Purine halogen exchange

Purines lithiated at C-2 or C-6 can be generated by way of halogen exchange with alkylUthiums, but it is important to maintain a very low temperature in order to avoid subsequent equihbration to the more stable... 

Methods to synthesise 6-fluoro substituted purines have included reactions involving tertiary amine displacement of a 6-halo substituent and subsequent fluoride displacement of the intermediate, diazotization-fluorodediazonation strategies, direct HALEX (HALogen Exchange) reactions, ring closure of an appropriately substituted precursor and SnAt chemistry on a 6-nitropurine. 

The exchange of a halogen to a classical nitrogen or oxygen nucleophile usually proceeds readily on the purine skeleton, without the necessity of using a transition metal catalyst. There are certain cases, however, where the palladium catalyzed carbon-heteroatom bond formation might take preference over noncatalysed methods. Inosine derivatives, for example,... 

A halogen - metal exchange reaction between butyllithium and an appropriately A-protected halopurine has been applied for C-C bond formation of intact purines. Operation at low temperature is required in order to avoid diversionary attacks on the heterocyclic ring, e.g. formation of 17. ... 

These reactions, involving nucleophilic displacement of other halogens by fluoride anion are important industrially and of some use in the laboratory for electron-deficient rings. The exchange/equilibrium of with is of use in PET (see 31.2.3). Nitro is also a good leaving group for this process in a number of systems purines (27.5), pyridines (8.3.2) and 1,2,4-triazoles (29.1.1.2). 

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