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 in human blood plasma 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, Cu(II) ion in the presence of a reducing agent, or copper metal.
1. A copper catalyzed process for preparing a 1,4-disubstituted 1,2,3-triazole comprising:
contacting a human blood plasma solution of an organic azide and a terminal alkyne with a source of catalytic Cu(I) ion to form by cycloaddition a 1,4-disubstituted 1,2,3-triazole.
2. The process of claim 1 wherein the solution further comprises at least one ligand comprising at least one functional group selected from the group consisting of a nitrile, an isonitrile, a primary amine, a secondary amine, a tertiary amine, a nitrogen bearing heterocycle, a carboxylate, a halide, an alcohol, a thiol, a sulfide, a phosphine, and a phosphite.
3. The process of claim 1 wherein the solution further comprises at least one polyvalent ligand comprising one or more functional groups selected from the group consisting of a nitrile, an isonitrile, a primary amine, a secondary amine, a tertiary amine, a nitrogen bearing heterocycle, a carboxylate, a halide, an alcohol, a thiol, a sulfide, a phosphine, and a phosphite.
4. The process of claim 1 wherein the source of catalytic Cu(I) ion comprises a Cu(I) salt.
5. The process of claim 1 wherein the source of catalytic Cu(I) comprises Cu(II) ion in combination with a reducing agent.
6. The process of claim 1 wherein the source of catalytic Cu(I) comprises copper metal.
7. A copper catalyzed process for preparing a 1,4-disubstituted 1,2,3-triazole comprising:
contacting an aqueous solution of an organic azide and a terminal alkyne with a source of Cu(I) ion and a ligand for Cu(I) to form a 1,4-disubstituted 1,2,3-triazole, wherein the aqueous solution comprises water and a cosolvent.
8. The process of claim 7 wherein the cosolvent comprises a nitrile.
9. The process of claim 8 wherein the nitrile comprises acetonitrile.
10. The process of claim 1 wherein the cosolvent comprises an alcohol.
11. The process of claim 10 wherein the alcohol comprises ethanol or tert-butanol.
12. The process of claim 7 wherein the ligand comprises one or more functional groups selected from the group consisting of a nitrile, an isonitrile, a primary amine, a secondary amine, a tertiary amine, a nitrogen bearing heterocycle, a carboxylate, a halide, an alcohol, a thiol, a sulfide, a phosphine, and a phosphite.
13. The process of claim 7 wherein the source of Cu(I) ion comprises a Cu(I) salt.
14. The process of claim 7 wherein the source of catalytic Cu(I) comprises Cu(II) ion in combination with a reducing agent.
15. The process of claim 14 wherein the reducing agent comprises ascorbate.
16. The process of claim 14 wherein the Cu(II) ion is provided as a Cu(II) salt.
17. The process of claim 14 wherein the Cu(II) salt comprises CuSO 4 or a hydrate thereof.
18. The process of claim 7 wherein the source of catalytic Cu(I) comprises copper metal.
19. A copper catalyzed process for preparing a 1,4-disubstituted 1,2,3-triazole comprising:
contacting an aqueous solution of an organic azide and a terminal alkyne with a source of Cu(I) ion and a ligand for Cu(I) to form a 1,4-disubstituted 1,2,3-triazole, wherein the aqueous solution comprises water and a cosolvent comprising ethanol, acetonitrile, or a combination thereof; and the source of Cu(I) ion comprises a Cu(II) salt and ascorbate.
20. The process of claim 19 wherein the ligand comprises one or more functional groups selected from the group consisting of a nitrile, an isonitrile, a primary amine, a secondary amine, a tertiary amine, a nitrogen bearing heterocycle, a carboxylate, a halide, an alcohol, a thiol, a sulfide, a phosphine, and a phosphite.