The Hydrolysis of Phthalide, Thiophthalide, and Methyl o-Methoxybenzoate in Highly Alkaline Media. Curvature in the khyd vs Profile

Article abstract of DOI:10.1021/jo00095a047

The hydrolyses of phthalide (2a) and thiophthalide (3) have been studied in highly alkaline media, T = 25 deg C, μ = 3 (KCl).For both esters, an upward curvature in the plot of k_hyd vs is observed, suggestive of the onset of a second order in process in the hydrolysis.Carbonyl 18O-exchange studies indicated that no 18O is lost from the ester recovered from the hydrolysis media at times up to 3t_1/2 hydrolysis.Solvent kinetic isotope (skie) studies indicate that for 3, (k_hyd)_H2O/D2O is inverse throughout the entire range of .The lack of 18O-exchange and the inverse nature of the skie on k_hyd suggest that the curvature in the k_hyd vs plots is not due to the involvement of two hydroxides in the hydrolytic process.A correlation of the k_hyd data with the acidity function H_- appropriate for highly alkaline media is linear and suggests the involvement of a single hydroxide throughout the entire range.A reinvestigation of the alkaline hydrolysis of methyl o-methoxybenzoate (4) accompanied by 18O-exchange studies failed to detect unambiguous evidence for a bona fide second order in process.