (d, J ¼ 1.7 Hz, 2H), 4.06 (s, 3H), 3.04 (s, 1H), 7.55 (s, 3H), 7.52–7.47 (m, 1H), 7.30 (d, J ¼ 2.7 Hz, 1H), 4.07 (s,
2.14 (d, J ¼ 11.9 Hz, 2H), 1.96 (d, J ¼ 12.9 Hz, 2H), 1.80 (d, J ¼ 3H), 4.00 (s, 3H). 13C NMR (101 MHz, CDCl3) d 166.95, 160.85,
11.7 Hz, 2H), 1.53 (d, J ¼ 12.8 Hz, 4H). 13C NMR (101 MHz, 157.16, 151.27, 139.01, 135.33, 129.61, 128.90, 127.44, 126.52,
CDCl3) d 167.41, 164.84, 135.05, 133.30, 131.54, 128.28, 127.48, 120.95, 119.26, 118.10, 108.10, 55.55, 52.67. HRMS (ESI): m/z
126.90, 125.07, 122.40, 120.96, 52.60, 46.99, 32.91, 26.58, 26.18. called for C18H15NO3 [M + H]+, 294.1125; found, 294.1133.
HRMS (ESI): m/z called for C21H21NO3 [M + H]+, 320.1645;
found, 320.1648.
8-Methoxy-4-methoxycarbonyl-2-phenylquinoline
(4at).
Yield, 90%; primrose yellow solid; mp 217–218 ꢀC; Rf 0.49
6-Methoxy-4-methoxycarbonyl-2-cyclohexylquinoline (4ao). (petroleum ether/ethyl acetate ¼ 10 : 1); IR (KBr): 1724, 1588,
Yield, 90%; primrose yellow solid; mp 203–204 ꢀC; Rf 0.50 1342, 1247, 1187, 1141, 765, 684 cmꢁ1 1H NMR (400 MHz,
;
(petroleum ether/ethyl acetate ¼ 10 : 1); IR (KBr): 1733, 1598, CDCl3) d 8.37 (s, 1H), 8.25 (d, J ¼ 8.5 Hz, 1H), 8.20 (d, J ¼ 8.3 Hz,
1349, 1253, 1206, 1152, 775, 697 cmꢁ1
;
1H NMR (400 MHz, 2H), 7.51 (s, 1H), 7.10 (d, J ¼ 7.6 Hz, 1H), 7.04 (d, J ¼ 8.3 Hz, 2H),
CDCl3) d 8.17 (d, J ¼ 2.7 Hz, 1H), 7.99 (d, J ¼ 9.2 Hz, 1H), 7.85 (s, 4.11 (s, 3H), 4.06 (s, 3H), 3.89 (s, 3H). 13C NMR (101 MHz, CDCl3)
1H), 7.37 (dd, J ¼ 9.2, 2.8 Hz, 1H), 4.03 (s, 3H), 3.96 (s, 3H), 2.01 d 167.08, 161.07, 155.59, 155.10, 141.29, 135.71, 131.58, 128.94,
(s, 1H), 1.77–1.59 (m, 4H), 1.33–1.24 (m, 4H), 1.01–0.89 (m, 2H). 127.54, 124.77, 120.21, 117.13, 114.27, 108.38, 56.25, 55.39,
13C NMR (101 MHz, CDCl3) d 167.13, 163.49, 158.51, 145.18, 52.69. HRMS (ESI): m/z called for C19H17NO4 [M + H]+, 323.1154;
133.01, 130.96, 130.88, 125.14, 122.22, 121.43, 103.32, 55.53, found, 323.1158.
52.43, 47.08, 32.81, 26.51, 26.04. HRMS (ESI): m/z called for
18H21NO3 [M + Na]+, 322.1414; found, 322.1421.
