November 2012
An Efficient Synthesis of New 5‐(1‐Aryl‐1H‐pyrazole‐4‐yl)‐1H‐tetrazoles from
1‐Aryl‐1H‐pyrazole‐4‐carbonitriles via [3 + 2] Cycloaddition Reaction
1427
and 8.91 (1H, s); 13C‐NMR (75 MHz, DMSO) δ 108.6, 119.7, 128.5,
130.2, 130.7, 131.5, 133.1, 137.0, 138.7, and 149.4. Anal. Calcd. for
C10H6N6Cl2 (281.11): C, 42.73; H, 2.15; N, 29.90. Found: C, 42.66;
H, 2.20; N, 29.98.
5‐[1‐(3′,4′‐Dichlorophenyl)‐1H‐pyrazole‐4‐yl)]‐1H‐tetrazole
(4f). Yield 80%; mp 243–245°C; IR (KBr): 3141 (NH), 1637
(C═N, tetrazole); 1H‐NMR (300 MHz, DMSO) δ 7.92 (1H, d, J =
9.0 Hz), 8.07 (1H, dd, J = 9.0;2.7 Hz), 8.37 (1H, d, J = 2.7 Hz),
8.46 (1H, s), and 9.38 (1H, s); 13C‐NMR (75 MHz, DMSO) δ
108.6, 119.9, 128.0, 129.2, 130.9, 132.6, 132.9, 135.1, 138.7, and
149.3. Anal. Calcd. for C10H6N6Cl2 (281.11): C, 42.73; H, 2.15;
N, 29.90. Found: C, 42.68; H, 2.21; N, 29.95.
5‐[1‐(3′,5′‐Dichlorophenyl)‐1H‐pyrazole‐4‐yl)]‐1H‐tetrazole
(4g). Yield 85%; mp 258–260°C; IR (KBr): 3100 (NH), 1639
(C═N, tetrazole); 1H‐NMR (300 MHz, DMSO) δ 7.69 (1H, d, J =
2.1 Hz), 8.18 (2H, d, J = 2.1 Hz), 8.37 (1H, s), and 9.30 (1H, s);
13C‐NMR (75 MHz, DMSO) δ 108.5, 119.8, 127.9, 128.4, 130.1,
131.5, 131.0, 134.3, 137.6, and 149.5. Anal. Calcd. for
C10H6N6Cl2 (281.11): C, 42.73; H, 2.15; N, 29.90. Found: C,
42.69; H, 2.10; N, 29.98.
Acknowledgments. The authors thank the Fundação de Amparo
à Pesquisa do Estado do Rio de Janeiro (FAPERJ), Conselho
Nacional de Desenvolvimento Científico e Tecnológico (CNPq),
Coordenação de Aperfeiçoamento de Pessoal Docente (CAPES)
and Universidade Federal Fluminense (PROPP‐UFF) for
fellowships and financial support.
REFERENCES AND NOTES
[1] Katritzky, A. R. Chem Rev 2004, 104, 2125.
[2] Gupta, R. R.; Khan, M. T. H. Topics Heterocyclic Chemistry:
Bioactive Heterocycles IV; Springer: Berlin, 2007; Vol. 10, p 1.
[3] Bekhit, A. A.; Ashour, H. M. A.; Ghany, Y. S. A.; Bekhit, A.
E. A.; Baraka, A. Eur J Med Chem 2008, 43, 456.
[4] Kees, K. L.; Fitzgerald, J. J.; Steiner, K. E.; Mattes, J. F.;
Mihan, B.; Tosi, T.; Mondoro, D.; McCaleb, M. L. J Med Chem 1996,
39, 3920.
[5] Kotagiri, V. K.; Suthrapu, S.; Reddy, J. M.; Rao, C. P.;
Bollugoddu, V.; Bhattacharya, A.; Bandichhor, R. Org Process Res Dev
2007, 11, 910.
[6] Fancelli, D.; Moll, J.; Varasi, M.; Bravo, R.; Artico, R.; Berta,
D.; Bindi, S.; Cameron, A.; Candiani, I.; Cappella, P.; Carpinelli, P.;
Croci, W.; Forte, B.; Giorgini, M. L.; Klapwijk, J.; Marsiglio, A.; Pesenti,
E.; Rocchetti, M.; Roletto, F.; Severino, D.; Soncini, C.; Storici, P.;
Tonani, R.; Zugnoni, P.; Vianello, P. J Med Chem 2006, 49, 7247.
