Three-Component Povarov Reaction with Alcohols as Alkene Precursors: Efficient Access to 2-Arylquinolines

Article abstract of DOI:10.1002/ejoc.201601343

An atom-economic and efficient approach to the synthesis of 2-arylquinolines has been developed. The protocol involves an iron-catalysed cascade N-alkylation/aerobic oxidation/Povarov reaction, and the desired quinolines were prepared in moderate to excellent yields from readily accessible anilines, aldehydes, and EtOH/nPrOH, with water as the only side-product. The aniline substrates also act as a recyclable transfer medium for EtOH/nPrOH through an in-situ N-alkylation/oxidation process. This makes EtOH/nPrOH an economical and environmentally friendly precursor of alkenes as well as the solvent.

Full text of DOI:10.1002/ejoc.201601343

DOI: 10.1002/ejoc.201601343
Full Paper
Quinoline Synthesis
Three-Component Povarov Reaction with Alcohols as Alkene
Precursors: Efficient Access to 2-Arylquinolines
Xinjian Li,[a,b] Qi Xing,[a] Pan Li,[a] Jingjing Zhao,[a] and Fuwei Li*[a]
Abstract: An atom-economic and efficient approach to the side-product. The aniline substrates also act as a recyclable
synthesis of 2-arylquinolines has been developed. The protocol transfer medium for EtOH/nPrOH through an in-situ N-alkyl-
involves an iron-catalysed cascade N-alkylation/aerobic oxid- ation/oxidation process. This makes EtOH/nPrOH an economical
ation/Povarov reaction, and the desired quinolines were pre- and environmentally friendly precursor of alkenes as well as the
pared in moderate to excellent yields from readily accessible solvent.
anilines, aldehydes, and EtOH/nPrOH, with water as the only
Introduction
the construction of 2-substituted quinolines from arylamines,
aldehydes, and electron-deficient acrylic acid through a palla-
dium-catalysed reaction involving a decarboxylation process
(Scheme 1c).[8] Furthermore, as early as in 1938, acetylene was
used in place of alkenes for the construction of 2-substituted
quinolines, with a copper or mercury catalyst, although low
yields were obtained (Scheme 1d).[9] Recently, Shimizu et al.
reported an iridium-catalysed two-step cyclization/oxidation re-
action with acetaldehyde as the alkene surrogate, which gave
2-substituted quinolines in quite low yields (Scheme 1e).[10a]
Very recently, alcohols were successfully used as the precursors
for aldehydes by Khusnutdinov's group in the synthesis of 2-
phenylquinolines; an argon atmosphere was needed, and only
three examples were reported.[10b] Despite the progress that
has been made in the synthesis of 2-substituted quinolines, the
reactions suffer from low yields, and require precious or toxic
metal catalysts and/or activated alkene substrates bearing leav-
ing groups. Therefore, there is still a need to explore the use of
greener and more atom-economical starting materials as well
as efficient catalyst systems to avoid these drawbacks.
Multicomponent cascade reactions are powerful protocols that
allow the synthesis of series of complex heterocycles.[1] Among
these domino processes, the Povarov-type reaction represents
an elegant method for the construction of the quinoline skele-
ton.[2] This transformation involves: 1) imine formation from an
aniline and a carbonyl compound; 2) Mannich-type reaction of
the imine with an activated alkene; 3) intramolecular aromatic
electrophilic substitution and subsequent oxidation to give the
quinoline nucleus. This process is compatible with a range of
anilines and carbonyl derivatives, and over the years much ef-
fort has been put into expanding the range of activated olefin
substrates that can be used in the reaction.[3] To date, alkynes,
aldehydes, and α-keto esters have also been successfully used
in this reaction in place of alkenes.[4] However, these methods
generally provide 3- or 4-substituted quinolines. In contrast, re-
search related to the synthesis of quinolines substituted at the
2-position but unsubstituted at the 3- and 4-positions remains
rare.[5] Since the substitution patterns on quinoline rings have
a great influence on the properties of these compounds,[6] the
development of new and efficient methods for the preparation
of differently substituted quinolines, based on the ideas of high
efficiency and atom economy, is highly desirable.
For several of these rare reports of the synthesis of 2-substi-
tuted quinolines, electron-rich vinyl ethers and enamines
bearing leaving groups were needed as starting materials
(Scheme 1a and b).[7] Recently, Jiang and coworkers achieved
[a] State Key Laboratory for Oxo Synthesis and Selective Oxidation, Suzhou
Research Institute of LICP, Lanzhou Institute of Chemical Physics (LICP),
Chinese Academy of Sciences,
Lanzhou 730000, P. R. China
E-mail: fuweili@licp.cas.cn
Scheme 1. Synthesis of 2-arylquinolines.
http://www.licp.cas.cn/rcjy/zgjgwry/yjy-lfw/
[b] University of Chinese Academy of Sciences,
Beijing 100049, P. R. China
Alcohols are easily available, and have been widely used for
the synthesis of alkenes. Based on previous elegant work on
quinoline synthesis, we wondered whether we could construct
quinolines from easily accessible anilines, aldehydes, and alco-
Supporting information for this article is available on the WWW under
http://dx.doi.org/10.1002/ejoc.201601343.
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hols through a Povarov-type multicomponent reaction, in tries 10–12). Next, we studied the influence of different halide
which the alcohols act as green and efficient precursors for alk- species. NaI and I2 gave yields similar to that obtained with KI,
enes. C–N bond construction between amines and alcohols has but TBAI (tetrabutylammonium iodide) and KBr proved to be
been intensively investigated, and great successes have been less efficient (Table 1, entries 13–16). TfOH also gave an efficient
achieved.[11] Inspired by this, we assumed that in-situ C–N-bond reaction, while the use of TFA (trifluoroacetic acid) caused a
coupling between anilines and alcohols and subsequent oxid- slight decrease in the yield (Table 1, entries 17 and 18). In addi-
ation might provide an indirect route for the construction of tion, lowering the reaction temperature to 120 °C resulted in a
electron-rich enamines, which could be used as the alkene decreased yield (Table 1, entry 19). It is notable that the reac-
components for the Povarov-type reaction to construct the cor- tion could also be smoothly carried out under an air atmos-
responding quinoline skeleton. The aniline leaving group would phere, although this gave a slightly lower yield (Table 1, en-
return to the reaction system for another circulation; this could try 20).
simultaneously avoid the waste generated through the use of
traditional leaving groups and also the preparation of activated
Table 1. Optimization of reaction conditions.[a]
alkenes. As we know, iron, an inexpensive, abundant, and non-
toxic metal, offers a wide range of oxidation and spin states.[12]
These features make it a potential catalyst for oxidation through
single-electron catalysis under an oxygen atmosphere.[13] In a
continuation of our previous research into heterocycle synthe-
sis, in this paper we report an iron-catalysed aerobic oxidative
Povarov reaction for quinoline synthesis from anilines, alde-
hydes, and alcohols (Scheme 1f). In this reaction, alcohols were
used as precursors of alkenes for the first time, and good results
were achieved.
