D. S. Bose, R. K. Kumar / Tetrahedron Letters 47 (2006) 813–816
815
example, 2-butanone reacted with 2-aminoaryl ketones
to give the corresponding substituted quinolines without
any side products (Table 1, entry 3). Interestingly, cyclic
ketones such as 4-tert-butylcyclohexanone and cyclo-
octanone reacted with 2-amino aryl ketones to afford the
respective tricyclic quinolines in good yields. In general,
the reaction is very clean, rapid, efficient and involves a
Tagari, P.; Young, R. N. Bioorg. Med. Chem. Lett. 1998,
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3
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. (a) Maguire, M. P.; Sheets, K. R.; McVety, K.; Spada, A.
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Chung, Y. M.; Im, Y. J. Tetrahedron Lett. 2002, 43, 6209–
6211; (c) Legros, J.-Y.; Primault, G.; Fiaud, J.-C. Tetra-
hedron 2001, 57, 2507–2514.
1
3,14
simple work-up procedure.
Unlike previous meth-
ods, the reported protocol does not require high tempera-
tures to produce quinoline derivatives. In order to
improve the yields, we performed reactions using differ-
ent quantities of reagents. The optimum results were
obtained with a 0.1:1:1 ratio of CeCl Æ7H O, o-aminoaryl
5
6
. (a) Agrawal, A. K.; Jenekhe, S. A. Chem. Mater. 1996, 8,
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79–589; (b) Jenekhe, S. A.; Lu, L.; Alam, M. M.
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2
Macromolecules 2001, 34, 7315–7324; (c) Jegou, G.;
Jenekhe, S. A. Macromolecules 2001, 34, 7926–7928.
. (a) Jones, G. In Comprehensive Heterocyclic Chemistry II;
Katritzky, A. R., Rees, C. W., Eds.; Pergamon Press: New
York, 1996; Vol. 5, p 167; (b) Cho, C. S.; Oh, B. H.; Kim,
T. J.; Kim, T. J.; Shim, S. C. Chem. Commun. 2000, 1885–
1886; (c) Jiang, B.; Si, Y. G. J. Org. Chem. 2002, 67, 9449–
9451.
7. (a) Skraup, H. Chem. Ber. 1880, 13, 2086; (b) Friedl a¨ nder,
P. Chem. Ber. 1882, 15, 2572; (c) Mansake, R. H.; Kulka,
M. Org. React. 1953, 7, 59–98; (d) Linderman, R. J.;
Kirollos, K. S. Tetrahedron Lett. 1990, 31, 2689–2693; (e)
Theoclitou, M. E.; Robinson, L. A. Tetrahedron Lett.
ketone, a-methylene ketone or b-diketones. Higher
amounts of catalyst did not improve the results to any
greater extent. Solvents such as CH CN, THF and EtOH
3
proved to be effective. After the reaction was complete as
monitored by TLC, the product was isolated by simple
filtration. When the filtered solution containing CeCl3
catalyst was reused, only a slight decrease in the yield
from 95% to 88% was observed after the third run (Table
1
, entry 1). In another experiment, when the filtered solu-
tion containing the catalyst was used after 3 months of
storage, it was observed that the catalyst was still quite
active (no appreciable change in the yield of the product
2
002, 43, 3907–3910.
. (a) Cheng, C.-C.; Yan, S.-J. Org. React. 1982, 28, 37–201;
b) Thummel, R. P. Synlett 1992, 1–12; (c) Eckert, H.
was apparent), which demonstrated that CeCl is stable
3
8
and does not undergo any deterioration. This study demon-
(
strates that CeCl can be effectively employed as a reus-
3
Angew. Chem., Int. Ed. Engl. 1981, 20, 208–210; (d)
Gladiali, S.; Chelucci, G.; Mudadu, M. S.; Gastaut, M. A.;
Thummel, R. P. J. Org. Chem. 2001, 66, 400–405.
able catalyst for Friedl a¨ nder annulation. In the absence
of catalyst, the reaction did not yield any product even
after longer reaction times (10–15 h). Furthermore, the
condensation of o-aminobenzophenone with ethyl aceto-
acetate in the presence of concd H SO afforded the
9. Fehnel, E. A. J. Org. Chem. 1966, 31, 2899–2902.
0. (a) Strekowski, L.; Czarny, A.; Lee, H. J. Fluorine Chem.
