Amberlyst-15-catalyzed novel synthesis of quinoline derivatives in ionic liquid

Article abstract of DOI:10.1002/jccs.200800135

In recent years, ionic liquids have attracted much attention as useful synthetic solvents. Compared with classical molecular solvents, the ionic liquids are environmentally benign reaction media. A variety of quinoline derivatives have been synthesized un

Full text of DOI:10.1002/jccs.200800135

Journal of the Chinese Chemical Society, 2008, 55, 915-918
915
Amberlyst-15-catalyzed Novel Synthesis of Quinoline Derivatives in Ionic
Liquid
Rei-Sheu Houa (
You-Teng Xieb (
aChung Hwa College of Medical Technology, Tainan 717, Taiwan, R.O.C.
), Jian-Long Wub (
), Hui-Ting Chengb (
),
) and Ling-Ching Chenb* (
)
bGraduate Institute of Pharmaceutical Sciences, College of Pharmacy, Kaohsiung Medical University,
Kaohsiung, Taiwan 807, R.O.C.
In recent years, ionic liquids have attracted much attention as useful synthetic solvents. Compared
with classical molecular solvents, the ionic liquids are environmentally benign reaction media. A variety
of quinoline derivatives have been synthesized under ionic liquid conditions using Amberlyst-15 as cata-
lyst.
Keywords: Ionic liquid; Amberlyst-15; Quinoline.
INTRODUCTION
Room temperature ionic liquids (RTIL) are liquids
that are composed entirely of ions. In fact, ionic liquids can
now be produced which remain liquid at room temperature
and below (even as low as -90 °C) and appear to be unde-
manding and inexpensive to manufacture.1 Ionic liquids of-
fer an attractive alternative to conventional organic liquids
for clean synthesis, as they are easy to recycle, lack flam-
mability, and possess effectively no vapour pressure. Com-
pared with classical molecular solvents, the ionic liquids
are environmentally benign reaction media.2 To date, some
of the more important reactions have been carried out and
investigated in ionic liquids, for example, Friedel-Crafts
reaction,3 alkoxycarbonylation,4 hydrogenation,5 Diels-
Alder reaction,6 Wittig reaction,7 Heck reaction,8 Trost-
Tsuji coupling,9 ring-closing metathesis (RCM),10 Suzuki
cross-coupling,11 Fischer indole synthesis,12 1,3-dipolar
cycloaddition reaction,13 Beckmann rearrangement,14 the
Knoevenagel and Robinson annulation reactions,15 etc.
Recently, the use of ion exchange resins in organic
synthesis has received great attention.16 Amberlyst-1517-18
is a porous sulfonated polystyrene resin that serves as an
excellent source of strong acid in nonaqueous media (Fig.
1). It has been used in various catalyzed reactions, e.g.,
esterification, etherification, oxidation, hydration of ole-
fins, condensation, cyclization and electrophilic aromatic
substitution. It is easy to measure, safe to use, and readily
removed at the end of the reaction. An additional advantage
is that the catalyst can be regenerated and used several
times. We report here using Amberlyst-15 as catalyst to
Fig. 1
synthesize quinolines via Friedländer reaction in ionic liq-
uid.19
RESULTS AND DISCUSSION
Treatment of 2-aminobenzophenone (1) and aryl ke-
tones (2) with Amberlyst-15 as catalyst in ionic liquid
1-n-butyl-3-methylimidazolium hexafluorophoaphate,
[Bmin][PF6] at 80 °C for 3 h caused cyclodehydration to
give quinolines (3) in good yields (Scheme I). The results
are given in Table 1. When the reaction is conducted in a
conventional solvent, such as acetonitrile, the preparation
of 2,4-diphenylquinoline (3a) needs refluxing for 10 h.20
The ionic liquid [Bmin][PF6] can be typically recov-
ered by extracting out the product first and filtering the sus-
pension followed by vacuum drying. The recovered sol-
vent can be reused without loss of activity.
In summary, our results herein demonstrate that the
use of 2-aminobenzophenone and arylketones in ionic liq-
uid [Bmim][PF6] can be performed rapidly for Friedländer
reaction to prepare quinoline derivatives using Amberlyst-
15 as catalyst. The ionic liquid plays the dual role of sol-

