T. H. Babu et al. / Tetrahedron Letters 50 (2009) 2881–2884
2883
Table 1 (continued)
at room temperature. Further merits of this method are its gener-
ality, shorter-reaction time, and easy work-up.
Entry
RX (2)
Product (4)
Time (h)
Yielda (%)
Acknowledgment
One of the authors, T.H. thanks the Council of Scientific and
Industrial Research, New Delhi, India for the research fellowship.
N
Br
5
3.0
78
References and notes
4e
1. Murakami, Y.; Kikuchi, J.; Hisaeda, Y.; Hayashida, O. Chem. Rev. 1996, 96, 721.
2. (a) Coleman, C. A.; Rose, J. G.; Murray, C. J. J. Am. Chem. Soc. 1992, 114, 9755; (b)
Fukuzumi, S.; Nishizawa, N.; Tanaka, T. J. Org. Chem. 1984, 49, 3571.
3. (a) Fukuzumi, S.; Mochizuki, S.; Tanaka, T. J. Am. Chem. Soc. 1989, 111, 1497; (b)
Tanner, D. D.; Singh, H. K.; Kharrat, A.; Stein, A. R. J. Org. Chem. 1987, 52, 2141;
(c) Tanner, D. D.; Stein, A. R. J. Org. Chem. 1988, 53, 1642.
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37, 1410; (b) Fukuzumi, S.; Ishikama, M.; Tanaka, T. Tetrahedron 1984, 42, 1021.
5. Liu, Q.; Li, J.; Shen, X.-X.; Xing, R.-G.; Yang, J.; Liu, Z.; Zhou, B. Tetrahedron Lett.
2009, 50, 1026.
N
6
2.5
75
Ph
Br
Ph
4f
6. Garden, S. J.; Guimaraes, C. R. W.; Correa, M. B.; Oliviera, C. A. F.; Pinto, A. C.;
Bicca de Alencastro, R. J. Org. Chem. 2003, 68, 8815.
7. Itoh, T.; Nagata, K.; Miyazaki, M.; Ishikawa, H.; Kurihara, A.; Ohsawa, A.
Tetrahedron 2004, 60, 6649; Itoh, T.; Nagata, K.; Kurihara, A.; Miyazaki, M.;
Ohsawa, A. Tetrahedron Lett. 2002, 43, 3105.
8. For review, see: (a) Huang, Y. Synlett 2007, 2304; (b) Ouellet, S. G.; Walji, Abbas
M.; Macmillan, D. W. C. Acc. Chem. Res. 2007, 40, 1327.
N
Br
7
2.5
74
9. For review, see: Katritzky, A. R.; Rachwal, S.; Rachwal, B. Tetrahedron 1996, 52,
15031.
10. For examples, see: (a) Jacquemond-Collet, I.; Benoit-Vical, F.; Valentin, A.;
Stanislas, E.; Mallié, M.; Fourasté, I. Planta Med. 2002, 68, 68; (b) Wallace, O. B.;
Lauwers, K. S.; Jones, S. A.; Dodge, J. A. Bioorg. Med. Chem. Lett. 2003, 13, 1907;
(c) Di Fabio, R.; Tranquillini, E.; Bertani, B.; Alvaro, G.; Micheli, F.; Sabbatini, F.;
Pizzi, M. D.; Pentassuglia, G.; Pasquarello, A.; Messeri, T.; Donati, D.; Ratti, E.;
Arban, R.; Dal Forno, G.; Reggiani, A.; Barnaby, R. J. Bioorg. Med. Chem. Lett.
2003, 13, 3863; (d) Asolkar, R. N.; Schröder, D.; Heckmann, R.; Lang, S.;
Wagner-Döbler, I.; Laatsch, H. J. Antibiot. 2004, 57, 17; (e) Lombardo, L. J.;
Camuso, A.; Clark, J.; Fager, K.; Gullo-Brown, J.; Hunt, J. T.; Inigo, I.; Kan, D.;
Koplowitz, B.; Lee, F.; McGlinchey, K.; Qian, L. G.; Ricca, C.; Rovnyak, G.;
Traeger, S.; Tokarski, J.; Williams, D. K.; Wu, L. I.; Zhao, Y. F.; Manne, V.; Bhide,
R. S. Bioorg. Med. Chem. Lett. 2005, 15, 1895; (f) Nallan, L.; Bauer, K. D.; Bendale,
P.; Rivas, K.; Yokoyama, K.; Horney, C. P.; Pendyala, P. R.; Floyd, D.; Lombardo,
L. J.; Williams, D. K.; Hamilton, A.; Sebti, S.; Windsor, W. T.; Weber, P. C.;
Buckner, F. S.; Chakrabarti, D.; Gelb, M. H.; Van Voorhis, W. C. J. Med. Chem.
