Neighbouring group participation by the carboxy group in the solvolysis of the dipeptides in acetic acid

Abstract

The acid-catalysed solvolysis of the dipeptides in acetic acid solution occurs readily both in the presence and absence of water. The rates increase with increasing methylation, which is consistent with a mechanism involving a ring-closure pathway by the terminal carboxy group. The experimentally determined rate law is:

f × rate × [H₂O]/[dipeptidium(1+) ClO₄^-][ΣH⁺] = k₁ + k₂[H₂O]²

where f is the salt effect factor and ΣH⁺ is the acetic acidium perchlorate concentration after correcting for the presence of oxonium perchlorate.

The k₁ values increase with increasing methylation, as required for a ring-closure mechanism, and the inverse water term in this component of the rate is ascribed to a medium effect. The ratecontrolling step is defined as being the acid-catalysed ring fission of a rapidly formed intermediate, oxazalone acetic acid solvate. The k₂ component of the rate is first order with respect to water and would appear to refer to the normal mode of solvolysis. But the much higher values of k₂ for the heavily methylated compounds as compared with Gly-Gly are incompatible with the much lower activities shown by these compounds when reacting by the normal mode of solvolysis. Since k₂ passes through a minimum with increasing methylation, it is suggested that it is a composite of the normal and ring-closure modes of solvolysis. The rate-controlling step for this latter reaction is the acid-catalysed reaction of water with the oxazolone acetic acid solvate. The increasing rates arising from increasing methylation are due to increasing stabilities of the oxazolone solvate ring systems resulting in a kinetically favourable displacement of this equilibrium towards the ring system.

Infrared analysis shows that the oxazolone of Aibu-Aibu readily undergoes a fast reaction with acidified acetic acid to form a stable acetic acid solvate with the complete disappearance of all oxazolone absorption frequencies. Aibu-Aibu on heating in acidified acetic acid solution rapidly forms the same oxazolone acetic acid solvate with no evidence of any oxazolone absorption frequencies. The solvolysis of optically active Gly-Val demonstrates that the oxazolone is not formed as an intermediate because the Val produced retains its optical activity with no evidence of any racemization.