Skip to main content
SpringerLink
Log in

One-pot diastreoselective synthesis of highly functionalized cyclohexenones: 2-oxo-N,4,6-triarylcyclohex-3-enecarboxamides

  • Full-Length Paper
  • Published:
Molecular Diversity Aims and scope Submit manuscript

Abstract

A series of 2-oxo-N,4,6-triarylcyclohex-3-enecarboxamides were synthesized by condensing acetophenone and aromatic aldehydes with acetoacetanilide in ethanol in the presence of 2-hydroxyethylammonium acetate (2-HEAA) as a basic ionic liquid at ambient conditions. This process is simple, efficient and environmentally benign and proceeds in high yield, short reaction times and there is no need for column chromatography purification.

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
Fig. 2
Fig. 3
Scheme 2

Similar content being viewed by others

References

  1. Awasthi SK, Mishra N, Kumar B, Sharma M, Bhattacharya A, Mishra LC, Bhasin VK (2009) Potent antimalarial activity of newly synthesized substituted chalcone analogs in vitro. Med Chem Res 18:407–420. doi:10.3390/molecules170910331

    Article  CAS  Google Scholar 

  2. Lim SS, Kim HS, Lee DU (2007) In vitro antimalarial activity of flavonoids and chalcones. Bull Korean Chem Soc 28:2495–2497

    Article  CAS  Google Scholar 

  3. Rahman MA (2011) Chalcone: a valuable insight into the recent advances and potential pharmacological activities. Chem Sci J 2011:1–16. doi:10.4172/2150-3494.1000021

    Google Scholar 

  4. Saini RK, Choudhary AS, Joshi YC, Joshi P (2005) Solvent free synthesis of chalcones and their antibacterial activities. E-J Chem 2:224–227. doi:10.1155/2005/294094

    Article  Google Scholar 

  5. Hussain MA (2001) Synthesis of aurentiacin. Indian J Chem 40B:324–326

    Google Scholar 

  6. Baradia R, Rao JT (2004) Synthesis and antimicrobial activity of some \(\alpha,\!\beta \)-unsaturated aromatic ketones. Asian J Chem 16:1194–1196

    Google Scholar 

  7. Ilango K, Valentina P, Saluja G (2010) Synthesis and in vitro anticancer activity of some substituted chalcones derivatives. Res J Pharm Biol Chem Sci 1:354–359

    CAS  Google Scholar 

  8. Zhang XW, Zhao DH, Quan YC, Sun LP, Yin XM, Guan LP (2010) Synthesis and evaluation of anti-inflammatory activity of substituted chalcone derivatives. Med Chem Res 19:403–412. doi:10.1007/s00044-009-9202-z

    Article  CAS  Google Scholar 

  9. Bhatia NM, Mahadik KR, Bhatia MS (2009) QSAR analysis of 1,3-diaryl-2-propen-1-ones and their indole analogs for designing potent antibacterial agents. Chem Pap 63:456–463

    Article  CAS  Google Scholar 

  10. Kaushik S, Kumar N, Drabu S (2010) Synthesis and anticonvulsant activities of phenoxychalcones. T Ph Res 3:257–262

    Google Scholar 

  11. Romagnoli R, Baraldi PG, Carrion MD, Cara CL, Cruz-Lopez O, Preti D (2008) Design, synthesis, and biological evaluation of thiophene analogues of chalcones. Bioorg Med Chem 16:5367–5376. doi:10.1016/j.bmc.2008.04.026

    Article  PubMed  CAS  Google Scholar 

  12. Lahtchev KL, Batovska DI, Parushev SP, Ubiyvovk VM, Sibirny AA (2008) Antifungal activity of chalcones: a mechanistic study using various yeast strains. Eur J Med Chem 43:2220–2228. doi:10.1016/j.ejmech.2007.12.027

    Article  PubMed  CAS  Google Scholar 

  13. Bag S, Ramar S, Degani MS (2009) Synthesis and biological evaluation of \(\alpha, \!\beta \)-unsaturated ketone as potential antifungal agents. Med Chem Res 18:309–316. doi: 10.1007/s00044-008-9128-x

