Mild and simple access to diverse 4-amino-substituted 2-phenyl-1,2,3,4- tetrahydroquinolines and 2-phenylquinolines based on a multicomponent imino diels-alder reaction

Article abstract of DOI:10.1080/00397910903221035

A straightforward synthesis of new 1-(2-phenyl-1,2,3,4-tetrahydroquinolin- 4-yl) pyrrolidin-2-ones/azepan-2-one from N-vinyl caprolactam/N-vinylpyrrolidin- 2-one and N-benzylideneaniline via the imino Diels-Alder reaction has been reported for the first time. Antimony(III) chloride has been shown to effectively catalyze imino-Diels-Alder reaction to afford both 2-phenylquinoline and 2-phenyl-1,2,3,4-tetrahydroquinolin derivatives in excellent yields at ambient temperature. The cis diastereoselectivity to give cis 2-phenyl-1,2,3,4-tetrahydroquinolines is also highlighted in this reaction. Copyrigh

Full text of DOI:10.1080/00397910903221035

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Mild and Simple Access to Diverse 4-
Amino-substituted 2-Phenyl-1,2,3,4-
tetrahydroquinolines and 2-
Phenylquinolines Based on a
Multicomponent Imino Diels–Alder
Reaction
P. Prabhakara Varma a , Bailure S. Sherigara a , Kittappa M.
Mahadevan b & Vijaykumar Hulikal c
a Department of Postgraduate Studies and Research in Chemistry,
School of Chemical Sciences, Kuvempu University, Shankaraghatta,
Karnataka, India
b Department of Chemistry, School of Chemical Sciences, Kuvempu
University, Karnataka, India
c Bioorganics and Applied Materials Pvt. Ltd., Bangalore, India
Version of record first published: 07 Jul 2010.
To cite this article: P. Prabhakara Varma , Bailure S. Sherigara , Kittappa M. Mahadevan &
Vijaykumar Hulikal (2010): Mild and Simple Access to Diverse 4-Amino-substituted 2-Phenyl-1,2,3,4-
tetrahydroquinolines and 2-Phenylquinolines Based on a Multicomponent Imino Diels–Alder Reaction,
Synthetic Communications: An International Journal for Rapid Communication of Synthetic Organic
Chemistry, 40:15, 2220-2231
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Synthetic Communications1, 40: 2220–2231, 2010
Copyright # Taylor & Francis Group, LLC
ISSN: 0039-7911 print=1532-2432 online
DOI: 10.1080/00397910903221035
MILD AND SIMPLE ACCESS TO DIVERSE 4-AMINO-
SUBSTITUTED 2-PHENYL-1,2,3,4-TETRAHYDRO-
QUINOLINES AND 2-PHENYLQUINOLINES BASED
ON A MULTICOMPONENT IMINO DIELS–ALDER
REACTION
P. Prabhakara Varma,1 Bailure S. Sherigara,1
Kittappa M. Mahadevan,2 and Vijaykumar Hulikal3
1Department of Postgraduate Studies and Research in Chemistry, School of
Chemical Sciences, Kuvempu University, Shankaraghatta, Karnataka, India
2Department of Chemistry, School of Chemical Sciences, Kuvempu
University, Karnataka, India
3Bioorganics and Applied Materials Pvt. Ltd., Bangalore, India
A
straightforward synthesis of new 1-(2-phenyl-1,2,3,4-tetrahydroquinolin-4-yl)
pyrrolidin-2-ones/azepan-2-one from N-vinyl caprolactam/N-vinylpyrrolidin-2-one and
N-benzylideneaniline via the imino Diels–Alder reaction has been reported for the first time.
Antimony(III) chloride has been shown to effectively catalyze imino-Diels–Alder reaction
to afford both 2-phenylquinoline and 2-phenyl-1,2,3,4-tetrahydroquinolin derivatives in
excellent yields at ambient temperature. The cis diastereoselectivity to give cis 2-phenyl-
1,2,3,4-tetrahydroquinolines is also highlighted in this reaction.
Keywords: Antimony trichloride; 2-phenylquinolines; tetrahydroquinoline; N-vinylcaprolactam=
N-vinylpyrrolidin-2-one
INTRODUCTION
The structural core of quinoline has generally been synthesized by various
conventional reactions such as Skraup,[1] Doebner–von Miller,[2] Friedla¨nder,[3]
Pfitzinger,[4] Conrad–Limpach,[5] and Combes[6] syntheses. These classical syntheses
are well known and frequently used for the preparation of pharmaceutical agents,
ligands, and functional materials bearing a quinoline backbone. However, current
methods for quinoline synthesis often do not allow for adequate diversity and sub-
stitution on the quinoline ring system.[7] Recent developments in the chemistry of
quinoline derivatives have demonstrated that new metal-catalyzed coupling cycliza-
tions or acid-catalyzed cycloaddition of appropriate precursors could compete with
classical synthesis in the efficacy and rapidity of the quinoline construction.[8–15]
Received April 24, 2009.
