It also depends on the nature of compounds you are going to conjugate. For some substances Cu catalysis is not acceptable. I should also recommend you to get sure that both of your innitial compounds are giving clear solutions in the reaction solvents.

If your reaction components (educts) are water soluble you should use that as the solvent. I would also prefer the CuSO4/NaAsc/DIEA procedure for click reactions in solution. On the solid support you may want to switch to other Cu(I) sources.

I have examined the mixture of H2O/PEG400 as the reaction solvent and CuSO4/NaAsc as Cu(I) source several times and the results were very good. this conditions gave the products with high yields and the reaction times were distinguishably decreased.

Cu2+ and ascorbic acid in Acetonitrile as solvent

Other option is ter-ButylONO as a reagent and solvent with Cu1+ catalyst

It depends on what solvent you used for reaction, if you use water or DMSO, CuSO4-NaLAc is often the best; if you use DMF, often use CuBr. And co-catalyst like BiPy also often used.

I agree with Jinshan Go, it depends on kind of solvent! Please look at the offer above.

CuSO4/Ascorbic acid can often work well for such reactions.

Hi,

Generally I use Cu(II) (CuSO4.5H2O) with sodium ascorbate to generate in situ the Cu(I) active catalyst. As solvent, you can use a mixture 1:1 in volume of methylene chloride and water, or THF and water, to have a homogeneous mixture. Then, depending on the number of click reaction do you have to perform per molecule, you can just stire the reaction at room temperature overnight, or, if you have a lot of building blocks to click you can use the express method. She consists on performing the reaction with THF and water on a microwave oven during 2 or 3 hours at 80°C.

Also a very important thing that can change completely the yield of your reactio, is le volume of solvent. Try to be the more concentrate you can. For example, when I perform a click reaction (12 click per molecule) on 100mg of C60 dodeca azide, I use only 0.5 mL of each solvent, if I put more, the yield decreases rapidely.

So I hope that I was usefull. Godd luck and a lot of pleasure with this reaction.

Bye.

Alternatively, you can use a biphasic mixture DCM/H2O at room temperature under vigorous stirring with CuBr, it's really efficient and fast...

There is no direct formula for this reaction, you will probably have to try various conditions for better results depending on your substrates. Within our group, we found that one method does not work the same for different substrates. We use either Cu(I) in THF under inert conditions or Cu(II)/NaAscorbate go with aqueous mixtures. 5 mol% CuI works perfectly in THF at room temperature and the results are reproducible. Filter off CuI through celite when the reaction is complete.

We have several procedures but I list two below two greener procedures in the order of ease of opeartion and execution.

The first one is extremely easy -simply uses copper sulfate and Chitosan.

The second one can use a magnetic core bearing catalysts that has glutathione appended to it and decorated with copper on top. This one requires some effort to make the catalyst but once you have it, you can keep using it again and again and retrieve it magnetically.

1. Copper on Chitosan: Recyclable Heterogeneous Catalyst for Azide-Alkyne Cycloaddition Reactions.

R. B. Nasir Baig and R. S. Varma: Green Chem., 15, 1839-1843 (2013).

2. A Highly Active Magnetically Recoverable NanoFerrite - Glutathione- Copper Catalyst for Huisgen 1, 3-Dipolar Cyclo additions.

R. B. Nasir Baig, R. S. Varma: Green Chem., 14, 625-632 (2012).

Hi,

The Cu(II)-sodium ascorbate system for click chemistry is widely used. However, it is limited to substrates which are tolerant of water. Work was presented on a click reaction that works well in organic solvents (or employing neat reagents).

CuBr(PPh3) serves as an effective commercially available (or easily synthesised from CuBr2 and PPh3) catalyst and can be employed at very low loadings and at room temp. The ligated system serves to stabilise the relatively sensitive catalytic Cu(I) species.

For more on this work see:

Regards,

Arkesh

http://pubs.acs.org/doi/pdf/10.1021/jo200085j

we can find so many procedures for azide-alkyne click reaction.

among them three best catalysts are

1. CuSO4/ Na-ascorbate in t-butyl alcohol and water solvent system

2. Copper iodide+ Di isopropyl ethyl amine(DIPEA)

3. CuBr(PPh3) with a tertiary amine.

tersiyer bütanol-su (1:1) ya da THF:tert-butanol-su (3:1:1) en iyi çözücü, oda sıcaklığından 50 dereceye kadar ısıtabilirsin.

