Figure 1. Brönsted plot for the basic hydrolysis of Z-aryl hydrogen phthalates. The pKa of the phenols were taken from Jencks, W. P.; Gildrist, M. J. Am. Chem. Soc. 1968, 90, 2622 and from .CRC Handbook of Biochemistry and Molecular Biology, Easman, G.. A. Editor, 3rd Edition, Cleveland, Ohio, CRC Press, 1977.
Considering that the pKa of benzyl alcohol can be estimated as 14.3,9 we calculate the second order rate constant for the hydrolysis of 1 as 2.7×10-5 M-1s-1. This value is about two orders of magnitude smaller than the experimental value. It is important to notice that the Brönsted plot for the reaction of hydroxide ion with substituted phenyl acetates fall one order of magnitude bellow that for the reaction with acetates of substituted alcohols.10
The discrepancy between the calculated and observed values may be explained taking into account relevant discussion existent in the literature which indicate that for the hydrolysis of aryl esters there is no barrier for the expulsion of the aryloxide leaving group, therefore the reaction can be considered to be concerted. On the other hand, for the hydrolysis of esters with poorer leaving groups, the mechanism of hydrolysis involves a tetrahedral intermediate.11,12,13,14
The hydrolysis reaction of 1 was studied at pH=12.80 and at NaOH=0.45 M in the presence of variable concentration of hydroxypropyl-ß-cyclodextrin (HPCD) (Table 3). This compound is a derivative of ß-cyclodextrin, that have some of the primary and secondary hydroxyl groups substituted with hydroxypropyl group. The HPCD that we used has an average degree of substitution of 5.9. The chemical behaviour of HPCD is similar to that of the unsubstituted ß- cyclodextrin.15
In all cases the reaction is inhibited by hydroxypropyl-ß-cyclodextrin and the plot of kobs vs HPCD concentration is non-linear (Figure 2 is representative). On the other hand alpha and gamma cyclodextrin do not affect the rate, which point to the importance of the size of the cavity for the inhibition.
