1802
C. Mukhopadhyay et al. / Tetrahedron Letters 51 (2010) 1797–1802
19. Huang, X. Q.; Li, H. X.; Wang, J. X.; Jia, X. F. Chin. Chem. Lett. 2005, 16, 607.
20. Kidwai, M.; Rastogi, S.; Thakur, R.; Saxena, S. Zeitschrift fuer Naturforschung, B:
Chem. Sci. 2004, 59, 606.
21. Nagarapu, L.; Peddiraju, A. R.; Apuri, S. Catal. Commun. 2007, 8, 1973.
22. Heravi, M. M.; Bakhtiari, K.; Daroogheha, Z.; Bamoharram, F. F. Catal. Commun.
2007, 8, 1991.
intermediate B via iminium catalysis which condenses with the
condensation product of amine and ketones to form the intermedi-
ate C which on dehydration gives the dihydropyridines (D). Dihy-
dropyridine on subsequent oxidation and 1,4-elimination of
water produces the final product.
23. Zotova, N.; Franzke, A.; Armstrong, A.; Blackmond, D. G. J. Am. Chem. Soc. 2007,
129, 15100.
24. List, B.; Pojarliev, P.; Biller, W. T. J. Am. Chem. Soc. 2002, 124, 827.
25. Hahn, B. T.; Froehlich, R.; Harms, K.; Glorius, F. Angew. Chem., Int. Ed. 2008, 47,
9985.
26. (a) Ramachary, D. B.; Chowdari, N. S.; Barbas, C. F., III Angew. Chem. 2003, 115,
4365; (b) Xie, H.; Zu, L.; Oueis, H. R.; Li, H.; Wang, J.; Wang, W. Org. Lett. 2008,
10, 1923.
3. Conclusion
In conclusion, a novel, facile, one-pot, multicomponent method-
ology38 for the synthesis of substituted pyridines catalyzed by
15 mol% of L-proline has been developed in high yield. Compared
27. Kotrusz, P.; Toma, S. Molecules 2006, 11, 197.
to the previously reported methods, most of which required ele-
vated temperatures,18–22 this methodology proceeds smoothly at
room temperature and therefore is able to sustain a large number
of functional groups. Mild reaction conditions, easy work-up, clean
reaction profile, shorter reaction time, and wide range of substrate
applicability are the key advantages of this methodology.
28. Guo, S.-R.; Yuan, Y.-Q. Synth. Commun. 2008, 38, 2722.
29. (a) Yadav, J. S.; Kumar, S. P.; Kondaji, G.; Rao, R. S.; Nagaiah, K. Chem. Lett. 2004,
33, 1168; (b) Mabry, J.; Ganem, B. Tetrahedron Lett. 2006, 47, 55.
30. Kumar, A.; Maurya, R. A. Tetrahedron 2007, 63, 1946.
31. (a) Varala, R.; Nasreen, A.; Enugala, R.; Adapa, S. R. Tetrahedron Lett. 2007, 48,
69; (b) Borah, B. M.; Das, G. Tetrahedron Lett. 2006, 47, 3135; (c) Li, G.-I.; Zhao,
G. J. Org. Chem. 2005, 70, 4272; (d) Yanagisawa, A.; Nakamura, Y.; Arai, T.
Tetrahedron: Asymmetry 2004, 15, 1909.
32. Ramachary, D. B.; Kishor, M. J. Org. Chem. 2007, 72, 5056.
33. Ramachary, D. B.; Barbas, C. F., III Org. Lett. 2005, 7, 1577.
34. Ramachary, D. B.; Anebouselvy, K.; Chowdari, N. S.; Barbas, C. F., III J. Org. Chem.
2004, 69, 5838.
35. Ramachary, D. B.; Ramakumar, K.; Narayana, V. V. J. Org. Chem. 2007, 72, 1458.
36. Mukhopadhyay, C.; Tapaswi, P. K. Tetrahedron Lett. 2008, 49, 6237.
37. Thapa, P.; Karki, R.; Basnet, A.; Thapa, U.; Choi, H.; Na, Y.; Jahng, Y.; Lee, C.;
Kwon, Y.; Jeong, B. S.; Lee, E. S. Bull. Korean Chem. Soc. 2008, 29, 1605.
