Four-component, one-pot synthesis of 2-aryl-4-thionylquinoline derivatives and their aromatization

Article abstract of DOI:10.1080/00397910802219288

Four-component, one-pot condensation of dimedon, thiophene-2-carbaldehyde, ammonium acetate, and numerous acetophenones yielded novel 2-aryl-4- thionylquinoline derivatives. The structures were characterized by 1H NMR, 13C NMR, IR, and elemental analysis.

Full text of DOI:10.1080/00397910802219288

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Four-Component, One-
Pot Synthesis of 2-Aryl-4-
Thionylquinoline Derivatives
and Their Aromatization
Mustafa Ceylan a & Esra Fíndík a
a Department of Chemistry , Faculty of Arts and
Sciences, Gaziosmanpasa University , Tokat, Turkey
Published online: 09 Sep 2008.
To cite this article: Mustafa Ceylan & Esra Fíndík (2008) Four-Component, One-Pot
Synthesis of 2-Aryl-4-Thionylquinoline Derivatives and Their Aromatization, Synthetic
Communications: An International Journal for Rapid Communication of Synthetic
Organic Chemistry, 38:15, 2584-2596, DOI: 10.1080/00397910802219288
To link to this article: http://dx.doi.org/10.1080/00397910802219288
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Synthetic Communications1, 38: 2584–2596, 2008
Copyright # Taylor & Francis Group, LLC
ISSN: 0039-7911 print/1532-2432 online
DOI: 10.1080/00397910802219288
Four-Component, One-Pot Synthesis of
2-Aryl-4-Thionylquinoline Derivatives
and Their Aromatization
´
´
Mustafa Ceylan and Esra Fındık
Department of Chemistry, Faculty of Arts and Sciences, Gaziosmanpasa
University, Tokat, Turkey
Abstract: Four-component, one-pot condensation of dimedon, thiophene-2-
carbaldehyde, ammonium acetate, and numerous acetophenones yielded novel
2-aryl-4-thionylquinoline derivatives. The structures were characterized by
1H NMR, 13C NMR, IR, and elemental analysis.
Keywords: Ammonium acetate, 2-aryl-4-thionylquinoline, dimedon, four-
component coupling reactions
The synthesis of oxygen-, nitrogen-, or sulfur-containing heterocycles is
of importance in organic and medicinal chemistry.[1] Among these struc-
tures, quinolines,[2] tetrahydroquinolines,[3] and their derivatives are
excellent precursors of potential drugs.[4]
Quinolines and their derivatives, which usually possess diverse
biological activities, play important roles as versatile building 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 anti-
asthmatic, antibacterial, anti-inflammatory, 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] Doebner–von Miller,[9] Conrad–Limbach,[10]
Received in the U.K. September 18, 2007
Address correspondence to Mustafa Ceylan, Department of Chemistry,
Faculty of Arts and Sciences, Gaziosmanpasa University, 60250 Tokat, Turkey.
E-mail: mceylan@gop.edu.tr
2584

Four-Component, One-Pot Synthesis of 2-Aryl-4-Thionylquinoline
2585
Scheme 1.
Combes,[11] and Pfitzinger[12] quinoline syntheses. A number of general
synthetic methods have also been reported.[13] However, some of
these methods suffer from several disadvantages such as harsh reaction
conditions, multiple steps, a large amount of promoters, and=or long
reaction time.[14]
In this study, we reported synthesis of 2-aryl-4-thionylquinoline deri-
vatives (5a–j) by a one-pot, four-component condensation of dimedon
(1), thiophene-2-carbaldehyde (3), ammonium acetate (4), and numerous
acetophenone derivatives (2a–j).
The quinoline derivatives (5a–j and 6a–j) were synthesized by
one-pot, four-component condensation of dimedon (1), thiophene-2-
carbaldehyde (3), ammonium acetate (4), and numerous acetophenone
derivatives 2a–j (Scheme 1, Table 1). Also, compound 5 converted to
compound 6 with effect of air oxygen action.
Table 1. Four-component, one-pot synthesis of 2-aryl-4-thionylquinoline
derivatives
Products
Entry
ArX
Time (h)
5
Yield (%)a
6
Yield (%)a
1
2
3
4
5
6
7
8
9
10
4-OHPh
3-BrPh
3-NH2Ph
3-CH3OPh
3-ClPh
3-NO2Ph
3-pyridyl
3-furyl
4-CH3Ph
4-ClPh
3
3
3
3
3
3
3
3
3
3
5a
5b
5c
5d
5e
5f
51
62
72
71
64
60
57
73
65
67
6a
6b
6c
6d
6e
6f
9
17
22
15
13
37
38
12
18
18
5g
5h
5i
6g
6h
6i
5j
6j
aYield of isolated products.

´ ´
M. Ceylan and E. Fındık
2586
Table 2. Effective of solvent on the reaction
Entry
Solvent
H2O
CH3COOH
DMSO
CH3CH2OH
CHCl3
CH3CN
DMF
Time (h)
Isolated yield (%)
1
2
3
4
5
6
7
9
7
4
2.5
5
–
–
85
15
23
75
93
4
3
Structures of the synthesized compounds 5a–j were assigned by
elemental analyses and 1H NMR and IR spectral data. 1H NMR spectra
of all the derivatives 5 show the signals as AB system of the protons H3
and H4 at d ¼ 5.92–4.87 ppm, the AB system signals of ꢀCH2 protons in
moiety of dimedon at d ¼ 2.48–2.04 ppm, and the signal of amine NH
proton at d ¼ 8.14–6.30 ppm.
The formation mechanism of compounds (5a–j) can be explained by
a Hantzsch-type reaction.
We examined the effect of solvent for the reaction of 4-chloroaceto-
phenone, thiophene-2-carbaldehyde, dimedon, and ammonium acetate
(Table 2). Among the solvents tested, dimethylformamide (DMF) gave
the best result. Although the yield was moderate in the cases of dimethyl-
sulphoxide (DMSO) and CH3CN, the yield was very low in the cases of
CH3CH2OH and CHCl3 and the reaction did not occur in H2O and
CH3COOH.
In addition, the oxidation of 5a–j with DDQ (dichloro dicyano quinone)
in benzene at room temperature for 2 h gave the aromatic 6a–j (Scheme 2).
This reaction formed only desired heterocyclic compounds (5, 6)
in one step, and no other by-products were isolated. Accordingly,
we suggest that the present reaction is a convenient synthetic method
of preparing the 2-aryl-4-thionylquinoline derivatives.
Scheme 2.

