82 JOURNAL OF CHEMICAL RESEARCH 2011
2
3
4
5
T. Narender, Shweta and S. Gupta, Bioorg. Med. Chem. Lett., 2009, 14,
3913.
J.C.A. Tanaka, C.C. da Silva, I.C.P. Ferreira, G.M.C. Machado, L.L. Leon
and A.J.B. de Oliveira, Phytomedicine, 2007, 14, 377.
V. Lakshmi, K. Pandey, A. Kapil, N. Singh, M. Samant and A. Dube,
Phytomedicine, 2007, 14, 36.
E.C. Torres-Santos, D. Lopes, R. Rodrigues Oliveira, J.P.P. Carauta,
C.A. Bandeira Falcao, M.A.C. Kaplan, and B. Rossi-Bergmann,
Phytomedicine, 2004, 11, 114.
(CDCl3) δ: 9.24 (s, 1H, H-5), 7.20–6.40 (m, 7H, aromatic), 5.26
(s, 1H, H-12), 4.48 (q, 2H, CH2, J = 7.5 Hz), 3.28 (q, 4H, 2CH2, J =
7.5 Hz), 1.40 (t, 3H, CH3, J = 7.5 Hz), 1.11 (t, 6H, 2CH3, J = 7.5 Hz);
13C NMR (125 MHz) (DMSO-d6) δ: 158.17 (C-6b), 155.49 (CO),
154.90 (CO ester), 150.67 (C-6a), 149.76 (C-7a), 148.37 (C-9), 142.43
(C-5), 129.95 (C-11), 110.08 (C-11a), 107.84 (C-10), 101.16 (C-8),
99.04 (C-12a), 65.60 (CH2 ester), 44.50 (CH2), 38.44 (C-12), 14.23
(CH3 ester), 12.48 (CH3), 138.83, 132.97, 129.77, 128.74 (aromatic);
MS m/z (%): 495 [M++2], (30.24), 493 [M]+, (100), 480 (35), 478
(96), 452 (1), 450 (3), 408 (17), 406 (43), 380 (6), 378 (14), 266 (43),
238 (20), 182 (15), 100 (5), 68 (5); Anal. Calcd for C25H24ClN5O4:
C, 60.79; H, 4.90; N, 14.18. Found: C, 60.80; H, 4.95; N, 14.20%.
Reaction of 3b with triethyl orthoformate: A mixture of β-
enaminoester 3b (0.01 mmol), triethyl orthoformate (0.01 mmol) and
Ac2O (30 mL) was refluxed for 3 h. The solvent was removed under
reduced pressure and the separated solid was recrystallised from
benzene to give 12 and the compound 13 was separated from the fil-
trate of the reaction and recrystallised from ethanol. The physical and
spectra data of the compounds 12 and 13 are as follows.
Ethyl 4-(4-chlorophenyl)-7-(diethylamino)-2-formylamino-4H-chro-
mene-3-carboxylate (12): Colourless needles; m.p. 175–176 °C; 35%;
IR (KBr) υ (cm−1): 3251, 3217 (NH), 3087, 3038, 3022, 2972, 2926,
(CH stretching), 1700, 1677 (CO); 1H NMR (500 MHz) (CDCl3)
δ: 10.85 (d, 1H, CH, J = 10.0 Hz), 9.14 (d, 1H, NH, J = 10.0 Hz),
7.19–6.22 (m,7H, aromatic), 4.79 (s, 1H, H-4), 4.03 (q, 2H, CH2,
J = 7.5 Hz), 3.24 (q, 4H, 2CH2, J = 7.1 Hz), 1.09 (t, 3H, CH3, J =
7.5 Hz),1.07 (t, 6H, 2CH3, J = 7.1 Hz); 13C NMR (125 MHz) (CDCl3)
δ: 168.09 (CO ester), 159.80 (CO), 152.89 (C-2), 148. 89 (C-8a),
147.83 (C-7), 129.82 (C-5), 110.37 (C-4a), 109.72 (C-6), 98.01 (C-8),
6 Q.-B. Han, N.-Y. Yang, H.-L. Tian, C.-F. Qiao, J.-Z. Song, D.C. Chang,
S.-L. Chen, K.Q. Luo and H.-X. Xu, Phytochemistry, 2008, 69, 2187.
7
W. Kemnitzer, J. Drewe, S. Jiang, H. Zhang, C. Crogan-Grundy,
D. Labreque, M. bubenick, G. Attardo, R. Denis, S. Lamothe, H. Gourdeau,
B. Tseng, S. Kasibhatla and S. Xiong Cai, J. Med. Chem., 2008, 51, 417.
I.V. Magedov, M. Manpadi, M.A. Ogasawara, A.S. Dhawan, S. Rogelj,
S. van Slambrouk, W.F.A. Steelant, N.M. Evdokimov, P.Y. Uglinskii,
E.M. Elias, E.J. Knee, P. Tongwa, M. Yu. Antipin and A. Kornienko, J.
Med. Chem., 2008, 51, 2561.
8
9
M. Longobardi, A. Bargagna, E. Mariani, P. Schenone, E. Marmo, Il
Farmaco, 1990, 45, 399.
