Heterocyclic Chemistry at a Glance, Second Edition. John A. Joule and Keith Mills.
© 2013 John Wiley & Sons, Ltd. Published 2013 by John Wiley & Sons, Ltd.
14
Heterocycles with More than Two Heteroatoms:
Higher Azoles (5-Membered) and
Higher Azines (6-Membered)
Higher Azoles
Introduction
Any or all of the carbon atoms in all the fi ve-membered heterocyclic systems described in previous chapters could,
in theory, be replaced by nitrogen. Using nitrogen, oxygen and sulfur, there are 18 possible azoles with three or more
heteroatoms, of which 13 are known. (Three of the unknown parents are those that contain no carbon.) However,
the tautomers of the three systems containing only nitrogen as the heteroatom could also be considered as individual
azoles and do show differences in aromaticity and reactivity when fi xed by substitution on nitrogen. Of course, the
more heteroatoms there are present, the less opportunity there is for chemistry at carbon!
When a ring contains several heteroatom–heteroatom and heteroatom–carbon bonds, there is the probability of
thermodynamic instability and the possibility of kinetic instability, and the latter particularly if the juxtaposition of
these atoms could allow facile extrusion of stable molecules such as nitrogen (gas) or even elemental carbon or sulfur.
In fact, some of this class of compounds do fi nd use as commercial explosives (see pages 184–186) but, on the other
hand, many are quite docile. Amongst tetrazoles, in particular, there are examples of both aspects – some are excep-
tionally dangerous compounds and others are used as building blocks of medicines (for examples see pages 133 and
168). Indeed many of the higher azoles are of great importance in medicinal chemistry and in industry.
Higher azoles containing nitrogen as the only ring heteroatom:
triazoles, tetrazole and pentazole
There are four higher azoles containing only nitrogen as the heteroatom – two triazoles, tetrazole and pentazole. The
triazoles and tetrazole each exist as mixtures of two tautomers. Of the parent compounds, only pentazole has not
been isolated, indeed only a few unstable derivatives have been prepared. The other three systems have very extensive
chemistry.
The triazoles are weak bases but relatively acidic – about the same as phenol. Tetrazoles are even weaker bases but
more acidic – about the same as a carboxylic acid, and they are used as isosteric replacements for carboxylic acids in a
number of drugs.