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.
Introduction
There are some ideas and reagents and reaction methodologies and reactivity patterns that turn up again and
again in heterocyclic chemistry and we summarise and explain these in detail in this chapter, so that they do not
have to be discussed in detail at each separate occurrence in the rest of the book. In heteroaromatic chemistry,
electrophilic substitution (mainly of hydrogen) is important for the fi ve-membered heterocycles and nucleophilic
substitution (mainly of halogen) is important for six-membered heterocycles. The use of transition metal cataly-
sis, especially palladium-catalysis, is so important in heterocyclic chemistry that we devote the whole of Chapter 4
to that topic.
Acidity and basicity
Many heterocyclic compounds contain a ring nitrogen. In some, especially fi ve-membered heterocycles, the nitro-
gen may carry a hydrogen. It is vital to the understanding of the chemistry of such nitrogen-containing hetero-
cycles to know whether, and to what extent, they are basic – will form salts with protic acids or complexes with
Lewis acids, and for heterocycles with N-hydrogen, and to what extent they are acidic – will lose the N-hydrogen as
a proton to an appropriately strong base. As a measure of these properties we use pKa values to express the acidity
of heterocycles with N-hydrogen and pKaH values to express base strength. The lower the pKavalue the more acidic;
the higher the pKaHvalue the more basic. It may be enough to simply remember this trend; a little more detail is
given below.
For an acid AH dissociating in water:
The corresponding equation for a base involves the dissociation of the conjugate acid of the base, so we use pKaH.