Journal of the Chinese Chemical Society, 2008, 55, 915-918 915

Amberlyst-15-catalyzed Novel Synthesis of Quinoline Derivatives in Ionic

Rei-Sheu Houa ( ), Jian-Long Wub ( ), Hui-Ting Chengb ( ),

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- Fig. 1
mability, and possess effectively no vapour pressure. Com-
pared with classical molecular solvents, the ionic liquids synthesize quinolines via Friedländer reaction in ionic liq-
are environmentally benign reaction media.2 To date, some uid.19
of the more important reactions have been carried out and
investigated in ionic liquids, for example, Friedel-Crafts RESULTS AND DISCUSSION
reaction,3 alkoxycarbonylation, 4 hydrogenation,5 Diels- Treatment of 2-aminobenzophenone (1) and aryl ke-
Alder reaction,6 Wittig reaction,7 Heck reaction,8 Trost- tones (2) with Amberlyst-15 as catalyst in ionic liquid
Tsuji coupling,9 ring-closing metathesis (RCM),10 Suzuki 1-n-butyl-3-methylimidazolium hexafluorophoaphate,
cross-coupling,11 Fischer indole synthesis,12 1,3-dipolar [Bmin][PF6] at 80 °C for 3 h caused cyclodehydration to
cycloaddition reaction,13 Beckmann rearrangement,14 the give quinolines (3) in good yields (Scheme I). The results
Knoevenagel and Robinson annulation reactions,15 etc. are given in Table 1. When the reaction is conducted in a
Recently, the use of ion exchange resins in organic conventional solvent, such as acetonitrile, the preparation
synthesis has received great attention.16 Amberlyst-1517-18 of 2,4-diphenylquinoline (3a) needs refluxing for 10 h.20
is a porous sulfonated polystyrene resin that serves as an The ionic liquid [Bmin][PF6] can be typically recov-
excellent source of strong acid in nonaqueous media (Fig. ered by extracting out the product first and filtering the sus-
1). It has been used in various catalyzed reactions, e.g., pension followed by vacuum drying. The recovered sol-
esterification, etherification, oxidation, hydration of ole- vent can be reused without loss of activity.
fins, condensation, cyclization and electrophilic aromatic In summary, our results herein demonstrate that the
substitution. It is easy to measure, safe to use, and readily use of 2-aminobenzophenone and arylketones in ionic liq-
removed at the end of the reaction. An additional advantage uid [Bmim][PF6] can be performed rapidly for Friedländer
is that the catalyst can be regenerated and used several reaction to prepare quinoline derivatives using Amberlyst-
times. We report here using Amberlyst-15 as catalyst to 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

Table 1. Synthesis of quinoline derivatives 1584, 1541 cm-1. 1H NMR (CDCl3) d: 7.45-7.59 (m, 9H),
Entry Product R1 R2 Yield (%) 7.74 (ddd, J = 1.2, 6.8, 15.2 Hz, 1H), 7.83 (s, 1H), 7.92 (dd,
1 3a Ph H 78 J = 0.8, 8.4 Hz, 1H), 8.20 (d, J = 8.4 Hz, 2H), 8.26 (d, J =
2 3b 4-MeC6H4 H 73 8.4 Hz, 1H). 13C NMR (CDCl3, 100 MHz) d: 119.3, 125.6,
3 3c 4-MeOC6H4 H 75 125.7, 126.3, 127.5, 128.4, 128.5, 128.8, 129.3, 129.4,
4 3d 4-FC6H4 H 77 129.5 130.0, 138.3, 139.6, 148.7, 149.1, 156.8. MS (EI)
5 3e 4-ClC6H4 H 80
6 3f 4-BrC6H4 H 82
m/z: 281 (M+), 280, 202, 176, 139, 125.
7 3g 2-Furyl H 72 2-(4-Methylphenyl)-4-phenylquinoline (3b)
8 3h 2-Thienyl H 76 mp 95-96 °C (Lit. 22, mp 116-117 °C). IR (KBr) n:
9 3i 4-NO2C6H4 H 84 3049, 1624, 1548 cm-1. 1H NMR (CDCl3) d: 2.43 (s, 3H),
10 3j Ph CH3 81
7.34 (d, J = 8.0 Hz, 2H), 7.44-7.58 (m, 6H), 7.71-7.75 (m,
11 3k Ph Ph 76
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,
vent and promoter. Separation of products from the ionic 100 MHz) d: 21.3, 119.1, 125.5, 125.6, 126.0, 127.3,
liquids is very straightforward, as is recycling of the ionic 128.3, 128.5, 129.3, 129.5, 129.9, 136.7, 138.4, 139.3,
liquid. 148.7, 148.9, 156.7. MS (EI) m/z : 295 (M+), 294, 202, 145,
139.
EXPERIMENTAL SECTION 2-(4-Methoxyphenyl)-4-phenylquinoline (3c)
All melting points are uncorrected. The IR spectra mp 78-79 °C (Lit.21, mp 77-79 °C). IR (KBr) n: 1736
were recorded on a Shimadzu IR-27 G spectrophotometer. cm . H NMR (CDCl3) d: 3.89 (s, 3H), 7.06 (ddd, J = 2.6,
-1 1