Address correspondence to P. Prabhakara Varma, Department of Postgraduate Studies and
Research in Chemistry, School of Chemical Sciences, Kuvempu University, Shankaraghatta,
Karnataka, India. E-mail: mady_kmm@yahoo.co.uk
2220

MILD AND SIMPLE ACCESS TO QUINOLINES
2221
These new developments have prompted us to explore novel methods and
modifications of existing reactions in synthesizing substituted quinolines using
antimony trichloride as an efficient catalyst.
In this context, we are interested in the design of new methodologies to prepare
4-aminoquinolines containing various substituents. These substituents could regulate
important biological functions and increase the biological activity of these types of
compounds, in a way similar to that reported for other pharmaceuticals.[16]
Hence, the present study has been focused on the investigation of SbCl3-
catalyzed method of synthesis of quinoline nucleus involving direct introduction
of an amino or a substituted amino group at the 4-position of tetrahydroquinolines
and a general method for a one-pot synthesis of 2-phenylquinolines in acetonitrile
medium.
RESULTS AND DISCUSSION
The imino-Diels–Alder reaction of N-vinylcaprolactam in the synthesis of
tetrahydroquinolines with N-benzylideneaniline shows stereoselective preference
analogous to those of other dienophiles.[17,18] Recently, Jia et al. reported synthesis
of 4-lactam-N-yl-tetrahydroquinolines with N-arylimines and N-vinyllactams via
imino-Diels–Alder reaction.[19] Initially, we found that the reaction of N-benzylide-
neaniline 1a (1 mmol) with N-vinylpyrroledin-2-one 2a (1 mmol) in acetonitrile in
the presence of SbCl3 (10 mol%) at room temperature produced compounds 3a–h
in good to excellent yields; this reaction is faster than the reaction of the other
reported imino-Diels–Alder reaction[20] (Scheme 1), and the results of our study are
summarized in Table 1.
Further, the SbCl3-catalyzed reaction of N-benzylideneaniline 1a (1 mmol) was
extended to N-vinylcaprolactam 2b (1 mmol) in acetonitrile at room temperature
(Scheme 2). In this reaction (apart from the expected 2-phenyl-1,2,3,4-tetrahydroqui-
noline, 4a–j), 2-phenylquinoline (5a–g) was obtained in almost the same yield
(5–10%) as in the previous reaction. Through careful spectral analysis, the structure
of 2-phenylquinoline (5a–h) was established. The formation of 2-phenylquinoline
Scheme 1. Synthesis of 1-(2-phenyl-1,2,3,4-tetrahydroquinolin-4-yl)pyrrolidin-2-one with N-benzylidene-
aniline=N-vinylpyrroledin-2-one in acetonitrile in the presence of SbCl3 (10 mol%) at room
temperature.

2222
P. P. VARMA ET AL.
Table 1. SbCl3-catalyzed cycloaddition of N-benzylideneaniline 1a with N-vinyl pyrrolidin-2-one 2a in
acetonitrile at room temperature
Entry
R1
R2
R3
Product
Time (min)
Yield (%)a
1
2
3
4
5
6
7
8
H
Cl
H
H
H
H
3a
3b
3c
3d
3e
3f
30
40
25
25
25
25
30
40
93
96
91
91
90
87
93
91
OCH3
H
H
H
H
NO2
H
CH3
H
H
CH3
H
H
H
Br
Cl
H
3g
3h
H
aIsolated yield. Compounds 5a–h formed to an extent of about 5–10%.
(5a–h) and 5–10% yield stimulated our interest for further investigation. See results
in Table 2.
To ascertain the formation of 2-phenylquinoline and to transform this com-
pound into a major product, we contemplated to carry out this reaction at reflux
temperature of the solvent. When we did, as expected we got only 2-phenylquinoline
5a–h as major products in excellent yield (Scheme 3).The results of this study are
summarized in Table 3.
Recently, Kouznetsov et al. reported
a BiCl3-catalyzed synthesis of
2pheny-1,2,3,4-tetrahydroquinolines.[18] Further, to oxidize these derivatives into
2-phenylquinolines, the products were heated over S8 at 260–280 ꢀC for 10–15 min.