1
2
000, 104, 281–284; (b) Hu, Y. Z.; Zhang, G.; Thummel,
2
4
R. P. Org. Lett. 2003, 5, 2251–2253; (c) Arcadi, A.;
Chiarini, M.; Di Giuseppe, S.; Marinelli, F. Synlett 2003,
quinoline product in only 65% yield (entry 1).
2
03–206; (d) Yadav, J. S.; Reddy, B. V. S.; Premalatha, K.
In conclusion, we have demonstrated a simple and effi-
cient procedure for the synthesis of quinolines, including
Synlett 2004, 963–966; (e) McNaughton, B. R.; Miller, B.
L. Org. Lett. 2003, 5, 4257–4259; (f) Walser, A.; Flynn, T.;
Fryer, R. I. J. Heterocycl. Chem. 1975, 12, 737–741; (g)
Sik, C. C.; Jin, S. H.; Chul, S. S. J. Heterocycl. Chem.
2005, 42, 1219–1222.
polycyclic quinolines, by employing CeCl Æ7H O as a
3
2
reusable catalyst. The salient features of this method
include operational simplicity, improved reaction rates,
high yields of products and avoidance of the use of haz-
ardous acids or bases.
11. Marshman, R. W. Aldrichim. Acta 1995, 28, 77–84, and
references cited therein.
1
2. (a) Bose, D. S.; Sudharshan, S.; Chavhan, S. W. ARKI-
VOC 2005, iii, 228–236; (b) Bose, D. S.; Fatima, L.;
Mereyala, H. B. J. Org. Chem. 2003, 68, 587–590; (c) Bose,
D. S.; Rudradas, A. P.; Mereyala, H. B. Tetrahedron Lett.
Acknowledgements
2
002, 43, 9195–9197.
3. Typical procedure: A mixture of o-aminobenzophenone
1.97 g, 10 mmol), ethyl acetoacetate (1.30 g, 10 mmol)
and CeCl Æ7H O (930 mg, 25 mol %) in acetonitrile (5 mL)
One of the authors (R.K.K.) thanks UGC, New Delhi,
for financial support and the authors thank Dr. J. S.
Yadav, Director, IICT for his constant encouragement.
1
(
3
2
was stirred at room temperature for 90 min. After com-
pletion of the reaction (monitored by TLC), the mixture
was diluted with ethyl acetate (30 mL), and washed with
water (15 mL), dried (Na SO ) and concentrated. The
References and notes
2
4
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. J. Org. Chem.
residue was purified by silica gel column chromatography
(10% ethyl acetate in hexane) to afford the pure product
(2.76 g). The aqueous layer containing the catalyst could
be evaporated under reduced pressure to give a white
solid. The catalyst was recovered and reused in subsequent
reactions, three times without losing any significant
activity (reaction yields 95%, 92% and 88%).
1
996, 61, 3398–3405; (b) Chen, Y. L.; Fang, K. C.; Sheu, J.
Y.; Hsu, S. L.; Tzeng, C. C. J. Med. Chem. 2001, 44, 2374–
377; (c) Roma, G.; Braccio, M. D.; Grossi, G.; Mattioli,
2
F.; Ghia, M. Eur. J. Med. Chem. 2000, 35, 1021–1035.
. (a) Kalluraya, B.; Sreenivasa, S. Farmaco 1998, 53, 399–
2
14. Selected analytical data for the products from entries 4, 5
1
4
04; (b) Dube, D.; Blouin, M.; Brideau, C.; Chan, C.-C.;
and 7: Entry 4: mp 105–106 °C; H NMR (300 MHz,
Desmarais, S.; Ethier, D.; Falgueyret, J. P.; Friesen, R.
W.; Girard, M.; Girard, Y.; Guay, J.; Riendeau, D.;
CDCl ): d 1.96 (s, 3H), 2.65 (s, 3H), 7.33–7.72 (m, 8H),
3
1
3
8.04 (d, J = 8.0 Hz, 1H). C NMR (75 MHz, CDCl ): d
3