1
H NMR and 13C NMR spectra were recorded on a Varian 2.6, 9.2 Hz, 2H), 7.44-7.58 (m, 6H), 7.69-7.75 (m, 1H),
Unity Plus 400 MHz. Chemical shifts (d) were measured in 7.79 (s, 1H), 7.89 (ddd, J = 0.8, 0.8, 8.4 Hz, 1H), 8.19 (ddd,
ppm with respect to TMS. MS were obtained on a JEOL J = 2.4, 2.4, 9.2 Hz, 2H), 8.24 (ddd, J = 0.6, 0.8, 8.4 Hz,
JMS D-300 instrument. 1H). 13C NMR (CDCl3, 100 MHz) d: 55.3, 114.1, 118.8,
Typical procedure for the preparation of 2,4-diphen- 125.4, 125.5, 125.9, 128.3, 128.5, 128.8, 129.4, 129.5,
ylquinoline (3a) 129.8, 130.1, 132.0, 137.4, 138.4, 148.7, 149.0, 156.3,
To a solution of acetophenone (2a) (120 mg, 1.0 160.8. MS (EI) m/z: 311 (M+ ), 310, 268, 267, 140, 139,
mmol) and 2-aminobenzophenone (197 mg, 1.0 mmol) in 132.
[Bmin][PF6] (2 mL) was added Amberlyst-15 (100 mg, 0.5 2-(4-Fluorophenyl)-4-phenylquinoline (3d)
mmole), and the mixture was stirred at 80 °C for 3 h and fil- mp 63-64 °C. IR (KBr) n: 3056, 1593, 1546 cm-1. 1H
tered after cooling. Subsequently, the filtrate was extracted NMR (CDCl3) d: 7.19-7.24 (m, 2H), 7.47-7.57 (m, 6H),
with ethyl acetate. The organic layer was washed with satu- 7.72-7.76 (m, 1H), 7.78 (s, 1H), 7.91 (dd, J = 1.0, 8.4 Hz,
rated NaCl(aq), dried over MgSO4, then concentrated under 1H), 8.18-8.24 (m, 3H). 13C NMR (CDCl3, 100 MHz) d:
reduced pressure and the residue was chromatographed on 115.4, 115.7, 118.7, 125.5, 126.2, 128.3, 128.4, 129.2,
silica gel eluting with ethyl acetate-hexane (1:5) to give 3a. 129.3, 129.4, 129.5, 129.8, 135.5, 135.6, 138.1, 148.6,
mp 110-111 °C (Lit.21, mp 112-113 °C). IR (KBr) n: 3050, 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 C 12H 14NF: C, 84.26, H, (EI) m/z: 326 (M+), 325, 280, 278, 202, 176, 139.
4.71, N, 4.68; Found: C, 84.39, H, 4.54, N, 4.53. 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:
mp 104-105 °C (Lit.23, mp 106 °C). IR (KBr) n: 3055, 3048, 1609, 1568 cm-1. 1H NMR (CDCl3) d: 2.17 (s, 3H),
1589, 1542 cm-1. 1H NMR (CDCl3) d: 7.47-7.57 (m, 8H), 7.32-7.34 (m, 2H), 7.40-7.58 (m, 8H), 7.62-7.68 (m, 3H),
