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Synlett 2005(19): 2927-2930  
DOI: 10.1055/s-2005-921904
LETTER
© Georg Thieme Verlag Stuttgart · New York

Layered Zirconium Sulfophenyl Phosphonate as Heterogeneous Catalyst in the Synthesis of Pyrazoles and 4,5,6,7-Tetrahydro-1(2)H-indazoles

Massimo Curini*a, Ornelio Rosati*a, Valerio Campagnaa, Francesca Montanaria, Giancarlo Cravottob, Mauro Boccalinic
a Dipartimento di Chimica e Tecnologia del Farmaco, Università degli Studi, Via del Liceo 1, 06123 Perugia, Italy
Fax: +39(075)5855116; e-Mail: curmax@unipg.it;
b Dipartimento di Scienza e Tecnologia del Farmaco, Università degli Studi, Via P. Giuria 9, 10125 Torino, Italy
c Dipartimento Chimica Organica ‘U. Schiff’, Via della Lastruccia 13, 50019 Sesto F.no, Firenze, Italy
e-Mail: ornros@unipg.it;
Further Information

Publication History

Received 31 August 2005
Publication Date:
04 November 2005 (online)

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Abstract

Pyrazoles and tetrahydroindazoles may be prepared by condensation of 1,3-diones and hydrazines under layered zirconium sulfophenyl phosphonate catalysis, in solvent-free conditions.

Key words

zirconium sulfophenyl phosphonate - heterogeneous catalysis - solvent free reactions - pyrazoles - indazoles

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Typical Reaction Procedure
To the mixture of 1,3-dione (1 mmol) and α-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.
Selected Experimental Data.
Methyl 5-Ethyl-3-methyl-1 H -pyrazole-1-carboxylate.
Colorless oil. 1H NMR (400 MHz, CDCl3): δ = 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): δ = 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-1 H -pyrazole.
White solid: mp 152-153 °C. 1H NMR (200 MHz, CDCl3): δ = 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): δ = 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.
2-(2,4-Dinitrophenyl)-3-methyl-4,5,6,7-tetrahydro-2 H -indazole.
Pale yellow solid: mp 156-158 °C. 1H NMR (400 MHz, CDCl3): δ = 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): δ = 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.

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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).