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This book is deliberated for undergraduate, graduate level students and researchers of Organic chemistry to provide them detailed study and knowledge regarded synthesis of Thiochromeno-fused quinoline heterocyclic derivatives by Domino Knoevenagel-hetero-Diels-Alder (DKHDA) reaction and their biological evaluation.The book contains narrative information of preceding work done on quinoline heterocycles, a novel synthetic way using TBA-HS under solvent free condition and an ionic liquid (ILs) which is a greener approach to synthesize it, spectral analysis using 1H, 13C, 2D NMR, DQF-COSY and NOESY, and single crystal X-ray diffraction studies of all the synthesized compounds and their biological study to investigate their potency and application.I hope this book will work as a supportive future reference of DKHDA synthesis of Thiochromeno-fused quinoline scaffolds and their biological applications for the students, researchers and chemists and assist them to plan a new and more proficient route using DOMINO method.