82 Pyrroles
Pericyclic reactions
Pyrroles, as aromatic molecules, do not generally behave as dienes. However, when an electron-withdrawing substitu-
ent is located on the nitrogen, its effect, both inductive and mesomeric, reduces the aromatic character to the extent
that such molecules will take part in Diels–Alder processes as the diene component. The reactions of N-Boc-pyrrole
have been widely exploited: its reaction with dimethyl acetylenedicarboxylate is illustrative.
Reactivity of side-chain substituents
The electron-rich character of the pyrrole ring gives rise to some important properties of side-chain substituents.
Pyrrole carboxylic acids readily decarboxylate, refl ecting C-protonation to cations from which carbon dioxide is lost, as
indicated. Several methods for the ring synthesis of pyrroles produce pyrrole-esters and these can be readily hydrolysed
and decarboxylated, if the ester is not required.
Dialkylaminomethyl-pyrroles, easily produced in Mannich substitutions, can be utilised in further elaborations, as the
amine group (or an ammonium group derived from the amine by quaternisation) can be easily displaced by nucle-
ophiles such as cyanide, as in the example shown. These are not direct displacements but involve ring-N-hydrogen
deprotonation and an intermediate azafulvene, to which the nucleophile adds, as shown, in an extended aza-Michael-
type addition.
The 2-(hydroxyalkyl)-pyrroles, which result from reaction with an aldehyde or ketone with acid catalysis, readily lose
water generating an electrophilic azafulvenium species. In some cases these can be trapped, for example by a second
equivalent of the pyrrole; dipyrromethane can be made in this way.
The ‘pigments of life’
Not even a brief description of pyrrole chemistry can ignore the biological signifi cance of the two pigments – heme and
chlorophyll – which are central to all life (see page 162). It is amazing how easy it is to construct such apparently complex
macrocycles, the reactions involved all being understandable with just the discussions above. For example, reaction of pyr-
role and acetone, with acid catalysis, gives rise to a macrocycle in high yield, the intermediates shown illustrating: (i) selec-
tive electrophilic substitution, (ii) easy elimination of benzylic side-chain hydroxyl, then (iii) attack by the azafulvenium
cation as an electrophile on a second pyrrole at its -position. The process then continues in a similar vein.