Zinc coordination, functionalized with amides

A limited number of mechanistic studies of stoichiometric amide hydrolysis reactions promoted by Zn(II) complexes have been reported. Groves and Chambers reported studies of the zinc-mediated hydrolysis of an internal amide substrate wherein amide carbonyl coordination to the zinc center is not possible (Scheme 15).93 Examination of the rate of this reaction as a function of pH (6.5-10.5) yielded a kinetic pKa = 9.16. First-order rate constants at 70 °C (/i = 0.5 (NaC104)) for the Zn-OH2 and Zn-OH-mediated amide hydrolysis reactions differed by a factor of 100 when the data was fit to Equation (1) for the proposed mechanism shown in Scheme 16. The activation parameters determined for this reaction (Ai7 = 22(1) kcal mol-1 and AS = — 18(3) eu) are consistent with an intramolecular hydrolysis process wherein a zinc-bound hydroxide acts as an intramolecular nucleophile to attack the amide carbonyl in the ratedetermining step. 

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