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

Massimo Curini; Ornelio Rosati; Valerio Campagna; Francesca Montanari; Giancarlo Cravotto; Mauro Boccalini

doi:10.1055/s-2005-921904

LETTER

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 Campagna^a, Francesca Montanari^a, Giancarlo Cravotto^b, Mauro Boccalini^c
^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;

Abstract

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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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References

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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:

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7

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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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).

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