Nucleophilicity basicity versus

As shown in Figure 8.37, a reasonably linear correlation of log fca versus log Ky, was obtained for this series of nucleophiles. Basicity alone cannot explain nucleophilicity, however, as evidenced by reactions in which the nucleophilic atom is different. For example, phenoxide is more than 10 times more basic than thiophenoxide, but thiophenoxide is more than 10 times more nucleophilic than phenoxide. Uggerud concluded that strong bases have large intrinsic barriers for nucleophilic reaction but stabilize the products relative to reactants, so basicity and nucleophilicity are strongly correlated only for highly exothermic reactions. ... 

In an earlier report Bach and coworkers suggested that MesN and MesP had nearly the same gas-phase barriers with peroxyformic acid (AA 5 = 0.5 kcalmol", MP4//MP2/6-31G ) and that their relative reactivity in protic solvent is better attributed to a much greater ground-state solvation of the more basic tertiary amine than the polarizability of the phosphorus. In a more recent study, a 3.3 kcalmol" barrier difference was observed with HCO3H in favor of the P nucleophile at B3LYP/6-31- -G(d,p) (3.0 versus —0.3 kcalmol". Table 12). Thus, the less reactive f-BuO—OH is a more discriminating oxidant with a later TS and the difference in barrier heights for N versus P oxidation widens. These data also point out that rate differences should be compared for a common set of nucleophiles and that when you use oxidants of different reactivity you should... 

SN1 versus S There are two different mechanisms involved in the nucleophilic substitution of alkyl halides. When polar aprotic solvents are used, the SN2 mechanism is preferred. Primary alkyl halides react more quickly than secondary alkyl halides, with tertiary alkyl halides hardly reacting at all. Under protic solvent conditions with non-basic nucleophiles (e.g. dissolving the alkyl halide in water or alcohol), the SN1 mechanism is preferred and the order of reactivity is reversed. Tertiary alkyl halides are more reactive than secondary alkyl halides and primary alkyl halides do not react at all. 

The enzyme can also catalyze the transfer of the terminal phosphoryl of ATP to water i.e., it acts as an ATPase but at a rate 5 x 106 times slower than the above reaction. The basic and nucleophilic properties of water versus the C-6 hydroxyl of glucose are sufficiently similar to suggest no marked differences in rate. Therefore, the explanation of the rate difference is that glucose induces a conformational change that establishes the correct active-site geometry in the enzyme, whereas a water molecule is too small to do so. 

For any sort of linear free-energy correlation, a very interesting issue to explore is that of using the pK of the nucleophile rather than the reaction exothermicity itself Not untypically, discussions of nucleophilicity (a kinetic quantity) versus basicity or proton affinity (a thermodynamic quantity) result. In principle, no reason exists to use the pK of the nucleophile rather... 

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