Metal-Free One-Pot Four-Component Cascade Annulation in Ionic Liquids at Room Temperature: Convergent Access to Thiazoloquinolinone Derivatives

An efficient, eco-friendly, and highly convergent one-pot route to privileged thiazoloquinolinone derivatives has been developed via four-component cascade coupling (4CCC) of alpha-enolic dithioesters, cysteamine/2-aminothiophenols, aldehydes, and cyclic 1,3-diketones in recyclable [EMIM] [EtSO4] ionic liquid at room temperature for the first time. The reaction proceeds via a N,S-acetal formation, Knoevenagel condensation, aza-ene reaction, imine-enamine/keto-enol tautomerization, and intramolecular N-cyclization cascade sequence. The merit of the protocol is highlighted by its efficacy of forming consecutive five new bonds (two C-C, two C-N, and one C-S) and two rings with all reactants being efficiently utilized. The operational simplicity, sustainability, mild conditions, excellent yields, tolerance of wide functional groups, and avoidance of expensive/toxic reagents are additional attributes to this domino four-component protocol. Notably, the products were easily separated from the ionic liquid, and thus the ionic liquid obtained was reused four times without considerable loss of any activity.