Transition-State Effects in the Divalent Metal Ion Catalysis of Acetal Hydrolysis

Article abstract of DOI:10.1021/ja00533a017

The rates of hydrolysis of a series of substituted benzaldehyde methyl 8-quinolyl acetals have been determined in 50percent dioxane-H2O (v/v) at 30 deg C.The reactions involve hydronium ion catalyzed hydrolysis of the neutral and protonated species.Hammett ρ values are -3.1 and -2.6, respectively.These acetals are also subject to general acid catalysis.Divalent metal ions (Cu²⁺, Co²⁺, Ni²⁺, Mn²⁺, and Zn²⁺) exert a large catalytic effect even though binding to the reactant is very weak.For example, a 0.02 M concentration of Ni²⁺ (1000-fold excess) at pH 7.2 produces a 2x10⁵ enhancement in k_obsd for hydrolysis of 3,4-dichlorobenzaldehyde methyl 8-quinolyl acetal, but there is no indication of saturation effects.The rate constants for metal ion catalysis of the hydrolysis of the substituted benzaldehyde methyl 8-quinolyl acetals vary with changing substituents in the same manner as those for the hydronium ion catalysed reactions.At constant metal ion concentration k_obsd is pH independent at pH values above the pK_a of the quinolone nitrogen.Metal ion catalysis must be due to a transition-state effect in which the leaving group is stabilized.Incorporation of a second functional group which can chelate the metal ion, as in 3,4-dichlorobenzaldehyde 8-(2-carboxyquinolyl) methyl acetal, leads to strong binding to the reactant; i.e., saturation effects are observed at low ion concentrations (10^-2-10^-3 M), but catalytic effects at >0.01 M metal ion concentration are slightly less than with the 8-quinolyl acetals where reactant binding is weak.This emphasizes the importance of transition-state binding in these reactions.