Regioselective and stereoselective synthesis of epithiomethanoiminoindeno[1,2-b]furan-3-carbonitrile: heterocyclic [3.3.3]propellanes


Synthesis of heteropropellanes in one step: the reaction between dicyanomethylene-1,3-indanedione (CNIND) and N-substituted-2-(2,4-dinitrophenyl)hydrazinecarbothioamides, furnished (3aR,8bS,Z)-2-amino-9-substituted-10-(2-(2,4-dinitrophenyl)hydrazono)-4-oxo-4H-3a,8b-(epithiomethanoimino)indeno[1,2-b]furan-3-carbonitrile as a type of (2,4-dinitrophenyl)hydrazono[3.3.3]propellanes in good yields as single diastereomers. Structure determination and confirmation of the synthesized products have been achieved using various and modern spectroscopic techniques such as IR, NMR (1H NMR and 13C NMR), mass spectrometry, as well as X-ray crystal analysis. The X-ray structure data cleared that the molecule of 7a was crystalized as monoclinic, space group C2/c (no.15).

Graphic abstract

This is a preview of subscription content, access via your institution.

Scheme 1
Scheme 2
Fig. 1
Scheme 3
Fig. 2


  1. 1.

    Wiberg KB (1989) Small ring propellanes. Chem Rev 89:975–983.

    CAS  Article  Google Scholar 

  2. 2.

    Ginsburg D (1975) Propellanes. Structure and reactions. Verlag Chemie, Weinheim, p 272

    Google Scholar 

  3. 3.

    Pihko AJ, Koskinen AMP (2005) Synthesis of propellane-containing natural products. Tetrahedron 61:8769–8807.

    CAS  Article  Google Scholar 

  4. 4.

    Dilmaç AM, Spuling E, de Meijere A, Bräse S (2017) Propellanes—from a chemical curiosity to “explosive” materials and natural products. Angew Chem Int Ed Engl 56:5684–5718.

    CAS  Article  PubMed  Google Scholar 

  5. 5.

    Debroy P, Lindeman SV, Rathore R (2007) Hexabenzo[4.4.4]propellane: a helical molecular platform for the construction of electroactive materials. Org Lett 9:4091–4094.

    CAS  Article  PubMed  Google Scholar 

  6. 6.

    Müller B, Bally T, Pappas R, Williams F (2010) Spectroscopic and computational studies on the rearrangement of ionized [1.1.1]propellane and some of its valence isomers: the key role of vibronic coupling. J Am Chem Soc 132:14649–14660.

    CAS  Article  PubMed  Google Scholar 

  7. 7.

    Nagasea H, Nakajima R, Yamamotoa N, Hirayama S, Iwai T, Nemoto T, Gouda H, Hirono S, Fujii H (2014) Design and synthesis of quinolinopropellane derivatives with selective d opioid receptor agonism. Bioorg Med Chem Lett 24:2851–2854.

    CAS  Article  Google Scholar 

  8. 8.

    Rey-Carrizo M, Barniol-Xicota M, Ma C, Frigolé-Vivas M, Torres E, Naesens L, Llabrés S, Juárez-Jiménez J, Luque FJ, DeGrado WF, Lamb RA, Pinto LH, Vázquez S (2014) Easily accessible polycyclic amines that inhibit the wild-type and amantadine-resistant mutants of the M2 channel of influenza a virus. J Med Chem 57:5738–5747.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  9. 9.

    Qian-Cutrone J, Gao Q, Huang S, Klohr SE, Veitch JA, Shu YZ (1994) Arthrinone, a novel fungal metabolite from Arthrinium sp. FA 1744. J Nat Prod 57:1656–1660.

    CAS  Article  Google Scholar 

  10. 10.

    Konishi M, Ohkuma H, Tsuno T, Oki T, VanDuyne GD, Clardy J (1990) Crystal and molecular structure of dynemicin A: a novel 1,5-diyn-3-ene antitumor antibiotic. J Am Chem Soc 112:3715–3716.

    CAS  Article  Google Scholar 

  11. 11.

    Chu M, Truumees I, Patel MG, Gullo VP, Puar MS, McPhail AT (1994) Structure of Sch 49209: a novel antitumor agent from the fungus Nattrassia mangiferae. J Org Chem 59:1222–1223.

    CAS  Article  Google Scholar 

  12. 12.

    Tian X, Li L, Hu Y, Zhang H, Liu Y, Chen H, Ding G, Zou Z (2013) Dichrocephones A and B, two cytotoxic sesquiterpenoids with the unique [3.3.3] propellane nucleus skeleton from Dichrocephala benthamii. RSC Adv 3:7880–7883.

    CAS  Article  Google Scholar 

  13. 13.

    Zhu H, Chen C, Tong Q, Li XN, Yang J, Xue Y, Luo Z, Wang J, Yao G, Zhang Y (2016) Epicochalasines A and B: two bioactive merocytochalasans bearing caged epicoccine dimer units from Aspergillus flavipes. Angew Chem Int Ed Engl 55:3486–3490.