Angew. Chem. Int. Ed., 2006, 45, 8235-8238

We have used also:

1. CuSO4/ Na-ascorbate in t-butyl alcohol and water

2. Copper iodide+ Di isopropyl ethyl amine(DIPEA)

3. CuBr(PPh3) with a tertiary amine.

The Cu(I)-catalyzed Huisgen’s 1,3-dipolar cycloaddition reaction between

alkynes and azides is one of the prototype reactions in click chemistry.

Better u see the reference : Kolb, H. C.; Finn, M. G.; Sharpless, K. B. Angew. Chem., Int. Ed. 2001, 40, 2004

Very recently our group reported based on this problem.. check this reference

Adv. Synth. Catal. 2013, 355, 2982 – 2991

Dear Hamidou,

we're using the CuAAC mainly for bio-conjugation, but since we also made some organic compounds in our lab as well (using CuAAC) here are my advices:

-) if you're running long reactions and cannot use well degassed, dry organic solvents (try to avoid huge amounts of DMF, MeCN and DMSO - there was a paper about it, screening solvent influence in CuAAC - I'll see if I can find it), use a stabilizing ligand, such as TBTA (Fokin et al.) or THPTA (Finn et al.)

-) depending on your solvents, use the right CuAAC conditions. For us this usually was either

A) the original Sharpless protocol with t-butanol/water and CuSO4 and Na-ascorbate, or

B) using low loadings (approx 1 mol-% per alkyne) of Cu(MeCN)4PF6 in dry, degassed THF, as suggested by the groups of Fokin and Finn; or

C) the CuBr-based protocols of BG Davis.

For the Cu(I) protocols (B, C) we noticed that there quite sensitive towards air, whereas Cu(MeCN)4PF6 is more stable then CuBr.

-) The quality/purity of the Cu(I) species matters! So always try to buy the higher purity grade.

I'll hope that helped!

Cheers,

Lukas

You should have a look at thepublications by P. Pale (universitéof Strasburg, France). His group has developped nice methods for efficient click chemistry.

the easiest way is mixing CuSO4 and sodium ascorbate (0.15 eq: 0.45 eq respectively) in water and adding the resultant solution to the mixture of the alkyne and azide in dichloromethane. Normally this procedure works well in most cases... but in some cases you need to use more complex ligands of Cu. Good luck

First add copper sulphate solublize it in water then add co-solvent. Next add ligand (THPTA or any water soluble ligand) then add azide and then alkyne at the end add sodium ascorbate.

Thanks folks i appreciate your inputs.My work is now published in J. Materials chemistry C.

http://pubs.rsc.org/en/content/articlelanding/2015/tc/c5tc01445j#!divAbstract

Hi, does any one knows what would be the best time for click reaction?For how many minutes ?

2- Moreover, whether we need to optimize protocol for each kind of cells.

3- Third question is whether EDTA can completely stop the reaction? 

There are so many attractive pathways.

From our own group, I can list two of them.

1. We used magnetic nano supported glutathione to anchor Cu and did the chemistry in benign conditions. (see attached).

2. The most simplest protocol would be to use copper sulphate and chitosan, common cheap ingredients you can find anywhere and do the chemistry in water (see attached)

Thankyou so much, I will go through it

Hi Kanwal, I did the coupling reaction in my Ph.D. time as suggested by DInesh sawant and Assali. But now a days lot of report are available. even we can carryout the reactions in water in green approach ..

Article Nickel-Catalyzed Azide-Alkyne Cycloaddition To Access 1,5-Di...

other wise you can go through the following like

one is chemical review... it will help you screen the reaction parrameter

Article Cu-Catalyzed Azide−Alkyne Cycloaddition

the other papers you can refer if you are interested in the click chemistry

Article Autocatalytic Cycles in a Copper-Catalyzed Azide-Alkyne Cycl...

https://pubs.acs.org/doi/abs/10.1021/acscatal.7b02558

Article Practical Considerations, Challenges, and Limitations of Bio...

Article Azide-alkyne cycloaddition reactions in water: Via recyclabl...

Hope it will help you to solve the issue... Best Regrds

DOI:10.1016/j.bmcl.2010.08.104

Thankyou guys, we have already optimised and published that work

Article Capturing the interactome of newly transcribed RNA

Hi,

Thank you everyone. I asked this question in the forum back in 2013 and the thread is still active with more comments, questions and answers. Over 16000 views so far!

Giving the huge interest in this question about alkyne-azide click reaction, I am inviting interested researchers to join me to write a review paper on advances in CuAAC reactions. Feel free to contact me here or email me at [email protected] .

Looking forward to hearing from you.

Cheers,

Hamidou Keita, PhD

Hi,

Why are using DMF in Click reactions.