Acid catalysis of acetal hydrolysis

Highly-efficient general acid catalysis of acetal hydrolysis is involved in the reactions of glycosidase enzymes such as lysozyme (Dunn and Bruice, 1973)... 

The acid catalysis of the hydrolysis of acetic anhydride was later investigated by Gold and Hilton292 using aqueous solutions of hydrochloric, perchloric, sulphuric and phosphoric acids at 0°C. The first-order rate coefficient for hydrolysis is approximately proportional to h0 for all of these acids over a wide range of concentrations and this correlation is far better than with log [H+ ]. The mechanism proposed by these authors is... 

General Acid Catalysis of Acetal, Ketal. and Orthoester Hydrolysis. Fife, T. H. Acc. Chem. Res. 1972, 5, 264. 

In the case of apparent general acid catalysis of acetylimidazole hydrolysis, the mechanism can be defined as a specific acid-general base process by comparison with the general base catalysis of N-methyl,N -acetylimidazolium ion. The rate of disappearance of N-methyl,N -acetylimidazolium ion in water at 25° is proportional to the concentration of the basic form of buffer components such as acetate, phosphate, N-methylimidazole, etc., (equation 30) (Wolfenden and Jencks, 1961). The buffer terms show a 1 1 correlation with the general acid-catalyzed rate of acetylimidazole disappearance (Jencks and Carriuolo, 1959) in water at 25°, when the rate expression for the latter reaction is written in terms of equation (32) rather than equation (31), that is, in terms of a general base-catalyzed hydration of protonated acetylimidazole (pX= 3-6). 

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... 

The most efficient system of this sort - and the only one to show intramolecular general acid catalysis of the hydrolysis of a methoxymethyl acetal derived from an aliphatic alcohol - is compound 3.13, based on the most reactive aromatic system... 

Intermolecular general acid catalysis of the hydrolysis of acetals and ketals Fig. 8 shows, in general terms, the reaction profile for the specific acid-catalysed hydrolysis of an acetal or a ketal. 

Intramolecular general acid catalysis of the hydrolysis of acetals, ketals and glycosides... 

Acetal Hydrolysis- Acid-base catalysis of acetal hydrolysis is important for the mechanism of glycosldase action. ... 

Dean, K.E.S., Kirby, A.J. Conceted general acid and nucleophilic catalysis of acetal hydrolysis a simple model for the lysozyme mechanism. J. Chem. Soc. Perkin Trans. 2. 2002, 428-132. 

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. 

Employing this as a guide, the author and his coworkers were successful in conclusively demonstrating general acid catalysis in the hydrolysis of three different types of acetals and ketals, 2- p-substituted phenoxy) tetrahydropyrans having electron withdrawing... 

This sensitivity to substitution of neutral hydrolysis means that the pH-independent reaction gradually becomes more important than the hydroxide reaction at the high pH end of the region, and becomes much more rapidly more important than acid-catalyzed hydrolysis at low pH. Thus from Fig. 13, the acid-catalyzed reaction can be seen to be significant for the hydrolysis of ethyl acetate between pH 4 and 5, and for phenyl acetate about pH 2 but for 2,4-dinitrophenyl acetate the acid-catalyzed reaction is not detectable at pH 1, and is presumably important only in relatively strong acid. It seems certain that this fast neutral hydrolysis is at any rate a partial explanation for the low efficiency of acid catalysis in the hydrolysis of very weakly basic esters, such as the trifluoroacetates and oxalates, in moderately concentrated acid (see p. 145). 

Bunton and Fendler297 have shown that fluoride ion will catalyse the hydrolysis of acetic and succinic anhydrides in water and aqueous dioxan. In water, the rate of loss of acetic anhydride is greater than the rate of formation of acetic acid, showing the build up of acetyl fluoride. The hydrolysis of succinic anhydride is also catalysed by fluoride ion but no build up of succinyl fluoride is seen. The catalysis of anhydride hydrolysis by pyridine has been discussed in the previous section, and it is perhaps sufficient to mention here that the catalytic coefficient for pyridine is about 30,000 times greater than that for acetate ion in 50% aqueous acetone at 25°C. 

Intermolecular general acid-catalysis occurs in a very limited number of known hydrolysis reactions. The hydrolysis of simple amides is susceptible to general acid catalysis by acetic acid at elevated temperatures. General acid catalysis in phosphate buffers is observable in one instance, the lactonization of 2-(hydroxymethyl)-benzoic acid (Weeks, 1965). Small intermolecular general acid terms have been observed 11 ... 

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