Hydrogen bonding intramolecular catalytic hydrolysis

Compound 3.13 (Scheme 2.22) is hydrolyzed with a half-life of 3.5 h in water at 39 °C, some 10 times faster than expected for the spontaneous hydrolysis of a methoxymethyl acetal of a tertiary alcohol, corresponding to a transition state stabilization of 14 kcal (58 kj) mol [47], and at the rate expected for the methoxymethyl derivative of an alcohol of pKa about 4. Perhaps significantly, this is almost equal to the pKa (4-18) of the catalytic COOH group of 3.13. (Which also confirms that there is no significant intramolecular hydrogen bonding in the reactant.)... 

In another estimate (Kirby and Percy, 1989), the carboxyl group in l-methoxymethoxy-8-naphthoic acid and the dimethylammonium group in the l-methoxymethoxy-8-A, A -dimethylnaphthylammonium ion are estimated to lead to rate increases by intramolecular catalysis of < ca. 900 and 1.9 X 10 compared to the value of ca. 1 x 10 calculated for the intramolecular catalytic effect of the carboxyl group in 2-methoxymethoxybenzoic acid. The salicylate ion remains the most efficient leaving group thus far discovered that can take part in hydrogen-bond catalysis of the hydrolysis of acetals. 

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