(2,2,6,6-Tetramethylpiperidin-1-yl)oxyl or (2,2,6,6-tetramethylpiperidin-1-yl)oxidanyl, commonly known as TEMPO, is a chemical compound with the formula (CH2)3(CMe2)2NO. This heterocyclic compound is a red-orange, sublimable solid. As a stable aminoxyl radical, it has applications in chemistry and biochemistry.[1] TEMPO is used as a radical marker, 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 radical polymerization.[2]
Structure of TEMPO. The N–O distance is 1.284 Å.[4].
The structure has been confirmed by X-ray crystallography. The reactive radical is well shielded by the four methyl groups.
The stability of this radical can be attributed to the delocalization of the radical to form a two-center three-electron N–O bond. The stability is reminiscent of the stability of nitric oxide and nitrogen dioxide. Additional stability is attributed to the steric protection provided by the four methyl groups adjacent to the aminoxyl group. These methyl groups serve as inert substituents, whereas any CH center adjacent to the aminoxyl would be subject to abstraction by the aminoxyl.[5]
One typical reaction example is the oxidation of (S)-(−)-2-methyl-1-butanol to (S)-(+)-2-methylbutanal:[7] 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.[8] TEMPO oxidations also exhibit chemoselectivity, being inert towards secondary alcohols, but the reagent will convert aldehydes to carboxylic acids.
The oxidation of TEMPO can be highly selective. It has been proven that secondary alcohols are more likely to be oxidized by TEMPO under an acidic environment. The reason is when in this condition, secondary alcohols are more easily to provide an H- ion.[9]
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.[10]
TEMPO can also be employed in nitroxide-mediated radical polymerization (NMP), a controlled free radical polymerization technique that allows better control over the final molecular weight distribution. The TEMPO free radical can be added to the end of a growing polymer chain, creating a "dormant" chain that stops polymerizing. However, the linkage between the polymer chain and TEMPO is weak, and can be broken upon heating, which then allows the polymerization to continue. Thus, the chemist can control the extent of polymerization and also synthesize narrowly distributed polymer chains.
Industrial applications and analogues
TEMPO is sufficiently inexpensive for use on a laboratory scale.[11] There is also industrial-scale manufacturer which can provide TEMPO at a reasonable price in large quantity.[12] Structurally related analogues do exist, which are largely based on 4-hydroxy-TEMPO (TEMPOL). This is produced from acetone and ammonia, via triacetone amine, making it much less expensive. Other alternatives include polymer-supported TEMPO catalysts, which are economic due to their recyclability.[13]
^Montanari, F.; Quici, S.; Henry-Riyad, H.; Tidwell, T. T. (2005). "2,2,6,6-Tetramethylpiperidin-1-oxyl". Encyclopedia of Reagents for Organic Synthesis. John Wiley & Sons. doi:10.1002/047084289X.rt069.pub2. ISBN0471936235.
^Lebedev, O. L.; Kazarnovskii, S. N. (1960). "[Catalytic oxidation of aliphatic amines with hydrogen peroxide]". Zhur. Obshch. Khim. 30 (5): 1631–1635. CAN 55:7792.
^Yonekuta Yasunori, Oyaizu Kenichi, Nishide Hiroyuki (2007). "Structural Implication of Oxoammonium Cations for Reversible Organic One-electron Redox Reaction to Nitroxide Radicals". Chem. Lett. 36 (7): 866–867. doi:10.1246/cl.2007.866.{{cite journal}}: CS1 maint: multiple names: authors list (link)
^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". Boletín de la Sociedad Chilena de Química. 45 (1): 123–129. doi:10.4067/S0366-16442000000100016.
^Galli, C. (2009). "Nitroxyl radicals". Chemistry of Hydroxylamines, Oximes and Hydroxamic Acids. Vol. 2. John Wiley & Sons. pp. 705–750. ISBN978-0-470-51261-6. LCCN 2008046989.
^Anelli, P. L.; Montanari, F.; Quici, S. (1990). "A General Synthetic Method for the Oxidation of Primary Alcohols to Aldehydes: (S)-(+)-2-Methylbutanal". Organic Syntheses. 69: 212.{{cite journal}}: CS1 maint: multiple names: authors list (link); Collective Volume, vol. 8, p. 367
^Zhao, M. M.; Li, J.; Mano, E.; Song, Z. J.; Tschaen, D. M. (2005). "Oxidation of Primary Alcohols to Carboxylic Acids with Sodium Chlorite catalyzed by TEMPO and Bleach: 4-Methoxyphenylacetic Acid". Organic Syntheses. 81: 195.{{cite journal}}: CS1 maint: multiple names: authors list (link)
^"Detailed study about TEMPO oxidation". LISKON-CHEM.
