140 Heterocycles with More than Two Heteroatoms: Higher Azoles (5-Membered) and Higher Azines (6-Membered)
The thermal stabilities of the known parent systems vary from 1,2,3-triazine, which decomposes at about 200 °C, to
1,3,5-triazine, which is stable to over 600 °C.
Nucleophilic substitution at carbon
Nucleophilic substitutions and additions are the most important reactions of the higher azines, electrophilic substitu-
tions on carbon being unknown. They are generally more reactive in these nucleophilic reactions than the diazines, due
to the inductive effect of the extra nitrogen(s), for example the parent systems and many derivatives react with water
in acidic or basic solution.
There are some substitutions on carbon that might appear to be electrophilic, for example bromination of 1,3,5-triazine,
but this almost certainly proceeds via electrophilic attack on nitrogen, followed by nucleophilic addition of bromide on
carbon, as indicated below.
1,3,5-Triazine readily but reversibly adds ammonia and simple amines (contrast the requirement for hot sodamide in
the Chichibabin reaction for pyridine, page 35) but the aromatised amino- and alkylamino-derivatives can be obtained
by trapping the adduct using a permanganate oxidant.
The susceptibility of 1,3,5-triazine to nucleophilic attack with ring opening makes it a synthetically useful equivalent of
formate or formamide for the synthesis of other heterocycles, for example imidazoles and benzimidazoles.
Palladium(0)-catalysed reactions
There are relatively few examples of cross-couplings with the higher azines but the halo-derivatives are good substrates.
A Sonogashira example is given below.
Pericyclic reactions
A principal chemical application of triazines and tetrazines is as electron-defi cient ‘dienes’ in Inverse Electron Demand
Diels–Alder (IEDDA) cycloadditions. These processes produce either pyridines or diazines via reverse Diels–Alder
elimination of hydrogen cyanide, a nitrile, or nitrogen from the initial adduct.