Nucleophilic versus general base catalysis

An often occurring mechanistic problem is the diagnosis of general base or nucleophilic catalysis which give identical kinetics. Imidazole is a well known catalyst for the hydrolysis of 4-nitrophenyl acetate in water and it is known to involve nucleophilic attack because iV-acetylimidazole has been observed from ultraviolet spectral work [17]. The absence of a solvent deuterium isotope effect confirms the operation of the nucleophilic pathway (Table 7) because a primary isotope effect is expected for the general base mechanism. 

This method is of use where it is not possible to observe an intermediate for 

Isotope effects for nucleophilic (n) and general base (g.b.) reactions 

This table is taken largely from a compilation in Johnson s review (Johnson, S.L. (1967) Adv. Phys. Org. Chem. 5, 237) persual of the data indicates that care must be taken in interpreting solvent isotope effects in the intermediate range 1.5-2.0. 

The cause of the low primary isotope effects compared with those predicted by Bell (Table 3) for heteroatoms has been a considerable puzzle. The work of Bergman et al. [15] and Cox and Jencks [16] indicates that the isotope effect depends sharply on 4pA between attacking base and donor acid. Since all the A K values for Table 7 differ markedly from zero it is not surprising that low isotope effects are observed. Of course the pK dependence of the isotope effect imparts considerable uncertainty and a low value (for example 1-1.5) may reflect simply a large p T difference a large isotope effect ( 2.5) of course requires the proton transfer to be rate-limiting. 

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NUCLEOPHILIC Versus GENERAL BASE CATALYSIS BY ACETATE ION OF THE HYDROLYSIS OF ARYL ACETATES IN WATER AT pH 5.0 AND IONIC STRENGTH... 

King, J. A., Jr. Nucleophilic versus general base catalysis in carbonyl substitution reactions the influence of acylpyridinium/acylammonium salt formation on the observed reaction rate. Trends in Organic Chemistry QQ7, 6, 67-89. 

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