Metal-Free, One-Pot, Rapid Synthesis of Tetrahydropyridines Using Acetic Acid as Solvent and Catalyst at Room Temperature

Abstract

Acetic acid–promoted, one-pot synthesis of tetrahydropyridines has been developed under metal-catalyst-free conditions via a tandem reaction. High atom economy, good yield, simple procedure, no expensive column chromatography, shorter reaction time, and metal-free and mild reaction conditions are some of the important features of this protocol. The current methodology provides an alternative approach for not only highly substituted tetrahydropyridines (THPs) but also fully substituted tetrahydropyridines (FTHPs) in moderate to good yields. The plausible mechanism for the formation of THPs was greatly promoted by the H⁺ ion coming from acetic acid.

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GRAPHICAL ABSTRACT

Keywords:

• Acetic acid
• acetoacetic esters
• diastereoselectivity
• intramolecular Mannich cyclization
• tandem reaction
• tetrahydropyridines

ACKNOWLEDGMENTS

B. U. M. and M. S. K. thank VIT management for providing financial support through research associateships (RA). The authors express their gratitude to P. G. Aravindan, SAS, VIT, Vellore, and G. Sekar, IIT, Madras, India, for crystal data. B. U. M. thanks CSIR for providing SRF.

Notes

^a Conditions: Ethyl acetoacetate (0.5 mmol), benzaldehyde (1 mmol), and aniline (1 mmol) in solvent (3 ml), with stirring in room temperature.

^b Isolated yields.

^a Conditions: 1,3-dicarbonyl compound (0.5 mmol), aromatic aldehyde (1 mmol), and aniline (1 mmol) in 2.5 ml of acetic acid with stirring at room temperature.

^b Isolated yields.