Synthesis of 2(5H)-Furanone Derivatives with Symmetrical and Unsymmetrical Bis-1,2,3-triazole Structure

Abstract

The interesting bioactivities of 2(5H)-furanone, 1,2,3-triazole, and amino acid derivatives have promoted their combination into one multifunctional molecule. The symmetrical bis-1,2,3-triazoles and mono-1,2,3-triazoles with one free azide group are synthesized respectively by controlling the molar ratio of reactants, N-[5-alkoxy-2(5H)-furanonyl] amino acid propargyl ester and 1,4-diazidobutane. The unsymmetrical bis-1,2,3-triazoles are afforded by the subsequent reaction of mono-1,2,3-triazoles with other terminal alkynes with good to excellent yields in a short time under the same mild “click” reaction conditions. The 32 new compounds obtained in the reactions are characterized by Fourier transform infrared, ¹H NMR, ¹³C NMR, mass spectrometry, and elemental analysis. Because of the diversity of four or five basic units in molecule, this methodology provides easy access to different chiral 2(5H)-furanone compounds with polyheterocyclic structure, especially with unsymmetrical bis-1,2,3-triazole moiety. Importantly, a simple approach is provided for the synthesis of unsymmetrical bis-1,2,3-triazoles using common diazides.

GRAPHICAL ABSTRACT

Keywords:

• Bis-1,2,3-triazole
• click chemistry
• 2(5H)-furanone
• synthetic method
• unsymmetrical

ACKNOWLEDGMENT

We thank X. Y. Chen in RWTH Aachen University for her help.

Notes

^a Reaction conditions: Cu(OAc)₂ · H₂O 0.05 equiv., Cu 0.1 equiv., solvent CH₃CN, rt, reaction time 12–16 h according to TLC monitoring.

^b Isolated yield.

^a Reaction conditions: Cu(OAc)₂ · H₂O 0.05 equiv., Cu 0.1 equiv., solvent CH₃CN, rt; for the synthesis of 2, the molar ratio of 1,4-diazidobutane to 1 was 0.5:1, and the reaction time was about 16 h according to TLC monitoring; for the synthesis of 3, the molar ratio of 1,4-diazidobutane to 1 was 2:1, and the reaction time was about 12 h according to TLC monitoring.

^b Isolated yield on the basis of 1.

^a Reaction conditions: 3d 1 mmol, 4a 2 mmol, Cu(OAc)₂ · H₂O 0.05 equiv., Cu 0.1 equiv., rt, solvent CH₃CN.

^b Isolated yield.

^a Reaction conditions: 3 1 mmol, 4 2 mmol, Cu(OAc)₂ · H₂O 0.05 equiv., Cu 0.1 equiv., rt, solvent CH₃CN, 2 h.

^b Isolated yield.

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