However, in our case, either product can be easily obtained in excellent yield in
a one-pot, two-component reaction of N-benzylideneaniline (1a–h) and N-
vinylcaprolactam=N-vinylpyrrolidin-2-one in the presence of SbCl3 as a catalyst at
room temperature, giving 2-pheny-1,2,3,4-tetrahydroquinolines, and the same at
reflux temperature produced 2-phenylquinolines. Hence, this investigation is novel
and superior over the other methods as we discussed in the introduction for the
preparation of structurally diversified quinolines and tetrahydroquinolines.
Similarly, the three-component, one-pot syntheses of tetrahydroquinolines and
2-phenylquinolines were also achieved in the presence of SbCl3 as a catalyst.
Scheme 2. Synthesis of 1-(2-phenyl-1,2,3,4-tetrahydroquinolin-4-yl)azepan-2-one with N-benzylidene-
aniline=N-vinylcaprolactam in acetonitrile in the presence of SbCl3 (10 mol%) at room temperature.

MILD AND SIMPLE ACCESS TO QUINOLINES
2223
Table 2. SbCl3-catalyzed synthesis of 1-(2-phenyl-1,2,3,4-tetrahydroquinolin-4-yl)azepan-2-one (4a–j)
Entry
R1
R2
R3
Product
Time (min)
Yield (%)a
1
2
H
Cl
H
H
H
H
H
H
H
H
H
H
H
H
4a
4b
4c
4d
4e
4f
30
35
35
35
70
70
35
70
35
70
90
91
90
91
92
91
90
92
90
92
3
F
Br
H
4
H
5
OCH3
CH3
H
H
6
H
7
Cl
NO2
Cl
F
4g
4h
4i
8
OCH3
Br
OCH3
9
10
4j
aIsolated yield. Compounds 5a–h formed to an extent of about 5–10%.
Thus, the reaction of 3-nitrobenzaldehyde, p-anisidine, and 2b was performed
(Scheme 4, Table 4). In our series, only p-anisidine underwent a smooth reaction
with 3-nitrobenzaldehydes in the presence of 10 mol% SbCl3 (Scheme 4) to afford
the expected 2-pheny-1,2,3,4-tetrahydroquinolines and 2-phenylquinolines under
different conditions in good yields (Table 4). Through this reaction, we noticed that
the SbCl3 facilitates the Schiff’s base formation in the initial stage (monitored by
thin-layer chromatography, TLC) followed by cycloaddition with 2b to afford
corresponding tetrahydroquinolines. At reflux temperature, they produced only
2-phenylquinolines. All the substituted 2-pheny-1,2,3,4-tetrahydroquinolines (3a–h,
4a–h) and 2-phenylquinolines (5a–h) obtained were purified by SiO2 column chroma-
tography (petroleum ether=ethyl acetate 9:1 v=v). From the spectral analysis, we
found that 2-pheny-1,2,3,4-tetrahydroquinolines exist as cis isomers. Hence, the
reaction is highly stereoselective in nature.
Thus, the results are interpreted in terms of a different mechanism for the
elimination of the caprolactam=pyrrolidin-2-one rings and a molecule of hydrogen
catalyzed by SbCl3. The accomplishment of such elimination followed by aromatiza-
tion has not been previously reported in the literature. In our earliest studies, the
N-vinyl pyrrolidin-2-one underwent a one-pot, two-component multistep imino-
Diels–Alder reaction with a series of aryl amines in the presence of 4-nitrophthalic
Scheme 3. Synthesis of 2-phenylquinoline with N-benzylideneaniline=N-vinyl caprolactam in acetonitrile
in the presence of SbCl3 (10 mol%) at reflux temperature.

2224
P. P. VARMA ET AL.
Table 3. Synthesis of 2-phenylquinoline from N-benzylideneaniline (1a–h) and N-vinylcaprolactam=
N-vinylpyrrolidin-2-one in the presence of SbCl3 in acetonitrile at reflux temperature
Entry
R1
R2
R3
Product
Time (min)
Yield (%)a
1
2
3
4
5
6
7
H
H
H
H
H
H
H
H
H
H
Cl
H
5a
5b
5c
5d
5e
5f
30
30
35
35
70
70
70
60
68
69
69
79
80
80
F
Br
NO2
H
CH3
OCH3
OCH3
H
F
5g
aIsolated yield.
acid as a catalyst to give (2-methyl-1,2,3,4-tetrahydroquinolin-4-yl)-pyrrolidin-
2-one.[21] Impressed by these results, the reaction between aniline (1 mmol) and
N-vinylpyrrolidin-2-one (2 mmol) was carried out in the presence of 10 mol% SbCl3
in acetonitrile at reflux temperature, but this reaction did not give the expected
2-methylquinolines (Scheme 5).
