Unique structural properties of 2,4,6-tri-tert-butylanilide: isomerization and switching between separable amide rotamers through the reaction of anilide enolates

Abstract

Herein, we report a unique structural property of 2,4,6-tri-tert-butylanilide, which can be separated into its amide rotamers at room temperature. Interconversion between the rotamers of anilide enolates occurs readily at room temperature and their reaction with electrophiles gives mixtures of the rotamers in a ratio that depends on the reactivity of the corresponding electrophile. That is, the reaction of the 2,4,6-tri-tert-butylacetanilide enolate with reactive electrophiles, such as allyl bromide or protic acids, gives mixtures of the anilide rotamers in which the E rotamer is the major component, whereas less-reactive electrophiles, such as 1-bromopropane and 2-iodopropane, yield mixtures of the rotamers in which the Z rotamer is the major component. The rotameric ratio of the product is also strongly dependent on the reactivity of the anilide enolate. Switching between the anilide rotamers can be achieved through protonation of a less-reactive enolate by a less-reactive protic acid and thermal isomerization of the anilide.