Diazines 49Unlike the purines, these pyrimidine bases and their nucleosides and nucleotides generally do not have a great deal of
biological signifi cance outside of their participation in nucleic acids. However, an exception is uridine di/triphosphate,
which has a key role in glucose metabolism and the biosynthesis of glycogen. Pyrazines have widespread natural occur-
rences, in low concentrations (see Food and Drink, page 186), but pyridazines are rare in nature.
Electrophilic addition to nitrogen
The inductive and mesomeric effects of the second nitrogen lead to a considerable reduction in the basicity of the
parent diazines relative to pyridine (pKaH 5.2). However, secondary effects result in a different order of basicity
between the individual diazines than would be predicted based simply on induction. In particular, destabilising
interactions between the adjacent nitrogen lone pairs in pyridazine lead to a relatively higher basicity. Only in very
strong acid can a proton be added to both nitrogens, giving doubly protonated salts.
The diazines react with alkyl halides to give quaternary salts, although somewhat less readily than does pyridine. Pyridazine
is the most reactive. Steric hindrance by substituents adjacent to ring nitrogens generally governs regioselectivity.
All three diazines react with peracids to give N-oxides, but less acidic conditions are required for pyrimidine, due to the
susceptibility of pyrimidine N-oxide to acid-catalysed decomposition.
Electrophilic substitution at carbon
Direct electrophilic attack at carbon in simple diazines is unusual. Pyrimidine can be brominated under conditions
similar to those required for pyridine, reaction occurring at the 5-position – the only position that is not or to nitro-
gen and therefore equivalent to a -position in pyridine – in fact it is the only such position in any diazine. Chlorination
of 2-methylpyrazine occurs under such mild conditions that some mechanism other than a classical aromatic elec-
trophilic substitution must be involved: addition of chlorine across the 3,4-imine unit, initiated by electro philic attack
on nitrogen, then loss of hydrogen chloride, is the most likely sequence.