Azide alkyne Huisgen cycloaddition
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The '''Azide-Alkyne Huisgen Cycloaddition''' is a [[1,3-dipolar cycloaddition]] between an [[azide]] and a terminal or internal [[alkyne]] to give a [[1,2,3-Triazole|1,2,3-triazole]]. [[Rolf Huisgen]] <ref>
{{cite journal
| journal = Proceedings of the Chemical Society of London
| pages = 357
| year= 1961
| title = Cenetary Lecture - 1,3-Dipolar Cycloadditions
| author = Huisgen, R.}}
</ref> was the first to understand the scope of this [[organic reaction]]. American [[chemist]] [[K. Barry Sharpless]] has referred to this [[cycloaddition]] as "the cream of the crop" of [[click chemistry]]. <ref>
{{cite journal | author = H. C. Kolb, M. G. Finn and K. B. Sharpless | title = Click Chemistry: Diverse Chemical Function from a Few Good Reactions | year = 2001 | journal = [[Angewandte Chemie International Edition]] | volume = 40 | issue = 11 | pages = 2004–2021 | doi = 10.1002/1521-3773(20010601)40:11<2004::AID-ANIE2004>3.0.CO;2-5}}
</ref>
[[Image:Huisgen.png|center|Huisgen 1,3-dipolar cycloaddition]]
In the reaction above <ref>''Development and Applications of Click Chemistry'' Gregory C. Patton November 8, '''2004''' [http://www.chemistry.uiuc.edu/research/organic/seminar_extracts/2004_2005/08_Patton_Abstract.pdf http://www.scs.uiuc.edu Online]</ref> azide '''2''' reacts neatly with alkyne '''1''' to afford the triazole '''3''' as a mixture of 1,4-adduct and 1,5-adduct at 98 [[°C]] in 18 hours.
==Variants of the Huisgen reaction==
A notable variant of the Huisgen 1,3-dipolar cycloaddition is the copper(I) catalyzed variant, in which organic azides and terminal alkynes are united to afford 1,4-regioisomers of 1,2,3-triazoles as sole products. The copper(I)-catalyzed variant was first reported for solid phase synthesis of peptidotriazoles by Morten Meldal and co-workers at the Carlsberg Laboratory in Denmark.<ref>>{{cite journal
| journal = Journal of Organic Chemistry
| volume= 67
| pages = 3057–3064
| year= 2002
| url = http://pubs.acs.org/cgi-bin/article.cgi/joceah/2002/67/i09/pdf/jo011148j.pdf
| title = Peptidotriazoles on Solid Phase: [1,2,3]-Triazoles by Regiospecific
Copper(I)-Catalyzed 1,3-Dipolar Cycloadditions of Terminal
Alkynes to Azides
| author = Christian W. Tornøe, Caspar Christensen, and Morten Meldal
| doi = 10.1021/jo011148j}}
</ref>
While the copper(I) catalyzed variant gives rise to a triazole from a terminal alkyne and an azide, formally it is not a 1,3-dipolar cycloaddition and thus should not be termed a Huisgen cycloaddition. This reaction is better termed the Copper(I)-catalyzed Azide-Alkyne Cycloaddition (CuAAC). But it is certainly a click reaction. While the reaction can be performed using commercial sources of copper(I) such as cuprous bromide or iodide, the reaction works much better using a mixture of copper(II) (e.g. copper(II) sulfate) and a reducing agent (e.g. sodium ascorbate) to produce Cu(I) in situ. As Cu(I) is unstable in aqueous solvents, stabilizing ligands are effective for improving the reaction outcome, especially if [[tris-(benzyltriazolylmethyl)amine]] (TBTA) is used. The reaction can be run in a variety of solvents, and mixtures of water and a variety of (partially) miscible organic solvents including alcohols, DMSO, DMF, tBuOH and acetone work well. Owing to the powerful coordinating ability of nitriles towards Cu(I) it is best to avoid acetonitrile as the solvent.