Four-Component, One-Pot Synthesis of 2-Aryl-4-Thionylquinoline
EXPERIMENTAL
2587
1H and 13C NMR spectra were recorded with Bruker AC 400 instru-
1
ments. As internal standards, we used TMS (d 0.00) for H NMR and
CDCl3 (d 77.0) for 13C NMR spectroscopy. J values are given in hertz.
The multiplicities of the signals in the H NMR spectra are abbreviated
1
to s (singlet), d (doublet), t (triplet), q (quartet), m (multiplet), br (broad),
and combinations 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 an
Electrothermal 9100 apparatus.
All column chromatographies were performed on silica gel (60–230
mesh, Merck).
General Procedure for Synthesis of 2-Aryl-4-thionylquinolines (5a–j)
A mixture of dimedon (0.3 g, 2.2 mmol), thiophene-2-carbaldehyde (0.25
g, 2.2 mmol), acetophenone derivative (0.34 g, 2.2 mmol), and ammonium
acetate (0.19 g, 2.2 mmol) in DMF (5 ml) was heated in the sealed tube at
100 ꢁC (oil bath temperature) for 3 h. Water was added to the mixture and
extracted with CH2Cl2 (3 ꢂ 20 mL), dried over anhydrous Na2SO4, and
evaporated. Crude products were purified by column chromatography
on silica gel or preparative thin-layer chromatography (TLC,
20- ꢂ 20-cm plates, 2 mm thick) using n-hexane=EtOAc (9:1) as eluent.
While the first fraction was 6, the second fraction was 5. The solid
products were crystallized in n-hexane=EtOAc (9:1).
Data
2-(4-Hydroxyphenyl)-7,7-dimethyl-4-(thiophen-2-yl)-7,8-dihydroquinolin-
5(1H,4H-,6H)-one (5a): Yellowish liquid; 51%; 1H NMR (400 MHz,
DMSO-d6) d ¼ 8.14 (s, 1H, NH), 7.23 (brd, J ¼ 8.8 Hz, 2H, ArH,
AA0 part of AA0XX0 system), 6.97 (t, J ¼ 3.6 Hz, 1H, thionyl), 6.77
(m, 2H, thionyl), 6.74 (brd, J ¼ 8.8 Hz, 2H, ArH, XX0 part of AA0XX0
0
system), 5.06 (dd, J3,4 ¼ 5.6, J3,thionyl3 ¼ 1.6 Hz, 1H, olefinic), 4.88 (d,
J ¼ 5.6 Hz, 1H, allylic), 3.32 (s, 1 H, OH), 2.34 (d, J ¼ 16.4 Hz, A part
of AB system, 1H, ꢀCH2), 2.31 (d, J ¼ 16.4 Hz, B part of AB system,
1H, ꢀCH2), 2.15 (d, J ¼ 16.4 Hz, A part of AB system, 1H, ꢀCH2),
2.06 (d, J ¼ 16.4 Hz, B part of AB system, 1H, ꢀCH2), 1.00 (s, 3H),
0.92 (s, 3H); 13C NMR (100 MHz, CDCl3) d ¼ 195.23, 157.93, 153.72,
152.67, 135.38, 127.37 (2C), 126.71, 126.52, 123.13, 122.51, 115.47
(2C), 106.94, 103.19, 50.83, 40.91, 32.21, 32.03, 29.66, 27.09; IR (KBr

