Synthesis of 2-Substituted Quinolines from 2-Aminostyryl Ketones Using Iodide as a Catalyst

Article abstract of DOI:10.1021/acs.joc.8b00552

A new protocol for the synthesis of 2-substituted quinolines from 2-aminostyryl ketones has been developed using iodide as a nucleophilic catalyst. Conjugate addition of iodide to 2-aminostyryl ketones yielded the corresponding β-iodoketones, which could have a conformation where the amino and carbonyl groups are proximal through free rotation about the C_α-C_β single bond. Subsequent condensation between the amino and carbonyl groups followed by elimination of hydrogen iodide provided the corresponding quinolines, with regeneration of the iodide catalyst.

Full text of DOI:10.1021/acs.joc.8b00552

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Synthesis of 2-Substituted Quinolines from 2-
Aminostyryl Ketones Using Iodide as a Catalyst
So Young Lee, Jiye Jeon, and Cheol-Hong Cheon
J. Org. Chem., Just Accepted Manuscript • DOI: 10.1021/acs.joc.8b00552 • Publication Date (Web): 17 Apr 2018
Downloaded from http://pubs.acs.org on April 17, 2018
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Synthesis of 2-Substituted Quinolines from 2-Aminostyryl
Ketones Using Iodide as a Catalyst
So Young Lee†, Jiye Jeon † and Cheol-Hong Cheon*
Department of Chemistry, Korea University, 145 Anamꢀro, Seongbukꢀgu, Seoul 02841,
Republic of Korea, Phone: +82ꢀ2ꢀ3290ꢀ3147; Fax: +82ꢀ2ꢀ3290ꢀ3121; Eꢀmail:
cheon@korea.ac.kr
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† These authors equally contributed to this work.
Abstract: A new protocol for the synthesis of 2ꢀsubstituted quinolines from 2ꢀaminostyryl
ketones has been developed using iodide as a nucleophilic catalyst. Conjugate addition of
iodide to 2ꢀaminostyryl ketones yielded the corresponding βꢀiodoketones, which could have a
conformation where the amino and carbonyl groups are proximal through free rotation about
the CαꢀCβ single bond. Subsequent condensation between the amino and carbonyl groups
followed by elimination of hydrogen iodide provided the corresponding quinolines, with
regeneration of the iodide catalyst.
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Introduction
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Since quinolines are privileged scaffolds found in a number of biologically active
natural products and are used in pharmaceuticals and materials science, numerous quinoline
derivatives bearing a different substituent(s) at specific positions have been prepared.1 Among
the various quinoline derivatives developed, 2ꢀsubstituted quinolines are particularly
important as they are not only associated with a wide range of biological properties such as
antimalarial and antitumor activity,2 but are also used as key building blocks in materials
science (Figure 1).3 Consequently, a great deal of efforts have been devoted to the
development of new protocols for the synthesis of 2ꢀsubstituted quinolines.4ꢀ6
NH
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N
N
HN
N
HO
N
H
N
CH3
Ir
3
N
F
N
N
CF3
CF3
AMG-319
Mefloquine
OLED materials
H2NO2S
HN
COOH
O
ONa
CH3
F
NO2
N
N
HO
F
Sirtuin inhibitor
Brequinar sodium
Figure 1. Representative Quinoline Derivatives Carrrying a Substituent at the 2ꢀPosition
One important approach for the synthesis of 2ꢀsubstituted quinolines 1 is through the
dehydrative cyclization of 2ꢀaminostyryl ketone derivatives 2 (Scheme 1).6 However, in
general, the conversion of 2ꢀaminostyryl ketones 2 to quinolines 1 is unlikely to take place,
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because ketones 2 exist in the stable (E)ꢀconfiguration, where the amino group cannot
approach the carbonyl group to undergo the condensation reaction (Scheme 1a).7 Thus, most
previous methods have exploited the conversion of the stable, but unreactive (E)ꢀ
configuration of 2 into the unstable, but reactive (Z)ꢀconfiguration, where the two amino and
carbonyl groups are located in a close position, using either photoisomerization, a
stoichiometric amount of I2 or PhSeCl in the presence of a base, or a strong acid under reflux
conditions (Scheme 1b).6 However, considering the importance of 2ꢀsubstituted quinoline
derivatives 1, the development of efficient and operationally simple and convenient synthetic
protocols to access these scaffolds still remains a highly pursued target in both academia and
industry.
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a) general reactivity of 2-aminostyryl ketones 2 in the synthesis of quinolines 1
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O
amino group cannot approach
carbonyl group in this configuration
R
X
distant
position
NH2
no formation of quinolines 1
(E)-2
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b) previous works: use of configuration change of a double bond
hv,
O
I2 or PhSeCl + base,
or H+ + heat
X
R
X
N
R
(E)-2
NH2
1
configurational
change
condensation
X
O
R
(high Ea)
NH2
(Z)-2
c) this work: use of conformational change of a single bond
O
I
(cat.)
X
R
X
wet solvent
N
R
(E)-2
1
NH2
conden-
sation;
then - HI
I
I
I
I
O
conformational change
R
X
X
(small Ea)
O
NH2
R
NH2
6 (s-cis conformer)
6 (s-trans conformer)
Scheme 1. (a) General Reactivity of 2ꢀAminostyryl Ketones 2 and (bꢀc) Comparison of
Previous and Present Methods for the Synthesis of Quinolines 1 from Ketones 2
Herein, we describe the development of a novel approach toward the synthesis of 2ꢀ
substituted quinolines 1 from 2ꢀaminostyryl ketones 2 using tetrabutylammonium iodide
(TBAI) as a nucleophilic catalyst (Scheme 1c).8 Iodide underwent conjugate addition to 2,
leading to the corresponding βꢀiodoketones 6, which could adopt the sꢀcis conformation
where the amino and carbonyl groups can be proximally located via free rotation about the
CαꢀCβ single bond. Subsequent condensation between these two groups followed by the
elimination of hydrogen iodide provided the corresponding quinolines 1 and iodide was
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regenerated as the nucleophilic catalyst. Various 2ꢀaminostyryl ketones 2 could be applicable
to this protocol and the desired quinoline products 1 were obtained in excellent yields.
Furthermore, the resulting quinoline products 1 could be directly subjected to other
transformations without isolation of quinoline products 1. Broad substrate scope, no need of
any special equipments and a stoichiometric amount of reagents, and extremely simple
operation will be other features of this transformation.
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Result and Discussions
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Since the proximity of the amino and carbonyl groups in ketones 2 is the prerequisite
for the success of this protocol,7,9 we attempted to find an alternative and more efficient way
to promote this transformation. Particularly, we noticed that the energy barrier for the free
rotation about a CꢀC single bond (around 6 kcal·molꢀ1) is significantly smaller than that for
the E/Z isomerization of a CꢀC double bond (around 65 kcal·molꢀ1).10 Based on this energy
consideration, we envisioned that the amino and carbonyl groups could be brought into
proximity with a much lower energy cost if the double bond in ketones 2 could be converted
into a single bond. One way to accomplish this is the use of a nucleophile capable of
conjugate addition to the α,βꢀunsaturated carbonyl moiety present in ketones 2 (Scheme 2).
The nucleophile could convert α,βꢀunsaturated ketones 2 into the corresponding saturated
ketones 6 via conjugate addition of the nucleophile, and the saturated ketones 6 could adopt
the sꢀcis conformation where the amino and carbonyl groups can be proximally located via
free rotation about the CαꢀCβ single bond. Subsequent condensation between these two groups
followed by the elimination of the nucleophile from the resulting dihydroquinolines 7 could
provide the corresponding quinolines 1, with a regeneration of the catalyst.
