3637-10-3

Basic information

• Product Name: 4-HYDROXY-TEMPO
• Synonyms: 1,4-Dihydroxy-2,2,6,6-tetramethylpiperidine;2,2,6,6-tetramethyl-piperidine-1,4-diol;4-Piperidinol, 2,2,6,6-tetramethyl-, 1-oxide;HYDROXY-TEMPO;2,2,6,6-TETRAMETHYL-4-HYDROXY-1-PIPERIDINYLOXY;2,2,6,6-TETRAMETHYL-4-PIPERIDINOL 1-OXYL;4-HYDROXY-TEMPO;4-HYDROXY-2,2,6,6-TETRAMETHYLPIPERIDINYLOXY FREE RADICAL
• CAS NO: 3637-10-3
• Molecular Formula: C₉H₁₉NO₂
• Molecular Weight: 172.24
• EINECS: 218-761-4
• Mol File: 3637-10-3.mol
• Article Data: 25

Chemical Properties

• Melting Point: 69-71 °C(lit.)
• Boiling Point: 260.2 °C at 760 mmHg
• Flash Point: 111 °C
• Appearance: /
• Density: 1.029 g/cm³
• Storage Temp.: 2-8°C
• PKA: 14.02±0.70(Predicted)
• CAS DataBase Reference: 4-HYDROXY-TEMPO(CAS DataBase Reference)
• NIST Chemistry Reference: 4-HYDROXY-TEMPO(3637-10-3)
• EPA Substance Registry System: 4-HYDROXY-TEMPO(3637-10-3)

Safety Data

• Hazard Codes: Xn
• Statements: 22-36/37/38
• Safety Statements: 26-36
• WGK Germany: 1
• RTECS: TN8991000
• Hazardous Substances Data: 3637-10-3(Hazardous Substances Data)

Usage

Description

4-HYDROXY-TEMPO, also known as 2,2,6,6-Tetramethylpiperidine-1,4-diol, is a compound that serves as a free radical scavenger and has demonstrated radioprotective properties both in vitro and in vivo. Its unique structure allows it to effectively neutralize free radicals, making it a valuable compound in various applications.

Uses

Used in Chemical Synthesis:
4-HYDROXY-TEMPO is used as a reagent in the stereoselective preparation of tetrasubstituted triarylated olefins. This application takes advantage of its free radical scavenging properties to facilitate the Pd-catalyzed sequential oxidative Heck arylation of alkenes with arylboronic acids, using nitroxides as oxidants. This process is particularly useful in the synthesis of complex organic molecules with high selectivity and yield.
Used in Antioxidant Applications:
As a free radical scavenger, 4-HYDROXY-TEMPO is employed in various antioxidant applications to protect cells and tissues from oxidative damage. Its ability to neutralize free radicals makes it a promising candidate for use in the development of antioxidants that can help prevent or mitigate the effects of oxidative stress-related conditions.
Used in Radioprotection:
4-HYDROXY-TEMPO has shown potential as an in vitro and in vivo radioprotector, making it a valuable compound for applications involving radiation exposure. It can be used to protect cells and tissues from the damaging effects of radiation, which is particularly relevant in the fields of medical radiation therapy, nuclear medicine, and radiation protection for workers in related industries.
Used in Material Science:
The free radical scavenging properties of 4-HYDROXY-TEMPO can also be utilized in material science applications, such as the stabilization of polymers and other materials against oxidative degradation. By incorporating 4-HYDROXY-TEMPO into the material's structure, it can help improve the material's resistance to oxidative damage, leading to enhanced durability and longevity.

Synthetic route

4-hydroxy-2,2,6,6-tetramethylpiperidine (2403-88-5) → tempol (3637-10-3)

Conditions	Yield
With 3,3-dimethyldioxirane In acetone at 0℃; for 2h;	99%
With sodium tungstate; ethylenediaminetetraacetic acid; dihydrogen peroxide In water
With DMd In acetone
Multi-step reaction with 2 steps 1: sodium tungstate monohydrate; dihydrogen peroxide / methanol; water / 50 h / 20 °C / Inert atmosphere 2: phenylhydrazine / chloroform-d1 View Scheme

tempol (2226-96-2) → tempol (3637-10-3)

Conditions	Yield
With formaldehyd; dihydrogen peroxide; copper(l) chloride at 30℃; for 16h;	87%
With ethylenediaminetetraacetic acid; β-nicotinamide adenine dinucleotide reduced; hypoxanthine; catalase; xanthine oxidase pH=7.4; Kinetics; aq. phosphate buffer;

TEMPOL (45985-24-8, 2226-96-2) → tempol (3637-10-3)

