Three-step synthesis of 2,4-diaryl-5,6,7,8-tetrahydroquinoline derivatives

Article abstract of DOI:10.1002/jhet.409

(Chemical Equation Presented) Addition of cylohexanone to chalcones, obtained from the appropriate acetophenone and benzaldehyde derivatives, under solvent-free conditions gave 1,5-diketones in good yields. Treatment of 1,5-diketones with ammonium acetate in acetic acid afforded directly 2,4-diaryl-5,6,7,8-tetrahydroquinoline derivatives (7a-u) in high yields. The structures of 7a-u were elucidated by ¹H NMR, ¹³C NMR, IR, and elemental analysis.

Full text of DOI:10.1002/jhet.409

September 2010
Three-Step Synthesis of 2,4-Diaryl-5,6,7,8-tetrahydroquinoline
Derivatives
1017
Hayreddin Gezegen, Alparslan Dingil, and Mustafa Ceylan*
Department of Chemistry, Faculty of Arts and Sciences, Gaziosmanpasa University,
Tokat 60250, Turkey
*E-mail: mceylan@gop.edu.tr
Received October 1, 2009
DOI 10.1002/jhet.409
Published online 11 July 2010 in Wiley Online Library (wileyonlinelibrary.com).
Addition of cylohexanone to chalcones, obtained from the appropriate acetophenone and benzalde-
hyde derivatives, under solvent-free conditions gave 1,5-diketones in good yields. Treatment of 1,5-
diketones with ammonium acetate in acetic acid afforded directly 2,4-diaryl-5,6,7,8-tetrahydroquinoline
1
derivatives (7a–u) in high yields. The structures of 7a–u were elucidated by H NMR, 13C NMR, IR,
and elemental analysis.
J. Heterocyclic Chem., 47, 1017 (2010).
INTRODUCTION
In this study, we report that the synthesis of novel
2,4-diaryl-5,6,7,8-tetrahydroquinoline derivatives 7a–u
via cyclization of 1,5-diketones 5a–u with ammonium
acetate in acetic acid.
The synthesis of oxygen, nitrogen, or sulfur-contain-
ing heterocycles is of importance in the organic and me-
dicinal chemistry [1]. Among these structures, quino-
lines [2], tetrahydroquinolines [3], and their derivatives
are excellent precursor of potential drugs [4]. Quinoline
and their derivatives, which usually possess diverse bio-
logical activities, play important roles as versatile build-
ing blocks for the synthesis of natural products and as
therapeutic agents [5]. In particular, 2-arylquinolines are
biologically active and occur in structures of a number
of antimalarial compounds and antitumor agents [6].
The biological activity of quinoline compounds has
been found to possess antiasthmatic, antibacterial, anti-
anflammatory, and antihypertensive properties [7].
Therefore, the synthesis of quinolines has attracted
much attention in organic synthesis. The classic methods
for the synthesis of quinolines include Skraup [8], Doeb-
ner-Von Miller [9], Conrad and Limbach [10], Combes
[11], and Pfizinger [12] quinoline syntheses. A number
of general synthetic methods have also been reported
[13]. However, some of these methods suffer from sev-
eral disadvantages such as harsh reaction conditions,
multi steps, a large amount of promoters, and long reac-
tion time [14].
RESULTS AND DISCUSSION
The general synthetic strategy used to prepare the
chalcone derivatives (3a–u) was based on Claisen-
Schmidt condensation, which was reported previously
[15]. Chalcone derivatives (3a–u) were prepared by
base-catalyzed condensation of appropriate substituted
acetophenone with benzaldehyde in good yields
(Scheme 1). All chalcone derivatives (3a–u) are well-
known [16–26] according to our literature surveys. The
structures of 3a–u were characterized on the basis of
1
spectral data (IR, H NMR, and 13C NMR) and compar-
ison with authentic samples. After the structures of 3a–u
were determined, they were submitted to additional
reaction of cyclohexanone (4). Addition of cyclohexa-
none to chalcones was performed according to our pre-
viously published method [27] in the presence of PTC
(phase transfer catalyst ¼ triethylammonium chloride)
in solvent-free conditions. 1,5-Diketone derivatives 5a–u
were obtained in moderate to good yields (Scheme 1,
C
V
2010 HeteroCorporation

1018
H. Gezegen, A. Dingil, and M. Ceylan
Vol 47
Scheme 1
Table 1). In this series, the compounds 5a–g are known
in the literature [21,27–29]. The structures of other 1,5-
diketones (5h–u) were determined by spectroscopic
studies (1H, 13C NMR, IR, and elemental analysis). In
the 1H NMR spectrum of 5a–h, the protons of
PhCOCH2 gave an AB system that is characteristic sig-
nals for these compounds. While part A of the AB sys-
tem is shown as a doublet of doublet at d ¼ 3.50–3.42
(J ¼ 15.7–16.7 and 3.9–4.5 Hz) and that of part B is
shown as a doublet of doublet at d ¼ 3.23–3.15 (J ¼
15.7–16.7 and 9.5–9.6 Hz).
Treatment of 1,5-diketones 5a–u with NH4OAc (am-
monium acetate) in AcOH at reflux condition for 2.5–5
h afforded directly 2,4-diaryl-5,6,7,8-tetrahydroquinoline
derivatives 7a–u in excellent yields (Scheme 1, Table
2). The compounds 7a–u were purified by column chro-
matography (on a silica gel) eluting CHCl3/n-hexane
(1:1).
Table 1
Table 2
Synthesized 1,5-diketones (5a–u).
Synthesized 2,4-diaryl-5,6,7,8-tetrahydroquinoline derivatives (7a–u).
Entry
Products
X
Y
Yield (%)
Entry
Products
X
Y
Yield (%)
1
2
3
5a
5b
5c
5d
5e
5f
5g
5h
5i
5j
5k
5l
5m
5n
5o
5p
5r
5s
H
2-OCH3
3-OCH3
4-OCH3
2-Cl
4-Cl
2-Br
4-Br
4-OH
H
H
H
H
83
40
78
78
65
72
63
56
66
77
50
69
60
60
50
70
90
94
97
75
1
2
3
7a
7b
7c
7d
7e
7f
7g
7h
7i
7j
7k
7l
7m
7n
7o
7p
7r
7s
H
2-OCH3
3-OCH3
4-OCH3
2-Cl
4-Cl
2-Br
4-Br
4-OH
H
H
H
H
82
99
83
86
94
98
66
92
80
88
71
87
99
90
82
98
94
81
90
97
4
H
4
H
5
6
H
H
5
6
H
H
7
8
H
H
7
8
H
H
9
H
9
H
10
11
12
13
14
15
16
17
18
19
20
2-OCH3
4-OCH3
2-Cl
3-Cl
4-Cl
2-Br
3-Br
4-Br
4-CH3
4-Cl
4-Cl
10
11
12
13
14
15
16
17
18
19
20
2-OCH3
4-OCH3
2-Cl
3-Cl
4-Cl
2-Br
3-Br
4-Br
4-CH3
4-Cl
4-Cl
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
5t
5u
4-OCH3
4-Cl
7t
7u
4-OCH3
4-Cl
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

September 2010
Three-Step Synthesis of 2,4-Diaryl-5,6,7,8-tetrahydroquinoline Derivatives
1019
1
(CCl4/n-hexane, 3:1). H NMR (200 MHz, CDCl3) d ¼ 7.43–
6.85 (m, 9H), 3.86 (s, 3H), 3.80–3.68 (m, 1H), 2.72–2.63 (m,
1H), 3.44–3.33 (m, 2H), 2.72–2.28 (m, 3H), 1.95–1.24 (m,
5H). 13C NMR (50 MHz, CDCl3) d ¼ 215.4, 203.2, 160.1,
144.5, 134.9, 132.1, 130.9, 130.6 (2C), 130.2 (2C), 128.3,
122.5, 113.3, 57.9, 57.5, 50.8, 43.8, 42.6, 33.8, 30.3, and 25.6.
