RATE-DETERMINING CARBONYL HYDRATION IN THE INTRAMOLECULAR HYDROLYSIS OF PHENACYL PHOSPHONATE ESTERS - ISOTOPIC PROBES AND ACTIVATION PARAMETERS

4-Nitrophenyl 4-substituted-phenacyl methylphosphonate esters (CH3, H, CH3O, NO2, and Cl) decompose in aqueous buffers 1-4 orders of magnitu de faster than analogs with alkoxy substituents not containing a beta- carbonyl group. This is consistent with an intramolecular displacement of 4-nitrophenol by the anion of the carbonyl hydrate. O-18 incorpora tion into the hydrolysis product of the 4-CH3 derivative from (H2O)-O- 18 in alkaline solution is 50%. This indicates a rapid protonic equili brium between the carbonyl hydrate and the medium but slower equilibra tion of the carbonyl O with the medium than cyclization. General base- catalyzed water attack in formation of the carbonyl hydrate is rate de termining followed by cyclization with a rate constant > 10(6) s-1. Su pportive evidence is provided by buffer dependence, small normal solve nt isotope effects, effect of 4-substituents in the phenacyl group (rh o = 1.83 +/- 0.15), and activation parameters DELTAH(double-dagger) = 49 +/- 2 kJ/mol and DELTAS(double-dagger) = -118 +/- 6 J/(mol K) for t he phosphate dianion-catalyzed reaction and DELTAH(double-dagger) = 21 .5 +/- 0.8 kJ/mol and DELTAS(double-dagger) = 183 +/- 3 J/(mol K) for the Tris base-catalyzed reaction. Inverse dependence of the rate const ants for the phosphate dianion-catalyzed reaction on increasing ionic strength and solvent polarity also support the proposed mechanism. The solvent isotope effect for nucleophilic addition of increasing concen trations of lyoxide ion decreases from approximately 2.0 to 0.9. The n ormal effect may indicate significant solvent restructuring as the neg ative charge is redistributed at the transition state in dilute soluti ons of lyoxide ion. The activation parameters for the reaction of hydr oxide ion are DELTAH(double-dagger) = 35.9 +/- 0.1 kJ/mol and DELTAS(d ouble-dagger) = -59.8 +/- 0.4 J/(mol K). The compounds have a built-in trap for the carbonyl hydrate formed with instantaneous release of a signal molecule, 4-nitrophenol, and thus are ideally suited for the me asurement of hydration rates of aryl alkyl ketones.