Rate-Determining Carbonyl Hydration in the Intramolecular Hydrolysis of Phenacyl Phosphonate Esters: Isotopic Probes and Activation Parameters

Article abstract of DOI:10.1021/ja00076a001

4-Nitrophenyl 4-substituted-phenacyl methylphosphonate esters (CH3, H, CH3O, NO2, and Cl) decompose in aqueous buffers 1-4 orders of magnitude faster than analogs with alkoxy substituents not containing a β-carbonyl group.This is consistent with an intramolecular displacement of 4-nitrophenol by the anion of the carbonyl hydrate. 18O incorporation into the hydrolysis product of the 4-CH3 derivative from H2(18O) in alkaline solution is 50percent.This indicates a rapid protonic equilibrium between the carbonyl hydrate and the medium but slower equilibration of the carbonyl O with the medium than cyclization.General base-catalyzed water attack in formation of the carbonyl hydrate is rate determining followed by cyclization with a rate constant >10⁶ s^-1.Supportive evidence is provided by buffer dependence, small normal solvent isotope effects, effect of 4-substituents in the phenacyl group (ρ=1.83+/-0.15), and activation parameters ΔH^<*>=49+/-2 kJ/mol and ΔS^<*>=-118+/-6 J/(mol K) for the phosphate dianion-catalyzed reaction and ΔH^<*>=21.5+/-0.8 kJ/mol and ΔS^<*>=183+/-3 J/(mol K) for the Tris base-catalyzed reaction.Inverse dependence of the rate constants 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 concentrations of lyoxide ion decreases from ca.2.0 to 0.9.The normal effect may indicate significant solvent restructuring as the negative charge is redistributed at the transition state in dilute solutions of lyoxide ion.The activation parameters for the reaction of hydroxide ion are ΔH^<*>=35.9+/-0.1 kJ/mol and ΔS^<*>=-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 measurement of hydration rates of aryl alkyl ketones.