´ ´
M. Ceylan and E. Fındık
2588
disc) cmꢀ1: 3899, 2960, 1652, 1610, 1494, 1275, 1243, 1050, 1025, 1003,
763, 632. Anal. calcd. for C21H21NO2S: C, 71.76; H, 6.02; N, 3.99;
S, 9.12. Found: C, 72.37; H, 5.82; N, 3.65; S, 9.18.
2-(3-Bromophenyl)-7,7-dimethyl-4-(thiophen-2-yl)-7,8-dihydroquinolin-5-
(1H,4H,-6H)-one (5b): Yellowish liquid; 62%; 1H NMR (400 MHz,
CDCl3) d ¼ 7.61 (t, J ¼ 1.6 Hz, 1H, ArH), 7.46 (bd, J ¼ 8.0 Hz, 1H,
ArH), 7.38 (bt, J ¼ 8.0, 1.2 Hz, 1H, ArH), 7.25 (t, J ¼ 7.8 Hz, 1H,
ArH), 7.09 (dd, J ¼ 4.5, 1.8 Hz, 1H, thionyl), 6.99 (bs, 1H, ꢀNH),
6.88 (m, 2H, thionyl), 5.34 (dd, J3,4 ¼ 5.6, J3,thionyl3 ¼ 1.8 Hz, 1H,
olefinic), 5.01 (d, J ¼ 5.6 Hz, 1H, allylic), 2.35 (d, J ¼ 16.8 Hz, A part
of AB system, 1H, ꢀCH2), 2.26 (d, J ¼ 16.8 Hz, B part of AB system,
1H, ꢀCH2), 2.19 (d, J ¼ 16.4 Hz, A part of AB system, 1H, ꢀCH2),
2.13 (d, J ¼ 16.4 Hz, B part of AB system, 1H, ꢀCH2), 1.07 (s, 3H),
1.01 (s, 3H); 13C NMR (100 MHz, CDCl3) d ¼ 195.75, 152.31, 151.59,
137.71, 133.80, 131.59, 130.29, 128.68, 126.70, 124.37, 123.59, 123.07,
122.84, 107.83, 106.86, 50.64, 41.49, 32.36, 32.14, 29.58, 27.16 ; IR
(KBr disc) cmꢀ1: 3244, 3069, 2957, 2869, 1684, 1593, 1474, 1387,
1240, 785, 761, 612. Anal. calcd. for C21H20BrNOS: C, 60.87; H,
4.87; N, 3.38; S, 7.74. Found:C, 60.47; H, 4.50; N, 3.19; S, 7.85.
2-(3-Aminophenyl)-7,7-dimethyl-4-(thiophen-2-yl)-7,8-dihydroquinolin-5-
(1H,4H,-6H)-one (5c): Yellowish liquid; 72%; 1H NMR (400 MHz,
CDCl3) d ¼ 7.13 (t, J ¼ 8.0 Hz, 1H, ArH), 7.08 (dd, J ¼ 4.8, 1.4 Hz,
1H, thionyl), 6.88 (m, 2H, thionyl), 6.81 (brd, J ¼ 7.6 Hz, 1H, ArH),
6.74 (t, J ¼ 2 Hz, 1H, ArH), 6.64 (ddd, J ¼ 8.0, 2.0, 0.8 Hz, 1H,
ArH), 6.60 (s, 1H, ꢀNH), 5.31 (dd, J3,4 ¼ 5.6, J3,thionyl3 ¼ 1.4 Hz, 1H,
olefinic), 5.04 (d, J ¼ 5.6 Hz, 1H, allylic), 3.63 (brs, 2H, ꢀNH2 ) 2.36
(d, J ¼ 16.4 Hz, A part of AB system, 1H, ꢀCH2 ), 2.26 (d, J ¼ 16.4 Hz,
Hz, B part of AB system, 1H, ꢀCH2), 2.22 (d, J ¼ 16.2 Hz, A part of
AB system, 1H, ꢀCH2), 2.16 (d, J ¼ 16.2 Hz, B part of AB system,
1H, ꢀCH2), 1.06 (s, 3H), 1.00 (s, 3H); 13C NMR (100 MHz, CDCl3)
d ¼ 195.68, 152.73, 151.32, 146.90, 136.73, 135.12, 129.74, 126.64,
123.48, 123.04, 115.47, 115.44, 112.15, 107.89, 105.33, 50.68, 41.64,
32.38, 32.09, 29.54, 27.17; IR (KBr disc) cmꢀ1: 3342, 3066, 3006,
2956, 2869, 1587, 1486, 1388, 1332, 1253, 754, 696. Anal. calcd. for
C21H22N2OS: C, 71.97; H, 6.33; N, 7.99; S, 9.15. Found: C, 72.02; H,
5.99; N, 8.04; S, 9.35.
2-(3-Methoxyphenyl)-7,7-dimethyl-4-(thiophen-2-yl)-7,8-dihydroquinolin-5-
(1H,4H-,6H)-one (5d): Yellowish liquid; 71%; 1H NMR (400 MHz,
CDCl3) d ¼ 7.29 (t, J ¼ 8.0 Hz, 1H, ArH), 7.18 (dd, J ¼ 3.6, 1.6 Hz,
1H, thionyl), 7.09 (m, 1H, ArH), 7.03 (d, J ¼ 8.0 Hz, 1H, ArH), 6.99