IR (KCl): 3058, 3026, 2925, 2854, 1703, 1666, 1483, 1433,
1284, 1242, 1022, 752, 698, and 567 cmꢁ1. Anal. Calcd. for:
C22H24O3: C, 78.54; H, 7.19. Found: C, 78.15; H, 7.48.
2-(3-(3-Methxyphenyl)-3-oxo-1-phenylpropyl)cylohexanone
(5c). Yield 78%; colorless crystals; mp 89–92ꢀC (CCl4/n-hex-
ane, 3:1). 1H NMR (200 MHz, CDCl3) d ¼ 7.55–7.03 (m,
9H), 3.81 (s, 3H), 3.88–3.66 (m, 1H), 3.50 (dd, J ¼ 16.1, 4.0
Hz, 1H), 3.20 (dd, J ¼ 16.1, 9.6 Hz, 1H), 2.79–2.55 (m, 1H),
2.51–2.38 (m, 2H), 2.01–1.22 (m, 6H). 13C NMR (50 MHz,
CDCl3) d ¼ 215.5, 200.6, 161.7, 143.9, 140.4, 131.4, 130.5
(2C), 130.4 (2C), 128.6, 122.8, 121.5, 114.5, 57.8, 57.4, 46.4,
44.4, 43.3, 34.5, 30.6, and 26.2. IR (KCl): 3058, 3028, 2931,
2912, 2852, 1709, 1678, 1581, 1431, 1259, 1049, 987, 700,
and 573 cmꢁ1. Anal. Calcd. for: C22H24O3: C, 78.54; H, 7.19.
Found: C, 78.20; H, 7.42.
Structures of 7a–u were confirmed by their spectral
(IR, NMR, and elemental analyses) data. In the 1H
NMR spectrum of 7a–u, the H4 proton gave a singlet
(between d ¼ 7.60 and 7.30 ppm) that is characteristic
signals for these compounds. All spectral data are con-
sistent with the titled compounds.
In conclusion, we have described a mild, efficient,
and convenient method for the synthesis of 2,4-diaryl-
5,6,7,8-tetrahydroquinoline derivatives from cheap and
easily available materials such as acetophenone and
benzaldehyde derivatives, cyclohexanone and ammo-
nium acetate.
EXPERIMENTAL
1H and 13C NMR spectra were recorded with Bruker AC
400 instruments. As internal standards, we used TMS (d 0.00)
1
for H NMR and CDCl3 (d 77.0) for 13C NMR spectroscopy.
J values are given in hertz. The multiplicities of the signals in
2-(3-(4-Methoxyphenyl)-3-oxo-1-phenylpropyl)cyclohexanone
(5d). Yield 78%; colorless crystals; mp 128–130ꢀC (CCl4/n-
hexane, 3:1). H NMR (400 MHz, CDCl3) d ¼ 7.91–7.89 (m,
1
the H NMR spectra are abbreviated to s (singlet), d (doublet),
t (triplet), q (quartet), m (multiplet), br (broad), and combina-
tions thereof. IR spectra were recorded on a Jasco FT/IR-430
spectrometer. Elemental analyses were performed using a
LECO CHNS 932 elemental analyzer. Melting points were
measured on Electrothermal 9100 apparatus. All column chro-
matographies were performed on silica gel (60–230 mesh,
Merck).
General procedure for the synthesis of chalcones
3a–u. To a solution of acetophenone derivative (1 mmol) in
ethanol (20 mL) was added NaOH (8 mL, 2.5M NaOH) and
benzaldehyde derivative (1 mmol) at room temperature. The
mixture was stirred for 3 h. Then the mixture was washed
with diluted HCl and extracted with CHCl3. The organic layer
was dried over Na2SO4 and the solvent was removed in vac-
uum. The residue was purified on a silica gel column eluting
with CHCl3/n-hexane (3:7) and/or crystallized from CHCl3/n-
hexane (3:7).
General procedure for the synthesis of 1,5-diketones
5a–u. To a mixture of chalcone (1a) (10 mmol) and cycylohex-
anone (4) (20 mmol) were added solid KOH (0.06% mol) with
a few drop of water and PTC (benzyltrithylammonium chloride)
(0.06% mol) and stirred for 3–4 h at room temperature. Then,
the mixture was extracted with 20 mL of CHCl3 and dried over
Na2SO4. After the solvent was taken off in vacuum, the crude
product was crystallized from CCl4/hexane (3:1).
2-(3-Oxo-1,3-diphenlpropyl)cyclohexanone (5a). Yield
83%; colorless crystals; mp 146–148ꢀC (CCl4/n-hexane, 3:1).
1H NMR (200 MHz, CDCl3) d ¼ 7.93–7.89 (m, 2H), 7.55–
7.41 (m, 3H), 7.37–7.13 (m, 5H), 3.78–3.68 (m, 1H), 3.50 (dd,
J ¼ 16.2, 4.1 Hz, 1H), 3.23 (dd, J ¼ 16.2, 9.5 Hz, 1H), 2.75–
2.68 (m, 1H), 2.68–2.32 (m, 2H), 2.01–1.51 (m, 5H), 1.50–
1.24 (m, 1H). 13C NMR (50 MHz, CDCl3) d ¼ 215.6, 200.8,
144.1, 139.1, 134.8, 130.5 (2C), 130.4 (2C), 130.3 (2C), 130.2
(2C), 57.8, 46.2, 44.3, 43.1, 34.5, 30.5, and 26.1. IR (KCl):
3056, 33025, 2939, 2918, 2854, 1708, 1683, 1596, 1446, 1340,
1216, 746, 696, and 567 cmꢁ1. Anal. Calcd. for: C21H22O2: C,
82.32; H, 7.24. Found: C, 81.98; H, 7.22.
1
2H), 6.91–6.87 (m, 2H), 7.88–7.14 (m, 5H), 3.84 (s, 3H),
3.75–3.69 (m, 1H), 2.75–2.69 (m, 1H), 3.42 (dd, J ¼ 15.7, 4.0
Hz, 1H), 3.17 (dd, J ¼ 15.7, 9.5 Hz, 1H), 2.55–2.48 (m, 1H),
2.02–1.92 (m, 1H), 1.80–1.50 (m, 5H), 1.31–1.10 (m, 1H). 13C
NMR (100 MHz, CDCl3) d ¼ 213.9, 197.5, 163.5, 142.3,
130.4, 130.7 (2C), 128.7 (2C), 128.6 (2C), 126.8 (1C), 113.8
(1C), 56.1, 55.6, 44.1, 42.5, 41.5, 32.6, 28.7, and 24.2. IR
(KCl): 3057, 3026, 2933, 2852, 1707, 1672, 1603, 1420, 1255,
1167, 984, 816, 698, and 565 cmꢁ1. Anal. Calcd. for:
C22H24O3: C, 78.54; H, 7.19. Found: C, 78.30; H, 7.18.
2-(3-(2-Chlorophenyl)-3-oxo-1-phenylpropyl)cyclohexanone
(5e). Yield 65%; colorless crystals; mp 120–124ꢀC (CCl4/n-
hexane, 3:1). H NMR (200 MHz, CDCl3) d ¼ 7.43–7.11 (m,
1
9H), 3.71–3.59 (m, 1H), 3.46 (dd, J ¼ 16.6, 4.5 Hz, 1H), 3.23
(dd, J ¼ 16.6, 9.5 Hz, 1H), 2.72–2.60 (m, 1H), 2.55–2.34 (m,
2H), 1.99–1.22 (m, 6H). 13C NMR (50 MHz, CDCl3) d ¼
215.2, 203.8, 143.7, 141.5, 132.7, 133.3, 132.2, 130.9, 130.5
(2C), 128.7 (2C), 57.7, 50.2, 44.2, 43.0, 34.2, 30.4, and 26.0.
IR (KCl): 3058, 3026, 2933, 2918, 2854, 1705, 1691, 1431,
1369, 1122, 1072, 983, 750, 721, and 567 cmꢁ1. Anal. Calcd.
for: C21H21ClO2: C, 74.00; H, 6.21. Found: C, 73.74; H, 6.23.
