Ferrocenoylation of Uracil Derivatives: Study of Reaction Regioselectivity and Biological Activity

The <i>N</i>-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 <i>N</i>1 product, while reactions in CH₃CN produced both <i>N</i>1 and <i>N</i>1/<i>N</i>3 products, with ratios depending on the reaction conditions. The highest yield of <i>N</i>1/<i>N</i>3-diferrocenoyl uracil was achieved with an extended reaction time of 90 min using uracil and triethylamine. Optimised conditions were applied to <i>C</i>5-uracil derivatives, producing <i>N</i>1 and <i>N</i>1/<i>N</i>3 products. Regioselectivity and <i>N</i>-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.