Four-Component, One-Pot Synthesis of 2-Aryl-4-Thionylquinoline
2589
(t, J ¼ 2.4 Hz, 1H, ArH), 6.89 (m, 2H, ArH and thionyl), 6.49 (brs, 1H, ꢀNH),
5.37 (dd, J3,4 ¼ 5.2, J3,thionyl3 ¼ 1.6 Hz, 1H, olefinic), 5.04 (d, J ¼ 5.2 Hz,
1H, allylic), 3.81 (s, 3H, -OCH3), 2.38 (d, J ¼ 16.4 Hz, A part of AB
system, 1H, ꢀCH2), 2.27 (d, J ¼ 16.4 Hz, B part of AB system, 1H,
ꢀCH2), 2.25 (d, J ¼ 16.2 Hz, A part of AB system, 1H, ꢀCH2), 2.20
(d, J ¼ 16.2 Hz, B part of AB system, 1H, ꢀCH2), 1.07 (s, 3H), 1.01
(s, 3H); 13C NMR (100 MHz, CDCl3) d ¼ 195.62, 159.90, 152.47,
137.08, 134.79, 129.92, 126.63, 123.52, 123.11, 117.79, 114.10, 111.33,
105.85, 55.45, 50.65, 41.71, 32.41, 32.07, 29.53, 28.30, 27.16; IR (KBr
disc) cmꢀ1: 3253, 3068, 2958, 2888, 2870, 2835, 1684, 1577, 1488,
1252, 1044, 784, 697. Anal. calcd. for C22H23NO2S: C, 72.30; H, 6.34;
N, 3.83; S, 8.77. Found: C, 72.23; H, 6.52; N, 3.55; S, 8.92.
2-(3-Chlorophenyl)-7,7-dimethyl-4-(thiophen-2-yl)-7,8-dihydroquinolin-5-
(1H,4H,-6H)-one (5e): Yellowish liquid; 64%; 1H NMR (400 MHz,
CDCl3) d ¼ 7.44 (m, 1H, ArH), 7.31 (m, 3H, ArH), 7.10 (m, 1H, thio-
nyl), 6.88 (m, 2H, thionyl), 6.74 (s, 1H, ꢀNH), 5.35 (dd, J ¼ 5.2,
1.8 Hz, 1H, olefinic), 5.02 (d, J ¼ 5.2 Hz, 1H, allylic), 2.39 (d,
J ¼ 16.8 Hz, A part of AB system, 1H, ꢀCH2), 2.29 (d, J ¼ 16.8 Hz,
B part of AB system, 1H, ꢀCH2), 2.20 (d, J ¼ 16.4 Hz, A part of
AB system, 1H, ꢀCH2), 2.14 (d, J ¼ 16.4 Hz, B part of AB system,
1H, ꢀCH2), 1.07 (s, 3H), 1.01 (s, 3H); 13C NMR (100 MHz, CDCl3)
d ¼ 195.72, 152.23, 134.72, 133.84, 130.07, 128.70, 127.60, 126.69,
125.74, 125.46, 123.81, 123.59, 123.10, 107.96, 106.79, 50.63, 41.58,
32.38, 32.11, 29.53, 27.16; IR (KBr disc) cmꢀ1: 3245, 3070, 2958,
2869, 1594, 1494, 1388, 1241, 1058, 786, 761, 694. Anal. calcd. for
C21H20ClNOS: C, 68.19; H, 5.45; N, 3.79; S, 8.67. Found: C, 67.89;
H, 4.93; N, 4.15; S, 8.48.
2-(3-Nitrophenyl)-7,7-dimethyl-4-(thiophen-2-yl)-7,8-dihydroquinolin-5-
(1H,4H,-6H)-one (5f): Yellowish liquid; 60%; 1H NMR (400 MHz,
CDCl3 ) d ¼ 8.32 (t, J ¼ 1.8 Hz, 1H, ArH), 8.15 (brt, J ¼ 8.4 Hz, 1H,
ArH), 7.80 (d, J ¼ 8.0 Hz, 1H, ArH), 7.75 (s, 1H, ꢀNH), 7.49 (t,
J ¼ 8.4 Hz, 1H, ArH), 7.08 (dd, J ¼ 4.8, 1.3 Hz, 1H, thionyl), 6.86
(m, 2H, thionyl), 5.41 (dd, J3,4 ¼ 5.5, J3,thionyl3 ¼ 1.3 Hz, 1H, olefinic),
4.98 (d, J ¼ 5.5 Hz, 1H, allylic), 2.40 (d, J ¼ 16.8 Hz, A part of AB sys-
tem, 1H, ꢀCH2), 2.32 (d, J ¼ 16.8 Hz, B part of AB system, 1H,
ꢀCH2), 2.19 (d, J ¼ 16.4 Hz, A part of AB system, 1H, ꢀCH2), 2.13
(d, J ¼ 16.4 Hz, B part of AB system, 1H, ꢀCH2), 1.06 (s, 3H), 1.01
(s, 3H); 13C NMR (100 MHz, CDCl3) d ¼ 195.89, 152.11, 148.31,
137.24, 133.31, 131.94, 129.95, 129.72, 126.77, 123.68, 123.20,
123.06, 120.53, 107.97, 107.59, 50.69, 41.18, 32.30, 32.25, 29.62,
27.12; IR (KBr disc) cmꢀ1: 3289, 3085, 2958, 2888, 2869, 1592, 1531,