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Scheme 2. Working Hypothesis
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With this working hypothesis in mind, we first explored various nucleophiles as a
possible catalyst in this transformation (Table 1). It was found that a nucleophile significantly
facilitated this transformation; no formation of the desired product 1a was observed in the
absence of a nucleophile (entry 1), while the desired product 1a was obtained in 88% yield
when 2ꢀaminostyryl phenyl ketone 2a was treated with a stoichiometric amount of
benzylamine (entry 2) . With these interesting results in hand, other amine sources were tested
as the nucleophilic catalyst in this transformation. Aromatic amine could be used as the
nucleophilic catalyst leading to the desired product 1a in 79% yield (entry 3), whereas
sterically hindered bulky secondary amine did not provide 1a (entry 4). According to our
working hypothesis in Scheme 2, a nucleophile could be regenerated after the quinoline
formation, and thus, the same transformation was attempted to be performed with 10 mol% of
benzylamine. Unfortunately, however, with a 10 mol% of benzylamine the quinoline product
1a was obtained only in 34% yield (entry 5). Next, several other nucleophiles were tested as a
catalyst in this transformation (entries 5ꢀ8). The nucleophilicity of a catalyst was found to
have a strong influence on this transformation. Alcohol did not catalyze this reaction at all
(entry 6), but more nucleophilic thiol and phosphine afforded the desired product 1a in
moderate to good yield (entries 7 and 8).
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Since a catalyst should be a good nucleophile to undergo facile conjugate addition to
2ꢀaminostyryl ketone 2 and be a good leaving group from intermediate 7 leading to the
quinoline product 1a, a halide was next explored as a catalyst in this transformation (entries 9ꢀ
11). Gratifyingly, when the reaction was carried out in the presence of a catalytic amount of
TBAI, the desired product 1a was obtained in quantitative yield after 12 h (entry 9). However,
less nucleophilic halides, such as bromide and chloride, provided 1a in 66% and 54% yields,
respectively (entries 10 and 11). Furthermore, other nucleophiles, such as hydroxide and
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alkoxide, were tested as a catalyst in this quinoline synthesis (entries 12 and 13). However,
these nucleophilic anions failed to act as a nucleophile; either no reaction or the formation of
side product was observed with these nucleophiles. Since iodide provided the desired product
1a in the highest yield among the nucleophiles tested, iodide was selected as the optimal
nucleophilic catalyst for further investigation.
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Table 1. Screening of Nucleophiles
entry
1
(mol%)
ꢀ
time (h)
24
yielda (%)
Nu
ꢀ
N.R.b
2
benzylamine
pꢀanisidine
diisopropylamine
benzylamine
benzyl alcohol
benzyl mercaptan
triphenylphosphine
TBAI
100
100
100
10
12
88
3
12
79
4
12
N.R.b
5
12
34
6
10
12
N.R.b
7
10
12
80
8
10
12
65
>99
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TBABr
10
12
66
TBACl
10
12
54
NaOH
10
12
side reactionc
N.R.b
NaOMe
10
12
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a Yield was determined by 1H NMR analysis of the crude mixture.
b No Reaction
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c Several unidentifiable products were formed.
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With iodide as the optimal nucleophilic catalyst in this transformation, we further
investigated other reaction parameters in this transformation (Table 2). Interestingly, water
was found to play a crucial role in this transformation (entries 1 and 2). When the reaction
was performed with 10 mol% of iodide in the absence of water (i.e., in the presence of
molecular sieves), the yield of 1a significantly decreased and the starting material 2a
remained unreacted even after a long reaction time (entry 2).11 Furthermore, the reaction
atmosphere was found to slightly influence the efficiency of this transformation. When the
reaction was performed under an argon atmosphere, quinoline 1a was obtained in lower yield
than in the reaction in an open flask (entries 1 and 3). Thus, the transformation was carried out
in an open flask in the further investigations.
Next, the effect of the reaction medium on this transformation was investigated
(entries 1, 4−9), indicating that the choice of reaction medium had a considerable influence on
the efficiency of this transformation. The reaction in 1,2ꢀdichloroethane (DCE) provided the
desired product 1a in quantitative yield within 12 h (entry 1), whereas the use of other
solvents afforded 1a in very low yield and a considerable amount of the starting material 2a
remained unreacted in the reaction mixture (entries 4−9). Finally, the effect of the reaction
temperature on this transformation was investigated and was found to have a beneficial effect
on the reaction rate (entries 1, 10−14). The reaction performed below 60 oC proceeded slowly
to provide the desired product 1a in no or low yield (entries 10−12), while the reactions went
o
to completion at the temperature above 80 C (entry 3 vs. entries 13 and 14). Although the
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reaction proceeded slightly faster above 80 C, 80 C was selected as optimal for the simple
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operation of this protocol.12
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Table 2. Optimization of Reaction Conditions
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entry
1
solvent
ClCH2CH2Cl
ClCH2CH2Cl
ClCH2CH2Cl
MeOH
temp (oC)
80
time (h)
12
yielda (%)
>99
trace
71
2b
3c
4
80
12
80
12
80
24
17
5
EtOH
80
24
17
6
toluene
80
12
7
7
1,4ꢀdioxane
CH2Cl2
80
12
7
8
80
24
12
9
CHCl3
80
24
trace
trace
trace
18
10
11
12
13d
14d
ClCH2CH2Cl
ClCH2CH2Cl
ClCH2CH2Cl
ClCH2CH2Cl
ClCH2CH2Cl
rt
12
40
12
60
12
90
11
97
100
10
98
a Yield was determined by 1H NMR analysis of the crude mixture.
b Reaction was performed in the presence of 4 Å molecular sieves.
c Under an argon atmosphere.
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Table 3. Substrate Scope
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Entry
R1
Ph
R2
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
R3
H
time (h)
12
yield (%)
99
1
1
2
1a
1b
1c
1d
1e
1f
4ꢀMeOC6H4
4ꢀMeC6H4
4ꢀFC6H4
4ꢀClC6H4
4ꢀBrC6H4
4ꢀMeO2CC6H4
2ꢀMeC6H4
3ꢀMeC6H4
2ꢀBrC6H4
3ꢀBrC6H4
1ꢀnaphthyl
2ꢀnaphthyl
2ꢀfuryl
H
16
83
3
H
17
93
4
H
11
96
5
H
14
99
6
H
15
99
7
H
10
99
1g
1h
1i
8
H
21
95
9
H
20
89
10
11
12
13
14
15
16
17
18
H
13
97
1j
H
13
98
1k
1l
H
13
99
H
15
99
1m
1n
1o
1p
1q
1r
H
15
96
2ꢀthienyl
Ph
H
11
98
6ꢀF
6ꢀCl
6ꢀBr
13
99
Ph
15
96
Ph
15
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Ph
4ꢀMeOC6H4
Ph
H
H
6ꢀOMe
6ꢀOMe
7ꢀBr
6,8ꢀBr2
H
11
11
20
20
10
12
12
87
95
94
82
80
40
31
1s
1t
21a
22b
23
H
1u
1v
1w
1x
1y
Ph
H
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Ph
Me
H
24
Methyl
Isopropyl
H
25a
H
H
a 20 mol% TBAI was used.
b 40 mol% TBAI was used.
