Circumventive Catalysis: Contrasting Reaction Patterns of Tertiary and Primary Amines with Cyclic Anhydrides and the Avoidance of Intermediates

Article abstract of DOI:10.1021/ja00191a033

The aminolysis of cyclic anhydrides proceeds via initial formation of a zwitterionic tetrahedral intermediate which tautomerizes to an uncharged intermediate.The aminolysis of acyclic anhydrides does not involve formation of the uncharged tautomer.The dichotomy of the reaction patterns was investigated by examining the reaction of tertiary amines with cyclic anhydrides.These amines catalyze the hydrolysis of acyclic anhydrides through the formation of reactive acylammonium ions.Pyridine, which reacts with acyclic anhydrides, does not promote the hydrolysis of maleicanhydride and does not form detectable intermediates (pH 7.3, 25 deg C). 4-(Dimethylamino)pyridine does not promote the hydrolysis of succinic anhydride (the reaction with pyridine was not observed due to spectral overlap) but does produce the succinyl 4-(dimethylamino)pyridinium ion (pH 7.3, 7.8, 8.3, 9.0).The divergence in reactivity patterns between the cyclic and acyclic species is consistent with the function of the tautomerization step being the circumvention of an O-protonated amide carboxylate species.Presumably, these are generated from the cyclic anhydrides but are reconverted too fast for hydrolysis to compete.Tautomerization permits the less reactive N-protonated amide to form and this reacts with water.Catalysis by added acids permits the reaction to circumvent the O-protonated amide with a neighboring carboxylate group.Such circumventive catalysis permits release of products where their departure would normally be hindered by their affinity.