Ferrocenoylation of Uracil Derivatives: Study of Reaction Regioselectivity and Biological Activity
Jasmina Lapić1, Ivana Kuzman1, Ruža Frkanec2
1Faculty of Food Technology and Biotechnology, University of Zagreb, Pierottijeva 6, 10000 Zagreb, Croatia.
Abstract:
The N-ferrocenoylation of uracil was studied to evaluate regioselectivity and optimise preparation protocols. Regioselectivity was monitored under various reaction conditions, with particular attention paid to the effects of the solvent and the base. Reactions in DMF were regiospecific, yielding only the N1 product, while reactions in CH3CN produced both N1 and N1/N3 products, with ratios depending on the reaction conditions. The highest yield of N1/N3-diferrocenoyl uracil was achieved with an extended reaction time of 90 min using uracil and triethylamine. Optimised conditions were applied to C5-uracil derivatives, producing N1 and N1/N3 products. Regioselectivity and N-substitution were confirmed by NMR, and solvent effects were supported by quantum chemical calculations. The resulting ferrocene-pyrimidine conjugates exhibited oxidative and immunomodulatory activity, highlighting their biological potential.
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