Facile synthesis of substituted quinolines by iron(iii)-catalyzed cascade reaction between anilines, aldehydes and nitroalkanes

Article abstract of DOI:10.1039/c9ob01294j

A library of substituted quinolines has been synthesized by the reaction of aldehydes, anilines and nitroalkanes using a catalytic amount of Fe(iii) chloride. The reaction is a simple, efficient, one-pot, three-component domino strategy in ambient air which afforded the products in high yields. A probable pathway of the reaction is a sequential aza-Henry reaction/cyclization/denitration. The use of commercially available chemicals as starting materials, an inexpensive metal catalyst, aerobic reaction conditions, tolerance of a wide range of functional groups, and operational simplicity are the notable advantages of this present protocol.

Full text of DOI:10.1039/c9ob01294j

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ARTICLE
Facile synthesis of substituted quinolines by iron(III)-catalyzed
cascade reaction between anilines, aldehydes and nitroalkanes
Sachinta Mahato,a Anindita Mukherjee,b Sougata Santra,*b Grigory V. Zyryanovbc and Adinath
Received 00th January 20xx,
Accepted 00th January 20xx
Majee*a
DOI: 10.1039/x0xx00000x
A library of substituted quinolines have been synthesized by the reaction of aldehydes, anilines and nitroalkanes using a
catalytic amount of Fe(III) chloride. The reaction is a simple, efficient, one-pot, three-component domino strategy under
ambient air which afforded the products in high yields. Probable pathway of the reaction is a sequential aza-Henry
reaction/cyclization/denitration. The use of commercially available chemicals as starting materials, inexpensive metal
catalyst, aerobic reaction conditions, tolerance of a wide range of functional groups, and operational simplicity are the
notable advantages of this present protocol.
www.rsc.org/
Owing to their low cost, sustainability, ready availability,
nontoxicity, and environmental friendliness iron-based
catalysts have been shown to endorse a broad range of
organic transformations, such as cross-couplings, allylations,
hydrogenations, and direct C-H bond functionalization.5
Introduction
In recent years, multicomponent reactions (MCRs) are
considered as powerful synthetic tool to synthesize
a
structurally complex molecules1 with fascinating biological
properties through the formation of several carbon-carbon
and carbon-heteroatom bonds in a one-pot manner.2 MCRs
are believed as efficient chemical approaches since they avoid
time-consuming and costly purification processes, as well as
protection-deprotection steps.3 For these reasons, MCRs are
particularly well suited for miscellany-oriented synthesis and
library synthesis of drugs like compounds, which are crucial
part of the research in agrochemical and pharmaceutical
companies.
It is worthy to mention that the multicomponent reaction
in domino strategy is the best options to generate complex
heterocycles and natural products with several degrees of
structural diversity in one-pot.4 In addition, the development
of new environmentally benign processes that are both
technologically and economically practical is the modern trend
in the community of synthetic organic chemists. Typically, the
use of nonhazardous, inexpensive metals has attracted
interest in organic synthesis to catalyze relevant reactions.
NEt2
OMe
OMe
HO
HO
HN
N
O
O
N
O
N
OMe
Cl
N
N
O
Dictamnine
Chloroquine
Quinine
Orixinone
Cl
N
Cl
N
O
N
F3C
N
F3C
N
N
H
H
N
H
H
H
N
H
N
OH
Luotonine A
N
N
OH
Meflooquine (MFQ)
Chloroquine (CQ)
Hydroxychloroquine (HCQ)
Figure 1 Some biologically active compounds containing quinoline moiety.
Among the nitrogen-containing heterocycles, quinoline and
its derivatives have proven to be an important structural
scaffold in many pharmaceuticals. Interestingly, these
quinoline-based compounds have been shown to have a
diverse range of biological activities, for instance, antimalarial,6
antimicrobial,7 anti-inflammatories,8 anthelmintics,9 anti-HIV-1
and analgesic activities (Figure 1).10 Some of them are used as
functional materials and metal complexes11 for organic light-
emitting diodes (OLEDs)12 in materials chemistry.13 Optically
active quinolines are used in asymmetric synthesis as
catalysts.14 For an instant, 2-arylquinoline scaffolds show a
wide range of biological properties, such as P-selectin
antagonism, antimalarial, and antitumor activities.15 Owing to
their broad range of activities, several methods have been
developed for the synthesis of 2-arylquinoline derivatives such
as formal [3+3]-cyclo-addition reaction between anilines and
a. Department of Chemistry; Visva-Bharati (A Central University), Santiniketan
731235, India. Email: adinath.majee@visva-bharati.ac.in
b. Department of Organic and Biomolecular Chemistry, Chemical Engineering
Institute, Ural Federal University, 19 Mira Street, 620002, Yekaterinburg, Russian
Federation. Email: sougatasantra85@gmail.com
c. I. Ya. Postovskiy Institute of Organic Synthesis, Ural Division of the Russian
Academy of Sciences, 22 S. Kovalevskoy Street, 620219 Yekaterinburg, Russian
Federation.Address here.
Electronic Supplementary Information (ESI) available: Experimental procedure,
scanned copies of 1H and 13C NMR spectra of the synthesized compounds. See
DOI: 10.1039/x0xx00000x
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Journal Name
cinnamaldehydes which is known as Doebner-Miller reactions
and catalyzed by Lewis acids or Brønsted acids.16 Using this
strategy Torok’s group developed a microwave-assisted acid-
catalyzed synthesis of 2-arylquinolines from anilines and
cinnamaldehydes.17 The important classical approach for the
synthesis of 2-arylquinolines is the Friedländer reaction of
methyl ketones with 2-aminobenzaldehyde.18
View3Article Online
NO2
DOI: 10.1039/C9OB01294J
R
(a) Our Previous Works:
X = CH
N
H
path a
X
R3
+
+
R3
NO2
NH2
path b
X = N
CHO
N
N
R3
N
(b) This work:
Some other approaches are Ru-catalyzed oxidative
cyclization of 2-aminobenzyl alcohol with ketones,19 reactions
of ketones with 2-amino benzylamines for 24-72 h,20
palladium-catalyzed allylic C-H functionalization using anilines
R1
R1
R3
R2
+
+
NO2
R3 = H, CH3, C2H5, C3H7
R2
NH2
CHO
and allylbenzene.21 Recently,
a
copper-catalyzed C-H
Scheme 2 Synthesis of β-nitroamines, imidazo[1,2-a]pyridines and 2-arylquinolines.
cyclization of anilines with ketones and DMSO in the presence
of oxygen has been reported to synthesize 2-arylquinoline.22
Although the reported methods have their own merit in terms
of application; most of the methods suffer from at least one of
the following disadvantages such as low to moderate yields,
long reaction time, requirement of oxygen atmosphere,
vigorous reaction conditions, use of toxic as well as expensive
metals and complex reagent combination, and especially raw
materials with particular structure. Hence, in addition to the
existing methods, there is enough room to construct the 2-
arylquinoline moiety from readily available and simple starting
materials employing inexpensive metal catalysts with
environmentally benign reaction conditions.
Results and discussion
For the initial study, we started by choosing 4-methoxyaniline
(1a, 0.5 mmol) and benzaldehyde (2a, 0.5 mmol) as the model
substrates for this reaction using 20 mol% FeCl3 as the catalyst
in nitroethane (3a) as a solvent for 6 h at 60 ᵒC under ambient
air. Gratifyingly, the expected product 6-methoxy-2-
phenylquinoline (4a) was obtained in 32% yield (entry 1, Table
1). Inspired by this result, we increased the temperature to 90
ᵒC and 88% yield was obtained (entry 2, Table 1). FeCl3 was
found to be the most effective one among various iron salts
such as FeCl2, FeBr3, FeBr2, Fe(acac)3, Fe(OTf)3, FeSO4 (entries
3-8, Table 1). We have also tested with CuCl2 and CuI as
catalysts but not effective for this conversion (entries 9-10,
Table 1). By increasing temperature, the reaction did not
improve whereas, decreasing the temperature lowered the
yield to 32% (entry 11 & entry 12 Table 1). In addition,
increasing the amount of catalyst (30 mol%) no considerable
improvement was observed (entry 13, Table 1) whereas
decreasing the amount of catalyst (10 mol%) decreased the
yield (entry 14, Table 1). As well, by increasing the time no
further improvement of yield was observed but in 3 h 54%
yield was obtained (entries 15-16, Table 1). In the absence of
any catalyst, no product formation was observed (entry 17,
Table 1). Other common Lewis acids like AlCl3 and ZnCl2 were
not effective for this reaction (entries 18 and 19, Table 1).
Thus, optimal reaction conditions were obtained using 4-
methoxyaniline (1a, 0.5 mmol), benzaldehyde (2a, 0.5 mmol)
in presence of 20 mol% of FeCl3 in 2 mL of nitroethane (3a) at
90 ᵒC for 6 h (entry 2, Table 1) under ambient air.
Previous works:
O
OH
NH2
Ru-catalyst
Solvent
(a)
(Ref. 19)
+
+
Ph
Ph
N
Ph
O
NH2
NH2
Cu-catalyst
Solvent
(b)
(c)
(d)
(Ref. 20)
(Ref. 21)
N
N
Ph
Ph
Pd-catalyst
Solvent
+
Ph
NH2
O
O
S
Cu-catalyst, O2
+
(Ref. 22)
+
Ph
NH2
No external solvent
N
Ph
NO2
(e)
This work:
+
NH2
Ph CHO
Fe-catalyst
N
Ph
No external solvent
Scheme 1 Different strategies for the synthesis of 2-arylquinolines.
