18 Common Reaction Types in Heterocyclic Chemistry
of the acidifi ed protons) and [MeO(H)C=NMe 2 ] (which reacts with the anion generated) a fi nal loss of methanol
producing the enamine.
Brederick’s reagent, (Me 2 N) 2 CHOt-Bu, can also be utilised for the generation of dimethylaminomethylene derivatives.
Here, t-butoxide is the base and dimethylamine is the unit lost in the fi nal stage. In the example below, the acidifi ed
group is a methyl at a pyridine -position (cf. page 40).
Formation and hydrolysis of imine/enamine
Very frequently in heterocyclic ring syntheses, the interaction (often acid-catalysed) of an amine with a ketone or alde-
hyde carbonyl group is involved. After nucleophilic addition of the amine to the carbonyl carbon, and proton transfers,
a carbinolamine is generated which can lose water to form an imine then this, in turn, can tautomerise to form an
enamine. Further, the reverse sequence can also easily occur – only a few simple imines are stable to hydrolysis, but
particularly, when these are cyclic. Imines and enamines are often intermediates, whether stable or not, en route, via a
series of equilibria, to an aromatic heterocycle.