Purines 127(regarding reactivity, rates and selectivity) between different permutations of leaving group and nucleophile is very
complex.
Halide located at any of the three available carbons – C-2, C-6 and C-8 – is readily displaced. In a 9-substituted purine,
which cannot form an N-anion, the relative reactivity is 8 6 2. However, in a 9H-purine, this is modifi ed to 6 8 2,
the demotion of the 8-position being associated with anion formation in the fi ve-membered ring. The presence of an
amino group reduces the reactivity of a purine halide but it is enhanced by electron-withdrawing oxo groups. One
illustration of relative reactivity is the conditions required for the reactions of 2- and 6-chloropurines with hydrazine.
Halo-oxo-purines react easily, even with poor nucleophiles.
Other useful leaving groups include trifl ate, alkylthio and arylthio, and sulfone, the last also being involved in the
sulfi nate-catalysed displacement of halide. Signifi cantly, in this process, sulfi nate is more reactive than cyanide as a
nucleophile for the displacement of chloride but is also more reactive than chloride as a leaving group, as illustrated by
the stoichiometric reactions shown below.
A similar device commonly used to activate purine chlorides is reaction with a tertiary amine, such as trimethylamine,
giving a quaternary salt that has greatly enhanced reactivity. This can also be carried out as separate steps or in situ.
Even primary amino groups can be easily converted into leaving groups by conversion into a 1,2,4-triazole.