50 Diazines
The amino-diazines, benefi ting from activation by the electron-releasing substituent, generally undergo electrophilic
substitution under normal conditions. Oxy-diazines are similarly activated for electrophilic substitution but this prob-
ably owes more to the enamine-like system present in the keto-tautomer, which allows electron donation from the ring
nitrogen. With two activating groups, even mild electrophiles can bring about substitution.
N-Oxides are also useful substrates for electrophilic substitution, another parallel to the chemistry of pyridines.
Nucleophilic substitution
The simple diazines are much more susceptible to nucleophilic attack than is pyridine. Pyrimidine, for example, is
decomposed by hot aqueous alkali due to attack by hydroxide. Pyrimidine also reacts cleanly with hydrazine to give
pyrazole as the result of an ANRORC sequence (Addition of Nucleophile Ring Opening Ring Closure).
Substitution of hydrogen
All three diazines undergo ready addition of Grignard reagents and alkyl- and aryllithiums, at the carbon of one of
the imine units, to give dihydro-intermediates that can be easily re-aromatised, the overall effect being nucleophilic
substitution of hydrogen. This reaction is particularly useful for chlorodiazines and it is notable that attack occurs at a
carbon that does not bear a halogen. (This should be contrasted with attack by soft nucleophiles (see below).)
Amination can be achieved effi ciently – amide anion adds easily (but reversibly) to the diazines but, in contrast to the
Chichibabin reaction of pyridines, the presence of an oxidant is required for the fi nal aromatisation.