With these optimized reaction conditions (10 mol% of TBAI, wet DCE, open flask, 80
oC) in hand, the substrate scope of ketones 2 was further investigated in this transformation
(Table 3). Various 2ꢀaminostyryl aryl ketones 2 could be applied in this protocol to afford the
2ꢀaryl substituted quinolines 1 (entries 1−11). The electronic effect of the aryl group slightly
affected this transformation (entries 1ꢀ7); the ketones 2 bearing an electronꢀdeficient aryl
group provided the desired products 1 in slightly better yields than those with electronꢀrich
aryl groups. Furthermore, the position of the substituent on the aryl group in ketones 2 had
little influence on the efficiency of this transformation (entries 3, 6, and 8−11). The desired
products 1 were obtained in excellent yields regardless of the position of the substituent on
the aryl ring. Furthermore, 2ꢀaminostyryl ketones carrying fused aromatic and heteroaromatic
moieties were tolerated in this transformation, and the desired products 1 were obtained in
excellent yields (entries 12−15).
The effect of the substituent on the 2ꢀaminophenyl ring in ketones 2 was further
explored on the efficiency of this transformation (entries 16−22). When several 2ꢀaminostyryl
ketones derivatives 2 bearing a different substituent were subjected to the standard conditions,
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the desired disubstituted quinoline products 1 were obtained in excellent yields regardless of
the electronic nature of the substituent (entries 16ꢀ20). Next, the position of a substituent on
the phenyl ring in 2ꢀaminostyryl scaffold was further investigated and was found to have little
effect on this transformation (entries 18, 21 and 22). A substrate bearing a substituent on the
vinyl moiety in the 2ꢀaminostyryl group was also applicable in this protocol, and the desired
2,3ꢀdisubstituted quinoline 1w was obtained in high yield (entry 23). Unfortunately, however,
this protocol was limited for application to ketones 2 carrying aliphatic groups; the desired
quinoline products 1 were obtained in only moderate yields and rather complex mixtures were
obtained (entries 24 and 25).
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Scheme 3. A GramꢀScale Transformation
To test the practicality of the developed method, the transformation was carried out on
the gramꢀscale (Scheme 3). When 20 mmol of 2a was subjected to the standard conditions,
the desired product 1a was obtained in quantitative yield. Notably, after completion of this
transformation, 1a could be easily isolated by removal of TBAI through simple aqueous
extraction.
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standard
conditions
DIBAL-H (4 equiv)
N
2g
N
rt, 15 min
O
6
7
OH
1g
3 (71%)
(over two steps)
not isolated
OMe
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ArB(OH)2
standard
conditions
Pd(PPh3)4 (10 mol%)
N
2f
N
Ba(OH)2 8H2O
dioxane:H2O (3:1)
100 oC
Ar
4
Br
1f
not isolated
4a
4b
4c
C6H5
Ar
4-MeOC6H4 4-F3CC6H4
yield (%)a 91
a two-step yield from 2f
73
65
Scheme 4. Direct Transformation of Quinolines
With these results in hand, we further attempted to demonstrate the versatility of this
protocol (Scheme 4). Particularly, since this protocol required no additional reagents except
TBAI, and the reaction proceeded very cleanly without the formation of any other sideꢀ
products, attempts were made to develop a oneꢀpot protocol where the resulting quinoline
products 1 were directly subjected to other transformations without their complete isolations.
First, quinoline 3 bearing a 4ꢀhydroxymethylphenyl group could be prepared by reduction of
the ester moiety in quinoline 1g to an alcohol in the same reaction mixture. Reaction of 2g
under the standard conditions followed by direct reduction of the resulting quinoline 1g with
DIBAL in the same pot at room temperature afforded quinoline 3 in 72% yield over two steps.
Furthermore, several biaryl substituted quinolines 413 could be prepared through the direct
SuzukiꢀMiyaura reaction of quinoline 1f without its complete isolation. The treatment of
ketone 2f with TBAI provided 1f, and without complete isolation of 1f, the crude mixture was
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subjected to SuzukiꢀMiyaura reactions with several aryl boronic acids to provide the expected
4
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biaryl substituted quinolines 4 in good to high yields over two steps.14
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Conclusions
In conclusion, a new protocol was developed for the synthesis of 2ꢀsubstituted
quinolines from 2ꢀaminostyryl ketones using iodide as a nucleophilic catalyst. Conjugate
addition of iodide to 2ꢀaminostyryl ketones 2 led to βꢀiodoketones 6, which could adopt the sꢀ
cis conformation via free rotation about the CαꢀCβ bond. In this conformation, intramolecular
imine formation between the carbonyl and the amino groups followed by elimination of HI
provided the desired 2ꢀsubstituted quinolines 1. Various 2ꢀsubstituted quinolines 1 could be
prepared from the corresponding ketones 2 in excellent yields. Furthermore, the utility of this
transformation was demonstrated by direct application of the resulting quinolines to other
transformations without prior isolation. Further application of this protocol to the synthesis of
other important quinoline compounds are currently underway in our laboratory and will be
reported in due course.
Experimental Section
General. All reactions were carried out in an ovenꢀdried glassware in an open flask, unless
otherwise noted. Except as otherwise indicated, all reactions were magnetically stirred and
monitored by analytical thin layer chromatography (TLC) using preꢀcoated silica gel glass
plates (0.25 mm) with F254 indicator. Visualization was accomplished by UV light (254 nm),
with a combination of potassium permanganate and/or phosphomolybdic acid solution as an
indicator. Flash column chromatography was performed using silica gel 60 (230 – 400 mesh).
Yields refer to chromatographically and spectroscopically pure compounds, unless otherwise
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noted. Commercial grade reagents and solvents were used without further purification. 2ꢀ
Nitrobenzaldehydes and all methyl ketones were purchased from commercial suppliers and
used without further purification. 2ꢀAminostyryl ketone derivatives 2 were prepared by a
protocol reported in the literature through aldol condensation of methyl ketone derivatives
with 2ꢀnitrobenzaldehydes followed by the reduction of a nitro group into an amino group.15a,b
1H NMR and 13C NMR spectra were recorded at 500 MHz and 125 MHz spectrometers,
respectively. Tetramethylsilane (δ: 0.0 ppm) and a residual NMR solvent (either CDCl3 (δc:
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77.16 ppm) were used as internal standards for H NMR and C NMR spectra, respectively.
The proton spectra are reported as follows: δ (position of proton, multiplicity, coupling
constant J, number of protons). Multiplicities are indicated by s (singlet), d (doublet), t
(triplet), q (quartet), p (quintet), h (septet), m (multiplet) and br (broad). High resolution mass
spectra (HRMS) were recorded on a quadrupole timeꢀofꢀflight mass spectrometer (QTOFꢀ
MS) in electrospray ionization (ESI) mode as ionization method.
