Talk:Azide-alkyne Huisgen cycloaddition

Question: Does anybody beside Tim or his labmates call the triazole catalyst "Tim's catalyst"? Is this in the literature, or is it a misuse of Wikipedia? In any case, I agree that this article does a poor job of summarizing the utility and mechanism of this increasingly important reaction, and look forward to having the time to correct it.134.84.138.62 17:57, 12 February 2007 (UTC)


 * you are right, Tim's ligand does not produce hits on google and the article should be renamed to TBTA or (tris-(benzyl-triazolylmethyl)amine) or better still merged to here V8rik 21:32, 12 February 2007 (UTC)

I have certain doubts
, that the Huisgen 1,3 dipolar cycloaddition is only the reaction of alkynes with azides:

“Huisgen Cycloadditions are exergonic fusion processes that unite two unsaturated reactants and provide fast access to an enormous variety of five-membered Heterocycles”. Sharpless, Angew. Chem. Int. Ed., 2002, 41, 2596

In addition, the copper-catalyzed version is NOT a 1,3-dipolar addition, because it is stepwise. The links to copper-catalyzed variants are not helpful. I strongly recommend to reedit the whole article.

In addition I have searched "Huisgen Cycloaddition" in Scifinder, showing up the following publications which have nothing to do with alkynes and azides:

Domingo, Luis R.; Picher, M. Teresa. A DFT study of the Huisgen 1,3-dipolar cycloaddition between hindered thiocarbonyl ylides and tetracyanoethylene. Tetrahedron (2004),  60(23),  5053-5058. CODEN: TETRAB ISSN:0040-4020. CAN 141:123296 AN 2004:404880    CAPLUS

Singal, Kewal Krishan; Giare, Rubina. "Huisgen reaction" of diarylnitrilimines with N-arylmaleimides leading to the synthesis of 1-(2,4-dibromophenyl)-3,5-diaryl-3a,4,6,6a-tetrahydro-1H,5H-pyrrolo[3,4-c]pyrazole-4,6-diones. Indian Journal of Heterocyclic Chemistry (1998),  8(2),  121-124. CODEN: IJCHEI ISSN:0971-1627. CAN 130:237509 AN 1999:68719    CAPLUS

Sustmann, Reiner. Rolf Huisgen's contribution to organic chemistry, emphasizing 1,3-dipolar cycloadditions. Heterocycles (1995),  40(1),  1-18. CODEN: HTCYAM ISSN:0385-5414. CAN 122:132224 AN 1995:332236    CAPLUS

Butler, Richard N.; Coyne, Anthony G.; Cunningham, William J.; Moloney, Eamon M.; Burke, Luke A. Water and the Huisgen cycloaddition reaction: A focus on polar contributions to the transition state in the reactions of dicyano(phthalazinium)methanide with substituted styrenes and benzylidene acetones. Helvetica Chimica Acta (2005),  88(7),  1611-1629. CODEN: HCACAV ISSN:0018-019X. AN 2005:842555   CAPLUS


 * I have reverted your edits because your edit was simply not according to Wiki guidelines (start with definition and article name in bold bold, no references to the discussion page)
 * your Sharpless 2002 definition appears to me the definition reserved for click chemistry.
 * I can also see from your references that the huisgen reaction is used in a liberal way. The 1998 article title has Huisgen reaction between parenthesis, maybe that solves the question
 * concerning the stepwise vs 1,3-dipolar reaction type: I have provided literature that says 1,3-dipolar, if you have literature that says otherwise plase make an edit and broaden the article
 * please do make edits as you seem fit but do consult the Wiki guidelines V8rik 18:03, 2 October 2005 (UTC)

Yes, please answer the question if this article which is now displayed as Huisgen Cycloadditon is right ? Once again: the huisgen reaction is in general the 1,3-dipolar addition. It is not the specific addition of azides to alkines. As long as you write that the huisgen cycloaddition is the specific addition of alkines to azides, the article does not respect Huisgen's work for the development of these cycloadditions in general. That's something to do with respect.

Ok back to the copper-catalyzed (stepwise) cycloaddition: a stepwise reaction is not (per definition) a 1,3-dipolar cycloaddition. The mechanism of the copper-catalyzed reactions can be found here: V. V. Rostovtsev, L. G. Green, V. V. Fokin, K. B. Sharpless, Angew. Chem., 2002, 114, 2708-2711.

In addition, it is not me giving a definition of "Click chemistry" it is your article about Huisgen Cycloaddition. But I strongly recommend not to mix all these things together. Just put all the click chemistry in a seperat article. And reduce the article about Huisgen Cycloadditon to the only correct definition: The Huisgen Cycloadditions are 1,3 Cycloadditions and vice versa !

Ok I have edited by myself. Clearly stating that the alkyne azide cycloadditon is only an example. That's my version: Due to Rolf Huisgen's contribution to....

And I have moved the things about click in the introduction (it is not so bad - just to mention). In my point of view, the azide-alkyne chemistry can always be shortened, and moved to a more specific file. But the mistakes are now corrected (please also correct my bad english).

