An Efficient Multicomponent, One-Pot Synthesis of Betti Bases Acid Catalyzed at Ambient Temperature

Abstract

The synthesis of aminobenzylnaphthols is achieved through a multicomponent reaction (MCR) involving 2-naphthol, a variety of amines, and aldehydes as starting materials. This one-pot approach is widely utilized in organic synthesis for its ability to efficiently construct complex molecular frameworks in a single step, minimizing the need for purification of intermediates and reducing reaction time. Aminonaphthols, which possess 1,3-aminooxygenated functional groups, are of considerable interest due to their broad biological activity and synthetic versatility. These compounds frequently serve as key intermediates in the synthesis of pharmaceutical agents and bioactive natural products, and are often recognized as pharmacophores in medicinal chemistry. Their unique structural features make them valuable candidates for further derivatization and development in drug discovery.

Introduction

Aminonaphthols, important biologically active compounds containing 1,3-amino-oxygenated groups, have attracted considerable attention for their diverse biological activities and synthetic versatility. Their synthesis began with modified Mannich reactions and has since expanded with various nitrogen sources and stereochemical applications, including use as chiral auxiliaries and catalysts. Green chemistry approaches—such as microwave-assisted methods, aqueous media, and nano-catalysts—have been explored to improve sustainability.

The study focused on synthesizing 1-aminobenzyl-2-naphthols (Betti bases) via reactions of azomethines (Schiff bases formed from amines and aldehydes) with 2-naphthol. Three reaction schemes were tested using different acidic catalysts and solvents to optimize yields. Scheme IB (using phosphoric acid and sodium phosphate in THF) proved most effective.

The results showed that electron-donating substituents on the aldehyde enhanced reaction efficiency and yields. The proposed mechanism involves acid-catalyzed formation of azomethines, followed by nucleophilic attack by 2-naphthol to form the desired aminonaphthol derivatives. These compounds have potential applications in medicinal chemistry and organic synthesis due to their broad utility and biological activity.

Conclusion

A three-component, one-pot synthesis of aminonaphthols has been successfully developed using a catalytic system comprising phosphoric acid (H?PO?) and monosodium phosphate (NaH?PO4). This method proceeds under mild, ambient temperature conditions, offering a practical and environmentally friendly alternative to conventional multistep processes. The synergistic effect of the dual acid catalyst system promotes high yields and selectivity, making it suitable for sustainable organic synthesis. The use of equimolar amounts of phosphoric acid (H?PO?) and monosodium phosphate (NaH?PO4) not only facilitates excellent product yields but also enhances operational simplicity and broadens substrate scope. This efficient, environmentally benign methodology represents a valuable addition to the synthetic toolbox in both organic and medicinal chemistry. Owing to its practical execution and alignment with green chemistry principles, this strategy holds significant promise for the synthesis of structurally diverse and biologically relevant aminonaphthol derivatives.

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Copyright

Copyright © 2025 Sushma Rani, M. K. Singh. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.