Co-operative catalysis of the cleavage of an amide by neighbouring carboxy group in alkaline medium

Abstract

The k_obs–[ŌH] profile obtained at 30 °C reveals an insignificant contribution of water-catalysed cleavage of non-ionized ethyl N-(o-carboxybenzoyl)carbamate (EBCH) compared with its hydroxide ion-catalysed or kinetically equivalent water-catalysed cleavage of ionized ethyl N-(o-carboxybenzoyl)carbamate (EBC^–). A similar k_obs–[ŌH] profile obtained for the cleavage of N-(3-bromopropyl) phthalamic acid (NBPPH) reveals both water and hydroxide catalysis. The rate constant (k_w) for water-catalysed cleavage of NBPPH is ca. 10⁴-fold larger than that for phenyl acetate. The presence of water catalysis in the cleavage of NBPPH is attributed to the probable occurrence of co-operative catalysis while the absence of such catalysis in the cleavage of EBCH is presumably the consequence of the non-occurrence of co-operative catalysis in this case. The pK_a of the imide proton of EBCH is 11.3 at 30 °C while no ionization of the amide proton of NBPPH could be detected spectrally within the pH range 10.23–12.00 and 0.05M-NaOH at 30 °C.