Heterocycles with More than Two Heteroatoms: Higher Azoles (5-Membered) and Higher Azines (6-Membered) 137N-Acylbenzotriazoles, which are stable, more easily handled and milder electrophiles than acid chlorides or anhy-
drides, can be prepared from a large variety of acids, including N-protected -amino acids, by simple reaction of ben-
zotriazole with an acid chloride, generated in situ using thionyl chloride. N-Acylbenzotriazoles have been widely used
asN-, O-, S- and C-acylating agents. In particular they can be used to form amide bonds in the synthesis of peptides,
that is, as N-acylating agents. An illustrative example is shown below.
In addition to the important role of benzotriazole as a synthetic auxiliary, there are other ways in which the ring
system can be utilised. Perhaps the most important of these is the relatively mild, neutral oxidative degradation of
1-aminobenzotriazoles, used to generate benzynes.
Higher azoles also containing ring sulfur or oxygen: oxa- and thiadiazoles
There are eight possible oxa- and thiadiazoles and all are known, stable compounds apart from 1,2,3-oxadiazole, which
is unstable with respect to a ring-open tautomer. However, mesoionic derivatives of 1,2,3-oxadiazole – sydnones – are
useful stable intermediates. Only one divalent heteroatom can be incorporated into a simple fi ve-membered, aromatic
heterocycle, unless a carbonyl is also present. These systems are named with the non-nitrogen atom numbered as 1, and
the positions of the nitrogen atoms shown with reference to the divalent atom.
Relative aromaticities and stabilities
Predicting precise interactions between the heteroatoms in these systems is not easy but the general stability/reactivity
can be implied from their relative aromaticities, based on bond lengths and NMR (nuclear magnetic resonance) data.