Entry
Metal catalyst
Acid
Halide salt
Yield [%]
1
2
3
4
5
6
7
8
FeCl3·6H2O
FeCl3·6H2O
FeCl3·6H2O
FeCl3·6H2O
–
Fe(acac)3
Fe(OTf)3
Fe(OTf)2
FeCl2
CuCl2
AlCl3
ZnCl2
FeCl3·6H2O
FeCl3·6H2O
FeCl3·6H2O
FeCl3·6H2O
FeCl3·6H2O
FeCl3·6H2O
FeCl3·6H2O
FeCl3·6H2O
–
–
KI
–
KI
KI
KI
KI
KI
KI
KI
KI
KI
NaI
I2
TBAI
KBr
KI
24
PTSA
PTSA
–
81 (81)[b]
48
26
17
9
14
14
58
10
16
14
81
78
52
31
81
71
52
PTSA
PTSA
PTSA
PTSA
PTSA
PTSA
PTSA
PTSA
PTSA
PTSA
PTSA
PTSA
TfOH
TFA
Results and Discussion
9
10
11
12
13
14
15
16
17
18
19[c]
20[d]
Initially, the reaction of p-chloroaniline (1a) and 3,4-dimethoxy-
benzaldehyde (2a) in ethanol was chosen as a model reaction
to optimize the reaction conditions. To our delight, when sub-
strates 1a and 2a were treated with FeCl3·6H2O (10 mol-%) in
ethanol under an oxygen atmosphere, the desired product 3aa
was obtained in 24 % yield (Table 1, entry 1). On the basis of
previous work on N-alkylation, we assumed that the aromatic
amine could react with the alcohol to give an N-alkyl amine
derivative with the assistance of acid and halide anions. So we
mixed 1a with a catalytic amount (20 mol-%) of p-toluene-
sulfonic acid (PTSA) and KI in ethanol, and a 32 % yield of 4-
chloro-N-ethylaniline was isolated, along with a trace amount
of 4-chloro-N,N-diethylaniline (Equation S2 in the Supporting
Information). Encouraged by this result, we added PTSA
KI
KI
KI
PTSA
PTSA
77
[a] Reaction conditions: 1a (0.66 mmol), 2a (0.30 mmol), catalyst (10 mol-%),
acid (20 mol-%), halide salt (20 mol-%), ethanol (3 mL), oxygen atmosphere
(1 atm), 140 °C, 12 h. HPLC yields. [b] Isolated yield. [c] 120 °C. [d] 1 atm air
was used instead of O2. TFA = trifluoroacetic acid.
With optimal reaction conditions identified, we went on to
(20 mol-%) and KI (20 mol-%) to the reaction system, and the investigate the scope of the reaction. We first investigated the
yield increased dramatically from 24 to 81 % (Table 1, entry 2). scope of the reaction with respect to the aldehyde component.
Significantly diminished yields were obtained in the absence of As shown in Scheme 2, the reaction of 4-chloroaniline with un-
PTSA or KI; this indicates that acid and KI are both essential for substituted benzaldehyde proceeded smoothly, giving 3ab in
this transformation (Table 1, entries 3 and 4). Furthermore, a 63 % yield. For substituted benzaldehydes, both electron-do-
control experiment was carried out without the iron catalyst, nating (-Me, -OMe, -tBu) and electron-withdrawing (-Cl, -Br,
and the desired product was formed in poor yield (Table 1, -NO2) substituents on the benzene ring of benzaldehyde deriva-
entry 5). Subsequently, several metal salts were investigated to tives were well tolerated under the standard conditions, giving
examine their catalytic efficiency in the reaction. When iron the desired products 3ac–3ai in moderate to good yields. For
salts with different anions were used, such as Fe(acac)3, example, p-methoxybenzaldehyde underwent the reaction
Fe(OTf)3, or Fe(OTf)2, yields of 3aa of only 9–14 % were ob- smoothly, providing 3ad in yields as high as 93 %. The sterically
tained; while a moderate yield was obtained with FeCl2 as the hindered 2-methoxybenzaldehyde also reacted with 4-chloro-
catalyst (Table 1, entries 6–9). Thus, the anion component of the aniline to give the corresponding product 3af in 72 % yield. To
iron salt has a pronounced effect on its catalytic performance. our delight, the strongly electron-withdrawing nitro group was
Significantly, under similar reaction conditions, other metal salts also well tolerated, and 3ai was formed in 72 % yield. Notably,
such as CuCl2, AlCl3, and ZnCl2 all showed lower reactivities, benzaldehyde substituted with an active halogen group (-Br)
and yields of 3aa of only 10–16 % were obtained (Table 1, en- gave the corresponding halogen-substituted 2-phenylquinoline
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3ah in excellent yield, thus providing the potential for further
functionalization. Disubstituted (3,5-dimethoxy, 2,6-dichloro)
benzaldehydes were also suitable for this reaction, providing
the corresponding products 3aj and 3ak in moderate to good
yields. We were delighted to find that 2-naphthaldehyde also
underwent the reaction efficiently to give 3al in up to 92 %
yield. Heterocyclic aldehydes also gave the target products
3am, 3an in moderate yields, but aliphatic aldehydes were not
suitable for this reaction. A scaled-up reaction of p-methoxy-
benzaldehyde and p-chloroaniline worked well under the stan-
dard conditions to give the target product 3ad in 80 % yield
(1.07 g); this demonstrates the high efficiency of this transfor-
mation.
Scheme 3. Scope of the reaction in terms of aromatic amines. Reaction condi-
tions:
1 (0.66 mmol), 2d (0.30 mmol), FeCl3·6H2O (0.03 mmol), PTSA
(0.06 mmol), KI (0.06 mmol), oxygen atmosphere (1 atm), C2H5OH (3 mL),
12 h. Isolated yields.
ated anilines to yield imine intermediates, except for N-ethyl
anilines and N-propyl anilines. As a result, the cascade reaction
stopped at this oxidation step, so the reaction could not be
used with other alcohols.
Scheme 4. The cascade reaction in n-propanol instead of ethanol. Reaction
conditions: 1 (0.66 mmol), 2 (0.30 mmol), FeCl3·6H2O (0.03 mmol), PTSA
(0.06 mmol), KI (0.06 mmol), oxygen atmosphere (1 atm), n-propanol (3 mL),
12 h. Isolated yields.