^Ciriminna, R.; Pagliaro, M. (2010). "Industrial Oxidations with Organocatalyst TEMPO and Its Derivatives". Organic Process Research & Development. 14 (1): 245–251. doi:10.1021/op900059x.
External links
TEMPO
February 06, 2023
tempo, tetramethylpiperidin, oxyl, tetramethylpiperidin, oxidanyl, commonly, known, chemical, compound, with, formula, cme2, this, heterocyclic, compound, orange, sublimable, solid, stable, aminoxyl, radical, applications, chemistry, biochemistry, used, radica. 2 2 6 6 Tetramethylpiperidin 1 yl oxyl or 2 2 6 6 tetramethylpiperidin 1 yl oxidanyl commonly known as TEMPO is a chemical compound with the formula CH2 3 CMe2 2NO This heterocyclic compound is a red orange sublimable solid As a stable aminoxyl radical it has applications in chemistry and biochemistry 1 TEMPO is used as a radical marker 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 radical polymerization 2 TEMPO NamesPreferred IUPAC name 2 2 6 6 Tetramethylpiperidin 1 yl oxylOther names 2 2 6 6 Tetramethylpiperidin 1 yl oxidanylIdentifiersCAS Number 2564 83 2 Y3D model JSmol Interactive imageChEBI CHEBI 32849 YChEMBL ChEMBL606971 YChemSpider 2006285 YECHA InfoCard 100 018 081EC Number 219 888 8PubChem CID 2724126RTECS number TN8991900UNII VQN7359ICQ YCompTox Dashboard EPA DTXSID2073300InChI InChI 1S C9H18NO c1 8 2 6 5 7 9 3 4 10 8 11 h5 7H2 1 4H3 YKey QYTDEUPAUMOIOP UHFFFAOYSA N YInChI 1 C9H18NO c1 8 2 6 5 7 9 3 4 10 8 11 h5 7H2 1 4H3Key QYTDEUPAUMOIOP UHFFFAOYAPSMILES CC1 CCCC N1 O C C CPropertiesChemical formula C9H18NOMolar mass 156 25 g molMelting point 36 to 38 C 97 to 100 F 309 to 311 K Boiling point sublimes under vacuumHazardsGHS labelling PictogramsSignal word DangerHazard statements H314Precautionary statements P260 P264 P273 P280 P301 P330 P331 P303 P361 P353 P304 P340 P305 P351 P338 P310 P321 P363 P405 P501Safety data sheet SDS External MSDSExcept where otherwise noted data are given for materials in their standard state at 25 C 77 F 100 kPa Y verify what is Y N Infobox references Contents 1 Preparation 2 Structure and bonding 3 Application in organic synthesis 4 Industrial applications and analogues 5 See also 6 References 7 External linksPreparation EditTEMPO was discovered by Lebedev and Kazarnowskii in 1960 3 It is prepared by oxidation of 2 2 6 6 tetramethylpiperidine Structure and bonding Edit Structure of TEMPO The N O distance is 1 284 A 4 The structure has been confirmed by X ray crystallography The reactive radical is well shielded by the four methyl groups The stability of this radical can be attributed to the delocalization of the radical to form a two center three electron N O bond The stability is reminiscent of the stability of nitric oxide and nitrogen dioxide Additional stability is attributed to the steric protection provided by the four methyl groups adjacent to the aminoxyl group These methyl groups serve as inert substituents whereas any CH center adjacent to the aminoxyl would be subject to abstraction by the aminoxyl 5 Regardless of the reasons for the stability of the radical the O H bond in the hydrogenated derivative the hydroxylamine 1 hydroxy 2 2 6 6 tetramethylpiperidine TEMPO H is weak With an O H bond dissociation energy of about 70 kcal mol 290 kJ mol this bond is about 30 weaker than a typical O H bond 6 Application in organic synthesis EditSee also Oxoammonium catalyzed oxidation 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 7 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 8 TEMPO oxidations also exhibit chemoselectivity being inert towards secondary alcohols but the reagent will convert aldehydes to carboxylic acids The oxidation of TEMPO can be highly selective It has been proven that secondary alcohols are more likely to be oxidized by TEMPO under an acidic environment The reason is when in this