ABSTRACT
Five- and six-membered ring heterocyclic compounds are relatively easily formed from appropriately substituted alicyclic molecules; the formation of smaller rings is disfavoured by inherent ring strain and larger rings by entropic effects that lower the possibility of the reacting termini positioning themselves appropriately for ring closure. Acetoacetic ester and other 1,3-dicarbonyl-containing compounds are widely employed in heterocyclic synthesis. Pyrrole is an extremely weak base because protonation on carbon or nitrogen destroys the aromatic system, with loss of aromatic stabilization energy; pyrrolidine has the basic strength of a normal secondary amine. Nicotine can be prepared from the pyridine carboxylic acid by reaction with two mole equivalents of the alkyllithium; reaction of the ensuing ketone with hydroxylamine is followed by reduction with lithium aluminium hydride to the amine, which cyclizes in the presence of hydrobromic acid.
