Regioselective Multicomponent
Synthesis of Fully Substituted Pyrazoles and Bispyrazoles Catalyzed
by Zinc Triflate

Shirin Safaei; Iraj Mohammadpoor-Baltork; Ahmad Reza Khosropour; Majid Moghadam; Shahram Tangestaninejad; Valiollah Mirkhani

doi:10.1055/s-0030-1261202

LETTER

Regioselective Multicomponent Synthesis of Fully Substituted Pyrazoles and Bispyrazoles Catalyzed by Zinc Triflate

Shirin Safaei, Iraj Mohammadpoor-Baltork*, Ahmad Reza Khosropour*, Majid Moghadam, Shahram Tangestaninejad, Valiollah Mirkhani
Catalysis Division, Department of Chemistry, University of Isfahan, Isfahan 81746-73441, Iran
Fax: +98(311)6689732; e-Mail: imbaltork@sci.ui.ac.ir; e-Mail: arkhosropour@sci.ui.ac.ir;

Abstract

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Abstract

A variety of fully substituted pyrazoles were easily prepared through a three-component condensation of aldehydes, arylhydrazines, and ethyl acetoacetate in the presence of catalytic amounts of zinc triflate [Zn(OTf)₂] under solvent-free conditions. Selective synthesis of symmetrical and unsymmetrical bispyrazoles from dialdehydes in high yields can be considered as a notable advantage of this method.

Key words

pyrazoles - aldehydes - arylhydrazines - zinc triflate - solvent-free

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References and Notes

<A NAME="RD12311ST-1A">1a</A> Taylor EC. Patel HH. Tetrahedron 1992, 48: 8089

<A NAME="RD12311ST-1B">1b</A> Sondhi SM. Singhal N. Verma RP. Arora SK. Dastidar SG. Indian J. Chem., Sect. B: Org. Chem. Incl. Med. Chem. 2001, 40: 113

<A NAME="RD12311ST-1C">1c</A> Banday AH. Mir BP. Lone IH. Suri KA. Kumar HMS. Steroids 2010, 75: 805

<A NAME="RD12311ST-1D">1d</A> Lv PC. Li HQ. Sun J. Zhou Y. Zhu HL. Bioorg. Med. Chem. 2010, 18: 4606

<A NAME="RD12311ST-2A">2a</A> Oezdemir Z. Kandilci HB. Guemuesel B. Calis U. Bilgin AA. Eur. J. Med. Chem. 2007, 373

<A NAME="RD12311ST-2B">2b</A> Nauduri D. Reddy GB. Chem. Pharm. Bull. 1998, 46: 1254

<A NAME="RD12311ST-2C">2c</A> Bekhit AA. Fahmy HTY. Rostom SAF. Bekhit AEDA. Eur. J. Med. Chem. 2010, 6027

<A NAME="RD12311ST-3A">3a</A> Raman N. Kulandaisamy A. Jeyasubramanian K. Synth. React. Inorg. Met. 2002, 32: 1583

<A NAME="RD12311ST-3B">3b</A> Raman N. Kulandaisamy A. Jeyasubramanian K. Synth. React. Inorg. Met. 2004, 34: 17

<A NAME="RD12311ST-3C">3c</A> Manikannan R. Venkatesan R. Muthusubramanian S. Yogeeswari P. Sriram D. Bioorg. Med. Chem. Lett. 2010, 20: 6920

<A NAME="RD12311ST-4A">4a</A> Idrees GA. Aly OM. El-Din AA. Abuo-Rahma G. Radwan MF. Eur. J. Med. Chem. 2009, 3973

<A NAME="RD12311ST-4B">4b</A> Palaska E. Sahin G. Kelicen P. Durlu NT. Altinok G. Farmaco 2002, 57: 101

<A NAME="RD12311ST-5A">5a</A> Nilsson S. Kuiper G. Gustafsson JA. Trends Endocrinol. Metab. 1998, 9: 387

<A NAME="RD12311ST-5B">5b</A> Stauffer SR. Katzenellenbogen JA. J. Comb. Chem. 2000, 2: 318

<A NAME="RD12311ST-6A">6a</A> Palazzino G. Cecchi L. Melani F. Colotta V. Filacchioni G. Martini C. Lucacchini A. J. Med. Chem. 1987, 30: 1737

<A NAME="RD12311ST-6B">6b</A> Thapa D. Lee JS. Heo SW. Lee YR. Kang KW. Kwak MK. Choi HG. Kim JA. Thapa D. Eur. J. Pharmacology 2011, 650: 64

<A NAME="RD12311ST-7">7</A> Donohue SR. Halldin C. Pike VW. Tetrahedron Lett. 2008, 49: 2789

<A NAME="RD12311ST-8">8</A> Ismail MAH. Lehmann J. Abou El Ella DA. Albohy A. Abouzid KAM. Med. Chem. Res. 2009, 18: 725

<A NAME="RD12311ST-9A">9a</A> Chen C. Jordan RF. J. Organomet. Chem. 2010, 695: 2543

<A NAME="RD12311ST-9B">9b</A> Mukherjee A. Sarkar A. Tetrahedron Lett. 2005, 46: 15

<A NAME="RD12311ST-10A">10a</A> Katritzky AR. Wang M. Zhang S. Voronkov MV. J. Org. Chem. 2001, 66: 6787

<A NAME="RD12311ST-10B">10b</A> Wang Z. Qin H. Green Chem. 2004, 6: 90

<A NAME="RD12311ST-10C">10c</A> Polshettiwar V. Varma RS. Tetrahedron Lett. 2008, 49: 397

<A NAME="RD12311ST-10D">10d</A> Xiong W. Chen JX. Liu MC. Ding JC. Wu HY. Su WK. J. Braz. Chem. Soc. 2009, 20: 367

<A NAME="RD12311ST-10E">10e</A> Mikhaylichenko SN. Patel SM. Dalili S. Chesnyuk AA. Zaplishny VN. Tetrahedron Lett. 2009, 50: 2505

<A NAME="RD12311ST-10F">10f</A> Polshettiwar V. Varma RS. Tetrahedron 2010, 66: 1091

<A NAME="RD12311ST-11A">11a</A> Elguero J. In Comprehensive Heterocyclic Chemistry II Vol. 3: Katritzky AR. Rees CW. Scriven EFV. Pergamon Press; Oxford: 1996. p.1

<A NAME="RD12311ST-11B">11b</A> Willy B. Müller TJJ. Eur. J. Org. Chem. 2008, 4157

<A NAME="RD12311ST-11C">11c</A> Grotjahn DB. Van S.. Combs D. Lev DA. Schneider C. Rideout M. Meyer C. Hernandez G. Mejorado L. J. Org. Chem. 2002, 67: 9200

<A NAME="RD12311ST-11D">11d</A> Song L.-P. Zhu S.-Z. J. Fluorine Chem. 2001, 111: 201

<A NAME="RD12311ST-11E">11e</A> Gosselin F. Oshea PD. Webster RA. Reamer RA. Synlett 2006, 3267

<A NAME="RD12311ST-12A">12a</A> Safaei-Ghomi J. Bamoniri AH. Soltanian-Telkabadi M. Chem. Heterocycl. Compd. 2006, 42: 892

<A NAME="RD12311ST-12B">12b</A> Katritzky AR. Wang M. Zhang S. Voronkov MV. J. Org. Chem. 2001, 66: 6787

<A NAME="RD12311ST-12C">12c</A> Huang YR. Katzenellenbogen JA. Org. Lett. 2000, 2: 2833

<A NAME="RD12311ST-12D">12d</A> Landge MS. Schmidt A. Outerbridge V. Torok B. Synlett 2007, 1600

<A NAME="RD12311ST-12E">12e</A> Pinto DCGA. Silva AMS. Cavaleiro JAS. Elguero J. Eur. J. Org. Chem. 2003, 747

<A NAME="RD12311ST-13A">13a</A> Suryakiran N. Srikanth RT. Asha LK. Prabhakar P. Venkateswarla Y. J. Mol. Catal. A: Chem. 2006, 258: 371

<A NAME="RD12311ST-13B">13b</A> Dorsch JB. Mcelvain SM. J. Am. Chem. Soc. 1932, 54: 2960

<A NAME="RD12311ST-13C">13c</A> Wang G. Liu X. Zhao G. Tetrahedron: Asymmetry 2005, 16: 1873

<A NAME="RD12311ST-14A">14a</A> Le Fevre G. Hamelin J. Tetrahedron 1980, 36: 887

<A NAME="RD12311ST-14B">14b</A> Kobayashi S. Hirabayashi R. Shimizu H. Ishitani H. Yamashita Y. Tetrahedron Lett. 2003, 44: 3351

<A NAME="RD12311ST-14C">14c</A> Deng X. Mani NS. Org. Lett. 2006, 8: 3505

<A NAME="RD12311ST-14D">14d</A> Deng X. Mani NS. Org. Lett. 2008, 10: 1307

<A NAME="RD12311ST-15A">15a</A> Bardakos V. Sucrow W. Fehlauer A. Chem. Ber. 1975, 108: 2161

<A NAME="RD12311ST-15B">15b</A> Baumes R. Jacquier R. Tarrago G. Bull. Soc. Chim. Fr. 1976, 260

<A NAME="RD12311ST-16">16</A> Alex K. Tillack A. Schwarz N. Beller M. Org. Lett. 2008, 10: 2377

<A NAME="RD12311ST-17">17</A> Liu H.-L. Jiang H.-F. Zhang M. Yao W.-J. Zhu Q.-H. Tang Z. Tetrahedron Lett. 2008, 49: 3805

<A NAME="RD12311ST-18A">18a</A> Ahmed MSM. Kobayashi K. Mori A. Org. Lett. 2005, 7: 4489

<A NAME="RD12311ST-18B">18b</A> Stonehouse JP. Chekmarev DS. Ivanova NV. Lang S. Pairaudeau G. Smith N. Stocks MJ. Sviridov SI. Utkina LM. Synlett 2008, 100

<A NAME="RD12311ST-19A">19a</A> Aggarwal KV. Vicente DJ. Bonnert VR. J. Org. Chem. 2003, 68: 5381

<A NAME="RD12311ST-19B">19b</A> Huisgen R. Angew. Chem., Int. Ed. Engl. 1963, 2: 565

<A NAME="RD12311ST-19C">19c</A> Cheung KMJ. Reynisson J. Donald EM. Tetrahedron Lett. 2010, 51: 5915

<A NAME="RD12311ST-20A">20a</A> Suen YF. Hope H. Nantz MH. Haddadin MJ. Kurth MJ. J. Org. Chem. 2005, 70: 8468

<A NAME="RD12311ST-20B">20b</A> Neumann JJ. Suri M. Glorius F. Angew. Chem. Int. Ed. 2010, 49: 1

<A NAME="RD12311ST-20C">20c</A> Gosselin F. O’Shea PD. Webster RA. Reamer RA. Tillyer RD. Grabowski EJJ. Synlett 2006, 3267

<A NAME="RD12311ST-21A">21a</A> Shen L. Cao S. Liu N. Wu J. Zhu L. Qian X. Synlett 2008, 1341

<A NAME="RD12311ST-21B">21b</A> Shen L. Zhang J. Cao S. Yu J. Liu N. Wu J. Qian X. Synlett 2008, 3058

<A NAME="RD12311ST-22A">22a</A> Multicomponent Reactions Zhu J. Bienayme H. Wiley-VCH; Weinheim: 2005.

