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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

    References

  • 1 Kabalka GW. Pagni RM. Tetrahedron  1997,  53:  7999 ; and references cited therein
    CrossrefGoogle Scholar
  • 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:
  • 2a Umansky B. Engelhardt J. Hall WK. J. Catal.  1991,  127:  128 
    CrossrefGoogle Scholar
  • 2b Hammett LP. Deyrup AJ. J. Am. Chem. Soc.  1932,  54:  2721 
    CrossrefGoogle Scholar
  • 3 Curini M. Rosati O. Costantino U. Curr. Org. Chem.  2004,  8:  591 
    CrossrefGoogle Scholar
  • 4a Kizer DE. Miller RB. Kurth MJ. Tetrahedron Lett.  1999,  40:  3535 
    Google Scholar
  • 4b Kees KL. Fitgzerald SJ. Steiner KE. Mattes JF. Mihan B. Tosi T. Montoro D. McCaleb ML. J. Med. Chem.  1996,  39:  3920 
    Google Scholar
  • 4c Huang YR. Katzenellenbogen JA. Org. Lett.  2000,  2:  2833 
    Google Scholar
  • 4d Lyga JW. Patera RM. Plummer MJ. Halling BP. Yukas DA. Pest. Sci.  1994,  42:  29 
    Google Scholar
  • 5a Elguero J. In Comprehensive Heterocyclic Chemistry   Vol. 3:  Katrizky AR. Rees CW. Scriven EFV. Pergamon Press; Oxford: 1996.  p.1-75  
    CrossrefGoogle Scholar
  • 5b Lee KY. Kim JM. Kim JN. Tetrahedron Lett.  2003,  44:  6737 ; and references cited therein
    CrossrefGoogle Scholar
  • 6a Texier-Boullet F. Klein B. Hamelin J. Synthesis  1986,  409 
    CrossrefGoogle Scholar
  • 6b Sreekumar R. Padmakumar R. Synth. Commun.  1998,  28:  1661 
    CrossrefGoogle Scholar
  • 8 Wang ZX. Qin HL. Green Chem.  2004,  6:  90 
    CrossrefGoogle Scholar
  • 9 Zelenin KN. Alekseyev VV. Tygysheva AR. Yakimovitch SI. Tetrahedron  1995,  51:  11251 
    CrossrefGoogle Scholar
  • 10a Alberola A. Calvo L. Ortega AG. Sádaba ML. Sañudo MC. Granda SG. Rodríguez EG. Heterocycles  1999,  51:  2675 
    CrossrefGoogle Scholar
  • 10b Kashima C. Tsuruoka S. Mizuhara S. Tetrahedron  1998,  54:  14679 
    CrossrefGoogle Scholar
  • 11 Oehler E. Zbiral E. Chem. Ber.  1980,  113:  2852 
    Google Scholar
  • 12 Elguero J. Martinez A. Singh SP. Kumar D. J. Heterocycl. Chem.  1991,  28:  647 
    Google Scholar
  • 14 Curini M. Rosati O. Pisani E. Costantino U. Synlett  1996,  333 
    Article in Thieme ConnectGoogle Scholar
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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).