2-(3-(4-Chlorophenyl)-3-oxo-1-phenylpropyl)cyclohexanone
(5f). Yield 72%; colorless crystals; mp 113–116ꢀC (CCl4/n-
1
hexane, 3:1). H NMR (200 MHz, CDCl3) d ¼ 7.94–7.83 (m,
2H), 7.42–7.29 (m, 2H), 7.27–7.12 (m, 5H), 3.68–3.61 (m,
1H), 3.54 (dd, J ¼ 15.8, 4.0 Hz, 1H), 3.15, (dd, J ¼ 15.8, 9.6
Hz, 1H), 2.74–2.66 (m, 1H), 2.51–2.35 (m, 2H), 2.02–1.21 (m,
6H). 13C NMR (50 MHz, CDCl3) d ¼ 215.7, 199.6, 143.7,
141.2, 137.4, 131.7 (2C), 130.7 (2C), 130.6 (2C), 130.3 (2C),
128.7, 57.8, 46.4, 44.5, 43.4, 34.7, 30.6, and 26.3. IR (KCl):
3057, 3024, 2939, 2918, 2852, 1707, 1685, 1589, 1446, 1398,
1215, 1095, 982, 816, 696, and 567 cmꢁ1. Anal. Calcd. for:
C21H21ClO2: C, 74.00; H, 6.21. Found: C, 73.68; H, 6.26.
2-(3-(2-Bromophenyl)-3-oxo-1-phenylpropyl)cyclohexanone
(5g). Yield 63%; colorless crystals; mp 120–122ꢀC (CCl4/n-
1
hexane, 3:1). H NMR (200 MHz, CDCl3) d ¼ 7.53–7.49 (m,
2-(3-(2-Methoxyphenyl)-3-oxo-1-phenylpropyl)cyclohex-
anone (5b). Yield 40%; colorless crystals; mp 108–111ꢀC
1H), 7.31–7.09 (m, 8H), 3.46 (dd, J ¼ 16.7, 4.4 Hz, 1H), 3.21
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

1020
H. Gezegen, A. Dingil, and M. Ceylan
Vol 47
(dd, J ¼ 16.7, 9.5 Hz, 1H), 3.72–3.62 (m, 1H), 2.73–2.61 (m,
1H), 2.55–2.32 (m, 2H), 1.99–1.22 (m, 6H). 13C NMR (50
MHz, CDCl3) d ¼ 215.2, 204.5, 143.6, 143.6, 135.5, 133.3,
130.5 (2C), 130.5 (2C), 130.3, 129.2, 128.7, 120.6, 57.6, 49.9,
44.2, 42.9, 34.2, 30.4, and 26.0. IR (KCl): 3055, 3026, 2933,
2918, 2854, 1705, 1693, 1404, 1369, 1122, 1030, 983, 750,
698, and 567 cmꢁ1. Anal. Calcd. for: C21H21BrO2: C, 65.46;
H, 5.49. Found: C, 65.08; H, 5.83.
cmꢁ1. Anal. Calcd. for: C22H24O3: C, 78.54; H, 7.19. Found:
C, 78.20; H, 7.42.
2-(1-(2-Chlorophenyl)-3-oxo-3-phenylpropyl)cyclohexanone
(5l). Yield 66%; colorless crystals; mp 126–128ꢀC (CCl4/n-
1
hexane, 3:1). H NMR (400 MHz, CDCl3) d ¼ 7.94 (dd, J ¼
14.6 Hz, J ¼ 7.2 Hz, 2H), 7.48 (dd, J ¼ 14.6 Hz, J ¼ 7.2 Hz,
1H), 7.40 (t, J ¼ 7.6 Hz, 2H), 7.33–7.23 (m, 2H), 7.15 (t, J ¼
7.2 Hz, 1H), 7.12–7.04 (m, 1H), 3.55 (dt, J ¼ 16.8, 3.6 Hz,
1H), 3.40 (dd, J ¼ 10, 3.6 Hz, 1H), 2.86–2.42 (m, 1H), 2.54–
2.26 (m, 2H), 1.99 (br s, 1H), 1.85–1.50 (m, 5H), 1.48–1.59
(m, 1H). 13C NMR (100 MHz, CDCl3) d ¼ 213.0, 198.5,
139.8, 136.9, 134.0, 132.8, 129.8, 128.4 (2C), 128.1 (2C),
127.6, 127.0, 126.5, 53.4, 42.9, 42.7, 38.7, 32.6, 28.6, and
24.8. IR (KCl): 3085, 3061, 2936, 2928, 2859, 1698, 1680,
1592, 1574, 1447, 1223, 1119, 981, 748, and 687 cmꢁ1. Anal.
Calcd. for: C21H21ClO2: C, 74.00; H, 6.21. Found: C, 73.89;
H, 6.25.
2-(3-(4-Bromophenyl)-3-oxo-1-phenylpropyl)cyclohexanone
(5h). Yield 56%; colorless crystals; mp 146–149ꢀC (CCl4/n-
hexane, 3:1). 1H NMR (400 MHz, CDCl3) d ¼ 7.79 (d, J ¼
8.4 Hz, 2H), 7.55 (d, J ¼ 8.4 Hz 2H), 7.26 (t, J ¼ 7.2 Hz,
2H), 7.19–7.14 (m, 3H), 3.66 (td, J ¼ 8.8, 3.6 Hz, 1H), 3.50
(dd, J ¼ 15.6, 4.0 Hz, 1H), 3.15 (dd, J ¼ 16.0, 9.6 Hz, 1H),
2.72 (td, J ¼ 10.0, 4.2 Hz, 1H), 2.53–2.48 (m, 1H), 2.44–2.36
(m, 1H), 2.02–1.98 (m, 1H), 1.80–1.50 (m, 4H), 1.28–1.19 (m,
1H). 13C NMR (100 MHz, CDCl3) d ¼ 213.6, 197.89, 141.7,
135.7, 131.8 (2C), 129.8 (2C), 128.5 (2C), 128.3 (2C), 127.9,
126.7, 55.6, 44.4, 42.5, 41.4, 32.7, 28.6, and 24.3. IR (KCl):
3056, 3023, 2938, 2917, 2854, 1706, 1687, 1586, 1397, 1229,
1071, 982, 812, 698, and 569 cmꢁ1. Anal. Calcd. for:
C21H21BrO2: C, 65.46; H, 5.49. Found: C, 65.08; H, 5.87.
2-(3-(4-Hydroxyphenyl)-3-oxo-1-phenylpropyl)cyclohexanone
(5i). Yield 66%; colorless crystals; mp 149–151ꢀC (CCl4/n-
hexane, 3:1). 1H NMR (400 MHz, CDCl3) d ¼ 7.80 (d, J ¼
8.6 Hz, 2H), 7.28–7.23 (m, 3H), 7.19 (d, J ¼ 7.2 Hz, 2H),
6.81 (d, J ¼ 8.6 Hz, 2H), 3.75 (dt, J ¼ 9.6, 4.4 Hz, 1H), 3.42
(dd, J ¼ 16.1, 4.2 Hz 1H), 3.16 (dd, J ¼ 16.1, 9.2 Hz, 1H),
2.79–2.70 (m, 1H), 2.63–2.55 (m, 1H), 2.46–2.38 (m, 1H),
1.98–1.90 (m, 1H), 1.85–1.76 (m, 1H), 1.70–1.52 (m, 3H),
1.36–1.26 (m, 1H). 13C NMR (100 MHz, CDCl3) d ¼ 215.9,
197.6, 160.6, 141.9, 130.8 (2C), 129.6, 128.5 (2C), 128.4 (2C),
126.7, 115.3 (2C), 56.0, 43.9, 42.0, 41.2, 32.3, 28.5, and 23.6.
IR (KCl): 3116, 3054, 3024, 2931, 2857, 1707, 1678, 1428,
1245, 1136, 984, 814, 699, and 567 cmꢁ1. Anal. Calcd. for:
C21H22O3: C, 78.23; H, 6.88. Found: C, 78.12; H, 6.87.
