Acyl-oxygen cleavage

The saponification of 0 labeled ethyl propanoate was desenbed in Section 20 11 as one of the significant expenments that demonstrated acyl-oxygen cleavage in ester hydrolysis The 0 labeled ethyl propanoate used in this expenment was prepared from 0 labeled ethyl alcohol which in turn was obtained from acetaldehyde and 0 enriched water Wnte a senes of equations... 

Oxiranones (a-lactones) (Section 5.05.3.2.1), e.g. (6), in accord with their putative facile opening to zwitterions (Scheme 18), usually react readily with nucleophiles by alkyl-oxygen cleavage (Scheme 41) (71JA557), rather than the acyl-oxygen cleavage common for esters. 

Anionic polymerization proceeds by acyl-oxygen cleavage for almost all lactones, consistent with the mechanism for alkaline saponification of esters [Duda and Penczek, 2001 Hofman et al., 1985 Kricheldorf et al., 1988], For example, initiation by methoxide ion proceeds as... 

As can be seen in some of the above examples, the reactions of nucleophiles with /3-lactones are subject to modifications depending on the structure of the lactone. A good example can be seen in reactions of 3,3-dichloro-2-oxetanones, which react with various nucleophiles only by acylation (acyl-oxygen cleavage) (equation 57) (73JHC239). 

It also occurs at a measurable rate at low temperatures for the protonated esters of secondary alcohols, but is not important for primary alkyl esters. Acyl-oxygen cleavage, on the other hand, becomes significant only in very... 

The final increase in the rate of hydrolysis of the esters of primary aliphatic alcohols, in 85-100% H2SO, is presumably due to acyl-oxygen cleavage, since methyl acetate reacts faster than the ethyl ester, which would not be the case for alkyl-oxygen cleavage. So also may be the rapid hydrolysis of aryl acetates at moderate acidity, since aryl-oxygen cleavage is not expected to be so rapid a reaction. 

Positive evidence that the acyl-oxygen bond is broken on ester hydrolysis and formation is available from experiments using H2,80. Hydrolysis in the enriched solvent results in a net incorporation of, sO into the carboxylic acid produced if acyl-oxygen cleavage occurs, viz-... 

All these reactions involve acyl-oxygen cleavage. This has been demon-... 

It is generally assumed that the ionized carboxyl group R COO- is not susceptible to nucleophilic attack, and essentially all the available evidence supports this assumption. A solitary exception is discussed below (p. 160). Thus ester formation with acyl-oxygen cleavage, and oxygen exchange with the solvent, are not expected under alkaline conditions. There is no reason, however, why they should not occur in neutral solution, where a significant proportion of the undissociated acid (R COOH) is present, and both reactions are well established under these conditions. 

The broad outline of the mechanism of catalysis of ester hydrolysis by hydroxide ion is not in doubt. The reaction is well known to involve acyl-oxygen cleavage, and seems invariably to be of the second order, being first order in both ester and hydroxide anion. General base catalysis in the usual sense is not a possibility, the partial removal of a proton from water cannot generate a species more reactive than hydroxide ion, so direct nucleophilic attack must be involved. (However, if it is accepted that the high ionic nobility of the hydroxide ion in water is explained by a Grotthus-type mechanism... 

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