Scheme 2. Scope of the reaction in terms of aromatic aldehydes.[a] Reaction
conditions: [a] 1a (0.66 mmol), 2 (0.30 mmol), FeCl3·6H2O (0.03 mmol), PTSA
(0.06 mmol), KI (0.06 mmol), oxygen atmosphere (1 atm), C2H5OH (3 mL),
12 h. Isolated yields. [b] 1a (11 mmol), 2d (5 mmol), FeCl3·6H2O (0.5 mmol),
PTSA (1 mmol), KI (1 mmol), oxygen atmosphere (1 atm), C2H5OH (20 mL),
24 h; 1.07 g of 3ad was isolated.
A series of control experiments was carried out to gain infor-
mation about the reaction mechanism (Scheme 5). Firstly, when
methanol was used instead of ethanol, none of the target prod-
uct was generated [Equation (1)]. This result confirms that eth-
anol participates in the reaction as a carbon source. In the be-
ginning, we envisioned a possibility that aromatic amines might
react with alcohols in the presence of PTSA and KI to form N-
ethylaniline, which could then be converted into an enamine
through oxidative dehydrogenation. To verify this speculation,
we replaced KI with ethyl iodide (50 mol-%). As expected, the
We next investigated the scope of the reaction in terms of
the aniline component. As shown in Scheme 3, anilines with
electron-donating groups and electron-withdrawing groups
were generally tolerated, and gave the desired quinoline deriva-
tives 3bd–3hd in moderate to good yields. The reaction of 3-
chloroaniline also proceeded smoothly at the less sterically hin-
dered position, selectively giving 3id in 77 % yield.
We also investigated the reactivity of other alcohols. To our reaction proceeded well, and provided the desired product in
delight, n-propanol also participated efficiently in this reaction. 88 % yield [Equation (2)]. Furthermore, a reaction mixture of
Similarly to the reaction with ethanol, both electron-donating aniline, imine, and N-ethylaniline in ethanol under the standard
and electron-withdrawing substituents were tolerated in this conditions gave the desired product in 71 % yield [Equa-
reaction, and a series of 2,3-disubstituted quinoline derivatives tion (3)]. Here, aniline was present to prevent the hydrolysis of
were formed selectively in moderate to good yields (Scheme 4). the imine. Similarly, a good yield was also achieved when meth-
Unfortunately, other alcohols could not act as alkene precursors anol was used instead of ethanol [Equation (4)]. These results
for this transformation, though N-alkylation of anilines with confirm the involvement of N-ethylaniline and imine intermedi-
other alcohols did proceed smoothly under the same reaction ates in the reaction. To obtain more information about the reac-
conditions (Equation S15 in the Supporting Information). Con- tion mechanism, we carried out the reaction of aniline, imine,
trol experiments (Equations S16–22 in the Supporting Informa- and N-ethylaniline without an FeIII catalyst, and found the yield
tion) indicated that Fe catalysts were not effective for the aero- of the desired product 3ad decreased a lot [Equation (5)]. In
bic oxidative dehydrogenation of the in-situ-generated N-alkyl- contrast, when this reaction was carried out with an iron cata-
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lyst in the absence of PTSA (20 mol-%) and KI (20 mol-%), 3ad generated from the corresponding amine and aldehyde,
was obtained in good yield (68 %) [Equation (6)]. These results through a Povarov process to generate tetrahydroquinoline de-
indicate that the Fe catalyst might play an important role in the rivative E. Under acidic conditions, E is converted into dihydro-
oxidation of 1a1. In addition, a series of control experiments quinoline derivative F, and aniline is released for the next cycle.
was also carried out by using the reactant mixture of p-chloro- Finally, F undergoes further oxidative aromatization to give the
aniline (1a) with acetaldehyde (Equation S9 in the Supporting target compound.
Information). The results indicated that the N-vinylalinine might
be an intermediate of this reaction, and that the Fe catalyst
does play a key role in the oxidation of 1a1.
Conclusions
In conclusion, we have developed a simple, new, and efficient
catalytic approach for the synthesis of 2-arylquinoline deriva-
tives from readily accessible anilines, aldehydes, and alcohols.
In this reaction, environmentally benign oxygen and a salt of
naturally abundant iron were used as the oxidant and catalyst,
respectively. In addition, alcohols were used as precursors of
alkenes in this transformation for the first time. The reaction
proceeds through an in-situ N-alkylation/oxidation process.
Good results were achieved, and the reaction was also carried
out on a gram scale. Further investigations into the application
of this method in organic synthesis are currently underway in
our laboratory.
Experimental Section
General Procedure for Quinoline Synthesis: A Schlenk tube
(50 mL) with a magnetic stirrer bar was loaded with 1 (0.66 mmol),
2 (0.30 mmol), FeCl3·6H2O (10 mol-%), PTSA (20 mol-%), KI (20 mol-
%), and C2H5OH (3 mL). Then a gas exchange was carried out three
times, and the Schlenk tube was filled with oxygen gas. The mixture
was stirred at 140 °C for 12 h, then it was cooled to room tempera-
ture, and transferred into a flask (100 mL). The solvent was removed,
and the residue was purified by column chromatography (petro-
leum ether/EtOAc) to give the desired quinoline 3 and 4.
Scheme 5. Control experiments to investigate the mechanism.
Based on the above experimental results, we propose a plau-
sible mechanism as shown in Scheme 6. Initially, aniline (A) re-
acts with ethyl iodide, generated from ethanol and KI under
acidic conditions, to produce B1 and B2. Subsequently, B1 was
oxidized by O2 under the catalysis of the iron catalyst to give
C2 (path a). Intermediate C2 could also be generated through
the reaction of amines and acetaldehyde (generated from the
oxidation of ethanol; path b). Then, C1 reacts with imine D,
General Procedure for the Large-Scale Reaction: Compound 1a
(11 mmol), 2d (5 mmol), FeCl3·6H2O (10 mol-%), PTSA (20 mol-%),
KI (20 mol-%), and C2H5OH (20 mL) were put into a Schlenk tube
(250 mL) with a magnetic stirrer bar. Then the general procedure
for quinoline synthesis was followed, but the reaction time was
increased to 24 h. This gave 3ad (1.07 g, 80 %).
6-Chloro-2-(3,4-dimethoxyphenyl)quinoline (3aa): Yellow solid;
m.p. 117–119 °C. Rf = 0.16 (petroleum ether/EtOAc, 8:1). 1H NMR
(400 MHz, CDCl3): δ = 8.09–8.02 (m, 2 H), 7.87–7.81 (m, 2 H), 7.76
(d, J = 2.3 Hz, 1 H), 7.66–7.59 (m, 2 H), 6.97 (d, J = 8.4 Hz, 1 H), 4.04
(s, 3 H), 3.95 (s, 3 H) ppm. 13C NMR (100 MHz, CDCl3): δ = 156.9,
150.5, 149.4, 146.5, 135.6, 132.0, 131.5, 131.0, 130.4, 127.4, 126.1,
120.2, 119.3, 111.0, 110.2, 56.0, 56.0 ppm. HRMS (ESI): calcd. for
C17H15ClNO2 [M + H]+ 300.0786; found 300.0774.
