Fluorination of pyrimidines. Part 2. Mechanistic aspects of the reaction of acetyl hypofluorite with uracil and cytosine derivatives

Abstract

The reaction of acetyl hypofluorite (AcOF) with uracil, cytosine, and some N-1-substituted derivatives dissolved in either acetic acid or water has been investigated. Analysis by radio-h.p.l.c., using ¹⁸F as a tracer, and by ¹H n.m.r. revealed that a substituent at N-1 of uracil has a remarkable effect on the stability of the intermediate 6-acetoxy-5-fluoro-5,6-dihydrouracils. Substitution at N-1 of cytosine did not really enhance the stability of the intermediate adducts. In addition, it was found that these cytosine adducts rapidly deaminate in water yielding their corresponding uracil analogues.