7.74-7.77 (m, 1H), 7.79 (s, 1H), 7.91 (d, J = 8.0 Hz, 1H), 8.20 (d, J = 8.4 Hz, 1H). 13C NMR (CDCl3, 100 MHz) d:
8.14-8.18 (m, 2H), 8.23 (d, J = 8.4 Hz, 1H). 13C NMR 18.5, 115.8, 126.1, 126.5, 126.9, 127.7, 127.9, 128.0,
(CDCl3, 100 MHz) d: 118.6, 125.6, 125.7, 126.5, 128.4, 128.2, 128.4, 128.6, 128.8, 129.2, 129.3, 137.5, 141.3,
128.6, 128.8, 128.9, 129.5, 129.6, 130.0, 136.5, 137.9, 146.1, 147.6, 160.6. MS (EI) m/z: 295 (M+), 294, 217, 189,
138.2, 148.7, 149.4, 155.4. MS (EI) m/z: 317 (M++2), 315 139.
(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:
mp 111-112 °C (Lit.24, mp 128-129 °C). IR (KBr) n: 3052, 1603, 1547 cm-1. 1H NMR (CDCl3) d: 6.88-6.91 (m,
3029, 1584, 1539 cm-1. 1H NMR (CDCl3) d: 7.48-7.57 (m, 2H), 6.99-7.02 (m, 3H), 7.14-7.16 (m, 2H), 7.21-7.23 (m,
6H), 7.64-7.67 (m, 2H), 7.73-7.87 (m, 2H), 7.91 (dd, J = 3H), 7.26-7.31 (m, 3H), 7.38-7.40 (m, 2H), 7.46 (ddd, J =
1.0, 8.4 Hz, 1H), 8.08-8.11 (m, 2H), 8.24 (d, J = 8.4 Hz, 1.2, 6.8, 8.4 Hz, 1H), 7.59 (dd, J = 1.2, 8.4 Hz, 1H), 7.74
1H). 13C NMR (CDCl3, 100 MHz) d: 118.7, 123.8, 125.5, (ddd, J = 1.2, 6.8, 8.4 Hz, 1H), 8.28 (d, J = 8.4 Hz, 1H). 13C
125.7, 126.4, 128.4, 128.5, 129.0, 129.4, 129.6, 130.0, NMR (CDCl3, 100 MHz) d: 126.2, 126.4, 126.5, 127.1,
131.8, 138.1, 138.3, 148.6, 149.3, 155.3. MS (EI) m/z: 361 127.2, 127.4, 127.5, 127.6, 129.2, 129.5, 129.8, 130.1,
(M++2), 360 (M++1), 359 (M+), 279, 278, 202, 139. 131.2, 132.8, 136.8, 138.2, 141.0, 147.2, 147.5, 158.8. MS
2-(2-Furyl)-4-phenylquinoline (3g) (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 = ACKNOWLEDGEMENT
1.6, 3.6 Hz, 1H), 7.25 (m, 1H), 7.43-7.57 (m, 6H), 7.63 (dd, We gratefully acknowledge the National Council Sci-
J = 0.6, 1.8 Hz, 1H), 7.74 (ddd, J = 1.0, 6.8, 8.4 Hz, 1H), ence of the Republic of China for financial support of this
7.78 (s, 1H), 7.87 (dd, J = 1.2, 8.4 Hz, 1H), 8.21 (d, J = 8.4 work (Grant No. 94-2113-M-037-008).
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, Received March 6, 2008.
129.8, 138.0, 144.0, 148.4, 148.5, 148.9, 153.6. MS (EI)
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