One-Pot, Three-Component Coupling Synthesis of [(Benzothiazol-2-ylamino)(aryl)methyl]isoquinolinols under Catalyst- and Solvent-Free Conditions

Abstract

One-pot three-component coupling procedure has been developed for the synthesis of (2'-aminobenzothiazolomethyl-aryl)-hydroxyisoquinolines via the reaction of hydroxyisoquinolines, aryl/heteroaryl/aliphatic aldehydes with 2-aminobenzothiazoles under catalyst- and solvent-free conditions. The developed 2'-aminobenzothiazolomethylation procedure is suitable to execute even on gram scale with a broad scope. The 2'-aminobenzothiazolomethylated products (Betti bases) were formed through the initial nucleophilic C-attack of hydroxyisoquinolines on aldehydes to generate the ortho-Quinone Methide (o-QM) as an intermediate followed by the subsequent 1,4-aza-Michael addition of 2-aminobenzothiazoles. Betti bases have significance in medicinal chemistry due to their wide range of pharmacological applications and they are useful ligands and catalysts in asymmetric synthesis.