S. K. De, R. A. Gibbs / Tetrahedron Letters 46 (2005) 1647–1649
1649
Chem., Int. Ed. Engl. 1981, 20, 208; (d) Gladiali, S.;
Chelucci, G.; Mudadu, M. S.; Gastaut, M. A.; Thummel,
R. P. J. Org. Chem. 2001, 66, 400.
did notform any significantamounts of undesirable side
products. Unlike previously reported methods, the pres-
ent method does not require high temperatures to
produce quinoline derivatives. The condensation of
2-aminobenzophenone with ethyl acetoacetate in the
presence of concd H2SO4 afforded the quinoline product
only in 65% yield (entry 1). Among the various metal tri-
flates such as Nd(OTf)3, Lu(OTf)3, Cu(OTf)2, Yb(OTf)3,
Ce(OTf)3 studied for this reaction, Y(OTf)3 employed
here gave better yields with short reaction times. It
should be mentioned that the Sc(OTf)3 gave similar re-
sults under identical conditions but it is more expensive
than Y(OTf)3. The results shown in Table 1 clearly indi-
cate the scope and generality of the reaction with respect
to various 2-aminoaryl ketones and a wide array of a-
methylene ketones.
8. Fehnel, E. A. J. Heterocycl. Chem. 1966, 31, 2899.
9. (a) Strekowski, L.; Czamy, A. J. Fluoresc. Chem. 2000,
104, 281; (b) Hu, Y. Z.; Zang, G.; Thummel, R. P. Org.
Lett. 2003, 5, 2251; (c) Arcadi, A.; Chiarini, M.; Di
Giuseppe, S.; Marinelli, F. Synlett 2003, 203; (d)
McNaughton, B. R.; Miller, B. L. Org. Lett. 2003, 5,
4257; (e) Yadav, J. S.; Reddy, B. V.; Premlatha, K. Synlett
2004, 963; (f) Yadav, J. S.; Reddy, B. V.; Sreedhar, P.;
Rao, R. S.; Nagaiah, K. Synthesis 2004, 2381; (g)
Mogilaih, K.; Reddy, C. S. Synth. Commun. 2003, 33,
3131; (h) Walser, A.; Flyll, T.; Fryer, R. I. J. Heterocycl.
Chem. 1975, 12, 737.
10. (a) Kobayashi, S. Eur. J. Org. Chem. 1999, 15; (b)
Kobayashi, S. Synlett 1994, 689.
11. De, S. K. Tetrahedron Lett. 2004, 45, 2339.
12. (a) De, S. K. Tetrahedron Lett. 2003, 44, 9055; (b) De, S.
K. Tetrahedron Lett. 2004, 45, 1035; (c) De, S. K.
Tetrahedron Lett. 2004, 45, 2919; (d) De, S. K.; Gibbs,
R. A. Tetrahedron Lett. 2004, 45, 7407; (e) De, S. K.;
Gibbs, R. A. Tetrahedron Lett. 2004, 45, 8141.
In conclusion, we have demonstrated a simple and effi-
cient procedure for the synthesis of quinolines, including
polycyclic quinolines, using ytrrium triflate as a reusable
catalyst. The significant features of this method include
(a) operational simplicity, (b) inexpensive reagents, (c)
high yields of products, and (d) the use of relatively non-
toxic reagents and solvents.
13. Typical procedure: A mixture of 2-aminobenzophenone
(197 mg, 1 mmol), ethyl acetoacetate (169 mg, 1.3 mmol),
and Y(OTf)3 (108 mg, 0.2 mmol) in ethanol or acetonitrile
(5 mL) was stirred at room temperature for 4 h. After
completion of the reaction (TLC), the reaction mixture
was diluted with ethyl acetate (30 mL), and washed with
water (15 mL), dried (MgSO4), and concentrated. The
residue was purified by silica gel column chromatography
(10% ethyl acetate in hexane) to afford a pure product. The
aqueous layer containing the catalyst could be evaporated
under reduced pressure to give a white solid. The IR
spectrum of the recovered catalyst was identical to that of
the commercially available catalyst (Aldrich), which could
be reused for the next reaction, without losing any
significant activity. The catalyst has been recovered and
reused for four times (reaction yields 89%, 82%, 77%, and
61%).