A detailled look to the Sharpless phrase: "Huisgen Cycloadditions are exergonic fusion processes that unite two unsaturated reactants and provide fast access to an enormous variety of five-membered Heterocycles" Sharpless gives a straigt forward definition of Huisgen Cycloadditions. Nothing more an nothing less. In addition, can you find "Alkyne" and "Azides" in the following article titles:

-"Huisgen reaction" of diarylnitrilimines with N-arylmaleimides leading to the synthesis of 1-(2,4-dibromophenyl)-3,5-diaryl-3a,4,6,6a-tetrahydro-1H,5H-pyrrolo[3,4-c]pyrazole-4,6-diones. -A DFT study of the Huisgen 1,3-dipolar cycloaddition between hindered thiocarbonyl ylides and tetracyanoethylene.

And so on. I can find more examples of Huisgen reactions in Scifinder which are not related to alkynes and azides than the other way round...

Thanks for your reply, a couple of points: V8rik 17:24, 3 October 2005 (UTC)
 * with regard to respect, in my defence: I created the article in the first place because I like the chemistry Huisgen developed.......
 * I invite you to edit the article and state somewhere that research shows the copper variant is stepwise and not concerted. And make sure to add the reference to the reference list.
 * I am unable to do more research now but suppose for now you have a point then I would like to make the suggestion that this article is moved to a new article name for instance alkyne-azide cycloaddion and that you make your points in the 1,3-dipolar cycloaddition article. The articles linking to this article make reference to the alkyne-azide reaction and not 1,3-dipolar additions in general.
 * Your lastest edit still does not comply with Wiki standards, scan 100 random articles and you will see the same format adopted by the entire Wiki community on every page

Ok, the contribution of Huisgen is more than just the Alkine Azid Chemistry (that's now clearly stated by "Example for...". If we both love Huisgen's contribution, then a wider definition might be more interesting. Could you please do the style corrections ? I have not so much time left. And I will check the Copper-catalyzed reactions. Because Sharpless self stated, the mechanism is not fully elucidated...

Here's the latest publication on the mechanism of the copper-catalyzed versions: http://pubs.acs.org/cgi-bin/sample.cgi/jacsat/2005/127/i01/abs/ja0471525.html Quoting: Huisgen Cycloadditon becomes non-concerted... (Question: does a non-concerted Huisgen Cycloaddition exists per definitionem ?). As you can see the term is used for different substrates. But the non-concerted reactions does not fit with "1,3-dipolar"... So I strongly disagree with Sharpless inflationary use of "Huisgen Cycloaddition".

proper bibliography
I am not sure if this is the page to make such remarks BUT I would like to say that I am surprised with the selection of bibliography concerning the 1,3-dipolar azide alkyne cycloaddition ... It seems focused on minor contributions and totally ignoring the pioneers. Any expert on the field would find that this is NOT the appropriate scientific documentation. This is why, scientific articles should be signed.
 * Yes, this is the place to make such remarks. The great thing about Wikipedia is that if you don't like the article the way that it is, you can make whatever changes you feel would improve it. (Keep in mind though, that this is intended to be an encyclopia article, not a scientific publication, so the standards for "appropriate scientific documentation" are going to be lower.) Please feel free to add whichever references you think are appropriate.    Wikipedia articles get better when people like you and their knowledge.  And finally, this article is "signed" in the sense that changes are tracked and each person's contributions can be determined. Edgar181 14:36, 4 December 2005 (UTC)

''Thank you so much for your very prompt answer. As soon as I figure out the system I will certainly try to add some more bibliography. I guess that my question was more general in the sense that though it is great to have a free encyclopedic system, there must be a safety valve prevending it from leading to misconceptions about scientific facts or turning into just free advertising. The Wikipedia concept is so much more important than this ... In several areas covered within Wikipedia, errors might be acceptable and easily fixable. But when one refers to a specific scientific publication and its facts, shouldn't it be certain that he has a full understanding of it? (Think of medical publications for example). This is the reason for suggesting signed articles. I should add that most of the scientists would probably love to contribute to an open access system.''

Cu-catalyzed azide-alkyne cycloaddition (CuAAC)
Dear Sirs,

Fokin and Sharpless do not use "Huisgen Cycloaddition" anymore in the context of Cu-catalyzed alkyne-azides cycloadditions. The reason is clear: the stepwise process for the Cu-catalyzed addition, as proven by different papers written by Fokin (http://pubs.acs.org/cgi-bin/sample.cgi/jacsat/2005/127/i01/abs/ja0471525.html) is not in concordance with a thermally induced, concerted cycloaddition. Huisgen Cycloaddition is another name for "1,3-dipolar cycloaddition" and vice versa. The Cu-catalyzed process is currently named as "Cu(I)-catalyzed azide-alkyne cycloaddition (CuAAC). See: dx.doi.org/10.1021/ja054114s Please recheck all the examples.

Figure Error: "Cp*"
The final figure of the article referring to ruthenium catalyzed variants (mysteriously captioned within the picture as "figure 2...") does not contain Cp* but, rather, its protonated analogue. Indeed, the precatalyst (as shown) is a 16e- species as opposed to the correct 18e- Cp*RuL2X. This figures should likely be replaced with one that fixes this inaccuracy and is an original work (as opposed to a likely screencap). Jgwest91 (talk) 04:33, 31 July 2013 (UTC)