4-Ethoxyl-2-[4-methylphenyl]benzoquinoline (4bb). Yield,
93%; primrose yellow solid; mp 221–225 ꢀC; Rf 0.43 (petroleum
C
6-Methoxy-4-methoxycarbonyl-2-furylquinoline (4ap). Yield, ether/ethyl acetate ¼ 10 : 1); IR (KBr): 3078, 2962, 2931, 1611,
91%; claybank; mp 210–211 C; Rf 0.51 (petroleum ether/ethyl 1510, 1459 cmꢁ1
;
1H NMR (400 MHz, CDCl3) d 9.52 (d, J ¼
ꢀ
acetate ¼ 10 : 1); IR (KBr): 1720, 1583, 1340, 1243, 1194, 1142, 8.0 Hz, 1H), 8.32 (d, J ¼ 8.8 Hz, 2H), 7.91 (d, J ¼ 4.9 Hz, 2H), 7.81
764, 683 cmꢁ1; 1H NMR (400 MHz, CDCl3) d 8.35 (s, 1H), 8.20 (d, (d, J ¼ 7.4 Hz, 4H), 7.09 (d, J ¼ 8.8 Hz, 2H), 3.91 (s, 3H), 3.18 (s,
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2H), 1.46 (s, 3H). 13C NMR (101 MHz, CDCl3) d 160.67, 154.90,
150.16, 146.21, 133.54, 132.75, 132.34, 128.72, 127.84, 127.53,
126.65, 125.17, 123.52, 120.95, 117.52, 114.16, 55.41, 25.84,
14.64. HRMS (ESI): m/z called for C21H21NO3 [M + H]+, 336.1594;
found, 336.1589. HRMS (ESI): m/z called for C22H19NO [M + H]+,
314.1539; found, 314.1542.
4-Propyl-2-[4-methylphenyl]benzoquinoline (4bc). Yield,
94%; white solid; mp 229–221 ꢀC; Rf 0.45 (petroleum ether/ethyl
acetate ¼ 10 : 1); IR (KBr): 3076, 2957, 2929, 1597, 1498, 1456
cmꢁ1; 1H NMR (400 MHz, CDCl3) d 9.55 (d, J ¼ 8.1 Hz, 1H), 8.33
(d, J ¼ 8.8 Hz, 2H), 7.90 (s, 2H), 7.79 (s, 4H), 7.10 (d, J ¼ 8.8 Hz,
2H), 3.91 (s, 3H), 3.11 (s, 2H), 1.87 (d, J ¼ 7.6 Hz, 2H), 1.09 (s,
3H). 13C NMR (101 MHz, CDCl3) d 160.68, 154.66, 148.71,
133.55, 132.72, 132.35, 128.73, 127.86, 127.55, 126.66, 125.18,
123.74, 121.16, 118.48, 114.16, 55.41, 34.90, 23.71, 14.20. HRMS
(ESI): m/z called for C23H21NO [M + H]+, 328.1696; found,
328.1702.
6-Fluoro-4-butyl-2-phenylquinoline (4bh). Yield, 91%; white
solid; mp 245–246 ꢀC; Rf 0.43 (petroleum ether/ethyl acetate ¼
1
10 : 1); IR (KBr): 3070, 2951, 2922, 1592, 1491, 1453 cmꢁ1; H
NMR (400 MHz, CDCl3) d 7.96 (dd, J ¼ 7.5, 1.7 Hz, 2H), 7.46 (s,
2H), 7.16 (d, J ¼ 4.8 Hz, 2H), 7.08 (s, 2H), 5.95 (s, 1H), 2.37 (s,
2H), 1.52 (s, 2H), 1.32 (s, 2H), 0.86 (s, 3H). 13C NMR (101 MHz,
CDCl3) d 188.92, 167.07, 162.06, 159.61, 140.10, 134.50, 134.47,
130.86, 128.25, 127.38, 127.30, 127.04, 116.10, 92.83, 31.90,
30.34, 22.34, 13.63. HRMS (ESI): m/z called for C19H18FN [M +
H]+, 280.1455; found, 280.1457.
6-Chloro-4-butyl-2-phenylquinoline (4bi). Yield, 92%; white
solid; mp 237–238 ꢀC; Rf 0.45 (petroleum ether/ethyl acetate ¼
1
10 : 1); IR (KBr): 3071, 2953, 2924, 1593, 1491, 1452 cmꢁ1; H
NMR (400 MHz, CDCl3) d 7.97 (d, J ¼ 1.3 Hz, 2H), 7.47 (s, 2H),
7.36 (s, 2H), 7.13 (s, 2H), 5.97 (s, 1H), 2.41 (s, 2H), 1.53 (s, 2H),
1.34 (s, 2H), 0.87 (s, 3H). 13C NMR (101 MHz, CDCl3) d 189.04,
166.39, 139.99, 137.17, 131.43, 130.98, 129.30, 128.28, 127.07,
126.42, 93.37, 31.96, 30.33, 22.35, 13.68. HRMS (ESI): m/z called
for C19H18ClN [M + H]+, 296.1107; found, 296.1109.