Conditions	Yield
With sodium dithionite In water; acetone for 0.5h; Ambient temperature;	80%
With sodium L-ascorbate pH=7;
With air; sodium ascorbate Mechanism; spin loss rate, further nitroxide free radicals, var.:illumination, atmosphere:N2, ferric chloride;

TEMPOL (45985-24-8, 2226-96-2) + para-xylene (106-42-3) → tempol (3637-10-3) + 1-N-[(4-methylbenzyl)oxy]-4-hydroxy-2,2,6,6-tetramethylpiperidine

Conditions	Yield
for 48h; Heating;	A n/a B 59%
Heating;

TEMPOL (45985-24-8, 2226-96-2) + m-xylene (108-38-3) → tempol (3637-10-3) + 1-N-[(3-methylbenzyl)oxy]-4-hydroxy-2,2,6,6-tetramethylpiperidine

Conditions	Yield
at 135 - 136℃; for 69h;	A n/a B 51%
Heating;

TEMPOL (45985-24-8, 2226-96-2) + toluene (108-88-3) → tempol (3637-10-3) + benzyl-4-hydroxy-2,2,6,6-tetramethylpiperidinyl-1-oxyl (26460-91-3)

Conditions	Yield
at 143℃; for 53h;	A n/a B 30%
Heating;

TEMPOL (45985-24-8, 2226-96-2) + trans-3,4-dideuteriohex-3-ene (446055-01-2) → C15H27(2)H2NO2 + C15H27(2)H2NO2 + tempol (3637-10-3)

Conditions	Yield
at 64℃; for 72h; Title compound not separated from byproducts;	A 20% B n/a C n/a

TEMPOL (45985-24-8, 2226-96-2) + cis-1,2-dideuterio-cyclooctene (79839-64-8) → C17H29(2)H2NO2 + C17H29(2)H2NO2 + tempol (3637-10-3)

Conditions	Yield
at 88℃; for 48h; Title compound not separated from byproducts;	A 18% B n/a C n/a

TEMPOL (45985-24-8, 2226-96-2) + cyclohexene-d21,2 (20696-89-3) → tempol (3637-10-3) + 1-N-[(1,2-dideuteriocyclohex-2-en-1-yl)oxy]-4-hydroxy-2,2,6,6-tetramethylpiperidine + 1-N-[(2,3-dideuteriocyclohex-2-en-1-yl)oxy]-4-hydroxy-2,2,6,6-tetramethylpiperidine

Conditions	Yield
at 70℃; for 72h; Title compound not separated from byproducts;	A n/a B 15.5% C n/a

TEMPOL (45985-24-8, 2226-96-2) + ethylbenzene (100-41-4) → tempol (3637-10-3) + 4-hydroxy-1-((1'-phenylethyl)oxy)-2,2,6,6-tetramethylpiperidine (132416-36-5)

Conditions	Yield
at 133℃;	A n/a B 6%
at 133℃; for 26h;	A 12.57 g B 6%

3,10-dimethyl-5,10-dihydro-1H-benzo[g]pteridine-2,4-dione (90828-05-0) + TEMPOL (45985-24-8, 2226-96-2) → tempol (3637-10-3) + 3,10-dimethylisoalloxazine (4074-59-3)

Conditions	Yield
In water at 25℃; Rate constant; pH=6.65;

TEMPOL (45985-24-8, 2226-96-2) + 3,9-Dimethyl-9,10-dihydro-1H-1,3,7,9,10-pentaaza-anthracene-2,4-dione → tempol (3637-10-3) + 3,10-dimethyl-8-azaisoalloxazine (86927-00-6)

Conditions	Yield
In water at 25℃; Rate constant; pH=6.65;

TEMPOL (45985-24-8, 2226-96-2) + C4H10NS (86101-37-3) → tempol (3637-10-3) + 3-Methylsulfanyl-propylideneamine

Conditions	Yield
Rate constant;

TEMPOL (45985-24-8, 2226-96-2) + C4H10NS*H(1+) (86101-38-4) → tempol (3637-10-3) + 3-Methylsulfanyl-propylideneamine

Conditions	Yield
With oxonium Rate constant;

TEMPOL (45985-24-8, 2226-96-2) + 1-15N-1-hydroxy-2,2,4,4,5,5-pentamethyl-3-imidazoline 3-oxide → tempol (3637-10-3) + C8H15N(15)NO2

Conditions	Yield
In chloroform at 19.9℃; Equilibrium constant; Thermodynamic data; ΔG;

