Nuclcophilic substitution reactions of 5‐acetoxymethyl‐and 5‐p‐nitrophenoxymethyluraeils

The synthesis of a number of 5‐acetoxymethyl‐ and 5‐p‐nitrophenoxymethyluracils and their nucleophilic substitution reactions with sodium methoxide and sodium borohydride are reported. These reactions all appear to involve intermediates with carbonium ion character, the formation of which are dependent upon structural features of the heterocycle. Most facile reactions occur when the 1‐position of the heterocycle can accommodate a negative charge to assist in the formation of highly reactive 5‐methenyluracil (VII) intermediates. Where ionization is precluded, as with 1‐methyl derivatives (IVb, VIb) displacements are retarded but may be assisted by addition of a nucleophilc to the 6‐position of the heterocycle. Analogous 1,3‐dialkylpyrimidines may react with nucleophiles at the 4‐carbonyl group to give anomalous products. Biological connotations of these reactions are discussed.