2930
M. Curini et al.
LETTER
O
O
OH
O
(7) Typical Reaction Procedure
To the mixture of 1,3-dione (1 mmol) and a-Zr(CH3PO3)1.2
(O3PC6H4SO3H)0.8 (25 mg, ca. 6 mol%) was added
hydrazine derivative (1 mmol) under strirring, under
nitrogen and in neat. The mixture was left to react at 40 °C
(60 °C in the case of 2,4-dinitrophenylhydrazine), and
monitored by TLC. The reaction mixture was diluted with
CH2Cl2, filtered on Buchner funnel, then concentrated under
vacuum. In some entries a chromatography on silica gel was
required in order to purify the pyrazole or tetrahydroindazole
derivatives. The structures of all regioisomers were
determined on the basis of the typical 1H NMR chemical
shifts and NOESY experiments.
5%
95%
PhNHNH2
Ph
N
N
Ph
Selected Experimental Data.
Scheme 2
Methyl 5-Ethyl-3-methyl-1H-pyrazole-1-carboxylate.
Colorless oil. 1H NMR (400 MHz, CDCl3): d = 1.27 (t,
J = 7.5 Hz, 3 H, CH3), 2.28 (s, 3 H, CH3), 2.97 (q, J = 14.8,
7.5 Hz, 2 H, CH2), 4.02 (s, 3 H, OCH3), 6.02 (s, 1 H, H-
pyrazole). 13C NMR (50 MHz, CDCl3): d = 12.4, 13.7, 21.2,
54.2, 108.7, 150.6, 151.3, 152.6. GCMS: m/z = 168, 153,
137, 123, 109, 95.
1-(2,4-Dinitrophenyl)-3-methyl-5-phenyl-1H-pyrazole.
White solid: mp 152–153 °C. 1H NMR (200 MHz, CDCl3):
d = 2.40 (s, 3 H, CH3), 6.43 (s, 1 H, H-pyrazole), 7.18–7.47
(m, 8 H, ArH), 8.38 (dd, J = 9.2, 3.0 Hz, 1 H, PhH), 8.77 (d,
J = 3.0 Hz, 1 H, PhH). 13C NMR (50 MHz, CDCl3): d = 13.6,
109.4, 120.8, 127.1, 128.5 (double), 129.0 (double), 129.2,
129.6, 138.2, 145.0, 143.3, 143.8, 152.7. GCMS: m/z = 324,
294, 232, 219, 190, 105, 89, 77.
Acknowledgment
Financial support from MIUR, National Project ‘Sviluppo di
processi ecocompatibili nella sintesi organica’ and CEMIN (Centro
di Eccellenza Materiali Innovativi Nanostrutturati per applicazioni
chimiche, fisiche e biomediche) is gratefully acknowledged.
References
(1) Kabalka, G. W.; Pagni, R. M. Tetrahedron 1997, 53, 7999;
and references cited therein.
2-(2,4-Dinitrophenyl)-3-methyl-4,5,6,7-tetrahydro-2H-
indazole.
(2) Measurement of the acid strength: 0.5 g of zirconium
sulfophenyl phosphonate, previously dried at 160 °C for 12
h, were dispersed in 3 mL of benzene in a test tube. Then, 0.2
mg of the chosen Hammet indicator were added to the
dispersion held under stirring. The colour changes were
evaluated after 30 min. For more detailed information see:
(a) Umansky, B.; Engelhardt, J.; Hall, W. K. J. Catal. 1991,
127, 128. (b) Hammett, L. P.; Deyrup, A. J. J. Am. Chem.
Soc. 1932, 54, 2721.
Pale yellow solid: mp 156–158 °C. 1H NMR (400 MHz,
CDCl3): d = 1.82 (m, 4 H), 2.20 (s, 3 H, CH3), 2.52 (m, 2 H),
2.69 (m, 2 H), 7.71 (d, J = 8.8 Hz, 1 H, ArH), 8.53 (dd,
J = 8.8, 2.5 Hz, 1 H, ArH), 8.80 (d, J = 2.5 Hz, 1 H, ArH).
13C NMR (50 MHz, CDCl3): d = 10.2, 20.4, 23.0 (double),
23.3, 117.7, 121.0, 127.2, 128.8, 135.7, 138.3, 145.2, 145.6,
153.5. GCMS: m/z = 302, 285, 255, 209, 181, 135, 115.
(8) Wang, Z. X.; Qin, H. L. Green Chem. 2004, 6, 90.
(9) Zelenin, K. N.; Alekseyev, V. V.; Tygysheva, A. R.;
Yakimovitch, S. I. Tetrahedron 1995, 51, 11251.
(10) (a) Alberola, A.; Calvo, L.; Ortega, A. G.; Sádaba, M. L.;
Sañudo, M. C.; Granda, S. G.; Rodríguez, E. G.
(3) Curini, M.; Rosati, O.; Costantino, U. Curr. Org. Chem.
2004, 8, 591.
(4) (a) Kizer, D. E.; Miller, R. B.; Kurth, M. J. Tetrahedron Lett.
1999, 40, 3535. (b) Kees, K. L.; Fitgzerald, S. J.; Steiner, K.
E.; Mattes, J. F.; Mihan, B.; Tosi, T.; Montoro, D.; McCaleb,
M. L. J. Med. Chem. 1996, 39, 3920. (c) Huang, Y. R.;
Katzenellenbogen, J. A. Org. Lett. 2000, 2, 2833. (d) Lyga,
J. W.; Patera, R. M.; Plummer, M. J.; Halling, B. P.; Yukas,
D. A. Pest. Sci. 1994, 42, 29.
(5) (a) Elguero, J. In Comprehensive Heterocyclic Chemistry,
Vol. 3; Katrizky, A. R.; Rees, C. W.; Scriven, E. F. V., Eds.;
Pergamon Press: Oxford, 1996, 1–75. (b) Lee, K. Y.; Kim,
J. M.; Kim, J. N. Tetrahedron Lett. 2003, 44, 6737; and
references cited therein.
Heterocycles 1999, 51, 2675. (b) Kashima, C.; Tsuruoka,
S.; Mizuhara, S. Tetrahedron 1998, 54, 14679.
(11) Oehler, E.; Zbiral, E. Chem. Ber. 1980, 113, 2852.
(12) Elguero, J.; Martinez, A.; Singh, S. P.; Kumar, D. J.
Heterocycl. Chem. 1991, 28, 647.
(13) The catalyst, washed with CH2Cl2 and dried at 120 °C for 12
h can be reused for several experiments. The reaction of 2,3-
hexanedione and phenylhydrazine has been repeated 3 times
with the following yields: 82% (2 h), 84% (2 h), 79% (2 h).
(14) Curini, M.; Rosati, O.; Pisani, E.; Costantino, U. Synlett
1996, 333.
(6) (a) Texier-Boullet, F.; Klein, B.; Hamelin, J. Synthesis 1986,
409. (b) Sreekumar, R.; Padmakumar, R. Synth. Commun.
1998, 28, 1661.
Synlett 2005, No. 19, 2927–2930 © Thieme Stuttgart · New York