THE EFFECT OF ACID STRENGTH ON THE MITSUNOBU ESTERIFICATION REACTION - CARBOXYL VS HYDROXYL REACTIVITY

In the presence of carboxylic acids, the adduct formed between triphen ylphosphine and diisopropyl azodicarboxylate reacts to form mono- and bis-acylated hydrazides and the carboxylic acid anhydrides. These prod ucts are formed via attack of the carboxylate on the triphenylphosphon ium group of the adduct, with weaker acids reacting much faster than s tronger acids. This provides an explanation for the observation in the literature that acids stronger than acetic acid, such as 4-nitrobenzo ic acid and chloroacetic acid, provide better yields in esterification reactions, since reaction of the alcohol with the phosphonium group o f the adduct is more rapid than the competing reaction of the carboxyl ate for the phosphonium group.