Effect of cyclodextrin on the intramolecular catalysis of aryl hydrogen phthalate ester hydrolysis

Abstract

The kinetics of the hydrolysis of Z-phenyl hydrogen phthalate (Z = H, p-Me, m-Me, m-Cl and p-Cl) was studied in the presence of hydroxypropyl-β-cyclodextrin (HPCD) at pH 2.00, 3.00 and 12.00. In acid solutions these reactions involve two kinetic processes, which correspond to the formation and decomposition of phthalic anhydride. At pH 12 only the formation of phthalic anhydride could be measured because it decomposes very fast under these conditions. The rate constant for the formation of phthalic anhydride decreases as the HPCD concentration increases whereas the decomposition of phthalic anhydride is almost constant. The kinetic results are interpreted in terms of the formation of an inclusion complex of the neutral, K_CD^AH, or ionized substrate, K_CD^A, with HPCD. In all cases K_CD^AH > K_CD^A, so part of the observed inhibition is due to an increase in the amount of substrate in its unreactive neutral form. Comparison of the rate constants for the reaction of the complexed substrates with those in the bulk solution indicates that the transition state for the cyclodextrin-mediated reaction is less stabilised than the ionised substrate with values of ΔΔG ranging from 0.28 to 1.59 kcal mol⁻¹ depending on the substituent on the aryl ring.