Reaction mechanisms in peptide synthesis. Part 1. Semiquantitative characteristics of the reactivity of 2-methyl-5(4H)-oxazolone with water and ammonia in the gas phase and weakly polar media.

2,4-Dialkyl-5(4H)-oxazolones are well-recognized intermediates in some aminolysis reactions in peptide synthesis. Using the MOPAC molecular orbital programs, detailed geometric and energetic characteristics of the elementary reaction pathways for the additions of water and ammonia to 2-methyl-5(4H)-oxazolone have been determined at the AM1 level. The results demonstrate that the additions must be parsed into a two-step mechanism involving formation of the alpha-hydroxyimine followed by tautomerization to the parent N-acetylamino acid or amide.