Typical reactivity of the diazines pyridazine, pyrimidine and pyrazine

A very characteristic feature of diazine chemistry, which is associated with their strongly electron-poor nature, is that they add nucleophilic reagents easily. Without halide 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 nucleophilic displacements, the intermediates being particularly well stabilised. 

All positions on each of the diazines, with the sole exception of the 5-position 

Despite this particularly strong propensity for nucleophilic addition, C-lithia-tion of diazines can be achieved either by metal-halogen exchange or by deprotonation ortho to chloro or alkoxyl substituents, though very low temperatures must be utilised in order to avoid nucleophilic addition of the reagent. 

In line with their susceptibility to nucleophilic addition, diazines also undergo Minisci radical substitution with ease. 

Further examples of the enhancement of those facets of pyridine chemistry associated with the azomethine electron withdrawal include a general stability towards oxidative degradation but, on the other hand, a tendency to undergo rather easy reduction of the ring. 

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Typical Reactivity of the Diazines Pyridazine, Pyrimidine and Pyrazine... 

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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