Overview Of Acid Derivative Chemistry

Acid derivatives undergo generally the same types of reactions, but they do so at vastly different rates. This is good, because it lets us transform them selectively.

The reactivity order of acid derivatives is: acid chlorides, anhydrides, esters, then amides.

Acid chlorides and anhydrides react quickly with all reagents, and can exhibit some selection regarding the extent of reaction (e.g., cuprate addition)

Esters react modestly well with all reagents except the very weakest ones (cuprates and LiAlHOtBu3). Little specificity is seen, because ketones and aldehydes are more reactive.

Carboxylic acids are a special case. They rarely react properly with anionic nucleophiles, because the acid-base reaction is instantaneous, converting the acid to the nearly inert carboxylate anion. Under acidic conditions, they are about as reactive as esters. Under basic conditions, they are about as reactive as a stone.

Amides are the most sluggish, so we have to bash them to get reaction. LAH, OH-/much heat, H3O+ and much heat. Even fairly reactive Grignard reagents don't reliably react with amides, although part of the problem here lies with the acidity of the amide NH.

Reactivity Table