    Article  CAS  Google Scholar 

  14. Lunardi F, Guzela M, Rodrigues AT, Corre R, Eger-Mangrich I, Steindel M, Grisard EC, Assreuy J, Calixto JB, Santos ARS (2003) Trypanocidal and leishmanicidal properties of substitution-containing chalcones. Antimicrob Agents Chemother 47:1449–1451. doi:10.1128/AAC.47.4.1449-1451.2003

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  15. Cheng MS, Shi R, Kenyon G (2000) A solid phase synthesis of chalcones by Claisen-Schmidt condensations. Chin Chem Lett 11:851–854

    CAS  Google Scholar 

  16. Begum NA, Roy N, Laskar RA, Roy K (2010) Mosquito larvicidal studies of some chalcone analogues and their derived products: structure-activity relationship analysis. Med Chem Res 19: 1–14

    Google Scholar 

  17. Awasthi SK, Mishra N, Dixit SK, Singh A, Yadav M, Yadav SS, Rathaur S (2009) Antifilarial activity of 1,3-diarylpropen-1-one: effect on glutathione-S-transferase, a phase II detoxification enzyme. Am J Trop Med Hyg 80:764–768

    PubMed  CAS  Google Scholar 

  18. Hamdi N, Fischmeister C, Puerta MC, Valerga P (2010) A rapid access to new coumarinyl chalcone and substituted chromeno[4,3-c]pyrazol-4(1H)-ones and their antibacterial and DPPH radical scavenging activities. Med Chem Res 19:1–16. doi:10.2478/s11696-009-0026-6

    Google Scholar 

  19. Vogel S, Ohmayer S, Brunner G, Heilmann J (2008) Natural and non-natural prenylated chalcones: synthesis, cytotoxicity and anti-oxidative activity. Bioorg Med Chem 16:4286–4293. doi:10.1016/j.bmc.2008.02.079

    Article  PubMed  CAS  Google Scholar 

  20. Sivakumar PM, Prabhakar PK, Doble M (2010) Synthesis, antioxidant evaluation and quantitative structure-activity relationship studies of chalcones. Med Chem Res 19:1–17. doi:10.1007/s00044-010-9342-1

    Google Scholar 

  21. Yayli N, Ucuncu O, Yasar A, Kucuk M, Akyuz E, Karaoglu SA (2006) Synthesis and biological activities of N-alkyl derivatives of o-, m-, and p-nitro (E)-4-azachalcones and stereoselective photochemistry in solution with theoretical calculations. Turk J Chem 30:505–514

    CAS  Google Scholar 

  22. Najafian M, Ebrahim-Habibi A, Hezareh N, Yaghmaei P, Parivar K, Larijani B (2010) Trans-chalcone: a novel small molecule inhibitor of mammalian alpha-amylase. Mol Biol Rep 10:271–274. doi:10.1007/s11033-010-0271-3

    Google Scholar 

  23. Chimenti F, Fioravanti R, Bolasco A, Chimenti P, Secci D, Rossi F, Yanez M, Francisco OF, Ortuso F, Alcaro S (2009) Chalcones: a valid scaffold for monoamine oxidases inhibitors. J Med Chem 10:1–8. doi:10.1021/jm801590u

    Google Scholar 

  24. Zarghi A, Zebardast T, Hakimion F, Shirazi FH, Rao PNP, Knaus EE (2006) Synthesis and biological evaluation of 1,3-diphenylprop-2-en-1-ones possessing a methanesulfonamido or an azido pharmacophore as cyclooxygenase-1/-2 inhibitors. Bioorg Med Chem 14:7044–7050. doi:10.1016/j.bmc.2006.06.022

    Article  PubMed  CAS  Google Scholar 

  25. Sibi MP, Manyem S (2000) Enantioselective conjugate additions. Tetrahedron 56:8033–8061. doi:10.1016/S0040-4020(00)00618-9

