Intramolecular General Acid Catalysis of Glycoside Hydrolysis

6 Intramolecular General Acid Catalysis of Glycoside Hydrolysis 

Intramolecular general acid catalysis is normally detected in the first instance by a horizontal portion on the plot of logiokobs versus pH, governed by the add dissociation constant of the substrate. Thus, the hydrolyses of various salicyl acetals (including the P-D-glucopyranoside below pH 10, where a base-catalysed process occurs) obey the rate law of eqn (3.7), where ko is the first-order rate constant for hydrolysis of the neutral molecule and ka is the second-order rate constant for the acid-catalysed hydrolysis of the neutral molecule  

The appearance of the plot of logiokobs versus pH is of two parallel lines of gradient—1 joined by an inflection, which, if the acid catalysis is efficient enough, can become a large horizontal region. 

The effectiveness of intramolecular catalysis is quantitated by the effective molarity of the reaction, the ratio of the first-order rate constant for the intramolecular reaction to the second-order rate constant for a sterically and electronically analogous reaction. Effective molarities have a theoretical maximum of 10 M, but in small molecule systems rarely come anywhere near this. 

Estimates of effective molarities in general acid catalysis of acetals require the analogous intermolecular reaction to be observable and therefore, as we have seen in the previous section, for the oxocarbenium ion to be particularly stable. The termolecular processes corresponding to the hydrolysis of salicyl 

---