Direct spectrophotometric observation of an O-acylisourea intermediate: concerted general acid catalysis in the reaction of acetate ion with a water-soluble carbodi-imide

Abstract

The rate constants for formation and decay of O-acylureas from carbodi-imide and acids have been measured using aqueous media. The O-acetylisourea from acetate and N-ethyl-N′-(3-trimethylammoniopropyl)carbodi-imide (ETC) possesses an acidic group of pK 6.8 and decomposes (k₂) in its acid form as the dication by reaction with acetate ion or water. The reaction of the carboxylate anion with ETC is general acid catalysed (k₁=Σk_HA[RCO₂^–][HA]) and the deuterium oxide solvent isotope effect indicates a rate-limiting proton transfer except for the oxonium ion acting as acid. The Brønsted α value for variation of the structure of HA (0.67) is consistent with a proton transfer concerted with nucleophilic attack by the acetate anion. A concerted mechanism is consistent with the weak basicity of the carbodiimide and the weak acidity of the isourea adduct. The third-order term involving acetic acid, acetate ion, and carbodi-imide carries ca. 60% of the total reaction flux at pH 6.80 and 1 M total acetic acid buffer concentration. At this pH ca. 40% of the reaction flux goes through the stepwise ‘Khorana’ mechanism with specific acid catalysis. Intramolecular general acid catalysis is demonstrated to occur in the reaction of 2,2-diethylmalonic acid monoanion with ETC and the effective molarity compared with intermolecular catalysis is 15M. Attack of carboxylate anions on ETC with N-chloroethylmorpholinium ion as the general acid has a Brønsted type β_Nof 0.46.