Heterocyclic Chemistry, Fifth Edition

27.8.2
 Amino - Purines 
27.8.2.1
 Alkylation 
Alkylation under neutral conditions involves attack at a nuclear nitrogen; Dimroth rearrangement ( 27.1.1.2 ) 
of these salts affords side - chain - alkylated purines. However, direct introduction of substituents onto a side -
chain nitrogen can be achieved by reductive N - alkylation. 
84
A related method involves reduction of an 
isolated benzotriazolyl intermediate, which allows more control over the process. 
85

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528
 Heterocyclic 
Chemistry
27.8.2.2
 Acylation 
Amino - purines behave just like anilines with anhydrides and acid chlorides, giving amides, but these are 
somewhat more easily hydrolysed. Both mono 
- 
and diacylation can be utilised as a protecting - group 
strategy.
27.8.2.3
 Diazotisation 
The reaction of 2 - and 6 - amino groups with nitrous acid is similar to that of 2 - amino - pyridines, in that 
diazonium salts are produced but, relative to phenyldiazonium salts, these are unstable. Despite this, they 
can be utilised for the introduction of groups such as halide 
86
or, oxygen by reaction with water, with loss 
of nitrogen. 8 - Diazonium salts are considerably more stable. 
87
In 2 - aminoadenosine, selective diazotisation 
occurs at the 2 - amino group. 
52
Diazotisation can also be carried out in basic solution and in this way acid - sensitive deoxyribosides can 
be tolerated. 
88
A nucleophilic displacement of amino by hydroxy can be effected enzymatically using 
adenosine deaminase; this is a useful practical method because it is a very selective transformation under 
mild conditions. 
89
Chemical hydrolysis requires more vigorous conditions. 
The related reaction with alkyl nitrites generates purinyl radicals, which will effi ciently abstract halogen 
from halogenated solvents, and this procedure is generally to be preferred for the transformation of an 
amino - purine into a halo - purine. 
90
These reactions can be improved/enhanced by the addition of antimony 
trichloride. 
91
Comparably, the use of dimethyl disulfi de produces methylthio - purines, 
92
and trimethylsilyl 
azide, azido - purines. 
93

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Purines: Reactions and Synthesis 529