engleski

Ferrocenoyl-Substituted Pyrimidine Nucleobases. Experimental and Computational Study of Regioselective Acylation of Uracil, Thymine, and 5-Fluorouracil

Uracil, thymine, and 5-fluorouracil (5-FU) have been ferrocenoylated selectively at the N1-position. Deprotonated pyrimidine nucleobases, prepared by sodium hydride (NaH) in dimethylformamide (DMF), reacted with ferrocenoyl chloride (FcCOCl), or ferrocenoyl ethyl carbonate (FcCOOCOOEt), in DMF to obtain a single product. Regioselectivity of these reactions have been analyzed in detail using NMR spectroscopy and quantum chemical calculations. 1H and 19F NMR spectra of reaction mixtures, and 13C NMR and 2D NOESY spectra of products, confirm the formation of the N1-isomer only. The calculated energy barrier for acetylation at the N3-position is significantly higher (> 40 kJ/mol), which suggests that the analogous reaction at the N1-position is kinetically controlled. The nucleophilic addition of pyrimidine bases to the carbonyl group of FcCOCl proceeds by a concerted SN2-like mechanism with the absence of the generally assumed tetrahedral intermediate.

Acylation; Density functional calculations; Nucleobases; Reaction mechanisms; Regioselectivity

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