Decomposition of N-nitrosopeptides in strong acids

Abstract

Decomposition of the N-nitrosodipeptides obtained from N-(N′-acetyl-L-prolyl)glycine and N-(N′-acetyl-L-propyl)-L-alanine in aqueous acid at 25 °C involves both deamination and denitrosation. Both reactions occur concurrently via different conjugate acid intermediates, with denitrosation being predominant at high acidity. Acidity dependences and inverse solvent deuterium isotope effects [k(H₂SO₄)/k(D₂SO₄)ca. 0.7] suggest that deamination involves rate limiting attack by H₂O on an O-conjugate acid, formed in a rapid pre-equilibrium. For denitrosation, H⁺ transfer to the amide N-atom is considered rate limiting because of the substantial normal solvent deuterium isotope effects [k(H₂SO₄)/k(D₂SO₄)ca. 2.5] and Bunnett ω values in the range –0.1 to –0.5: the N-conjugate acid formed breaks down rapidly to products. Both the kinetics and mechanisms for decomposition of these N-nitrosodipeptides are very similar to those of alicyclic N-nitrosamides.