2-(1-(3-chlorophenyl)-3-oxo-3-phenylpropyl)cyclohexanone
1
(5m). Yield 60%; colorless crystals; mp 124–127ꢀC. H NMR
(400 MHz, CDCl3) d ¼ 7.91 (d, J ¼ 7.6 Hz, 2H), 7.52 (t, J ¼
7.2 Hz, 1H), 7.42 (t, J ¼ 7,6 Hz, 2H), 7.21–7.10 (m, 4H), 3.73
(m, 1H), 3.51 (dd, J ¼ 16.8, 4.0 Hz, 1H), 3.23 (dd, J ¼ 16.4,
9.6 Hz, 1H), 2.71 (m, 1H), 2.52–2.38 (m, 2H), 2.02–1.99 (m,
1H), 1.80–1.55 (m, 4H), 1.27–1.23 (m, 1H). 13C NMR (100
MHz, CDCl3) d ¼ 213.0, 189.3, 144.4, 128.5 (2C), 128.1
(2C), 134.2, 132.9, 129.7, 128.4, 126.9, 126.8, 55.5, 43.8,
42.8, 40.7, 32.6, 28.5, and 24.4. IR (KCl): 3083, 3059, 2932,
2924, 2858, 1698, 1681, 1593, 1571, 1449, 1360, 1232, 1127,
983, 748, and 685 cmꢁ1. Anal. Calcd. for: C21H21ClO2: C,
74.00; H, 6.21. Found: C, 73.77; H, 6.22.
2-(1-(4-Chlorophenyl)-3-oxo-3-phenylpropyl)cyclohexanone
(5n). Yield 60%; colorless crystals; mp 122–125ꢀC. 1H NMR
(400 MHz, CDCl3) d ¼ 7.91 (d, J ¼ 7.2 Hz, 2H), 7.52 (t, J ¼
7.2 Hz, 1H), 7.42 (t, J ¼ 7.6 Hz, 2H), 7.23 (d, J ¼ 6.4 Hz,
2H), 7.13 (d, J ¼ 6.4 Hz, 2H), 3.72 (m, 1H), 3.51 (dd, J ¼
16.4, 4.0 Hz, 1H), 3.21 (dd, J ¼ 16.4, 10.0 Hz, 1H), 2,71 (m,
1H), 2.51–2.47 (m, 1H), 2.42–2.37 (m, 1H), 2.03–1.99 (m,
1H), 1.80–1.53 (m, 4H), 1.26–1.20 (m, 1H). 13C NMR (100
MHz, CDCl3) d ¼ 213.1, 198.5, 129.8 (2C), 128.6 (2C) 128.5
(2C), 128.1 (2C), 140.6, 136.5, 132.9, 128.4, 132.2, 55.6, 43.9,
42.5, 40.5, 32.5, 28.5, and 24.4. IR (KCl): 3085, 3060, 2940,
2921, 2856, 1698, 1682, 1594, 1491, 1446, 1217, 1096, 984,
826, 750, and 688 cmꢁ1. Anal. Calcd. for: C21H21ClO2: C,
74.00; H, 6.21. Found: C, 73.84; H, 6.23.
2-(1-(2-Bromophenyl)-3-oxo-3-phenylpropyl)cyclohexanone
(5o). Yield 50%; colorless crystals; mp 92–95ꢀC. 1H NMR
(400 MHz, CDCl3) d ¼ 7.99 (d, J ¼ 8.2 Hz, 2H), 7.55–7.50
(m, 2H), 7.44 (t, J ¼ 7.2 Hz, 2H), 7.27–7.19 (m, 2H), 7.04 (t,
J ¼ 7.6 Hz, 1H), 3.55 (dd, J ¼ 16.4, 4.4 Hz, 1H), 3.38 (dd, J
¼ 16.4, 9.6 Hz, 1H), 2.78–2.75 (m, 1H), 2.54–2.30 (m, 2H),
2.01–1.59 (m, 7H). 13C NMR (100 MHz, CDCl3) d ¼ 211.4,
198.6, 128.5 (2C), 128.2 (2C) 141.3, 136.8, 133.3, 132.9,
128.8, 127.8, 127.1, 125.2, 53.5, 42.3, 38.8, 38.3, 28.6, 27.6,
and 25.0. IR (KCl): 3054, 3025, 2933, 2917, 2854, 1704,
1693, 1583, 1403, 1369, 1230, 1122, 983, 750, 698, and 566
cmꢁ1. Anal. Calcd. for: C21H21BrO2: C, 65.46; H, 5.49.
Found: C, 65.26; H, 5.64.
2-(1-(2-Methoxyphenyl)-3-oxo-3-phenylpropyl)cyclohexanone
1
(5j). Yield 77%; viscous oil. H NMR (400 MHz, CDCl3) d ¼
8.00–7.91 (m, 2H), 7.54–7.47 (m, 1H), 7.43–7.38 (m, 2H),
7.23–7.05 (m, 2H), 6.88–6.80 (m, 2H), 3.74 (s, 3H), 3.50–3.30
(m, 2H), 2.99–2.97 (m, 1H), 2.55–2.26 (m, 2H), 1.99 (br s,
1H), 1.92–1.53 (m, 5H), 1.28–1.23 (m, 1H). 13C NMR (100
MHz, CDCl3) d ¼ 214.3, 199.5, 157.7, 137.2, 132.7, 130.2,
128.7, 128.4, 128.3 (2C), 128.2 (2C), 127.7, 127.3, 55.3, 42.9,
39.1, 32.8, 28.7, 27.7, and 24.4. IR (KCl): 3055, 2956, 2926,
2855, 1699, 1682, 1517, 1443, 1297, 1245, 1174, 987, 824,
725, and 566 cmꢁ1. Anal. Calcd. for: C22H24O3: C, 78.54; H,
7.19. Found: C, 78.32; H, 7.28.
2-(1-(4-Methoxyphenyl)-3-oxo-3-phenylpropyl)cyclohexanone
(5k). Yield 50%; colorless crystals; mp 136–139ꢀC (CCl4/n-
hexane, 3:1). 1H NMR (400 MHz, CDCl3) d ¼ 7.92 (d, J ¼
7.2 Hz, 2H), 7.51 (t, J ¼ 7.2 Hz, 1H), 7.41 (t, J ¼ 7.2 Hz,
2H), 7.09 (d, J ¼ 8.4 Hz, 2H), 6.79 (d, J ¼ 8.4 Hz, 2H), 3.75
(s, 3H), 3.68 (m, 1H), 3.47 (dd, J ¼ 16.0, 4.0 Hz, 1H), 3.18
(dd, J ¼ 16.0, 9.6 Hz, 1H), 2,68 (m, 1H), 2.52–2.48 (m, 1H),
2.41–2.37 (m, 1H), 1.98–1.95 (m, 1H), 1.80–1.66 (m, 3H),
1.57–1.53 (m, 1H),1.28–1.24 (m, 1H). 13C NMR (100 MHz,
CDCl3) d ¼ 213.8, 198.9, 158.1, 113.8 (2C), 128.4 (2C),
128.2 (2C), 56.0, 55.1, 44.4, 42.3, 40.4, 32.4, 28.6, and 24.1.