38. General experimental procedure for substituted pyridine formation: In a 50 mL
round-bottomed flask, aldehyde (1 mmol), indan-1,3-dione (1 mmol), 2-acetyl
thiophene or 2-acetyl fluorene (1 mmol), and ammonium acetate (1.3 mmol)
Acknowledgments
We thank the CAS Instrumentation Facility, Department of
Chemistry, University of Calcutta, for spectral data. One of the
authors (P.K.T.) thanks the University Grants Commission, New
Delhi for his fellowship (SRF).
Supplementary data
were stirred in the presence of 15 mol % of
L-proline in ethanol (2 mL) at room
temperature for the stipulated time (Table 2). The progress of the reaction was
monitored by TLC. After completion of the reaction, the reaction mixture was
diluted with water (5 mL) and extracted with ethylacetate (3 Â 10 mL). The
organic layer was dried over anhydrous Na2SO4, concentrated, and
recrystallized from hot ethanol to afford the pure product. In the case of
2,4,6-triaryl pyridines (Scheme 2, Table 3), same procedure was followed
except taking 2 mmol of either 2-acetyl thiophene or 2-acetyl fluorine or
acetophenone. The IR, 1H NMR, and 13C NMR data of three representative
compounds are given below: The spectral data for all the other new
compounds are given in the Supplementary data.
Supplementary data associated with this article can be found, in
References and notes
1. (a) J. Zhu, H. Bienaymé (Eds.), Multicomponent reactions, Wiley-VCH,
Weinheim, 2005, Reviews.; (b) Dömling, A. Chem. Rev. 2006, 106, 17.
2. (a) Kalinski, C.; Lemoine, H.; Schmidt, J.; Burdack, C.; Kolb, J.; Umkehrer, M.;
Ross, G. Synlett. 2008, 4007; (b) Samai, S.; Nandi, G. C.; Singh, P.; Singh, M. S.
Tetrahedron 2009, 65, 10155.
4-(4-Bromophenyl)-2-thiophen-2-yl-indeno[1,2-b]pyridin-5-one (Table 2, entry
1): yellow solid, mp 232 °C (EtOH); IR (KBr): 3087, 2372, 1706, 1573, 1535,
1433, and 1087 cmÀ1 1H NMR (300 MHz, CDCl3) d: 7.95 (d, J = 7.2 Hz, 1H), 7.77
;
3. Lu, X.; Lin, S. J. Org. Chem. 2005, 70, 9651.
(dd, J = 3.7 and 1.1 Hz, 1H), 7.68–7.50 (m, 7H), 7.44 (dt, J = 7.5 and 0.9 Hz, 1H),
7.39 (s, 1H), 7.17 (dd, J = 3.8 and 3.7 Hz, 1H); 13C NMR (75 MHz, CDCl3) d: 190.6,
166.7, 152.2, 148.2, 143.9, 142.5, 135.4, 134.8, 134.1, 131.5, 131.2, 130.6, 129.8,
128.4, 126.8, 124.2, 123.6, 122.1, 121.1, 118.6; Anal. Calcd for C22H12BrNOS: C,
63.17; H, 2.89; N, 3.35. Found: C, 63.05; H, 2.99; N, 3.37.
4. Prueksaritanont, T.; Freidinger, R. M.; Pettibone, D. J.; Bock, M. G. J. Med. Chem.
2004, 47, 6439.
5. Jetti, R. K. R.; Nagia, A.; Xue, F.; Mark, T. C. W. Chem. Commun. 2001, 919.
6. Kim, B. Y.; Ahn, J. B.; Lee, H. W.; Kang, S. K.; Lee, J. H.; Shin, J. S.; Ahn, S. K.; Hong,
C. I.; Yoon, S. S. Eur. J. Med. Chem. 2004, 39, 433.
7. Krohnke, F. Synthesis 1976, 1.
8. Potts, K. T.; Cipullo, M. J.; Ralli, P.; Theodoridis, G. J. Am.Chem. Soc. 1981, 103,
3584.
