Synthetic modeling of zinc thiolates: Quantitative assessment of hydrogen bonding in modulating sulfur alkylation rates

A series of mononuclear zinc thiolate complexes have been prepared and fully characterized. The reactions of the complexes with alkyl halides, leading to zinc halides and the corresponding thioethers, have been examined by kinetic methods. In toluene, the reactions obey a second-order rate law displaying activation parameters consistent with a S(N)2 attack of the zinc-bound thiolate on the carbon electrophile. Intramolecular hydrogen bonding of an amide N-H to the thiolate sulfur reduces the nucleophilicity and consequently, the rate of alkylation more than 30-fold at 25degreesC. The H-bonding shows an inverse H/D isotope effect of 0.33 (60degreesC) ascribed to differential H-bonding for the two isotopomers due to zero point energy differences. These model studies provide quantitative evaluation of H-bonding on reaction rates relevant to zinc thiol-activating proteins.