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Staudinger reaction

The Staudinger reaction is a chemical reaction of an organic azide with a phosphineorphosphite produces an iminophosphorane.^[1][2] The reaction was discovered by and named after Hermann Staudinger.^[3] The reaction follows this stoichiometry:

R₃P + R'N₃ → R₃P=NR' + N₂

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. Triphenylphosphineortributylphosphine 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.^[4]

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.

Of interest in chemical biology is the Staudinger ligation, which has been called one of the most important bioconjugation methods.^[5] 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.

1. Staudinger Reaction at organic-chemistry.org accessed 060906.
2. Julia-Staudinger Reaction