6-Methyl-4-butyl-2-phenylquinoline (4bd). Yield, 91%; white
solid; mp 222–223 ꢀC; Rf 0.47 (petroleum ether/ethyl acetate ¼
1
10 : 1); IR (KBr): 3071, 2954, 2923, 1596, 1491, 1451 cmꢁ1; H
6-Bromo-4-butyl-2-phenylquinoline (4bj). Yield, 92%; white
solid; mp 240–241 ꢀC; Rf 0.47 (petroleum ether/ethyl acetate ¼
NMR (400 MHz, CDCl3) d 7.94 (s, 2H), 7.46 (s, 2H), 7.14 (d, J ¼
34.7 Hz, 4H), 5.92 (s, 1H), 2.38 (s, 5H), 1.55 (s, 2H), 1.33 (s, 2H),
0.87 (s, 3H). 13C NMR (101 MHz, CDCl3) d 188.57, 167.29,
140.31, 135.88, 135.77, 130.67, 129.71, 128.19, 126.99, 125.33,
92.55, 31.95, 30.40, 22.36, 20.94, 13.67. HRMS (ESI): m/z called
for C20H21N [M + H]+, 276.1713; found, 276.1716.
1
10 : 1); IR (KBr): 3073, 2954, 2925, 1597, 1495, 1451 cmꢁ1; H
NMR (400 MHz, CDCl3) d 7.94 (dd, J ¼ 7.9, 1.6 Hz, 2H), 7.50 (s,
4H), 7.09 (s, 2H), 5.96 (s, 1H), 2.42 (d, J ¼ 8.0 Hz, 2H), 1.53 (d, J ¼
7.5 Hz, 2H), 1.34 (d, J ¼ 7.5 Hz, 2H), 0.88 (s, 3H). 13C NMR (101
MHz, CDCl3) d 189.12, 166.30, 139.96, 137.68, 132.28, 130.98,
128.28, 127.05, 126.74, 119.23, 93.45, 31.97, 30.34, 22.35, 13.67.
HRMS (ESI): m/z called for C19H18BrN [M + H]+, 340.0696; found,
340.0693.
5,7-Dimethyl-4-butyl-2-phenylquinoline (4be). Yield, 93%;
white solid; mp 219–220 ꢀC; Rf 0.46 (petroleum ether/ethyl
acetate ¼ 10 : 1); IR (KBr): 3078, 2961, 2929, 1563, 1498, 1457
cmꢁ1
;
1H NMR (400 MHz, CDCl3) d 7.99 (s, 2H), 7.47 (d, J ¼
6-Iodo-4-butyl-2-phenylquinoline (4bk). Yield, 94%; white
solid; mp 245–246 ꢀC; Rf 0.51 (petroleum ether/ethyl acetate ¼
6.1 Hz, 2H), 6.91 (s, 1H), 6.85 (s, 2H), 5.95 (s, 1H), 2.47 (s, 2H),
2.36 (s, 6H), 1.60 (s, 2H), 1.38 (s, 2H), 0.91 (s, 3H). 13C NMR (101
MHz, CDCl3) d 188.50, 167.03, 140.37, 138.81, 138.31, 130.69,
128.21, 127.64, 127.03, 122.89, 92.70, 31.97, 30.47, 22.38, 21.24,
13.69. HRMS (ESI): m/z called for C21H23N [M + H]+, 290.1817;
found, 290.1819.
1
10 : 1); IR (KBr): 3075, 2959, 2928, 1599, 1495, 1453 cmꢁ1; H
NMR (400 MHz, CDCl3) d 7.98–7.90 (m, 2H), 7.71 (d, J ¼ 8.5 Hz,
2H), 7.47 (s, 2H), 6.97 (s, 2H), 5.96 (s, 1H), 2.44 (s, 2H), 1.55 (s,
2H), 1.35 (d, J ¼ 7.5 Hz, 2H), 0.89 (s, 3H). 13C NMR (101 MHz,
CDCl3) d 189.13, 166.17, 139.95, 138.39, 138.24, 130.99, 128.27,
127.05, 126.90, 93.55, 90.04, 31.98, 30.34, 22.35, 13.67. HRMS
(ESI): m/z called for C19H18IN [M + H]+, 388.0533; found,
388.0537.
6-Methyl-4-pentyl-2-phenylquinoline (4bf). Yield, 91%; white
solid; mp 215–216 ꢀC; Rf 0.47 (petroleum ether/ethyl acetate ¼
1
10 : 1); IR (KBr): 3075, 2959, 2928, 1599, 1495, 1453 cmꢁ1; H
NMR (400 MHz, CDCl3) d 7.95 (d, J ¼ 6.5 Hz, 2H), 7.47 (s, 2H),
7.20 (d, J ¼ 7.8 Hz, 2H), 7.09 (d, J ¼ 7.8 Hz, 2H), 5.92 (s, 1H), 2.39
(s, 5H), 1.56 (s, 2H), 1.28 (s, 4H), 0.86 (s, 3H). 13C NMR (101
MHz, CDCl3) d 188.57, 167.32, 140.32, 135.89, 135.78, 130.67,
129.72, 128.19, 126.99, 125.33, 92.54, 32.21, 31.39, 27.93, 22.19,
20.94, 13.81. HRMS (ESI): m/z called for C21H23N [M + H]+,
290.1817; found, 290.1819.
