Ester hydrolysis acyl-oxygen fission

Isotopic substitution. A classic example is the demonstration by Polanyi and Szabo (37) of acyl-oxygen fission in the alkaline hydrolysis of -amyl acetate. An ester could undergo cleavage at two locations, as indicated in 3. 

Transesterification occurs by mechanisms that are identical with those of ester hydrolysis—except that ROH replaces HOH—that is, by the acyl-oxygen fission mechanisms. When alkyl fission takes place, the products are the acid and the ether. 

Isotopes can also be used to solve mechanistic problems that are non-kinetic. Thus the aqueous hydrolysis of esters to yield an acid and an alcohol could, in theory, proceed by cleavage at (a) alkyl/ oxygen fission, or (b) acyl/oxygen fission ... 

If the reaction is carried out in water enriched in the heavier oxygen isotope 180, (a) will lead to an alcohol which is 180 enriched and an acid which is not, while (b) will lead to an l80 enriched acid but a normal alcohol. Most simple esters are in fact found to yield an lsO enriched acid indicating that hydrolysis, under these conditions, proceeds via (b) acyl/oxygen fission (p. 238). It should of course be emphasised that these results are only valid provided that neither acid nor alcohol, once formed, can itself exchange its oxygen with water enriched in 180, as has indeed been shown to be the case. 

Of the mechanisms of carboxylic ester hydrolysis, that for the base-catalyzed reaction is the best understood. It generally proceeds by bimolecular attack of hydroxide ion on the carbonyl group, forming a tetrahedral intermediate, followed by elimination with acyl-oxygen fission ... 

Thiols are more acidic than the corresponding alcohols and are converted into their salts using alkali metal hydroxides or alkoxides. The thiolate salts are powerful nucleophiles, a property which has been used in the cleavage of methyl esters and methyl ethers. The combination of a hard acid and a soft base such as lithium propanethiolate (Li SPr) may favour attack on the methyl group of an ester and lead to alkyl-oxygen fission of the ester, rather than the more common addition of a nucleophile to the carbonyl group and consequently acyl-oxygen fission. This is particularly useful in the hydrolysis of hindered esters. 

The hydrolysis of esters may take place by two general pathways involving either acyl-oxygen fission (Scheme 3.71a) or alkyl-oxygen... 

An important example of acyl transfer reactions is ester hydrolysis, where two sites of bond cleavage, both leading to the same product, are possible. The possibilities, shown in structure 1, are denoted acyl-oxygen fission (Ac) and alkyl-oxygen fission (Al). 

II. Unimolecular Acid-Catalyzed Reactions Involving Acyl-Oxygen Fission. At least one instance is known in which decomposition of the protonated complex does not seem to depend upon the attack of water or an alcohol molecule. It is the formation or hydrolysis of esters of 2,4,6-trimethylbenzoic acid in sulfuric acid solution. Since cryoscopic studies have shown that the acid gives a molar freezing point depression of four (p. 39), and the ester five (p. 225), we must conclude that decomposition of the protonated complex to the acyl carbonium ion 0... 

For the saponification of esters, evidence similar to that on p. 227 indicates that the reaction usually proceeds with acyl-oxygen fission. The most self-contained proof again has been obtained by the use of Ols. The alkaline hydrolysis of amyl acetate in water containing this isotope showed that the amyl alcohol which was formed contained only O16 18... 

There is abundant evidence (see, e.g. Ingold, 1953, Chapter XIV) that the hydrolysis of simple aliphatic esters catalyzed by the hydroxo-nium ion occurs with acyl-oxygen fission by the bimolecular attack of a molecule of water on the protonated ester. It has, however, been suggested recently (Tal vik and Pal m, 1959) that ethyl acetate hydrolyzes by the unimolecular mechanism... 

NucleophiUc substitution at carbonyl carbon, takes place in bimolecu-lar carboxylic ester hydrolysis with acyl-oxygen fission (21) by the... 

The observation that R-2-octyl acetate yields R-2-octanol with 99% retention rules out the possibility that the reaction occurs by alkyl-oxygen fission [10]. This mechanism is consistent with the normal mode of ester hydrolysis which also occurs by acyl-oxygen fission. Neither amides nor nitriles were affected by superoxide under phase transfer conditions [10]. The data on ester cleavage by superoxide ion is summarized in Table 8.3. 

Where X = alkoxy and R = H this represents the hydrolysis of an alkyl ester. One of the earliest chemical applications of 018-enriched water was Polanyi and Szabo s demonstration in 1934 that the alkaline hydrolysis of n-pentyl acetate proceeds by acyl-oxygen bond fission. 

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