Metal-Free Approaches towards N-Heterocycles and Diarylmethanes under Batch as well as Continuous-Flow Conditions

Abstract

This thesis work is divided into two parts Part A & Part B. Part A includes the synthesis of nitrogen-containing heterocycles from 2-(tosylamino)aryl-substituted p-QMs and ortho- aminobenzyl alcohols under batch process and, Part B involves the synthesis of diarylmethanes under continuous-flow conditions using microreaction technology. Part A: Synthesis of Nitrogen-containing Heterocycles from 2-(Tosylamino)aryl- substituted para-Quinone Methides & ortho-Aminobenzyl alcohols Part A is sub-divided into two chapters. Chapter 1: A One-pot Approach to the Synthesis of 2,3-Disubstituted Indoles from 2- (Tosylamino)aryl-substituted para-Quinone Methides This chapter discusses the reactivity profile of p-QMs and 2-(tosylamino)aryl- substituted para-quinone methides, and their application in the synthesis of nitrogen- containing heterocycles. 2,3-Disubstituted indoles are important heterocyclic scaffolds and, are often found as an integral part of many natural and unnatural molecules that possess remarkable therapeutic properties (Figure 1). While exploring the synthesis of heterocyclic compounds, we envisioned that it could be possible to synthesize 2,3-disubstituted indole derivatives from 2-(tosylamino)aryl-substituted p-QMs. A combination of inorganic and organic base is found to be effective for the desired transformation. This is a multi-step transformation and proceeds through inorganic base mediated N-alkylation of 2- (tosylamino)aryl-substituted p-QM with bromomethyl aryl ketone followed by 1,6 intramolecular cyclization and eliminative isomerization/aromatization to provide a variety of 2,3-substituted indoles in moderate to good yields (Scheme 1).