Synthesis of quinolines tetrahydroacridines and related N heterocycles via novel synthetic methods

Abstract

Quinolines are a class of N-heterocycles, recognized as essential motifs in newlinepharmaceuticals, agrochemicals, and functional materials owing to their wide-ranging applications. These scaffolds were well known for their medicinal properties, such as antitumor, antimalarial, antiplasmodial, etc. On that account, the construction of these molecules has seized considerable attention of chemists associated with organic synthesis and drug discovery research. According to literature review, despite remarkable advancements in the synthesis of 2-amino quinolines, 2-Alkyl/Aryl newlinesubstituted quinolines and their derivatives, the described methodologies often rely on newlinetransition-metal-catalysts, high reaction temperature and longer reaction times, which newlinelimit the substrate scope. Indenoquinolines, naphthridines and tetrahydro acridines, newlinebeing novel molecules, remain underexplored, highlighting the need for more efficient newlinemethods. In this thesis, we describe our studies on the development of a transition metal-free, mild, and operationally friendly method for the synthesis of 2-amino quinolines, 2- alkyl/aryl substituted quinolines, tetrahydro acridines and related scaffolds. We developed a KOtBu-mediated reaction between 2-amino arylcarbaldehydes and benzyl/alkyl cyanides toward the expeditious formation of 2-aminoquinolines under transition metal-free conditions. The described transformation proceeds through an insitu-generated enamine intermediate from benzyl/alkyl cyanides under KOtBumediated reaction conditions. The substituted 2-aminoquinolines were realized with excellent yields at room temperature and a shorter reaction time. The designed process exhibits operational simplicity and broad functional group tolerance in delivering products of high significance. We have developed an expeditious strategy for the synthesis of diverse quinolines, indenoquinolines and acridines using KOtBu-mediated reaction conditions.