Month 2013
A Facile One Pot Synthesis of New Tricyclic Coumarins from Single Synthon
1
(KBr) cmÀ1: 3429, 1733, 1618, 1596; H-NMR (CDCl3 + TFA)
δ 2.54 (3H, s), 6.36 (1H, s), 7.11 (1H, d, J = 9.0 Hz), 7.73
(1H, d, J = 9.0 Hz), 9.50 (1H, s); 13C NMR (CDCl3 + TFA)
δ 161.12, 152.56, 143.17, 142.12, 128.19, 123.23, 119.24,
115.29, 112.50, 110.34, 18.56; ESI-MS m/z 201 (M+H)
(27%), m/z 173 (M+H) (100%). Anal. Calcd. for C11H8N2O2:
C, 65.99; H, 4.03; N, 13.99%; Found: C, 65.79; H, 3.88;
N, 12.87%.
Acknowledgments. We thank the University Sophisticated
Instrument Center, KUD for IR, 1H-NMR, and 13C-NMR,
respectively. We also thank SAIF-CDRI Lucknow for ESI-MS
Data. R G. Kalkhambkar is grateful to Karnatak University and
Karnatak Science College Dharwad for the University Research
Studentship. We thank the reviewer for nice comments and
valuable suggestions.
Isonicotic acid-[7-hydroxy-4-methyl-2-oxo-2H-chromen-8-
ylmethylene]-hydrazide (11).
A mixture of 8-formyl-7-
REFERENCES AND NOTES
hydroxy-4-methyl coumarin (1) (1.2 g, 6 mmol) and isonicotinic
acidhydrazide (0.822 g, 6 mmol) in 20 mL ethanol-acetic acid
mixture (2:1) was refluxed on water bath for 6 h. The reaction
was monitored by TLC, after completion of the reaction the
solvent was removed under reduced pressure; the separated
solid was filtered, washed with excess of cold water, dried, and
crystallized from acetic. Yield: 78%; green crystalline solid
(acetic acid); mp: 290À292°C; Rf 0.60 (benzene); IR (KBr)
cmÀ1: 3454, 3261, 1715, 1674, 1612; 1H NMR (DMSO-d6)
δ 2.48 (3H, s), 6.32 (1H, s), 6.95 (6H, m), 9.10 (1H, s), 11.35
(1H, s), 12.48 (1H, br s); 13C NMR (DMSO-d6) δ 160.93,
160.79, 158.84, 153.35, 152.39, 150.26, 144.40, 138.96,
127.94, 121.19, 113.21, 111.60, 110.56, 113.45, 112.68,
105.18, 18.03; ESI-MS m/z 324 (M+H) (100%); Anal. calc. for
C17H13N3O4: C, 63.15; H, 4.05; N, 13.00%; Found: C, 63.10;
H, 3.90; N, 12.87%.
[1] Part of this work was presented at the 7th Tetrahedron Interna-
tional Symposium, on “Recent Challenges in Organic Chemistry”, held in
Kyoto, Japan, May 23-25, 2006.
[2] Kulkarni, M. V.; Kulkarni, G. M.; Lin, C. H.; Sun, C. M. Curr
Med Chem 2006, 13, 2795.
[3] Khan, I. A.; Kulkarni, M. V.; Sun, C. M. Eur J Med Chem
2005, 40, 1168.
[4] Ghate, M. D.; Kusanur, R. A.; Kulkarni, M. V. Eur J Med
Chem 2005, 40, 882.
[5] Kalkhambkar, R. G.; Kulkarni, G. M.; Kamanavalli, C. M.;
Premkumar, N.; Asdaq, S. M. B.; Sun, C. M. Eur J Med Chem 2008,
43, 2178.
[6] Kalkhambkar, R. G.; Kulkarni, G. M.; Rao, N. R.;
Shivakumar, H. Eur J Med Chem 2007, 42, 1272.
[7] Kalkhambkar, R. G.; Aridoss, G.; Kulkarni, G. M.; Bapset, R. M.;
Mudaraddi, T. Y.; Premkumar, N.; Jeong, Y. T. Monatsh Chem 2011, 142, 305.
[8] Ghate, M. D.; Kulkarni, M. V.; Shobha, R.; Kattimani, S. Y.
Eur J Med Chem 2003, 38, 297.
[9] Finn, G. J.; Creaven, B. S.; Egan, D. A. Cancer Lett 2004, 214, 43.
[10] Hwua, J. R.; Singha, R.; Honga, S. C.; Changa, Y. H.; Dasa,
A. R.; Neyts, C. J. Antiviral Res 2008, 77, 157.
[11] Doucet, L. C.;Dive, G.;Wouters, J. BioorgMedChem2000, 8, 1489.
[12] Kashman, Y.; Gustafson, K. R.; Fuller, W. R.; Cardellina, J.
H.; McMohan, J. B.; Currous, M. J.; Buckheiy, R. W.; Hughes, S. H.;
Cragg, G. M.; Boyd, M. P. J Med Chem 1992, 35, 2735.
[13] Spino, C.; Dodier, M.; Sootheeswaran, S. Bioorg Med Chem
Lett 1988, 8, 3475.
[14] Goddard, J. P.; Reymond, J. L. Trends Biotechnol 2004, 22, 363.
[15] Katerinopoulos, H. E. Curr Pharm Des 2004, 10, 3835.
