Month 2015
Synthesis and Cytotoxic Evaluation of Pyrrole Hetarylazoles Containing
Benzimidazole/Pyrazolone/1,3,4-Oxadiazole Motifs
REFERENCES AND NOTES
Synthesis of 2-pyrrolylmethylene-5-phenyl-1,3,4-oxadiazol-2-
amine (14). 2-Pyrrole carboxaldehyde (10 mmol) and few
[1] Kumar, V.; Kaue, K.; Gupta, G. K.; Sharma, A. K. Eur J Med
Chem 2013, 69, 735.
drops of glacial acetic acid were added to a solution of 13
(10 mmol) in anhydrous ethanol (20 mL) at room
temperature. The reaction mixture was refluxed for 2h
and then cooled at room temperature. The solid formed
was filtered and washed with ether to provide the desired
Schiff base. (14): white solid, yield (74%), mp 203–205°
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1
C; H NMR (DMSO): δ 7.68–7.45 (m, 5H, Ar-H), 8.73
(s, 1H, CH¼N) ppm. IR (KBr): 1713, 1618, 1582, 1391,
1293, 1245, 1023, 694cmꢀ1
.
[7] Khalilullah, H.; Ahsan, M. J.; Hedaitullah, M.; Khan, S.;
Ahmed, B. Mini Rev Med Chem 2012, 12, 789.
Synthesis of N-substituted benzyl pyrrole-1,3,4-oxadiazole
Schiff bases (15a–c): General procedure. To an ice-cooled
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[9] Kharb, R.; Yar, M. S.; Sharma, P. C. Curr Med Chem 2011,
18, 3265.
solution of 14 (10 mmol) in DMF was added NaH (60%
in mineral oil, 11.8mmol), and the mixture was stirred at
0°C for 30min. To the mixture were added 4-substituted
benzyl chlorides (10 mmol) at 0°C and stirred at room
temperature for 8 h. The mixture was acidified with
saturated aqueous solution of NH4Cl and extracted twice
with EtOAc. The organic layers were combined, washed
with brine, dried over anhydrous MgSO4, and
concentrated under vacuum. The residue was purified by
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J. G.; de Athavde-Filho, P. F. Molecules 2012, 17, 10192.
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2013, 13, 1725.
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silica gel column chromatography.
N-((1-(4-Fluorobenzyl)-1H-pyrrol-2-yl)methylene)-5-phenyl-1,
3,4-oxadiazol-2-amine (15a).
Yellow solid (89%), mp
1
165–168°C; H-NMR (CDCl3): δ 5.58 (s, 2H, Ph–CH2),
7.05–7.15 (m, 3H, CH-pyrrole), 6.97–7.82 (m, 9H, Ar-H),
10.77 (s, 1H, CH¼N). Analysis for: С20H15FN4O, Found,
%: С 69.36; Н 4.08; N 16.52. Calc, %: С 69.35; Н 4.37;
N 16.18.
N-((1-(4-nitrobenzyl)-1H-pyrrol-2-yl)methylene)-5-phenyl-1,3,
4-oxadiazol-2-amine (15b). Orange solid (68%), mp 155–
1
158°C; H-NMR (CDCl3): δ 5.85 (s, 2H, Ph–CH2), 6.65–
7.35 (m, 3H, CH-pyr), 7.30–7.90 (m, 9H, Ar-H), 10.85 (s,
1H, –CH¼N). Analysis for: С20H15N5O3, Found, %: С
64.12; Н 4.36; N 18.43. Calc, %: С 64.34; Н 4.05; N 18.76.
[24] Khalil, N. A.; Ahmed, E. M.; Mohamed, K. O.; Nissan, Y. M.;
Zaitone, S. A. Bioorg Med Chem 2014, 22, 2080.
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Noronha, J.; Fernandes, E.; Abel, J.; Veira, S. C. Eur J Med Chem
2010, 45, 2258.
N-((1-(4-isopropylbenzyl)-1H-pyrrol-2-yl)methylene)-5-phenyl-1,
3,4-oxadiazol-2-amine (15c).
Yellow crystal (91%); mp
168–169°C; 1H-NMR (CDCl3): δ 3.83 (s, 3H CH3),
6.81–7.57 (m, 9H, Ar-H), 10.41 (s, 1H, –N¼CH).
Analysis for: С23H22N4O, Found, %: С 74.38; Н 5.41; N
15.06. Calc, %: С 74.57; Н 5.99; N 15.12.
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Khalil, M. Eur J Med Chem 2012, 56, 254.
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Reith, M.; Dutta, A. K. Bioorg Med Chem 2013, 21, 3164.
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H. K. Eur J Med Chem 2013, 62, 410.
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Yang, G.-F. Bioorg Med Chem 2014, 22, 5194.
[31] Wang, X.-Q.; Liu, L. X.; Li, Y.; Sun, C. J.; Chen, W.; Li, L.;
Zhang, H. B.; Yang, X. D. Eur J Med Chem 2013, 62, 111.
Acknowledgments. The authors are grateful to the National
Institute of Health, the National Institute of General Medical
Sciences, the MBRS Program (GM 08111), and the Research
Center at Minority Institutions Grant (RCMI) RR 03020. Also,
much gratitude goes to the FAMU School of Graduate Studies,
Faculty Research Award Program.
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet