Skip to main content
SpringerLink
Log in

Urea/thiourea: efficient, inexpensive and reusable catalysts for the synthesis of pyrazole derivatives with 2-iminothiazolidin-4-one and 2,4-thiazolidinediones under solvent-free conditions

  • Original Article
  • Published:
Molecular Diversity Aims and scope Submit manuscript

Abstract

An efficient and green synthesis of pyrazolyl-2,4-thiazolidinediones/pyrazolyl-2-iminothiazolidine-4-ones 7(a–j) has been developed using urea/thiourea as catalyst. Two methods (A and B) have been introduced for the synthesis of these compounds. Method A performed well for the condensation of pyrazole-4-carboxaldehydes 4(a–e) with 2-iminothiazolidin-4-one 5a and with 2,4-thiazolidinedione 5b at 110 \(^{\circ }\hbox {C}\) for 16–20 min to furnish (Z)-5-((1,3-diphenyl-1H-pyrazol-4-yl)methylene)thiazolidine-2,4-diones 7(a–j) in excellent yields. In method B, the pyrazole-4-carboxaldehydes 4(a–e) were condensed with urea/thiourea at 110 \(^{\circ }\hbox {C}\) for 10 min to give key intermediates 6(a–j) which were later condensed with 5a and 5b to afford 7(a–j) via the elimination of urea/thiourea rather than the formation of a Biginelli product. These two protocols are inexpensive, eco-friendly and high yielding to provide the final products.

Graphical Abstract

The synthesis of compound 7f

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Scheme 1
Scheme 2
Scheme 3
Fig. 2
Scheme 4
Fig. 3
Scheme 5

Similar content being viewed by others

References

  1. Bekhit AA, Ashour HM, Bekhit AD, Bekhit SA (2009) Synthesis and biological evaluation of novel pyrazole derivatives as anti-inflammatory antimicrobial agents. Med Chem 5:103–117. doi:10.2174/157340609787582936

    Article  CAS  PubMed  Google Scholar 

  2. Manojkumar P, Ravi TK, Subbuchettiar G (2009) Synthesis of coumarin heterocyclic derivatives with antioxidant activity and in vitro cytotoxic activity against tumour cells. Acta Pharm 59:159–170. doi:10.2478/v10007-009-0018-7

    Article  CAS  PubMed  Google Scholar 

  3. Sauzem PD, Santann SG, Machado P, Duarte MM, Ferreira J, Mello CF, Beck P, Bonacorso HG, Zanatta N, Martins MA, Rubin MA (2009) Effect of 5-trifluoromethyl-4,5-dihydro-1H-pyrazoles on chronic inflammatory pain model in rats. Eur J Pharmacol 616:91–100. doi:10.1016/j.ejphar.2009.06.008

    Article  CAS  PubMed  Google Scholar 

  4. Damljanovic I, Vukicevic M, Radulovic N, Palic R, Ellmerer E, Ratkovic Z, Joksovic MD, Vukicevic RD (2009) Synthesis and antimicrobial activity of some new pyrazole derivatives containing a ferrocene unit. Bioorg Med Chem Lett 19:1093–1096. doi:10.1016/j.bmcl.2009.01.006

    Article  CAS  PubMed  Google Scholar 

  5. Gao HM, Hong JS (2008) Why neurodegenerative diseases are progressive: uncontrolled inflammation drives disease progression. Trends Immunol 29:357–365. doi:10.1016/j.it.2008.05.002

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. Carroll RT, Dluzen DE, Stinnett H, Awalex PS, Funk MO, Geldenhuys W (2011) Structure-activity relationship and docking studies of thiazolidinedione-type compounds with monoamine oxidase B. Bioorg Med Chem Lett 21:4798–4803. doi:10.1016/j.bmcl.2011.06.060

    Article  CAS  PubMed  Google Scholar 

  7. Liu XF, Zheng CJ, Sun LP, Piao HR (2011) Synthesis of new chalcone derivatives bearing 2,4-thiazolidinedione and benzoic acid moieties as potential anti-bacterial agents. Eur J Med Chem 46:3469–3473. doi:10.1016/j.ejmech.2011.05.012

    Article  CAS  PubMed  Google Scholar 

  8. Sunduru N, Srivastava K, Rajakumar S, Puri SK, Saxena JK, Chauhan PMS (2009) Synthesis of novel thiourea, thiazolidinedione and thioparabanic acid derivatives of 4-aminoquinoline as potent antimalarials. Bioorg Med Chem Lett 19:2570–2573. doi:10.1016/j.bmcl.2009.03.026

    Article  CAS  PubMed  Google Scholar 

  9. Tomasic T, Masic LP (2009) Rhodanine as a privileged scaffold in drug discovery. Curr Med Chem 16:1596–1629. doi:10.2174/092986709788186200

    Article  CAS  PubMed  Google Scholar 

  10. Irvine MW, Patrick GL, Kewney J, Hastings SF, MacKenzie S (2008) Rhodanine derivatives as novel inhibitors of PDE4. Bioorg Med Chem Lett 18:2032–2037. doi:10.1016/j.bmcl.2008.01.117

    Article  CAS  PubMed  Google Scholar 

  11. Komatsu T, Hirano T, Songkram C, Kagechika EKH (2007) Novel thyroid hormone receptor antagonists with an N-alkylated diphenylamine skeleton. Bioorg Med Chem 15:3115–31126. doi:10.1016/j.bmc.2007.02.053