´ ´
M. Ceylan and E. Fındık
2590
1496, 1348, 1243, 754, 694. Anal. calcd. for C21H20N2O3S: C, 66.29; H,
5.30; N, 7.36; S, 8.43. Found: C, 61.94; H, 4.97; N, 7.40; S, 7.28.
7,7-Dimethyl-2-(pyridin-3-yl)-4-(thiophen-2-yl)-7,8-dihydroquinolin-5(1H,-
4H,6H)-one (5g): Yellowish crystal; mp 157–159 ꢁC; 57%; 1H NMR
(400 MHz, CDCl3) d ¼ 8.51 (d, J ¼ 4.8 Hz, 1H, ArH), 8.01 (s, 1H,
ꢀNH), 7.68 (m, 2H, ArH), 7.23 (m, 1H, thionyl), 7.09 (d, J ¼ 4.8 Hz,
1H, ArH), 6.93 (d, J ¼ 3.2 Hz, 1H, thionyl), 6.88 (t, J ¼ 4.8 Hz, 1H, thio-
nyl), 5.91 (d, J ¼ 5.4 Hz, 1H, olefinic), 5.16 (d, J ¼ 5.4 Hz, 1H, allylic),
2.46 (d, J ¼ 16.4 Hz, A part of AB system, 1H, ꢀCH2), 2.40
(d, J ¼ 16.4 Hz, B part of AB system, 1H, ꢀCH2), 2.30 (d, J ¼ 16.4 Hz,
A part of AB system, 1H, ꢀCH2), 2.25 (d, J ¼ 16.4 Hz, B part of AB sys-
tem, 1H, -CH2), 1.11 (s, 3H), 1.07 (s, 3H); 13C NMR (100 MHz, CDCl3)
d ¼ 195.37, 151.97, 150.71, 149.95, 149.01, 136.75, 132.19, 126.67, 123.67,
123.28, 123.07, 118.73, 107.50, 106.24, 50.77, 41.79, 32.56, 32.26, 29.42,
27.40; IR (KBr disc) cmꢀ1: 3365, 3066, 2958, 2888, 2869, 1631, 1565,
1469, 1436, 1386, 1282, 1122, 910, 782, 732, 696. Anal. calcd. for
C20H20N2OS: C, 71.40; H, 5.99; N, 8.33; S, 9.53. Found: C, 71.67;
H, 5.89; N, 8.43; S, 9.68.
2-(Furan-3-yl)-7,7-dimethyl-4-(thiophen-2-yl)-7,8-dihydroquinolin-5(1H,-
1
4H,6H)-one (5h): Yellowish liquid; 73%; H NMR (400 MHz, CDCl3)
d ¼ 7.41 (m, 1H, furyl), 7.10 (d, J ¼ 4.8 Hz, 1H, thionyl), 6.89 (m, 2H),
6.50 (d, J ¼ 3.2 Hz, 1H, thionyl), 6.45 (m, 1H, furyl), 6.34 (s, 1H,
ꢀNH), 5.56 (d, J ¼ 5.2 Hz, 1H, olefinic), 5.07 (d, J ¼ 5.2 Hz, 1H, allylic),
2.41 (d, J ¼ 16.4 Hz, A part of AB system, 1H, ꢀCH2), 2.30 (d,
J ¼ 16.4 Hz, B part of AB system, 1H, ꢀCH2), 2.26 (d, J ¼ 16.4 Hz, A
part of AB system, 1H, ꢀCH2), 2.20 (d, J ¼ 16.4 Hz, B part of AB sys-
tem, 1H, ꢀCH2), 1.11 (s, 3H), 1.06 (s, 3H); 13C NMR (100 MHz, CDCl3)
d ¼ 196.01, 151.96, 141.85, 126.63, 126.27, 123.61, 123.26, 118.77, 110.47,
108.27, 105.39, 103.38, 101.56, 50.68, 41.88, 32.53, 31.43, 29.40, 27.32; IR
(KBr disc) cmꢀ1: 3297, 2958, 2927, 2869, 1592, 1498, 1382, 1247, 1153,
754, 696. Anal. calcd. for C19H19NO2S: C, 70.12; H, 5.88; N, 4.30; S,
9.85. Found: C, 70.33; H, 6.15; N, 4.33; S, 9.91.
2-(4-Methylphenyl)-7,7-dimethyl-4-(thiophen-2-yl)-7,8-dihydroquinolin-5(1H,-
1
4H,-6H)-one (5i): Yellowish liquid; 65%; H NMR (400 MHz, CDCl3 )
d ¼ 8.11 (s, 1H, ꢀNH), 7.24 (d, J ¼ 7.8 Hz, AA0 part of AA0BB0 system,
2H, ArH), 7.03 (d, J ¼ 7.8 Hz, BB0 part of AA0BB0 system, 2H, ArH),
6.92 (m, 1H, thionyl), 6.72 (m, 2H, thionyl), 5.09 (d, J ¼ 5.4 Hz, 1H, olefi-
nic), 4.84 (d, J ¼ 5.4 Hz, 1H, allylic), 2.30 (d, J ¼ 16.2 Hz, A part of AB
system, 1H, ꢀCH2), 2.23 (d, J ¼ 16.2 Hz, B part of AB system, 1H,
ꢀCH2), 2.21 (s, 3H, ꢀCH3), 2.10 (d, J ¼ 16.4 Hz, A part of AB system,
1H, ꢀCH2), 2.01 (d, J ¼ 16.4 Hz, B part of AB system, 1H, ꢀCH2), 1.17

Four-Component, One-Pot Synthesis of 2-Aryl-4-Thionylquinoline
2591
(s, 3H), 0.96 (s, 3H); 13C NMR (100 MHz, CDCl3) d ¼ 194.09, 152.53,
151.48, 137.37, 134.50, 131.94, 128.17 (2C), 125.57, 125.07 (2C), 122.25,
121.67, 106.07, 103.79, 49.94, 40.03, 31.30, 31.15, 28.73, 26.20, 20.25; IR
(KBr disc) cmꢀ1: 3415, 2956, 1683, 1610, 1535, 1245, 1025, 1002, 825,
700. Anal. calcd. for C22H23NOS: C, 75.61; H, 6.63; N, 4.01; S, 9.17. Found:
C, 75.14; H, 6.57; N, 4.43; S, 9.23.
2-(4-Chlorophenyl)-7,7-dimethyl-4-(thiophen-2-yl)-7,8-dihydroquinolin-5-
(1H,4H,-6H)-one (5j): Yellowish crystal; mp 206–208 ꢁC; 67%; 1H NMR
(400 MHz, CDCl3) d ¼ 7.37 (brd, J ¼ 5.2 Hz, AA0 part of AA0BB0
system, 2H, ArH), 7.34 (brd, J ¼ 5.2 Hz, BB0 part of AA0BB0 system,
2H, ArH), 7.10 (brd, J ¼ 4.8 Hz, 1H, thionyl), 6.99 (m, 2H, thionyl),
6.30 (s, 1H, ꢀNH), 5.35 (dd, J ¼ 5.2, 1.6 Hz, 1H, olefinic), 5.05
(d, J ¼ 5.2 Hz, 1H, allylic), 2.41 (d, J ¼ 16.4 Hz, A part of AB system,
1H, ꢀCH2), 2.29 (d, J ¼ 16.4 Hz, B part of AB system, 1H, ꢀCH2),
2.25 (d, J ¼ 16.4 Hz, A part of AB system, 1H, ꢀCH2), 2.20
(d, J ¼ 16.4 Hz, B part of AB system, 1H, ꢀCH2), 1.10 (s, 3H), 1.03
(s, 3H); 13C NMR (100 MHz, CDCl3) d ¼ 195.51, 152.23, 150.66,
134.59, 134.11, 133.90, 129.03 (2C), 126.81 (2C), 126.70, 123.60,
123.16, 108.25, 106.28, 50.67, 41.81, 32.46, 32.08, 29.54, 27.18; IR
(KBr disc) cmꢀ1: 3426, 2958, 2869, 1658, 1612, 1490, 1388, 1051,
1025, 1006, 825, 761, 696. Anal. calcd. for C21H20ClNOS: C, 68.19;
H, 5.45; N, 3.79; S, 8.67. Found: C, 68.66; H, 5.47; N, 4.11; S, 8.32.
General Procedure for Synthesis of 2-Aryl-4-thionylquinolines (6a–j)
DDQ (0.35 g, 1.58 mmol) was added to a stirred solution of 2-aryl-4-
thionylquinolines (0.28 g, 0.79 mmol) in 10 mL of benzene and stirred
at room temperature for 2 h. The solvent (benzene) was removed under
reduced pressure. CH2Cl2 (50 mL) was added to the residue and filtered
to remove precipitated material. The extract was washed with water
(50 mL) and dried over MgSO4. After the solvent was evaporated, the
residue was chromatographed on a silica-gel column, eluting with
EtOAc=hexane (1:9).
Data
2-(4-Hydroxyphenyl)-7,7-dimethyl-4-(thiophen-2-yl)-7,8-dihydroquinolin-5-
(6H)-one (6a): Yellowish liquid; 75%; 1H NMR (400 MHz, CDCl3)
d ¼ 7.94 (brd, J ¼ 8.8 Hz, AA0 part of AA0BB0 system, 2H, ArH), 7.56
(s, 1H, H3), 7.45 (d, J ¼ 4.8 Hz, 1H, thionyl), 7.27 (s, 1H, -OH), 7.19
(d, J ¼ 3.6 Hz, 1H, thionyl), 7.11 (dd, J ¼ 4.8, 3.6 Hz, 1H, thionyl),
6.88 (brd, J ¼ 8.8 Hz, BB0 part of AA0BB0 system, 2H, ArH), 3.44