<A NAME="RD12311ST-22B">22b</A> Orru RVA. de Greef M. Synthesis 2003, 1471

<A NAME="RD12311ST-22C">22c</A> Dömling A. Chem. Rev. 2006, 106: 17

<A NAME="RD12311ST-22D">22d</A> Weber L. Illgen K. Almstetter M. Synlett 1999, 366

<A NAME="RD12311ST-22E">22e</A> Nicolaou KC. Edmonds DJ. Bulger PG. Angew. Chem. Int. Ed. 2006, 45: 7134

<A NAME="RD12311ST-23A">23a</A> Mohammadpoor-Baltork I. Tangestaninejad S. Moghadam M. Mirkhani V. Anvar S. Mirjafari A. Synlett 2010, 3104

<A NAME="RD12311ST-23B">23b</A> Mohammadpoor-Baltork I. Moghadam M. Tangestaninejad S. Mirkhani V. Eskandari Z. Ultrason. Sonochem. 2010, 17: 857

<A NAME="RD12311ST-23C">23c</A> Mohammadpoor-Baltork I. Khosropour AR. Hojati SF. Catal. Commun. 2007, 8: 200

<A NAME="RD12311ST-23D">23d</A> Mohammadpoor-Baltork I. Khosropour AR. Hojati SF. Synlett 2005, 2747

<A NAME="RD12311ST-23E">23e</A> Mohammadpoor-Baltork I. Khosropour AR. Hojati SF. Catal. Commun. 2007, 8: 1865

<A NAME="RD12311ST-23F">23f</A> Khosropour AR. Mohammadpoor-Baltork I. Ghorbankhani H. Catal. Commun. 2006, 7: 713

<A NAME="RD12311ST-23G">23g</A> Khosropour AR. Mohammadpoor-Baltork I. Ghorbankhani H. Tetrahedron Lett. 2006, 47: 3561

General Procedure for the Synthesis of Fully Substituted Pyrazoles A mixture of aldehyde 1 (1 mmol) and arylhydrazine 2 (1 mmol) was stirred for 20 min, then ethyl acetoacetate 3 (1.5 mmol) and Zn(OTf)₂ (0.02 mmol) were added, and the mixture was stirred at 120 ˚C for the appropriate time according to Table [²] . The progress of the reaction was monitored by TLC (eluent: n-hexane-EtOAc, 10:1). After completion of the reaction, the mixture was cooled to r.t., and the crude product was purified by chromatography on silica gel (eluent: n-hexane-EtOAc, 10:1) or by recrystallization from EtOH to afford the pure product.

<A NAME="RD12311ST-25A">25a</A> Li K. Mohlala MS. Segapelo TV. Shumbula PM. Guzei IA. Darkwa J. Polyhedron 2008, 27: 1017

<A NAME="RD12311ST-25B">25b</A> Boixassa A. Pons J. Ros J. Mathieu R. Lugan N.
J. Organomet. Chem. 2003, 682: 233

<A NAME="RD12311ST-25C">25c</A> de León A. Pons J. García-Antón J. Ros J. Polyhedron 2010, 29: 2318

General Procedure for the Synthesis of Fully Substituted Bispyrazoles A mixture of dialdehyde 5 (1 mmol) and arylhydrazine 2 (2 mmol) was stirred for 20 min (for unsymmetrical bispyrazoles, a mixture of dialdehyde 5 (1 mmol) and arylhydrazine 2 (1 mmol) was stirred for 20 min, then arylhydrazine 6 (1 mmol) was added and stirred for further 20 min). Ethyl acetoacetate 3 (4 mmol) and Zn(OTf)₂ (0.04 mmol) were added, and the mixture was heated at 120 ˚C for the appropriate time (Table [³] ). The progress of the reaction was monitored by TLC (eluent: n-hexane-EtOAc, 10:1). After completion of the reaction, the mixture was cooled to r.t., and the crude product was purified by chromatography on silica gel (eluent: n-hexane-EtOAc, 10:1) or by recrystallization from EtOH to give the pure product.

CCDC 817131 contains the supplementary crystallographic data for this paper. These data can be obtained free of charge via http://www.ccdc.cam.ac.uk/conts/retrieving.html [or from the Cambridge Crystallographic Data Centre, 12 Union Road, Cambridge CB2 1EZ, UK; fax: +44 (1223)336033;
e-mail: deposit@ccdc.cam.ac.uk].

<A NAME="RD12311ST-28">28</A> Shah JN. Shah KC. J. Org. Chem. 1978, 43: 1266