Mild hydrolysis or alcoholysis of amides. Ti(IV) catalyzed conversion of primary carboxamides to carboxylic acids or esters

Article abstract of DOI:10.1139/v94-022

Reaction of primary amides (e.g., 1a or 6-13) or O-methylhydroxamates (1b and 1c) with a catalytic amount of TiCI₄ and one equivalent of aqueous HCI converts these compounds in good yields to carboxylic esters (when an alcohol is used as solvent) or to carboxylic acids (when 9:1 dioxane:H₂O is used as solvent). These conversions are chemoselective for primary amides: mono- and dialkyl amides are not affected by the reaction conditions. The hydrolysis conditions described do not compromise the stereochemical integrity of an adjacent chiral center. This is exemplified by the hydrolysis of naproxen amide (34) to naproxen (33) without detectable racemization as determined by chiral HPLC.