Copper-catalysed ligation of azides and acetylenes
View Patent ↗A copper catalyzed click chemistry ligation process is employed to bind azides and terminal acetylenes to provide 1,4-disubstituted 1,2,3-triazole triazoles. The process comprises contacting an organic azide and a terminal alkyne with a source of reactive Cu(I) ion for a time sufficient to form by cycloaddition a 1,4-disubstituted 1,2,3-triazole. The source of reactive Cu(I) ion can be, for example, a Cu(I) salt or copper metal. The process is preferably carried out in a solvent, such as an aqueous alcohol. Optionally, the process can be performed in a solvent that comprises a ligand for Cu(I) and an amine.
1. A copper catalyzed process for preparing a 1,4-disubstituted 1,2,3-triazole comprising:
contacting an organic azide and a terminal alkyne with Cu(I) ion in the presence of a ligand for Cu(I) to form a 1,4-disubstituted 1,2,3-triazole compound; wherein the ligand for Cu(I) is selected from the group consisting of a nitrile, an alcohol, and a combination thereof.
2. The process of claim 1 wherein the ligand for Cu(I) comprises an alcohol.
3. The process of claim 1 wherein the ligand for Cu(I) comprises a nitrile.
4. The process of claim 3 wherein the nitrile comprises acetonitrile.
5. The process of claim 1 wherein the azide and alkyne are contacted in equimolar amounts.
6. A copper catalyzed process for preparing a 1,4-disubstituted-1,2,3-triazole comprising contacting a solution of an organic azide and a terminal alkyne with Cu(I) ion in the presence of a ligand for Cu(I) to form a 1,4-disubstituted-1,2,3-triazole compound, wherein the ligand is selected from the group consisting of an alcohol, a nitrile and a combination thereof.
7. The process of claim 6 wherein the ligand for Cu(I) comprises an alcohol.
8. The process of claim 6 wherein the ligand for Cu(I) comprises a nitrile.
9. The process of claim 8 wherein the nitrile comprises acetonitrile.
10. The process of claim 6 wherein the azide and alkyne are contacted in equimolar amounts.
11. The process of claim 6 wherein the solution is an aqueous solution.
12. The process of claim 6 wherein the solution comprises an alcohol as a solvent.
13. The process of claim 6 wherein the solution comprises acetonitrile as a solvent.
14. A copper catalyzed process for preparing a 1,4-disubstituted-1,2,3-triazole comprising contacting a solution of an organic azide and a terminal alkyne with a catalytic amount of Cu(I) ion to form a 1,4-disubstituted-1,2,3-triazole compound; wherein the solution also comprises a ligand for Cu(I) selected from the group consisting of a nitrile, a nitrite, an isonitrile, an amine, a carboxylate, a halide, an alcohol, a thiol, and a combination thereof.
15. The process of claim 14 wherein the solution is an aqueous solution.
16. The process of claim 14 wherein the solution comprises an alcohol as a solvent.
17. The process of claim 14 wherein the solution comprises acetonitrile as a solvent.