All unknown 2ꢀaminostyryl ketones (2g, 2h, 2i, 2j, 2p, 2t, 2v and 2y) were prepared from
methyl ketone derivatives and 2ꢀnitrobenzaldehydes via a modified method reported in the
literature procedure.15a,b
Synthesis of 2-aminostyryl ketone derivatives 2
To a mixture of a 2ꢀnitrobenzaldehyde derivative (4.0 mmol), sodium hydroxide (16 mg, 0.40
mmol) and potassium carbonate (55 mg, 0.40 mmol) was added a methyl ketone derivative
o
(4.0 mmol) at 25 C. The reaction stirred for 30 min at room temperature. After complete
consumption of the 2ꢀnitrobenzaldehyde derivative, the reaction mixture was quenched by the
addition of H2O and extracted with ethyl acetate. The organic layer was combined, dried over
MgSO4, and concentrated in vacuo. The crude mixture was purified by recrystallization with
ethanol to provide the desired (E)ꢀ2ꢀnitrostyryl ketone as a pale yellow solid in about 60ꢀ70%
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yield. To a solution of the resulting (E)ꢀ2ꢀnitrostyryl ketone derivative (2.5 mmol) in ethanol
(25 mL) was added iron powder (70 mg, 13 mmol), followed by HCl (1.0 N, 1.3 mL/ 1.3
mmol), and the resulting mixture was virgorously stirred at 80 oC. After complete
consumption of the (E)ꢀ2ꢀnitrostyryl ketone derivative, the reaction mixture was cooled to
room temperature, diluted with ethyl acetate and filtered through a Celite pad. The filtrate was
washed with saturated Na2CO3 aqueous solution and the aqueous phase was extracted with
ethyl acetate. The combinded organic phases were dried over MgSO4, and concentrated in
vacuo. The crude material was purified by recrystallization with a mixture of methylene
chloride and hexanes to provide the desired (E)ꢀ2ꢀaminostyryl ketone 2.
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(E)ꢀ2ꢀAminophenylstyryl 4ꢀMethoxycarbonylphenyl Ketone (2g)
Compound 2g was obtained as an orange solid (0.42 g, 60%) after purification by
recrystallization with methylene chloride and hexanes. Rf = 0.3 (ethyl acetate/hexanes = 1:5).
1H NMR (500 MHz, CDCl3, ppm): δ 8.15 (d, J = 8.2 Hz, 2H), 8.05 (d, J = 8.1 Hz, 2H), 8.01
(d, J = 15.4 Hz, 1H), 7.54 (d, J = 7.8 Hz, 1H), 7.46 (d, J = 15.4 Hz, 1H), 7.22 (t, J = 7.6 Hz,
1H), 6.80 (t, J = 7.6 Hz, 1H), 6.73 (d, J = 8.1 Hz, 1H), 4.11 (br. s., 2H), 3.96 (s, 3H). 13C{1H}
NMR (125 MHz, CDCl3, ppm): δ 189.9, 166.5, 146.6, 141.9, 141.1, 133.6, 132.2, 130.0,
128.4, 128.3, 121.4, 120.0, 119.1, 117.0, 52.6. HRMS (ESIꢀTOF) m/z: [M + Na]+ Calcd for
C17H15NO3Na 304.0944; Found 304.0944.
(E)ꢀ2ꢀAminophenylstyryl 2ꢀMethylphenyl Ketone (2h)
Compound 2h was obtained as a yellow solid (0.39 g, 65%) after purification by
recrystallization with methylene chloride and hexanes. Rf = 0.3 (ethyl acetate/hexanes = 1:5).
1H NMR (500 MHz, CDCl3, ppm): δ 7.70 (d, J = 15.7 Hz, 1H), 7.53 (d, J = 7.0 Hz, 1H), 7.46
(d, J = 7.9 Hz, 1H), 7.38 (m, 1H), 7.28 (d, J = 7.3 Hz, 2H), 7.19 (m, 1H), 7.10 (d, J = 15.7 Hz,
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1H), 6.78 (t, J = 7.6 Hz, 1H), 6.70 (d, J = 8.1 Hz, 1H), 4.02 (br. s., 2H), 2.48 (s, 3H). 13C{1H}
NMR (125 MHz, CDCl3, ppm): δ 196.1, 146.2, 140.9, 139.3, 137.1, 131.9, 131.5, 130.6,
128.2 (2C), 126.2, 125.6, 120.0, 119.0, 116.9, 20.5. HRMS (ESIꢀTOF) m/z: [M + Na]+ Calcd
for C16H15NONa 260.1046; Found 260.1048.
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(E)ꢀ2ꢀAminophenylstyryl 3ꢀMethylphenyl Ketone (2i)
Compound 2i was obtained as a yellow solid (0.39 g, 66%) after purification by
recrystallization with methylene chloride and hexanes. Rf = 0.3 (ethyl acetate/hexanes = 1:5).
1H NMR (500 MHz, CDCl3, ppm): δ 7.98 (d, J = 15.4 Hz, 1H), 7.84 (s., 2H), 7.51 (m, 2H),
7.40 (s., 2H), 7.21 (t, J = 7.6 Hz, 1H), 6.81 (t, J = 7.4 Hz, 1H), 6.73 (d, J = 8.1 Hz, 1H), 4.06
(br. s., 2H), 2.45 (s, 3H). 13C{1H} NMR (125 MHz, CDCl3, ppm): δ 190.6, 146.3, 140.0,
138.6, 138.5, 133.7, 131.8, 129.1, 128.6, 128.3, 125.8, 122.1, 120.5, 119.1, 116.9, 21.6.
HRMS (ESIꢀTOF) m/z: [M + Na]+ Calcd for C16H15NONa 260.1046; Found 260.1047.
(E)ꢀ2ꢀAminophenylstyryl 2ꢀBromophenyl Ketone (2j)
Compound 2j was obtained as a yellow solid (0.48 g, 63%) after purification by
recrystallization with methylene chloride and hexanes. Rf = 0.3 (ethyl acetate/hexanes = 1:5).
1H NMR (500 MHz, CDCl3, ppm): δ 7.67 (d, J = 9.8 Hz, 1H), 7.64 (d, J = 1.7 Hz, 1H), 7.43
(m, 3H), 7.33 (dt, J = 7.6, 1.8 Hz, 1H), 7.20 (t, J = 7.6 Hz, 1H), 7.05 (d, J = 15.9 Hz, 1H),
6.79 (t, J = 7.6 Hz, 1H), 6.71 (d, J = 8.1 Hz, 1H), 3.98 (br. s., 2H). 13C{1H} NMR (125 MHz,
CDCl3, ppm): δ 194.5, 146.3, 141.9, 141.5, 133.6, 132.2, 131.6, 129.5, 128.6, 127.6, 125.8,
120.0, 119.6, 119.2, 117.0. HRMS (ESIꢀTOF) m/z: [M + Na]+ Calcd for C15H12BrNONa
323.9994; Found 323.9994.
(E)ꢀ2ꢀAminoꢀ5ꢀFluorophenylstyryl Phenyl Ketone (2p)
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Compound 2p was obtained as a yellow solid (0.40 g, 67%) after purification by
recrystallization with methylene chloride and hexanes. Rf = 0.3 (ethyl acetate/hexanes = 1:5).
1H NMR (500 MHz, CDCl3, ppm): δ 8.03 (d, J = 7.5 Hz, 2H), 7.92 (d, J = 15.3 Hz, 1H), 7.60
(m, 1H), 7.52 (m, 2H), 7.47 (d, J = 15.3 Hz, 1H), 7.24 (dd, J = 9.5, 2.9 Hz, 1H), 6.95 (dt, J =
8.3, 2.9 Hz, 1H), 6.68 (dd, J = 8.9, 4.9 Hz, 1H), 3.92 (br. s., 2H). 13C{1H} NMR (125 MHz,
CDCl3, ppm): δ 190.0, 157.3, 155.4, 142.6, 138.9, 138.2, 133.1, 128.8, 128.6, 122.8, 121.3,
118.9, 118.8, 118.2, 118.1, 113.5, 113.3. HRMS (ESIꢀTOF) m/z: [M + Na]+ Calcd for
C15H12FNONa 264.0795; Found 264.0793.
