Abstract
Depending on the reaction conditions, two alternative cyclizations are possible for [3 + 3] cyclocondensation of pyrazolone derivative 1a and ethyl cyanoacetate of type pyrano [2,3-c] pyrazol-6(1H)-one 2 and pyrano [2,3-c] pyrazol-4(1H)-one 3. Keeping of enaminic system 3 and benzylidene malononitrile in the presence of catalytic amount of trimethylamine resulted in pyridine cyclization affording pyrazolopyranopyridine derivative 4, not 5. The pyrazolone derivative 6a was obtained as a result of the acid-mediated addition reaction between compound 1a, urea and/or ammonium thiocyanate. In addition, the bispyrazolone of type 6b was obtained from the condensation reaction of urea and pyrazolone derivative. The spiro compound 7 was obtained from the double-addition reaction of pyrazolone to cinnamoyl isothiocyanate. A one-pot three-component condensation of a 3-hydroxybenzaldehyde, pyrazolone 1a, urea and/or thiourea under Biginelli conditions resulted in tetrahydropyrazolo pyrimidine derivatives 8a and 8b, respectively. The acid-mediated reaction of benzaldehyde and pyrazolone derivative 1a in the presence of Ac2O yielded styrylpyrazole derivative 9. The polyfunctionalized product 9 reacted with hydrazine to furnish pyrazolotriazoloe of type 10. Treatment of styrylpyrazole derivative 9 with aniline furnished the aniline derivative 11 and none of the expected polyheterocyclic derivative 12 was obtained. Compound 9 undergoes pyridine cyclization to produce 13 under the effect of urea. N-phenyl pyrazolone converted into pyrano-dipyrazolone derivative 14. Pyran of type 14 underwent a ring transformation upon treatment with urea and/or thiourea to give the same dipyrazolo pyrimidine derivative 15. The newly synthesized compounds were characterized by FT-IR, 1H-NMR, 13C-NMR, ESI/LC-MS and elemental analysis.
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A.A. Bekhit, H.M. Ashour, Y.S.A. Ghany, A.E.-D.A. Bekhit, A. Baraka, Eur. J. Med. Chem. 43(3), 456–463 (2008)
J. Frigola, A. Colombo, J. Pares, L. Martinez, R. Sagarra, R. Roser, Eur. J. Med. Chem. 24(4), 435–445 (1989)
M. Abdel-Aziz, G.E.-D.A. Abuo-Rahma, A.A. Hassan, Eur. J. Med. Chem. 44(9), 3480–3487 (2009)
D. Castagnolo, F. Manetti, M. Radi, B. Bechi, M. Pagano, A. De Logu, R. Meleddu, M. Saddi, M. Botta, Bioorg. Med. Chem. 17(15), 5716–5721 (2009)
O.M. Ahmed, M.A. Mohamed, R.R. Ahmed, S.A. Ahmed, Eur. J. Med. Chem. 44(9), 3519–3523 (2009)
A.A. Bekhit, T. Abdel-Aziem, Bioorg. Med. Chem. 12(8), 1935–1945 (2004)
S. Bondock, R. Rabie, H.A. Etman, A.A. Fadda, Eur. J. Med. Chem. 43(10), 2122–2129 (2008)
L.-C. Chou, L.-J. Huang, J.-S. Yang, F.-Y. Lee, C.-M. Teng, S.-C. Kuo, Bioorg. Med. Chem. 15(4), 1732–1740 (2007)
G. Daidone, B. Maggio, D. Raffa, S. Plescia, D. Schillaci, M.V. Raimondi, Il Farmaco 59(5), 413–417 (2004)
F. Manetti, C. Brullo, M. Magnani, F. Mosci, B. Chelli, E. Crespan, S. Schenone, A. Naldini, O. Bruno, M.L. Trincavelli, J. Med. Chem. 51(5), 1252–1259 (2008)
P. Manojkumar, T. Ravi, S. Gopalakrishnan, Eur. J. Med. Chem. 44(11), 4690–4694 (2009)
M. Barceló, E. Ravina, C.F. Masaguer, E. Domínguez, F.M. Areias, J. Brea, M.I. Loza, Bioorg. Med. Chem. Lett. 17(17), 4873–4877 (2007)
A.E. Cho, V. Guallar, B.J. Berne, R. Friesner, J. Comput. Chem. 26(9), 915–931 (2005)
P. Pospisil, G. Folkers, J. Pharm. Sci. 29, 81–92 (2004)
M.F. Brana, A. Gradillas, A.G. Ovalles, B. López, N. Acero, F. Llinares, D.M. Mingarro, Bioorg. Med. Chem. 14(1), 9–16 (2006)
S.A. El-Hawash, E.-S.A. Badawey, I.M. El-Ashmawey, Eur. J. Med. Chem. 41(2), 155–165 (2006)
W. Hamama, Synth. Commun. 31(9), 1335–1345 (2001)
Y. Li, H.-Q. Zhang, J. Liu, X.-P. Yang, Z.-J. Liu, J. Agric. Food Chem. 54(10), 3636–3640 (2006)
A.O. Zoss, G. Hennion, J. Am. Chem. Soc. 63(4), 1151–1153 (1941)
P.N. Dube, S.S. Bule, Y.V. Ushir, M.R. Kumbhare, P.R. Dighe, Med. Chem. Res. 24(3), 1070–1076 (2015)
H.M. Al-Matar, K.D. Khalil, A.Y. Adam, M.H. Elnagdi, Molecules 15, 6619–6629 (2010)
F. Bigi, S. Carloni, B. Frullanti, R. Maggi, G. Sartori, Tetrahedron Lett. 40(17), 3465–3468 (1999)
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Shehab, W.S., Assy, M.G., Moustafa, H.Y. et al. Cyclization of pyrazolones: novel synthesis of pyrano, pyrido, pyrimido and spiropyrazole derivatives. J IRAN CHEM SOC 15, 2349–2355 (2018). https://doi.org/10.1007/s13738-018-1423-y
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DOI: https://doi.org/10.1007/s13738-018-1423-y