[16] Knobler, R. M.; Honigsmann, H.; Edelson, R. L. In Psoralen
DNA Photobiology; Gasparro, F. P., Ed.; CRC Press: Boca Raton, FL,
1988; Vol. 2, p 117.
7-Hydroxy-4-methyl-8-[phenyl-hydrazonomethyl]-chromen-
2-one (12).
A mixture of 8-formyl-7-hydroxy-4-methyl
coumarin (1) (1.2 g, 6 mmol) and phenyl hydrazine (0.64 g, 6
mmol) in 20 mL ethanol-acetic acid mixture (2:1) was refluxed on
water bath for 6 h. The reaction was monitored by TLC, after
completion of the reaction the solvent was removed under
reduced pressure, the separated solid was filtered, washed with
excess of cold water, dried and crystallized from acetic acid.
Yield: 77%; pale green crystalline solid (ethanol + dioxan);
mp: 268À270°C; Rf 0.78 (benzene); IR (KBr) cmÀ1: 3461,
3269, 1714, 1597; 1H NMR (DMSO-d6) δ 2.44 (3H, s), 6.28
(1H, s), 6.84 (7H, m), 8.66 (1H, s), 10.98 (1H, s), 12.08 (1H, br
s); 13C NMR (DMSO-d6) δ 159.33, 153.75, 152.77, 151.12,
143.54, 133.53, 129.43, 125.78, 124.90, 119.82, 113.80,
112.82, 111.99, 111.68, 110.62, 106.63, 18.24; Anal. calc. for
C17H14N2O3: C, 69.38; H, 4.79; N, 9.52%; Found: C, 69.41; H,
4.50; N, 9.27%.
[17] Dall'Acqua, F.; Vedaldi, D.; Caffieri, S.; Guiotto, A.; Bordin,
F.; Rodighiero, P. Natl Cancer Inst Monogr 1984, 66, 55.
[18] Chibisova, T. A.; Soloveva, N. P.; Pozhidocva, N. Y. Russ J
Chem 1999, 35, 263.
2-Hydroxy-benzoicacid-[7-hydroxy-4-methyl-2-oxo-2H-
chromen-8-yl-methylene]-hydrazide (13). A mixture of 8-
formyl-7-hydroxy-4-methyl coumarin (1) (1.2 g, 6 mmol) and
salicylic acid hydrazide (0.91 g, 6 mmol) in 20 mL ethanol-acetic
acid mixture (2:1) was refluxed on water bath for 6 h. The
reaction was monitored by TLC, after completion of the
reaction the solvent was removed under reduced pressure; the
separated solid was filtered, washed with excess of cold
water, dried and crystallized from acetic acid. Yield: 74%;
Pale green crystalline solid (DMF); mp: 294À296°C; Rf 0.58
(benzene); IR (KBr) cmÀ1: 3416, 3273, 1713, 1654, 1611;
1H NMR (DMSO-d6) δ 2.47 (3H, s), 6.30 (1H, s), 6.92
(6H, m), 9.16 (1H, s), 11.45 (1H, s), 12.38 (1H, br s), 12.76
(1H, br s); 13C-NMR (DMSO-d6) δ 160.08, 159.19, 153.85,
152.67, 151.12, 144.40, 133.32, 128.39, 125.78, 119.04,
117.33, 116.82, 113.45, 112.68, 111.22, 105.48, 18.26; ESI-
MS m/z 339 (M+H) (100%); Anal. Calc. for C18H14N2O5:
C, 63.90; H, 4.17; N, 8.28%; Found: C, 63.61; H, 4.10;
N, 8.17%.
[19] Gomez, G.; Curtos, J.; Uriate, S. L. Synthesis 2002, 1, 43.
[20] Mulawad, V. V.; Shirodkar, J. M. Ind J Chem 2002, 41B, 1263.
[21] Soman, S. S. Ind J Chem 1999, 38B, 545.
[22] Brito, F. V.; Silva, A. J. M.; Melo, P. A. Bioorg Med Chem
Lett 2001, 11, 283.
[23] Bonsignore, L.; Giuseppe, L. J Het Chem 2000, 35, 117.
[24] Mulawad, V. V.; Mahadakar, B. S. Ind J Chem 1999, 38B, 33.
[25] Tarmura, Y.; Fujita, M. J Het Chem 1998, 19, 289.
[26] Nore, D.; Honkanan, E. J Het Chem 1990, 17, 985.
[27] Furer, G. Prog Med Chem 1994, 20, 85.
[28] Khan, I. A.; Kulkarni, M. V.; Gopal, M.; Shahabudeen, M. S.;
Sun, C. M. Bioorg Med Chem Lett 2005, 15, 3587.
[29] Sanghiv, Y. S.; Larson, S. B.; Revenkar, G. R. Med Chem
1999, 32, 945.
[30] Filton, A. O.; Smalley, R. K. Practical Heterocyclic Chemistry;
Academic Press: London, 1968; p 97.
[31] Duff, J. Chem Soc 1941, 547. DOI: 10.1039/JR9410000547
[32] Kokila, M. K.; Nirmala, K. A.; Kulkarni, M. V.; Shivaprakash,
N. C. Acta Cryst 1992, C48, 1619.
[33] Yuvaraj, H.; Gayathri, D.; Kalkhambkar, R. G.; Kulkarni, G.
M.; Bapset, R. M. Acta Cryst 2011, E67, 323.
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet