Skip to main content
SpringerLink
Log in

1,3-Dipolar cycloaddition of benzyl azide to two highly functionalized alkynes

  • Original Paper
  • Published:
Monatshefte für Chemie - Chemical Monthly Aims and scope Submit manuscript

Abstract

Benzyl azide undergoes [3 + 2] cycloaddition when reacted with 3,3,4,4-tetraethoxybut-1-yne, a ketal, and the corresponding ketone, 1,1-diethoxybut-3-yn-2-one, in the presence of a Cu(I) salt in various solvents. The outcome is sensitive to the structure of the alkyne and the nature of the metal salt. Both alkynes give the corresponding 1,4-disubstituted 1,2,3-triazoles in up to 70% yield, but the ketone also affords a minor amount of the 1,5-disubstituted analogue. When CuI is used as catalyst, the ketal in addition furnishes some 1-benzyl-5-iodo-4-(1,1,2,2-tetraethoxyethyl)-1,2,3-triazole. On the other hand, when the reaction was carried out under Ru(II) catalysis, no 1,2,3-triazole formation was observed for any of the substrates; the ketal did not react at all, whereas the ketone underwent cyclotrimerization and gave 1,3,5-tris(2,2-diethoxyacetyl)benzene in 60% yield. No reaction occurred when the magnesium acetylide of 3,3,4,4-tetraethoxybut-1-yne was reacted with benzyl azide.

Graphical Abstract

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

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

Similar content being viewed by others

References

  1. Wamhoff H (1984) In: Katritzky AR, Rees CW, Potts KT (eds) Comprehensive heterocyclic chemistry; the structure, reactions, synthesis and uses of heterocyclic compounds, vol 5. Pergamon Press, Oxford, p 723

  2. Dehne H (1994) In: Schumann E (ed) Methoden der Organischen Chemie (Houben-Weyl), vol E8d. Thieme, Stuttgart, p 305

  3. Baures PW (1999) Org Lett 1:249

    Article  CAS  Google Scholar 

  4. Harrison T, Owens AP, Williams BJ, Swain CJ, Williams A, Carlson EJ, Rycroft W, Tattersall FD, Cascieri MA, Chicchi GG, Sadowski S, Rupnoak NM, Hargreaves RJ (2001) J Med Chem 44:4296