6-Chloro-2-phenylquinoline (3ab):[14] White solid; m.p. 111–
114 °C. Rf = 0.74 (petroleum ether/EtOAc, 8:1). 1H NMR (400 MHz,
CDCl3): δ = 8.18–8.08 (m, 4 H), 7.90 (d, J = 8.6 Hz, 1 H), 7.81 (d, J =
2.3 Hz, 1 H), 7.66 (dd, J = 9.0, 2.3 Hz, 1 H), 7.58–7.45 (m, 3 H) ppm.
13C NMR (100 MHz, CDCl3): δ = 157.6, 146.7, 139.2, 135.8, 131. 9,
131.3, 130.6, 129.6, 128.9 (two peaks overlapping), 127.7, 127.5 (two
peaks overlapping), 126.1, 119.78 ppm. HRMS (ESI): calcd. for
C
15H11ClN [M + H]+ 240.0575; found 240.0578.
6-Chloro-2-(p-tolyl)quinoline (3ac): White solid; m.p. 1623–171 °C.
Rf = 0.74 (petroleum ether/EtOAc, 8:1). 1H NMR (400 MHz, CDCl3):
δ = 8.13–8.03 (m, 4 H), 7.87 (d, J = 8.7 Hz, 1 H), 7.79 (d, J = 2.1 Hz,
1 H), 7.64 (dd, J = 9.0, 2.3 Hz, 1 H), 7.34 (d, J = 7.9 Hz, 2 H), 2.44 (s,
Scheme 6. Proposed reaction mechanism.
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3 H) ppm. 13C NMR (100 MHz, CDCl3): δ = 157.5, 146.7, 139.7, 136.4,
1 H), 7.80 (d, J = 8.6 Hz, 1 H), 7.74 (d, J = 2.2 Hz, 1 H), 7.63 (dd, J =
135.7, 131.6, 131.2, 130.4, 129.6 (two peaks overlapping), 127.6, 9.0, 2.3 Hz, 1 H), 7.30 (d, J = 2.3 Hz, 2 H), 6.58 (t, J = 2.2 Hz, 1 H),
127.4 (two peaks overlapping), 126.1, 119.6, 21.3 ppm. HRMS (ESI):
3.89 (s, 6 H) ppm. 13C NMR (100 MHz, CDCl3): δ = 161.2, 157.2, 146.5,
141.3, 135.8, 132.0, 131.3, 130.5, 127.9, 126.1, 119.9, 105.6, 101.8,
55.5 (two peaks overlapping) ppm. HRMS (ESI): calcd. for
calcd. for C16H13ClN [M + H]+ 254.0731; found 254.0729.
6-Chloro-2-(4-methoxyphenyl)quinoline (3ad): Yellow solid; m.p.
162 °C. Rf = 0.54 (petroleum ether/EtOAc, 8:1). 1H NMR (400 MHz,
C
17H15ClNO2 [M + H]+ 300.0786; found 300.0788.
CDCl3): δ = 8.12 (d, J = 8.8 Hz, 2 H), 8.06 (d, J = 8.8 Hz, 2 H), 7.83 6-Chloro-2-(2,6-dichlorophenyl)quinoline (3ak): Brown solid;
(d, J = 8.6 Hz, 1 H), 7.76 (s, 1 H), 7.63 (dd, J = 9.0, 2.3 Hz, 1 H), 7.04
m.p. 91–96 °C. Rf = 0.58 (petroleum ether/EtOAc, 8:1). 1H NMR
(d, J = 8.8 Hz, 2 H), 3.88 (s, 3 H) ppm. 13C NMR (100 MHz, CDCl3): (400 MHz, CDCl3): δ = 8.19 (d, J = 8.4 Hz, 1 H), 8.12 (d, J = 9.0 Hz,
δ = 161.0, 157.0, 146.6, 135.6, 131.7, 131.4, 131.1, 130.4, 128.8 (two
peaks overlapping), 127.4, 126.1, 119.3, 114.3 (two peaks overlap-
ping), 55.4 ppm. HRMS (ESI): calcd. for C16H13ClNO [M + H]+
270.0680; found 270.0683.
1 H), 7.88 (d, J = 2.2 Hz, 1 H), 7.69 (dd, J = 9.0, 2.3 Hz, 1 H), 7.48–
7.42 (m, 3 H), 7.32 (dd, J = 8.7, 7.5 Hz, 1 H) ppm. 13C NMR (100 MHz,
CDCl3): δ = 156.1, 146.3, 138.3, 135.6, 134.5, 132.9, 131.3, 130.7,
130.1, 128.3, 127.9, 126.3, 123.4 ppm. HRMS (ESI): calcd. for
C
15H9Cl3N [M + H]+ 307.9795; found 307.9784.
2-[4-(tert-Butyl)phenyl]-6-chloroquinoline (3ae): White solid;
m.p. 174–176 °C. Rf = 0.82 (petroleum ether/EtOAc, 8:1). 1H NMR 6-Chloro-2-(naphthalen-2-yl)quinoline (3al): White solid; m.p.
(400 MHz, CDCl3): δ = 8.13–8.06 (m, 4 H), 7.88 (t, J = 8.2 Hz, 1 H),
7.78 (d, J = 2.0 Hz, 1 H), 7.65 (dd, J = 9.0, 2.3 Hz, 1 H), 7.56 (d, J =
8.5 Hz, 2 H), 1.39 (s, 9 H) ppm. 13C NMR (100 MHz, CDCl3): δ = 157.5,
171–176 °C. Rf = 0.62 (petroleum ether/EtOAc, 8:1). 1H NMR
(400 MHz, CDCl3): δ = 8.60 (d, J = 1.0 Hz, 1 H), 8.35 (dd, J = 8.6,
1.8 Hz, 1 H), 8.14 (dd, J = 8.8, 2.1 Hz, 2 H), 8.06–7.97 (m, 3 H), 7.93–
152.8, 146.7, 136.4, 135.6, 131.6, 131.3, 130.4, 127.6, 127.2 (two 7.87 (m, 1 H), 7.81 (d, J = 2.3 Hz, 1 H), 7.68 (dd, J = 9.0, 2.3 Hz, 1 H),
peaks overlapping), 126.1, 125.9 (two peaks overlapping), 119.7, 7.58–7.51 (m, 2 H) ppm. 13C NMR (100 MHz, CDCl3): δ = 157.3, 146.7,
34.7, 31.3 ppm. HRMS (ESI): calcd. for C19H19ClN [M + H]+ 296.1201; 136.5, 135.8, 133.9, 133.4, 131.9, 131.3, 130.6, 128.8, 128.6, 127.7
found 296.1199.
