Acid-Catalyzed Hydrolysis of Glycofuranosides

On the other side, the electronegativity of the C2 or the C5 substituent has a profound influence on the rate of acid-catalyzed hydrolysis of glycopyranosides, as is shown in Tables 3.5, 3.6, and 3.7. 

Unlike numerous kinetic and mechanistic studies of acid-catalyzed hydrolysis of glycopyranosides [5, 7, 9, 12, 16, 24-30] that led to the conclusion that glycopyranosides are hydrolyzed via an A-1 mechanism (the molecularity of the reaction and the entropy of activation (positive AS ), dissociation of methanol, and the formation of oxocarbenium ion transition state intermediate) (42 in Fig. 3.9), the acid-catalyzed hydrolysis of glycofuranosides has been studied much less [4, 9, 31-34]. 

Although there were a number of kinetic studies of the acid-catalyzed hydrolysis of sucrose (containing a ketofuranoside) [35-38] and of methyl and benzyl fructofuranoside [39], the first systematic kinetic and mechanistic study of acid-catalyzed hydrolysis of glycofuranosides was reported by Capon and Thacker [40] (see Table 3.8). 

The first thing that can be seen from Table 3.8 is that the entropies of activation for the hydrolysis of all glycofuranosides studied are negative. This is in strong contrast to the positive values obtained with pyranosides [9, 12, 16, 29, 30], suggesting that glycofuranosides and glycopyranosides must react via different mechanisms. 

The solvent deuterium isotope effect for the hydrolysis of methyl a-o-xylofuranoside in IM hydrochloric acid at 25° is q/ h o = 2.5 is consistent with the initial rapid and reversible proton transfer to form a conjugate acid of the furanoside which could be theoretically either 43 or 44 (Fig. 3.10). 

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