TEMPO
| TEMPO | |
|---|---|
 |
|
|
Other names
(2,2,6,6-Tetramethyl-piperidin-1-yl)oxyl |
|
| Identifiers | |
| CAS number | 2564-83-2  |
| PubChem | 2724126 |
| ChemSpider | 2006285 |
| ChEBI | CHEBI:32849 |
| ChEMBL | CHEMBL606971 |
| RTECS number | TN8991900 |
| Jmol-3D images | Image 1 |
|
|
|
|
| Properties | |
| Molecular formula | C9H18NO |
| Molar mass | 156.25 g/mol |
| Melting point |
36–38 °C |
| Boiling point |
sublimes under vacuum |
| Hazards | |
| MSDS | External MSDS |
| R-phrases | R34 |
| S-phrases | S26 S36/37/39 S45 |
 (verify) (what is:  / ?)Except where noted otherwise, data are given for materials in their standard state (at 25 °C, 100 kPa) |
|
| Infobox references | |
(2,2,6,6-Tetramethylpiperidin-1-yl)oxyl, or (2,2,6,6-tetramethylpiperidin-1-yl)oxidanyl or TEMPO is a chemical compound with the formula (CH2)3(CMe2)2NO (see diagram). This heterocycle is a red-orange, sublimable solid. As a stable radical, it has applications throughout chemistry and biochemistry.[1] TEMPO was discovered by Lebedev and Kazarnowskii in 1960.[2] It is prepared by oxidation of 2,2,6,6-tetramethylpiperidine. TEMPO is widely used as a radical trap, as a structural probe for biological systems in conjunction with electron spin resonance spectroscopy, as a reagent in organic synthesis, and as a mediator in controlled free radical polymerization.[3] The stability of this radical is attributed to the steric protection provided by the four methyl groups adjacent to the nitroxyl group.[4]
[edit] Application in organic synthesis
TEMPO is employed in organic synthesis as a catalyst for the oxidation of primary alcohols to aldehydes. The actual oxidant is the N-oxoammonium salt. In a catalytic cycle with sodium hypochlorite as the stoichiometric oxidant, hypochlorous acid generates the N-oxoammonium salt from TEMPO.
One typical reaction example is the oxidation of (S)-(-)-2-methyl-1-butanol to (S)-(+)-2-methylbutanal.[5] 4-Methoxyphenethyl alcohol is oxidized to the corresponding carboxylic acid in a system of catalytic TEMPO and sodium hypochlorite and a stoichiometric amount of sodium chlorite.[6] TEMPO oxidations also exhibit chemoselectivity, being inert towards secondary alcohols, but the reagent will convert aldehydes to carboxylic acids.
In cases where secondary oxidizing agents cause side reactions, it is possible to stoichiometrically convert TEMPO to the oxoammonium salt in a separate step. For example, in the oxidation of geraniol to geranial, 4-acetamido-TEMPO is first oxidized to the oxoammonium tetrafluoroborate.[7]
[edit] Industrial applications
TEMPO itself is expensive and therefore TEMPO derivatives are often used such as 4-hydroxy-TEMPO (TEMPOL) or 4-acetamido-TEMPO that have cheaper precursors. Examples of TEMPO use in chemical industry are bisnoralcohol (a steroid) to bisnoraldehyde conversion by Upjohn and retinol to retinal conversion by Novartis. One industrial method employs H5PV2Mo10O40 as co-oxidant, the reduced form of which can be reoxidized by atmospheric oxygen. Polymer-supported TEMPO catalysts are also commercially available.[8]
[edit] References
- ^ Barriga, S (2001). "2,2,6,6-Tetramethylpiperidine-1-oxyl (TEMPO)". Synlett (4): 563. doi:10.1055/s-2001-12332.
- ^ Lebedev, O. L.; Kazarnovskii, S. N. Zhur. Obshch. Khim. 1960, volume 30(5), pages 1631-1635.
- ^ Montanari, F.; Quici, S.; Henry-Riyad, H.; Tidwell, T. T. “2,2,6,6-Tetramethylpiperidin-1-oxyl” Encyclopedia of Reagents for Organic Synthesis; John Wiley & Sons, 2005. DOI: 10.1002/047084289X.rt069.pub2
- ^ Zanocco, A. L.; Canetem., A. Y.; Melendez, M. X. (2000). "A Kinetic Study of the Reaction between 2-p-methoxyphenyl-4-phenyl-2-oxazolin-5-one and 2,2,6,6-Tetramethyl-1-piperidinyl-n-oxide". Bol. Soc. Chil. Quím. 45: 123–129. doi:10.4067/S0366-16442000000100016. http://www.scielo.cl/scielo.php?pid=S0366-16442000000100016&script=sci_arttext.
- ^ P. L. Anelli, F. Montanari, S. Quici, "A General Synthetic Method for the Oxidation of Primary Alcohols to Aldehydes: (S)-(+)-2-Methylbutanal", Org. Synth., http://www.orgsyn.org/orgsyn/orgsyn/prepContent.asp?prep=cv8p0367; Coll. Vol. 8: 367
- ^ Zhao, M. M.; Li, J.;Mano, E.; Song, Z. J.; Tschaen, D. M., "Oxidation of Primary Alcohols to Carboxylic Acids with Sodium Chlorite catalyzed by TEMPO and Bleach: 4-Methoxyphenylacetic Acid", Org. Synth. 81: 195, http://www.orgsyn.org/orgsyn/orgsyn/prepContent.asp?prep=v81p0195
- ^ Bobbitt, J. M.; Merbouh, N., "2,6-Octadienal, 3,7-dimethyl-, (2E)-", Org. Synth. 82: 80, http://www.orgsyn.org/orgsyn/orgsyn/prepContent.asp?prep=v82p0080
- ^ Ciriminna, R.; Pagliaro, M. (2010). "Industrial Oxidations with Organocatalyst TEMPO and Its Derivatives". Organic Process Research & Development 14: 245–251. doi:10.1021/op900059x.
