View PDF Version
 
DOI: 10.1039/A707343G (Paper) Reference Section for: J. Chem. Soc., Perkin Trans. 1, 1998, 915-924

Antitumour polycyclic acridines. Part 3.1 A two-step conversion of 9-azidoacridine to 7H-pyrido[4,3,2-kl[hair space]]acridines by Graebe–Ullmann thermolysis of substituted 9-(1,2,3-triazol-1-yl)acridines

(Note: The full text of this document is currently only available in the PDF Version )

Damien J. Hagan, David Chan, Carl H. Schwalbe and Malcolm F. G. Stevens

Abstract

9-Azidoacridine 5 reacted with a series of alkynes to form mixtures of regioisomeric 9-(4- and 5-substituted-1,2,3-triazol-1-yl)acridines 6, except for the reaction with trimethylsilylacetylene which gave a single regioisomer. Structural assignments have been confirmed by 1H NMR and NOE experiments and the X-ray structure of 9-(4-butyl-1,2,3-triazol-1-yl)acridine 6a corroborates the positioning of the butyl group and shows that the plane of the triazole ring intersects that of the acridine moiety by 65.97(5)° in the crystal structure. Graebe–Ullmann fragmentation of the triazolylacridines was monitored by differential scanning calorimetry and preparative thermolytic conversion to 2- or 3-substituted 7H-pyrido[4,3,2-kl[hair space]]acridines 8 was performed in hot diphenyl ether. Whereas 9-[4-(3-chloropropyl)-1,2,3-triazol-1-yl]acridine 11 cyclised to 3-(3-chloropropyl)-7H-pyrido[4,3,2-kl[hair space]]acridine 13, the isomeric triazole 12 afforded the pentacyclic salt 1H,8H-2,3-dihydroindolizino[7,6,5-kl[hair space]]acridinium chloride 15.

References

  1. Part 2. E. Giménez-Arnau, S. Missailidis and M. F. G. Stevens, Anti-Cancer Drug Des., 1998, in the press Search PubMed.
  2. D. J. Hagan, E. Giménez-Arnau, C. H. Schwalbe and M. F. G. Stevens, J. Chem. Soc., Perkin Trans. 1, 1997, 2739 RSC.
  3. C. Graebe and F. Ullmann, Justus Liebigs Ann. Chem., 1896, 291, 16.
  4. L. A. McDonald, G. S. Eldredge, L. R. Barrows and C. M. Ireland, J. Med. Chem., 1994, 37, 3819 CrossRef CAS; T. F. Molinski, Chem. Rev., 1993, 93, 1825 CrossRef CAS.
  5. D. J. Hagan, Ph.D. Thesis, University of Nottingham, 1996.
  6. G. A. Reynolds, J. Org. Chem., 1964, 29, 3733 CAS.
  7. G. Mitchell and C. W. Rees, J. Chem. Soc., Perkin Trans. 1, 1987, 403 RSC.
  8. A. C. Mair and M. F. G. Stevens, J. Chem. Soc., Perkin Trans. 1, 1972, 161 RSC.
  9. D. J. Hlasta and J. H. Ackerman, J. Org. Chem., 1994, 59, 6184 CrossRef CAS; A. Padwa and M. W. Wannamaker, Tetrahedron, 1990, 46, 1145 CrossRef CAS.
  10. G. Mitchell and C. W. Rees, J. Chem. Soc., Perkin Trans. 1, 1987, 413 RSC.
  11. British Patent Appl., 1997, No. 6452002 Search PubMed.
  12. P. Main, G. Germain and M. M. Woolfson, MULTAN84. A System of Computer Programs for the Automatic Solution of Crystal Structures from X-ray Diffraction Data, Universities of York, England, and Louvain, Belgium, 1984.
  13. G. M. Sheldrick, SHELXL93. Program for the Refinement of Crystal Structures, University of Göttingen, Germany, 1993.
  14. C. K. Johnson, ORTEPII, Report ORNL-5136, Oak Ridge National Laboratory, Tennessee, USA, 1976.
Click here to see how this site uses Cookies. View our privacy policy here.