916 J. Chin. Chem. Soc., Vol. 55, No. 4, 2008
Hou et al.
Scheme I
1584, 1541 cm-1. 1H NMR (CDCl3) d: 7.45-7.59 (m, 9H),
7.74 (ddd, J = 1.2, 6.8, 15.2 Hz, 1H), 7.83 (s, 1H), 7.92 (dd,
J = 0.8, 8.4 Hz, 1H), 8.20 (d, J = 8.4 Hz, 2H), 8.26 (d, J =
8.4 Hz, 1H). 13C NMR (CDCl3, 100 MHz) d: 119.3, 125.6,
125.7, 126.3, 127.5, 128.4, 128.5, 128.8, 129.3, 129.4,
129.5 130.0, 138.3, 139.6, 148.7, 149.1, 156.8. MS (EI)
m/z: 281 (M+), 280, 202, 176, 139, 125.
Table 1. Synthesis of quinoline derivatives
Entry
Product
R1
R2
Yield (%)
1
3a
3b
3c
3d
3e
3f
Ph
H
H
78
73
75
77
80
82
72
76
84
81
76
2
4-MeC6H4
4-MeOC6H4
4-FC6H4
4-ClC6H4
4-BrC6H4
2-Furyl
3
H
4
H
5
H
6
H
2-(4-Methylphenyl)-4-phenylquinoline (3b)
7
3g
3h
3i
H
mp 95-96 °C (Lit.22, mp 116-117 °C). IR (KBr) n:
3049, 1624, 1548 cm-1. 1H NMR (CDCl3) d: 2.43 (s, 3H),
7.34 (d, J = 8.0 Hz, 2H), 7.44-7.58 (m, 6H), 7.71-7.75 (m,
1H), 7.81 (s, 1H), 7.89 (dd, J = 1.0, 8.0 Hz, 1H), 8.10 (d, J =
8.0 Hz, 2H), 8.23 (d, J = 8.0 Hz, 1H). 13C NMR (CDCl3,
100 MHz) d: 21.3, 119.1, 125.5, 125.6, 126.0, 127.3,
128.3, 128.5, 129.3, 129.5, 129.9, 136.7, 138.4, 139.3,
148.7, 148.9, 156.7. MS (EI) m/z : 295 (M+), 294, 202, 145,
139.
8
2-Thienyl
4-NO2C6H4
Ph
H
9
H
10
11
3j
CH3
Ph
3k
Ph
vent and promoter. Separation of products from the ionic
liquids is very straightforward, as is recycling of the ionic
liquid.
2-(4-Methoxyphenyl)-4-phenylquinoline (3c)
EXPERIMENTAL SECTION
mp 78-79 °C (Lit.21, mp 77-79 °C). IR (KBr) n: 1736
cm-1. 1H NMR (CDCl3) d: 3.89 (s, 3H), 7.06 (ddd, J = 2.6,
2.6, 9.2 Hz, 2H), 7.44-7.58 (m, 6H), 7.69-7.75 (m, 1H),
7.79 (s, 1H), 7.89 (ddd, J = 0.8, 0.8, 8.4 Hz, 1H), 8.19 (ddd,
J = 2.4, 2.4, 9.2 Hz, 2H), 8.24 (ddd, J = 0.6, 0.8, 8.4 Hz,
1H). 13C NMR (CDCl3, 100 MHz) d: 55.3, 114.1, 118.8,
125.4, 125.5, 125.9, 128.3, 128.5, 128.8, 129.4, 129.5,
129.8, 130.1, 132.0, 137.4, 138.4, 148.7, 149.0, 156.3,
160.8. MS (EI) m/z: 311 (M+), 310, 268, 267, 140, 139,
132.
All melting points are uncorrected. The IR spectra
were recorded on a Shimadzu IR-27 G spectrophotometer.
1H NMR and 13C NMR spectra were recorded on a Varian
Unity Plus 400 MHz. Chemical shifts (d) were measured in
ppm with respect to TMS. MS were obtained on a JEOL
JMS D-300 instrument.
Typical procedure for the preparation of 2,4-diphen-
ylquinoline (3a)
To a solution of acetophenone (2a) (120 mg, 1.0
mmol) and 2-aminobenzophenone (197 mg, 1.0 mmol) in
[Bmin][PF6] (2 mL) was added Amberlyst-15 (100 mg, 0.5
mmole), and the mixture was stirred at 80 °C for 3 h and fil-
tered after cooling. Subsequently, the filtrate was extracted
with ethyl acetate. The organic layer was washed with satu-
rated NaCl(aq), dried over MgSO4, then concentrated under
reduced pressure and the residue was chromatographed on
silica gel eluting with ethyl acetate-hexane (1:5) to give 3a.
mp 110-111 °C (Lit.21, mp 112-113 °C). IR (KBr) n: 3050,
2-(4-Fluorophenyl)-4-phenylquinoline (3d)
mp 63-64 °C. IR (KBr) n: 3056, 1593, 1546 cm-1. 1H
NMR (CDCl3) d: 7.19-7.24 (m, 2H), 7.47-7.57 (m, 6H),
7.72-7.76 (m, 1H), 7.78 (s, 1H), 7.91 (dd, J = 1.0, 8.4 Hz,
1H), 8.18-8.24 (m, 3H). 13C NMR (CDCl3, 100 MHz) d:
115.4, 115.7, 118.7, 125.5, 126.2, 128.3, 128.4, 129.2,
129.3, 129.4, 129.5, 129.8, 135.5, 135.6, 138.1, 148.6,
149.1, 155.5, 162.4. MS (EI) m/z: 299 (M+), 298, 220, 202,