Recently, we developed a one-pot methodology for the
synthesis of β-nitroamines via a three-component coupling of
an amine, an aldehyde, and a nitroethane using an aza-Henry
reaction (Scheme 2a, path a).23 We also developed that an
amine having two nucleophilic sites such as 2-aminopyridine
could afford a cyclic structure (namely imidazo[1,2-a]pyridine)
via a sequential aza-Henry reaction/cyclization/denitration
process (Scheme 2a, path b).24 Using this same strategy,
herein, we report a FeCl3-catalyzed one-pot simple protocol
for the synthesis of 2-arylquinolines by a three-component
coupling of simple anilines, aldehydes, and nitroalkanes
(Scheme 1e and Scheme 2b).
Table 1 Optimization of the reaction conditionsa)
NH2
CHO
MeO
, 2 mL)
Catalyst
+
N
3a
(
C2H5NO2
Heating
OMe
1a
4a
2a
2 | J. Name., 2012, 00, 1-3
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Entry
1
2
3
4
5
6
7
8
Catalysts (mol%)
FeCl3 (20)
FeCl3 (20)
FeCl2 (20)
FeBr3 (20)
FeBr2 (20)
Fe(acac)3 (20)
Fe(OTf)3 (20)
FeSO4 (20)
CuCl2 (20)
CuI (20)
FeCl3 (20)
FeCl3 (20)
FeCl3 (10)
FeCl3 (30)
FeCl3 (20)
FeCl3 (20)
----
Temp.
60 °C
90 °C
90 °C
90 °C
90 °C
90 °C
90 °C
90 °C
90 °C
90 °C
110 °C
40 °C
90 °C
90 °C
90 °C
90 °C
90 °C
90 °C
90 °C
Time (h)
Yieldsb (%)
32
88
30
60
methoxyaniline (1a) as well as other with substitVuietwedArtaicnleiOlinnlienes
to prove the general applicability of this methodology. First,
DOI: 10.1039/C9OB01294J
6
6
6
6
6
6
6
6
6
6
6
6
6
6
10
3
6
6
6
the effect of substituents of aryl aldehydes was tested. The
results are summarized in Scheme 3. In most cases, the desired
products were obtained in good to excellent yields (4a–4p).
We have mentioned in the optimization that simple
benzaldehyde (2a) gave the desired product 4a in 88% yield.
Other benzaldehydes bearing electron-donating substituents
such as Me, OMe (4b, 4c, 4d and 4e) and electron withdrawing
substituents such as F, Cl, Br reacted well to afford the
corresponding 2-arylquinoline derivatives (4f, 4g, 4h and 4i).
Strong electron-withdrawing group like CF3 in the
benzaldehyde moiety also successfully gave the desired
product without any difficulty (4j). The SMe group was also
well tolerated under this reaction conditions and the desired
compound (4k) has been synthesized with excellent yield
(89%). Aldehyde containing acid sensitive group was
unaffected under the present reaction conditions which
signifies the mildness of the reaction conditions (4l). We have
also tested 2-naphthaldehyde and 1-naphthaldehyde which
also reacted smoothly under the optimized conditions
obtaining 78% and 73% yields respectively (4m and 4n). In
addition, heteroaryl aldehydes reacted well without
accompanying self-condensation or ring cleavage (4o and 4p).
50
ND
ND
ND
trace
<20
78
32
64
87
88
9
10
11
12
13
14
15
16
17
18
19
54
ND
NDc
trace
AlCl3 (20)
ZnCl2 (20)
a Reaction conditions: Carried out with 0.5 mmol of 1a and 0.5 mmol of 2a in the
presence of catalyst in presence of 2 mL of nitroethane (3a).b Isolated yields. c Not
detected in TLC.
After having the optimized reaction conditions in hand,
various aldehydes (2) were introduced to react with 4-
NH2
MeO
FeCl3 (20 mol%)
(Aryl/Heteroaryl) CHO
+
3a
, 2 mL)
C2H5NO2
(
N
Aryl/Heteroaryl
90 oC, 6 h
2
OMe
1a
4
MeO
MeO
MeO
MeO
Me
MeO
MeO
Me
N
N
4c,
N
N
OMe
76%
4b,
4d,
92%
80%
4a,
4e,
4i,
88%
MeO
MeO
MeO
OMe
N
N
N
N
Br
F
Cl
4f,
90%
4h,
85%
4g,
58%
88%
MeO
MeO
MeO
Br
N
N
N
N
SMe
F3C
O
4l,
90%
4k, 8
83%
9%
4j,
68%
O
MeO
MeO
MeO
MeO
S
O
N
N
N
N
4p,
62%
4o,
80%
4m,
4n,
73%
78%
Scheme 3 Synthesis of 2-(aryl/heteroaryl)quinolines from various aldehydes. Reaction conditions: 0.5 mmol of 1a and 0.5 mmol of 2 in the presence of 20 mol% FeCl3 in 2 mL of
nitroethane (3a) at 90 °C for 6 h.
Then our attention was turned to the use of substituted derivatives (5e, 5f, 5g, 5h and 5i). The nitrile and carbonyl
anilines to extend the general applicability of the reaction functionalities were also well tolerated under the present
conditions as summarized in Scheme 4. Simple aniline reaction conditions and gave 90% and 88% yields respectively
produced the desired product 5a in 78% yield. Other anilines (5j and 5k). We have also observed that the presence of both
bearing electron-donating substituents such as Me, OMe (5b, electron-withdrawing and electron-donating substituents in
5c and 5d) and electron-withdrawing substituents such as F, Cl, same aniline moiety afforded the corresponding quinoline
Br reacted well to afford the corresponding 2-arylquinoline derivatives in excellent yields (5l and 5m).
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NH2
CHO
FeCl3 (20 mol%)
R1
+
3a
, 2 mL)
N
C2H5NO2
(
R1
90 oC, 6 h
5
1
2a
Me
F
N
N
Me
N
N
N
OMe
5d
5c
, 68%
5b
, 75%
5a
, 78%
, 70%
5e
, 62%
Cl
Br
NC
Cl
N
N
N
N
N
Cl
5g
, 70%
5f
, 64%
5i
, 78%
5j
, 90%
5h
, 67%
EtOOC
Me
Me
N
N
N
Cl
Br
5m
5k
, 88%
, 91%
5l
, 90%
Scheme 4. Synthesis of 2-arylquinolines from different substituted anilines. Reaction conditions: 0.5 mmol of 1 and 0.5 mmol of 2a in the presence of 20 mol% FeCl3 in 2 mL of
nitroethane (3a) at 90 °C for 6 h.
In addition, a wide range of both substituted anilines and
NH2
CHO
benzaldehydes were employed to prove the wide applications
of our present procedure (6a-6j) (Scheme 5). Several sensitive
functionalities such as, halogens like F, Cl, Br (6a, 6b, 6c, 6d,
6e, 6g, 6h and 6j), OMe (6f and 6i), SMe (6e) were unaffected
under the present reaction conditions and the desired
products were obtained in 64–92% yields.
Finally, we have examined different nitroalkanes (3) such
as nitropropane, nitrobutane and nitropentane to prove the
general applicability of our methodology (Scheme 6). When we
used nitropropane (3b) the reaction proceeded smoothly and
afforded the desired products in good to excellent yields (7a–
7j) for all cases. We are delighted to mention that under the
same reaction conditions nitrobutane gave the corresponding
quinolines (7k-7o) in good yields. Finally, the nitropentane has
also been tested and we were able to synthesize 2,4,6-
disubstituted quinolines (7p, 7q) in satisfactory yields.
R1
FeCl3 (20 mol%)
N
+
3a
, 2 mL)
C2H5NO2
(
R1
R2
90 oC, 6 h
R2
6
2
1
Cl
Cl
Cl
Cl
Me
N
N
6b,
N
CH3
Cl
F
6c,
88%
89%
6a,
90%
Me
N
N
N
Cl
SMe
Br
OMe
6d,
72%
6e,
92%
6f,
90%
Me
Br
N
N
Me
N
OMe
To extend the scope of the present methodology, we
examined aliphatic aldehydes also (Scheme 7). After careful
6g,
6h, 64%
77%
6i,
82%
1
evaluation of the H and 13C NMR spectra, we came to the
N
point that the obtained products were 2,3-dialkyl-substituted
quinolines. Here, the nitroethane did not take part in the
reaction, only acted as a solvent. This phenomenon was
previously reported by Shimizu et al.25
Cl
6j
, 80%
Scheme 5 Synthesis of 2-arylquinolines by the three-component reaction with different
anilines, aldehydes and nitroethane. Reaction conditions: 0.5 mmol of 1 and 0.5 mmol
of 2 in the presence of 20 mol% FeCl3 in 2 mL of nitroethane (3a) at 90 °C for 6 h.
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It is worthy to mention that all these reactions were
performed under an open atmosphere and are not sensitive to
R3
N
View Article Online
DOI: 10.1039/C9OB01294J
NH2
CHO
R1
FeCl3 (20 mol%)
NO2
air and moisture. All the known synthesized compounds have
been characterized by spectral data and the new compounds
by spectral and analytical data. The reaction conditions were
mild enough and gave no decomposition of the products or
polymerization of the starting materials. We have not
observed any by-products for all the reaction combinations
giving rise to high yields of desired products and
regioselectivity of the protocol.
3
(
, 2 mL)
R3
90 oC, 6 h
R1
R2
R2
R3 = CH3,
7
3b
R3 = C2H5,
R3 = C3H7,
1
2
3c
3d
MeO
Cl
Ph
Me
MeO
Ph
N
N
N
Ph
N
7a
, 84%
7c
, 80%
7d
, 93%
7b
, 90%
MeO
MeO
MeO
NH2
CHO
MeO
N
N
N
FeCl3 (20 mol%)
+
7e
, 92%
7g
, 91%
OMe
MeO
7f
, 90%
Br
Cl
N
3a
( , 10 mL)
C2H5NO2
4a
(85%, 1 g)
OMe
1a
MeO
MeO
90 °C, 6 h
2a
S
N
(
)
N
5 mmol, 615 mg
N
, 88%
(
)
5 mmol, 530 mg
7i
, 89%
7j
, 91%
7h
Scheme 8 Gram scale reaction.