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(E)ꢀ2ꢀAminoꢀ5ꢀMethoxyphenylstyryl 4ꢀMethoxyphenyl Ketone (2t)
Compound 2t was obtained as a red solid (0.46 g, 65%) after purification by recrystallization
1
with methylene chloride and hexanes. Rf = 0.3 (ethyl acetate/hexanes = 1:5). H NMR (500
MHz, CDCl3, ppm): δ 8.04 (d, J = 8.7 Hz, 2H), 7.95 (d, J = 15.3 Hz, 1H), 7.47 (d, J = 15.4 Hz,
1H), 7.05 (d, J = 2.7 Hz, 1H), 6.99 (d, J = 8.7 Hz, 2H), 6.85 (dd, J = 8.7, 2.7 Hz, 1H), 6.69 (d,
J = 8.7 Hz, 1H), 3.89 (s, 3 H), 3.80 (s, 5 H). 13C{1H} NMR (125 MHz, CDCl3, ppm): δ 188.7,
163.5, 152.9, 140.4, 139.3, 131.3, 130.9, 122.2, 121.6, 118.7, 118.5, 114.0, 112.0, 56.0, 55.7.
HRMS (ESIꢀTOF) m/z: [M + H]+ Calcd for C17H18NO3 284.1281; Found 284.1282.
(E)ꢀ2ꢀAminoꢀ3,5ꢀdibromophenylstyryl Phenyl Ketone (2v)
Compound 2v was obtained as a yellow solid (0.66 g, 69%) after purification by
recrystallization with methylene chloride and hexanes. Rf = 0.3 (ethyl acetate/hexanes = 1:5).
1H NMR (500 MHz, CDCl3, ppm): δ 8.03 (m, 2H), 7.85 (d, J = 15.3 Hz, 1H), 7.62 (m, 1H),
7.60 (m, 1H), 7.57 (d, J = 2.1 Hz, 1H), 7.53 (m, 2H), 7.48 (d, J = 15.3 Hz, 1H), 4.54 (br. s.,
2H). 13C{1H} NMR (125 MHz, CDCl3, ppm): δ 189.6, 142.6, 138.1, 137.9, 136.3, 133.4,
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129.6, 128.9, 128.7, 124.3, 122.9, 111.4, 109.9. HRMS (ESIꢀTOF) m/z: [M + Na]+ Calcd for
C15H11Br2NONa 401.9100; Found 401.9093.
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(E)ꢀ2ꢀAminophenylstyryl Isopropyl Ketone (2y)
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Compound 2y was obtained as yellow oil (0.28 g, 60%) after purification by column
chromatography on silica using a mixture of ethyl acetate and hexanes (1:6) as an eluent. Rf =
1
0.3 (ethyl acetate/hexanes = 1:5). H NMR (500 MHz, CDCl3, ppm): δ 7.78 (d, J = 15.7 Hz,
1H), 7.43 (d, J = 7.8 Hz, 1H), 7.18 (m, 1H), 6.77 (m, 2H), 6.71 (d, J = 7.9 Hz, 1H), 3.98 (br.
s., 2H), 2.87 (td, J = 13.8, 6.9 Hz, 1H), 1.18 (d, J = 6.9 Hz, 6H). 13C{1H} NMR (125 MHz,
CDCl3, ppm): δ 203.8, 146.1, 137.8, 131.5, 128.2, 124.4, 120.2, 119.1, 116.9, 40.0, 18.6.
HRMS (ESIꢀTOF) m/z: [M + Na]+ Calcd for C12H15NONa 212.1046; Found 212.1045.
General procedure for the synthesis of 2-substituted quinoline derivatives 1 (Table 2).
To a solution of (E)ꢀ2ꢀaminostyryl ketone derivative 2 (0.20 mmol) in 1,2ꢀdichloroethane (2.0
mL) was added tetrabutylammonium iodide (7.4 mg, 0.020 mmol) at room temperature. The
reaction mixture was stirred at 80 oC in an open flask and monitored by TLC. After complete
consumption of compound 2, the reaction mixture was cooled to room temperature and
concentrated under reduced pressure. Then the crude reaction mixture was quenched with
water, and extracted with and ethyl acetate. The organic layer was combined, dried over
MgSO4, and concentrated. Even after extraction, the crude mixture was generally pure enough
to use without further purification. If necessary, the crude mixture was purified by short flash
column chromatography on silica to provide the desired product 1.
2ꢀPhenylquinoline (1a)
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Compound 1a was obtained as a white solid (41 mg, 99%) after purification by column
chromatography on silica using a mixture of ethyl acetate and hexanes (1:6) as an eluent.
Spectroscopic data were matched with the reported values.16 Rf = 0.4 (ethyl acetate/hexanes =
1:10). 1H NMR (500 MHz, CDCl3, ppm): δ 8.23 (d, J = 8.5 Hz, 1H), 8.18 (m, 3H), 7.89 (d, J
= 8.5 Hz, 1H), 7.84 (d, J = 8.1 Hz, 1H), 7.74 (t, J = 7.6 Hz, 1H), 7.54 (t, J = 7.2 Hz, 3H), 7.48
(m, 1H). 13C{1H} NMR (125 MHz, CDCl3, ppm): δ 157.5, 148.5, 139.9, 136.9, 129.9, 129.8,
129.5, 129.0, 127.7, 127.6, 127.3, 126.4, 119.2.
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2ꢀ(4ꢀMethoxyphenyl)quinoline (1b)
Compound 1b was obtained as a pale yellow solid (44 mg, 83%) after purification by column
chromatography on silica using a mixture of ethyl acetate and hexanes (1:6) as an eluent.
Spectroscopic data were matched with the reported values.16 Rf = 0.4 (ethyl acetate/hexanes =
1:7). 1H NMR (500 MHz, CDCl3, ppm): δ 8.19 (d, J = 8.7 Hz, 1H), 8.15 (m, 3H), 7.84 (d, J =
8.5 Hz, 1H), 7.81 (dd, J = 8.1, 1.1 Hz, 1H), 7.71 (ddd, J = 8.4, 6.9, 1.4 Hz, 1H), 7.50 (ddd, J =
8.0, 6.9, 1.1 Hz, 1H), 7.05 (m, 2H), 3.89 (s, 3H). 13C{1H} NMR (125 MHz, CDCl3, ppm): δ
161.0, 157.0, 148.4, 138.8, 132.4, 129.7 (2C), 129.0, 127.6, 127.0, 126.0, 118.7, 114.4, 55.5.
2ꢀ(4ꢀMethylphenyl)quinoline (1c)
Compound 1c was obtained as a pale yellow solid (40 mg, 93%) after purification by column
chromatography on silica using a mixture of ethyl acetate and hexanes (1:6) as an eluent.
Spectroscopic data were matched with the reported values.16 Rf = 0.4 (ethyl acetate/hexanes =
1:10). 1H NMR (500 MHz, CDCl3, ppm): δ 8.20 (d, J = 8.5 Hz, 1H), 8.17 (d, J = 8.4 Hz, 1H),
8.06 (d, J = 8.2 Hz, 2H), 7.87 (d, J = 8.5 Hz, 1H), 7.82 (d, J = 8.1 Hz, 1H), 7.72 (ddd, J = 8.4,
6.9, 1.4 Hz, 1H), 7.51 (m, 1H), 7.34 (d, J = 8.1 Hz, 2H), 2.44 (s, 3H). 13C{1H} NMR (125
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Compound 1d was obtained as a light green solid (43 mg, 96%) after purification by column
chromatography on silica using a mixture of ethyl acetate and hexanes (1:6) as an eluent.
