The
Staudinger reaction or
Staudinger reduction is a
chemical reactionA chemical reaction is a process that leads to the transformation of one set of chemical substances to another. Chemical reactions can be either spontaneous, requiring no input of energy, or non-spontaneous, typically following the input of some type of energy, such as heat, light or electricity...
in which the combination of an
azideAzide is the anion with the formula N3−. It is the conjugate base of hydrazoic acid. N3− is a linear anion that is isoelectronic with CO2 and N2O. Per valence bond theory, azide can be described by several resonance structures, an important one being N−=N+=N−...
with a
phosphinePhosphine is the compound with the chemical formula PH3. It is a colorless, flammable, toxic gas. Pure phosphine is odourless, but technical grade samples have a highly unpleasant odor like garlic or rotting fish, due to the presence of substituted phosphine and diphosphine...
or
phosphiteA phosphite is a salt of phosphorous acid. The phosphite ion is a polyatomic ion with a phosphorus central atom where phosphorus has an oxidation state of +3...
produces an iminophosphorane intermediate. Combined with the
hydrolysisHydrolysis is a chemical reaction during which molecules of water are split into hydrogen cations and hydroxide anions in the process of a chemical mechanism. It is the type of reaction that is used to break down certain polymers, especially those made by condensation polymerization...
of the aza-ylide to produce a
phosphine oxidePhosphine oxides are either inorganic phosphorus compounds such as phosphoryl trichloride or organophosphorus compounds with the formula OPR3, where R = alkyl or aryl...
and an
amineAmines are organic compounds and functional groups that contain a basic nitrogen atom with a lone pair. Amines are derivatives of ammonia, wherein one or more hydrogen atoms have been replaced by a substituent such as an alkyl or aryl group. Important amines include amino acids, biogenic amines,...
, this reaction is a mild method of reducing an azide to an amine.
TriphenylphosphineTriphenylphosphine is a common organophosphorus compound with the formula P3 - often abbreviated to PPh3 or Ph3P. It is widely used in the synthesis of organic and organometallic compounds. PPh3 exists as relatively air stable, colorless crystals at room temperature...
is commonly used as the
reducing agentA reducing agent is the element or compound in a reduction-oxidation reaction that donates an electron to another species; however, since the reducer loses an electron we say it is "oxidized"...
, yielding
triphenylphosphine oxideTriphenylphosphine oxide is the chemical compound with the formula OP3. Often chemists abbreviate the formula by writing Ph3PO or PPh3O . This white crystalline compound is a common side product in reactions involving triphenylphosphine...
as the side product in addition to the amine.
The reaction was invented by and named after
Hermann Staudinger- External links :* Staudinger's * Staudinger's Nobel Lecture *....
.
An example of a Staudinger reduction is the
organic synthesisOrganic synthesis is a special branch of chemical synthesis and is concerned with the construction of organic compounds via organic reactions. Organic molecules can often contain a higher level of complexity compared to purely inorganic compounds, so the synthesis of organic compounds has...
of this pinwheel compound:
Reaction mechanism
The
reaction mechanismIn chemistry, a reaction mechanism is the step by step sequence of elementary reactions by which overall chemical change occurs.Although only the net chemical change is directly observable for most chemical reactions, experiments can often be designed that suggest the possible sequence of steps in...
centers around the formation of an iminophosphorane through
nucleophilic additionIn organic chemistry, a nucleophilic addition reaction is an addition reaction where in a chemical compound a π bond is removed by the creation of two new covalent bonds by the addition of a nucleophile....
of the
phosphinePhosphine is the compound with the chemical formula PH3. It is a colorless, flammable, toxic gas. Pure phosphine is odourless, but technical grade samples have a highly unpleasant odor like garlic or rotting fish, due to the presence of substituted phosphine and diphosphine...
at the terminal nitrogen atom of the azide and expulsion of nitrogen. This intermediate is then hydrolyzed in the second step to the
amineAmines are organic compounds and functional groups that contain a basic nitrogen atom with a lone pair. Amines are derivatives of ammonia, wherein one or more hydrogen atoms have been replaced by a substituent such as an alkyl or aryl group. Important amines include amino acids, biogenic amines,...
and
triphenylphosphine oxideTriphenylphosphine oxide is the chemical compound with the formula OP3. Often chemists abbreviate the formula by writing Ph3PO or PPh3O . This white crystalline compound is a common side product in reactions involving triphenylphosphine...
Staudinger ligation
Developed by Saxon and
BertozziCarolyn Ruth Bertozzi is an American chemist. She is the T.Z. and Irmgard Chu Distinguished Professor of Chemistry and Professor of Molecular and Cell Biology at the University of California, Berkeley; Professor of Molecular and Cellular Pharmacology at the University of California, San...
in 2000, the
Staudinger ligation is a modification of the classical Staudinger reaction in which an electrophilic
trapIn chemistry, a chemical trap is a chemical compound that is used to detect a certain molecule when* The concentration of this molecule is very small and below detection limit...
(usually a methyl ester) is placed on the triaryl phosphine. In aqueous media, the aza-ylide intermediate rearranges, to produce an
amideIn chemistry, an amide is an organic compound that contains the functional group consisting of a carbonyl group linked to a nitrogen atom . The term refers both to a class of compounds and a functional group within those compounds. The term amide also refers to deprotonated form of ammonia or an...
linkage and the phosphine oxide, and is so named the Staudinger ligation because it ligates two molecules together, whereas in the classical Staudinger reaction, the two products are not covalently linked after hydrolysis. The general schematic for the Staudinger ligation is shown below
Applications
The Staudinger ligation has seen many applications in the field of
chemical biologyChemical biology is a scientific discipline spanning the fields of chemistry and biology that involves the application of chemical techniques and tools, often compounds produced through synthetic chemistry, to the study and manipulation of biological systems. This is a subtle difference from...
.
In one application this reaction is used to create a bond between a
nucleosideNucleosides are glycosylamines consisting of a nucleobase bound to a ribose or deoxyribose sugar via a beta-glycosidic linkage...
and a fluorescent marker:
External links
- Staudinger Reaction at organic-chemistry.org accessed 060906.