IR (KCl): 3035, 2965, 2943, 2920, 2852, 1699, 1679, 1610,
1514, 1445, 1294, 1247, 1177, 1027, 987, 821, 723, and 563
2-(1-(3-Bromophenyl)-3-oxo-3-phenylpropyl)cyclohexanone
(5p). Yield 70%; colorless crystals; mp 113–116ꢀC. 1H NMR
(400 MHz, CDCl3) d ¼ 7.91 (d, J ¼ 7.2 Hz, 2H), 7.52 (t, J ¼
7.6 Hz, 1H), 7.42 (t, J ¼ 7.6 Hz, 2H), 7.34 (s, 1H), 7.30 (d, J
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

September 2010
Three-Step Synthesis of 2,4-Diaryl-5,6,7,8-tetrahydroquinoline Derivatives
1021
¼ 7.2 Hz, 1H), 7.17–6.96 (m, 2H), 3.71 (m, 1H), 3.50 (dd, J
¼ 16.8, 4.0 Hz, 1H), 3.22 (dd, J ¼ 16.4, 9.6 Hz, 1H), 2.72–
2.69 (m, 1H), 2.51–2.47 (m, 1H), 2.42–2.37 (m, 1H), 2.02–
1.99 (m, 1H), 1.78–1.55 (m, 4H), 1.27–1.22 (m, 1H). 13C
NMR (100 MHz, CDCl3) d ¼ 212.9, 198.3, 128.5 (2C), 128.1
(2C), 144.7, 122.6, 144.7, 136.8, 132.9, 131.2, 129.8, 27.3,
55.5, 43.8, 42.5, 40.7, 32.6, 28.5, and 24.4. IR (KCl): 3057,
2940, 2927, 2847, 1697, 1681, 1565, 1446, 1233, 1128, 979,
749, 687, and 590 cmꢁ1. Anal. Calcd. for: C21H21BrO2: C,
65.46; H, 5.49. Found: C, 65.31; H, 5.73.
2-(1-(4-Bromopheyl)-3-oxo-3-phenylpropyl)cyclohexanone
(5r). Yield 90%; colorless crystals; mp 122–125ꢀC. 1H NMR
(400 MHz, CDCl3) d ¼ 7.91 (d, J ¼ 7.6 Hz, 2H), 7.53 (t, J ¼
7.2 Hz, 1H), 7.41 (t, J ¼ 6.4 Hz, 2H), 7.38 (d, J ¼ 8.4 Hz,
2H), 7.08 (d, J ¼ 8.4 Hz, 2H), 3.71 (m, 1H), 3.51 (dd, J ¼
16.4, 3.6 Hz, 1H), 3.20 (dd, J ¼ 16.4, 9.6 Hz, 1H), 2.71–2.67
(m, 1H), 2.51–2.47 (m, 1H), 2.42–2.38 (m, 1H), 2.02–1.99 (m,
1H), 1.81–1.51 (m, 4H), 1.26–1.21 (m, 1H). 13C NMR (100
MHz, CDCl3) d ¼ 213.1, 198.5, 131.6 (2C), 130.2 (2C) 128.5
(2C), 128.1 (2C), 141.1, 136.8, 132.9, 120.4, 55.5, 43.9, 42.5,
40.5, 32.5, 28.5, and 24.4. IR (KCl): 3061, 2935, 2911, 2853,
1697, 1682, 1593, 1487, 1446, 1217, 1128, 1009, 824, 749,
and 688 cmꢁ1. Anal. Calcd. for: C21H21BrO2: C, 65.46; H,
5.49. Found: C, 65.19; H, 5.56.
2-(1-(4-Methylphenyl)-3-oxo-3-phenylpropyl)cyclohexanone
(5s). Yield 94%; colorless crystals; mp 130–133ꢀC. 1H NMR
(400 MHz, CDCl3) d ¼ 7.93 (d, J ¼ 7.6 Hz, 2H), 7.51 (t, J ¼
7.2 Hz, 1H), 7.41 (t, J ¼ 7.2 Hz, 2H), 7.08–7.05 (m, 4H), 3.71
(m, 1H), 3.50 (dd, J ¼ 16.0, 4.0 Hz, 1H), 3.21 (dd, J ¼ 16.4,
9.6 Hz, 1H), 2.70 (m, 1H), 2.28 (s, 3H), 2.54–2.49 (m, 1H),
2.42–2.38 (m, 1H), 2.01–1.97 (m, 1H), 1.80–1.65 (m, 3H),
1.57–1.54 (m, 1H), 1.28–1.24 (m, 1H). 13C NMR (100 MHz,
CDCl3, ppm): d ¼ 213.8, 198.9, 129.2 (2C), 128.4 (2C) 128.2
(2C), 128.2 (2C), 138.9, 137.0, 136.1, 132.8, 55.9, 44.3, 42.3,
40.7, 32.5, 28.6, 24.1, and 21.0. IR (KCl): 3033, 2942, 2923,
2857, 1698, 1671, 1596, 1449, 1249, 1125, 819, 760, 694, and
558 cmꢁ1. Anal. Calcd. for: C22H24O2: C, 82.46; H, 7.55.
Found: C, 82.19; H, 7.56.
40.7, 32.7, 28.6, and 24.5. IR (KCl): 3024, 2938, 2862, 1704,
1685, 1589, 1490, 1092, 1012, 984, 827, 756, and 530 cmꢁ1
Anal. Calcd. for: C21H20Cl2O2: C, 67.21; H, 5.37. Found: C,
67.14; H, 5.32.
.
General procedure for synthesis of 2,4-diaryl-5,6,7,8-tet-
rahydroquinoline derivatives (7a-5u). The 1,5-diketone (5)
(1.5 mmol) and ammonium acetate (NH4OAc) (4.5 mmol)
were dissolved in acetic acid (10 mL) and refluxed for 2–5
h. After the removal of acetic acid in vacuum, the residue
was added with CHCl3 (30 mL) and washed with diluted
NaHCO3. Organic layer was dried over Na2SO4. Removal of
the solvent in vacuum gave the 2,4-diaryl-5,6,7,8-tetrahydro-
qinoline derivative (7). The crude product was purified by
column chromatography (on a silica gel) eluting with hexane/
CHCl3 (1:1).
2,4-Diphenyl-5,6,7,8-tetrahydroquinoline (7a). Yield 82%;
1
yellowish viscous oil. H NMR (400 MHz, CDCl3): d ¼ 8.01
(d, J ¼ 8.5 Hz, 2H), 7.44–7.36 (m, 9H), 3.01 (t, J ¼ 6.5 Hz,
2H), 2.69 (t, J ¼ 6.2 Hz, 2H), 2.07–1.93 (m, 2H), 1.82–1.75
(m, 2H). 13C NMR (100 MHz, CDCl3): d ¼ 157.6, 154.3,
150.3, 139.7, 128.7, 128.6, 128.5, 128.4, 128.3, 127.7, 127.1,
126.9, 119.5, 33.4, 27.3, 23.1, and 23.0. IR (KCl): 3060, 3027,
2977, 1582, 1494, 1446, 1236, 1018, 982, 846, 752, 700, and
665 cmꢁ1. Anal. Calcd. for: C21H19N: C, 88.38; H, 6.71; N,
4.91. Found: C, 88.23; H, 6.79; N, 4.98.
2-(2-Methoxyphenyl)-4-phenyl-5,6,7,8-tetrahydroquinoline
(7b). Yield 99%; yellowish crystals, mp 90–93ꢀC. 1H NMR
(400 MHz, CDCl3): d ¼ 7.75 (dd, J ¼ 7.6, 1.6 Hz, 1H), 7.50
(s, 1H), 7.46 (d, J ¼ 7.2 Hz, 2H), 7.43–7.34 (m, 4H), 7.09 (t,
J ¼ 7.6 Hz, 1H), 6.99 (d, J ¼ 8.4 Hz, 1H), 3.83 (s, 3H), 3.13
(t, J ¼ 6.4 Hz, 2H), 2.70 (t, J ¼ 6.0, 2H), 1.99–1.93 (m, 2H),
1.80–1.74 (m, 2H). 13C NMR (100 MHz, CDCl3): d ¼ 157.2,
156.9, 152.9, 149.2, 139.8, 131.2, 129.6, 129.4, 128.8 (2C),
128.3 (2C) 128.1, 127.7, 123.4, 120.8, 111.3, 55.6, 33.1, 27.4,
23.2, and 23.1. IR (KCl): 3058, 3008, 2936, 1600, 1585, 1493,
1436, 1381, 1243, 1026, 890, 753, 701, and 665 cmꢁ1. Anal.
Calcd. for: C22H21NO: C, 83.78; H, 6.71; N, 4.44. Found: C,
83.69; H, 6.67; N, 4.24.
