Radical anions from 5-fluorouracil derivatives. A theoretical study of their cleavage and orbital isomerism

Abstract

Theoretical calculations were performed on the dissociation of radical anions of 5-fluorouracils substituted at N1. The reaction (1-CR1R2R3-5-fluorouracil)−→(5-fluorouracil)−+R1R2R3C was calculated for several substituents R, including the N1–C5 dimers 1. Two main types of radical anions were observed. Radical anions of π type have the unpaired spin density located at the carbonyl and C–C double bond conjugated system of the uracil ring while the σ species present unpaired spin density mainly at the N1–C(R1R2R3) bond. The electronic nature of the most stable radical anion was found to be determined by the electron affinity of the substituent at N1.The activation barrier for the cleavage of π radical anions arises from its avoided crossing with the σ potential surface. The σ radical anions, which have stabilised SOMOs, dissociate with lower activation barriers than the π intermediates. These observations correlate with the lengthening and increment of unpaired spin density at their N1–C bond. Gas phase calculations are compared with results in aqueous solution. Other fragmentation paths are proposed for substituents like RNO2 or halogen.