TEMPOL (45985-24-8, 2226-96-2) → tempol (3637-10-3) + C18H35N2O4 + C18H34N2O4

Conditions	Yield
In water Kinetics; Irradiation; various doses of γ-irradiation; various concentration 2,2,6,6-tetramethyl-4-piperidinol-1-oxyl; deaerated or with N2O saturated solutions;

TEMPOL (45985-24-8, 2226-96-2) → tempol (3637-10-3) + 3,10-dimethylisoalloxazine (4074-59-3)

Conditions	Yield
reduced 3,10-dimethylisoalloxazine In water at 25℃; pH=6.65;

TEMPOL (45985-24-8, 2226-96-2) + diphenyl hydrazine (122-66-7) → tempol (3637-10-3) + Azobenzene (1227476-15-4)

Conditions	Yield
In hexane at 20℃; Rate constant;

4-hydroxy-1-((1'-phenylethyl)oxy)-2,2,6,6-tetramethylpiperidine (132416-36-5) → styrene (100-42-5) + tempol (3637-10-3)

Conditions	Yield
In acetonitrile at 140℃; Kinetics;

2,2,6,6-Tetramethyl-4-piperidone (826-36-8) → tempol (3637-10-3)

Conditions	Yield
Multi-step reaction with 2 steps 1: NaBH4 2: 99 percent / dimethyldioxirane / acetone / 2 h / 0 °C View Scheme
Multi-step reaction with 3 steps 1: sodium tetrahydroborate / ethanol / 6 h / 20 °C 2: sodium tungstate monohydrate; dihydrogen peroxide / methanol; water / 50 h / 20 °C / Inert atmosphere 3: phenylhydrazine / chloroform-d1 View Scheme

tempol (3637-10-3) + poly(methacrylic acid) (79-41-4) → C13H23NO3

Conditions	Yield
With titanium(IV) isobutoxide In cyclohexane at 110℃; for 10h;	90%

tempol (3637-10-3) + phenylmalonic acid (2613-89-0) → C27H42N2O6

Conditions	Yield
Stage #1: tempol; phenylmalonic acid With dmap In dichloromethane for 0.5h; Inert atmosphere; Stage #2: With dicyclohexyl-carbodiimide In dichloromethane at -10 - 20℃; for 6h; Inert atmosphere;	88.6%

tempol (3637-10-3) → TEMPOL (45985-24-8, 2226-96-2)

Conditions	Yield
With hydrogenchloride; sodium nitrite In water	88%
With air; copper diacetate In methanol for 1h; without Cu-ion; oxidation of similar N-hydroxy-amines;	90 % Spectr.
With dihydrogen peroxide; ethylene diamine tetraacetic acid tetrasodium salt; potassium tungstate In water at 25℃; Rate constant;
With methyl(oxo)diperoxorhenium(VII); dihydrogen peroxide In water; acetonitrile at 24.85℃; Kinetics; Oxidation;

tempol (3637-10-3) + 3-phenylglutaric acid (4165-96-2) → C29H46N2O6

Conditions	Yield
Stage #1: tempol; 3-phenylglutaric acid With dmap In dichloromethane for 0.5h; Inert atmosphere; Stage #2: With dicyclohexyl-carbodiimide In dichloromethane at -5 - 20℃; for 8h; Inert atmosphere;	86.3%

tempol (3637-10-3) + 2-cyclohexylmalonic acid (4354-67-0) → C27H48N2O6

Conditions	Yield
Stage #1: tempol; 2-cyclohexylmalonic acid With dmap In dichloromethane for 0.5h; Inert atmosphere; Stage #2: With dicyclohexyl-carbodiimide In dichloromethane at -10 - 20℃; for 6h; Inert atmosphere;	83.6%

tempol (3637-10-3) + 3-cyclohexylglutaric acid (71300-20-4) → C29H52N2O6

Conditions	Yield
Stage #1: tempol; 3-cyclohexylglutaric acid With dmap In dichloromethane for 0.5h; Inert atmosphere; Stage #2: With dicyclohexyl-carbodiimide In dichloromethane at -5 - 20℃; for 8h; Inert atmosphere;	78.6%

tempol (3637-10-3) → 4-Acetoxy-2,2,6,6-tetramethylpiperidin-1-yl Acetate

Conditions	Yield
With acetic anhydride; sodium hydrogencarbonate; triethylamine In dichloromethane	76%
	40%

tempol (3637-10-3) + dilauryl peroxide (105-74-8) → 1-undecanoxy-2,2,6,6-tetramethyl piperidine-4-one (863636-51-5)

