For ester hydrolysis

The most important species m the mechanism for ester hydrolysis is the tetrahe dral intermediate Evidence m support of the existence of the tetrahedral intermediate... 

In basic solution, a mechanism similar to the Bac2 mechanism for ester hydrolysis is believed to operate ... 

R = CH3 and AR = C6H4NO2.) Actually Scheme XXV and Eq. (3-176) both take place, with some of the hydroxamic acid being formed directly and some via the intermediate. (Note that each of these reactions is itself complex, presumably occurring via a tetrahedral intermediate as shown in Scheme XXII for ester hydrolysis.)... 

Apply the steady-state approximation to Scheme XXII for ester hydrolysis to find how the experimental second-order rate constant qh is related to the elementary rate constants. 

Most acid-catalyzed hydrolyses of carboxylic acid derivatives proceed by the A2 mechanism, as shown for ester hydrolysis ... 

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-... 

There is much evidence for this mechanism, similar to that discussed for ester hydrolysis. A MO study on the mechanism of amide hydrolysis is available. In certain cases, kinetic studies have shown that the reaction is second order in OH , indicating that 107 can lose a proton to give 108. Depending on the nature... 

The most effective catalyst for the hydrolysis of p-nitrophenyl acetate was reported to be a cycloheptaamylose derivative containing approximately two imidazole groups per cycloheptaamylose molecule (Cramer and Mackensen, 1970). At pH 7.5 and 23°, this material accelerates the rate of release of phenol from p-nitrophenyl acetate by a factor of 300 when compared with the hydrolysis of this substrate in the absence of catalyst. However, when compared with an equivalent concentration of imidazole, which is an effective catalyst for ester hydrolysis at neutral pHs, the rate accelerations imposed by this cycloheptaamylose derivative are only two- to threefold. Cramer and Mackensen attributed this rate enhancement to nucleophilic displacement of phenol from the included ester by a cycloheptaamylose hydroxyl group, assisted internally by the attached imidazole group... 

Compound 56 is the first branch point intermediate in the analog syntheses, furnishing 90 upon oxidative cyclization with MnC>2 and deprotection with Mgl2. Intermediate 56 was also benzylated to protect the C5,C5 -naphthols in preparation for ester hydrolysis, which provided the next key branch point intermediate, bisacid 91. Ester hydrolysis here with aqueous base was surprising facile relative to intermediate 62, en route to (+)-calphostin D (Scheme 7.14). Presumably, the smaller C7,C7 -groups alleviate the steric gearing that hinders the reactivity of the C3,C3 -esters. 

Using dicyclohexyl-18-crown-6 it is possible to dissolve potassium hydroxide in benzene at a concentration which exceeds 0.15 mol dm-3 (Pedersen, 1967). The free OH- has been shown to be an excellent reagent for ester hydrolysis under such conditions. The related solubilization of potassium permanganate in benzene, to yield purple benzene , enables oxidations to be performed in this solvent (Hiraoka, 1982). Thus, it is possible to oxidize a range of alkenes, alcohols, aldehydes, and alkylbenzenes under mild conditions using this solubilized reagent. For example, purple benzene will oxidize many alkenes or alcohols virtually instantaneously at room temperature to yield the corresponding carboxylic acids in near-quantitative yields (Sam Simmons, 1972). 

Aspirin is an ester, bnt it still contains a carboxylic acid fnnction (p/Ca 3.5). In aqueous solntion, there will thus be significant ionization. However, this ionization now provides an acid catalyst for ester hydrolysis and initiates autolysis (autohydrolysis). The hydrolysis product salicylic acid (pACa 3.0) is also acidic both aspirin and salicylic acid are aromatic acids and are rather stronger acids than aliphatic compounds such as acetic acid (pACa 4.8) (see Section 4.3.5). An aqueous solution of aspirin has a half-life of about 40 days at room temperature. In other words, after about 40 days, half of the material has been hydrolysed, and the biological activity will have deteriorated similarly. 

Parenthetically, it should be noted that there is evidence for the accumulation of an acylenzyme (i.e., a mixed anhydride with Glu-270) in the carboxypeptidase A-catalyzed hydrolysis of esters at low temperature, but this evidence does not include confirmation by chemical trapping experiments (Makinen et al, 1979 Kuo and Makinen, 1982 Suh et al., 1985). This would imply a nucleophilic, rather than promoted-water, pathway for ester hydrolysis. Sander and Witzel (1985) provided the only... 

Lipases play an important role in organic synthesis and also in flavour biotechnology. Pig pancreatic extract and especially many microbial lipases are used for ester hydrolysis, esterification (alcohol and acid), transesterification (ester and... 

Amides. Metal ions catalyze the hydrolysis of a variety of amides, including acylamino acids, dipeptides and tripeptides, and amino acid amides. In all these compounds it is possible for a metal ion to complex with one or more ligand groups, either amine or carboxylate ion functions, in addition to the amide group. Thus the structural prerequisites for the metal ion catalysis of amide hydrolysis are the same as those for ester hydrolysis. 

TABLE 10.14 Classification of the eight mechanisms for ester hydrolysis and formationHJ... 

Further evidence for this mechanism is that a small but detectable amount of 180 exchange (see p. 332) has been found in the acid-catalyzed hydrolysis of benzamide.551 (180 exchange has also been detected for the base-catalyzed process,562 in accord with the Bac2 mechanism). Kinetic data have shown that three molecules of water are involved in the ratedetermining step,563 suggesting that, as in the Aac2 mechanism for ester hydrolysis (0-10), additional water molecules take part in a process such as... 

Two types of esterification reaction that can be studied with water as solvent are lactone formation, in which the alcohol is part of the same molecule as the acid, and the lsO-exchange reaction of carboxylic acids, which makes it possible to examine A-2 reactions of carboxylic acids under the conditions used for ester hydrolysis. Work in both these fields confirms the similarities between ester hydrolysis and formation. The hydrolysis and formation of y-butyrolactone have already been discussed (p. 109). We deal here with the lsO-exchange reactions of carboxylic acids. 

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