On the Alkylation of 5-Fluorouracil-Some Recent Findings

Since its discovery 5-fluorouracil ¹(1,5-FU), an important anticancer drug, has been the subject of study for the preparation of some suitable derivatives² which may have better therapeutic efficacy. These are prepared through silylation method³, mercuri salt method⁴ and direct alkylation method⁵ of 5-FU. It was reported⁵ that the direct alkylation of 5-FU with saturated and allylic type halides under controlled conditions occur at N₃ (3-) and N₁ (1-) position respectively in contrast to alkylation of uracil where N₁ alkylated products are obtained in both cases. The position of alkylation in 5-FU was determined, with analogy from uracil⁶, by the bathochromic shift in UV from the neutral pH to alkaline pH of the 3-substituted product compared to no such shift of the 1-substituted product.