TEMPO
Encyclopedia
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. TEMPO was discovered by Lebedev and Kazarnowskii in 1960. 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
. The stability of this radical is attributed to the steric protection provided by the four methyl groups adjacent to the nitroxyl group.
as a catalyst for the oxidation of primary alcohol
s to aldehyde
s. 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. 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
. TEMPO oxidations also exhibit chemoselectivity
, being inert towards a 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.
(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.
Chemical compound
A chemical compound is a pure chemical substance consisting of two or more different chemical elements that can be separated into simpler substances by chemical reactions. Chemical compounds have a unique and defined chemical structure; they consist of a fixed ratio of atoms that are held together...
with the formula (CH2)3(CMe2)2NO (see diagram). This heterocycle
Heterocyclic compound
A heterocyclic compound is a cyclic compound which has atoms of at least two different elements as members of its ring. The counterparts of heterocyclic compounds are homocyclic compounds, the rings of which are made of a single element....
is a red-orange, sublimable solid. As a stable radical, it has applications throughout chemistry and biochemistry. TEMPO was discovered by Lebedev and Kazarnowskii in 1960. It is prepared by oxidation of 2,2,6,6-tetramethylpiperidine
2,2,6,6-Tetramethylpiperidine
2,2,6,6-Tetramethylpiperidine or TMP or HTMP is a clear liquid with an amine odor. This amine is used in chemistry as a hindered base because it can dissolve in organic solvents unlike ordinary bases such as potassium hydroxide....
. 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
Organic synthesis
Organic 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...
, and as a mediator in controlled free radical polymerization
Radical polymerization
Free radical polymerization is a method of polymerization by which a polymer forms by the successive addition of free radical building blocks. Free radicals can be formed via a number of different mechanisms usually involving separate initiator molecules...
. The stability of this radical is attributed to the steric protection provided by the four methyl groups adjacent to the nitroxyl group.
Application in organic synthesis
TEMPO is employed in organic synthesisOrganic synthesis
Organic 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...
as a catalyst for the oxidation of primary alcohol
Alcohol
In chemistry, an alcohol is an organic compound in which the hydroxy functional group is bound to a carbon atom. In particular, this carbon center should be saturated, having single bonds to three other atoms....
s to aldehyde
Aldehyde
An aldehyde is an organic compound containing a formyl group. This functional group, with the structure R-CHO, consists of a carbonyl center bonded to hydrogen and an R group....
s. The actual oxidant is the N-oxoammonium salt
N-oxoammonium salt
N-Oxoammonium salts in organic chemistry are a class of organic compounds sharing a functional group with the general structure R1R2N+=O X- where X- is the counterion. The N-oxoammonium salt from TEMPO is used for oxidation of alcohols to carbonyl groups....
. In a catalytic cycle
Catalytic cycle
A catalytic cycle in chemistry is a term for a multistep reaction mechanism that involves a catalyst . The catalytic cycle is the main method for describing the role of catalysts in biochemistry, organometallic chemistry, materials science, etc. Often such cycles show the conversion of a...
with sodium hypochlorite as the stoichiometric oxidant, hypochlorous acid
Hypochlorous acid
Hypochlorous acid is a weak acid with the chemical formula HClO. It forms when chlorine dissolves in water. It cannot be isolated in pure form due to rapid equilibration with its precursor...
generates the N-oxoammonium salt from TEMPO.
One typical reaction example is the oxidation of (S)-(-)-2-methyl-1-butanol to (S)-(+)-2-methylbutanal. 4-Methoxyphenethyl alcohol is oxidized to the corresponding carboxylic acid
Carboxylic acid
Carboxylic acids are organic acids characterized by the presence of at least one carboxyl group. The general formula of a carboxylic acid is R-COOH, where R is some monovalent functional group...
in a system of catalytic TEMPO and sodium hypochlorite and a stoichiometric amount of sodium chlorite
Sodium chlorite
Sodium chlorite is a chemical compound used in the manufacture of paper.-Use:The main application of sodium chlorite is the generation of chlorine dioxide for bleaching and stripping of textiles, pulp, and paper. It is also used for disinfection of a few municipal water treatment plants after...
. TEMPO oxidations also exhibit chemoselectivity
Chemoselectivity
Chemical reactions are defined usually in small contexts , such generalizations are a matter of utility. The preferential outcome of one instance of a generalized reaction over a set of other plausible reactions, is defined as chemoselectivity...
, being inert towards a 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
Geraniol
Geraniol is a monoterpenoid and an alcohol. It is the primary part of rose oil, palmarosa oil, and citronella oil . It also occurs in small quantities in geranium, lemon, and many other essential oils. It appears as a clear to pale-yellow oil that is insoluble in water, but soluble in most common...
to geranial, 4-acetamido-TEMPO is first oxidized to the oxoammonium tetrafluoroborate.
Industrial applications
TEMPO itself is expensive and therefore TEMPO derivatives are often used such as 4-hydroxy-TEMPO4-Hydroxy-TEMPO
4-Hydroxy-TEMPO or TEMPOL, formally 4-hydroxy-2,2,6,6-tetramethylpiperidin-1-oxyl, is a heterocyclic compound. Like the related TEMPO, it is used as a catalyst, chemical oxidant.-External links:...
(TEMPOL) or 4-acetamido-TEMPO that have cheaper precursors. Examples of TEMPO use in chemical industry are bisnoralcohol (a steroid
Steroid
A steroid is a type of organic compound that contains a characteristic arrangement of four cycloalkane rings that are joined to each other. Examples of steroids include the dietary fat cholesterol, the sex hormones estradiol and testosterone, and the anti-inflammatory drug dexamethasone.The core...
) to bisnoraldehyde conversion by Upjohn
Upjohn
The Upjohn Company was a pharmaceutical manufacturing firm founded in 1886 in Kalamazoo, Michigan by Dr. William E. Upjohn, an 1875 graduate of the University of Michigan medical school. The company was originally formed to make friable pills, which were specifically designed to be easily digested...
and retinol
Retinol
Retinol is one of the animal forms of vitamin A. It is a diterpenoid and an alcohol. It is convertible to other forms of vitamin A, and the retinyl ester derivative of the alcohol serves as the storage form of the vitamin in animals....
to retinal
Retinal
Retinal, also called retinaldehyde or vitamin A aldehyde, is one of the many forms of vitamin A . Retinal is a polyene chromophore, and bound to proteins called opsins, is the chemical basis of animal vision...
conversion by Novartis
Novartis
Novartis International AG is a multinational pharmaceutical company based in Basel, Switzerland, ranking number three in sales among the world-wide industry...
. 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.