2005, 48, 3704.
4g
N
O
OEt
Br
8
3.0
75
O
OEt
4h
11. For some recent publications, see: (a) Fujita, K.; Yamaguchi, R. Synlett 2005,
560; (b) Lam, K. H.; Xu, L. J.; Feng, L. C.; Fan, Q. H.; Lam, F. L.; Lo, W. H.; Chan, A.
S. C. Adv. Synth. Catal. 2005, 347, 1755; (c) Xu, L. K.; Lam, K. H.; Ji, J. X.; Wu, J.;
Fan, Q. H.; Lo, W. H.; Chan, A. S. C. Chem. Commun. 2005, 1390; (d) Lu, S. M.;
Han, X. W.; Zhou, Y. G. Adv. Synth. Catal. 2004, 346, 909; (e) Yang, P. Y.; Zhou, Y.
G. Tetrahedron: Asymmetry 2004, 15, 1145; (f) Wang, W. B.; Lu, S. M.; Yang, P.
Y.; Han, X. W.; Zhou, Y. G. J. Am. Chem. Soc. 2003, 125, 10536; (g) Michael, J. P.
Nat. Prod. Rep. 2005, 22, 627.
12. (a) Ranu, B. C.; Jana, U.; Sarkar, A. Synth. Commun. 1998, 28, 485; (b) Srikrishna,
A.; Reddy, T. J.; Viswajanani, R. Tetrahedron 1996, 52, 1631; (c) Nose, A.; Kudo,
T. Chem. Pharm. Bull. 1984, 32, 2421.
13. Rueping, M.; Theissmann, T.; Antonchick, A. P. Synlett 2006, 1071.
14. Wang, D.-W.; Zeng, W.; Zhou, Y.-G. Tetrahedron: Asymmetry 2007, 18, 1103.
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Magesh, C. J.; Perumal, P. T. Synthesis 2004, 69; (c) Senthil Kumar, R.;
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S. V.; Perumal, P. T. Bioorg. Med. Chem. Lett. 2004, 14, 2035.
N
9
10
11
CH3I
0.5
6.0
0.5
0.5
74
75
70
75
CH3
4i
4j
N
CH3CH2I
16. (a) Shanthi, G.; Perumal, P. T. Tetrahedron Lett. 2008, 49, 7139; (b) Shanthi, G.;
Perumal, P. T. Tetrahedron Lett. 2007, 48, 6785.
N
CH3
CH3I
CH3
4k
17. General procedure for the synthesis of N-substituted tetrahydroquinolines 4a-l.
Representative experimental procedure for N-acetyl tetrahydroquinoline 4a: To a
stirred solution of quinoline 1 (1 mmol), acetyl chloride 2a (1.5 mmol) was
added in CH2Cl2 (5 mL). To the formed quinolinium salt, Hantzsch
dihydropyridine (2.0 mmol) was added and stirred at room temperature.
After the completion of the reaction as indicated by TLC, the reaction mixture
was washed with water. The combined extract was washed with brine, dried
over anhydrous Na2SO4, and concentrated in vacuo. The crude product was
purified by column chromatography (Merck, 100–200 mesh, ethyl acetate, pet
ether, 1:9) to afford 1-(3,4-dihydro-2H-quinolin-1-yl)-ethanone.
H3C
12
CH3I
N
CH3
4l
Spectral data for selected compounds:
1-(3,4-Dihydro-2H-quinolin-1-yl)-ethanone (4a): Yellow liquid. Yield: 73%. 1H
NMR (500 MHz, CDCl3) d 1.94 (q, 2H), 2.20 (s, 3H), 2.70 (t, 2H), 3.78 (t, 2H),
7.15(m 4H,). 13C NMR (125 MHz, CDCl3) d 23.0, 24.0, 26.8, 39.4, 124.3, 125.3,
a
Isolated yield.
126.0, 127.6, 128.4, 134.0, 170.1. IR mmax: 2937, 2841, 1728, 1656, 1491, 1379,
We propose a plausible mechanism for the formation of product
4 (Scheme 3).
In conclusion, we have developed a simple method for the syn-
thesis of N-substituted tetrahydroquinolines without any catalyst
1328, 1261, 1204, 760 cmÀ1. Mass (ESI): 176 (M+1). Anal. Calcd for C11H13NO:
C, 75.40; H, 7.48; N, 7.99. Found: C, 75.34; H, 7.43; N, 7.96.
3,4-Dihydro-2H-quinoline-1-carboxylic acid ethyl ester (4b): pale yellow liquid.
Yield: 75%. 1H NMR (500 MHz, CDCl3) d 1.32 (t, 3H), 1.93 (q, 2H), 2.75 (t, 2H),