4-(4-Bromophenyl)-2-(9H-fluoren-2-yl)-indeno[1,2-b]pyridin-5-one (Table 2,
entry 8): yellow solid, mp 250–252 °C (EtOH); IR (KBr): 3086, 2942, 1707,
1572, 1548, 1466, 745, and 730 cmÀ1 1H NMR (300 MHz, CDCl3) d: 8.37 (s, 1H),
;
8.17 (d, J = 8.1 Hz, 1H), 8.02 (d, J = 7.5 Hz, 1H), 7.88 (d, J = 7.8 Hz, 1H), 7.85 (d,
J = 7.5 Hz, 1H), 7.84–7.51 (m, 8H), 7.46–7.33 (m, 3H), 4.00 (s, 2H); 13C NMR
(75 MHz, CDCl3) d: 191.0, 166.6, 161.5, 148.1, 144.1, 143.9, 143.0, 141.0, 137.2,
136.6, 135.5, 134.9, 134.4, 131.5, 131.1, 130.7, 127.5, 127.0, 126.4, 125.2, 124.1,
123.7, 122.3, 121.0, 120.5, 120.5, 120.2, 37.0; Anal. Calcd for C31H18BrNO: C,
74.41; H, 3.63; N, 2.80. Found: C, 74.30; H, 3.72; N, 2.82.
9. Kobayashi, T.; Kakiuchi, H.; Kato, H. Bull. Chem. Soc. Jpn. 1991, 64, 392.
10. Palacios, F.; De Retana, A. M. O.; Oyarzabal, J. Tetrahedron Lett. 1996, 37, 4577.
11. Tu, S.; Li, T.; Shi, F.; Fang, F.; Zhu, S.; Wei, X.; Zong, Z. Chem. Lett. 2005, 34, 732.
12. Adib, M.; Tahermansouri, H.; Koloogani, S. A.; Mohammadiand, B.; Bijanzadeh,
H. R. Tetrahedron Lett. 2006, 47, 5957.
13. (a) Tamami, B.; Yeganeh, H. Polymer 2001, 42, 415; (b) Li, L.; Kikuchi, R.;
Kakimoto, M.; Jikei, M.; Takahashi, A. High Perform. Polym. 2005, 17, 135.
14. Smith, C. B.; Raston, C. L.; Sobolev, A. N. Green Chem. 2005, 7, 650.
15. Winter, A.; van den Berg, A. M. J.; Hoogenboom, R.; Kickelbickand, G.; Schubert,
U. S. Synthesis 2006, 17, 2873.
16. Cave, G. W. V.; Raston, C. L. Tetrahedron Lett. 2005, 46, 2361.
17. Smith, N. M.; Raston, C. L.; Smith, C. B.; Sobolev, A. N. Green Chem. 2007, 9,
1185.
18. (a) Shujiang, T.; Runhong, J.; Bo, J.; Junyong, Z.; Yan, Z.; Changsheng, Y.; Shunjun,
J. Tetrahedron 2006, 63, 381; (b) Shujiang, T.; Runhong, J.; Bo, J.; Junyong, Z.; Yan,
Z. Tetrahedron Lett. 2007, 48, 1369; (c) Shujiang, T.; Bo, J.; Changsheng, Y.; Hong,
J.; Junyong, Z.; Runhong, J.; Yan, Z. Synthesis, 2007, 9, 1366.
4-(4-Chlorophenyl)-2,6-bis-(9H-fluoren-2-yl)-pyridine (Table 3, entry 1): white
solid, mp 248 °C (EtOH); IR (KBr): 3037, 2900, 2369, 1600, 1538, 1490, 1406,
1090, 828, and 738 cmÀ1 1H NMR (300 MHz, CDCl3) d: 8.41 (s, 2H), 8.21 (d,
;
J = 7.9 Hz, 2H), 7.94–7.80 (m, 6H), 7.70 (d, J = 8.9 Hz, 2H), 7.59 (d, J = 7.1 Hz,
2H), 7.50 (d, J = 8.3 Hz, 2H), 7.41 (d, J = 7.1 Hz, 2H), 7.34 (t, J = 7.1 Hz, 2H), 4.02
(s, 4H); 13C NMR (75 MHz, CDCl3) d: 157.9, 148.9, 143.9, 143.8, 142.8, 141.3,
138.1, 137.6, 135.2, 129.3, 128.5, 127.0, 126.9, 126.0, 125.1, 123.8, 120.2, 120.0,
116.6, 37.1; Anal. Calcd for C37H24ClN: C, 85.78; H, 4.67; N, 2.70. Found: C,
85.61; H, 4.82; N, 2.72.