10 C. Banzatti, U. Branzoli, P.P. Lovisolo, P. Melloni, P. Salvadori, Arzneim.
Forsch., 1984, 34, 864.
11 K.V. Sashidhara, A. Kumar, M. Kumar, A. Srivastava and A. Puri, Bioorg.
Med Chem. Lett., 2010, in press.
12 A. Ermili, G. Roma, M. Buonamici, A. Cuttica and M. Galante, Il Farmaco,
1979, 34, 535.
13 C. Bruhlmann, F. Ooms, P. Carrupt, B. Testa, M. Catto, F. Leonetti,
C. Altomare and A. Cartti, J. Med. Chem., 2001, 44, 3195.
14 S.R. Kesten, T.G. Heffner, S.J. Johnson, T.A. Pugsley, J.L. Wright and
D.L. Wise, J. Med. Chem., 1999, 42, 3718.
15 W.P. Smith, L.S. Sollis, D.P. Howes, C.P. Cherry, D.I. Starkey, N.K. Cobley,
J. Med. Chem., 1998, 41, 787.
86.19 (C-3), 60.64 (CH2 ester), 44.40 (CH2), 39.00 (C-4), 14.07 (CH3
16 R.N. Taylor, A. Cleasby, O. Singh, T. Sharzynski, J.A. Wonacott,
W.P. Smith, L.S. Sollis, D.P. Howes, C.P. Cherry, R. Bethell, P. Colman and
J. Varghese, J. Med. Chem., 1998, 41, 798.
13
ester) 12.49 (CH3) 145.57, 132.02, 129.02, 128.48 (aromatic);
C
NMR - DEPT spectrum at 135о CH, CH3 [positive (up)], CH2 (nega-
tive), revealed the following signals at δ 159.80 (CHO ↑), 129.82
(C-5 ↑), 129.02 (CH ↑ aromatic), 128.48 (CH ↑ aromatic), 109.74
(C-6 ↑), 98.01 (C-8 ↑), 60.62 (CH2 ester ↓), 44.40 (CH2 ↓), 39.00
(C-4 ↑), 14.07 (CH3 ester ↑), 12.49 (CH3 ↑). In the DEPT spectrum at
90° only CH signals are positive (up), and showed δ 159.80 (CHO
formyl ↑), 129.82 (C-5 ↑), 129.02 (CH ↑ aromatic), 128.48 (CH ↑
aromatic), 109.74 (C-6 ↑), 98.01 (C-8 ↑), 39.00 (C-4 ↑). In the DEPT
spectrum at 45° (CH, CH2 and CH3 positive) revealed signals at
δ 159.80 (CHO formyl ↑), 129.82 (C-5 ↑), 129.02 (CH ↑ aromatic),
128.48 (CH ↑ aromatic), 109.74 (C-6 ↑), 98.01 (C-8 ↑), 60.62
(CH2 ester ↑), 44.40 (CH2 ↑), 39.00 (C-4 ↑), 14.07 (CH3 ester ↑), 12.49
(CH3 ↑); MS m/z (%): 430 [M++2] (9), 428 [M]+, (31.5), 317 (17), 289
(97), 243 (100), 199 (19), 138 (35.5), 77 (56); Anal. Calcd for
C23H25ClN2O4: C, 64.41; H, 5.88; N, 6.53. Found: C, 64.30; H, 5.90;
N, 6.55%.
17 J.-F. Cheng, A. Ishikawa,Y. Ono, T. Arrhenius and A. Nadzan, Bioorg. Med
Chem. Lett., 2003, 13, 3647.
18 V.P. Sharma, Asian J. Chem., 2004, 16, 1966; Chem. Abstr., 142, 298061
19 V.P. Sharma, Indian J. Heterocycl. Chem., 2004, 14, 35; Chem. Abstr., 142,
373785.
20 P. Gebhardt, K. Dornberger, F.A. Gollmick, U. Gräfe, A. Härtl, H. Görls,
B. Schlegel and C. Hertweck Bioorg. Med Chem. Lett., 2007, 17, 2558.
21 G. Melagraki, A. Afantitis, O. Igglessi-Markopoulou, A. Detsi, M. Koufaki,
C. Kontogiorgis, Di. J. Hadjipavlou-Litina, Europ. J. Med. Chem., 2009,
44, 3020.
22 T. Symeonidis, K.C. Fylaktakidou, D.J. Hadjipavlou-Litina and K.E.
Litinas, Europ. J. Med. Chem., 2009, 44, 5012.
23 S. Begum, B. Saxena, Ma. Goyal, R. Ranjan, V.B. Joshi, Ch V. Rao,
S. Krishnamurthy and M. Sahai, Fitoterapia, 2010, 81, 178.
24 J.J. Anil, R.A. Kumar, S.A. Rasheed, S.P. Chandrika, A. Chandrasekhar,
S. Baby and A. Subramoniam, J. Ethnopharm., 2010, 130, 267.
25 K. Hiramoto, A. Nasuhara, K. Michiloshi, T. Kato and K. Kikugawa,
Mutat. Res., 1997, 395, 47.