    Article  CAS  Google Scholar 

  26. Berner OE, Tedeschi L, Enders D (2002) Asymmetric Michael additions to nitroalkenes. Eur J Org Chem 2002:1877–1894. doi:10.1002/1099-0690(200206)2002:12<1877::aid-ejoc1877>3.0.co;2-u

  27. Dalko PI, Moisan L (2004) In the golden age of organocatalysis. Angew Chem Int Ed 43:5138–5175. doi:10.1002/anie.200400650

    Article  CAS  Google Scholar 

  28. House HO (1972) Modern synthetic reactions, 2nd ed. Benjamin WA, Menlo Park, p 595

  29. Jung ME (1991) In: Trostand BM, Fleming I (eds) Comprehensive organic synthesis. Pergamon Press, Oxford, p 1

  30. Padmavathi V, Sharmila K, Reddy AS, Reddy DB (2001) Reactivity of 3,5-diaryl cyclohexanones—synthesis of spiro cyclohexanes. Indian J Chem 40B:11–14

    CAS  Google Scholar 

  31. Padmavathi V, Sharmila K, Balaiah A, Reddy AS, Reddy DB (2001) Cyclohexenone carboxylates. A versatile source for fused isoxazoles and pyrazoles. Synth Commun 31:2119–2126. doi:10.1081/SCC-100104462

    Article  CAS  Google Scholar 

  32. Reddy DB, Reddy AS, Padmavathi V (1998) Synthesis of annelated 1,2,3-selena- or -thia-diazoles. J Chem Res 784–785. doi: 10.1039/A804381G

  33. Gopalakrishnan M, Thanusu J, Kanagarajan V (2008) Synthesis and characterization of 4,6-diaryl-4,5-dihydro-2H-indazol-3-ols and 4,6-diaryl-2-phenyl-4,5-dihydro-2H-indazol-3-ols - a new series of fused indazole derivatives. Chem Hetero Comp 44:950–955. doi:10.1007/s10593-008-0137-y

    Article  CAS  Google Scholar 

  34. Padmavathi V, Sharmila K, Padmaja A, Reddy DB (1999) An efficient synthesis of 6,8-diarylcarbazoles via Fischer indole cyclizations. Heterocycl Commun 5:451–456. doi:10.1515/HC.1999.5.5.451

  35. Hoye TR, Tennakoon MA (2000) Synthesis (and alternative proof of configuration) of the scyphostatin C(1’)-C(20’) trienoyl fragment. Org Lett 2:1481–1483. doi:10.1021/ol0058386

  36. Hiromichi F, Naoyuki K, Yoshinari S, Yasushi N, Yasuyuki K (2002) Concise asymmetric synthesis of a model compound, \((4S,\!5S,\!6S)\)-6-(2,2-dimethoxy)ethyl-4,5-epoxy-6-hydroxy-2-cyclohexenone, for the cyclohexenone core of scyphostatin. Tetrahedron Lett 43:4825–4828. doi:10.1016/s0040-4039(02)00916-4

  37. Safaei-Ghomi J, Alishahi Z (2005) The preparation of some novel indazole derivatives by using chalcones. J Fudan Univ Nat Sci 44(5):789–790

    CAS  Google Scholar 

  38. Mc Bride C, Renhowe P, Heise C, Jansen J, Lapointe G, Ma S, Pineda R, Vora J, Wiesmann M, Shafer C (2006) Design and structure-activity relationship of \(3\!-\!\text{ benzimidazol }\!-\!2\!-\!\text{ yl }\!-\!1{\rm H}\)-indazoles as inhibitors of receptor tyrosine kinases. Bioorg Med Chem Lett 16:3595–3599. doi: 10.1016/j.bmcl.2006.03.069

