Nucleophilic Acyl Substitutions of Esters with Protic Nucleophiles Mediated by Amphoteric, Oxotitanium, and Vanadyl Species

A diverse array of oxometallic species were examined as catalysts in nucleophilic acyl substitution (NAS) reactions of methyl (or ethyl) esters with protic nucleophiles. Among them, oxotitanium acetylacetonate (TiO(acac)₂) and vanadyl chloride (VOCl₂−(THF)_x) served as the most efficient and water-tolerant catalysts. Transesterifications of methyl and/or ethyl esters with functionalized (including acid- or base-sensitive) 1° and 2° alcohols can be carried out chemoselectively in refluxed toluene or xylene in a 1:1 substrate stoichiometry using 1 mol % catalyst loading. The resultant products were furnished in 85−100% yields by simple aqueous workup to remove water-soluble catalysts. The new NAS protocol is also amenable to amines and thiols in 74−91% yields, albeit with higher loading (2.5 equiv) of protic nucleophiles. Representative examples of commercial interests such as Padimate O and antioxidant additives for plastics were also examined to demonstrate their practical applications. A 1:1 adduct between TiO(acac)₂ and a given 1-octadecanol was identified as (C₁₈H₃₇O)₂Ti(acac)₂ and was responsible for its subsequent NAS of methyl esters.