Facile One-Pot Synthesis of 1,2,3-Triazoles Featuring Oxygen, Nitrogen, and Sulfur Functionalized Pendant Arms

Abstract

A practical and efficient one-pot synthesis of novel 1,2,3-triazoles featuring nitrogen, oxygen, and sulfur functionalized pendant arms has been developed. The click reaction of mono-propargyl derivatives supported by aniline, thiophenol, and benzyl alcohol, with sodium azide and p-substituted benzyl halogenides, renders a series of N-substituted-1,2,3-triazoles in good yields under mild reaction conditions. The catalyst system was based in Cu(OAc)₂ · H₂O, sodium L-ascorbate, and 1,10-phenanthroline monohydrate, and all reactions were performed in a mixture H₂O–ethanol (4:1 v/v). Additionally, the preparation of bis-1,2,3-triazoles supported by di-propargylated aniline was carried out, demonstrating the versatility of the present methodology.

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GRAPHICAL ABSTRACT

Keywords:

• Catalysis
• click chemistry
• cycloaddition
• multicomponent synthesis
• 1,2,3-triazoles

ACKNOWLEDGMENTS

We are grateful to Consejo Nacional de Ciencia y Tecnología, CONACyT (Project 181448). D. M. E. also acknowledges “Beca de Retencion” (Application 192049) sponsored by CONACyT and UAM-Azcapotzalco. D. M. E., G. N. S., and L. L. R., acknowledge the SNI for the stipend.

Notes

Notes. Reagents and conditions: For methylaniline: 1.03 mmol of (I), Cu(OAc)₂ · H₂O 5 mol%, 1,10-phenanthroline 5 mol%, sodium ascorbate 1.03 mmol, 1.24 mmol of sodium azide, 1.24 mmol of p-substituted benzyl halogenide, stirring at room temperature for 18 h, EtOH/H₂O (4:1). For thiophenol: 0.61 mmol of I, Cu(OAc)₂ · H₂O 5 mol%, 1,10-phenanthroline monohydrate 5 mol%, sodium L-ascorbate 0.76 mmol, 0.83 mmol of sodium azide, 0.83 mmol of p-substituted benzyl halogenide, stirring at room temperature for 16 h, EtOH/H₂O (4:1).

Notes. Reagents and conditions: 0.7 mmol of III, Cu(OAc)₂ · H₂O 5 mol%, 1,10-phenanthroline 5 mol%, sodium ascorbate 0.7 mmol, 0.77 mmol of sodium azide, 0.83 mmol of p-substituted benzyl halogenide, stirring at room temperature for 36 h, EtOH/H₂O (4:1).

Notes. Reagents and conditions: 0.59 mmol of IV, Cu(OAc)₂ · H₂O 5 mol%, 1,10-phenanthroline 5 mol%, sodium L-ascorbate 0.59 mmol, 1.42 mmol of sodium azide, 1.42 mmol of p-substituted benzyl halogenide, stirring at room temperature for 24 h, EtOH/H₂O (4:1).