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.
Electrophilic addition to nitrogen
With simple pyridines, all electrophiles react, at least initially, by addition to the nitrogen, that is the electrophile
accepts the nitrogen lone electron pair to form a bond in the plane of the ring. Protonation, for example, occurs easily,
on nitrogen. Pyridine is a weaker base than typical aliphatic amines (pKaH values of 9–11), but is nevertheless widely
used in synthetic processes that require the presence of a base. Pyridines form stable crystalline, but often hygroscopic,
pyridinium salts with strong acids, for example hydrochloric acid, however, salts with weaker acids, such as acetic, read-
ily dissociate to reform the pyridine and the acid. Pyridinium salts are still aromatic, though the -system is further
polarised.
Alkyl halides react irreversibly with pyridines to give 1-alkylpyridinium salts. Both bromine and sulfur trioxide will
add to the nitrogen to form crystalline complexes. Acyl halides and sulfonyl halides react at nitrogen generating read-
ily hydrolysed N-acyl and N-sulfonyl pyridinium salts (1-acylpyridinium and 1-sulfonylpyridinium), which are the
actual electrophilic agents when pyridine is used as a nucleophilic catalyst in acylations and sulfonylations of alcohols
and amines.
Pyridines react easily with peracids to generate N-oxides and can be N-aminated with hydroxylamine-O-sulfonic acid.
Pyridine N-oxides can be converted into pyridines in several ways, for example with a phosphine (which forms the
corresponding phosphine oxide).
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Pyridines