O
O
MeO
MeO
MeO
MeO
FeCl3 (20 mol%)
N
C
H
(Eq. 1)
N
C2H5NO2 (2 mL)
90 oC, 6 h
N
N
N
Ph
MeO
7k
, 80%
Cl
7l
, 83%
A
4a
, Quantitative yield
7m
, 90%
MeO
MeO
MeO
NO2
Ph
MeO
No catalyst
90 oC, 1 h
N
+
+
Ph CHO
NO2
3a
N
N
H
NH2
(Eq. 2)
7o
, 92%
O
2a
Br
7n
, 91%
O
1a
10a
aza-Henry product
MeO
MeO
MeO
NO2
MeO
N
N
Ph
FeCl3 (20 mol%)
7p
, 78%
N
H
7q
, 86%
N
(Eq. 3)
(Eq. 4)
C2H5NO2 (2 mL)
90 oC, 6 h
Scheme 6 Synthesis of substituted quinolines in presence of other various nitroalkanes
(3). Reaction conditions: 0.5 mmol of 1 and 0.5 mmol of 2 in the presence of 20 mol%
FeCl3 in 2 mL of nitroalkane (3) at 90 °C for 6 h.
10a
4a
, Quantitative yield
aza-Henry product
NH2
+
NO2
FeCl3 (20 mol%)
90 oC, 6 h
No reaction
NH2
MeO
R1
MeO
FeCl3 (20 mol%)
R1
CHO
+
1a
10
R1
MeO
C2H5NO2 (2 mL)
90 oC, 6 h
N
8
Scheme 9 Additional experiments.
1a
9
R1 = Me, Et
Based on the literature22,24,25 and some additional
experiments performed (Scheme 9) we predict the possible
reaction pathway. First of all, we synthesized the
corresponding imine A by reacting with 4-methoxyaniline 1a
and benzaldehyde 2a in ethanol. When the imine A was
subjected to the optimized reaction conditions, the
corresponding 2-arylquinoline 4a was obtained in quantitative
yield (Eq. 1). Furthermore, the imine A has been isolated from
the reaction mixture by quenching the reaction after 30 min.
After another 1 h, we have also isolated the aza-Henry adduct
as intermediate B. This aza-Henry adduct has also been
isolated by the additional experiment (Eq. 2). When aza-Henry
adduct (10a) was subjected to the optimized reaction
conditions, the corresponding 2-arylquinoline 4a was obtained
in quantitative yield (Eq. 3). This experiment also proves that
10a was the key intermediate in our reaction. Moreover, the
formation of nitrostyrene (10) was not observed in the
MeO
MeO
N
N
a
b
a
b
9b,
40% , 84%
9a,
36% , 80%
Scheme 7 Synthesis of quinolines using aliphatic aldehydes. a)Reaction conditions:
0.5 mmol of 1a and 0.5 mmol of 8 in the presence of 20 mol% FeCl3 in 2 mL of
nitroethane at 90 °C for 6 h. bReaction conditions: 0.5 mmol of 1a and 2.5 mmol
of 8 in the presence of 20 mol% FeCl3 in 2 mL of nitroethane at 90 °C for 6 h.
Moreover, the impending synthetic applicability of this
protocol was investigated on the gram scale using the model
reaction in our laboratory setup. As shown in Scheme 8, the
reaction could afford 1 g of 4a in 85% yield without any
significant loss of its efficiency, demonstrating the potential
applications of the present method for a large-scale synthesis
of quinolines derivatives.
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Page 6 of 13
ARTICLE
Journal Name
reaction. Even we also performed a reaction between 4- rearrangement of nitro group aza-Henry intermediate (B)
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DOI: 10.1039/C9OB01294J
methoxyaniline 1a and β-methyl-β-nitrostyrene (10) under the produces another intermediate (C) with gem hydroxyl group
same reaction conditions but the reaction did not proceed at on nitrogen. Elimination of HNO and H2O22b,22c,23,24 and ortho
all (Eq. 4).
cyclisation of intermediate (C) produce a new carbon-carbon
bond with adjacent carbene (D) (Scheme 10). Finally,
rearrangement of carbene dihydroquinoline, on oxidation,
converted to the corresponding quinoline.
The above observations suggest that the reaction proceeds
through the initial formation of imine (A) which on reaction
with nitro alkane produces the aza-Henry adduct (B). By
R2
R3
O
N
NH2
R1
CHO
NO2
R3
N
O
FeCl3
R2
H
+
N
H
FeCl3
aza-Henry Reaction
R2
R1
R1
(A)
intermediate
(B)
R3
R3 OH
FeCl3
OH
H
R3
O
N
-HNO
-H2O
R1
R1
H
N
R1
OH
N
H
R2
N
R2
N
H
R2
H
(C)
R3
R3
R3
R1
R1
Rearrangement
R2
O
R1
N
H
N
N
R2
R2
H
(D)
Scheme 10 Proposed reaction pathway.
ethyl acetate (10 mL) and water (10 mL). Then the organic
layer was dried over anhydrous Na2SO4. After evaporation of
solvent, the crude product was collected and purified by
column chromatography on silica gel using petroleum
ether/ethyl acetate (1% to 2%) as eluent as white solid (4a,
103 mg, 88%).
Experimental Section
General information. NMR spectra were determined on a 400
MHz spectrometer as solutions in CDCl3. Chemical shifts are
expressed in parts per million (δ) and the signals were
reported as s (singlet), d (doublet), t (triplet), m (multiplet) and
coupling constants J were given in Hz. 13C NMR spectra were
recorded at 100 MHz in CDCl3 solution. Chemical shifts are
expressed in parts per million (δ) and are referenced to CDCl3
(δ = 77.16) as an internal standard. TLC was done on silica gel
coated glass slide (Silica gel G for TLC). Silica gel (60-120 mesh)
was used for column chromatography. Petroleum ether refers
to the fraction boiling in the range of 60-80 °C unless otherwise
mentioned. All solvents were dried and distilled before use.
Commercially available substrates were freshly distilled before
the reaction. Solvents, reagents and chemicals were purchased
commercially. All reactions involving moisture sensitive
reactants were executed using oven-dried glassware.
Typical procedure for the synthesis of 6-methoxy-2-
phenylquinoline (4a) on gram scale:
A mixture of 4-
methoxyaniline (1a, 5 mmol) and benzaldehyde (2a, 5 mmol)
in 10 mL of nitroethane (3a) was taken in a sealed tube. Then
ferric chloride (FeCl3, 20 mol%) was added to the reaction
mixture. Next, the reaction mixture was stirred at 90 °C for 6 h.
After completion of the reaction (TLC), the reaction mixture
was diluted with ethyl acetate (50 mL) and water (50 mL).
Then organic layer was dried over anhydrous Na2SO4. After
evaporation of solvent the crude product was collected and
purified by column chromatography on silica gel using
petroleum ether/ethyl acetate (1% to 2%) as eluent as white
solid (4a, 1 g, 85%).
General procedure for the synthesis of 6-methoxy-2-
phenylquinoline (4a): A mixture of 4-methoxyaniline (1a, 0.5
mmol) and benzaldehyde (2a, 0.5 mmol) was taken in 2 mL of
nitroethane (3a) in a sealed tube. Then ferric chloride (FeCl3,
20 mol%) was added to the reaction mixture. Next, the
reaction mixture was stirred at 90 °C for 6 h. After completion
of the reaction (TLC), the reaction mixture was diluted with
6-Methoxy-2-phenylquinoline (4a):21 White solid (103 mg,
88%), mp: 127-129 °C; H NMR (CDCl3, 400 MHz): δ 8.15-8.07
(m, 4H), 7.82 (d, J = 8.4 Hz, 1H), 7.54-7.50 (m, 2H), 7.47-7.45
(m, 1H), 7.41-7.38 (m, 1H), 7.07 (d, J = 2.8 Hz, 1H), 3.93 (s, 3H);
13C NMR (CDCl3, 100 MHz): δ 157.7, 155.1, 144.4, 139.9, 135.6,
131.3, 129.0, 128.9, 128.2, 127.4, 122.4, 119.3, 105.1, 55.6.
1
6 | J. Name., 2012, 00, 1-3
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Organic & Biomolecular Chemistry
Journal Name
ARTICLE
6-Methoxy-2-(p-tolyl)quinoline (4b): White solid (100 mg, Calcd. For C16H12BrNO: C, 61.17; H, 3.85; N, 4.46%; Found: C,
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1
DOI: 10.1039/C9OB01294J
80%), mp: 142-143 °C; H NMR (CDCl3, 400 MHz): δ 8.10-8.02 61.26; H, 3.92; N, 4.38%.
(m, 4H), 7.81 (d, J = 8.4 Hz, 1H), 7.39-7.36 (m, 1H), 7.32 (d, J =
8.0 Hz, 2H), 7.08 (d, J = 2.8 Hz, 1H), 3.94 (s, 3H), 2.43 (s, 3H); 2-(2-Bromophenyl)-6-methoxyquinoline (4i): Brown solid (130
1
13C NMR (CDCl3, 100 MHz): δ 157.7, 155.2, 144.5, 139.1, 137.1, mg, 83%), mp: 114-115 °C; H NMR (CDCl3, 400 MHz): δ 8.12-
135.6, 131.2, 129.7, 128.1, 127.3, 122.3, 119.2, 105.2, 55.7, 8.06 (m, 2H), 7.70-7.61 (m, 3H), 7.44-7.39 (m, 2H), 7.30-7.26
21.4. . Anal. Calcd. For C17H15NO: C, 81.90; H, 6.06; N, 5.62%; (m, 1H), 7.13 (d, J = 2.8 Hz, 1H), 3.96 (s, 3H); 13C NMR (CDCl3,
Found: C, 81.82; H, 6.01; N, 5.53%.
100 MHz): δ 158.2, 156.4, 144.1, 141.8, 134.5, 133.4, 131.7,
131.2, 129.9, 128.3, 127.9, 123.1, 122.5, 122.1, 105.2, 55.7.