´ ´
M. Ceylan and E. Fındık
2592
(s, 1H, -OH), 3.17 (s, 2H), 2.59 (s, 2H), 1.16 (s, 6H); 13C NMR (100 MHz,
CDCl3) d ¼ 197.96, 163.62, 159.23, 158.28, 144.62, 140.62, 129.24 (2C),
127.63, 127.08, 126.90, 123.55, 121.86, 115.97 (2C), 53.82, 47.57, 32.64,
29.70, 28.28 (2C); IR (KBr disc) cmꢀ1: 3072,3018, 2956, 2869, 1666,
1577, 1531, 1519, 1278, 1207, 1170, 836, 754. Anal. calcd. for
C21H19NO2S: C, 72.18; H, 5.48; N, 4.01; S, 9.18. Found: C, 72.58; H,
5.22; N, 3.95; S, 9.02.
2-(3-Bromophenyl)-7,7-dimethyl-4-(thiophen-2-yl)-7,8-dihydroquinolin-5-
(6H)-one (6b): Yellowish liquid; 88%; 1H NMR (400 MHz, CDCl3)
d ¼ 8.27 (s, 1H, ArH), 7.97 (d, J ¼ 8.0 Hz, 1H, ArH), 7.61 (s, 1H,
H3), 7.57 (d, J ¼ 8.0 Hz, 1H, ArH), 7.45 (d, J ¼ 5.2 Hz, 1H, thionyl),
7.34 (t, J ¼ 7.8 Hz, 1H, ArH), 7.20 (bd, J ¼ 3.6 Hz, 1H, thionyl), 7.11
(t, J ¼ 4.2 Hz, 1H, thionyl), 3.18 (s, 2H), 2.60 (s, 2H), 1.72 (s, 6H);
13C NMR (100 MHz, CDCl3) d ¼ 197.54, 163.73, 157.54, 144.65,
140.28, 139.93, 132.95, 130.50, 130.38, 128.21, 127.98, 127.14, 125.90,
124.56, 123.20, 122.31, 53.88, 47.82, 32.65, 28.34, 28.24; IR (KBr disc)
cmꢀ1: 3070, 3016, 2956, 2869, 1689, 1562, 1535, 1238, 1095, 1072, 856,
698. Anal. calcd. for C21H18BrNOS: C, 61.17; H, 4.40; N, 3.40;
S, 7.78. Found: C, 60.87; H, 4.77; N, 3.39; S, 7.55.
2-(3-Aminophenyl)-7,7-dimethyl-4-(thiophen-2-yl)-7,8-dihydroquinolin-5(6H)-
1
one (6c): Yellowish liquid; 77%; H NMR (400 MHz, CDCl3) d ¼ 7.60
(s, 1H, H3), 7.44 (m, 1H, ArH), 7.41–7.17 (m, 3H, 2ArH and thionyl),
7.18 (d, J ¼ 4.0 Hz, 1H, thionyl), 6.88 (t, J ¼ 1.2 Hz, 1H, ArH), 6.79
(dd, J ¼ 4.4, 1.2 Hz, 1H, thionyl), 3.18 (s, 2H), 2.59 (s, 2H), 1.16 (s, 6H);
13C NMR (100 MHz, CDCl3) d ¼ 190.03, 163.48, 161.88, 146.97, 144.30,
139.01, 129.80, 128.69, 127.62, 127.04, 126.84, 125.77, 117.72, 116.90,
114.01, 113.90, 53.89, 47.87, 32.63, 28.30, 26.70; IR (KBr disc) cmꢀ1:
3419, 2923, 2852, 1758, 1697, 1677, 1560, 1465, 1172, 796, 719. Anal. calcd.
for C21H20N2OS: C, 71.38; H, 5.79; N, 8.04; S, 9.20. Found: C, 71.02;
H, 5.30; N, 8.45; S, 9.30.
2-(3-Methoxyphenyl)-7,7-dimethyl-4-(thiophen-2-yl)-7,8-dihydroquinolin-5-
(6H)-one (6d): Yellowish liquid; 85%; 1H NMR (400 MHz, CDCl3)
d ¼ 7.64 (m, 3H, 2ArH and H3), 7.46 (d, J ¼ 4.8 Hz, 1H, thionyl), 7.41
(t, J ¼ 8.0 Hz, 1H, ArH), 7.20 (d, J ¼ 2.4 Hz, 1H, thionyl), 7.12
(t, J ¼ 4.8 Hz, 1H, thionyl), 7.03 (dd, J ¼ 8.0, 2.0 Hz, 1H, ArH), 3.92
(s, 3H, -OCH3), 3.21 (s, 2H), 2.60 (s, 2H), 1.18 (s, 3H), 1.15 (s, 3H);
13C NMR (100 MHz, CDCl3 ) d ¼ 197.72, 163.57, 160.11, 144.49,
140.54, 139.34, 129.91, 127.70, 127.09, 126.96, 124.27, 122.57, 119.87,
116.11, 112.67, 110.92, 55.45, 53.91, 47.80, 32.66, 28.31; IR (KBr
disc) cmꢀ1: 2956, 2869, 2834, 1687, 1573, 1536, 1492, 1278, 1253, 1045,

