Purines 125Electrophilic substitution at carbon
Simple purines are generally resistant to electrophilic substitution at carbon but oxo- and amino-compounds will
react, under fairly normal conditions, in the electron-rich imidazole ring at C-8.
Diverse 6-substituted purines can be ‘nitrated’ at C-2, although the mechanism is not direct electrophilic substitution.
The transformation is brought about using the mixed anhydride of trifl uoroacetic acid and nitric acid, generated in situ,
and is initiated by electrophilic attack on N-7. Addition of trifl uoroacetoxy to C-8 follows, then migration of the nitro
group to C-2, and fi nally re-aromatisation. This is a particularly useful reaction as nitro is a good leaving group for
subsequent nucleophilic substitution.
N-Deprotonation and N-metallated purines
N-Alkylation of purines that have a free imidazole NH is most commonly carried out under basic conditions, when
reaction occurs in the imidazole ring via an N-anion. This often results in a mixture of N-7/N-9 isomers, but such reac-
tions can be driven towards N-9 by the presence of bulky substituents at C-6.