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

Abstract

An efficient, eco-friendly, and highly convergent one-pot route to privileged thiazoloquinolinone derivatives has been developed via four-component cascade coupling (4CCC) of α-enolic dithioesters, cysteamine/2-aminothiophenols, aldehydes, and cyclic 1,3-diketones in recyclable [EMIM][EtSO] 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.

A decade update on the application of β-oxodithioesters in heterocyclic synthesis

“…Based on the above work, in 2018, Singh developed a greener and more efficient strategy to access thiazoloquinoline derivatives using a recyclable [EMIM][EtSO 4 ] ionic liquid as the solvent at room temperature via the same reaction process (Scheme 41B). 65 In addition, the ability of [EMIM][EtSO 4 ] in environmental remediation was evaluated and no degradation was observed during the reaction. Notably, the reusability of [EMIM][EtSO 4 ] in this transformation was studied and there was no significant loss of activity when [EMIM][EtSO 4 ] was reused four times.…”

Recent Advances in Green Synthesis of Functionalized Quinolines of Medicinal Impact (2018‐Present)

“…Singh et al Reported a one-pot four component cascade coupling of α-enolic dithioesters 284, cysteamine/2-aminothiophenols 285, aldehydes 286 and 1,3-diketones 106 by ecofriendly pathway in presence of [EMIM][EtSO 4 ] ionic liquid at room temperature to yield Thiazoloquinolinone 287 (Scheme 78). [118] The methodology proceeded via a sequence of N,S-acetal formation, Knoevenagel condensation, aza-ene reaction, imine-enamine/keto-enol tautomerization, and intramolecular N-cyclization.…”

Reagent‐Controlled Chemodivergent Approach to Thiazolines and Thiazines from α‐N‐Hydroxyimino Dithioesters

“…Molecules with more than one functional group have been proved to be excellent synthons towards the construction of important organic frameworks [7] . β‐Oxodithioesters bearing multiple reactive centers are versatile organic motifs, [8a] which have been employed widely in organic synthesis for the construction of various N,S‐heterocycles [8] such as isothiazoles, [8b] and thiazoloquinolines [8c] . Our group has a venerable concentration to utilize α‐N‐hydroxyimino‐β‐oxodithioesters to synthesize some N,S‐heterocycles such as thiazoles, [9a] 2,3‐dihydrothiazoles, [9a] and 1,4‐thiazine‐3‐ones [9b] via cascade annulation strategies.…”