What is the mechanism for the hydrolysis of an anhydride into a carboxylic acid using HCl as a catalyst?

Question

Christian Anderson · Accepted Answer

This is a fairly standard mechanism (or mechanistic pattern) that you should get to know.

It is practically identical for anhydrides as it is for acyl halides (particularly acyl chlorides) and esters, and similar variations are seen in the acid-catalyzed hydrolysis of nitriles, amides, etc, wherein the electron-dense atom (e.g. #"O"# in a carbonyl or #"N"# in a nitrile) takes on a proton and becomes susceptible to nucleophilic attack.

It is perfectly acceptable to assume one starts with hydronium when a strong acid like #"HCl"# is the acid catalyst.

The electron-dense carbonyl oxygen acquires a proton from the strong acid. Either carbonyl oxygen is fine, just not the ether oxygen.
Water then nucleophilically attacks the partially positive carbon, as oxygen withdraws electron density to break the carbonyl bond.
Proton transfer pt1.
Proton transfer pt2.
Tetrahedral collapse. You may choose which hydroxyl group does so, but it is usually the one that originated from the nucleophile that is typically used.
Regenerate the catalyst.
NOTE: You must replace #R_1# and #R_2# with #R# groups that correspond to your specific substrate.

Ellie Adams · Answer

undefined The mechanism for the hydrolysis of an anhydride into a carboxylic acid using HCl as a catalyst involves nucleophilic attack by water on the carbonyl carbon atom of the anhydride, followed by protonation of the carbonyl oxygen atom. This is then followed by a second nucleophilic attack by water on the acyl-oxygen atom, leading to the formation of a tetrahedral intermediate. Finally, proton transfer and elimination of the leaving group yield the carboxylic acid product.