6-Methoxy-2-(o-tolyl)quinoline (4c): Brown solid (89 mg, 76%), Anal. Calcd. For C16H12BrNO: C, 61.17; H, 3.85; N, 4.46%;
1
mp: 52-53 °C; H NMR (CDCl3, 400 MHz): δ 8.11-8.06 (m, 2H), Found: C, 61.09; H, 3.88; N, 4.52%.
7.50-7.48 (m, 2H), 7.41-7.38 (m, 1H), 7.33-7.30 (m, 3H), 7.12
(d, J = 2.8 Hz, 1H), 3.96 (s, 3H), 2.41 (s, 3H); 13C NMR (CDCl3, 6-Methoxy-2-(2-(trifluoromethyl)phenyl)quinoline (4j): Yellow
1
100 MHz): δ 157.9(2C), 144.1, 140.9, 136.1, 135.0, 131.1, oil (117 mg, 77%); H NMR (CDCl3, 400 MHz): δ 8.10 (d, J = 8.4
130.9, 129.8, 128.4, 127.8, 126.1, 122.7, 122.4, 105.1, 55.7, Hz, 1H), 8.05 (d, J = 9.2 Hz, 1H), 7.79 (d, J = 7.6 Hz, 1H), 7.66-
20.5. Anal. Calcd. For C17H15NO: C, 81.90; H, 6.06; N, 5.62%; 7.52 (m, 3H), 7.49 (d, J = 8.4 Hz, 1H), 7.42-7.39 (m, 1H), 7.13 (d,
Found: C, 81.98; H, 6.14; N, 5.53%.
J = 2.4 Hz, 1H), 3.95 (s, 3H); 13C NMR (CDCl3, 100 MHz): δ 158.2,
155.7, 143.9, 140.5, 134.8, 131.8 (2C), 128.7, 128.5, 128.3,
6-Methoxy-2-(4-methoxyphenyl)quinoline (4d):26 White solid 126.5 (q, J = 5 Hz), 125.7, 122.8, 122.3, 105.1, 55.7. Anal. Calcd.
1
(121 mg, 92%), mp: 180-182 °C; H NMR (CDCl3, 400 MHz): δ For C17H12F3NO: C, 67.33; H, 3.99; N, 4.62%; Found: C, 67.23; H,
8.11-8.03 (m, 4H), 7.77 (d, J = 8.8 Hz, 1H), 7.38-7.35 (m, 1H), 3.92; N, 4.57%.
7.06-7.02 (m, 3H), 3.93 (s, 3H), 3.87 (s, 3H); 13C NMR (CDCl3,
100 MHz): δ 160.6, 157.5, 154.8, 144.4, 135.5, 132.5, 131.1, 6-Methoxy-2-(4-(methylthio)phenyl)quinoline (4k): Yellow
128.6, 127.9, 122.3, 118.9, 114.3, 105.2, 55.6, 55.5.
solid (125 mg, 89%), mp: 148-149 °C; 1H NMR (CDCl3, 400
MHz): δ 8.09-8.03 (m, 4H), 7.80 (d, J = 8.8 Hz, 1H), 7.39-7.36
6-Methoxy-2-(2-methoxyphenyl)quinoline (4e): Yellow oil (79 (m, 3H), 7.08 (d, J = 2.8 Hz, 1H), 3.94 (s, 3H), 2.54 (s, 3H); 13
C
mg, 58%); 1H NMR (CDCl3, 400 MHz): δ 8.07-8.03 (m, 2H), 7.85- NMR (CDCl3, 100 MHz): δ 157.8, 154.5, 144.5, 139.9, 136.6,
7.81 (m, 2H), 7.42-7.34 (m, 2H), 7.14-7.10 (m, 2H), 7.04-7.02 135.6, 131.2, 128.2, 127.7, 126.7, 122.4, 119.0, 105.2, 55.7,
(m, 1H), 3.95 (s, 3H), 2.86 (s, 3H); 13C NMR (CDCl3, 100 MHz): δ 15.8. Anal. Calcd. For C17H15NOS: C, 72.57; H, 5.37; N, 4.98%;
157.7, 157.3, 154.8, 144.5, 134.1, 131.5, 131.2, 130.1, 128.1, Found: C, 72.50; H, 5.44; N, 4.91%.
123.8, 121.9, 121.4, 111.6, 105.1, 55.8, 55.7, 53.5. Anal. Calcd.
For C17H15NO2: C, 76.96; H, 5.70; N, 5.28%; Found: C, 76.87; H, 2-(Benzo[d][1,3]dioxol-5-yl)-6-methoxyquinoline (4l): Yellow
5.62; N, 5.20%.
solid (126 mg, 90%), mp: 125-127 °C; 1H NMR (CDCl3, 400
MHz): δ 8.06-8.01 (m, 2H), 7.74-7.69 (m, 2H), 7.62-7.60 (m,
2-(4-Fluorophenyl)-6-methoxyquinoline (4f):27 White solid 1H), 7.38-7.35 (m, 1H), 7.06 (d, J = 2.8 Hz, 1H), 6.93 (d, J = 8.0
1
(114 mg, 90%), mp: 122-123 °C; H NMR (CDCl3, 400 MHz): δ Hz, 1H), 6.03 (s, 2H), 3.93 (s, 3H); 13C NMR (CDCl3, 100 MHz): δ
8.14-8.09 (m, 3H), 8.06-8.03 (m, 1H), 7.78 (d, J = 8.4 Hz, 1H), 157.6, 154.5, 148.6, 148.5, 144.3, 135.6, 134.4, 131.1, 128.0,
7.40-7.37 (m, 1H), 7.21-7.17 (m, 2H), 7.08 (d, J = 2.8 Hz, 1H), 122.4, 121.4, 119.0, 108.6, 107.8, 105.1, 101.4, 55.6. Anal.
1
3.94 (s, 3H); 13C NMR (CDCl3, 100 MHz): δ 163.7 (d, JC-F = 247 Calcd. For C17H13NO3: C, 73.11; H, 4.69; N, 5.02%; Found: C,
4
Hz), 157.9, 154.1, 144.5, 136.1 (d, JC-F = 3 Hz), 135.7, 131.2, 73.18; H, 4.60; N, 5.09%.
3
2
129.2 (d, JC-F = 8 Hz), 128.2, 122.6, 119.0, 115.8 (d, JC-F = 22
Hz), 105.2, 55.7.
6-Methoxy-2-(naphthalen-2-yl)quinoline (4m):28 Brown solid
(111 mg, 78%), mp: 116-117 °C; H NMR (CDCl3, 400 MHz): δ
1
2-(4-Chlorophenyl)-6-methoxyquinoline (4g):27 White solid 8.58 (s, 1H), 8.36-8.33 (m, 1H), 8.16-8.11 (m, 2H), 8.00-7.98 (m,
(103 mg, 88%), mp: 193-195 °C; H NMR (CDCl3, 400 MHz): δ 3H), 7.90-7.88 (m, 1H), 7.53-7.51 (m, 2H), 7.42-7.39 (m, 1H),
1
8.12-8.03 (m, 4H), 7.79 (d, J = 8.4 Hz, 1H), 7.48-7.46 (m, 2H), 7.11 (d, J = 2.4 Hz, 1H), 3.96 (s, 3H); 13C NMR (CDCl3, 100 MHz):
7.40-7.37 (m, 1H), 7.09 (d, J = 2.8 Hz, 1H), 3.95 (s, 3H); 13C NMR δ 157.9, 155.0, 144.6, 137.2, 135.7, 133.8, 133.7, 131.3, 128.9,
(CDCl3, 100 MHz): δ 158.0, 153.8, 144.5, 138.3, 135.8, 135.2, 128.6, 128.3, 127.8, 126.8, 126.6, 126.4, 125.1, 122.5, 119.5,
131.3, 129.1, 128.7, 128.4, 122.7, 118.9, 105.2, 55.7.
105.2, 55.7.
2-(4-Bromophenyl)-6-methoxyquinoline (4h): White solid (133 6-Methoxy-2-(naphthalen-1-yl)quinoline (4n): Yellow solid
1
1
mg, 85%), mp: 218-219 °C; H NMR (CDCl3, 400 MHz): δ 8.12- (104 mg, 73%), mp: 94-95 °C; H NMR (CDCl3, 400 MHz): δ
8.01 (m, 4H), 7.79 (d, J = 8.4 Hz, 1H), 7.64-7.62 (m, 2H), 7.40- 8.17-8.15 (m, 3H), 7.95-7.93 (m, 2H), 7.73-7.71 (m, 1H), 7.65
7.37 (m, 1H), 7.08 (d, J = 2.8 Hz, 1H), 3.95 (s, 3H); 13C NMR (d, J = 8.4 Hz, 1H), 7.61-7.57 (m, 1H), 7.54-7.44 (m, 3H), 7.16
(CDCl3, 100 MHz): δ 158.0, 153.9, 144.5, 138.8, 135.8, 132.0, (d, J = 2.8 Hz, 1H), 3.97 (s, 3H); 13C NMR (CDCl3, 100 MHz): δ
131.3, 128.9, 128.4, 123.6, 122.7, 118.9, 105.1, 55.7. Anal. 158.0, 157.0, 144.3, 138.8, 135.1, 134.1, 131.4, 131.2, 129.0,
128.4, 128.1, 127.7, 126.5, 126.0, 125.8, 125.5, 125.3, 123.6,
This journal is © The Royal Society of Chemistry 20xx
J. Name., 2013, 00, 1-3 | 7
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Organic & Biomolecular Chemistry
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ARTICLE
Journal Name
122.5, 105.2, 55.7. Anal. Calcd. For C20H15NO: C, 84.19; H, 5.30; 6-Chloro-2-phenylquinoline (5f):21 Yellow solid (81 mg, 68%),
View Article Online
1
DOI: 10.1039/C9OB01294J
N, 4.91%; Found: C, 84.24; H, 5.21; N, 4.98%.
mp: 110-111 °C; H NMR (CDCl3, 400 MHz): δ 8.16-8.09 (m,
4H), 7.90 (d, J = 8.4 Hz, 1H), 7.81 (d, J = 2.4 Hz, 1H), 7.67-7.64
6-Methoxy-2-(thiophen-2-yl)quinoline (4o):28 White solid (96 (m, 1H), 7.55-7.46 (m, 3H); 13C NMR (CDCl3, 100 MHz): δ 157.7,
mg, 80%), mp: 135-136 °C; H NMR (CDCl3, 400 MHz): δ 8.04- 146.8, 139.4, 136.0, 132.1, 131.5, 130.7, 129.7, 129.0, 127.9,
1
7.98 (m, 2H), 7.75 (d, J = 8.4 Hz, 1H), 7.68-7.67 (m, 1H), 7.43- 127.7, 126.3, 119.9.