    CAS  Article  PubMed  Google Scholar 

  14. 14.

    Humphrey GR, Kuethe JT (2006) Practical methodologies for the synthesis of indoles. Chem Rev 106:2875–2911.

    CAS  Article  PubMed  Google Scholar 

  15. 15.

    Cacchi S, Fabrizi G (2005) Synthesis and functionalization of indoles through palladium-catalyzed reactions. Chem Rev 105:2873–2920.

    CAS  Article  PubMed  Google Scholar 

  16. 16.

    Battistuzzi G, Cacchi S, Fabrizi G (2002) Aerobic oxidation of N-alkylamides catalyzed by N-hydroxyphthalimide under mild conditions. Polar and ENTHALPIC EFFECTS. Eur J Org Chem 67:2671–2676.

    CAS  Article  Google Scholar 

  17. 17.

    Alizadeh A, Bayat F (2014) Highly convergent one-pot four-component regioselective synthesis of spiro-pyranopyrazoles and oxa-aza-[3.3.3]propellanes. Helv Chim Acta 97:694–700.

    CAS  Article  Google Scholar 

  18. 18.

    Alizadeh A, Rezvanian A, Zhu LG (2012) Synthesis of heterocyclic [3.3.3]propellanes via a sequential four-component reaction. J Org Chem 77:4385–4390.

    CAS  Article  PubMed  Google Scholar 

  19. 19.

    Alizadeh A, Bayat F, Zhu LG (2014) Regioselective multicomponent sequential synthesis of oxa-aza[3.3.3]propellanes. Aust J Chem 67:949–952.

    CAS  Article  Google Scholar 

  20. 20.

    Rezvanian A, Alizadeh A (2012) Powerful approach to synthesis of fused oxa-aza[3.3.3]propellanes via chemoselective sequential MCR in a single pot. Tetrahedron 68:10164–10168.

    CAS  Article  Google Scholar 

  21. 21.

    Zhang LJ, Yan CG (2013) One-pot domino reactions for synthesis of heterocyclic[3.3.3]propellanes and spiro[cyclopenta[b]pyridine-4,20-indenes]. Tetrahedron 69:4915–4921.

    CAS  Article  Google Scholar 

  22. 22.

    Shin M, Kim MH, Ha T, Jeon J, Chung K, Kim JS, Kim YG (2014) Synthesis of novel 2,4,6,8,10-pentaaza[3.3.3]propellane derivatives. Tetrahedron 70:1617–1620.

    CAS  Article  Google Scholar 

  23. 23.

    Shin M, Ha TH, Chung KH, Kim JS, Kim YG (2014) Nitration of 3,7,9,11-tetraoxo-2,4,6,8,10-pentaaza[3.3.3]propellane. Appl. Chem. Eng. 25:188–192.

    CAS  Article  Google Scholar 

  24. 24.

    Lee B, Shin M, Seo Y, Kim MH, Lee HR, Kim JS, Chung KH, Yoo D, Kim YG (2018) Synthesis of 2,4,6,8,9,11-hexaaza[3.3.3]propellanes as a new molecular skeleton for explosives. Tetrahedron 74:130–134.

    CAS  Article  Google Scholar 

  25. 25.

    Yang DL, Fu L, Li JR, Zhang Q, Shi DX (2016) Synthesis and crystal structure of 10-(4-nitrobenzyl)-3,7,9,11-tetraoxo-2,4,6,8,10-pentaaza[3.3.3]propellane. J Chem Res 40:341–344.

    CAS  Article  Google Scholar 

  26. 26.

    Yavari I, Khajeh-Khezri A, Halvagar MR (2018) A synthesis of thioxo[3.3.3]propellanes from acenaphthoquinone-malononitrile adduct, primary amines and CS2 in waterArab. J Chem 11:188–195.

    CAS  Article  Google Scholar 

  27. 27.

    Hassan AA, Mohamed NK, Abdel-Haleem LE, Bräse S, Nieger M (2016) Synthesis of new furo-imidazo[3.3.3]propellanes. Curr Org Synth 13:426–431.

    CAS  Article  Google Scholar 

  28. 28.

    Hassan AA, Mohamed SK, Abdel-Latif FF, Mostafa SM, Abdel-Aziz M, Magued JT, Akkurt M (2016) A novel method for the synthesis of furo-imidazo[3.3.3]propellanes from thiocarbonohydrazides. Synlett 27:412–416.

    CAS  Article  Google Scholar 

  29. 29.

    Hassan AA, Aly AA, Mohamed NK, El Shaieb KMA, Makhlouf MM, El-SMN Abdelhafez, Bräse S, Nieger M, Dalby KN, Kaoud TS (2019) Design, synthesis, and DNA interaction studies of furo-imidazo[3.3.3]propellane derivatives: potential anticancer agents. J Bioorg Chem 85:585–599.

