Organocatalyzed Sustainable Annulation to Construct 4‐Amino‐ and 4‐Thioquinoline Scaffolds as Potential Cancer Therapeutics

Abstract

An inventive and versatile one‐pot, atom‐economical, inexpensive organocatalyzed sustainable annulation strategy has been developed for the synthesis of bioactive 4‐arylamino/arylthio‐2,3‐substituted quinolines with excellent pharmaceutical potential as a candidate for anticancer activity, according to the outcome of performed molecular docking studies. This novel, metal‐free, eco‐benign, domino, multicomponent annulation protocol facilitates simultaneous C═N, C─C, C═C, and C─N/C─S bond formation utilizing an organic Brønsted acid catalyst, p‐TSA.H₂O. The reaction protocol proceeds through a benign and efficient pathway under both conventional heating and microwave irradiation conditions. Furthermore, prolific and diverse substrate scopes were explored through this methodology, including drug‐like architectures involving various nucleophiles such as 2‐alkynylanilines, thiophenols, aromatic amine, alkyl amine, amide, sulfonamide, and so forth. Herein, we have also established the proposed plausible mechanistic hypothesis through the relevant control experiments, prevailing literature supports, and HRMS kinetic study outcome.