7.42 (m, 1H), 7.36-7.33 (m, 1H), 7.15-7.13 (m, 1H), 7.05 (d, J =
2.8 Hz, 1H), 3.93 (s, 3H); 13C NMR (CDCl3, 100 MHz): δ 157.7, 7-Chloro-2-phenylquinoline (5g):22 Yellow solid (87 mg, 73%),
1
150.4, 145.7, 144.2, 135.5, 130.9, 128.3, 128.1, 128.0, 125.2, mp: 119-120 °C; H NMR (CDCl3, 400 MHz): δ 8.21-8.15 (m,
122.5, 118.1, 105.4, 55.7.
4H), 7.88 (d, J = 8.4 Hz, 1H), 7.76 (d, J = 8.8 Hz, 1H), 7.56-7.46
(m, 4H); 13C NMR (CDCl3, 100 MHz): δ 158.4, 148.8, 139.2,
2-(Furan-2-yl)-6-methoxyquinoline (4p): Yellow oil (75 mg, 136.7, 135.6, 129.8, 129.0, 128.8(2C), 127.7, 127.4, 125.7,
67%); 1H NMR (CDCl3, 400 MHz): δ 8.10 (s, 1H), 8.03 (d, J = 8.4 119.3.
Hz, 1H), 7.99 (d, J = 9.2 Hz, 1H), 7.57-7.53 (m, 2H), 7.37-7.34
1
(m, 1H), 7.08-7.06 (m, 2H), 3.93 (s, 3H); 13C NMR (CDCl3, 100 8-Chloro-2-phenylquinoline (5h)[29 Yellow oil (84 mg, 70%); H
MHz): δ 157.7, 149.6, 144.4, 144.0, 141.6, 135.4, 130.8, 128.1, NMR (CDCl3, 400 MHz): δ 8.31-8.28 (m, 2H), 8.22 (d, J = 8.8 Hz,
127.8, 122.3, 119.4, 109.2, 105.4, 55.7. Anal. Calcd. For 1H), 7.97 (d, J = 8.8 Hz, 1H), 7.86-7.83 (m, 1H), 7.75-7.73 (m,
C14H11NO2: C, 74.65; H, 4.92; N, 6.22%; Found: C, 74.72; H, 1H), 7.56-7.53 (m, 2H), 7.50-7.41 (m, 2H); 13C NMR (CDCl3, 100
4.83; N, 6.29%.
MHz): δ 157.6, 144.5, 139.2, 137.3, 134.1, 129.9, 129.0, 128.6,
127.8, 127.4, 126.7, 126.2, 119.5.
2-Phenylquinoline (5a):21 Yellow solid (82 mg, 80%), mp: 88-89
°C; H NMR (CDCl3, 400 MHz): δ 8.23 (d, J = 8.8 Hz, 1H), 8.19- 6-Bromo-2-phenylquinoline (5i):21 Yellow solid (111 mg, 78%),
1
1
8.16 (m, 3H), 7.88 (d, J = 8.4 Hz, 1H), 7.84-7.82 (m, 1H), 7.76- mp: 122-123 °C; H NMR (CDCl3, 400 MHz): δ 8.16-8.09 (m,
7.71 (m, 1H), 7.55-7.44 (m, 4H); 13C NMR (CDCl3, 100 MHz): δ 3H), 8.03 (d, J = 8.8 Hz, 1H), 7.97 (d, J = 2.4 Hz, 1H), 7.88 (d, J =
157.5, 148.4, 139.8, 136.9, 129.9, 129.8, 129.4, 129.0, 127.7, 8.8 Hz, 1H), 7.80-7.77 (m, 1H), 7.55-7.46 (m, 3H); 13C NMR
127.6, 127.3, 126.4, 119.2.
(CDCl3, 100 MHz): δ 157.8, 147.0, 139.3, 135.8, 133.2, 131.6,
129.7, 129.6, 129.0, 128.4, 127.6, 120.2, 119.9.
6-Methyl-2-phenylquinoline (5b):21 Yellow solid (93 mg, 85%),
mp: 92-93 °C; H NMR (CDCl3, 400 MHz): δ 8.20-8.18 (m, 2H), 2-Phenylquinoline-6-carbonitrile (5j):21 Yellow solid (103 mg,
1
1
8.12 (d, J = 8.4 Hz, 1H), 8.07 (d, J = 8.4 Hz, 1H), 7.80 (d, J = 8.4 90%), mp: 136-138 °C; H NMR (CDCl3, 400 MHz): δ 8.23-8.16
Hz, 1H), 7.58-7.53 (m, 4H), 7.50-7.46 (m, 1H), 2.54 (s, 3H); 13
C
(m, 5H), 7.96 (d, J = 8.8 Hz, 1H), 7.84-7.81 (m, 1H), 7.57-7.49
NMR (CDCl3, 100 MHz): δ 156.5, 146.9, 139.8, 136.1(2C), 131.9, (m, 3H); 13C NMR (CDCl3, 100 MHz): δ 160.0, 149.3, 138.6,
129.4, 129.1, 128.8, 127.5, 127.2, 126.4, 119.0, 21.6.
137.0, 133.8, 131.2, 130.4(2C), 129.1, 127.8, 126.5, 120.5,
118.8, 109.8.
7-Methyl-2-phenylquinoline (5c):21 Yellow solid (80 mg, 73%),
1
mp: 96-97 °C; H NMR (CDCl3, 400 MHz): δ 8.18-8.14 (m, 3H), Ethyl 2-phenylquinoline-6-carboxylate (5k): White solid (122
1
7.96 (s, 1H), 7.81 (d, J = 8.4 Hz, 1H), 7.72 (d, J = 8.0 Hz, 1H), mg, 88%), mp: 109-110 °C; H NMR (CDCl3, 400 MHz): δ 8.57
7.54-7.51 (m, 2H), 7.47-7.44 (m, 1H), 7.38-7.35 (m, 1H), 2.58 (s, (d, J = 2.0 Hz, 1H), 8.32-7.26 (m, 2H), 8.19-8.16 (m, 3H), 7.90
3H); 13C NMR (CDCl3, 100 MHz): δ 157.5, 148.7, 140.1, 140.0, (d, J = 8.8 Hz, 1H), 7.55-7.48 (m, 3H), 4.45 (q, J = 7.2 Hz, 2H)
136.6, 129.3, 128.9(2C), 128.7, 127.7, 127.2, 125.4, 118.3, 1.45 (t, J = 7.2 Hz, 3H); 13C NMR (CDCl3, 100 MHz): δ 166.3,
22.0.
159.3, 150.2, 139.2, 138.0, 130.6, 130.0, 129.3, 129.0, 128.1,
127.8, 126.3, 119.7, 61.4, 14.5. Anal. Calcd. For C18H15NO2: C,
8-Methoxy-2-phenylquinoline (5d):21 Yellow oil (82 mg, 70%); 77.96; H, 5.45; N, 5.05%; Found: C, 77.89; H, 5.37; N, 5.01%.
1H NMR (CDCl3, 400 MHz): δ 8.21-8.18 (m, 3H), 7.91 (d, J = 8.4
Hz, 1H), 7.53-7.49 (m, 2H), 7.47-7.39 (m, 3H), 7.09-7.06 (m, 8-Chloro-6-methyl-2-phenylquinoline (5l): Yellow solid (113
1H), 4.11 (s, 3H); 13C NMR (CDCl3, 100 MHz): δ 156.4, 155.7, mg, 90%), mp: 88-90 °C; 1H NMR (CDCl3, 400 MHz): δ 8.28-8.26
140.3, 139.9, 136.9, 129.3, 128.9, 128.4, 127.8, 126.6, 119.6, (m, 2H), 8.09 (d, J = 8.8 Hz, 1H), 7.89 (d, J = 8.4 Hz, 1H), 7.68 (d,
119.5, 108.2, 56.3.
J = 1.6 Hz, 1H), 7.55-7.52 (m, 2H), 7.49-7.46 (m, 2H), 2.50 (s,
3H); 13C NMR (CDCl3, 100 MHz): δ 156.6, 142.9, 139.2, 136.6,
6-Fluoro-2-phenylquinoline (5e):21 Yellow solid (72 mg, 65%), 136.4, 133.5, 131.9, 129.7, 129.0, 128.4, 127.6, 125.6, 119.4,
1
mp: 105-107 °C; H NMR (CDCl3, 400 MHz): δ 8.18-8.14 (m, 21.5. Anal. Calcd. For C16H12ClN: C, 75.74; H, 4.77; N, 5.52%;
4H), 7.90 (d, J = 8.8 Hz, 1H), 7.55-7.43 (m, 5H); 13C NMR (CDCl3, Found: C, 75.78; H, 4.87; N, 5.46%.
