ABC  Vol.3 No.6 , December 2013
Synthesis of C-8 alkyl xanthines by pentaamminecobalt(III) complex

Alkyl xanthines underwent selective homolytic aromatic substitution at C-8 position with alkyl groups of pentaamminecobalt(III) complex. In this process of synthesis, we used monoalkyl hydrazines as the radical source in aqueous ammonia solution. Evidence supporting coordination of the alkyl hydrazine to pentaamminecobalt(III) complex by radical trapping was in good agreement with literature. The products were characterized using GC-MS and 1H, 14N and 59Co NMR spectroscopy.


Cite this paper: Suravajhala, R. (2013) Synthesis of C-8 alkyl xanthines by pentaamminecobalt(III) complex. Advances in Biological Chemistry, 3, 521-524. doi: 10.4236/abc.2013.36058.

[1]   S.M. Kaiser and R. J. Quinn, “Adenosine Receptors as Potential Therapeutic Targets,” Drug Discovery Today, Vol. 4, No. 12, 1999, pp. 542-551.

[2]   A. Tenzer and M. Pruschy, “Potentiation of DNA-DamageInduced Cytotoxicity by G2Checkpoint Abrogators,” Current Medicinal Chemistry-Anti-Cancer Agents, Vol. 3, No. 1, 2003, pp. 35-46.

[3]   F. Borges, E. Fernandes and F. Roleira, “Progress towards the Discovery of Xanthine Oxidase Inhibitors,” Current Medicinal Chemistry, Vol. 9, No. 2, 2002, pp. 195-217.

[4]   F. Joo, “Aqueous Organometallic Catalysis,” Springer Series, Vol. 23, 2001, pp. 312-318.

[5]   S. Z. Zard, “Radical Reactions in Organic Synthesis,” Oxford University Press, Oxford, 2003.

[6]   M. F. Zady and J. L. Wong, “ Reactivities and Electronic Aspects of Nucleic Acid Heterocycles. Part 6. Kinetics and Mechanism of Carbon-8 Methylation of Purine Bases and Nucleosides by Methyl Radical,” Journal of the American Chemical Society, Vol. 99, No. 15, 1977, pp. 5096-5101.

[7]   E. Castagnino, S. Corsano, D. H. R. Barton and S. Z. Zard, “Decarboxylative Radical Addition onto Protonated Heteroaromatic Systems Including Purine Bases,” Tetrahedron Letters, Vol. 27, No. 52, 1986, pp. 6337-6338.

[8]   T. Itahara and N. Ide, “Free Radical Alkylation of 1,3-Dimethyluracils and Caffeine with Benzoyl Peroxide,” Bulletin of the Chemical Society of Japan, Vol. 65, No. 8, 1992, pp. 2045-2049.

[9]   P. Kofod, “The Pentaamminemethylcobalt(III) Cation: Synthesis and Spectroscopic Characterization,” Inorganic Chemistry, Vol. 34, No. 10, 1995, pp. 2768-2770.

[10]   J. Evans, “Biomolecular NMR Methods,” Oxford University Press, Oxford, 1995.

[11]   R. D. Jones, D. A. Summerville and F. Basolo, “Synthetic Oxygen Carriers Related to Biological Systems,” Chemical Reviews, Vol. 79, No. 2, 1979, pp. 139-179.

[12]   D. Nicholls, M. Rowley and R. Swindells, “Hydrazine Complexes of Cobalt(II) Chloride,” Journal of the Chemical Society, Vol. 5, 1996, pp. 950-953.

[13]   A. Anagnostopoulos and D. J. Nicholls, “Some Complexes of Hydrazine, Methylhydrazine and 1,1-Dimethylhydrazine with Cobalt(II) Salts,” Journal of Inorganic and Nuclear Chemistry, Vol. 38, No. 9, 1976, pp. 1615-1618.

[14]   A. A. Rahman, M. P. Brown, M. M. Harding, C. E. Keggan and D. Nichols, “Coordination Compounds of Ethylhydrazine and 2,2,2-Trifluoroethylhydrazine; Crystal and Molecular Structure of Dichlorotetrakis(2,2,2-Trifluoroethylhydrazine) Nickel(II),” Polyhedron, Vol. 7, No. 13, 1988, pp. 1147-1152.

[15]   P. Kofod, “Alkylcobalt(III) Compounds with Ammine Ligands,” Inorganic Chemistry Communications, Vol. 8, No. 10, 2005, pp. 943-946.

[16]   P. Kofod, “GMP and AMP as Methyl Radical Traps in the Reaction with Pentaamminemethylcobalt(III),” Journal of Inorganic Biochemistry, Vol. 98, No. 11, 2004, pp. 1978-1980.

[17]   S. C. F. Au-Yeung, S. Eaton and R. Donald, “A Model for Estimating 59Co nmr Chemical Shifts and Line Widths and Its Application to Cobalt Dioxygen Complexes,” Canadian Journal of Chemistry, Vol. 61, No. 10, 1983, pp. 2431-2441.

[18]   R. Suravajhala, N. Suri, M. Bhagat and A. K. Saxena, “Biological Evaluation of 8-Alkyl Xanthines as Potential Cytotoxic Agents,” Advances in Biological Chemistry, Vol. 3, No. 3, 2013, 314.