(two peaks overlapping), 127.2, 126.8, 126.4, 126.2, 124.8,
119.9 ppm. HRMS (ESI): calcd. for C19H13ClN [M + H]+ 290.0731;
found 290.0719.
6-Chloro-2-(2-methoxyphenyl)quinoline (3af): Yellow solid; m.p.
103–107 °C. Rf = 0.56 (petroleum ether/EtOAc, 8:1). 1H NMR
(400 MHz, CDCl3): δ = 8.10 (d, J = 9.0 Hz, 1 H), 8.04 (d, J = 8.6 Hz,
1 H), 7.93 (d, J = 8.6 Hz, 1 H), 7.86 (d, J = 7.5 Hz, 1 H), 7.80 (s, 1 H),
7.63 (dd, J = 9.0, 2.3 Hz, 1 H), 7.43 (ddd, J = 8.3, 7.5, 1.8 Hz, 1 H),
7.18–7.11 (m, 1 H), 7.04 (d, J = 8.3 Hz, 1 H), 3.87 (s, 3 H) ppm. 13C
NMR (100 MHz, CDCl3): δ = 157.3, 157.2, 146.6, 134.1, 131.7, 131.4,
6-Chloro-2-(thiophen-2-yl)quinoline (3am): White solid; m.p.
107–109 °C. Rf = 0.6 (petroleum ether/EtOAc, 8:1). 1H NMR
(400 MHz, CDCl3): δ = 8.00 (d, J = 7.4 Hz, 2 H), 7.84–7.67 (m, 3 H),
7.61 (d, J = 7.1 Hz, 1 H), 7.48 (s, 1 H), 7.15 (s, 1 H) ppm. 13C NMR
(100 MHz, CDCl3): δ = 152.5, 146.4, 144.9, 135.6, 131.6, 130.7, 130.6,
131.21, 130.5, 130.0, 129.2, 127.5, 126.0, 124.3, 121.3, 111.4, 128.9, 128.1, 127.6, 126.1, 126.1, 118.4 ppm. HRMS (ESI): calcd. for
55.6 ppm. HRMS (ESI): calcd. for C16H13ClNO [M + H]+ 270.0680;
found 270.0670.
C13H9ClNS [M + H]+ 246.0139; found 246.0137.
6-Chloro-2-(pyridin-4-yl)quinoline (3an):[16] Yellow solid; m.p.
167–169 °C. Rf = 0.12 (petroleum ether/EtOAc, 2:1). 1H NMR
(400 MHz, CDCl3): δ = 8.79 (d, J = 4.0 Hz, 2 H), 8.20 (d, J = 8.5 Hz,
1 H), 8.12 (d, J = 8.9 Hz, 1 H), 8.05 (d, J = 4.5 Hz, 2 H), 7.93 (d, J =
8.5 Hz, 1 H), 7.84 (s, 1 H), 7.70 (d, J = 8.3 Hz, 1 H) ppm. 13C NMR
(101 MHz, CDCl3): δ = 154.7, 150.6, 146.6, 146.1, 136.3, 133.0, 131.6,
131.1, 128.3, 126.2, 121.5, 119.3 ppm. HRMS (ESI): calcd. for
C14H10ClN2 [M + H]+ 241.0527; found 241.0521.
2-(4-Methoxyphenyl)quinoline (3bd):[17] White solid; m.p. 126–
129 °C. Rf = 0.48 (petroleum ether/EtOAc, 8:1). 1H NMR (400 MHz,
CDCl3): δ = 8.20–8.11 (m, 4 H), 7.85–7.77 (m, 2 H), 7.71 (dd, J = 8.2,
7.1 Hz, 1 H), 7.50 (t, J = 7.5 Hz, 1 H), 7.05 (d, J = 8.7 Hz, 2 H), 3.88
(s, 3 H) ppm. 13C NMR (100 MHz, CDCl3): δ = 160.8, 156.8, 148.3,
136.6, 132.2, 129.5, 129.5, 128.8 (two peaks overlapping), 127.4,
6-Chloro-2-(4-chlorophenyl)quinoline (3ag): White solid; m.p.
162–168 °C. Rf = 0.70 (petroleum ether/EtOAc, 8:1). 1H NMR
(400 MHz, CDCl3): δ = 8.14–8.05 (m, 4 H), 7.84 (d, J = 8.7 Hz, 1 H),
7.79 (d, J = 2.3 Hz, 1 H), 7.66 (dd, J = 9.0, 2.3 Hz, 1 H), 7.49 (dd, 2
H) ppm. 13C NMR (100 MHz, CDCl3): δ = 156.2, 146.6, 137.5, 136.0,
135.8, 132.1, 131.3, 130.7, 129.1 (two peaks overlapping), 128.7 (two
peaks overlapping), 127.7, 126.1, 119.3 ppm. HRMS (ESI): calcd. for
C15H10Cl2N [M + H]+ 274.0185; found 274.0173.
2-(4-Bromophenyl)-6-chloroquinoline (3ah): Yellow solid; m.p.
180–184 °C. Rf = 0.70 (petroleum ether/EtOAc, 8:1). 1H NMR
(400 MHz, CDCl3): δ = 8.13 (d, J = 8.6 Hz, 1 H), 8.08 (d, J = 9.0 Hz,
1 H), 8.06–8.02 (m, 2 H), 7.85 (d, J = 8.7 Hz, 1 H), 7.81 (d, J = 2.3 Hz,
1 H), 7.69–7.63 (m, 3 H) ppm. 13C NMR (100 MHz, CDCl3): δ = 156.
2, 146.6, 138.0, 136.0, 132.2, 132.0 (two peaks overlapping), 131.3, 126.9, 125.8, 118.5, 114.2 (two peaks overlapping), 55.3 ppm. HRMS
130.8, 129.0 (two peaks overlapping), 127.8, 126.2, 124.2,
119.3 ppm. HRMS (ESI): calcd. for C15H10BrN [M + H]+ 317.9680;
found 317.9665.
(ESI): calcd. for C16H14NO [M + H]+ 236.1070; found 236.1064.