Synthesis of Quinoline Derivatives
J. Chin. Chem. Soc., Vol. 55, No. 4, 2008 917
201, 139, 125. Anal. Calcd for C12H14NF: C, 84.26, H,
4.71, N, 4.68; Found: C, 84.39, H, 4.54, N, 4.53.
(EI) m/z: 326 (M+), 325, 280, 278, 202, 176, 139.
3-Methyl-2,4-diphenylquinoline (3j)
2-(4-Chlorophenyl)-4-phenylquinoline (3e)
mp 134-135 °C (Lit.25, mp 145-146 °C). IR (KBr) n:
3048, 1609, 1568 cm-1. 1H NMR (CDCl3) d: 2.17 (s, 3H),
7.32-7.34 (m, 2H), 7.40-7.58 (m, 8H), 7.62-7.68 (m, 3H),
8.20 (d, J = 8.4 Hz, 1H). 13C NMR (CDCl3, 100 MHz) d:
18.5, 115.8, 126.1, 126.5, 126.9, 127.7, 127.9, 128.0,
128.2, 128.4, 128.6, 128.8, 129.2, 129.3, 137.5, 141.3,
146.1, 147.6, 160.6. MS (EI) m/z: 295 (M+), 294, 217, 189,
139.
mp 104-105 °C (Lit.23, mp 106 °C). IR (KBr) n: 3055,
1589, 1542 cm-1. 1H NMR (CDCl3) d: 7.47-7.57 (m, 8H),
7.74-7.77 (m, 1H), 7.79 (s, 1H), 7.91 (d, J = 8.0 Hz, 1H),
8.14-8.18 (m, 2H), 8.23 (d, J = 8.4 Hz, 1H). 13C NMR
(CDCl3, 100 MHz) d: 118.6, 125.6, 125.7, 126.5, 128.4,
128.6, 128.8, 128.9, 129.5, 129.6, 130.0, 136.5, 137.9,
138.2, 148.7, 149.4, 155.4. MS (EI) m/z: 317 (M++2), 315
(M+), 314, 220, 202, 176, 139.
2,3,4-Triphenylquinoline (3k)
2-(4-Bromophenyl)-4-phenylquinoline (3f)
mp 190-191 °C (Lit.26, mp 189-190 °C). IR (KBr) n:
3052, 1603, 1547 cm-1. 1H NMR (CDCl3) d: 6.88-6.91 (m,
2H), 6.99-7.02 (m, 3H), 7.14-7.16 (m, 2H), 7.21-7.23 (m,
3H), 7.26-7.31 (m, 3H), 7.38-7.40 (m, 2H), 7.46 (ddd, J =
1.2, 6.8, 8.4 Hz, 1H), 7.59 (dd, J = 1.2, 8.4 Hz, 1H), 7.74
mp 111-112 °C (Lit.24, mp 128-129 °C). IR (KBr) n:
3029, 1584, 1539 cm-1. 1H NMR (CDCl3) d: 7.48-7.57 (m,
6H), 7.64-7.67 (m, 2H), 7.73-7.87 (m, 2H), 7.91 (dd, J =
1.0, 8.4 Hz, 1H), 8.08-8.11 (m, 2H), 8.24 (d, J = 8.4 Hz,
1H). 13C NMR (CDCl3, 100 MHz) d: 118.7, 123.8, 125.5,
125.7, 126.4, 128.4, 128.5, 129.0, 129.4, 129.6, 130.0,
131.8, 138.1, 138.3, 148.6, 149.3, 155.3. MS (EI) m/z: 361
(M++2), 360 (M++1), 359 (M+), 279, 278, 202, 139.
2-(2-Furyl)-4-phenylquinoline (3g)
(ddd, J = 1.2, 6.8, 8.4 Hz, 1H), 8.28 (d, J = 8.4 Hz, 1H). 13
C
NMR (CDCl3, 100 MHz) d: 126.2, 126.4, 126.5, 127.1,
127.2, 127.4, 127.5, 127.6, 129.2, 129.5, 129.8, 130.1,
131.2, 132.8, 136.8, 138.2, 141.0, 147.2, 147.5, 158.8. MS
(EI) m/z: 357 (M+), 356, 278, 176, 171.
mp 98-99 °C (Lit.22, mp 109-111 °C). IR (KBr) n:
3060, 1594, 1546 cm-1. 1H NMR (CDCl3) d: 6.60 (dd, J =
1.6, 3.6 Hz, 1H), 7.25 (m, 1H), 7.43-7.57 (m, 6H), 7.63 (dd,
J = 0.6, 1.8 Hz, 1H), 7.74 (ddd, J = 1.0, 6.8, 8.4 Hz, 1H),
7.78 (s, 1H), 7.87 (dd, J = 1.2, 8.4 Hz, 1H), 8.21 (d, J = 8.4
Hz, 1H). 13C NMR (CDCl3, 100 MHz) d: 110.1, 112.1,
117.6, 125.6, 125.7, 126.1, 128.3, 128.4, 129.4, 129.5,
129.8, 138.0, 144.0, 148.4, 148.5, 148.9, 153.6. MS (EI)
m/z: 271 (M+), 270, 243, 242, 241, 120.
ACKNOWLEDGEMENT
We gratefully acknowledge the National Council Sci-
ence of the Republic of China for financial support of this
work (Grant No. 94-2113-M-037-008).
Received March 6, 2008.
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