Acid catalysis ester hydrolysis

Specific acid catalysis is catalysis by the hydronium ion (in water) or the lyonium ion in general. Acid-catalyzed ester hydrolysis is an example. 

Specific acid catalysis (SAC) involves a rapid protonation of the compound followed by the slow step, which is accelerated in comparison with the uncatalysed reaction because of the greater reactivity of the protonated compound. You have just seen an example with an epoxide. Ester hydrolysis (or formation) is another. Water attacks esters veiy slowly it attacks protonated esters much more quickly. This is just the ordinary mechanism for acid-catalysed ester hydrolysis (or formation) given in Chapter 12. 

Unusual reaction orders are found in product-promoted or reactant-inhibited ("autocatalytic") reactions, the former with positive apparent order with respect to a product, the latter with negative apparent order with respect to a reactant (see Section 8.9). An example of a product-promoted reaction is acid-catalyzed ester hydrolysis. An example of a reactant-inhibited reaction has already been encountered, namely, olefin hydroformylation, whose order with respect to CO is negative (see eqn 6.12 in Section 6.3). Such behavior is also not uncommon in heterogeneous catalysis (see Section 9.3.2) and enzyme catalysis ("substrate-inhibited" reactions in biochemistry lingo, Section 8.3). A reaction having an order with respect to a silent partner—CO in a homogeneous hydrogenation—will be examined in some detail later in this chapter (see Examples 7.3 and 7.4). 

Pos twe-Tone Photoresists. The ester, carbonate, and ketal acidolysis reactions which form the basis of most positive tone CA resists are thought to proceed under specific acid catalysis (62). In this mechanism, illustrated in Figure 22 for the hydrolysis of tert-huty acetate (type A l) (63), the first step involves a rapid equihbrium where the proton is transferred between the photogenerated acid and the acid-labile protecting group ... 

A catalyst is a substance that increases the rate of a reaction, other than by a medium effect, regardless of the ultimate fate of this substance. For example, in hydroxide-catalyzed ester hydrolysis the catalyst OH is consumed by reaction with the product acid some writers, therefore, call this a hydroxide-promoted reaction, because the catalyst is not regenerated, although the essential chemical event is a catalysis. 

Poly(L-malate) decomposes spontaneously to L-ma-late by ester hydrolysis [2,4,5]. Hydrolytic degradation of the polymer sodium salt at pH 7.0 and 37°C results in a random cleavage of the polymer, the molecular mass decreasing by 50% after a period of 10 h [2]. The rate of hydrolysis is accelerated in acidic and alkaline solutions. This was first noted by changes in the activity of the polymer to inhibit DNA polymerase a of P. polycephalum [4]. The explanation of this phenomenon was that the degradation was slowest between pH 5-9 (Fig. 2) as would be expected if it were acid/base-catalyzed. In choosing a buffer, one should be aware of specific buffer catalysis. We found that the polymer was more stable in phosphate buffer than in Tris/HCl-buffer. 

The same framework of eight possible mechanisms that was discussed for ester hydrolysis can also be applied to amide hydrolysis. Both the acid- and base-catalyzed hydrolyses are essentially irreversible, since salts are formed in both cases. For basic catalysis the mechanism is Bac2-... 

Exactly the same considerations apply to the esterification of hindered acids (182) in the reverse direction. It will be noticed that this mechanism requires protonation on the less favoured (cf. p. 240) hydroxyl oxygen atom (185) to allow the formation of the acyl carbocationic intermediate (184). Apart from a number of R3C types, a very well known example is 2,4,6-trimethylbenzoic (mesitoic) acid (186), which will not esterify under ordinary acid-catalysis conditions—and nor will its esters (187) hydrolyse. Dissolving acid or ester in cone. H2S04 and pouring this solution into told alcohol or water, respectively, is. found to effect essentially quantitative esterification or hydrolysis as required the reaction proceeds via the acyl cation (188) ... 

The study of both carbonyl and carbon acid participation in ester hydrolysis has been used by Bowden and Last (1971) to evaluate certain of the factors suggested for important roles in enzymic catalysis. A first model concerns a comparison of the three formyl esters and shows that the proximity of the formyl to the ester group and internal strain increase in passing along the series, 1,2-benzoate, 1,8-naphthoate and 4,5-phenanthroate. The very large rate enhancements result from the proximity of the internal nucleophile once formed and from internal strain. Strain is increased or induced by the primary... 

Mineral surfaces may accelerate the rate of ester hydrolysis (Stone, 1989 Hoffmann, 1990 Torrents and Stone, 1991). One plausible scheme for this heterogeneous catalysis assumes a nucleophilic addition of the ester to the surface functional group, e.g., in case of a carboxylic acid ester... 

The term acid catalysis is often taken to mean proton catalysis ( specific acid catalysis ) in contrast to general acid catalysis. In this sense, acid-catalyzed hydrolysis begins with protonation of the carbonyl O-atom, which renders the carbonyl C-atom more susceptible to nucleophilic attack. The reaction continues as depicted in Fig. 7. l.a (Pathway a) with hydration of the car-bonium ion to form a tetrahedral intermediate. This is followed by acyl cleavage (heterolytic cleavage of the acyl-0 bond). Pathway b presents an mechanism that can be observed in the presence of concentrated inorganic acids, but which appears irrelevant to hydrolysis under physiological conditions. The same is true for another mechanism of alkyl cleavage not shown in Fig. 7.Fa. All mechanisms of proton-catalyzed ester hydrolysis are reversible. 

Fig. 7.1. a) Specific acid catalysis (proton catalysis) with acyl cleavage in ester hydrolysis. Pathway a is the common mechanism involving a tetrahedral intermediate. Pathway b is SN1 mechanism observed in the presence of concentrated inorganic acids. Not shown here is a mechanism of alkyl cleavage, which can also be observed in the presence of concentrated inorganic acids, b) Schematic mechanism of general acid catalysis in ester hydrolysis. 

The stability of these compounds is maximal at pH 4 - 6, and decreases very sharply at lower and higher pH values, and the mechanism and products of the reaction differed with pH. In the neutral range, hydrolysis yielded the aromatic sulfonamide and the ester, whereas, under acid catalysis in the low pH range, the products were the AT-acyl sulfonamide and an alcohol (R OH, Fig. 11.9). Of particular interest is that the tm values for hydrolysis of the N-sulfonyl imidates in 80% human plasma were 3-150 times lower than in buffer solution at identical pH and temperature. This was taken as evidence for enzymatic hydrolysis by human plasma hydrolases. Hydrolysis under these conditions yielded the sulfonamide and the ester in quantitative amounts. 

Suitably substituted acetals have been shown to hydrolyse rapidly by a mechanism that involves intramolecular general acid catalysis similar to that proposed for Glu-35 in (34), The largest effects have been found for acetals with the salicylate ion as the leaving group. For example, the spontaneous hydrolysis (35) of 2-methoxymethoxybenzoic acid [73] occurs 300-fold more rapidly than the same reaction of 4-methoxymethoxybenzoic acid [74] and ca. 600-fold more rapidly than the reaction of 2-methoxymethoxybenzoic acid methyl ester [75] (Capon et al, 1969 Dunn and Bruice, 1970). The... 

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