    Article  CAS  PubMed  Google Scholar 

  12. Prakash O, Deepak KA, Lohan P, Hussain K, Sanjiv A, Sharma C, Aneja KR (2012) Synthesis and antimicrobial activity of 5-((3-aryl-1-phenyl-1H-pyrazol-4-yl)methylene)thiazolidine-2,4-diones. Med Chem Res 21:2961–2968. doi:10.1186/2191-2858-1-15

    Article  CAS  Google Scholar 

  13. Amal M, Youssef M, Sydney W, Erika BV, El-Ashmawy IM, Andis K (2010) Synthesis and biological evaluation of novel pyrazolyl-2,4-thiazolidinediones as anti-inflammatory and neuroprotective agents. Bioorg Med Chem 18:2019–2028. doi:10.1016/j.bmc.2010.01.021

    Article  Google Scholar 

  14. Jawale DV, Pratap UR, Lingampalle DL, Mane RA (2011) Dicationic ionic liquid mediated synthesis of 5-arylidine-2,4-thiazolidinediones. Chin J Chem 29:942–946. doi:10.1002/cjoc.201190192

    Article  CAS  Google Scholar 

  15. Vachal P, Jacobsen EN (2002) Structure-based analysis and optimization of a highly enantio selective catalyst for the strecker reaction. J Am Chem Soc 124:10012–10014. doi:10.1021/ja027246j

  16. Cozzi F (2006) Immobilization of organic catalysts: when, why, and how. Adv Synth Catal 348:1367–1390. doi:10.1002/adsc.200606096

    Article  CAS  Google Scholar 

  17. Curran DP, Kuo LH (1995) Acceleration of a dipolar Claisen rearrangement by hydrogen bonding to a soluble diaryl urea. Tetrahedron Lett 36:6647–6650. doi:10.1016/00404-0399(50)1394-W

    CAS  Google Scholar 

  18. Okino T, Hoashi Y, Takemoto Y (2003) Thiourea-catalyzed nucleophilic addition of TMSCN and ketene silyl acetals to nitrones and aldehydes. Tetrahedron Lett 44:2817–2821. doi:10.1016/S0040-4039(03)00433-7

    Article  CAS  Google Scholar 

  19. Maher DJ, Connon SJ (2004) Acceleration of the DABCO-promoted Baylis–Hillman reaction using a recoverable H-bonding organocatalyst. Tetrahedron Lett 45:1301–1305. doi:10.1016/j.tetlet.2003.11.062

    Article  CAS  Google Scholar 

  20. Li JT, Li YW, Song YL, Chen GF (2012) Improved synthesis of 2,2\(^\prime \)-arylmethylenebis(3-hydroxy-5,5-dimethyl-2-cyclohexene-1-one) derivatives catalyzed by urea under ultrasound. Ultrason Sonochem 19:1–4. doi:10.1016/j.ultsonch.2011.05.001

    Article  PubMed  Google Scholar 

  21. Kira MA, Abdelraeman MO, Gadalla KZ (1969) The Vilsmeier–Haack reaction-III cyclization of hydrazones to pyrazoles. Tetrahedron Lett 2:109–110. doi:10.1016/S0040-4039(01)88217-4

    Article  Google Scholar 

  22. Prashantha BR, Adhikary LJ (2006) Microwave induced synthesis of the thiazolidine-2,4-dione motif and the efficient solvent free-solid phase parallel syntheses of 5-benzylidene-thiazolidine-2,4-dione and 5-benzylidene-2-thioxo-thiazolidine-4-one compounds. J Heterocycl Chem 43:897–903. doi:10.1002/jhet.5570430413

    Article  Google Scholar 

  23. Momos Y, Meguro K, Hithosi I, Hatanaka C, Satoru O, Shoda T (1991) Studies on antidiabetic agents. X. Synthesis and biological activities of pioglitazone and related compounds. Chem Pharm Bull 39:1440–1445. doi:10.1248/cpb.39.1440

    Article  Google Scholar 

Download references

Acknowledgements

The author are indebted to University Grants Commission, Govt. of India, New Delhi, for providing financial support to one of them (K.V.S) in the form of UGC-SRF. They are also thankful to the authorities of Jawaharlal Nehru Technological University Hyderabad for providing the laboratory facilities.

Author information

Authors and Affiliations

  1. Department of Chemistry, Jawaharlal Nehru Technological University Hyderabad, College of Engineering, Kukatpally, Hyderabad, T.S., 500 085, India

    Veera Swamy Konkala & Pramod Kumar Dubey

Authors
  1. Veera Swamy Konkala
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Pramod Kumar Dubey
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Veera Swamy Konkala.

Electronic supplementary material

Below is the link to the electronic supplementary material.

Supplementary material 1 (doc 2092 KB)

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Konkala, V.S., Dubey, P.K. Urea/thiourea: efficient, inexpensive and reusable catalysts for the synthesis of pyrazole derivatives with 2-iminothiazolidin-4-one and 2,4-thiazolidinediones under solvent-free conditions. Mol Divers 21, 283–291 (2017). https://doi.org/10.1007/s11030-016-9719-2

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11030-016-9719-2

Keywords

Search

Navigation