Nucleophilicity of 4‐(Alkylthio)‐3‐imidazoline Derived Enamines

Abstract

Imidazolidine‐4‐thiones (ITOs) are cyclic, secondary amines that were considered as potential prebiotic organocatalysts for light‐driven α‐alkylations of aldehydes by bromoacetonitrile (BAN). Recent studies showed that the initially supplied ITOs represent the pre‐catalyst because they undergo S‐alkylation with BAN to give 4‐(alkylthio)‐3‐imidazolines (TIMs). Given that the same reagent mix that undergoes light‐driven α‐alkylations is also effective in the dark, we synthesized ten ITO‐ or TIM‐derived enamines of aldehydes and characterized their nucleophilic reactivities by kinetic studies in acetonitrile. The experimental second‐order rate constants k ₂ for reactions of enamines with benzhydrylium ions (reference electrophiles) were evaluated by the Mayr‐Patz equation, lg k ₂(20 °C)= s _N( N+ E). The determined nucleophilicities N (and s _N) reveal the reactivity profiles of these enamines under prebiotically relevant conditions as well as their potential for use in organocatalytic synthesis.

Abstract

Enamine activation is a key method to enhance the reactivity of carbonyl compounds in α‐alkylation reactions. In spite of their possible role in prebiotic chemistry, enamines derived from aldehydes and 4‐(alkylthio)‐3‐imidazolines (TIMs) have scarcely been studied. Their reactivities have now been classified on the Mayr nucleophilicity scale by kinetic measurements. In addition, their Lewis basicities have been determined by DFT calculations and equilibrium measurements.