    Article  CAS  Google Scholar 

  39. Kim BC, Kim JL, Jhang YU (1994) Bull Korean Chem Soc 15(2): 97. Chem. Abstr 121:50097z

  40. Yamaguchi M, Maruyama N, Koga T, Kamei K, Akima M, Kuroki T, Hamana M, Ohi N (1995) Novel antiasthmatic agents with dual activities of thromboxane A2 synthetase inhibition and bronchodilation, VI: Indazole derivatives. Chem Pharm Bull 43(2):332–334

    Article  PubMed  CAS  Google Scholar 

  41. Gorge V, De L, Kim UT, Jing L (1998) Nonsymmetric P2/P2‘ cyclic urea HIV protease inhibitors. structure-activity relationship, bioavailability, and resistance profile of monoindazole-substituted P2 analogues. J Med Chem 41(13):2411–2423. doi:10.1021/jm980103g

    Article  Google Scholar 

  42. Vyas DH, Tala SD, Akbari JD, Dhaduk MF, Joshi HS (2009) Synthesis, antimicrobial and antitubercular activity of some cyclohexenone and indazole derivatives. Indian J Chem 48B:1405–1410

    CAS  Google Scholar 

  43. Abdel-Rahman AAH, Abdel-Megied AES, Hawata MAM, Kasem ER, Shabaan MT (2007) Synthesis and antimicrobial evaluation of some chalcones and their derived pyrazoles, pyrazolines, isoxazolines, and 5,6-dihydropyrimidine-2-(1H)-thiones. Monatshefte Chem 138:889–897. doi:10.1007/s00706-007-0700-8

    Article  CAS  Google Scholar 

  44. Ducki S, Forrest R, Hadfield JA, Kendall A, Lawrence NJ, McGown AT, Rennisonl D (1998) Potent antimitotic and cell growth inhibitory properties of substituted chalcones. Bioorg Med Chem Lett 8:1051–1056. doi:10.1016/S0960-894X(98)00162-0

    Article  PubMed  CAS  Google Scholar 

  45. Bhat BA, Dhar KL, Puri SC, Saxena AK, Shanmugavel M, Qazi GN (2005) Synthesis and biological evaluation of chalcones and their derived pyrazoles as potential cytotoxic agents. Bioorg Med Chem Lett 15:3177–3180. doi:10.1016/j.bmcl.2005.03.121

    Article  PubMed  CAS  Google Scholar 

  46. Sobhani S, Nasseri R, Honarmand M (2012) 2-Hydroxyethylammonium acetate as a reusable and cost-effective ionic liquid for the efficient synthesis of bis(pyrazolyl)methanes and 2-pyrazolyl-1-nitroalkanes. Can J Chem 90:798–804. doi:10.1139/v2012-059

    Article  CAS  Google Scholar 

  47. Yue C, Mao A, Wei Y, Lü M (2008) Knoevenagel condensation reaction catalyzed by task-specific ionic liquid under solvent-free conditions. Catal Commun 9:1571–1574. doi:10.1016/j.catcom.2008.01.002

    Article  CAS  Google Scholar 

Download references

Acknowledgments

Financial support from the Research Council of the University of Sistan and Baluchestan is gratefully acknowledged.

Author information

Authors and Affiliations

  1. Department of Chemistry, Faculty of Science, University of Sistan and Baluchestan, P. O. Box 98135-674, Zahedan, Iran

    Mir Rasul Mousavi, Malek Taher Maghsoodlou & Sayyed Mostafa Habibi-Khorassani

Authors
  1. Mir Rasul Mousavi
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Malek Taher Maghsoodlou
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Sayyed Mostafa Habibi-Khorassani
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Malek Taher Maghsoodlou.

Electronic supplementary material

Below is the link to the electronic supplementary material.

Supplementary material 1 (docx 2615 KB)

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Mousavi, M.R., Maghsoodlou, M.T. & Habibi-Khorassani, S.M. One-pot diastreoselective synthesis of highly functionalized cyclohexenones: 2-oxo-N,4,6-triarylcyclohex-3-enecarboxamides. Mol Divers 18, 821–828 (2014). https://doi.org/10.1007/s11030-014-9541-7

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11030-014-9541-7

Keywords

Search

Navigation