Alkyl benzoate esters, hydrolysis

Even alkyl benzoate esters give only a small amount of exchange imder basic hydrolysis conditions. This means that reversal of the hydroxide addition must be slow relative to the forward breakdown of the tetrahedral intermediate. ... 

Scheme 3.3 The mechanisms of acid- and base-catalysed hydrolysis of alkyl benzoate esters.

Treatment of A-acyloxy-A-alkoxybenzamides 76a with dilute aqueous sodium hydroxide, at room temperature, resulted in the rapid formation of alkyl benzoates 67.40 A crossover experiment using A-acetoxy-A-butoxy-/ -chlorobenzamide 26e and A-acetoxy-A-benzyloxybenzamide 27a resulted in the exclusive formation of butyl / -chlorobenzoate (46%) and benzyl benzoate (43%) esters along with the hydrolysis products, / -chlorobenzoic acid and benzoic acid indicating that ester formation involves an intramolecular process. 

This suggests that the hydrolysis of the ethyl ester involves the Aac1 mechanism, but that protonated isopropyl benzoate cleaves by alkyl-oxygen cleavage. A change in mechanism at this point would explain the order of reactivity towards hydrolysis of the various alkyl benzoates, observed by Kuhn18. 

Benzoxathiolium salts have proven to be effective masked acylating agents (79S223). 2-Substituted 1,3-benzoxathiolium tetrafluoroborates have now been utilized in the preparation of esters. Reaction of the salt (334) with two equivalents of an alcohol gave the 2-alkoxy-2-alkyl-benzoxathiole (335). Hydrolysis of (335) with red mercury(II) oxide and boron trifluoride etherate in aqueous THF delivered ethyl benzoate in excellent yield (Scheme 72). 

Aminolysis of phenyl dithioacetates,8 pyridinolysis of O-ethyl dithiocarbonates,9 reaction of pyrrolidine with O-ethyl 5-aryl dithiocarbonates,10 aminolysis of chlorothionformates,11 pyridinolysis of alkyl aryl thioncarbonates,12 reaction of anionic nucleophiles with nitrophenyl benzoate and its sulfur analogues,36 hydrolysis of methyl benzoate and phenyl acetate containing SMe, SOMe and S02Me substituents,42 solvolysis of phenyl chlorothioformate,79 synthesis of new thiadiazoles,124 examination of a neighbouring sulfonium group in ester hydrolysis,136 hydrolysis of V-type nerve agents,250 and the reactions of peroxymonosulfate ion with phosphorus(V) esters have all been looked at previously in this review. 

Some carboxylic acid esters undergo isotopic exchange as part of the mechanism of hydrolysis (Bender, 1951). Thus alkyl benzoates exchange... 

In our system, the acid chloride as the acylating agent was not applicable due to the basic conditions of the proposed transformation and the internal free nitrogen of the piperidyl moiety. However, the trioxifene acylation was adapted by preparing the phenyl ester of 5. Therefore, the required phenyl 4-[2-(l-piperidinyl)ethoxy]benzoate (9) was prepared by alkylating methyl 4-hydroxybenzoate with 2-(l-piperidinyl)ethyl chloride (6). Hydrolysis of the methyl ester provided the carboxylic acid that was converted to the acid chloride (8) using SOCI2 in a mixture of 1,2-dichloroethane and toluene. Acid chloride 8 was then reacted with sodium phenolate to provide 9 as a stable crystalline solid in 64% overall yield from the carboxylic acid. 

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