Water hydrolysis of carboxylic acid derivatives

All carboxylic acid derivatives are hydrolysed to carboxylic acids by the action of water as nucleophile. Acyl halides and anhydrides of low molecular weight are hydrolysed quite vigorously. Esters and amides react much more slowly, and hydrolysis normally requires acid or base catalysis. This is nicely 

Hydrolysis of an ester can be achieved by either base- or acid-catalysed reactions, and the nucleophilic substitution mechanisms follow processes that should 

The analgesic aspirin, acetylsalicylic acid, is an ester, hi this compound, the alcohol part is actually a phenol, salicylic acid. Aspirin is synthesized from salicylic acid by treatment with acetic anhydride. 

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. 

Even aspirin tablets that have been stored under less than ideal conditions and, therefore, have absorbed some water from the atmosphere, are likely to have suffered partial hydrolysis. The characteristic odour of acetic acid (vinegar) from a bottle of aspirin tablets will be an indicator that some hydrolysis has occurred. 

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