Heterocycles with More than Two Heteroatoms: Higher Azoles (5-Membered) and Higher Azines (6-Membered) 139Higher azines
Any or all of the carbon atoms in all the six-membered nitrogen-containing heterocyclic systems described in previ-
ous chapters could, in theory, be replaced by nitrogen. All three possible triazine parent systems are stable and have an
extensive chemistry but of the fi ve possible azines with four or more nitrogens, only 1,2,4,5-tetrazines are known as
monocyclic compounds. 1,2,3,5-Tetrazine rings can be prepared in fused systems, such as temozolomide (see below
and page 178), although this has the benefi t of pyridone-like stabilisation. Known 1,2,3,4-tetrazines are limited to
N-oxides in fused systems. Pentazines and hexazines are unknown.
Triazines are found in some drugs (cf. Chapter 18) but probably the best-known triazine is melamine (2,4,6-triamino-
1,3,5-triazine), which is used industrially to make plastics. ‘Cyanuric acid’ (1,3,5-triazine-2,4,6(1H,3H,5H)-trione)
was fi rst prepared in 1776 by Scheele by the pyrolysis of uric acid. Sodium dichloroisocyanurate is a very widely used
bleach-type disinfectant.
Replacement of carbon in an azine by oxygen or sulfur would not give a neutral aromatic compound, although a diva-
lent heteroatom can be accommodated when a carbonyl group is present – the equivalent of an azapyrone. Oxa- and
thia-diazinones are stable compounds and are useful in Diels–Alder reactions, as illustrated later.