2-(1-(4-Cholorophenyl)-3-(4-methokxyphenyl)-3-oxopropyl)
cyclohexanone (5t). Yield 97%; colorless crystals; mp 131–
2-(3-Methoxyphenyl)-4-phenyl-5,6,7,8-tetrahydroquinoline
(7c). Yield 93%; yellowish crystals, mp 99–102ꢀC. 1H NMR
(400 MHz, CDCl3): d ¼ 7.62 (m, 1H), 7.57 (d, J ¼ 7.6 Hz,
1H), 7.50–7.41 (m, 4H), 7.40–7.35 (m, 3H), 6.96 (dd, J ¼ 8.4,
2.4 Hz, 1H), 3.89 (s, 3H), 3.15 (t, J ¼ 7.2 Hz, 2H), 2.70 (t, J
¼ 6.4 Hz, 2H), 2.00–1.94 (m, 2H), 1.81–1.75 (m, 2H). 13C
NMR (100 MHz, CDCl3): d ¼ 160.01, 157.6, 154.1, 150.4,
139.6, 141.1, 129.7, 128.8, 128.6 (2C), 128.4 (2C), 127.9,
119.4 (2C), 112.2, 111.6, 55.4, 33.2, 27.4, 23.1, and 23.1. IR
(KCl): 3057, 3007, 2936, 2860, 1583, 1541, 1494, 1455, 1262,
1215, 1161, 1044, 872, 755, 701, and 599 cmꢁ1. Anal. Calcd.
for: C22H21NO: C, 83.78; H, 6.71; N, 4.44. Found: C, 83.71;
H, 6.45; N, 4.14.
2-(4-Methoxyphenyl)-4-phenyl-5,6,7,8-tetrahydroquinoline
(7d). Yield 86%; yellowish viscous oil. 1H NMR (400 MHz,
CDCl3): d ¼ 7.98 (d, J ¼ 8.8 Hz, 2H), 7.47 (d, J ¼ 7.2 Hz,
2H), 7.37–7.35 (m, 3H), 7.23 (t, J ¼ 8.0 Hz, 1H), 7,00 (d, J ¼
8.8 Hz, 2H), 3.86 (s, 3H), 3.11 (t, J ¼ 6.5 Hz, 2H), 2.66 (t, J
¼ 6.2 Hz, 2H), 1.99–1.93 (m, 2H), 1.80–1.74 (m, 2H). 13C
NMR (100 MHz, CDCl3): d ¼ 160.1, 157.5, 153.9, 150.2,
139.9, 132.5, 128.6 (2C), 128.3 (2C), 128.1 (2C), 127.7 (2C),
118.4, 111.0 (2C), 55.3, 33.4, 27.3, 23.2, and 23.1. IR (KCl):
3058, 3007, 2935, 2859, 1608, 1587, 1513, 1450, 1248, 1172,
1
134ꢀC. H NMR (300 MHz, CDCl3) d ¼ 7.92 (d, J ¼ 8.7 Hz,
2H), 7.22 (d, J ¼ 7.8 Hz, 2H), 7.12 (d, J ¼ 7.8 Hz, 2H), 6.88
(d, J ¼ 8.7 Hz, 2H), 3.83 (s, 3H), 3.71 (dt, J ¼ 9.6, 3.9 Hz,
1H), 3.46 (dt, J ¼ 15.9, 4.8 Hz, 1H), 3.12 (dd, J ¼ 15.9, 9.9
Hz, 1H), 2.69 (dt, J ¼ 9.9, 5.1 Hz, 1H), 2.54–2.23 (m, 2H),
2.05–1.45 (m, 5H), 1.29–1.15 (m, 1H). 13C NMR (75 MHz,
CDCl3) d ¼ 213.2, 197.0, 163.4, 140.6, 132.2, 130.5 (2C),
129.9, 129.8 (2C), 128.6 (2C), 113.6 (2C), 55.6, 55.4, 43.6,
42.5, 40.7, 32.5, 28.5, and 24.3. IR (KCl): 3048, 3016, 2933,
2852, 1704, 1670, 1575, 1421, 1257, 1174, 981, 815, and 570
cmꢁ1. Anal. Calcd. for: C22H23ClO3: C, 71.25; H, 6.25. Found:
C, 71.04; H, 6.21.
2-(1,3-Bis-(4-chlorophenyl)-3-oxopropyl)cyclohexanone
1
(5u). Yield 75%; colorless crystals; mp 101–104ꢀC. H NMR
(400 MHz, CDCl3) d ¼ 7.86 (d, J ¼ 8.50 Hz, 2H), 7.38 (d, J
¼ 7.9 Hz, 2H), 7.18 (d, J ¼ 8.5 Hz, 2H), 7.09 (d, J ¼ 7.9 Hz,
2H), 3.69–3.61 (m, 1H), 3.55–3.43 (m, 1H), 3.16–3.06 (m,
1H), 2.72–2.63 (m, 1H), 2.51–2.33 (m, 2H), 2.01 (br s, 1H),
1.81–1.49 (m, 4H), 1.27–1.15 (m, 1H). 13C NMR (100 MHz,
CDCl3) d ¼ 213.1, 197.3, 140.3, 139.4, 135.1, 132.3, 129.7
(2C), 129.6 (2C), 128.8 (2C), 128.7 (2C), 55.5, 44.1, 42.6,
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

1022
H. Gezegen, A. Dingil, and M. Ceylan
Vol 47
1032, 834, 754, 702, 666, and 570 cmꢁ1. Anal. Calcd. for:
C22H21NO: C, 83.78; H, 6.71; N, 4.44. Found: C, 83.63; H,
6.61; N, 4.28.
22.7. IR (KCl): 3112, 3058, 2936, 2855, 1589, 1515, 1445,
1296, 1242, 1175, 1033, 832, 755, and 687 cmꢁ1. Anal. Calcd.
for: C21H19NO: C, 83.69; H, 6.35; N, 4.65. Found: C, 83.44;
H, 6.29; N, 4.62.
2-(2-Chlorophenyl)-4-phenyl-5,6,7,8-tetrahydroquinoline
(7e). Yield 94%; yellowish viscous oil. 1H NMR (400 MHz,
CDCl3): d ¼ 7.65 (dd, J ¼ 7.2, 1.6 Hz, 1H), 7.47–7.41 (m,
3H), 7.40–7.34 (m, 5H), 7.32–7.30 (m, 1H), 3.13 (t, J ¼ 6.4
Hz, 2H), 2.73 (t, J ¼ 6.4 Hz, 2H), 2.00–1.94 (m, 2H), 1.81–
1.76 (m, 2H). 13C NMR (100 MHz, CDCl3): d ¼ 157.6, 153.6,
149.4, 139.4, 139.3, 132.3, 131.6, 130.0, 129.3, 128.8, 128.7
(2C), 128.4 (2C), 127.9, 127.0, 123.1, 33.2, 27.4, 23.1, and
23.0. IR (KCl): 3058, 3010, 2945, 2868, 1584, 1542, 1497,
1371, 1094, 995, 832, 750, 702, and 668 cmꢁ1. Anal. Calcd.
for: C21H18ClN: C, 78.86; H, 5.67; N, 4.38. Found: C, 78.76;
H, 5.53; N, 4.21.
4-(2-Methoxyphenyl)-2-phenyl-5,6,7,8-tetrahydroquinoline
(7j). Yield 88%; yellowish viscous oil. 1H NMR (400 MHz,
CDCl3): d ¼ 8.06 (d, J ¼ 7.2 Hz, 2H), 7.48–7.37 (m, 5H),
7.18 (dd, J ¼ 7.2 Hz, 1.4 Hz, 1H), 7.07 (t, J ¼ 7.2 Hz, 1H),
7.02 (d, J ¼ 8.4 Hz, 1H), 3.81 (s, 3H), 3.16–3.11 (m, 4H),
2.00–1.94 (m, 4H). 13C NMR (100 MHz, CDCl3): d ¼ 157.1,
156.3, 154.1, 147.6, 140.0, 130.3, 129.9, 129.4, 128.6, 128.3,
126.9, 120.6, 119.7, 110.8, 55.5, 33.4, 26.4, 23.2, and 22.8. IR
(KCl): 3059, 2937, 2856, 2838, 1584, 1514, 1445, 1292, 1243,
1175, 1030, 835, 752, and 695 cmꢁ1. Anal. Calcd. for:
C22H21NO: C, 83.78; H, 6.71; N, 4.44. Found: C, 83.71; H,
6.69; N, 4.35.