Four-Component, One-Pot Synthesis of 2-Aryl-4-Thionylquinoline
2593
784, 700. Anal. calcd. for C22H21NO2S: C, 72.70; H, 5.82; N, 3.85; S, 8.82.
Found: C, 72.41; H, 6.22; N, 4.25; S, 8.92.
2-(3-Chlorophenyl)-7,7-dimethyl-4-(thiophen-2-yl)-7,8-dihydroquinolin-5-
(6H)-one (6e): Yellowish liquid; 87%; 1H NMR (400 MHz, CDCl3)
d ¼ 8.11 (s, 1H, ArH), 7.93 (m, 1H, ArH), 7.63 (s, 1H, H3), 7.47
(d, J ¼ 5.2 Hz, 1H, thionyl), 7.41 (m, 2H, ArH), 7.22 (d, J ¼ 2.8 Hz,
1H, thionyl), 7.12 (dd, J ¼ 4.8, 3.6 Hz, 1H, thionyl), 3.19 (s, 2H), 2.61
(s, 2H), 1.17 (s, 6H); 13C NMR (100 MHz, CDCl3) d ¼ 197.60,
163.73, 157.73, 144.73, 140.26, 139.68, 135.05, 130.11, 130.06, 127.83,
127.61, 127.13 (2C), 125.45, 124.58, 122.40, 53.88, 47.79, 32.65, 28.30
(2C); IR (KBr disc) cmꢀ1: 2956, 2869, 1689, 1567, 1536, 1369, 1278,
790, 742, 696. Anal. calcd. for C21H18ClNOS: C, 68.56; H, 4.93;
N, 3.81; S, 8.72. Found: C, 68.29; H, 5.32; N, 4.15; S, 8.84.
2-(3-Nitrophenyl)-7,7-dimethyl-4-(thiophen-2-yl)-7,8-dihydroquinolin-5(6H)-
1
one (6f): Yellowish liquid; %85; H NMR (400MHz, CDCl3) d ¼ 8.96
(t, J ¼ 1.5 Hz, 1H, ArH), 8.42 (d, J ¼ 7.8 Hz, 1H, ArH), 8.32
(dd, J ¼ 8.1, 1.5 Hz, 1H, ArH), 7.72 (s, 1H, H3), 7.68 (t, J ¼ 8.1 Hz, 1H,
ArH), 7.48 (d, J ¼ 5.02Hz, 1H, thionyl), 7.21 (d, J ¼ 5.0 Hz, 1H, thionyl),
7.13 (dd, J ¼ 5.0, 3.2 Hz, 1H, thionyl), 3.2 (s, 2H), 2.62 (s, 2H), 1.16 (s, 6H);
13C NMR (100MHz, CDCl3) d ¼ 197.47, 163.97, 156.36, 148.82, 145.04,
139.95, 139.62, 133.04, 129.87, 128.04, 127.40, 127.33, 125.03, 123.15,
122.37, 122.32, 53.87, 47.78, 32.66, 28.30 (2C); IR (KBr disc) cmꢀ1: 3085,
2956, 2869, 1691, 1587, 1573, 1531, 1349, 1110, 1043, 723, 703. Anal. calcd.
for C21H18N2O3S: C, 66.65; H, 4.79; N, 7.40; S, 8.47. Found: C, 66.44;
H, 4.79; N, 7.71; S, 8.81.
7,7-Dimethyl-2-(pyridin-3-yl)-4-(thiophen-2-yl)-7,8-dihydroquinolin-5(6H)-
ꢁ
1
one (6 g): Yellowish crystal; mp 156–158 C; 90%; H NMR (400 MHz,
CDCl3) d ¼ 8.71 (d, J ¼ 4.8 Hz, 1H, ArH), 8.49 (d, J ¼ 8.0 Hz,
1H, ArH), 8.36 (s, 1H, H3), 7.86 (dt, J ¼ 6.4, 1.6 Hz, 1H, ArH), 7.44
(d, J ¼ 5.2 Hz, 1H, thionyl), 7.36 (bt, J ¼ 6.4 Hz, 1H, ArH), 7.24
(bd, J ¼ 3.6 Hz, 1H, thionyl), 7.11 ( bt, J ¼ 3.6 Hz, 1H, thionyl), 3.19
(s, 2H), 2.62 (s, 2H), 1.18 (s, 6H); 13C NMR (100 MHz, CDCl3)
d ¼ 212.07, 163.21, 157.73, 154.84, 149.40, 144.71, 140.54, 137.02,
127.85, 127.02, 126.98, 125.39, 124.54, 122.90, 122.11, 53.94, 47.85,
32.67, 28.32 (2C); IR (KBr disc) cmꢀ1: 3062, 2925, 2854, 1687, 1540,
1272, 1245, 1095, 790, 732. Anal. calcd. for C20H18N2OS: C, 71.83; H,
5.42; N, 8.38; S, 9.59. Found: C, 71.90; H, 5.74; N, 8.47; S, 10.01.
2-(Furan-3-yl)-7,7-dimethyl-4-(thiophen-2-yl)-7,8-dihydroquinolin-5(6H)-
1
one (6h): Yellowish liquid; 92%; H NMR (400 MHz, CDCl3) d ¼ 7.60