Finally, the structures of all the new products were established on the basis of
spectroscopic evidence, and all the products provided satisfactory elemental analysis.
1
The exclusive cis diastereoselectivity of the products were established by the H
1
NMR spectral analysis. The H NMR spectrum of compound 4h showed large vic-
inal coupling constants between H-4 and H-3ax (11.6 Hz) and H-2 and H-3ax
(11.4 Hz), which remain consistent with a trans-diaxial relationship between these
protons and hence with a cis relationship between the caprolactam ring and phenyl
Scheme 4. One-pot synthesis of 2-phenyl-1,2,3,4-tetrahydroquinoline via imino-Diels–Alder reaction with
P-anisidine with 3-nitro benzaldehyde in the presence of SbCl3 in acetonitrile at room temperature.

MILD AND SIMPLE ACCESS TO QUINOLINES
2225
Table 4. 2-Pheny-1,2,3,4-tetrahydroquinolines 4 prepared by three-component imino-Diels–Alder
reaction in presence of SbCl3 at room temperature in acetonitrile
Entry
1
R1
R2
H
R3
Product
4h
Time (min)
70
Yield (%)a
90
OCH3
NO2
aIsolated yield.
groups.[18] The cis configuration was also supported by nuclear Overhauser effect
spectroscopy (NOESY) as depicted in Fig. 1.
Thus, we propose
a
plausible mechanism for elimination of N-
vinylcaprolactam=N-vinylpyrrolidin-2-one at reflux temperature with subsequent
aromatization leading to 2-phenylquinolines. We have found that the elimination
and subsequent aromatization is possible only when aryl group is present at the
2-position and not with the -CH3 group (Schemes 3 and 5). In the case of 2-phenylte-
trahydroquinolines, the steric factor may favor elimination and aromatization to
give 2-phenylquinolines. It is assumed that the steric effect is not operative in the case
of e,e-cis-2-methyltetrahydroquinolines as the two rings occupy peripheral positions
(–CH3 group at the 2-position and caprolactam ring at the 4-position). The tentative
mechanism highlighting the involvement of steric factors presented in Scheme 6. The
results are rationalized in terms of a greater steric repulsion between the caprolactam
ring and the phenyl ring in a,a-cis-conformation of the tetrahydroquinolines
(transition substrate A). Hence, the release of the strain takes place by the trans-
1,2-elimination of the molecule of caprolactam followed aromatization in the pres-
ence of air and antimony chloride to give 2-phenylquinolines in one pot.
EXPERIMENTAL
General Procedure for the Synthesis of Tetrahydroquinolines
SbCl3 (10 mol%) was added to a stirred solution of N-benzylideneaniline
(1 mmol) and N-vinylpyrrolidin-2-one=N-vinylcaprolactam (1 mmol) in acetonitrile
(10 mL) at room temperature. After completion of the reaction (as indicated
by TLC), the mixture was extracted with ethyl acetate (2 ꢁ 20 mL), dried over
Scheme 5. Synthesis of 2-methyl-4-amino-subsubtituted-tetrahydroquinoline with aniline and N-
vinylpyrroledin-2-one at room temperature.

2226
P. P. VARMA ET AL.
Figure 1. NOSEY correlation showing cis diastereoselectivity for product 4h.
(anhydrous Na2SO4), and evaporated. The crude was purified by silica-gel column
chromatography using light petroleum ether–ethyl acetate (9=1, v=v).
General Procedure for the Synthesis of 2-Phenylquinolines
SbCl3 (10 mol%) was added to a solution of N-benzylideneaniline (1 mmol) and
N-vinylpyrroledin-2-one=N-vinylcaprolactam (1 mmol) in acetonitrile (10 mL). The
Scheme 6. Mechanism for elimination of the molecule of caprolactam followed by aromatization in the
presence of air and antimony chloride to give 2-phenylquinolines in one pot.

MILD AND SIMPLE ACCESS TO QUINOLINES
2227
contents were refluxed. After completion of the reaction (as indicated by TLC), the
mixture was extracted with ethyl acetate (2 ꢁ 20 mL), dried over (anhydrous
Na2SO4), and evaporated. The crude was subjected to silica-gel column chromato-
graphy with a petroleum ether–ethyl acetate (9=1, v=v) as eluent. Characterization
of the products is given next.
