Revisiting the Synthesis of Betti Bases: Facile, One-pot, and Efficient Synthesis of Betti Bases Promoted by FeCl3•6H2O.

Abstract

Betti bases are pharmaceutically and synthetically important scaffolds due to their diverse range of biological activities and applications in key synthetic transformations in organic synthesis. This work has been sought to contribute to the development, design, and implementation of an improved green methodology with higher atom economy and lower E-factor values for the synthesis of Betti bases. To realize our objectives, we screened out different catalysts and reaction conditions using one-pot multicomponent modified Mannich reaction/Betti reaction by employing 2-naphthol, benzaldehyde and pyrrolidine as model substrates. The developed methodology afforded functionalized Betti bases in 60-100% yields via FeCl3•6H2O catalyzed one-pot multi-component Betti reaction under neat conditions at 110 °C (5-15 min) using several aromatic aldehydes and secondary amines. A facile synthetic methodology with higher atom economy and lower E-factor values to synthesize Betti bases via FeCl3•6H2O catalyzed one-pot multicomponent Betti reaction of 2-naphthol, aromatic aldehydes, and secondary amines under neat conditions at 110 °C has been reported. The developed methodology offers various advantages, such as excellent yields (60-100%), short reaction time (5-15 min), wide substrate scope (12 examples), green reaction conditions, use of readily available catalyst, and easy purification (without column chromatography).