6-(4-Methoxyphenyl)-7,8,9,10-tetrahydrobenzophenanthridine
(4bg). Yield, 96%; white solid; mp 182–183 ꢀC; Rf 0.48 (petroleum
ether/ethyl acetate ¼ 10 : 1); IR (KBr): 3078, 2962, 2931, 1591,
1484, 1447 cmꢁ1; 1H NMR (400 MHz, CDCl3) d 9.37 (d, J ¼ 7.4 Hz,
1H), 7.89 (s, 2H), 7.82 (s, 1H), 7.71–7.63 (m, 4H), 7.05 (d, J ¼
8.6 Hz, 2H), 3.91 (s, 3H), 3.27 (s, 2H), 2.91 (s, 2H), 2.02 (s, 2H), 1.80
(s, 2H). 13C NMR (101 MHz, CDCl3) d 159.54, 142.11, 132.99,
130.85, 129.04, 127.43, 127.41, 126.91, 126.60, 124.94, 120.53,
113.46, 55.38, 29.13, 26.20, 22.89, 22.55. HRMS (ESI): m/z called
for C24H21NO [M + H]+, 340.1696; found, 340.1708.
2,4-Diphenylquinoline (4bl). Yield, 90%; white solid; mp
243–245 ꢀC; Rf 0.53 (petroleum ether/ethyl acetate ¼ 10 : 1); IR
1
(KBr): 3055, 3028, 2920, 1589, 1546, 1488, 1444 cmꢁ1; H NMR
(400 MHz, CDCl3) d 8.29 (d, J ¼ 8.4 Hz, 1H), 8.23 (d, J ¼ 7.3 Hz,
2H), 7.93 (d, J ¼ 8.3 Hz, 1H), 7.85 (s, 1H), 7.75 (s, 1H), 7.58 (d, J ¼
1.7 Hz, 7H), 7.51–7.46 (m, 2H). 13C NMR (101 MHz, CDCl3)
d 156.87, 149.15, 148.83, 139.66, 138.41, 130.14, 129.55, 129.49,
129.32, 128.81, 128.58, 128.38, 127.58, 126.31, 125.77, 125.62,
119.33. HRMS (ESI): m/z called for C21H15N [M + H]+, 282.1277;
found, 282.1279.
6-Methyl-2,4-diphenylquinoline (4bm). Yield, 91%; white
solid; mp 244–247 ꢀC; Rf 0.52 (petroleum ether/ethyl acetate ¼
1
10 : 1); IR (KBr): 3054, 2915, 1588, 1544, 1488, 1449 cmꢁ1; H
NMR (400 MHz, CDCl3) d 8.26 (s, 1H), 7.99 (s, 2H), 7.71 (s, 1H),
7.41 (s, 6H), 6.94 (s, 2H), 6.72 (d, J ¼ 7.5 Hz, 2H), 6.09 (s, 1H),
2.26 (s, 3H). 13C NMR (101 MHz, CDCl3) d 189.40, 161.72,
139.95, 136.78, 135.90, 134.10, 133.85, 133.05, 131.17, 130.78,
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129.56, 129.29, 128.48, 128.32, 127.20, 123.19, 96.54, 20.76.
HRMS (ESI): m/z called for C22H17N [M + H]+, 296.1443; found,
295.1445.
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6-Methoxy-4-ethyl-2-propylquinoline(4bn).
Yield,
90%;
yellow oil; mp 241–243 ꢀC; Rf 0.55 (petroleum ether/ethyl
acetate ¼ 10 : 1); IR (KBr): 3052, 2913, 1586, 1542, 1487, 1448
cmꢁ1; 1H NMR (400 MHz, CDCl3) d 7.82 (d, J ¼ 9.1 Hz, 1H), 7.66
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Acknowledgements
This work was supported by the grant from National Natural
Science Foundation of China (21571121, 21271124, and
21446014), and the Fundamental Research Funds for the
Central Universities (No. GK201302015, No. GK201501005) for
nancial support, the 111 Project (B14041), the Program for
Chang jiang Scholars and Innovative Research Team in
University (IRT_14R33), the Project Supported by Natural
Science Basic Research Plan in Shaanxi Province of China
(Program No. 2015JQ2056).
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