Hydrolysis of 2-Aminobenzoate Esters 157
the conjugated acid of the group considered. The higher the pK a
K K value the better its
leaving group ability. As the hydrolysis of an ester is an addition-elimination
f
process we should observe some dependence of the reaction rate with the OR
leaving group ability if the elimination step were rate-determining.
Esters 1-3 hydrolyze at comparable rates even when the leaving group abilities
of nitrophenol (pK a
K K = 7.0), phenol (pK a
K K = 10) and trifluoroethanol (p
a
K a
K K = 12.4) are
very different. Hence, the nature of the OR group has little effect on these hydrolysis reactions, as large differences on the rate constants should be expected
when passing from the better (nitrophenol) to the poorer leaving group (trifluoroethanol) (they differ by 5.4 pK a
K K units!). This experimental evidence is consistent
with a fast elimination step.
In Summary
The hydrolysis of 2-aminobenzoate esters in the range of pH 4 to 8.5 occurs by intramolecular general base catalysis of the 2-amino group. The amine enhances the
reactivity of the water by partially removing a proton as the water attacks the carbonyl group.
A Ad dd di it ti io on na al l C Co om mm me en nt ts s
This problem is based on the work by Fife TH, Singh R, Bembi R (2002) J. Org.
Chem. 67:3179-3183.
S Su ub bj je ec ct ts s o of f R Re ev vi is si io on n
General base and nucleophile catalysis. Solvent isotope effects. Leaving group
ability.