The Ritter reaction of 1,2-diolmonoesters with nitriles to 1- vic-amido-2-esters proceeds through dioxonium and nitrilium cation intermediates. To provide the basis for the reaction mechanism, novel forms of these cations were isolated, characterized, and studied by spectroscopic methods and single crystal X-ray analysis. Ground and transition state energies were determined both experimentally and theoretically. Taken together, these data suggest that the reaction proceeds via rapid formation of the dioxonium cation 9, followed by rate determining yet reversible ring opening by acetonitrile to the corresponding nitrilium cation 10 (computed Δ G⧧ = 24.7 kcal at 50 °C). Rapid, irreversible hydration of the latter affords the corresponding vic-acetamido ester. Controlled addition of H2O to the dioxonium cation 9 in acetonitrile- d3 results in near-quantitative production of deuterated acetamido ester 13a. Kinetics of this conversion (9 to 13a) are biphasic, and the slow phase is ascribed to either direct cation 9 attack by acetamide to form cation 16 via O-alkylation or by reversible ether formation. Deuterium labeling studies suggest O-alkylated cation 16 does not directly isomerize to N-alkylated cation 18; instead, it reverts to vic-amidoester 13a via the nitrilium pathway. Preliminary results indicate high regioselectivity for primary amide formation in the diol-Ritter sequence.