Pyridines 41Side-chain deprotonation (and thence reaction) of picolinium salts requires considerably milder base catalysis.
Pyridine carboxylic acids, like simple amino acids, exist mainly as zwitterions (internal salts). The zwitterion of pico-
linic acid decomposes on heating, with loss of carbon dioxide, to generate a transient ylide, which can be trapped if
the reaction is carried out in the presence of benzaldehyde. The 3-acid is usually called nicotinic acid and the 4-acid,
isonicotinic acid.
Oxygen substituents
The 2- and 4-hydroxypyridines exist predominantly in the tautomeric pyridone form, whereas 3-hydroxypyridines
exist only as the hydroxyl form.
The NH in pyridones is relatively acidic, with pKa values of about 11, and thus can be abstracted by mild base
to give anions, which alkylate mainly on nitrogen with primary halides. An important reaction of both - and
-pyridones, not shown at all by benzenoid phenols, is their ready conversion into halopyridines by reaction with
phosphorus halides. The process proceeds because the amide-like carbonyl oxygen acts as a nucleophilic centre
with the phosphorus halide generating a pyridinium salt to which halide adds, followed by 1,2-elimination (of
phosphorodichloridic acid when using phosphoric trichloride).
Electrophilic attack at carbonyl oxygen is also involved in the conversion of pyridones into trifl ates by reaction with
trifl uoromethanesulfonic anhydride (trifl ic anhydride) and a base; these derivatives are of particular interest in the
context of palladium(0)-catalysed cross-couplings.