100 MHz): δ 160.5 (d, 1JC-F = 247 Hz), 156.9, 145.5, 139.5, 136.3
4
3
(d, JC-F = 5 Hz), 132.3 (d, JC-F = 10 Hz), 129.5, 129.0, 127.7 (d, 8-Bromo-6-methyl-2-phenylquinoline (5m): Yellow solid (135
2JC-F = 22 Hz), 120.1, 119.9, 110.6 (d, 2JC-F = 22 Hz).
mg, 91%), mp: 94-96 °C; 1H NMR (CDCl3, 400 MHz): δ 8.31-8.29
(m, 2H), 8.09 (d, J = 8.8 Hz, 1H), 7.92-7.90 (m, 2H), 7.55-7.52
(m, 3H), 7.49-7.45 (m, 1H), 2.52 (s, 3H); 13C NMR (CDCl3, 100
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MHz): δ 156.8, 143.7, 139.1, 136.9, 136.7, 135.4, 129.7, 129.0, 13C NMR (CDCl3, 100 MHz): δ 158.0, 146.6, 141.9, V1ie3w6A.8rti,cl1e3O5nl.in1e,
128.4, 127.7, 126.4, 125.2, 119.3, 21.4. Anal. Calcd. For 133.3, 132.1, 131.7, 130.0, 129.5, 127.8D, O1I2: 170..310, 3192/C69.5O,B1012229.48J,
C16H12BrN: C, 64.45; H, 4.06; N, 4.70%; Found: C, 64.53; H, 122.0, 21.8. Anal. Calcd. For C16H12BrN: C, 64.45; H, 4.06; N,
4.12; N, 4.62%.
4.70%; Found: C, 64.37; H, 4.14; N, 4.78%.
6-Chloro-2-(p-tolyl)quinoline (6a):26 White solid (114 mg, 2-(2-Bromophenyl)-7-methylquinoline (6h): Yellow solid (95
1
90%), mp: 113-114 °C; H NMR (CDCl3, 400 MHz): δ 8.10-8.04 mg, 64%), mp: 76-77 °C; 1H NMR (CDCl3, 400 MHz): δ 8.17 (d, J
(m, 4H), 7.84 (d, J = 8.8 Hz, 1H), 7.76 (d, J = 2.0 Hz, 1H), 7.65- = 8.4 Hz, 1H), 7.96 (s, 1H), 7.76 (d, J = 8.4 Hz, 1H), 7.71-7.69 (m,
7.62 (m, 1H), 7.33 (d, J = 8.0 Hz, 2H), 2.44 (s, 3H); 13C NMR 1H), 7.64-7.61 (m, 2H), 7.46-7.41 (m, 2H), 7.31-7.27 (m, 1H),
(CDCl3, 100 MHz): δ 157.6, 146.8, 139.8, 136.5, 135.8, 131.8, 2.58 (s, 3H); 13C NMR (CDCl3, 100 MHz): δ 158.8, 148.3, 141.9,
131.3, 130.5, 129.7, 127.7, 127.5, 126.2, 119.7, 21.4
140.2, 135.5, 133.3, 131.6, 130.1, 130.0, 129.2, 128.8, 127.8,
127.3, 125.3, 122.0, 22.1. Anal. Calcd. For C16H12BrN: C, 64.45;
6-Chloro-2-(o-tolyl)quinoline (6b): Yellow solid (111 mg, 88%), H, 4.06; N, 4.70%; Found: C, 64.53; H, 4.01; N, 4.63%.
1
mp: 93-94 °C; H NMR (CDCl3, 400 MHz): δ 8.10 (d, J = 8.4 Hz,
2H), 7.82(d, J = 2.4 Hz, 1H), 7.68-7.65 (m, 1H), 7.56 (d, J = 8.4 2-(4-Methoxyphenyl)quinoline (6i):21 Brown solid (96 mg,
1
Hz, 1H), 7.51-7.49 (m, 1H), 7.36-7.32 (m, 3H), 2.42 (s, 3H); 13
C
82%), mp: 115-116 °C; H NMR (CDCl3, 400 MHz): δ 8.19-8.13
NMR (CDCl3, 100 MHz): δ 160.6, 146.3, 140.3, 136.1, 135.2, (m, 4H), 7.83 (d, J = 8.8 Hz, 1H), 7.80 (d, J = 8.4 Hz, 1H), 7.73-
132.1, 131.3, 131.0, 130.6, 129.7, 128.8, 127.4, 126.2, 126.1, 7.69 (m, 1H), 7.52-7.50 (m, 1H), 7.06-7.04 (m, 2H), 3.89 (s, 3H);
123.3, 20.4. Anal. Calcd. For C16H12ClN: C, 75.74; H, 13.97; N, 13C NMR (CDCl3, 100 MHz): δ 161.0, 157.1, 148.4, 136.7, 132.4,
5.52%; Found: C, 75.80; H, 4.71; N, 5.43%.
129.7, 129.0, 127.6, 127.0, 126.0, 118.7, 114.4, 55.5.
6-Chloro-2-(4-fluorophenyl)quinoline (6c): White solid (114 2-(4-Chlorophenyl)quinoline (6j):22 Yellow solid (96 mg, 80%),
1
1
mg, 89%), mp: 145-146 °C; H NMR (CDCl3, 400 MHz): δ 8.15- mp: 96-98 °C; H NMR (CDCl3, 400 MHz): δ 8.23 (d, J = 8.4 Hz,
8.05 (m, 4H), 7.82-7.77 (m, 2H), 7.66-7.63 (m, 1H), 7.22-7.18 1H), 8.17-8.11 (m, 3H), 7.85-7.82 (m, 2H), 7.76-7.72 (m, 1H),
1
(m, 2H); 13C NMR (CDCl3, 100 MHz): δ 166.5 (d, JC-F = 248 Hz), 7.56-7.49 (m, 3H); 13C NMR (CDCl3, 100 MHz): δ 156.2, 148.4,
4
156.5, 146.7, 136.0, 135.4 (d, JC-F = 3 Hz), 132.1, 131.3, 130.8, 138.2, 137.1, 135.7, 130.0, 129.8, 129.1, 129.0, 127.6, 127.4,
3
2
129.5 (d, JC-F = 8 Hz), 127.7, 126.2, 119.5, 116.0 (d, JC-F = 21 126.6, 118.7.
Hz). Anal. Calcd. For C15H9ClFN2: C, 69.91; H, 3.52; N, 5.44%;
Found: C, 69.98; H, 3.60; N, 5.49%.
4,6-Dimethyl-2-phenylquinoline (7a): Yellow oil (98 mg, 84%);
1H NMR (CDCl3, 400 MHz): δ 8.02 (d, J = 8.4 Hz, 1H), 7.92 (s,
6-Chloro-2-(4-chlorophenyl)quinoline (6d):26 White solid (99 1H), 7.60-7.58 (m, 2H), 7.53-7.43 (m, 5H), 2.54 (s, 3H), 2.45 (s,
1
mg, 72%), mp: 165-167 °C; H NMR (CDCl3, 400 MHz): δ 8.10- 3H); 13C NMR (CDCl3, 100 MHz): δ 159.7, 145.3, 141.1, 136.3,
8.05 (m, 4H), 7.82 (d, J = 8.8 Hz, 1H), 7.78 (d, J = 2.4 Hz, 1H), 136.2, 131.2, 129.2, 129.1, 129.0, 128.4, 128.2, 127.7, 125.6,
7.66-7.63 (m, 1H), 7.50-7.47 (m, 2H); 13C NMR (CDCl3, 100 21.7, 20.7. Anal. Calcd. For C17H15N: C, 87.52; H, 6.48; N,
MHz): δ 156.3, 146.7, 137.7, 136.1, 135.9, 132.3, 131.4, 130.9, 6.00%; Found: C, 87.57; H, 6.55; N, 6.07%.
129.2, 128.8, 127.9, 126.3, 119.4.
6-Methoxy-4-methyl-2-phenylquinoline (7b): Yellow solid (112
6-Chloro-2-(4-(methylthio)phenyl)quinoline (6e): Yellow solid mg, 90%), mp: 69-71 °C; 1H NMR (CDCl3, 400 MHz): δ 8.02 (d, J
1
(131 mg, 92%), mp: 108-109 °C; H NMR (CDCl3, 400 MHz): δ = 9.2 Hz, 1H), 7.90 (s, 1H), 7.59-7.57 (m, 2H), 7.50-7.46 (m, 2H),
8.09-8.05 (m, 4H), 7.84 (d, J = 8.8 Hz, 1H), 7.77 (d, J = 2.4 Hz, 7.44-7.42 (m, 1H), 7.33-7.30 (m, 1H), 7.03 (d, J = 2.8 Hz, 1H),
1H), 7.65-7.62 (m, 1H), 7.38-7.36 (m, 2H), 2.54 (s, 3H); 13C NMR 3.93 (s, 3H), 2.44 (s, 3H); 13C NMR (CDCl3, 100 MHz): δ 158.1,
(CDCl3, 100 MHz): δ 156.9, 146.7, 140.9, 135.9, 135.8, 131.9, 157.8, 142.8, 141.0, 135.7, 130.8, 129.5, 129.0, 128.6, 128.3,
131.3, 130.7, 127.8, 127.7, 126.4, 126.2, 119.4, 15.5. Anal. 128.1, 121.5, 104.3, 55.6, 20.7. Anal. Calcd. For C17H15NO: C,
Calcd. For C16H12ClNS: C, 67.24; H, 4.23; N, 4.90%; Found: C, 81.90; H, 6.06; N, 5.62%; Found: C, 81.84; H, 6.13; N, 5.71%.
67.17; H, 4.29; N, 4.98%.
