Effects of Divalent Metal Ions on Hydrolysis of Esters of 2-(Hydroxymethyl)picolinic Acid. Metal Ion Catalysis of the Carboxyl, Hydroxide Ion, and Water Reaction

Article abstract of DOI:10.1021/ja00372a024

The effects of divalent metal ions (Cu²⁺, Ni²⁺, Co²⁺, and Zn²⁺) on the hydrolysis reactions of phthalate, succinate, and acetate esters of 2-(hydroxymethyl)picolinic acid have been determined at 50 deg C.With these esters the metal ion saturates at low metal ion concentration (<0.01 M).Large rate enhancements are observed in the hydroxide ion catalyzed reactions at saturating concentrations of metal ion, ranging from 10⁴ with Ni²⁺ to 10⁶ with Co²⁺.A pH-independent reaction also occurs in the case of the phthalate monoester which is associated with the neighboring carboxyl nucleophilic reaction.Rate enhancements of 10²-10⁴ are obtained in this reaction at saturating concentrations of Ni²⁺, Co²⁺, and Cu²⁺.Rate constants in the Ni²⁺ and Co²⁺ catalyzed reaction are closely similar to those for 2-pyridylmethyl hydrogen phthalate with which metal ion binding is weak.Thus, metal ion catalysis of the nucleophilic reaction, which occurs through leaving group stabilization in the transition state, is not appreciably enhanced by increased strength of binding to the reactant.Such a reaction does not occur with Cu²⁺ in hydrolysis of succinate monoester, showing that when the leaving group is poor, steric fit of the nucleophile and the carbonyl must be excellent for a nucleophilic mechanism to occur even through the leaving group can be greatly stabilized by a metal ion, i.e., there cannot be degrees of freedom for rotation of the nucleophile away from the carbonyl.At pH < 3 k_obsd is pH independent in the Cu²⁺-catalyzed hydrolysis of the succinate and acetate esters due to a metal ion promoted water catalyzed reaction.Thus, three different mechanisms for metal ion catalysis can be observed in hydrolysis of esters of 2-(hydroxymethyl)picolinic acid: (1) catalysis of a neighboring carboxyl nucleophilic reaction, (2) metal ion promoted OH^- catalysis, and (3) metal ion promoted water catalysis.The first of these mechanisms is dependent upon the strength of binding of the metal ion to the leaving oxygen in the transition state, whereas the latter two mechanisms are facilitated by strength of bindind to the reactant.