4-(4-Methoxyphenyl)-2-phenyl-5,6,7,8-tetrahydroquinoline
(7k). Yield 71%; yellowish viscous oil. 1H NMR (400 MHz,
CDCl3): d ¼ 7.99 (d, J ¼ 7.6 Hz, 2H), 7.48–7.37 (m, 3H),
7.31 (d, J ¼ 8.4 Hz, 2H), 7.01 (d, J ¼ 8.4 Hz, 2H), 3.87 (s,
3H), 3.12 (t, J ¼ 6.4 Hz, 2H), 2.71 (t, J ¼ 4 Hz, 2H), 1.99–
1.93 (m, 2H), 1.81–1.75 (m, 2H). 13C NMR (100 MHz,
CDCl3): d ¼ 159.3, 157.6, 154.3, 150.1, 139.7, 131.9, 128.9
(2C), 128.8, 128.7 (2C), 128.5, 126.9 (2C), 119.5, 113.8 (2C),
55.3, 33.2, 27.5, 23.2, and 23.1. IR (KCl): 3059, 2934, 2859,
2835, 1609, 1588, 1511, 1442, 1290, 1247, 1177, 1032, 833,
754, and 696 cmꢁ1. Anal. Calcd. for: C22H21NO: C, 83.78; H,
6.71; N, 4.44. Found: C, 83.68; H, 6.70; N, 4.39.
2-(4-Chlorophenyl)-4-phenyl-5,6,7,8-tetrahydroquinoline
1
(7f). Yield 98%; yellowish crystals, mp 130–133ꢀC. H NMR
(400 MHz, CDCl3): d ¼ 7.93 (d, J ¼ 8.8 Hz, 2H), 7.46 (d, J
¼ 7.6 Hz, 2H), 7.43 (d, J ¼ 8.8 Hz, 2H), 7.39 (s, 1H), 7.36 (t,
J ¼ 6.4 Hz, 2H), 7.29 (t, J ¼ 6.4 Hz, 1H), 3.09 (t, J ¼ 6.4
Hz, 2H), 2.67 (t, J ¼ 6.3 Hz, 2H), 1.98–1.92 (m, 2H), 1.80–
1.71 (m, 2H). 13C NMR (100 MHz, CDCl3): d ¼ 157.8, 152.9,
150.5, 139.5, 138.1, 134.5, 128.9, 128.8 (2C), 128.5 (2C),
128.4 (2C), 128.2 (2C), 127.9, 118.9, 33.3, 27.3, 23.1, and
23.0. IR (KCl): 3059, 3025, 2937, 2861, 1586, 1540, 1492,
1448, 1215, 1091, 1013, 835, 755, 701, and 666 cmꢁ1. Anal.
Calcd. for: C21H18ClN: C, 78.86; H, 5.67; N, 4.38. Found: C,
78.73; H, 5.58; N, 4.34.
2-(2-Bromophenyl)-4-phenyl-5,6,7,8-tetrahydroquinoline
(7g). Yield 66%; yellowish viscous oil. 1H NMR (400 MHz,
CDCl3): d ¼ 7.66 (d, J ¼ 8.0 Hz, 1H), 7.59 (t, J ¼ 7.6 Hz,
1H), 7.32 (s, 1H), 7.22 (t, J ¼ 8.0 Hz, 1H), 7.47–7.37 (m,
6H), 3.12 (t, J ¼ 6.4 Hz, 2H), 2.73 (t, J ¼ 6.0 Hz, 2H), 2.00–
1.94 (m, 2H), 1.85–1.77 (m, 2H). 13C NMR (100 MHz,
CDCl3): d ¼ 157.4, 154.9, 149.4, 141.3, 139.3, 133.2, 131.6,
129.5, 128.8, 128.4 (2C), 128.7 (2C), 127.9, 127.6, 122.0,
123.0, 33.3, 27.3, 23.1, and 23.0. IR (KCl): 3057, 3027, 2935,
2859, 1583, 1540, 1494, 1447, 1381, 1217, 1025, 762, 701,
668, and 599 cmꢁ1. Anal. Calcd. for: C21H18BrN: C, 69.24; H,
4.98; N, 3.85. Found: C, 68.98; H, 4.93; N, 3.78.
2-(4-Bromophenyl)-4-phenyl-5,6,7,8-tetrahydroquinoline
(7h). Yield 92%; yellowish viscous oil. 1H NMR (400 MHz,
CDCl3): d ¼ 7.87 (d, J ¼ 8.4 Hz, 2H), 7.56 (d, J ¼ 8.4 Hz,
2H), 7.46 (m, 2H), 7.39 (s, 1H), 7.36–7.34 (m, 2H), 7.27 (t,
J ¼ 8.0 Hz, 1H), 3.01 (t, J ¼ 6.4 Hz, 2H), 2.67 (t, J ¼ 6,4
Hz, 2H), 1.98–1.92 (m, 2H), 1.80–1.74 (m, 2H). 13C NMR
(100 MHz, CDCl3): d ¼ 157.8, 152.9, 150.5, 139.5, 138.5,
131.7 (2C), 128.9, 128.6 (2C), 128.5 (2C), 128.4 (2C), 127.9,
122.9, 118.9, 33.3, 27.4, 23.1, and 23.0. IR (KCl): 3059,
3026, 2936, 2860, 1587, 1540, 1490, 1449, 1402, 1215,
1072, 1009, 832, 756, and 701 cmꢁ1. Anal. Calcd. for:
C21H18BrN: C, 69.24; H, 4.98; N, 3.85. Found: C, 69.03; H,
4.94; N, 3.73.
4-(2-Chlorophenyl)-2-phenyl-5,6,7,8-tetrahydroquinoline
(7l). Yield 87%; yellowish viscous oil. 1H NMR (400 MHz,
CDCl3): d ¼ 7.99 (br d, J ¼ 8.0 Hz, 2H), 7.47–7.23 (m, 8H),
2.55 (t, J ¼ 6.4 Hz, 2H), 2.46 (t, J ¼ 6.0 Hz, 2H), 1.99–1.93
(m, 2H), 1.83–1.73 (m, 2H). 13C NMR (100 MHz, CDCl3): d
¼ 157.6, 154.2, 147.9, 139.6, 138.4, 132.6, 130.2, 129.6,
129.4, 129.3, 129.2, 128.6, 128.5, 126.9, 126.8, 118.9, 33.2,
26.4, 23.1, and 22.7. IR (KCl): 3061, 3028, 2937, 2859, 1592,
1537, 1444, 1267, 1084, 1004, 854, 756, 697, and 663 cmꢁ1
.
Anal. Calcd. for: C21H18ClN: C, 78.86; H, 5.67; N, 4.38.
Found: C, 78.81; H, 5.64; N, 4.30.
4-(3-Chlorophenyl)-2-phenyl-5,6,7,8-tetrahydroquinoline
1
(7m). Yield 99%; yellowish viscous oil. H NMR (400 MHz,
CDCl3): d ¼ 7.98 (d, J ¼ 8.0 Hz, 2H), 7.46 (t, J ¼ 6.8 Hz,
2H), 7.40–7.36 (m, 5H), 7.25–7.22 (m, 1H), 3.12 (t, J ¼ 6.4
Hz, 2H), 2.65 (t, J ¼ 6.4 Hz, 2H), 1.99–1.88 (m, 2H), 1.81–
1.73 (m, 2H). 13C NMR (100 MHz, CDCl3): d ¼ 157.8, 154.4,
148.9, 118.9, 141.4, 139.4, 134.3, 129.7, 128.7 (2C), 128.6
(2C), 128.3, 127.9, 126.9 (2C), 126.8, 33.2, 27.2, 23.0, and
22.9. IR (KCl): 3061, 3030, 2937, 2860, 1586, 1541, 1443,
1380, 1216, 1078, 878, 755, and 697 cmꢁ1. Anal. Calcd. for:
C21H18ClN: C, 78.86; H, 5.67; N, 4.38. Found: C, 78.74; H,
5.62; N, 4.33.