2-(4-Methoxyphenyl)-6-methylquinoline (3cd):[18] White solid;
m.p. 138 °C. Rf = 0.46 (petroleum ether/EtOAc, 8:1). 1H NMR
6-Chloro-2-(3-nitrophenyl)quinoline (3ai):[15] White solid; m.p. (400 MHz, CDCl3): δ = 8.15–8.10 (m, 2 H), 8.08 (d, J = 8.6 Hz, 1 H),
101–118 °C. Rf = 0.42 (petroleum ether/EtOAc, 8:1). 1H NMR
(400 MHz, CDCl3): δ = 9.00 (t, J = 1.9 Hz, 1 H), 8.52–8.47 (m, 1 H),
8.29 (ddd, J = 8.2, 2.2, 0.9 Hz, 1 H), 8.17 (d, J = 8.6 Hz, 1 H), 8.08 (d,
8.03 (d, J = 8.4 Hz, 1 H), 7.79 (d, J = 8.6 Hz, 1 H), 7.54 (m, 2 H), 7.07–
7.02 (m, 2 H), 3.88 (s, 3 H), 2.54 (s, 3 H) ppm. 13C NMR (100 MHz,
CDCl3): δ = 160.6, 156.1, 146.9, 135.9, 135.7, 132.4, 131.8, 129.2,
J = 9.0 Hz, 1 H), 7.91 (d, J = 8.6 Hz, 1 H), 7.80 (d, J = 2.3 Hz, 1 H), 128.7 (two peaks overlapping), 126.9, 126.3, 118.5, 114.2 (two peaks
7.72–7.63 (m, 2 H) ppm. 13C NMR (100 MHz, CDCl3): δ = 154.5, 148.8,
overlapping), 55.4, 21.5 ppm. HRMS (ESI): calcd. for C17H16NO [M +
146.5, 140.7, 136.4, 133.1, 132.8, 131.4, 131.1, 129. 8, 128.0, 126.2, H]+ 250.1226; found 250.1228.
124.0, 122.3, 119.0 ppm. HRMS (ESI): calcd. for C15H10ClN2O2 [M +
6-Methoxy-2-(4-methoxyphenyl)quinoline (3dd):[19] White solid;
H]+ 385.0425; found 385.0426.
m.p. 178–183 °C. Rf = 0.30 (petroleum ether/EtOAc, 8:1). 1H NMR
(400 MHz, CDCl3): δ = 8.14–8.02 (m, 4 H), 7.78 (d, J = 8.6 Hz, 1 H),
6-Chloro-2-(3,5-dimethoxyphenyl)quinoline (3aj): Yellow solid;
m.p. 115–119 °C. Rf = 0.44 (petroleum ether/EtOAc, 8:1). 1H NMR 7.37 (dd, J = 9.1, 2.7 Hz, 1 H), 7.07 (d, J = 2.5 Hz, 1 H), 7.04 (d, J =
(400 MHz, CDCl3): δ = 8.08 (d, J = 9.0 Hz, 1 H), 8.04 (d, J = 8.7 Hz,
8.7 Hz, 2 H), 3.94 (s, 3 H), 3.88 (s, 3 H) ppm. 13C NMR (100 MHz,
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CDCl3): δ = 160.5, 157.4, 154.7, 144.3, 135.4, 132.4, 130.9, 128.5 (two 2-(4-Methoxyphenyl)-6,7-dimethylquinoline (3kd): Yellow solid;
peaks overlapping), 127.8, 122.1, 118.8, 114.2 (two peaks overlap-
ping), 105.1, 55.5, 55.4 ppm. HRMS (ESI): calcd. for C17H16NO2 [M +
H]+ 266.1176; found 266.1165.
m.p. 155–160 °C. Rf = 0.50 (petroleum ether/EtOAc, 8:1). 1H NMR
(400 MHz, CDCl3): δ = 8.14–8.09 (m, 2 H), 8.05 (d, J = 8.6 Hz, 1 H),
7.90 (s, 1 H), 7.74 (d, J = 8.6 Hz, 1 H), 7.53 (s, 1 H), 7.06–7.01 (m, 2
H), 3.88 (s, 3 H), 2.48 (s, 3 H), 2.44 (s, 3 H) ppm. 13C NMR (100 MHz,
CDCl3): δ = 160.6, 156.0, 147.4, 139.7, 135.7, 135.5, 132.6, 128.9,
128.7 (two peaks overlapping), 126.7, 125.5, 117.7, 114.1 (two peaks
overlapping), 55.4, 20.4, 20.0 ppm. HRMS (ESI): calcd. for C18H18NO
[M + H]+ 264.1383; found 264.1386.
2-(4-Methoxyphenyl)-6-phenoxyquinoline (3ed): White solid;
m.p. 140–145 °C. Rf = 0.48 (petroleum ether/EtOAc, 8:1). 1H NMR
(400 MHz, CDCl3): δ = 8.15–8.10 (m, 3 H), 8.02 (d, J = 8.7 Hz, 1 H),
7.80 (d, J = 8.7 Hz, 1 H), 7.48 (dd, J = 9.1, 2.7 Hz, 1 H), 7.40 (t, J =
7.9 Hz, 2 H), 7.23 (d, J = 2.6 Hz, 1 H), 7.18 (t, J = 7.4 Hz, 1 H), 7.11
(d, J = 7.8 Hz, 2 H), 7.05 (d, J = 8.8 Hz, 2 H), 3.89 (s, 3 H) ppm. 13C
NMR (100 MHz, CDCl3): δ = 160.7, 156.8, 155.7, 155.1, 145.1, 135.7,
132.2, 131.4, 129.9 (two peaks overlapping), 128.7 (two peaks over-
lapping), 127.6, 123.8, 123.2, 119.4 (two peaks overlapping), 118.9,
114.2 (two peaks overlapping), 112.9, 55.4 ppm. HRMS (ESI): calcd.
for C22H18NO2 [M + H]+ 328.1332; found 328.1327.
6-Chloro-3-methyl-2-phenylquinoline (4ab): Yellow solid; m.p.
76–80 °C. Rf = 0.56 (petroleum ether/EtOAc, 8:1). 1H NMR (400 MHz,
CDCl3): δ = 8.05 (d, J = 9.0 Hz, 1 H), 7.90 (s, 1 H), 7.74 (d, J = 2.3 Hz,
1 H), 7.61–7.56 (m, 3 H), 7.53–7.42 (m, 3 H), 2.46 (s, 3 H) ppm. 13C
NMR (100 MHz, CDCl3): δ = 160.7, 144.9, 140.4, 135.7, 132.0, 130. 9,
130.3, 129.6, 128.7 (two peaks overlapping), 128.3, 128.3 (two peaks
overlapping), 128.1, 125.3, 20.6 ppm. HRMS (ESI): calcd. for
C
16H13ClN [M + H]+ 254.0731; found 254.0736.
6-Fluoro-2-(4-methoxyphenyl)quinoline (3fd): White solid; m.p.
142–144 °C. Rf = 0.70 (petroleum ether/EtOAc, 8:1). 1H NMR
(400 MHz, CDCl3): δ = 8.16–8.07 (m, 4 H), 7.83 (d, J = 8.6 Hz, 1 H),
7.51–7.44 (m, 1 H), 7.40 (dd, J = 8.8, 2.8 Hz, 1 H), 7.08–7.02 (m, 2 H),
3.88 (s, 3 H) ppm. 13C NMR (100 MHz, CDCl3): δ = 160.8, 160.1 (d,
6-Chloro-3-methyl-2-(p-tolyl)quinoline (4ac): Yellow solid; m.p.
