Synthesis of the Two Isomeric Benzo Derivatives of 1-Hydroxy-7-azabenzotriazole and Preliminary Studies of Their Effectiveness as Coupling Reagents

Abstract

Coupling reactions involving carbodiimides involve two or more consecutive reactions, each of which is concentration dependent. It is often useful to add an additive, sometimes referred to as an auxiliary nucleophile, which reacts with these highly reactive intermediates, e.g. the O-acylisourea, symmetric anhydride or oxazolone to give an active ester which itself can take part in peptide bond formation thus reducing the lifetime of such intermediates with consequent reduction in by-product formation. The best results reported to date have been achieved with 1-hydroxybenzotriazole (HOBt) N-hydroxysuccinimide (HOSu), 3-hydroxy-3, 4-dihydro-1, 2, 3-benzotriazine-4-one (HODhbt) and particulary 1-hydroxy-7-azabenzotriazole (HOAt) [1].