cis-1-(2-Phenyl-1,2,3,4-tetrahydroquinolin-4-yl)azepan-2-one (4a)
Yellow oil. 1H NMR (300 MHz, CDCl3): d ¼ 1.21–2.04 (m, 7H), 2.14–2.21 (m, 1H),
2.63–2.67 (m, 2H), 3.04–3.23 (m, 2H), 4.01 (s, 1H, NH), 4.56 (d, J ¼ 11.1 Hz, 1H), 6.21
(dd, J ¼ 5.7, 11.7 Hz, 1H), 6.57 (d, J ¼ 8.1 Hz, 1H), 6.70 (t, J ¼ 8.1 Hz, 1H), 6.96 (d,
J ¼ 8.1 Hz, 1H), 7.05 (t, J ¼ 8.1 Hz, 1H), 7.29–7.45 (m, 5H). 13C NMR (100 MHz,
CDCl3): d ¼ 23.5, 29.5, 30.0, 36.0, 37.5, 44.7, 51.5, 56.5, 114.8, 119.9, 126.4,
127.3, 127.8, 127.4, 128.0, 128.7, 143.1, 146.5, 176.7. MS: m=z (%) ¼ 321.0 (M þ 1).
cis-1-(6-Chloro-2-phenyl-1,2,3,4-tetrahydroquinolin-4-yl)azepan-2-
one (4b)
White crystalline solid; mp 147–149 ꢀC; 1H NMR (300 MHz, DMSO-d6)
d ¼ 1.16–1.97 (m, 8H), 2.36–2.43 (m, 1H), 2.69–2.71 (m, 1H), 2.92–2.96 (m, 1H),
3.18–3.31 (m, 1H), 4.52–4.57 (m, 1H), 5.90–6.01 (m, 1H), 6.26(s, 1H), 6.62–6.70
(m, 2H), 6.94–6.97 (m, 1H), 7.26–7.47 (m, 5H). 13C NMR (100 MHz) 24.1, 29.8,
29.8, 30.2, 35.2, 42.3, 44.1, 51.5, 115.5, 122.3, 122.5, 126.5, 127.8, 128.0, 128.5,
128.7, 129.0, 129.1, 141.0, 143.8, 175.8. MS m=z (%) ¼ 355 (M þ 1). Anal. calcd.
for (C21H23ClN2O): C, 71.07; H, 6.53; N, 7.89. Found: C, 71.09; H, 6.51; N, 7.9.
cis-1-(6-Fluoro-2-phenyl-1,2,3,4-tetrahydroquinolin-4-yl)azepan-
2-one (4c)
Mp 121–125 ꢀC; 1H NMR (400 MHz, CDCl3) d ¼ 1.07–1.61 (m, 3H), 1.76–1.86
(m, 3H), 1.93–2.02 (m, 1H), 2.20 (ddd, J ¼ 8.5, 6.1, 2.3 Hz, 1H), 2.61–2.71 (m, 2H),
3.07 (dd, J ¼ 15.3, 6.5 Hz, 1H), 3.18–3.25 (m, 1H), 3.91 (s, 1H), 4.55 (dd, J ¼ 11.4,
2.0 Hz, 1H), 6.20 (dd, J ¼ 11.7, 5.5 Hz, 1H), 6.52 (dd, J ¼ 8.8, 4.7 Hz, 1H), 6.66
(dd, J ¼ 9.4, 3.0 Hz, 1H), 6.75–6.80 (m, 1H), 7.31–7.40 (m, 3H), 7.43–7.45 (m, 2H);
13C NMR (100 MHz) 24.0, 29.7, 29.5, 30.0, 35.8, 42.1, 44.1, 51.0, 115.3, 116.3,
123.0, 125.9, 114.0, 127.9, 128.6, 128.3, 128.9, 139.9, 141.4, 152.0, 175.7. MS m=z
(%) ¼ 339 (M þ 1). Anal. calcd. for (C21H23FN2O): C, 74.53; H, 6.85; N, 8.28.
Found: C, 74.54; H, 6.81; N, 7.88.
cis-1-(6-Bromo-2-phenyl-1,2,3,4-tetrahydroquinolin-4-yl)azepan-
2-one (4d)
White needles; mp 172–174 ꢀC; 1H NMR (400 MHz, CDCl3) d ¼ 1.37–1.39 (m,
1H), 1.59–1.62 (m, 2H), 1.81–1.86 (m, 3H), 1.92ꢂ2.01 (m, 1H), 2.14–2.17 (m, 1H),
2.61–2.73 (m, 2H), 3.05–3.26 (m, 2H), 4.02 (s, 1H), 4.55–4.58 (m, 1H), 6.17–6.19
(m, 1H), 6.45 (d, J ¼ 8.4 Hz, 1H), 7.01 (s, 1H), 7.12 (d, J ¼ 8.4, 1H), 7.33 (m, 5H);
13C NMR (100 MHz) 23.5, 29.5, 29.9, 35.5, 37.4, 44.7, 51.2, 56.4, 109.7, 116.4,

2228
P. P. VARMA ET AL.
122.1, 126.4, 128.0, 128.8, 129.5, 130.7, 142.6, 145.4, 176.8. MS m=z (%) ¼ 401
(M þ 1). Anal. calcd. for (C21H23BrN2O): C, 63.16; H 5.81; N, 7.02. Found: C,
63.07; H, 5.7; N, 7.09.
