Dissertations and Theses

Date of Award

2013

Document Type

Thesis

Department

Chemistry

First Advisor

Mahesh Lakshman

Keywords

Coumarins, triazoles, azides

Abstract

Triazole-containing compounds have shown great biological activity ranging from antiviral, antibacterial, to anticancer, to name a few. Coumarin derivatives have also shown interesting biological activities. The combination of these bioactive compounds appears to have great promise for new and future medicines. In this work, various 4-azido-coumarins were synthesized via the transformation of the 4-hydroxy derivatives to 4-benzotriazolyloxy coumarins by reaction with the peptide coupling agent (benzotriazol-1-yloxy)tris-(dimethylamino)phosphonium hexafluorophosphate (BOP), and 1,8-diazabicycloundec-7-ene (DBU) as the base, in tetrahydrofuran (THF) solvent. The 4-benzotriazolyloxy coumarins were converted to the 4-azidocoumarins by reaction with sodium azide (NaN3), and the overall process was simplified to a one-pot, two-step process. The methodology reduced the need for additional manipulations and purifications. Using the 4-azidocoumarins thus prepared, the 1,4-disubstituted-1,2,3 triazoles were synthesized via a copper-catalyzed alkyne-azide cycloaddition (CuAAC) reaction. CuAAC reactions of the azides were optimized by screening of various copper catalysts 6 and copper tetrakis acetonitrile hexafluorophosphate ([Cu(CH3CN)4]PF6) gave the best results in the experiments performed. Once the reaction conditions were optimized, various 4-(1,2,3-triazolyl) coumarins were synthesized in good to excellent yields.

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