NEIGHBORING CARBOXYL GROUP PARTICIPATION IN THE HYDROLYSIS OF ACETALS- HYDROLYSIS OF O-CARBOXYBENZALDEDHYDE CIS-1,2-CYCLOHEXANEDIYL AND TRANS-1,2-CYCLOHEXANEDIYL ACETALS

The plot of log k(obsd) vs pH for the hydrolysis of o-carboxybenzaldeh yde trans-1,2-cyclohexanediyl acetal at 50 degrees C in H2O has four u nit changes of slope in the pH range 2-9. The plot is here described b y proceeding from low pH to high pH. The observed hydronium ion- and w ater-catalyzed reactions at pH < 6 have rate constants that are simila r, but not identical, to those for hydrolysis of the acylal 3-[(trans- 2-hydroxycyclohexyl)oxy]phthalide, which was isolated from the reactio n at FH 3. and synthesized independently. The pH-log rate constant pro file for hydrolysis of the acetal bends downward near FH 6 to give a s lope of -1.0. Oxocarbonium ion hydrolysis is then a water reaction. At pH 7 the mechanism of the reaction changes to attack of OH- on the ox ocarbonium ion intermediate. A change in rate-determining step takes p lace at FH 8 to hydronium ion-catalyzed ring opening of the anionic sp ecies of the acetal, or the kinetically equivalent intramolecular gene ral acid catalysis in ring opening of the neutral species. The mechani sm involving general acid catalysis by the neighboring carboxyl group is strongly supported by the D2O solvent isotope effect. The o-carboxy l group enhances the rate of the acetal ring-opening reaction by a fac tor of 230 in comparison with the exactly analogous p-carboxyl-substit uted acetal. in contrast, the analogous p-OCH3-, p-NO2-, o- and p-COOC H3-, and p-COOH-substituted derivatives have uncomplicated linear pH-l og rate constant profiles with slopes of -1.0. A neighboring carboxyl group can participate in the hydrolysis of an acetal of an aliphatic a lcohol if the C-O bond breaking process is facilitated by the release of steric strain. The implications of these results for the mechanism of lysozyme-catalyzed reactions are discussed.