26 A.G. Martinez and L.J. Marco, Bioorg. Med. Chem. Lett., 1997, 7, 3165.
27 L.L. Andreani and E. Lapi, Bull. Chim. Farm., 1960, 99, 583.
28 Y.L. Zhang, B.Z. Chen, K.Q. Zheng, M.L. Xu and X.H. Lei, Yao Xue Bao,
1982, 17, 17; Chem. Abstr., 1982, 96, 135383e.
Ethyl 2-acetylamino-4-(4-chlorophenyl)-7-(diethylamino)-4H-chro-
mene-3-carboxylate (13): Yellow needles, m.p. 170–171 °C; 83%; IR
(KBr) υ (cm−1): 3300, 3217 (NH), 3088, 3021, 2972, 2927, (CH
stretching), 1698, 1677 (CO); 1H NMR (500 MHz) (CDCl3) δ: 11.02
(bs, 1H, NH), 7.20–6.21 (m,7H, aromatic), 4.79 (s, 1H, H-4), 4.04
(q, 2H, CH2, J =7.5 Hz), 3.25 (q, 4H, 2CH2, J = 7.1 Hz), 1.60 (s, 3H,
COCH3), 1.09 (t, 3H, CH3, J =7.5 Hz),1.08 (t, 6H, 2CH3, J = 7.1 Hz);
13C NMR (125 MHz) (CDCl3) δ: 168.09 (CO ester), 159.80 (CO),
153.15 (C-2), 148. 89 (C-8a), 147.83 (C-7), 129.82 (C-5), 110.38
(C-4a), 109.72 (C-6), 98.02 (C-8), 86.50 (C-3), 60.73 (CH2 ester),
44.40 (CH2), 39.00 (C-4), 29.71 (CH3 acetyl),14.06 (CH3 ester), 12.49
(CH3) 145.57, 132.02, 129.01, 128.48 (aromatic) ; MS m/z (%):
444 [M++2], (13), 442 [M]+, (32.5), 331 (58.), 289 (100), 243 (56),
199 (16), 150 (19), 115 (13), 77 (20). Anal. Calcd for C24H27ClN2O4:
C, 65.08; H, 6.14; N, 6.32. Found: C, 65.15; H, 6.20; N, 6.45%.
Reaction of 12 with hydrazine derivatives: A mixture of 12
(0.01 mmol), hydrazine hydrate (0.01 mmol) in EtOH was stirring at
room temperature or reflux for 1 h to give β-enaminoester (3b) (m.p.
and mixed m.p.) yield (81%).
29 E.C. Witte, P. Neubert and A. Roesch, Ger. Offen DE., 3427985 (1986);
Chem. Abstr., 1986, 104, 224915f.
30 W.O. Foye, Principi Di Chimica Farmaceutica; Piccin: Padova, Italy,
1991, 416.
31 L. Bonsignore, G. Loy, D. Secci and A. Calignano, Eur. J. Med. Chem.,
1993, 28, 517.
32 A. Gajbhiye, V. Mallareddy and G. Achaiah, Indian J Pharm Sci., 2008, 70,
118.
33 M. Ghate, R.A. Kusanur and M.V. Kulkarni, Eur. J. Med. Chem., 2005, 40,
882.
34 T. El-Sayed Ali and M.A. Ibrahim, J. Braz. Chem. Soc., 2010, 21, 1007.
35 V. Maddi, K.S. Raghu and M.N. Rao, J. Pharm. Sci., 1992, 81, 964.
36 B. Narasimhan, P. Kumar, D. Sharma, Acta Pharm. Sci., 2010, 52, 169.
37 K.M. Amin, M.M. Kamel, M.M. Anwar, M. Khedr and Y.M. Syam, Eur. J.
Med. Chem., 2010, 45, 2117.
38 R.S. Keri, K.M. Hosamani, R.V. Shingalapur and M.H. Hugar, Eur. J. Med.
Received 30 July 2010; accepted 16 December 2010
Paper 1000283 doi: 10.3184/174751911X12964930076728
Published online: 10 February 2011
Chem., 2010, 45, 2597.
39 G. Bianchi and A. Tava, Agric. Biol. Chem., 1987, 51, 2001.
40 A.M. El-Agrody, J. Chem. Res. (S), 1994, 280.
41 A.M. El-Agrody, H.A. Emam, M.H. El-Hakim, M.S. Abd El-Latif,
A.H. Fakery, J. Chem. Res. (S), 1997, 320.
42 A.M. El-Agrody, H.A. Emam, M.H. El-Hakim, M.S. Abd El-Latif,
A.H. Fakery, J. Chem. Res. (M), 1997, 2039.
References
1
D.B. daSilva, E.C.O. Tulli, G.C.G. Militao, L.V. Costa-Lotufo, C. Pessoa,
M.O. deMoraes, S. Albuquerque and J.M. deSiqueira, Phytomedicine,
2009,70, 590.
43 A.H. Bedair, N.A. El-Hady, M.S. Abd El-Latif, A.H. Fakery and A.M.
El-Agrody, Il Farmaco, 2000, 55, 708.