Typical Reactivity of the Diazine Pyridazine, Pyrimidine and Pyrazine

Typical Reactivity of the Diazines Pyridazine, Pyrimidine and Pyrazine 

Typical reactions of a diazine illustrated with pyrimidine 

Avery characteristic feature of the chemistry of diazines, which is associated with their strongly electron-poor nature, is that they add nucleophihc reagents easily. Without hahde to be displaced, such adducts require an oxidation to complete an overall substitution. However, halo-diazines, where the halide is a or y to a nitrogen, undergo very easy nucleophihc displacements, the intermediates being particularly well stabilised. In hne with their susceptibihty to nucleophihc addition, diazines also undergo substitution by nucleophihc radicals, in acid solution, with ease. 

Heterocyclic Chemistry 5th Edition John Joule and Keith Mills 2010 Blackwell Publishing Ltd 

All positions on each of the diazines, with the sole exception of the 5-position of a pyrimidine, are a and/or y to an imine ring nitrogen and, in considering nncleophilic addition/snbstitution, it mnst be remembered that there is also an additional nitrogen that is withdrawing electron density. As a consequence, all the monohalo-diazines are more reactive than either 2- or 4-halo-pyridines. The 2- and 4-halo-pyrimidines are particularly reactive because the anionic intermediates (shown below for attack on a 2-halo-pyrimidine) derive direct mesomeric stabilisation from both nitrogen atoms. 

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Typical reactivity of the diazines pyridazine, pyrimidine and pyrazine... 

Tetrafluoropyrimidine Perfluorinated diazines (pyrimidine, pyrazine, and pyridazine) are typically 1000 times more reactive toward nucleophiles than pentafluoropyridine. Various reactions of tetrafluoropyrimidine with a small range of nucleophiles have been reported (Fig. 8.15) and, in all cases, nucleophilic substitution occurs selectively at the 4-position, consistent with the mechanistic principles discussed above. 

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