6-Chloro-4-methyl-2-phenylquinoline (7c): Brown oil (101 mg,
2-(4-Methoxyphenyl)-6-methylquinoline (6f):28 White solid 80%); 1H NMR (CDCl3, 400 MHz): δ 8.05 (d, J = 8.8 Hz, 1H), 7.93
1
(113 mg, 90%), mp: 136-137 °C; H NMR (CDCl3, 400 MHz): δ (s, 1H), 7.76 (d, J = 2.4 Hz, 1H), 7.60-7.57 (m, 3H), 7.52-7.44 (m,
8.13-8.02 (m, 4H), 7.79 (d, J = 8.4 Hz, 1H), 7.56-7.52 (m, 2H), 3H), 2.47 (s, 3H); 13C NMR (CDCl3, 100 MHz): δ 161.0, 145.1,
7.04 (d, J = 8.8 Hz, 2H), 3.88 (s, 3H), 2.54 (m, 3H); 13C NMR 140.6, 135.9, 132.2, 131.1, 130.5, 129.8, 128.9, 128.5, 128.3,
(CDCl3, 100 MHz): δ 160.8, 156.2, 147.0, 136.1, 135.8, 132.6, 125.5, 20.8. Anal. Calcd. For C16H12ClN: C, 75.74; H, 4.77; N,
132.0, 129.3, 128.9, 127.0, 126.5, 118.7, 114.3, 55.5, 21.7.
5.52%; Found: C, 75.66; H, 4.84; 5.61%.
2-(2-Bromophenyl)-6-methylquinoline (6g): Brown solid (115 6-Methoxy-4-methyl-2-(p-tolyl)quinoline (7d): Light pink solid
1
mg, 77%), mp: 81-82 °C; 1H NMR (CDCl3, 400 MHz): δ 8.12 (d, J (122 mg, 93%), mp: 128-129 °C; H NMR (CDCl3, 400 MHz): δ
= 8.4 Hz, 1H), 8.07 (d, J = 8.8 Hz, 1H), 7.71-7.62 (m, 4H), 7.59- 8.01 (d, J = 9.2 Hz, 1H), 7.88 (s, 1H), 7.49-7.47 (m, 2H), 7.32-
7.57 (m, 1H), 7.46-7.42 (m, 1H), 7.31-7.27 (m, 1H), 2.57 (s, 3H); 7.27 (m, 3H), 7.03-7.02 (m, 1H), 3.93 (s, 3H), 2.45 (s, 3H), 2.43
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(s, 3H); 13C NMR (CDCl3, 100 MHz): δ 158.2, 157.8, 142.9, 157.8, 150.3, 145.4, 142.7, 136.4, 130.6, 1V2ie8w.7A,rticl1e2O8nl.in2e,
DOI: 10.1039/C9OB01294J
138.3, 137.8, 135.7, 130.9, 129.6, 129.0(2C), 128.6, 121.4, 127.6(2C), 127.2, 121.7, 104.2, 55.5, 21.8. Anal. Calcd. For
104.4, 55.6, 21.4, 20.8. Anal. Calcd. For C18H17NO: C, 82.10; H, C15H13NOS: C, 70.56; H, 5.13; N, 5.49%; Found: C, 70.50; H,
6.51; N, 5.32%; Found: C, C, 82.16; H, 6.58; N, 5.41%.
5.21; N, 5.59%.
6-Methoxy-2-(4-methoxyphenyl)-4-methylquinoline
(7e): 4-Ethyl-6-methoxy-2-phenylquinoline (7k): Yellow gummy
1
1
White solid (128 mg, 92%), mp: 92-94 °C; H NMR (CDCl3, 400 mass (105 mg, 80%); H NMR (CDCl3, 400 MHz): δ 8.01 (d, J =
MHz): δ 8.00 (d, J = 9.2 Hz, 1H), 7.88 (s, 1H), 7.55-7.53 (m, 2H), 9.2 Hz, 1H), 7.95 (s, 1H), 7.54-7.52 (m, 2H), 7.49-7.42 (m, 3H),
7.32-7.29 (m, 1H), 7.03-7.00 (m, 3H), 3.93 (s, 3H), 3.87 (s, 3H), 7.33-7.30 (m, 1H), 7.08 (d, J = 2.8 Hz, 1H), 3.94 (s, 3H), 2.77 (q,
2.46 (s, 3H); 13C NMR (CDCl3, 100 MHz): δ 159.6, 157.8(2C), J = 7.6 Hz, 2H), 1.19 (t, J = 7.6 Hz, 3H); 13C NMR (CDCl3, 100
142.9, 135.7, 133.6, 130.8, 130.4, 129.6, 128.5, 121.4, 113.8, MHz): δ 158.2, 157.9, 142.5, 141.0, 135.6, 134.0, 130.8, 128.9,
104.4, 55.6, 55.5, 20.9. Anal. Calcd. For C18H17NO2: C, 77.40; H, 128.4, 128.0, 127.0, 121.6, 104.5, 55.6, 26.1, 14.9. Anal. Calcd.
6.13; N, 5.01%; Found: C, 77.32; H, 6.08; N, 5.09%.
For C18H17NO: C, 82.10; H, 6.51; N, 5.32%; Found: C, 82.18; H,
6.46; N, 5.38%.
2-(4-Chlorophenyl)-6-methoxy-4-methylquinoline (7f): White
solid (127 mg, 90%), mp: 137-138 °C; 1H NMR (CDCl3, 400 4-Ethyl-6-methoxy-2-(p-tolyl)quinoline (7l): Yellow oil (115
MHz): δ 7.99 (d, J = 8.0 Hz, 1H), 7.90 (s, 1H), 7.55-7.51 (m, 2H), mg, 83%); 1H NMR (CDCl3, 400 MHz): δ 7.99 (d, J = 9.2 Hz, 1H),
7.46-7.43 (m, 2H), 7.33-7.30 (m, 1H), 7.03 (d, J = 6.4 Hz, 1H) 7.90 (s, 1H), 7.42-7.40 (m, 2H), 7.30-7.23 (m, 3H), 7.04 (d, J =
3.93 (s, 3H), 2.43 (s, 3H); 13C NMR (CDCl3, 100 MHz): δ 158.1, 2.4 Hz, 1H), 3.91 (s, 3H), 2.76 (q, J = 7.6 Hz, 2H), 2.40 (s, 3H),
156.8, 142.9, 139.5, 136.0, 134.2, 130.8, 130.5, 129.3, 128.8, 1.19 (t, J = 7.6 Hz, 3H); 13C NMR (CDCl3, 100 MHz): δ 158.3,
128.6, 121.8, 104.3, 55.6, 20.6. Anal. Calcd. For C17H14ClNO: C, 157.7, 142.5, 138.2, 137.7, 135.7, 133.8, 130.7, 129.0, 128.8,
71.96; H, 4.97; N, 4.94 %; Found: C, 71.87; H, 4.88; N, 4.83%.
128.7, 121.5, 104.5, 55.6, 26.1, 21.4, 14.9. Anal. Calcd. For
C19H19NO: C, 82.28; H, 6.90; N, 5.05%; Found: C, 82.18; H, 6.98;
2-(4-Bromophenyl)-6-methoxy-4-methylquinoline (7g): White N, 5.13%.
solid (149 mg, 91%), mp: 120-121 °C; 1H NMR (CDCl3, 400
MHz): δ 8.00-7.98 (m, 1H), 7.91 (s, 1H), 7.62-7.59 (m, 2H), 2-(4-Chlorophenyl)-4-ethyl-6-methoxyquinoline (7m): White
7.48-7.45 (m, 2H), 7.33-7.30 (m, 1H), 7.04-7.03 (m, 1H), 3.94 (s, solid (133 mg, 90%), mp: 90-92 °C; 1H NMR (CDCl3, 400 MHz): δ
3H), 2.43 (s, 3H); 13C NMR (CDCl3, 100 MHz): δ 158.0, 156.8, 7.99 (d, J = 9.2 Hz, 1H), 7.95 (s, 1H), 7.50-7.43 (m, 4H), 7.34-
142.8, 139.9, 136.0, 131.5, 130.8, 129.3(2C), 128.8, 122.5, 7.31 (m, 1H), 7.08 (d, J = 2.4 Hz, 1H), 3.95 (s, 3H), 2.76 (q, J =
121.8, 104.3, 55.7, 20.6. Anal. Calcd. For C17H14BrNO: C, 62.21; 7.6 Hz, 2H), 1.19 (t, J = 7.6 Hz, 3H); 13C NMR (CDCl3, 100 MHz):
H, 4.30; N, 4.27%; Found: C, 62.28; H, 4.39; N, 4.20%.
δ 158.0, 156.9, 142.6, 139.6, 135.5, 134.2(2C), 130.8, 130.4,
128.9, 128.6, 121.9, 104.5, 55.7, 26.1, 14.9. Anal. Calcd. For
C18H16ClNO: C, 72.60; H, 5.42; N, 4.70%; Found: C, 72.68; H,
2-(Benzo[d][1,3]dioxol-5-yl)-6-methoxy-4-methylquinoline
(7h): Light yellow solid (129 mg, 88%), mp: 125-126 °C; 1H NMR 5.37; N, 4.67%.
(CDCl3, 400 MHz): δ 7.98 (d, J = 8.8 Hz, 1H), 7.85 (s, 1H), 7.31-
7.28 (m, 1H), 7.08-7.03 (m, 2H), 7.01-7.00 (m, 1H), 6.91-6.89 2-(4-Bromophenyl)-4-ethyl-6-methoxyquinoline (7n): White
(m, 1H), 3.91 (s, 2H), 2.44 (s, 3H); 13C NMR (CDCl3, 100 MHz): δ solid (156 mg, 91%), mp: 99-100 °C; 1H NMR (CDCl3, 400 MHz):
157.8, 157.5, 147.6(2C), 142.8, 135.8, 135.0, 130.7, 129.5, δ 7.99 (d, J = 9.2 Hz, 1H), 7.95 (s, 1H), 7.62-7.59 (m, 2H), 7.45-
128.5, 122.9, 121.5, 109.8, 108.2, 104.3, 101.2, 55.6, 20.7. 7.40 (m, 2H), 7.34-7.31 (m, 1H), 7.08-7.07 (m, 1H), 3.94 (s, 3H),
Anal. Calcd. For C18H15NO3: C, 73.71; H, 5.15; N, 4.78%; Found: 2.76 (q, J = 7.6 Hz, 2H), 1.19 (t, J = 7.6 Hz, 3H); 13C NMR (CDCl3,
C, 73.80; H, 5.10; N, 4.68%.