85–89 °C. Rf = 0.60 (petroleum ether/EtOAc, 8:1). 1H NMR (400 MHz,
CDCl3): δ = 8.04 (d, J = 9.0 Hz, 1 H), 7.88 (s, 1 H), 7.73 (d, J = 2.3 Hz,
1 H), 7.57 (dd, J = 9.0, 2.3 Hz, 1 H), 7.51–7.47 (m, 2 H), 7.30 (d, J =
7.8 Hz, 2 H), 2.47 (s, 3 H), 2.43 (s, 3 H) ppm. 13C NMR (100 MHz,
CDCl3): δ = 160.8, 145.0, 138.2, 137.6, 135.6, 131.8, 130.9, 130.3,
129.5, 129.0 (two peaks overlapping), 128.7 (two peaks overlap-
ping), 128.0, 125.3, 21.3, 20.7 ppm. HRMS (ESI): calcd. for C17H15ClN
[M + H]+ 268.0888; found 268.0887.
J
J
C,F = 247.3 Hz), 156.2, 145.3, 135.9 (d, JC,F = 5.2 Hz), 131.9, 131.9 (d,
C,F = 9.0 Hz), 128.7, 127.3 (d, JC,F = 9.9 Hz), 119.6 (d, JC,F = 25.6 Hz),
119.2, 114.2, 110.4 (d, JC,F = 21.7 Hz), 55.3 ppm. HRMS (ESI): calcd.
for C16H13FNO [M + H]+ 254.0976; found 254.0981.
Ethyl
2-(4-Methoxyphenyl)quinoline-6-carboxylate
(3gd):
Yellow solid; m.p. 132–153 °C. Rf = 0.32 (petroleum ether/EtOAc,
8:1). 1H NMR (400 MHz, CDCl3): δ = 8.56 (s, 1 H), 8.33–8.24 (m, 2 H),
8.21–8.10 (m, 3 H), 7.89 (d, J = 8.6 Hz, 1 H), 7.05 (d, J = 8.6 Hz, 2 H),
4.45 (q, J = 7.0 Hz, 2 H), 3.91 (s, 3 H), 1.46 (t, J = 7.1 Hz, 3 H) ppm.
13C NMR (100 MHz, CDCl3): δ = 166.3, 161.2, 158.8, 150.2, 137.8,
131.6, 130.5, 129.6, 129.1 (two peaks overlapping), 127.6, 126.0,
119.1, 114.3 (two peaks overlapping), 61.2, 55.4, 14.4 ppm. HRMS
(ESI): calcd. for C19H18NO3 [M + H]+ 308.1281; found 308.1268.
6-Chloro-2-(4-methoxyphenyl)-3-methylquinoline (4ad): Yellow
solid; m.p. 133–139 °C. Rf = 0.36 (petroleum ether/EtOAc, 8:1). 1H
NMR (400 MHz, CDCl3): δ = 8.02 (d, J = 9.0 Hz, 1 H), 7.86 (s, 1 H),
7.71 (d, J = 2.2 Hz, 1 H), 7.59–7.53 (m, 3 H), 7.01 (d, J = 8.7 Hz, 2 H),
3.86 (s, 3 H), 2.47 (s, 3 H) ppm. 13C NMR (100 MHz, CDCl3): δ = 160.3,
159.8, 145.0, 135.7, 132. 9, 131.7, 130.8, 130.3, 130.2 (two peaks
overlapping), 129.5, 127.9, 125.2, 113.7 (two peaks overlapping),
55.3, 20.8 ppm. HRMS (ESI): calcd. for C17H15ClNO [M + H]+ 284.0837;
found 284.0836.
2-(4-Methoxyphenyl)-6-nitroquinoline (3hd): Yellow solid; m.p.
228–230 °C. Rf = 0.32 (petroleum ether/EtOAc, 8:1). 1H NMR
(400 MHz, CDCl3): δ = 8.77 (d, J = 2.5 Hz, 1 H), 8.47 (dd, J = 9.2,
2.5 Hz, 1 H), 8.34 (d, J = 8.7 Hz, 1 H), 8.25–8.17 (m, 3 H), 8.01 (d, J =
8.7 Hz, 1 H), 7.10–7.05 (m, 2 H), 3.91 (s, 3 H) ppm. 13C NMR (101 MHz,
CDCl3): δ = 161.8, 160.1, 150.6, 138.2, 131.1, 130.9, 129.3 (two peaks
overlapping), 125.5, 124.3, 124.3, 123.1, 120.1, 114.5 (two peaks
overlapping), 55.5 ppm. HRMS (ESI): calcd. for C16H13N2O3 [M + H]+
281.0921; found 281.0934.
2-[4-(tert-Butyl)phenyl]-6-chloro-3-methylquinoline
(4ae):
Yellow solid; m.p. 98–120 °C. Rf = 0.74 (petroleum ether/EtOAc, 8:1).
1H NMR (400 MHz, CDCl3): δ = 8.04 (d, J = 9.0 Hz, 1 H), 7.90 (s, 1 H),
7.74 (d, J = 2.2 Hz, 1 H), 7.57 (dd, J = 9.0, 2.2 Hz, 1 H), 7.55–7.49 (m,
4 H), 2.50 (s, 3 H), 1.38 (s, 9 H) ppm. 13C NMR (101 MHz, CDCl3): δ =
160.8, 151.4, 145.0, 137.6, 135.6, 131.8, 130.9, 130.4, 129.5, 128.5,
128.1, 127.0, 125.9, 125.3 (two peaks overlapping), 34.7, 31.3 (three
peaks overlapping), 20.7 ppm. HRMS (ESI): calcd. for C20H21ClN [M
+ H]+ 310.1357; found 310.1345.
7-Chloro-2-(4-methoxyphenyl)quinoline (3id): Yellow solid; m.p.
176–179 °C. Rf = 0.58 (petroleum ether/EtOAc, 8:1). 1H NMR
(400 MHz, CDCl3): δ = 8.17–8.10 (m, 4 H), 7.83 (d, J = 8.7 Hz, 1 H),
7.73 (d, J = 8.6 Hz, 1 H), 7.44 (dd, J = 8.6, 2.0 Hz, 1 H), 7.08–7.02 (m,
2 H), 3.89 (s, 3 H) ppm. 13C NMR (100 MHz, CDCl3): δ = 161.1, 157.8,
148.7, 136.4, 135.4, 131.7, 129.0 (two peaks overlapping), 128.6,
128.5, 126.9, 125.2, 118.6, 114.3 (two peaks overlapping), 55.4 ppm.
HRMS (ESI): calcd. for C16H13ClNO [M + H]+ 270.0680; found
270.0684.