condition secondary alcohols are more easily to provide an H ion 9 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 10 TEMPO can also be employed in nitroxide mediated radical polymerization NMP a controlled free radical polymerization technique that allows better control over the final molecular weight distribution The TEMPO free radical can be added to the end of a growing polymer chain creating a dormant chain that stops polymerizing However the linkage between the polymer chain and TEMPO is weak and can be broken upon heating which then allows the polymerization to continue Thus the chemist can control the extent of polymerization and also synthesize narrowly distributed polymer chains Industrial applications and analogues EditTEMPO is sufficiently inexpensive for use on a laboratory scale 11 There is also industrial scale manufacturer which can provide TEMPO at a reasonable price in large quantity 12 Structurally related analogues do exist which are largely based on 4 hydroxy TEMPO TEMPOL This is produced from acetone and ammonia via triacetone amine making it much less expensive Other alternatives include polymer supported TEMPO catalysts which are economic due to their recyclability 13 Industrial scale examples of TEMPO like compounds include hindered amine light stabilizers and polymerisation inhibitors See also Edit1 Hydroxy 2 2 6 6 tetramethylpiperidine the reduced derivative of TEMPO TEMPOL N HydroxyphthalimideReferences Edit Barriga S 2001 2 2 6 6 Tetramethylpiperidine 1 oxyl TEMPO PDF Synlett 2001 4 563 doi 10 1055 s 2001 12332 Montanari F Quici S Henry Riyad H Tidwell T T 2005 2 2 6 6 Tetramethylpiperidin 1 oxyl Encyclopedia of Reagents for Organic Synthesis John Wiley amp Sons doi 10 1002 047084289X rt069 pub2 ISBN 0471936235 Lebedev O L Kazarnovskii S N 1960 Catalytic oxidation of aliphatic amines with hydrogen peroxide Zhur Obshch Khim 30 5 1631 1635 CAN 55 7792 Yonekuta Yasunori Oyaizu Kenichi Nishide Hiroyuki 2007 Structural Implication of Oxoammonium Cations for Reversible Organic One electron Redox Reaction to Nitroxide Radicals Chem Lett 36 7 866 867 doi 10 1246 cl 2007 866 a href Template Cite journal html title Template Cite journal cite journal a CS1 maint multiple names authors list link 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 Boletin de la Sociedad Chilena de Quimica 45 1 123 129 doi 10 4067 S0366 16442000000100016 Galli C 2009 Nitroxyl radicals Chemistry of Hydroxylamines Oximes and Hydroxamic Acids Vol 2 John Wiley amp Sons pp 705 750 ISBN 978 0 470 51261 6 LCCN 2008046989 Anelli P L Montanari F Quici S 1990 A General Synthetic Method for the Oxidation of Primary Alcohols to Aldehydes S 2 Methylbutanal Organic Syntheses 69 212 a href Template Cite journal html title Template Cite journal cite journal a CS1 maint multiple names authors list link Collective Volume vol 8 p 367 Zhao M M Li J Mano E Song Z J Tschaen D M 2005 Oxidation of Primary Alcohols to Carboxylic Acids with Sodium Chlorite catalyzed by TEMPO and Bleach 4 Methoxyphenylacetic Acid Organic Syntheses 81 195 a href Template Cite journal html title Template Cite journal cite journal a CS1 maint multiple names authors list link Detailed study about TEMPO oxidation LISKON CHEM Bobbitt J M Merbouh N 2005 2 6 Octadienal 3 7 dimethyl 2E Organic Syntheses 82 80 a href Template Cite journal html title Template Cite journal cite journal a CS1 maint multiple names authors list link TEMPO Sigma Aldrich TEMPO LISKON industrial scale Ciriminna R Pagliaro M 2010 Industrial Oxidations with Organocatalyst TEMPO and Its Derivatives Organic Process Research amp Development 14 1 245 251 doi 10 1021 op900059x External links EditTEMPO Retrieved from https en wikipedia org w index php title TEMPO amp oldid 1123523682, wikipedia, wiki, book, books, library,
