Reactions involving acyl-oxygen bond formation

2 Reactions involving acyl-oxygen bond formation 

Bender et al.136 have measured the rate of incorporation of, 80 from enriched water into several substituted benzoic acids. The catalyst was 0.07 M HC1, and the solvent 33% dioxan-water. The rate coefficients for exchange at 80°C are given in Table 14, which also contains a comparison of these rate coefficients with those for the hydrolysis of the corresponding ethyl esters, measured by Timm and Hinshelwood128 in 60% acetone and 60% ethanol. As noted earlier by Roberts and Urey, the absolute rates are very similar for the two reactions. Also, as expected, the exchange rate of benzoic acid, with two equivalent oxygen atoms, is almost exactly twice as fast as that of ethyl benzoate, with only one ( h.vdM xch is 5.2 for the ester). 

11 Ratio of rate coefficients for exchange in 33% dioxan-water and the hydrolysis of the corresponding ethyl benzoates in 60% ethanol or acetone-water (mean of the two values) at 80°C in the presence of 0.05 M HCI. 

One of the characteristics of the acid-catalyzed hydrolysis of esters, that is shared by ester formation also, is that substituent effects on the rate coefficients are small, and not simply related to a values (see below, p. 131). The data in Table 14 show that this is also true for the, sO-exchange reaction of substituted benzoic acids. This is borne out by the relative constancy of the ratio khyJkexch for the different substituted acids it was not possible to obtain a meaningful p value from the data of Table 14, because of the small number of points and the large amount of scatter evident on the Hammett plot. Mesitoic acid is highly unreactive, compared with the m- and p-substi-tuted esters used, as is its methyl ester towards alkaline hydrolysis138, and presumably reacts by the seriously hindered Aac2 route. 

O Connor and Bunton and their coworkers have measured the rates of 180-exchange of a number of aliphatic carboxylic acids in acidic, basic and 

---

The reactions of these ions with acids and esters were also examined. Reaction 79, a displacement involving cleavage of the acyl-oxygen bond and the formation of acyllum ion products ... 

However, formic acid and all of the formates (all compounds where R=H) which were Investigated undergo alternate reactions to a greater or lesser extent. An alternate reaction which Is generally Important Is another four-center reaction, this one Involving breakage of the acyl-oxygen bond ... 

The first, and fundamental, piece of evidence necessary for a discussion of the detailed mechanism of any chemical change is the identification of the covalent bonds formed and broken this may or may not be the same thing as the identification of the products of the reaction. In the case of ester hydrolysis or formation the alternatives involve the cleavage or formation of bonds from oxygen to the carbon atom of either an alkyl or an acyl group, and it is in principle, and generally also in practice, a simple matter to distinguish between these alternatives. 

As with peptide hydrolysis, several enzyme systems exist that catalyze carboxylic and phosphoric ester hydrolysis without the need for a metal ion. They generally involve a serine residue as the nucleophile in turn, serine may be activated by hydrogen-bond formation—or even proton abstraction—by other acid-base groups in the active site. The reaction proceeds to form an acyl- or phosphory 1-enzyme intermediate, which is then hydrolyzed with readdition of a proton to the serine oxygen. Mechanisms of this type have been proposed for chymotrypsin. In glucose-6-phosphatase the nucleophile has been proposed to be a histidine residue. ... 

In a similar vein, the silver (Ag+) salts of carboxylic adds undergo decarboxylation in the presence of bromine (Br2) to produce silver bromide and bromoalkane (the Hunsdiecker reaction). The Hunsdiecker reaction also appears to involve radicals as shown in Scheme 9.101, where,in the first step,silver bromide precipitates from the reaction mixture with formation of an acyl hypobromite (RC(D2Br). Then, homolysis of the oxygen-bromine bond generates bromine atoms and the carboxyl radical, seen here as the same radical generated in Scheme 9.100. Following loss of carbon dioxide (CO2), it is held that the alkyl radical is captured by the bromine atom (Br ) to produce alkylbromide (1-bromoethane [CH3CH2Br]). 

---