cis-1-(6-Methyl-2-phenyl-1,2,3,4-tetrahydroquinolin-4-yl)azepan-
2-one (4f)
White needles; mp 129–130 ꢀC. 1H NMR (400 MHz, CDCl3) d ¼ 1.23–1.32 (m,
1H), 1.40–1.52 (m, 2H), 1.67–1.70 (m, 3H), 1.80–1.88 (m, 2H), 2.12 (s, 3H), 2.40 (dd,
J ¼ 13.6, 7.8 Hz, 1H), 2.68 (t, J ¼ 12.8 Hz, 1H), 2.92 (dd, J ¼ 15.0, 5.5 Hz, 1H),
3.12–3.18 (m, 1H), 4.47 (dd, J ¼ 10.0, 2.7 Hz, 1H), 5.81 (s, 1H), 6.0 (dd, J ¼ 10.7,
6.3 Hz, 1H), 6.53–6.76 (m, 3H), 7.28 (t, J ¼ 7.1 Hz, 1H), 7.35 (t, J ¼ 7.2 Hz, 2H),
7.45 (d, J ¼ 7.2 Hz, 2H). 13C NMR (100 MHz, CDCl3) 21.0, 24.0, 30.1, 29.8, 29.7,
36.1, 42.3, 44.2, 51.4, 114.1, 125.2, 121.0, 126.0, 127.2, 127.9, 128.8, 128.6, 129.0,
131.0, 141.0, 143.0, 175.8. MS m=z (%) ¼ 355 (M þ 1). Anal. calcd. for
(C21H23ClN2O): C, 79.0; H 7.84; N, 8.38. Found: C, 78.81; H, 7.64; N, 8.28.
cis-1-(2-(4-Chlorophenyl)-1,2,3,4-tetrahydroquinolin-4-yl)azepan-
2-one (4g)
White needles; mp 134–136 ꢀC. 1H NMR (400 MHz, CDCl3) d ¼ 0.86–1.38 (m,
3H), 1.74–1.98 (m, 4H), 2.13–2.18 (m, 1H), 2.61–2.67 (m, 2H), 3.07 (dd, J ¼ 15.2,
6.5 Hz, 1H), 3.15–3.26 (m, 1H), 3.9 (s, 1H), 4.55–4.58 (m, 1H), 6.21 (dd, J ¼ 12.0,
6.3 Hz, 1H), 6.60 (d, J ¼ 8.0 Hz, 1H), 6.72 (t, J ¼ 7.4 Hz, 1H), 6.93 (d, J ¼ 7.5 Hz,
1H), 7.05 (t, J ¼ 7.5 Hz, 1H), 7.34–7.40 (m, 4H); 13C NMR (100 MHz, CDCl3)
23.4, 29.4, 29.8, 36.0, 37.3, 44.6, 51.3, 55.8, 114.9, 118.1, 119.8, 127.1, 127.7, 127.9,
128.7, 133.2, 141.6, 146.2, 176.6. MS m=z (%) ¼ 355 (M þ 1). Anal. calcd. for
(C21H23ClN2O): C, 71.07; H 6.53; N, 7.89. Found: C, 70.82; H, 6.32; N, 7.56.
cis-1-(6-Methoxy-2-(3-nitrophenyl)-1,2,3,4-tetrahydroquinolin-4-
yl)azepan-2-one (4h)
1
Mp 147–149 ꢀC; H NMR (400 MHz, CDCl3) d ¼ 1.34–1.4 (m, 1H), 1.57–1.60
(m, 3H), 1.76–1.84 (m, 3H), 1.94–1.97 (m, 1H), 2.20 (ddd, J ¼ 8.2, 6.0, 2.0 Hz, 1H),
2.64–2.67 (m, 2H), 3.10–3.12 (m, 1H), 3.17–3.21 (m, 1H), 3.74 (s, 3H), 3.82 (s, 1H),
4.64 (dd, J ¼ 11.4, 2.0 Hz, 1H), 6.22 (dd, J ¼ 11.6, 6.0 Hz, 1H), 6.54 (d, J ¼ 2.4 Hz,
1H), 6.60 (d, J ¼ 8.6 Hz, 1H), 6.71 (dd, J ¼ 8.7, 3.0 Hz, 1H). 7.55 (t, J ¼ 12.0 Hz,
1H), 7.75 (d, J ¼ 7.6 Hz, 1H), 8.40 (s, 1H). 13C NMR (100 MHz, CDCl3) 24.0, 29.9,
29.8, 30.2, 36.2, 42.3, 44.3, 50.4, 56.0, 113.0, 113.3, 115.2, 118.5, 122.3, 123.6,
130.0, 134.5, 138.1, 141.9, 149.0, 150.1, 175.8. MS m=z (%) ¼ 396 (M þ 1). Anal. calcd.
