Kinetics and Mechanism of the Kmn04-Oxidative Catalysed Condensation Reaction of L-Proline to a Diketopiperazine: Evidence for Delayed Autocatalytic Behaviour

Abstract

The kinetics and mechanism of the KMn04-oxidative catalysed condensation reaction of L-proline, as a cyclic secondary amino acid, has been investigated spectrophotometrically. Product analysis has revealed, that in contrast to the usual reaction of α-amino acids, which results in an aldehyde species, a valuable diketopiperazine, namely cyclo(L-pro-L-pro), is obtained as the main product, providing a cheap, simple, efficient, and novel method. Conclusive evidence has demonstrated delayed autocatalytic activity involving Mn2+in this reaction, analogous to that shown by chain primary a-amino acids. It has been revealed that such activity can emerge when a certain concentration of Mn2 +is built up in the medium, to which we refer as the “critical concentration”. Moreover, the “critical concentration” for the appearance of “autocatalytic behaviour” in this oxidative process is affected by the nature of the amino acid used, as reported in previous studies, while the magnitude of the critical concentration depends on the sulfuric acid concentration. In considering “delayed autocatalytic behaviour” of Mn2+ions, rate equations satisfying experimental data for both catalytic and non- catalytic routes have been presented. The reaction shows a first-order dependence on permanganate ion concentration, both in the catalytic and non-catalytic pathways, and an apparent first-order dependence on Mn2 +ions in the catalytic pathway. The correspondence of the pseudo-order rate constants of the catalytic and non-catalytic pathways to the Arrhenius and Eyring laws verified both the “critical concentration” and “delayed autocatalytic behaviour” concepts. The activation parameters associated with the reaction pseudo-rate constants k, and k2are computed and discussed. Proposed mechanisms for both catalytic and non- catalytic routes include a diacyclperoxide intermediate, which leads to a C-2-symmetric chiral product having a diketopiperazine skeleton.