14. Spectral data for selected products: Ethyl 2-methyl-4-
phenylquinoline-3-carboxylate (entry 1): 1H NMR
(300 MHz, CDCl3): d 0.96 (t, J = 7 Hz, 3H), 2.81 (s,
3H), 4.06 (q, J = 7 Hz, 2H), 7.28–7.56 (m, 7H), 7.66–7.71
(m, 2H), 8.02 (d, J = 8 Hz, 1H); 13C NMR (75 MHz,
CDCl3): d 13.6, 23.3, 60.8, 96.1, 125.1, 126.1, 126.4, 127.8,
128.2, 129.1, 129.5, 135.7, 145.7, 147.8, 153.7, 167.7; EIMS
m/z 291 (M+), 247, 218, 177, 75, 43. 9-Phenyl-1,2,3,4-
tetrahydroacridine (entry 4): 1H NMR (300 MHz, CDCl3):
d 1.72–1.89 (m, 2H), 1.92–2.03 (m, 2H), 2.58 (t, J = 7 Hz,
2H), 3.17 (t, J = 7.2 Hz, 2H), 7.17–7.32 (m, 4H), 7.41–7.63
(m, 4H), 7.96 (d, J = 7.8 Hz, 1H); 13C NMR (75 MHz,
CDCl3): d 22.7, 23.1, 27.8, 34.1, 96.1, 1252, 125.6, 126.6,
127.5, 127.9, 128.2, 128.5, 128.7, 129.2, 137.3, 146.1, 146.5,
158.4; EIMS m/z 259 (M+), 230, 183, 77. 7-Chloro-9-
phenyl-2,3-dihydro-1H-cyclopenta[b]quinoline (entry 7):
1H NMR (300 MHz, CDCl3): d 2.16–2.27 (m, 2H), 2.96
(t, J = 7.2 Hz, 2H), 3.26 (t, J = 7.2 Hz, 2H); 7.24–7.37 (m,
2H), 7.46–7.62 (m, 5H), 8.21 (d, J = 8 Hz, 1H); 13C NMR
(75 MHz, CDCl3): d 23.2, 30.3, 35.1, 124.2, 126.9, 128.5,
129.2, 130.2, 131.2, 134.4, 135.6, 141.9, 146.3, 167.8; EIMS
m/z 279 (M+), 244, 202, 167, 121, 114, 94, 77. Ethyl 2,4-
dimethylquinoline-3-carboxylate (entry 8): 1H NMR
(300 MHz, CDCl3): d 1.76 (t, J = 7 Hz, 3H), 2.97 (s,
3H), 3.11 (s, 3H), 4.78 (q, J = 7 Hz, 2H), 7.80–8.06 (m,
3H), 8.41 (d, J = 8 Hz, 1H); 13C NMR (75 MHz, CDCl3):
d 14.1, 15.5, 23.6, 61.2, 123.6, 125.7, 126.1, 127.8, 129.7,
141.1, 147.2, 154.2, 168.9; EIMS m/z 229 (M+), 186, 158,
125, 77.
Acknowledgements
We thank the reviewers for their valuable suggestions
and comments.
References and notes
1. (a) Larsen, R. D.; Corley, E. G.; King, A. O.; Carrol, J.
D.; Davis, P.; Verhoeven, T. R.; Reider, P. J.; Labelle, M.;
Gauthier, J. Y.; Xiang, Y. B.; Zamboni, R. J. Org. Chem.
1996, 61, 3398; (b) Chen, Y. L.; Fang, K. C.; Sheu, J. Y.;
Hsu, S. L.; Tzeng, C. C. J. Med. Chem. 2001, 44, 2374; (c)
Roma, G.; Braccio, M. D.; Grossi, G.; Chia, M. Eur. J.
Med. Chem. 2000, 35, 1021.
2. Doube, D.; Bloun, M.; Brideau, C.; Chan, C.; Desmarais,
S.; Eithier, D.; Falgueyeret, J. P.; Friesen, R. W.; Girad,
M.; Girad, Y.; Guay, J.; Tagari, P.; Yong, R. N. Bioorg.
Med. Chem. Lett. 1998, 8, 1255.
3. (a) Maguire, M. P.; Sheets, K. R.; Mcvety, K.; Spada, A.
P.; Zilberstein, A. J. Med. Chem. 1994, 37, 2129; (b)
Bilker, O.; Lindo, V.; Panico, M.; Etiene, A. E.; Paxton,
T.; Dell, A.; Rogers, M.; Sinden, R. E.; Morris, H. R.
Nature 1998, 392, 289.
4. (a) Aggarwal, A. K.; Jenekhe, S. A. Macromolecules 1991,
24, 6806; (b) Zhang, X.; Shetty, A. S.; Jenekhe, S. A.
Macromolecules 1999, 32, 7422; (c) Jenekhe, S. A.; Lu, L.;
Alam, M. M. Macromolecules 2001, 34, 7315.
5. (a) Jones, G. In Comprehensive Heterocyclic Chemistry;
Katritzky, A. R., Ress, C. W., Eds.; Pergamon: New
York, 1996; Vol. 5, p 167; (b) Cho, C. S.; Oh, B. H.; Kim,
T. J.; Shim, S. C. J. Chem. Soc., Chem. Commun. 2000,
1885; (c) Jiang, B.; Si, Y. C. J. Org. Chem. 2002, 67, 9449.
6. (a) Skraup, H. Chem. Ber. 1880, 13, 2086; (b) Friedlander,
P. Ber. 1882, 15, 2572; (c) Mansake, R. H.; Kulka, M.
Org. React. 1953, 7, 59; (d) Linderman, R. J.; Kirollos, S.
K. Tetrahedron Lett. 1990, 31, 2689; (e) Theclitou, M. E.;
Robinson, L. A. Tetrahedron Lett. 2002, 43, 3907.
7. (a) Cheng, C. C.; Yan, S. J. Org. React. 1982, 28, 37; (b)
Thummel, R. P. Synlett 1992, 1; (c) Eckert, H. Angew.