for (C22H25N3O4): C, 66.82; H, 6.37; N, 10.63. Found: C, 66.57; H, 6.17; N, 10.4.
cis-1-(6-Bromo-2-(4-chlorophenyl)-1,2,3,4-tetrahydroquinolin-4-
yl)azepan-2-one (4i)
Mp: 147–149 ꢀC; 1H NMR (300 MHz, CDCl3) d ¼ 1.34–1.43 (m, 1H),
1.58–1.66 (m, 2H), 1.74–1.92 (m, 4H), 2.09–2.11 (m, 1H), 2.64–2.69 (m, 2H),

MILD AND SIMPLE ACCESS TO QUINOLINES
2229
3.06–3.09 (m, 1H), 3.18–3.21 (m, 1H), 4.0 (s, 1H), 4.53 (dd, J ¼ 11.3, 2.0 Hz, 1H),
6.14 (dd, J ¼ 11.6, 6.1 Hz, 1H), 6.46 (d, J ¼ 8.5 Hz, 1H), 7.01 (s, 1H), 7.12 (dd,
J ¼ 8.5, 2.2 Hz, 1H), 7.35–7.36 (m, 4H); 13C NMR (100 MHz, CDCl3) 24.0, 29.6,
29.8, 30.1, 35.1, 42.4, 44.3, 51.5, 112.0, 116.1, 123.5, 129.4, 129.7, 129.7, 129.1,
129.6, 132.0, 134.0, 138.0, 144.7, 175.8. MS m=z (%) ¼ 433 (M þ 1). Anal. calcd.
for (C21H22BrClN2O): C, 58.15; H, 5.11; N, 6.46. Found: C, 57.93; H, 4.92; N, 6.2.
cis-1-(6-Methoxy-2-(4-fluorophenyl)-1,2,3,4-tetrahydroquinolin-4-
yl)azepan-2-one (4j)
Mp: 165–166 ꢀC; 1H NMR (300 MHz, CDCl3) d ¼ 1.58–1.95 (m, 9H),
2.11–2.14 (m, 1H), 2.63–2.64 (m, 2H), 3.10–3.18 (m, 2H), 3.73 (s, 3H), 4.50 (dd,
J ¼ 11.4, 2.0 Hz, 1H), 6.15–6.39 (m, 1H), 6.52–6.56 (m, 2H), 6.70 (dd, J ¼ 8.6,
2.5 Hz, 1H), 7.36–7.43 (m, 2H); 13C NMR (100 MHz, CDCl3) 24.0, 29.9, 29.8,
30.0, 36.2, 42.5, 44.3, 51.4, 56.0, 112.2, 113.1, 115.7, 116.0, 116.0, 122.3, 127.6,
129.9, 135.9, 138.2, 150.0, 160.3, 175.8. MS m=z (%) ¼ 369.2 (M þ 1). Anal. calcd.
for (C22H25FN2O2): C, 71.72; H, 6.84; N, 7.60. Found: C, 71.43; H, 6.53; N, 7.31.
2-Phenylquinoline (5a)
1H NMR (300 MHz, DMSO-d6) d ¼ 7.49–7.61 (m, 4H), 7.75–7.79 (m, 1H),
7.98–8.28 (m, 5H), 8.44–8.47 (m, 1H); MS m=z (%) ¼ 207 (M þ 2); 13C NMR
(100 MHz, CDCl3) 120.0, 126.0, 127.5, 127.7, 127.9, 127.9, 128.9, 129.8, 130.3,
130.3, 130.9, 137.0, 138.6, 148.0, 157.0. Anal. calcd. for (C15H11N): C, 87.77; H,
5.40; N, 6.82. Found; C, 87.75; H, 5.30; N, 6.52.
2-(4-Chlorophenyl)quinoline (5b)
Mp: 107–108 ꢀC; 1H NMR (300 MHz, CDCl3) d ¼ 7.49–7.57 (m, 3H),
7.74–7.75 (m, 1H), 7.83–7.87 (m, 2H), 8.12–8.17 (m, 3H), 8.23–8.26 (m, 1H); MS
m=z (%) ¼ 240 (M þ 1). Anal. calcd. for (C15H10ClN); C, 75.16; H, 4.21; N, 5.84.
