Staudinger reaction
{{Short description|Chemical reaction}}
{{About||the reaction between imines and ketenes to form β-lactams|Staudinger synthesis}}
{{Reactionbox
| Name = Staudinger reaction
| Type = Organic redox reaction
| NamedAfter = Hermann Staudinger
| Section3 = {{Reactionbox Identifiers
| OrganicChemistryNamed = staudinger-reaction
| RSC_ontology_id = 0000066
}}
}}
The Staudinger reaction is a chemical reaction of an organic azide with a phosphine or phosphite produces an iminophosphorane.{{citation | last = Gololobov | first = Y. G. | year = 1981 | journal = Tetrahedron | volume = 37 | issue = 3 | pages = 437–472 | doi = 10.1016/S0040-4020(01)92417-2 | title = Sixty Years of Staudinger Reaction}}{{citation | last1= Gololobov | first1 = Y. G. | last2 = Kasukhin | first2 = L. F.| year = 1992 | journal = Tetrahedron | volume = 48 | issue = 8 | pages = 1353–1406 | doi = 10.1016/S0040-4020(01)92229-X | title = Recent Advances in the Staudinger Reaction}} The reaction was discovered by and named after Hermann Staudinger.{{citation |author1=Staudinger, H. |author2=Meyer, J. | year = 1919 | journal = Helv. Chim. Acta | volume = 2 | issue = 1 | pages = 635 | doi = 10.1002/hlca.19190020164 | title = Über neue organische Phosphorverbindungen III. Phosphinmethylenderivate und Phosphinimine|url=https://zenodo.org/record/1426801 }} The reaction follows this stoichiometry:
:R3P + R'N3 → R3P=NR' + N2
Staudinger reduction
The Staudinger reduction is conducted in two steps. First phosphine imine-forming reaction is conducted involving treatment of the azide with the phosphine. The intermediate, e.g. triphenylphosphine phenylimide, is then subjected to hydrolysis to produce a phosphine oxide and an amine:
:R3P=NR' + H2O → R3P=O + R'NH2
The overall conversion is a mild method of reducing an azide to an amine. Triphenylphosphine or tributylphosphine are most commonly used, yielding tributylphosphine oxide or triphenylphosphine oxide as a side product in addition to the desired amine. An example of a Staudinger reduction is the organic synthesis of the pinwheel compound 1,3,5-tris(aminomethyl)-2,4,6-triethylbenzene.{{citation |title = Preparation of 1,3,5-Tris(aminomethyl)-2,4,6-triethylbenzene from Two Versatile 1,3,5-Tri(halosubstituted) 2,4,6-Triethylbenzene Derivatives |author1=Karl J. Wallace |author2=Robert Hanes |author3=Eric Anslyn |author4=Jeroni Morey |author5=Kathleen V. Kilway |author6=Jay Siegeld | doi = 10.1055/s-2005-869963 |year = 2005 |journal = Synthesis |volume = 2005 |issue = 12 |pages = 2080}}
=Reaction mechanism=
The reaction mechanism centers around the formation of an iminophosphorane through nucleophilic addition of the aryl or alkyl phosphine at the terminal nitrogen atom of the organic azide and expulsion of diatomic nitrogen. The iminophosphorane is then hydrolyzed in the second step to the amine and a phosphine oxide byproduct.
Staudinger ligation
Of interest in chemical biology is the Staudinger ligation, which has been called one of the most important bioconjugation methods.{{cite journal |doi=10.1021/acs.chemrev.9b00665|title=The Staudinger Ligation |year=2020 |last1=Bednarek |first1=Christin |last2=Wehl |first2=Ilona |last3=Jung |first3=Nicole |last4=Schepers |first4=Ute |last5=Bräse |first5=Stefan |journal=Chemical Reviews |volume=120 |issue=10 |pages=4301–4354 |pmid=32356973 |s2cid=218480283 }} Two versions of the Staudinger ligation have been developed. Both begin with the classic iminophosphorane reaction.
In classical Staudinger ligation, the organophosphorus compound becomes incorporated into the peptide. Typically, appended to the organophosphorus component are reporter groups such as fluorophores. In traceless Staudinger ligation, the organophosphorus group dissociates giving a phosphorus-free bioconjugate.
References
{{Reflist}}
External links
- [https://www.organic-chemistry.org/namedreactions/staudinger-reaction.shtm Staudinger Reaction at organic-chemistry.org] accessed 060906.
- [http://www.chem-station.com/en/?p=2131 Julia-Staudinger Reaction]
Category:Organic redox reactions