Conditions	Yield
Stage #1: tempol; dilauryl peroxide In chlorobenzene at 70℃; for 9h; Stage #2: With sodium hypochlorite; 4-acetyl-1-oxy-2,2,6,6-tetramethyl piperidine In water; chlorobenzene at 0℃; for 6h;	50%

tempol (3637-10-3) + 4-hydroxy-2,2,6,6-tetramethyl-1-oxopiperidinium triflate → TEMPOL (45985-24-8, 2226-96-2)

Conditions	Yield
In acetonitrile at 24.85℃; Kinetics; comproportionation;

Upstream product

• 2403-88-5 4-hydroxy-2,2,6,6-tetramethylpiperidine 
• 90828-05-0 3,10-dimethyl-5,10-dihydro-1H-benzo[g]pteridine-2,4-dione 
• 45985-24-8 TEMPOL 
• 106-42-3 para-xylene 
• 100-41-4 ethylbenzene 
• 108-38-3 m-xylene 
• 132416-36-5 4-hydroxy-1-((1'-phenylethyl)oxy)-2,2,6,6-tetramethylpiperidine 
• 2226-96-2 tempol 
• 826-36-8 2,2,6,6-Tetramethyl-4-piperidone 
• 79839-64-8 cis-1,2-dideuterio-cyclooctene 
• 20696-89-3 cyclohexene-d₂^1,2 
• 446055-01-2 trans-3,4-dideuteriohex-3-ene 
• 108-88-3 toluene 
• 122-66-7 diphenyl hydrazine 

Downstream Products

• 45985-24-8 TEMPOL 
• 143-07-7 lauric acid 
• 863984-45-6 4-hydroxy-1-undecanoxy-2,2,6,6-tetramethylpiperidine 
• 863636-51-5 1-undecanoxy-2,2,6,6-tetramethyl piperidine-4-one 
• 1234306-16-1 1,3-bis(2,6-diisopropylphenyl)-2-(4-hydroxy-2,2,6,6-tetramethyl-piperidin-1-yl)isourea 
• 1234306-19-4 2-(4-hydroxy-2,2,6,6-tetramethyl-piperidin-1-yl)-1,3-di-p-tolyl-isourea 
• 1234306-11-6 1,3-dicyclohexyl-2-(4-hydroxy-2,2,6,6-tetramethyl-piperidin-1-yl)-isourea 

Relevant articles and documents

Nitroxide destruction and flavin-photosensitized damage in inner mitochondrial membranes

Nitroxide free radicals lost their paramagnetic absorption spectrum when they were illuminated with visible light in aged but not freshly isolated inner mitochondrial membranes (SMP's).The action spectrum of spin loss rates coincided with a flavin absorption spectrum.Spin loss consisted of one-electron reduction and "destruction", the latter being defined as spin loss that cannot be reversed by ferricyanide oxidation.By placing SMP's in gas permeable tubing and illuminating alternately under nitrogen and air, it was possible to discriminate qualitatively betweenspin reduction and destruction.Aerobic spin loss consisted entirely of destruction.When aged SMP's were centrifuged, spin loss was observed in supernatants but not pellets.Flavin fluorescence was observed in the supernatants, suggesting that free flavins catalyzed spin loss.However, addition of exogenous flavins to fresh SMP's did not cause spin loss; hence some other factor was required to cause nitroxide destruction.This factor accumulates during either aerobic or anaerobic aging of SMP's and may be present in mitochondria.Supernatants of aged SMP's, when added to freshly isolated SMP's, induced rapid nitroxide destruction, slightly accelerated photodamage to succinate oxidase, and considerably increased photo-induced lipid peroxidation.

Scavenging free radicals to preserve enhancement and extend relaxation times in NMR using dynamic nuclear polarization

Vitamin C for longer lifetimes: N-oxide radicals that are widely used for dynamic nuclear polarization can be reduced by scavengers such as sodium ascorbate (vitamin C) during the dissolution process, thus diminishing losses of polarization during the transfer and extending transverse and longitudinal relaxation times in NMR spectroscopy (see picture).

Antioxidant and antiradical activities of resorcinarene tetranitroxides

Resorcinarene oxazines bearing four TEMPO fragments at the wide rim of the macrocycle were prepared through the aminomethylation of resorcinarene octols with 4-amino-TEMPO and formaldehyde. Tetra-TEMPO resorcinarenes are efficient scavengers of 1,1-diphen

Synthesis and reduction kinetics of sterically shielded pyrrolidine nitroxides

A series of sterically shielded pyrrolidine nitroxides were synthesized, and their reduction by ascorbate (vitamin C) indicate that nitroxide 3, a tetraethyl derivative of 3-carboxy-PROXYL, is reduced at the slowest rate among known nitroxides, i.e., at a 60-fold slower rate than that for 3-carboxy-PROXYL.