NH-1,2,3-triazoles are also prepared from alkynes in a sequence called the [[Banert cascade]].
The utility of the Cu(I) catalyzed click reaction has also been demonstrated in the [[polymerization]] reaction of a bis-azide and a bis-alkyne with copper(I) and TBTA to a [[Conjugated system|conjugated]] [[fluorene]] based [[polymer]].<ref>{{cite journal
| journal = [[Chemical Communications]]
| volume= 34
| pages = 4333–4335
| year= 2005
| doi = 10.1039/b507776a
| url = http://www.rsc.org/Publishing/Journals/CC/article.asp?doi=b507776a
| title = Click-chemistry as an efficient synthetic tool for the preparation of novel conjugated polymers
| author = D. J. V. C. van Steenis, O. R. P. David, G. P. F. van Strijdonck, J. H. van Maarseveen and J. N. H. Reek}}
</ref> The [[degree of polymerization]] easily exceeds 50. With a stopper molecule such as [[phenyl azide]], well-defined [[phenyl]] [[end-group]]s are obtained.
[[Image:Clickpolymer.png|center|click polymer]]
The copper mediated azide-alkyne cycloaddition is receiving widespread use in material and surface sciences.<ref>{{cite journal
| journal = [[Australian Journal of Chemistry]]
| year= 2007
| volume= 60
| pages = 384–395
| doi = 10.1071/CH0645
| url = http://www.publish.csiro.au/view/journals/dsp_journal_fulltext.cfm?nid=51&f=CH06457| title = The Rise of Azide–Alkyne 1,3-Dipolar 'Click' Cycloaddition and its Application to Polymer Science and Surface Modification
| author = R.A. Evans| doi_brokendate = 2008-06-23}}
</ref> Most variations in coupling polymers with other polymers or small molecules have been explored. Current shortcomings are that the terminal alkyne appears to participate in [[free radical polymerization]]s. This requires protection of the terminal alkyne with a trimethyl silyl [[protecting group]] and subsequent deprotection after the radical reaction are completed. Similarly the use of organic solvents, copper (I) and inert atmospheres to do the cycloaddition with many polymers makes the "click" label inappropriate for such reactions. An aqueous protocol for performing the cycloaddition with free radical polymers is highly desirable.
The CuAAC click reaction also effectively couples [[polystyrene]] and [[bovine serum albumin]] (BSA) <ref>{{cite journal
| journal = Chemical Communications
| volume= 33
| pages = 4172–4174
| year= 2005
| doi = 10.1039/b508428h
| url = http://www.rsc.org/Publishing/Journals/CC/article.asp?doi=b508428h
| title = Preparation of biohybrid amphiphiles via the copper catalysed Huisgen [[3 + 2]] dipolar cycloaddition reaction
| author = A. J. Dirks, S. S. van Berkel, N. S. Hatzakis, J. A. Opsteen, F. L. van Delft, J. J. L. M. Cornelissen, A. E. Rowan, J. C. M. van Hest, F. P. J. T. Rutjes, R. J. M. Nolte}}
</ref>. The result is an [[amphiphilic]] biohybrid. BSA contains a [[thiol]] group at [[cysteine|Cys]]-34 which is functionalized with an [[alkyne]] group. Polystyrene has an [[azido]] [[end-group]] and the coupling takes place in a [[THF]] / [[phosphate]] [[buffer solution]] with [[Copper(II) sulfate]] and [[ascorbic acid]]. In water the biohybrid [[micelle]]s with a [[diameter]] of 30 to 70 [[nanometer]] form aggregates.
==References==
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<references/>
</div>
[[Category:Cycloadditions]]
[[ar:إضافة هويزن 3,1-ثنائية القطبية الحلقية]]
==External links==
* [http://clickchemicals.com] Click Chemicals. A new site all about click chemistry featuring in depth discussion, faq's and links to key papers.
[[Category:Name reactions]]