Spectroscopic data were matched with the reported values.16 Rf = 0.4 (ethyl acetate/hexanes =
1
1:10). H NMR (500 MHz, CDCl3, ppm): δ 8.23 (d, J = 8.4 Hz, 1H), 8.16 (m, 3H), 7.83 (m,
2H), 7.73 (ddd, J = 8.4, 7.0, 1.5 Hz, 1H), 7.53 (ddd, J = 8.1, 6.9, 1.1 Hz, 1H), 7.21 (m, 2H).
13C{1H} NMR (125 MHz, CDCl3, ppm): δ 164.9, 163.0, 156.4, 148.4, 137.1, 136.0, 130.0,
129.8, 129.6, 129.5, 127.6, 127.2, 126.5, 118.8, 116.0, 115.8.
2ꢀ(4ꢀChlorophenyl)quinoline (1e)
Compound 1e was obtained as a pale yellow solid (48 mg, 99 %) after purification by column
chromatography on silica using a mixture of ethyl acetate and hexanes (1:6) as an eluent.
Spectroscopic data were matched with the reported values.16 Rf = 0.4 (ethyl acetate/hexanes =
1:10). 1H NMR (500 MHz, CDCl3, ppm): δ 8.23 (d, J = 8.7 Hz, 1H), 8.16 (d, J = 8.5 Hz, 1H),
8.13 (m, 2H), 7.84 (m, 2H), 7.74 (dt, J = 7.7, 1.3 Hz, 1H), 7.55 (m, 1H), 7.50 (m, 2H).
13C{1H} NMR (125 MHz, CDCl3, ppm): δ 156.1, 148.4, 138.2, 137.1, 135.7, 130.0, 129.8,
129.1, 128.9, 127.6, 127.3, 126.6, 118.7.
2ꢀ(4ꢀBromophenyl)quinoline (1f)
Compound 1f was obtained as a pale yellow solid (58 mg, 99%) after purification by column
chromatography on silica using a mixture of ethyl acetate and hexanes (1:6) as an eluent.
Spectroscopic data were matched with the reported values.16 Rf = 0.4 (ethyl acetate/hexanes =
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1:10). 1H NMR (500 MHz, CDCl3, ppm): δ 8.24 (d, J = 8.5 Hz, 1H), 8.16 (d, J = 8.4 Hz, 1H),
8.06 (m, 2H), 7.84 (m, 2H), 7.74 (ddd, J = 8.5, 6.9, 1.4 Hz, 1H), 7.66 (m, 2H), 7.55 (ddd, J =
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8.0, 6.9, 1.1 Hz, 1H). C{1H} NMR (125 MHz, CDCl3, ppm): δ 156.2, 148.4, 138.7, 137.1,
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132.1, 130.0, 129.9, 129.2, 127.6, 127.4, 126.7, 124.1, 118.6.
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2ꢀ(4ꢀMethyoxycarbonylphenyl)quinoline (1g)
Compound 1g was obtained as a white solid (54 mg, 99%) after purification by column
chromatography on silica using a mixture of ethyl acetate and hexanes (1:6) as an eluent.
Spectroscopic data were matched with the reported values.17 Rf = 0.3 (ethyl acetate/hexanes =
1
1:7). H NMR (500 MHz, CDCl3, ppm): δ 8.26 (m, 3H), 8.20 (m, 3H), 7.92 (d, J = 8.5 Hz,
1H), 7.86 (dd, J = 8.1, 1.2 Hz, 1H), 7.76 (ddd, J = 8.4, 6.9, 1.4 Hz, 1H), 7.57 (ddd, J = 8.0, 6.9,
1.1 Hz, 1H), 3.97 (s, 3H). 13C{1H} NMR (125 MHz, CDCl3, ppm): δ 167.0, 156.1, 148.4,
143.8, 137.1, 130.7, 130.2, 130.0, 127.6 (2C), 127.5, 126.9, 119.0, 52.3.
2ꢀ(2ꢀMethylphenyl)quinoline (1h)
Compound 1h was obtained as a brown solid (42 mg, 95%) after purification by column
chromatography on silica using a mixture of ethyl acetate and hexanes (1:6) as an eluent.
Spectroscopic data were matched with the reported values.18 Rf = 0.3 (ethyl acetate/hexanes =
1:10). 1H NMR (500 MHz, CDCl3, ppm): δ 8.22 (d, J = 8.4 Hz, 1H), 8.17 (d, J = 8.5 Hz, 1H),
7.87 (dd, J = 8.1, 1.2 Hz, 1H), 7.74 (ddd, J = 8.4, 6.9, 1.4 Hz, 1H), 7.56 (m, 2H), 7.50 (m, 1H),
7.33 (m, 3H), 2.42 (s, 3H). 13C{1H} NMR (125 MHz, CDCl3, ppm): δ 160.4, 147.9, 140.8,
136.2, 136.1, 131.0, 129.8 (2C), 129.6, 128.6, 127.6, 126.8, 126.5, 126.1, 122.5, 20.5.
2ꢀ(3ꢀMethylphenyl)quinoline (1i)
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Compound 1i was obtained as a brown solid (39 mg, 90%) after purification by column
chromatography on silica using a mixture of ethyl acetate and hexanes (1:6) as an eluent.
Spectroscopic data were matched with the reported values.16 Rf = 0.4 (ethyl acetate/hexanes =
1:10). 1H NMR (500 MHz, CDCl3, ppm): δ 8.22 (d, J = 8.5 Hz, 1H), 8.18 (d, J = 8.4 Hz, 1H),
8.01 (s, 1H), 7.92 (m, 1H), 7.88 (d, J = 8.5 Hz, 1H), 7.83 (dd, J = 8.1, 1.4 Hz, 1H), 7.73 (ddd,
J = 8.4, 6.9, 1.4 Hz 1H), 7.53 (ddd, J = 8.0, 6.9, 1.1 Hz, 1H), 7.42 (t, J = 7.6 Hz, 1H), 7.29 (td,
J = 7.6, 0.6 Hz, 1H), 2.49 (s, 3H). 13C{1H} NMR (125 MHz, CDCl3, ppm): δ 157.6, 148.3,
139.7, 138.6, 136.8, 130.2, 129.8, 129.7, 128.8, 128.3, 127.5, 127.3, 126.3, 124.8, 119.2, 21.7.
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2ꢀ(2ꢀBromophenyl)quinoline (1j)
Compound 1j was obtained as a yellow solid (55 mg, 97%) after purification by column
chromatography on silica using a mixture of ethyl acetate and hexanes (1:6) as an eluent.
Spectroscopic data were matched with the reported values.16 Rf = 0.3 (ethyl acetate/hexanes =
1:10). 1H NMR (500 MHz, CDCl3, ppm): δ 8.23 (d, J = 8.4 Hz, 1H), 8.18 (d, J = 8.5 Hz, 1H),
7.88 (d, J = 8.2 Hz, 1H), 7.76 (ddd, J = 8.4, 6.9, 1.4 Hz, 1H), 7.71 (m, 2H), 7.64 (dd, J = 7.6,
1.8 Hz, 1H), 7.59 (td, J = 7.6, 1.1 Hz, 1H), 7.46 (td, J = 7.6, 1.1 Hz, 1H), 7.31 (td, J = 7.7, 1.7
Hz, 1H). 13C{1H} NMR (125 MHz, CDCl3, ppm): δ 158.9, 148.1, 141.8, 135.8, 133.4, 131.7,
130.1, 130.0, 129.8, 127.8, 127.7, 127.3, 127.0, 122.9, 122.0.
