Hello,
I am setting up some reactions by using standard click chemistry: Azide + Alkyne in DMF/water, Ascorbic acid, Copper (II). I am having problems with the reprudicibility of the reaction. Sometimes it works perfectly well, the other day it does not. Does anybody could give me and advice about the pitfalls of that reaction?
- Does it matter if I use CuSO4, CuCl2 or Cu(OAc)2 ?
- Does the order matter:? E.g. I add first Azide + Alkyne, next Ascorbic Acid, then Cu(II)
- Is there a "best" ratio (equivalents) of each reagent?
- What do you think about the pH, steric hindrance of the alkyne (heat?), solvant effects?
Many thanks for your hints and help!
Best,
Sebastian
Dear Sebastian, sorry to see that your very interesting chemical question has not yet received any expert answers. I'm sure that there are numerous RG members who are experienced with click chemistry. As an inorganic chemist I'm not an expert in this field. However, I made the experience that a lot of information about a certain research topic is easily available right here on RG. Just check the "Publications" and "Questions" sections of RG for "click chemistry" and related terms. For example, it might be helpful to check the answers given to the following closely related question which has been asked earlier on RG:
What is the best procedure for click reaction between alkyl azide and terminal alkyne group?
https://www.researchgate.net/post/What_is_the_best_procedure_for_click_reaction_between_alkyl_azide_and_terminal_alkyne_group
(33 answers)
For a good overview you might want to check the following useful review article:
Copper-Catalyzed Azide–Alkyne Click Chemistry for Bioconjugation
https://www.jenabioscience.com/images/741d0cd7d0/Presolski_2011_Download_pdf_(1).pdf
(please see the attached pdf file)
The following relevant link might also be helpful:
Click Chemistry Protocols
https://broadpharm.com/web/protocol_files/Click%20Chemistry%20Protocol.pdf
In general I think that you should follow the published procedure as closely as possible in order to avoid technical problems. Good luck with your research and best wishes!
Click Chemistry works well when the conditions are maintained properly and the starting material is of high purity..
Hello Madhukar,
thank you for your recommendation. I used HPLC-purified substances (>=95% purity)... I assume that it should another reason but I could also go higher with the threshold of purity the next time (e.g. >98%)