[7] Bavetsias, V.; Marriott, J. H.; Melin, C.; Kimbell, R.; Matusiak,
Z. S.; Boyle, F. T.; Jackman, A. L. J Med Chem 2000, 43, 1910.
[8] Barreca, M. L.; De Luca, L.; Iraci, N.; Chimirri, A. J Med
Chem 2006, 49, 3994.
[9] Walker, M. A.; Johnson, T.; Ma, Z.; Banville, J.; Remillard,
R.; Kim, O.; Zhang, Y.; Staab, A.; Wong, H.; Torri, A.; Samanta, H.;
Lin, Z.; Deminie, C.; Terry, B.; Krystal, M.; Meanwell, N. Bioorg Med
Chem Lett 2006, 16, 2920.
5‐[1‐(3′‐Bromophenyl)‐1H‐pyrazole‐4‐yl)]‐1H‐tetrazole (4h).
Yield 83%; mp 255–256°C; IR (KBr): 3120 (NH), 1639 (C═N,
tetrazole); 1H‐NMR (300 MHz, DMSO) δ 7.63 (1H, t, J = 8.1 Hz),
7.71 (1H, d, J = 8.1 Hz), 8.10 (1H, d, J = 8.1 Hz), 8.31 (1H, t,
J = 2.1 Hz), 8.43 (1H, s), and 9.37 (1H, s); 13C‐NMR (75
MHz, DMSO) δ 108.8, 118.0, 121.7, 122.3, 128.2, 130.0,
131.8, 140.2, 140.3, and 149.4. Anal. Calcd. for C10H7N6Br
(291.11): C, 41.26; H, 2.42; N, 28.87. Found: C, 41.13; H,
2.31; N, 29.01.
5‐[1‐(4′‐Bromophenyl)‐1H‐pyrazole‐4‐yl)]‐1H‐tetrazole, (4i).
Yield 69%; mp 249–250°C; IR (KBr): 3111 (NH), 1632 (C═N,
tetrazole); 1H‐NMR (300 MHz, DMSO) δ 7.86 (2H, d, J = 9.0 Hz),
8.05 (2H, d, J = 9.0 Hz), 8.42 (1H, s), and 9.23 (1H, s); 13C‐NMR
(75 MHz, DMSO) δ 109.8, 120.0, 121.8, 128.3, 133.2, 138.6,
140.5, and 150.0. Anal. Calcd. for C10H7N6Br (291.11): C, 41.26;
H, 2.42; N, 28.87. Found: C, 41.12; H, 2.33; N, 28.98.
5‐[1‐(2′‐Fluorophenyl)‐1H‐pyrazole‐4‐yl)]‐1H‐tetrazole (4j).
Yield 64%; mp 194–195°C; IR (KBr): 3101 (NH), 1634
(C═N, tetrazole); 1H‐NMR (300 MHz, DMSO) δ 7.50–7.56
(1H, m), 7.61–7.68 (2H, m), 7.99 (1H, t, J = 8.1 Hz), 8.47
(1H, s), and 8.96 (1H, d, J = 2.4 Hz); 13C‐NMR (75 MHz,
DMSO) δ 108.6, 117.8, 125.8, 126.5, 127.7, 127.8, 130.2,
131.8, 140.0, and 149.7. Anal. Calcd. for C10H7N6F
(230.21): C, 52.18; H, 3.06; N, 36.51. Found: C, 52.13; H,
2.99; N, 36.60.
5‐[1‐(4′‐Fluorophenyl)‐1H‐pyrazole‐4‐yl)]‐1H‐tetrazole (4k).
Yield 82%; mp 258–259°C; IR (KBr): 3136 (NH), 1635 (C═N,
tetrazole); 1H‐NMR (300 MHz, DMSO) δ 7.52 (2H, t, J =8.7 Hz),
8.09 (2H, dd, J = 9.3;4.8 Hz), 8.40 (1H, s), and 9.25 (1H, s);
13C‐NMR (75 MHz, DMSO) δ 108.6, 117.4, 121.5, 128.0,
135.7, 135.8, 139.8, and 149.3. Anal. Calcd. for C10H7N6F
(230.21): C, 52.18; H, 3.06; N, 36.51. Found: C, 52.10; H,
3.01; N, 36.58.