2ꢀ(3ꢀBromophenyl)quinoline (1k)
Compound 1k was obtained as a yellow solid (56 mg, 98%) after purification by column
chromatography on silica using a mixture of ethyl acetate and hexanes (1:6) as an eluent.
Spectroscopic data were matched with the reported values.18 Rf = 0.4 (ethyl acetate/hexanes =
1:10). 1H NMR (500 MHz, CDCl3, ppm): δ 8.36 (t, J = 1.8 Hz, 1H), 8.25 (d, J = 8.5 Hz, 1H),
8.17 (dd, J = 8.5, 0.8 Hz, 1H), 8.08 (dq, J = 7.8, 0.9 Hz, 1H), 7.85 (m, 2H), 7.75 (ddd, J = 8.5,
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6.9, 1.5 Hz, 1H), 7.59 (ddd, J = 7.9, 2.0, 0.9 Hz, 1H), 7.55 (ddd, J = 8.1, 6.9, 1.2 Hz, 1H),
7.40 (t, J = 7.9 Hz, 1H). 13C{1H} NMR (125 MHz, CDCl3, ppm): δ 155.7, 148.3, 141.7, 137.1,
132.3, 130.7, 130.4, 130.0, 129.9, 127.6, 127.4, 126.8, 126.1, 123.3, 118.7.
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2ꢀ(1ꢀNaphthyl)quinoline (1l)
Compound 1l was obtained as orange oil (53 mg, 99%) after purification by column
chromatography on silica using a mixture of ethyl acetate and hexanes (1:6) as an eluent.
Spectroscopic data were matched with the reported values.19 Rf = 0.3 (ethyl acetate/hexanes =
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1:10). H NMR (500 MHz, CDCl3, ppm): δ 8.30 (d, J = 8.4 Hz, 1H), 8.23 (m, 1H), 8.13 (m,
1H), 7.94 (m, 3H), 7.78 (ddd, J = 8.4, 6.9, 1.4 Hz, 1H), 7.72 (m, 2H), 7.61 (m, 2H), 7.50 (m,
2H). 13C{1H} NMR (125 MHz, CDCl3, ppm): δ 159.5, 148.2, 138.8, 136.4, 134.1, 131.4,
129.9, 129.8, 129.3, 128.5, 127.9, 127.7, 127.1, 126.7 (2C), 126.1, 125.8, 125.5, 123.4.
2ꢀ(2ꢀNaphthyl)quinoline (1m)
Compound 1m was obtained as a brown solid (54 mg, 99%) after purification by column
chromatography on silica using a mixture of ethyl acetate and hexanes (1:6) as an eluent.
Spectroscopic data were matched with the reported values.18 Rf = 0.4 (ethyl acetate/hexanes =
1:10). 1H NMR (500 MHz, CDCl3, ppm): δ 8.63 (d, J = 0.9 Hz, 1H), 8.38 (dd, J = 8.6, 1.8 Hz,
1H), 8.27 (d, J = 8.4 Hz, 1H), 8.23 (d, J = 8.4 Hz, 1H), 8.05 (d, J = 8.7 Hz, 1H), 8.01 (m, 2H),
7.91 (m, 1H), 7.86 (dd, J = 8.1, 1.2 Hz, 1H), 7.76 (ddd, J = 8.4, 6.9, 1.4 Hz, 1H), 7.54 ppm (m,
3 H). 13C{1H} NMR (125 MHz, CDCl3, ppm): δ 157.3, 148.5, 137.1, 137.0, 134.0, 133.7,
129.9 (2C), 129.0, 128.7, 127.9, 127.6, 127.4, 127.3, 126.9, 126.5, 125.2, 119.3.
2ꢀ(2ꢀFuryl)quinoline (1n)
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Compound 1n was obtained as a brown solid (46 mg, 96%) after purification by column
chromatography on silica using a mixture of ethyl acetate and hexanes (1:6) as an eluent.
Spectroscopic data were matched with the reported values.17 Rf = 0.3 (ethyl acetate/hexanes =
1:10). 1H NMR (500 MHz, CDCl3, ppm): δ 8.17 (d, J = 8.5 Hz, 1H), 8.13 (d, J = 8.4 Hz, 1H),
7.83 (d, J = 8.5 Hz, 1H), 7.78 (dd, J = 8.1, 1.2 Hz, 1H), 7.71 (ddd, J = 1.4, 6.9, 8.4 Hz, 1H),
7.63 (dd, J = 1.7, 0.8 Hz, 1H), 7.50 (ddd, J = 8.1, 6.9, 1.1 Hz, 1H), 7.22 (dd, J = 3.4, 0.7 Hz,
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1H), 6.59 (dd, J = 3.4, 1.8 Hz, 1H). C{1H} NMR (125 MHz, CDCl3, ppm): δ 153.8, 149.1,
148.2, 144.2, 136.8, 130.0, 129.5, 127.7, 127.3, 126.3, 117.6, 112.3, 110.2.
2ꢀ(2ꢀThienyl)quinoline (1o)
Compound 1o was obtained as a yellow solid (42 mg, 98%) after purification by column
chromatography on silica using a mixture of ethyl acetate and hexanes (1:6) as an eluent.
Spectroscopic data were matched with the reported values.6a Rf = 0.3 (ethyl acetate/hexanes =
1:10). 1H NMR (500 MHz, CDCl3, ppm): δ 8.14 (d, J = 8.4 Hz, 1H), 8.09 (d, J = 8.4 Hz, 1H),
7.81 (d, J = 8.5 Hz, 1H), 7.78 (dd, J = 8.1, 1.2 Hz, 1H), 7.74 (dd, J = 3.7, 1.1 Hz, 1H), 7.70
(ddd, J = 8.4, 6.9, 1.4 Hz, 1H), 7.48 (m, 2H), 7.16 ppm (dd, J = 5.0, 3.7 Hz, 1H). 13C{1H}
NMR (125 MHz, CDCl3, ppm): δ 152.4, 148.2, 145.5, 136.7, 129.9, 129.4, 128.7, 128.2,
127.6, 127.3, 126.2, 126.0, 117.7.
6ꢀFluoroꢀ2ꢀphenylquinoline (1p)
Compound 1p was obtained as a pale yellow solid (44 mg, 99%) after purification by column
chromatography on silica using a mixture of ethyl acetate and hexanes (1:6) as an eluent.
Spectroscopic data were matched with the reported values.18 Rf = 0.4 (ethyl acetate/hexanes =
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1:10). H NMR (500 MHz, CDCl3, ppm): δ 8.16 (m, 4H), 7.91 (d, J = 8.5 Hz, 1H), 7.54 (m,
2H), 7.48 (m, 3H). 13C{1H} NMR (125 MHz, CDCl3, ppm): δ 161.4, 159.5, 156.9 (2C), 145.5,
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6ꢀChloroꢀ2ꢀphenylquinoline (1q)
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Compound 1q was obtained as a pale yellow solid (46 mg, 96%) after purification by column
chromatography on silica using a mixture of ethyl acetate and hexanes (1:6) as an eluent.