Found; C, 74.95; H, 3.94; N, 5.53.
6-Fluoro-2-phenylquinoline (5c)
1
Mp: 85–87 ꢀC; H NMR (300 MHz, CDCl3) d ¼ 7.47–7.54 (m, 5H), 7.92 (s,
1H), 8.13–8. 20 (m, 4H); MS m=z (%) ¼ 224.0 (M þ 1). 13C NMR (100 MHz, CDCl3)
110.7, 119.2, 120.4, 127.1, 127.6, 127.8, 127.8, 130.2, 130.2, 131.8, 137.0, 138.0, 145.1,
156.2, 161.2. Anal. calcd. for (C15H10FN): C, 80.70; H, 4.51; N 6.27. Found: C,
80.44; H, 4.25, N, 6.08.
6-Bromo-2-(3-nitrophenyl)quinoline (5d)
Mp: 147–149 ꢀC; 1H NMR (300 MHz, CDCl3) d ¼ 7.72 (t, J ¼ 8.0 Hz, 1H), 7.84
(dd, J ¼ 9.0, 2.2 Hz, 1H), 8.0 (d, J ¼ 8.6 Hz, 1H), 8.04–8.08 (m, 2H), 8.22 (d,
J ¼ 8.6 Hz, 1H), 8.32–8.35 (m, 1H), 8.53–8.56 (m, 1H), 9.04–9.05 (m, 1H); MS m=z
(%) ¼ 329 (M þ 1); 13C NMR (100 MHz, CDCl3) 119.8, 120.0, 121.2, 122.5, 123.8,

2230
P. P. VARMA ET AL.
129.9, 130.8, 131.3, 134.0, 134.0, 137.6, 138.0, 148.1, 149.5, 157.2. Anal. calcd. for
(C15H9BrN2O2): C, 54.74; H, 2.76; N, 8.51. Found: C, 54.4; H, 2.57; N, 8.22.
6-Methyl-2-phenylquinoline (5e)
1
Mp: 108–110 ꢀC; H NMR (400 MHz, CDCl3) d ¼ 2.56 (s, 3H), 7.46–7.60 (m,
5H), 7.85 (d, J ¼ 8.6 Hz, 1H), 8.08 (d, J ¼ 8.5 Hz, 1H), 8.07–8.17 (m, 3H); 13C
NMR (100 MHz, CDCl3) 119.8, 120.0, 121.2, 122.5, 123.8, 129.9, 130.8, 131.3,
134.0, 134.0, 137.6, 138.0, 148.1, 149.5, 157.2; MS m=z (%) ¼ 220.2 (M þ 1). Anal.
calcd. for (C16H13N): C, 87.64; H, 5.98; N, 6.39. Found: C, 87.42; H, 5.68; N,6.2.
6-Methoxy-2-phenylquinoline (5f)
1
Mp: 128 ꢀC; H NMR (300 MHz, CDCl3) d ¼ 3.96 (s, 3H), 7.11 (d, J ¼ 2.8 Hz,
1H), 7.40–7.52 (m, 4H), 7.86 (d, J ¼ 8.6 Hz, 1H), 8.06–8.15 (m, 4H); 13C NMR
(100 MHz, CDCl3) 56, 106.2, 120.5, 123.0, 127.0, 127.6, 127.8, 127.8, 130.2, 130.2,
131.3, 136.8, 137.6, 143.0, 155.3, 158.1; MS m=z (%) ¼ 236.2 (M þ 1). Anal. calcd.
for (C16H13NO): C, 81.68; H, 5.57; N, 5.95. Found: C, 81.32; H, 5.38; N, 5.77.
2-(4-Fluorophenyl)-6-methoxyquinoline (5g)
Mp: 120–123 ꢀC; 1H NMR (300 MHz, CDCl3) d ¼ 3.95 (s, 3H), 7.10 (d,
J ¼ 2.7 Hz, 1H), 7.17–7.26 (m, 2H), 7.40 (dd, J ¼ 9.2, 3.0 Hz, 1H), 7.80 (d, J ¼ 8.6 Hz,
Hz, 1H), 8.03–8.15 (m, 4H); 13C NMR (100 MHz, CDCl3): 56, 106.3, 116.5, 116.5,
120.5, 123.0, 127.0, 129.3, 129.3, 130.8, 131.5, 137.4, 142.6, 155.2, 158.0, 162.0;
MS m=z (%) ¼ 254.0 (M þ 1). Anal. calcd. for (C16H12FNO): C, 75.88; H, 4.78; N,
5.53. Found; C, 75.51; H, 4.62; N, 5.38.
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