    CAS  Article  Google Scholar 

  30. 30.

    Nematpour M, Abedi E (2017) An efficient synthesis of novel sulfonyl[3.3.3]heteropropellanes from sulfonylacetamidines and ninhydrin-malononitrile adduct. J Sulfur Chem 38:229–235.

    CAS  Article  Google Scholar 

  31. 31.

    Rezvanian A, Alizadeh A, Zhu LG (2012) Chemo- and regioselective 4CR synthesis of oxathiaaza[3.3.3]propellanes via sequential C–S, C–N and C–O bond formation in a single pot. Synlett 23:2526–2530.

    CAS  Article  Google Scholar 

  32. 32.

    Hassan AA, Mohamed NK, Makhlouf MM, Bräse S, Nieger M (2015) Synthesis of oxa-aza- and bis-oxathiaaza[3.3.3]propellanes from dicyanomethylene-1,3-indanedione and 2,5-dithiobiureas. Synthesis 47:3036–3042.

    CAS  Article  Google Scholar 

  33. 33.

    Hassan AA, El-Shaieb KMA, Abd El-Aal AS, Bräse S, Nieger M (2016) Synthesis of bis-oxathiaaza[3.3.3]propellanes via nucleophilic addition of (1,ω-alkanediyl)bis(N′-organylthio-ureas) on dicyanomethylene-1,3-indanedione. Arkivoc (v): 406–415.

  34. 34.

    Hassan AA, Mohamed NK, Aly AA, Tawfeek HN, Hopf H, Bräse S, Nieger M (2019) Convenient diastereoselective synthesis of annulated 3-substituted-(5S*,6S*, Z)-2-(2-(2,4-dinitrophenyl)-hydrazono)-5,6-diphenyl-1,3-thiazinan-4-ones. Mol Divers.

    Article  PubMed  Google Scholar 

  35. 35.

    Hassan AA, Mohamed NK, Aly AA, Tawfeek HN, Bräse S, Nieger M (2019) Synthesis and crystallographic evaluation of diazenyl- and hydrazothiazoles. [5.5] sigmatropic rearrangement and formation of thiazolium bromide dehydrate. Mol Struct 1176:346–356.

    CAS  Article  Google Scholar 

  36. 36.

    Junek H, Fischer-Colbrie H, Hermetter A (1977) Synthesen mit Nitrilen, XLVIII. Merocyanine und Oxonole von Phenyl-indanyliden-acetonitrilen. Z. Naturforschung (B) 32b:898–903

  37. 37.

    Christian Reichardt, C (2011) Solvents and solvent effects in organic chemistry, 3 edn. WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim, p 710.

  38. 38.

    Cipiciani JA, Santini S, Savelli G (1999) Molecular complexes between substituted indoles and tetracyanoethylene. J Chem Soc Faraday Trans I 75:497–502.

    Article  Google Scholar 

  39. 39.

    Chatterjee S (1969) Studies of the charge-transfer complexes of 2-dicyanomethyleneindane-1,3-dione. J Chem Soc (B):725–729.

  40. 40.

    Sheldrick GM (2015) SHELXT: SHELXT—integrated space-group and crystal-structure-determination. Acta Crystallogr A 71:3–8.

    CAS  Article  Google Scholar 

  41. 41.

    Sheldrick GM (2015) SHELXL: crystal structure refionement with SHEXL. Acta Crystallogr C 71:3–8.

    CAS  Article  Google Scholar 

  42. 42.

    Spek AL (2015) PLATON SQUEEZE: a tool for the calculation of the disordered solvent contribution to the calculated structure factors. Acta Crystallogr C 71:9–18.

    CAS  Article  Google Scholar 

  43. 43.

    Sheldrick GM (2008) SHELXS: a short history of SHELX. Acta Crystallogr A 64:112–122.

    CAS  Article  PubMed  Google Scholar 

  44. 44.

    Parson S, Flack HD, Wagner T (2013) Use of intensity quotients and differences in absolute structure refinement. Acta Crystallogr B 69:249–259.

    CAS  Article  Google Scholar 

Download references


Alaa A. Hassan is indebted to the AvH-Foundation for the donation of a Shimadzu 408 IR instrument.

Author information



Corresponding author

Correspondence to Alaa A. Hassan.

Additional information

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Electronic supplementary material

Rights and permissions

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark

Cite this article

Hassan, A.A., Mohamed, N.K., Aly, A.A. et al. Regioselective and stereoselective synthesis of epithiomethanoiminoindeno[1,2-b]furan-3-carbonitrile: heterocyclic [3.3.3]propellanes. Mol Divers 25, 99–108 (2021).

Download citation


  • Annulated compounds
  • Heterocyclization
  • Imine-enamine tautomerism
  • Nucleophilic addition
  • Furothiazolo[3.3.3]propellanes
  • Thiosemicarbazides