6-Chloro-2-(2-methoxyphenyl)-3-methylquinoline (4af): Yellow
solid; m.p. 108–117 °C. Rf = 0.32 (petroleum ether/EtOAc, 8:1). 1H
NMR (400 MHz, CDCl3): δ = 8.05 (d, J = 9.0 Hz, 1 H), 7.86 (s, 1 H),
7.75 (d, J = 2.3 Hz, 1 H), 7.56 (dd, J = 9.0, 2.3 Hz, 1 H), 7.45–7.40 (m,
1 H), 7.32 (dd, J = 7.4, 1.7 Hz, 1 H), 7.09 (td, J = 7.4, 0.8 Hz, 1 H),
6.99 (d, J = 8.3 Hz, 1 H), 3.76 (s, 3 H), 2.29 (s, 3 H) ppm. 13C NMR
(100 MHz, CDCl3): δ = 159.6, 156.6, 144.9, 134.3, 132.1, 131.8, 130.9,
130.1, 129.9, 129.8, 129.2, 128.4, 125.3, 121.0, 110.8, 55.3, 19.2 ppm.
HRMS (ESI): calcd. for C17H15ClNO [M + H]+ 284.0837; found
284.0830.
2-(4-Methoxyphenyl)-8-methylquinoline (3jd): White solid; m.p.
85–88 °C. Rf = 0.68 (petroleum ether/EtOAc, 8:1). 1H NMR (400 MHz,
CDCl3): δ = 8.27–8.21 (m, 2 H), 8.14 (d, J = 8.6 Hz, 1 H), 7.85 (d, J =
8.6 Hz, 1 H), 7.64 (d, J = 8.1 Hz, 1 H), 7.56 (d, J = 6.9 Hz, 1 H), 7.41–
6-Chloro-2-(4-chlorophenyl)-3-methylquinoline (4ag): Yellow
solid; m.p. 177–185 °C. Rf = 0.66 (petroleum ether/EtOAc, 8:1). 1H
NMR (400 MHz, CDCl3): δ = 8.02 (d, J = 9.0 Hz, 1 H), 7.92 (s, 1 H),
7.74 (s, 1 H), 7.59 (dd, J = 9.0, 1.0 Hz, 1 H), 7.56–7.51 (m, 2 H), 7.47
7.36 (m, 1 H), 7.08–7.02 (m, 2 H), 3.90 (s, 3 H), 2.90 (s, 3 H) ppm. 13
C
NMR (100 MHz, CDCl3): δ = 160.7, 155.1, 147.1, 137.4, 136.8, 132.5,
129.6, 128.7 (two peaks overlapping), 126.8, 125.6, 125.3, 117.7, (d, J = 8.3 Hz, 2 H), 2.46 (s, 3 H) ppm. 13C NMR (100 MHz, CDCl3):
114.1 (two peaks overlapping), 55.4, 17.9 ppm. HRMS (ESI): calcd. δ = 159.4, 145.0, 138.8, 136.0, 134.5, 132.3, 130.9, 130.3 (two peaks
for C17H16NO [M + H]+ 250.1226; found 250.1219.
overlapping), 130.1, 129.8, 128.5 (two peaks overlapping), 128.2,
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125.3, 20.6 ppm. HRMS (ESI): calcd. for C16H16Cl2N [M + H]+
288.0341; found 288.0340.
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M. M. Alam, Macromolecules 2001, 34, 7315–7324.
2-(4-Bromophenyl)-6-chloro-3-methylquinoline (4ah): Yellow
solid; m.p. 166–184 °C. Rf = 0.68 (petroleum ether/EtOAc, 8:1). 1H
NMR (400 MHz, CDCl3): δ = 8.02 (dd, J = 8.8, 3.5 Hz, 1 H), 7.90 (s, 1
H), 7.73 (d, J = 2.1 Hz, 1 H), 7.64–7.61 (m, 2 H), 7.58 (dd, J = 9.0,
2.2 Hz, 1 H), 7.50–7.45 (m, 2 H), 2.45 (s, 3 H) ppm. 13C NMR (100 MHz,
CDCl3): δ = 159.4, 145.0, 139.3, 136.0, 132.3, 132.0, 131.5 (two peaks
overlapping), 130.9, 130.5 (two peaks overlapping), 130.0, 129.8,
129.0, 128.1, 125.3, 122.8, 20.6 ppm. HRMS (ESI): calcd. for
C
16H12BrClN [M + H]+ 331.9836; found 331.9827.
4-(6-Chloro-3-methylquinolin-2-yl)benzonitrile (4ai): Yellow
solid; m.p. 200–203 °C. Rf = 0.30 (petroleum ether/EtOAc, 8:1). 1H
NMR (400 MHz, CDCl3): δ = 8.01 (d, J = 9.0 Hz, 1 H), 7.95 (s, 1 H),
7.79 (d, J = 8.3 Hz, 2 H), 7.76 (d, J = 2.0 Hz, 1 H), 7.71 (d, J = 8.3 Hz,
2 H), 7.60 (dd, J = 9.0, 2.2 Hz, 1 H), 2.45 (s, 3 H) ppm. 13C NMR
(100 MHz, CDCl3): δ = 158.4, 144.9, 144.8, 136.3, 132.7, 132.1 (two
peaks overlapping), 130.9, 130.1, 129.7 (three peaks overlapping),
128.3, 125.4, 118.6, 112.2, 20.3 ppm. HRMS (ESI): calcd. for
C17H12ClN2 [M + H]+ 279.0684; found 279.0690.
[5]
6-Fluoro-2-(4-methoxyphenyl)-3-methylquinoline (4fd): Yellow
solid; m.p. 118–130 °C. Rf = 0.58 (petroleum ether/EtOAc, 8:1). 1H
NMR (400 MHz, CDCl3): δ = 8.09 (dd, J = 9.1, 5.4 Hz, 1 H), 7.92 (s, 1
H), 7.55 (d, J = 8.6 Hz, 2 H), 7.44–7.33 (m, 2 H), 7.02 (d, J = 8.6 Hz,
2 H), 3.87 (s, 3 H), 2.47 (s, 3 H) ppm. 13C NMR (100 MHz, CDCl3): δ =
160.3 (d, JC,F = 247.2 Hz), 159.7, 159.4 (d, JC,F = 2.7 Hz), 143.7, 136.0
[6]
(d, JC,F = 5.3 Hz), 133.0, 131.6 (d, JC,F = 9.2 Hz), 130.2, 127.9 (d, JC,F
=
10.1 Hz), 118.8 (d, JC,F = 25.7 Hz), 113.7, 109.5 (d, JC,F = 21.6 Hz),
55.3, 20.8 ppm. HRMS (ESI): calcd. for C17H15FNO [M + H ]+ 268.1132;
found 268.1139.
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Acknowledgments
This work was supported by the Chinese Academy of Sciences
and the National Natural Science Foundation of China
(21133011, 21373246, and 21522309).
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Keywords: Quinolines · Nitrogen heterocycles · Iron ·
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Received: October 24, 2016
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