Green Methodologies for Copper(I)-Catalyzed Azide-Alkyne Cycloadditions: A Comparative Study

Marissa Trujillo; Clayton Hull-Crew; Andrew Outlaw; Kevin Stewart; Loren Taylor; Laura George; Allison Duensing; Breanna Tracey; Allen Schoffstall

doi:10.3390/molecules24050973

Green Methodologies for Copper(I)-Catalyzed Azide-Alkyne Cycloadditions: A Comparative Study

Molecules. 2019 Mar 10;24(5):973. doi: 10.3390/molecules24050973.

Authors

Marissa Trujillo¹, Clayton Hull-Crew², Andrew Outlaw³, Kevin Stewart⁴, Loren Taylor⁵, Laura George⁶, Allison Duensing⁷, Breanna Tracey⁸, Allen Schoffstall⁹

Affiliations

¹ Department of Chemistry and Biochemistry, University of Colorado Colorado Springs, Colorado Springs, CO 80918, USA. mtrujil3@uccs.edu.
² Department of Chemistry and Biochemistry, University of Colorado Colorado Springs, Colorado Springs, CO 80918, USA. chullcre@uccs.edu.
³ Department of Chemistry and Biochemistry, University of Colorado Colorado Springs, Colorado Springs, CO 80918, USA. aoutlaw4@uccs.edu.
⁴ Department of Chemistry and Biochemistry, University of Colorado Colorado Springs, Colorado Springs, CO 80918, USA. kstewar4@uccs.edu.
⁵ Department of Chemistry and Biochemistry, University of Colorado Colorado Springs, Colorado Springs, CO 80918, USA. ltaylor6@uccs.edu.
⁶ Department of Chemistry and Biochemistry, University of Colorado Colorado Springs, Colorado Springs, CO 80918, USA. lgeorge@uccs.edu.
⁷ Department of Chemistry and Biochemistry, University of Colorado Colorado Springs, Colorado Springs, CO 80918, USA. allison.duensing@ucdenver.edu.
⁸ Department of Chemistry and Biochemistry, University of Colorado Colorado Springs, Colorado Springs, CO 80918, USA. breanna.tracey@outlook.com.
⁹ Department of Chemistry and Biochemistry, University of Colorado Colorado Springs, Colorado Springs, CO 80918, USA. aschoffs@uccs.edu.

Abstract

Successful copper(I)-catalyzed azide-alkyne cycloaddition (CuAAC) reactions may be achieved by several methods. In this paper, four synthetic protocols were performed for direct comparison of time required for the synthesis, yield, and purity of the 1H-1,2,3-triazole products. The methods with Cu(I) catalysts were conventional, microwave heating, solvent-free, and a method using glycerol solvent. The compounds synthesized in this paper were known non-fluorinated triazoles and new fluorinated triazoles. The results lead to the conclusion that the microwave method should be strongly considered for CuAAC syntheses.

Keywords: 1H-1,2,3-triazole; copper-catalyzed azide-alkyne cycloaddition (CuAAC); fluorotriazole; green chemistry; microwave heating; solvent-free reaction.

MeSH terms

Alkynes / chemistry
Catalysis
Click Chemistry
Copper / chemistry
Glycerol / chemistry
Green Chemistry Technology
Microwaves*

Substances

Alkynes
Copper
Glycerol