100 MHz): δ 158.0, 156.9, 142.6, 140.0, 135.4, 134.2, 131.6,
130.8, 130.7, 128.9, 122.4, 121.9, 104.5, 55.7, 26.1, 14.9. Anal.
6-Methoxy-4-methyl-2-(naphthalen-2-yl)quinoline (7i): White Calcd. For C18H16BrNO: C, 63.17; H, 4.71; N, 4.09%; Found: C,
solid (133 mg, 89%), mp: 132-134 °C; 1H NMR (CDCl3, 400 63.25; H, 4.80; N, 4.16%.
MHz): δ 8.06-8.04 (m, 2H), 7.96-7.89 (m, 4H), 7.74-7.71 (m,
1H), 7.54-7.50 (m, 2H), 7.36-7.33 (m, 1H), 7.07 (d, J = 2.8 Hz, 2-(Benzo[d][1,3]dioxol-5-yl)-4-ethyl-6-methoxyquinoline (7o):
1
1H), 3.95 (s, 3H), 2.50 (s, 3H); 13C NMR (CDCl3, 100 MHz): δ Yellow gummy (141 mg, 92%); H NMR (CDCl3, 400 MHz): δ
158.1, 158.0, 143.0, 138.6, 135.8, 133.4, 133.1, 131.0, 129.8, 7.99 (d, J = 9.2 Hz, 1H), 7.92 (s, 1H), 7.32-7.29 (m, 1H), 7.06-
128.7, 128.5, 128.3, 128.0, 127.8, 127.0, 126.4, 126.3, 121.6, 6.99 (m, 3H), 6.90 (d, J = 8.0 Hz, 1H), 6.01 (s, 2H), 3.93 (s, 3H),
104.5, 55.7, 20.8. Anal. Calcd. For C21H17NO: C, 84.25; H, 5.72; 2.79 (q, J = 7.6 Hz, 2H), 1.20 (t, J = 7.6 Hz, 3H); 13C NMR (CDCl3,
N, 4.68%; Found: C, 84.16; H, 5.79; N, 4.60%.
100 MHz): δ 157.8, 157.6, 147.6, 147.5, 142.5, 135.7, 135.0,
134.0, 130.7, 128.7, 122.7, 121.6, 109.7, 108.3, 104.5, 101.2,
6-Methoxy-4-methyl-2-(thiophen-2-yl)quinoline (7j): White 55.6, 26.1, 14.9. Anal. Calcd. For C19H17NO3: C, 74.25; H, 5.58;
solid (116 mg, 91%), mp: 98-100 °C; 1H NMR (CDCl3, 400 MHz): N, 4.56%; Found: C, 74.20; H, 5.68; N, 4.51%.
δ 7.88-7.86 (m, 1H), 7.71 (s, 1H), 7.44-7.43 (m, 1H), 7.34-7.33
(m, 1H), 7.21-7.18 (m, 1H), 7.05-7.03 (m, 1H), 6.85-6.84 (m, 6-Methoxy-2-phenyl-4-propylquinoline (7p): Yellow gummy
1H), 3.79 (s, 3H), 2.56 (s, 3H); 13C NMR (CDCl3, 100 MHz): δ (108 mg, 78%); 1H NMR (CDCl3, 400 MHz): δ 8.01 (d, J = 9.2 Hz,
10 | J. Name., 2012, 00, 1-3
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1H), 7.93 (s, 1H), 7.54-751 (m, 2H), 7.49-7.39 (m, 3H), 7.33- solvent is needed for this transformation. These advantages
View Article Online
DOI: 10.1039/C9OB01294J
7.30 (m, 1H), 7.07 (d, J = 9.2 Hz, 1H), 3.95 (s, 3H), 2.73 (t, J = render this protocol facile and suitable to create a diversified
8.0 Hz, 2H), 1.60-1.52 (m, 2H), 0.86 (t, J = 7.6 Hz, 3H); 13C NMR library of 2-arylquinoline derivatives.
(CDCl3, 100 MHz): δ 158.4, 157.9, 142.7, 141.3, 134.8, 134.2,
130.9, 129.0, 128.7, 128.4, 128.0, 121.6, 104.6, 55.7, 35.0,
23.9, 14.0. Anal. Calcd. For C19H19NO: C, 82.28; H, 6.90; N,
Acknowledgements
5.05%; Found: C, 82.21; H, 6.84; N, 5.01%.
A. Majee acknowledges financial support from the DST-RSF
Major Research Project (Ref. No. INT/RUS/RSF/P-08). S. Santra
is thankful to the Russian Science Foundation – Russia (Ref. #
18-73-00301) for funding. We are thankful to the DST-FIST and
UGC-SAP program.
6-Methoxy-4-propyl-2-(p-tolyl)quinoline (7q): Yellow oil (125
mg, 86%); 1H NMR (CDCl3, 400 MHz): δ 7.92 (d, J = 9.2 Hz, 1H),
7.83 (s, 1H), 7.35-7.33 (m, 2H), 7.24-7.18 (m, 3H), 6.99 (d, J =
2.4 Hz, 1H), 3.86 (s, 3H), 2.66 (t, J = 8.0 Hz, 2H), 2.34 (s, 3H),
1.54-1.45 (m, 2H), 0.79 (t, J = 7.6 Hz, 3H); 13C NMR (CDCl3, 100
MHz): δ 158.4, 157.8, 142.6, 138.3, 137.7, 134.6, 134.2, 130.8,
129.0, 128.8, 128.6, 121.5, 104.5, 55.6, 35.0, 23.8, 21.4, 14.0.
Anal. Calcd. For C20H21NO: C, 82.44; H, 7.26; N, 4.81%; Found:
C, 82.48; H, 7.33; N, 4.89%.
Conflicts of interest
There are no conflicts to declare.
Notes and references
2-Ethyl-6-methoxy-3-methylquinoline (9a):25 Pale yellow oil
1
(a) X. Guo and W. Hu, Acc Chem. Res., 2013, 46, 2427–2440;
(b) E. Ruijter, R. Scheffelaar and R. V. A. Orru, Angew. Chem.
Int. Ed., 2011, 50, 6234–6246. (c) A. Dömling, Chem. Rev.,
2006, 106, 17–89.
1
(80 mg, 80%); H NMR (CDCl3, 400 MHz): δ 7.91 (d, J = 9.2 Hz,
1H), 7.74 (s, 1H), 7.28-7.25 (m, 1H), 6.97 (d, J = 2.8 Hz, 1H),
3.90 (s, 3H), 2.95 (q, J = 7.6 Hz, 2H), 2.46 (s, 3H), 1.35 (t, J = 7.6
Hz, 3H); 13C NMR (CDCl3, 100 MHz): δ 160.8, 157.3, 142.7,
135.0, 130.0, 129.8, 128.3, 120.8, 104.6, 55.6, 29.3, 19.2, 13.1.
2
3
4
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3-Ethyl-6-methoxy-2-propylquinoline (9b):25 Pale yellow oil
1
(96 mg, 84%); H NMR (CDCl3, 400 MHz): δ 7.89 (d, J = 9.2 Hz,
1H), 7.75 (s, 1H), 7.26-7.23 (m, 1H), 7.00 (d, J = 2.8 Hz, 1H),
3.88 (s, 3H), 2.92-2.88 (m, 2H), 2.79 (q, J = 7.6 Hz, 2H), 1.82-
1.76 (m, 2H), 1.31 (t, J = 7.6 Hz, 3H), 1.03 (t, J = 7.6 Hz, 3H); 13
NMR (CDCl3, 100 MHz): δ 159.5, 157.3, 142.5, 135.8, 133.1,
130.0, 128.3, 120.9, 104.8, 55.6, 37.7, 25.3, 23.1, 14.6, 14.5.
C
5
4-Methoxy-N-(2-nitro-1-phenylpropyl)aniline (10a): Yellow oil
(132 mg, 92%); 1H NMR (CDCl3, 400 MHz): δ 7.35-7.33 (m, 2H),
7.31-7.28 (m, 3H), 6.69-6.67 (m, 2H), 6.55-6.53 (m, 2H), 4.87-
4.83 (m, 1H), 4.70 (d, J = 8.4 Hz, 1H), 4.16 (bs, 1H), 3.68 (s, 3H),
1.42 (d, J = 6.8 Hz, 3H); 13C NMR (CDCl3, 100 MHz): δ 153.1,
139.9, 138.1, 129.2, 128.6, 127.1, 115.9, 114.8, 87.8, 63.1,
55.7, 17.2. Anal. Calcd. For C16H18N2O3: C, 67.12; H, 6.34; N,
9.78%; Found: C, 67.04; H, 6.28; N, 9.86%.
6
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Conclusions
In summary, we have developed an iron(III)-catalyzed one-pot
three-component domino strategy for the expedient synthesis
of 2-arylquinolines under ambient atmosphere. Furthermore,
the present methodology is also applicable for the gram-scale
synthesis without any significant loss of its efficiency,
demonstrating the potential applications of the present
method for
a large-scale synthesis of 2-arylquinoline
derivatives. The present reaction most likely occurs via a
sequential aza-Henry reaction/cyclization/denitration. Readily
available chemicals as starting materials, an inexpensive metal
catalyst, aerobic reaction conditions, tolerance of a wide range
of functional groups, and operational simplicity are the notable
advantages of this present approach. Additionally, no external
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DOI: 10.1039/C9OB01294J
Graphical Abstract
R1
N
NH2
FeCl3 (20 mol%)
R
(Aryl/Heteroaryl) CHO
+
R
NO2
90 oC, 6 h
R1
Aryl/Heteroaryl
R1 = H, CH3, C2H5, C3H7
Aerobic reaction conditions
Cheap catalyst and reagents
High yields
58 examples
up to 93% yields
Broad substrate scope
No external solvents