Literature on 'click' chemistry claims that the reaction conditions required are mild and easy to achieve; in several articles it looks as though the CuAAC reaction is carried out without even an inert atmosphere.
However, organic azides carry potential risks, and some are supplied with warnings to store at -20 C and handle under an inert atmosphere. How rigorous should this be (glove box, or simple schlenk line)? Does the reaction itself have to be kept at -20 C?
Dear Jean, l have workef with aliphatic azided such as 2-azido ethanol, 1,3-diazido prop-2-ol and 3-azido propionic acid and they were stable in rt. When there are many axide groups in a compound, it should be handeled with care. Click reaction works well in rt and only in a few cases l have seen being heated.
I have carried out small amount of sodium azide/reactions even at room temperature, nothing untoward things happened. You are right we need to take of lots of precautions...I think the link will give insight ...
https://web.stanford.edu/dept/EHS/prod/researchlab/lab/safety_sheets/08-203.pdf
Dear Jean, it always depends on your azide component, but the most azides are pretty stable at 23°C. Infact azides are perfect protective groups for amines against various oxidative conditions. I work with geminal triazides (http://onlinelibrary.wiley.com/doi/10.1002/anie.201402433/suppinfo) which were perfectly stable at 23°C. Explosive properties of azides are always connected to theier C/N ratio. One azide moiety in a huge molecule will not cause any explosive properties, oen azide moiety in a small molecule can lead to explsovie properties. Nevertheless the chemical sorrounding of the particular azide is as well of importance. If you handle small amounts of your compound and use appropiate saftey equipment (Bust Shield, PSE) you should be fine. The click reaction is quite robust and fast, it will not make a difference if you do it under inert atmosphere or not, infact you may need less reducing agent like sodiumascorbate if you do it under inert atmosphere. Furthermore, you can always choose metal-free variants with cyclooctyne or acetylene dialkylcarboxylates, if your alkyne componente does not matter.
Totally agree with @Philipp Klahn.....
The total number of nitrogen atoms in your organic azide should not exceed that of carbon. Use the following equation to help evaluate if your azide is stable enough to work with, with N equal to the number of atoms:
(NC + NO) / NN ≥ 3
- n-nonyl azide (C/N=3) is the smallest organic azide that can be isolated and stored in its pure form (up to 20 grams).
- Azides with a C/N ratio greater than one and no more than 3 can be synthesized and isolated but should be stored below room temperature at no more than 1M concentration and at a maximum of 5 grams of material.2
- Organic azides with C/N
Thanks for the replies everyone, the azide I was considering has a C+O/N ratio of 1.8 which is why I am slightly wary of it. It sounds as though the reaction is feasible, and Philipp's comment about not needing an inert atmosphere is definitely useful! At any rate it sounds as though it could be OK to do this on a very small scale...
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