[10] Bekhit, A. A.; Ashour, H. M. A.; Ghany, Y. S. A.; Bekhit, A.
E. A.; Baraka, A. Eur J Med Chem 2008, 43, 456.
[11] Aly, A. A. Chin J Chem 2005, 83, 5.
[12] Chohan, Z. H.; Supuran, C. T.; Scozzafava, A. J. Enzyme
Inhib Med Chem 2004, 19, 79.
[13] Yet, L. Comprehensive Heterocyclic Chemistry III: Pyrazoles;
Elsevier: USA, 2008; p 1.
[14] Elguero, J. Comprehensive Heterocyclic Chemistry: Pyrazoles
and their Benzo Derivatives; Elsevier: USA; 1984; p 167.
[15] Borges, J. C.; Oliveira, C. D.; Pinheiro, L. C. S.; Marra, R. K.
F.; Khan, M. A.; Wardell, J. L.; Wardell, S. M. S. V.; Bernardino, A. M.
R. J Braz Chem Soc 2007, 18, 1571.
[16] Stanovnik, B.; Svete, J. Science of Synthesis; Thieme:
Stuttgart, 2002; Vol. 12, p 15.
[17] Stanovnik, B.; Svete, J. Chem Rev 2004, 104, 2433.
[18] Ostrovskii, V. A.; Koldobskii, G. I.; Trifonov, R. E. Compre-
hensive Heterocyclic Chemistry III: Tetrazoles; Elsevier: USA, 2008;
p 257.
[19] Santos, M. S.; Gomes, A. O.; Bernardino, A. M. R.; Souza, M.
C.; Khan, M. A.; Brito, M. A.; Castro, H. C.; Abreu, P. A.; Rodrigues, C.
R.; Léo, R. M. M.; Leon, L. L.; Canto‐Cavalheiro, M. M. J Braz Chem
Soc 2011, 22, 352.
[20] Charret, K. S.; Rodrigues, R. F.; Bernardino, A. M. R.; Gomes,
A. O.; Carvalho, A. V.; Canto‐Cavalheiro, M. M.; Leon, L. L.; Amaral, V.
F. Am J Trop Med Hyg 2009, 80, 568.
5‐[1‐(4′‐Methoxyphenyl)‐1H‐pyrazole‐4‐yl)]‐1H‐tetrazole
(4l). Yield 69%;mp 229–231°C; IR (KBr): 3121 (NH), 1634
(C═N, tetrazole); H‐NMR (300 MHz, DMSO) δ 3.93 (3H, s),
7.22 (2H, d, J = 9.0 Hz), 7.94 (2H, d, J = 9.0 Hz), 8.36 (1H,
s), and 9.14 (1H, s); 13C‐NMR (75 MHz, DMSO) δ 55.8,
108.2, 114.5, 121.8, 127.7, 132.7, 139.3, 149.5, and 158.1.
Anal. Calcd. for C11H10N6O (242.24): C, 54.54; H, 4.16; N,
34.69. Found: C, 54.35; H, 4.25; N, 34.51.
[21] Pinheiro, L. C. S.; Abreu, P. A; Afonso, I. F.; Leal, B.; Corrêa,
L. C. D.; Borges, J. C; Marques, I. P.; Lourenço, A. L.; Sathler, P.; Santos,
A. L.; Medeiros, C. A.; Cabral, L. M.; Júnior, M. L. O.; Romeiro, G. A.;
Ferreira, V. F.; Rodrigues, C. R.; Castro, H. C.; Bernardino, A. M. R. Curr
Microbiol 2008, 57, 463.
[22] Bernardino, A. M. R.; Castro, H. C.; Frugulhetti, I. C. P. P.;
Loureiro, N. I. V.; Azevedo, A. R.; Pinheiro, L. C. S.; Souza, T. M. L.;
Giongo, V.; Passamani, F.; Magalhães, U. O.; Albuquerque, M. G.;
Cabral, L. M.; Rodrigues, C. R. Bioorg Med Chem 2008, 16, 313.
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Journal of Heterocyclic Chemistry
DOI 10.1002/jhet