    Article  CAS  Google Scholar 

  5. Komeda S, Lutz M, Spek AL, Yamanaka Y, Sato T, Chikuma M, Reedijk J (2002) J Am Chem Soc 124:4738

    Article  CAS  Google Scholar 

  6. Dabak K, Sezer O, Akar A, Anac O (2003) Eur J Med Chem 38:215

    Article  CAS  Google Scholar 

  7. Hein CD, Liu X-M, Wang D (2008) Pharm Res 25:2216

    Article  CAS  Google Scholar 

  8. Moorhouse AD, Moses JE (2008) Chem Med Chem 3:715

    CAS  Google Scholar 

  9. Purcell WP, Singer JA (1967) J Phys Chem 71:4316

    Article  CAS  Google Scholar 

  10. Dimroth O, Fester G (1910) Ber Deutsch Chem Ges 43:2219

    CAS  Google Scholar 

  11. Sheehan JC, Robinson CA (1949) J Am Chem Soc 71:1436

    Article  CAS  Google Scholar 

  12. Hartzel LW, Benson FR (1954) J Am Chem Soc 76:667

    Article  Google Scholar 

  13. Woerner FP, Reimlinger H (1970) Chem Ber 103:1908

    Article  CAS  Google Scholar 

  14. Journet M, Cai D, Kowal JJ, Larsen RD (2001) Tetrahedron Lett 42:9117

    Article  CAS  Google Scholar 

  15. Jin T, Kamijo S, Yamamoto Y (2004) Eur J Org Chem 3789

  16. Fazio F, Bryan MC, Blixt O, Paulson JC, Wong C-H (2002) J Am Chem Soc 124:14397

    Article  CAS  Google Scholar 

  17. Löber S, Rodriguez-Loaiza P, Gmeiner P (2003) Org Lett 5:1753

    Article  Google Scholar 

  18. Tornøe CW, Christensen C, Meldal M (2002) J Org Chem 67:3057

    Article  Google Scholar 

  19. Tornøe CW, Sanderson SJ, Motram JC, Coombs GH, Meldal M (2004) Comb Chem 6:312

    Article  Google Scholar 

  20. Meldal M, Tornoe CW (2008) Chem Rev 108:2952

    Article  CAS  Google Scholar 

  21. Rostovtsev VV, Green LG, Fokin VV, Sharpless KB (2002) Angew Chem Int Edit 41:2596

    Article  CAS  Google Scholar 

  22. Chan TR, Fokin VV (2007) QSAR Comb Sci 26:1274

    Article  CAS  Google Scholar 

  23. Wang Q, Chan RC, Hilgraf R, Fokin VV, Sharpless KB, Finn MG (2003) J Am Chem Soc 125:3192

    Article  CAS  Google Scholar 

  24. Huisgen R (1963) Angew Chem 75:604

    Article  CAS  Google Scholar 

  25. Huisgen R, Szeimies G, Möbius L (1967) Chem Ber 100:2494

    Article  CAS  Google Scholar 

  26. Huisgen R (1984) In: Padwa A (ed) 1,3-Dipolar Cycloaddition Chemistry. Wiley, New York, vol 1, p 1

  27. Grimmett MR (1979) In: Barton D, Ollis WD, Sammes PG (eds) Comprehensive organic chemistry; the synthesis and reactions of organic compounds. Heterocyclic compounds, vol 4. Pergamon Press, Oxford, p 357 and p 402

  28. Sheehan JC, Robinson CA (1951) J Am Chem Soc 73:1207

    Article  CAS  Google Scholar 

  29. Moulin F (1952) Helv Chim Acta 35:167

    Article  CAS  Google Scholar 

  30. Kirmse W, Horner L (1958) Liebigs Ann Chem 614:1

    Article  CAS  Google Scholar 

  31. Huisgen R, Knorr R, Mobius L, Szeimies G (1965) Chem Ber 98:4014

    Article  CAS  Google Scholar 

  32. Sydnes LK (2000) Eur J Org Chem 3511

  33. Sydnes LK, Kvernenes OH, Valdersnes S (2005) Pure Appl Chem 77:119

    Article  CAS  Google Scholar 

  34. Kvernenes OH, Sydnes LK (2005) Org Synth 83:184

    Google Scholar 

  35. Sydnes LK, Holmelid B, Kvernenes OH, Sandberg M, Hodne M, Bakstad E (2007) Tetrahedron 63:4144

    Article  CAS  Google Scholar 

  36. Holmelid B, Kvernenes OH, Hodne M, Sydnes LK (2008) Arkivoc (vi):26

  37. Sydnes LK, Holmelid B, Myagmarsuren S, Hanstein M (2009) J Org Chem 74:3430

    Article  CAS  Google Scholar 

  38. Genin MJ, Allwine DA, Anderson DJ, Barbachyn MR, Emmert DE, Garmon SA, Graber DR, Grega KC, Hester JB, Hutchinson DK, Morris J, Reischer RD, Stper D, Yagi BH (2004) J Med Chem 43:953