Spectroscopic data were matched with the reported values.18 Rf = 0.4 (ethyl acetate/hexanes =
1:10). 1H NMR (500 MHz, CDCl3, ppm): δ 8.15 (m, 3H), 8.11 (d, J = 9.0 Hz, 1H), 7.91 (d, J
= 8.7 Hz, 1H), 7.82 (d, J = 2.3 Hz, 1H), 7.66 (dd, J = 8.9, 2.4 Hz, 1H), 7.54 (m, 2H), 7.48 (m,
1H). 13C{1H} NMR (125 MHz, CDCl3, ppm): δ 157.6, 146.7, 139.3, 135.9, 132.0, 131.4,
130.6, 129.7, 129.0, 127.8, 127.6, 126.2, 119.8.
6ꢀBromoꢀ2ꢀphenylquinoline (1r)
Compound 1r was obtained as an orange solid (57 mg, 99%) after purification by column
chromatography on silica using a mixture of ethyl acetate and hexanes (1:6) as an eluent.
Spectroscopic data were matched with the reported values.20 Rf = 0.4 (ethyl acetate/hexanes =
1:10). 1H NMR (500 MHz, CDCl3, ppm): δ 8.16 (d, J = 7.0 Hz, 2H), 8.13 (d, J = 8.9 Hz, 1H),
8.04 (d, J = 9.0 Hz, 1H), 7.99 (d, J = 2.0 Hz, 1H), 7.90 (d, J = 8.5 Hz, 1H), 7.79 (dd, J = 9.0,
2.1 Hz, 1H), 7.54 (m, 2H), 7.48 (m, 1H). 13C{1H} NMR (125 MHz, CDCl3, ppm): δ 157.8,
146.9, 139.3, 135.9, 133.2, 131.6, 129.7, 129.6, 129.0, 128.3, 127.6, 120.2, 119.9.
6ꢀMethyoxyꢀ2ꢀphenylquinoline (1s)
Compound 1s was obtained as a pale yellow solid (41 mg, 87%) after purification by column
chromatography on silica using a mixture of ethyl acetate and hexanes (1:6) as an eluent.
Spectroscopic data were matched with the reported values.20 Rf = 0.3 (ethyl acetate/hexanes =
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1:10). 1H NMR (500 MHz, CDCl3, ppm): δ 8.13 (m, 3H), 8.07 (d, J = 9.2 Hz, 1H), 7.84 (d, J
= 8.5 Hz, 1H), 7.52 (m, 2H), 7.44 (m, 1H), 7.39 (dd, J = 9.2, 2.7 Hz, 1H), 7.10 (d, J = 2.7 Hz,
1H), 3.95 (s, 3H). 13C{1H} NMR (125 MHz, CDCl3, ppm): δ 157.8, 155.2, 144.5, 139.9,
135.7, 131.3, 129.1, 129.0, 128.3, 127.4, 122.5, 119.4, 105.1, 55.7.
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6ꢀMethoxyꢀ2ꢀ(4ꢀmethoxyphenyl)quinoline (1t)
Compound 1t was obtained as orange oil (50 mg, 95%) after purification by column
chromatography on silica using a mixture of ethyl acetate and hexanes (1:5) as an eluent.
Spectroscopic data were matched with the reported values.21 Rf = 0.3 (ethyl acetate/hexanes =
1:8). 1H NMR (500 MHz, CDCl3, ppm): δ 8.09 (m, 3 H), 8.03 (d, J = 9.2 Hz, 1H), 7.79 (dd, J
= 8.5, 1.4 Hz, 1H), 7.36 (dd, J = 9.2, 2.7 Hz, 1H), 7.08 (d, J = 2.6 Hz, 1H), 7.04 (m, 2H), 3.94
(s, 3H), 3.88 (s, 3H) 13C{1H} NMR (125 MHz, CDCl3, ppm): δ 160.6, 157.5, 154.8 144.5,
135.6, 132.5, 131.1, 128.7, 127.9, 122.3, 119.0, 114.3, 105.2, 55.7, 55.5.
7ꢀBromoꢀ2ꢀphenylquinoline (1u)
Compound 1u was obtained as a pale yellow solid (53 mg, 94%) after purification by column
chromatography on silica using a mixture of ethyl acetate and hexanes (1:6) as an eluent.
Spectroscopic data were matched with the reported values.18 Rf = 0.3 (ethyl acetate/hexanes =
1:10). 1H NMR (500 MHz, CDCl3, ppm): δ 8.37 (s, 1H), 8.19 (d, J = 8.5 Hz, 1H), 8.16 (d, J =
7.6 Hz, 2H), 7.90 (d, J = 8.5 Hz, 1H), 7.70 (d, J = 8.5 Hz, 1H), 7.61 (d, J = 8.7 Hz, 1H), 7.54
(m, 2H), 7.48 (m, 1H). 13C{1H} NMR (125 MHz, CDCl3, ppm): δ 158.3, 149.0, 139.3, 136.8,
132.2, 129.9, 129.8, 129.1, 128.9, 127.7, 125.9, 123.9, 119.4.
6,8ꢀDibromoꢀ2ꢀphenylquinoline (1v)
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Compound 1v was obtained as orange oil (60 mg, 82%) after purification by column
chromatography on silica using a mixture of ethyl acetate and hexanes (1:6) as an eluent.
Spectroscopic data were matched with the reported values.22 Rf = 0.3 (ethyl acetate/hexanes =
1:10). 1H NMR (500 MHz, CDCl3, ppm): δ 8.30 (m, 2H), 8.16 (d, J = 2.1 Hz, 1H), 8.12 (d, J
= 8.5 Hz, 1H), 7.98 (d, J = 8.5 Hz, 1H), 7.95 (d, J = 2.1 Hz, 1H), 7.55 (m, 2H), 7.50 (m, 1H).
13C{1H} NMR (125 MHz, CDCl3, ppm): δ 157.9, 144.0, 138.6, 136.4, 136.1, 130.2, 129.4,
129.1, 129.0, 127.8, 126.7, 120.1, 119.4.
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3ꢀMethylꢀ2ꢀphenylquinoline (1w)
Compound 1w was obtained as orange oil (35 mg, 80%) after purification by column
chromatography on silica using a mixture of ethyl acetate and hexanes (1:6) as an eluent.
Spectroscopic data were matched with the reported values.18 Rf = 0.3 (ethyl acetate/hexanes =
1:10). 1H NMR (500 MHz, CDCl3, ppm): δ 8.13 (d, J = 8.5 Hz, 1H), 8.03 (s, 1H), 7.79 (d, J =
8.1 Hz, 1H), 7.66 (m, 1H), 7.59 (m, 2H), 7.51 (m, 3H), 7.44 (m, 1H), 2.47 (s, 3H). 13C{1H}
NMR (125 MHz, CDCl3, ppm): δ 160.6, 146.6, 140.8, 137.0, 129.4, 129.2, 129.0 (2C), 128.4,
128.3, 127.7, 126.9, 126.6, 20.7.
2ꢀMethylquinoline (1x)
Compound 1x was obtained as a white solid (12 mg, 43%) after purification by column
chromatography on silica using a mixture of ethyl acetate and hexanes (1:6) as an eluent.
Spectroscopic data were matched with the reported values.6a Rf = 0.3 (ethyl acetate/hexanes =
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1:5). H NMR (500 MHz, CDCl3, ppm): δ 8.03 (t, J = 9.7 Hz, 2H), 7.77 (d, J = 8.1 Hz, 1H),
7.68 (m, 1H), 7.48 (m, 1H), 7.29 (dd, J = 8.4, 1.2 Hz, 1H), 2.75 (d, J = 1.2 Hz, 3H). 13C{1H}
NMR (125 MHz, CDCl3, ppm): δ 159.2, 148.0, 136.3, 129.6, 128.8, 127.6, 126.6, 125.8,
122.2, 25.5.
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