´ ´
M. Ceylan and E. Fındık
2594
(brs, 2H, H3 and furyl), 7.45 (d, J ¼ 5.2 Hz, 1H, thionyl), 7.24 (m, 1H,
furyl), 7.19 (d, J ¼ 3.6 Hz, 1H, thionyl), 7.10 (t, J ¼ 4.8 Hz, 1H, thio-
nyl), 6.58 (dd, J ¼ 4.8, 1.4 Hz, 1H, furyl), 3.15 (s, 2H), 2.51 (s, 2H),
1.15 (s, 6H); 13C NMR (100 MHz, CDCl3) d ¼ 197.30, 163.85, 144.84,
144.59, 140.37, 127.76, 127.04 (2C), 123.87, 120.37 (2C), 112.54 (2C),
110.91, 52.49, 47.66, 32.56, 29.70, 28.25; IR (KBr disc) cmꢀ1: 3114,
2956, 2925, 2867, 1687, 1600, 1536, 1278, 1099, 1008, 746, 700. Anal.
calcd. for C19H17NO2S: C, 70.56; H, 5.30; N, 4.33; S, 9.91. Found: C,
70.55; H, 5.69; N, 4.33; S, 9.54.
2-(4-Methylphenyl)-7,7-dimethyl-4-(thiophen-2-yl)-7,8-dihydroquinolin-5-
(6H)-one (6i): Yellowish liquid; 76%; 1H NMR (400 MHz, CDCl3)
d ¼ 7.98 (d, J ¼ 8.0 Hz, 2H, ArH, AA0 part of AA0XX0 system), 7.63
(s, 1H, H3), 7.44 (d, J ¼ 5.2 Hz, 1H, thionyl), 7.30 (d, J ¼ 8.0 Hz, 2H,
ArH, XX0 part of AA0XX0 system), 7.19 (d, J ¼ 3.2 Hz, 1H, thionyl),
7.11 (t, J ¼ 5.2 Hz, 1H, thionyl), 3.18 (s, 2H), 2.59 (s, 2H), 2.44 (s,
3H, ꢀCH3), 1.17 (s, 6H); 13C NMR (100 MHz, CDCl3) d ¼ 197.14,
163.61, 159.41, 144.36, 140.72, 140.43, 135.15, 129.64 (2C), 127.89,
127.57, 127.36 (2C), 127.05, 126.81, 122.07, 53.89, 47.87, 32.64, 28.32,
28.23, 21.42; IR (KBr disc) cmꢀ1: 3070, 3014, 2956, 2927, 2869, 1687,
1573, 1536, 1371, 1276, 1184, 823, 755. Anal. calcd. for C22H21NOS:
C, 76.04; H, 6.09; N, 4.03; S, 9.23. Found: C, 75.84; H, 6.47; N, 4.27;
S, 9.49.
2-(4-Chlorophenyl)-7,7-dimethyl-4-(thiophen-2-yl)-7,8-dihydroquinolin-5-
(6H)-one (6j): Yellowish crystal; mp 119–120 ꢁC; %83; 1H NMR
(400 MHz, CDCl3) d ¼ 8.03 (d, J ¼ 8.8 Hz, AA0 part of AA0BB0 system,
2H, ArH), 7.67 (s, 1H, H3), 7.46 (d, J ¼ 8.8 Hz, BB0 part of AA0BB0 sys-
tem, 2H, ArH), 7.46 (m, 1H, thionyl), 7.20 (d, J ¼ 3.2 Hz, 1H, thionyl),
7.11 (dd, J ¼ 4.4, 3.2 Hz, 1H, thionyl), 3.18 (s, 2H), 2.60 (s, 2H), 1.17
(s, 6H); 13C NMR (100 MHz, CDCl3) d ¼ 197.56, 163.71, 157.99,
144.62, 140.36, 136.37, 136.33, 129.09 (2C), 128.72 (2C), 127.77, 127.12,
127.03, 124.33, 122.08, 53.88, 47.84, 32.63, 28.32 (2C); IR (KBr disc)
cmꢀ1: 3072, 3016, 2956, 2927, 2869, 1687, 1579, 1536, 1492, 1276, 1093,
1012, 853, 755. Anal. calcd. for C21H18ClNOS: C, 68.56; H, 4.93; N,
3.81; S, 8.72. Found: C, 68.69; H, 5.23; N, 4.27; S, 8.54.
ACKNOWLEDGMENT
The authors are indebted to the Department of Chemistry (Gaziosman-
pasa University) and the Scientific and Technical Research Council of
Turkey (Grant TUBITAK-TBAG 106T103) for financial support.

Four-Component, One-Pot Synthesis of 2-Aryl-4-Thionylquinoline
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