4-(4-Chlorophenyl)-2-phenyl-5,6,7,8-tetrahydroquinoline
(7n). Yield 90%; yellowish viscous oil. 1H NMR (400 MHz,
CDCl3): d ¼ 7.98 (d, J ¼ 7.2 Hz, 2H), 7.47–7.40 (m, 4H),
7.32 (t, J ¼ 4.4 Hz, 1H), 7.28 (d, J ¼ 8.4 Hz, 2H), 3.63 (s,
1H), 3.11 (t, J ¼ 6.4 Hz, 2H), 2.64 (t, J ¼ 6.4 Hz, 2H), 2.00–
1.93 (m, 2H), 1.80–1.74 (m, 2H). 13C NMR (100 MHz,
CDCl3): d ¼ 157.8, 154.4, 149.2, 139.4, 138.0, 133.9, 129.9
(2C), 128.8 (2C), 128.7, 128.6 (2C), 128.5, 126.9 (2C), 119.0,
33.2, 27.3, 23.0, and 23.0. IR (KCl): 3061, 3029, 2937, 2861,
1599, 1491, 1444, 1215, 1091, 1015, 832, 759, 697, and 666
4-(4-Phenyl-5,6,7,8-tetrahydroquinolin-2-yl)phenol (7i). Yield
1
80%; yellowish viscous oil. H NMR (400 MHz, CDCl3): d ¼
8.94 (br s, 1HAOH), 7.68 (d, J ¼ 8.0 Hz, 2H), 7.47–7.39 (m,
3H), 7.33–7.27 (m, 3H), 6.80 (br d, J ¼ 7.6 Hz, 2H), 3.14 (t, J
¼ 6.0 Hz, 2H), 2.64 (t, J ¼ 6.0 Hz, 2H), 1.99–1.88 (m, 2H),
1.75–1.71 (m, 2H). 13C NMR (100 MHz, CDCl3): d ¼ 158.3,
157.5, 156.7, 154.4, 151.7, 139.2, 129.5, 128.9, 128.7, 128.5,
128.4, 128.3, 128.0, 127.3, 119.8, 116.1, 31.9, 27.2, 22.8, and
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

September 2010
Three-Step Synthesis of 2,4-Diaryl-5,6,7,8-tetrahydroquinoline Derivatives
1023
cmꢁ1. Anal. Calcd. for: C21H18ClN: C, 78.86; H, 5.67; N,
4.38. Found: C, 78.85; H, 5.63; N, 4.31.
C22H20ClNO: C, 75.53; H, 5.76; N, 4.00. Found: C, 75.49; H,
5.70; N, 3.96.
4-(2-Bromophenyl)-2-phenyl-5,6,7,8-tetrahydroquinoline
(7o). Yield 82%; yellowish viscous oil. 1H NMR (400 MHz,
CDCl3): 8.05 (d, J ¼ 7.6 Hz, 2H), 7.71 (d, J ¼ 7.6 Hz, 1H),
7.48 (t, J ¼ 7.2 Hz, 2H), 7.42–7.39 (m, 3H), 7.30–7.23 (m,
2H), 3.20–3.11 (m, 2H), 2.62–2.55 (m, 1H), 2.48–2.39 (m,
1H), 2.00–1.94 (m, 2H), 1.84–1.78 (m, 2H). 13C NMR (100
MHz, CDCl3): d ¼ 157.8, 154.2, 149.5, 140.6, 139.6, 132.9,
130.1, 129.5, 128.9, 128.7 (2C), 128.6, 127.5, 126.9 (2C),
118.7, 122.6, 33.4, 26.6, 23.2, and 22.8. IR (KCl): 3060, 3031,
2936, 2859, 1596, 1543, 1442, 1382, 1216, 1025, 881, 758,
and 695 cmꢁ1. Anal. Calcd. for: C21H18BrN: C, 69.24; H,
4.98; N, 3.85. Found: C, 69.20; H, 4.96; N, 3.81.
2,4-Bis(4-chlorophenyl)-5,6,7,8-tetrahydroquinoline (7u). Yield
97%; yellowish viscous oil. 1H NMR (400 MHz, CDCl3): d
¼ 7.90 (d, J ¼ 8.0 Hz, 2H), 7.41 (br d, J ¼ 7.6 Hz, 2H),
7.39 (br d, J ¼ 7.32 Hz, 2H), 7.33 (s, 1H), 7.26 (d, J ¼ 8
Hz, 2H), 3.07 (t, J ¼ 6.8 Hz, 2H), 2.63 (t, J ¼ 6.4 Hz, 2H),
1.99–1.91 (m, 2H), 1.79–1.73 (m, 2H). 13C NMR (100 MHz,
CDCl3): d ¼ 157.9, 153.0, 149.3, 137.8, 137.7, 134.7, 134.0,
130.3, 128.8, 128.6, 128.2, 118.7, 33.1, 27.3, 23.0, and 22.9.
IR (KCl): 3015, 2938, 2862, 1597, 1539, 1491, 1446, 1215,
1090, 1014, 830, 755, and 665 cmꢁ1. Anal. Calcd. for:
C21H17Cl2N: C, 71.20; H, 4.84; N, 3.95 Found: C, 71.14; H,
4.79; N, 3.96.
4-(3-Bromophenyl)-2-phenyl-5,6,7,8-tetrahydroquinoline
(7p). Yield 98%; yellowish viscous oil. 1H NMR (400 MHz,
CDCl3): d ¼ 8.00 (d, J ¼ 7.4 Hz, 2H), 7.56–7.52 (m, 2H),
7.46 (t, J ¼ 7.7 Hz, 2H), 7.38 (s, 1H), 7.36–7.27 (m, 3H),
3.11 (t, J ¼ 6.5 Hz, 2H), 2.65 (t, J ¼ 6.2 Hz, 2H), 2.01–1.92
(m, 2H), 1.81–1.76 (m, 2H). 13C NMR (100 MHz, CDCl3): d
¼ 157.9, 154.4, 148.7, 141.8, 139.5, 131.5, 130.8, 129.9, 128.7
(2C), 128.6, 128.2, 127.3, 126.9 (2C), 122.5, 118.8, 33.4, 27.2,
23.1, and 23.0. IR (KCl): 3061, 3011, 2937, 2860, 1586, 1541,
Acknowledgment. The authors are indebted to the Gaziosman-
pasa University (Grant BAP-2007-25) for financial support of
this work.
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4-(4-Bromophenyl)-2-phenyl-5,6,7,8-tetrahydroquinoline
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2H), 7.46 (t, J ¼ 8.0 Hz, 2H), 7.39 (t, J ¼ 8.0 Hz, 1H), 7.38
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128.6, 128.3, 122.1, 118.9, 33.2, 27.3, 23.1, and 23.0. IR
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1
81%; yellowish viscous oil. H NMR (400 MHz, CDCl3): d ¼
8.01 (d, J ¼ 8.8 Hz, 2H), 7.48 (t, J ¼ 7.8 Hz, 2H), 7.44 (s,
1H), 7.40 (t, J ¼ 7.2 Hz, 1H), 7.31–7.27 (m, 4H), 3.14 (t, J ¼
6.6 Hz, 2H), 2.71 (t, J ¼ 6.3 Hz, 2H), 2.02–1.94 (m, 2H),
1.81–1.76 (m, 2H). 13C NMR (100 MHz, CDCl3): d ¼ 157.6,
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128.5 (2C), 128.4, 126.9 (2C), 119.4, 33.3, 27.4, 23.1, 23.1,
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