    Article  Google Scholar 

  39. Buckle DR, Rockell CJM, Smith H, Spicer BA (1986) J Med Chem 29:2262

    Article  CAS  Google Scholar 

  40. Wamhoff H (1984) In: Katrizky AR, Rees CW (eds) Comprehensive heterocyclic chemistry. Pergamon Press, Oxford, p 669

  41. Velazquez S, Alvarez R, Perez C, Gago F, De C, Balzarini J, Camaraza MJ (1998) Antiviral Chem Chemother 9:481

    CAS  Google Scholar 

  42. Font D, Jimeno C, Pericas MA (2006) Org Lett 8:4653

    Article  CAS  Google Scholar 

  43. Seo TS, Li Z, Ruparel H, Ju J (2003) J Org Chem 68:609

    Article  CAS  Google Scholar 

  44. Díez-González S, Correa A, Cavallo L, Nolan SP (2006) Chem Eur J 12:7558

    Article  Google Scholar 

  45. Wu P, Fokin VV (2004) Aldrichim Acta 40:7

    Google Scholar 

  46. Lu L-H, Wu J-H, Yang C-H (2008) J Chinese Chem Soc 55:414

    CAS  Google Scholar 

  47. Aragão-Leoneti V, Campo VL, Gomes AS, Field RA, Carvalho I (2010) Tetrahedron 66:9475

    Article  Google Scholar 

  48. Zhang L, Chen X, Xue P, Sun HHY, Williams ID, Sharpless KB, Fokin VV, Jia G (2005) J Am Chem Soc 127:15998

    Article  CAS  Google Scholar 

  49. Rasmussen LK, Boren BC, Fokin VV (2007) Org Lett 9:5337

    Article  CAS  Google Scholar 

  50. Sheradsky T (1971) In: Patai S (ed) The chemistry of the azido group. Interscience Publishers. Wiley, London, p 331

  51. Cohrt AE, Jensen JF, Nielsen TE (2010) Org Lett 12:5414

    Article  CAS  Google Scholar 

  52. Li L, Zhang G, Zhu A, Zhang L (2008) J Org Chem 73:3630

    Article  CAS  Google Scholar 

  53. Girard C, Oenen E, Aufort M, Beauviere S, Samson E, Herscovici J (2006) Org Lett 8:1689

    Article  CAS  Google Scholar 

  54. Sydnes LK, Sengee M (2011) Synthesis 3899

  55. Kirchner K, Calhorda MJ, Schmid R, Veiros LF (2003) J Am Chem Soc 125:11721

    Article  CAS  Google Scholar 

  56. Yamamoto Y, Arakawa T, Ogawa R, Itoh K (2003) J Am Chem Soc 125:12143

    Article  CAS  Google Scholar 

  57. Krasinski A, Fokin VV, Sharpless KB (2004) Org Lett 6:1237

    Article  CAS  Google Scholar 

  58. Odlo K, Hentzen J, Fournier J, Ducki S, Gani OABSM, Sylte I, Skrede M, Florenes VA, Hansen TV (2008) Bioorg Med Chem 16:4829

    Article  CAS  Google Scholar 

  59. Alvarez SG, Alvarez MT (1997) Synthesis 413

  60. Bruker AXS. APEX2 Software Suite, v 2010.1-2 (2010). Bruker AXS Inc, Madison, Wisconsin, USA

Download references

Acknowledgments

Financial support from the Higher Education Commission (HEC) of Pakistan (to TF), administered by The Norwegian Centre for International Cooperation in Higher Education (SIU), is acknowledged with considerable appreciation. Thanks are also due to Terje Lygre and Egil Nodland at the University of Bergen and Jostein Johansen at the University of Tromsø for recording the mass spectra.

Author information

Authors and Affiliations

  1. Department of Chemistry, University of Bergen, Allégt. 41, 5007, Bergen, Norway

    Tahir Farooq, Leiv K. Sydnes & Karl W. Törnroos

  2. Centre of Pharmacy, University of Bergen, Allégt. 41, 5007, Bergen, Norway

    Bengt Erik Haug

Authors
  1. Tahir Farooq
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Bengt Erik Haug
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Leiv K. Sydnes
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Karl W. Törnroos
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Leiv K. Sydnes.

Electronic supplementary material

Below is the link to the electronic supplementary material.

Supplementary material 1 (PDF 302 kb)

Rights and permissions

Reprints and permissions

About this article

Cite this article

Farooq, T., Haug, B.E., Sydnes, L.K. et al. 1,3-Dipolar cycloaddition of benzyl azide to two highly functionalized alkynes. Monatsh Chem 143, 505–512 (2012). https://doi.org/10.1007/s00706-011-0691-3

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00706-011-0691-3

Keywords

Search

Navigation