The Staudinger reaction is a
chemical reaction
A chemical reaction is a process that leads to the IUPAC nomenclature for organic transformations, chemical transformation of one set of chemical substances to another. Classically, chemical reactions encompass changes that only involve the pos ...
of an
organic azide
An organic azide is an organic compound that contains an azide (–) functional group. Because of the hazards associated with their use, few azides are used commercially although they exhibit interesting reactivity for researchers. Low molecular w ...
with a
phosphine
Phosphine (IUPAC name: phosphane) is a colorless, flammable, highly toxic compound with the chemical formula , classed as a pnictogen hydride. Pure phosphine is odorless, but technical grade samples have a highly unpleasant odor like rotting ...
or
phosphite
The general structure of a phosphite ester showing the lone pairs on the P
In organic chemistry, a phosphite ester or organophosphite usually refers to an organophosphorous compound with the formula P(OR)3. They can be considered as esters of a ...
produces an
iminophosphorane An ylide or ylid () is a electric charge, neutral Dipole, dipolar molecule containing a formally negatively charged atom (usually a carbanion) directly attached to a heteroatom with a formal positive charge (usually nitrogen, phosphorus or sulfur), ...
. The reaction was discovered by and named after
Hermann Staudinger
Hermann Staudinger (; 23 March 1881 – 8 September 1965) was a German organic chemist who demonstrated the existence of macromolecules, which he characterized as polymers. For this work he received the 1953 Nobel Prize in Chemistry.
He is also ...
. The reaction follows this stoichiometry:
:R
3P + R'N
3 → R
3P=NR' + N
2
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
Triphenylphosphine phenylimide is the organophosphorus compound with the formula Ph3P=NPh ( Ph = C6H5). It is a white solid that is soluble in organic solvents. The compound is a prototype of a large class of Staudinger reagents, resulting from ...
, is then subjected to
hydrolysis
Hydrolysis (; ) is any chemical reaction in which a molecule of water breaks one or more chemical bonds. The term is used broadly for substitution reaction, substitution, elimination reaction, elimination, and solvation reactions in which water ...
to produce a
phosphine oxide
Phosphine oxides are phosphorus compounds with the formula OPX3. When X = alkyl or aryl, these are organophosphine oxides. Triphenylphosphine oxide is an example. An inorganic phosphine oxide is phosphoryl chloride (POCl3).
Structure and bonding ...
and an
amine
In chemistry, amines (, ) are compounds and functional groups that contain a basic nitrogen atom with a lone pair. Amines are formally derivatives of ammonia (), wherein one or more hydrogen atoms have been replaced by a substituen ...
:
:R
3P=NR' + H
2O → R
3P=O + R'NH
2
The overall conversion is a mild method of
reducing an azide to an amine.
Triphenylphosphine
Triphenylphosphine (IUPAC name: triphenylphosphane) is a common organophosphorus compound with the formula P(C6H5)3 and often abbreviated to P Ph3 or Ph3P. It is widely used in the synthesis of organic and organometallic compounds. PPh3 exists a ...
or
tributylphosphine
Tributylphosphine is the organophosphorus compound with the formula P(CH). Abbreviated or PBu, it is a tertiary phosphine. It is an oily liquid at room temperature, with a nauseating odor. It reacts slowly with atmospheric oxygen, and rapidly with ...
are most commonly used, yielding tributylphosphine oxide or
triphenylphosphine oxide
Triphenylphosphine oxide (often abbreviated TPPO) is the organophosphorus compound with the formula OP(C6H5)3, also written as Ph3PO or PPh3O (Ph = phenyl, C6H5). This colourless crystalline compound is a common but potentially useful waste prod ...
as a side product in addition to the desired amine. An example of a Staudinger reduction is the
organic synthesis
Organic synthesis is a special branch of chemical synthesis and is concerned with the intentional construction of organic compounds. Organic molecules are often more complex than inorganic compounds, and their synthesis has developed into one o ...
of the pinwheel compound 1,3,5-tris(aminomethyl)-2,4,6-triethylbenzene.
Reaction mechanism
The
reaction mechanism
In chemistry, a reaction mechanism is the step by step sequence of elementary reactions by which overall chemical change occurs.
A chemical mechanism is a theoretical conjecture that tries to describe in detail what takes place at each stage of ...
centers around the formation of an
iminophosphorane An ylide or ylid () is a electric charge, neutral Dipole, dipolar molecule containing a formally negatively charged atom (usually a carbanion) directly attached to a heteroatom with a formal positive charge (usually nitrogen, phosphorus or sulfur), ...
through
nucleophilic addition
In organic chemistry, a nucleophilic addition reaction is an addition reaction where a chemical compound with an electrophilic double or triple bond reacts with a nucleophile, such that the double or triple bond is broken. Nucleophilic additions di ...
of the aryl or alkyl
phosphine
Phosphine (IUPAC name: phosphane) is a colorless, flammable, highly toxic compound with the chemical formula , classed as a pnictogen hydride. Pure phosphine is odorless, but technical grade samples have a highly unpleasant odor like rotting ...
at the terminal nitrogen atom of the organic azide and expulsion of
diatomic
Diatomic molecules () are molecules composed of only two atoms, of the same or different chemical elements. If a diatomic molecule consists of two atoms of the same element, such as hydrogen () or oxygen (), then it is said to be homonuclear. Ot ...
nitrogen
Nitrogen is the chemical element with the symbol N and atomic number 7. Nitrogen is a nonmetal and the lightest member of group 15 of the periodic table, often called the pnictogens. It is a common element in the universe, estimated at se ...
. The iminophosphorane is then hydrolyzed in the second step to the amine and a phosphine oxide byproduct.
Staudinger ligation
Of interest in
chemical biology
Chemical biology is a scientific discipline spanning the fields of chemistry and biology. The discipline involves the application of chemical techniques, analysis, and often small molecules produced through synthetic chemistry, to the study and ma ...
is the Staudinger ligation, which has been called one of the most important bioconjugation methods.
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
Staudinger Reaction at organic-chemistry.orgaccessed 060906.
Julia-Staudinger Reaction
Organic redox reactions
Carbohydrate chemistry
Name reactions