Intramolecular migration of an amino-group via a transannular process during the reaction of O-salicyloylglycolamides in alkaline solution: an analogue of the reverse of the Brenner aminoacyl insertion reaction

Abstract

O-Saticyloylglycolamides undergo cleavage in the pH range 7–13 to yield salicylamide and salicylate anion in the high and low ranges respectively. Scanning the u.v: spectrum during reaction gives evidence for the accumulation and decay of intermediates at both ends of the pH range. Intermediates are not observed to accumulate during alkaline hydrolysis of O-benzoylglycolamides and benzamides are also not products. Amine is transferred intramolecularly in the salicyloyl reaction as judged from the absence of ammonia in the reactant solution. We postulate that the initial reaction involves the attack of the 2-oxyanion on the amido-group to yield a seven membered ring tetrahedral adduct: diacylamide and O-saliyloylisoamide intermediates are formed by transannular migration of oxygen or the amino-group from the tetrahedral centre to the ester carbonyl. The formation of the diacylamide is inhibited at low pH but when formed it cleaves to give salicylamide. The reaction of O-saliyloylglycolamides to produce salicylamide is essentially an analogue of the reverse of the Brenner aminoacyl insertion reaction. The driving force for the extrusion of the acid from the salicyloyl compound is probably the hydrolysis of the ester link. The effective molarity for the intramolecular attack of oxyanion on the amide has an estimated upper limit of ca. 10⁸M.