Frémy's salt

Frémy's salt

Names
IUPAC name Potassium nitrosodisulfonate
Identifiers
CAS Number	14293-70-0
PubChem	3032624
Properties
Chemical formula	K2NO(SO3)2
Molar mass	268.33 g/mol (potassium salt)
Hazards
Main hazards	Harmful (Xn)
R-phrases	R14 R20/21/22
S-phrases	S36
Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa).
Infobox references

Frémy's salt, discovered in 1845 by Edmond Frémy (1814–1894),^[1] is a chemical compound and a strong oxidizing agent. The formal name is disodium nitrosodisulfonate or Na₂NO(SO₃)₂, but the expression "Frémy's salt" refers equally well to potassium nitrosodisulfonate, also known as potassium peroxylamine disulfonate. Frémy’s salt (chemical formula: (K₄[ON(SO₃)₂]₂) is commonly known as potassium nitrodisulfonate radical dianion (NDS) and potassium peroxylamine disulfonate (K₂[NO(SO₃)₂]). NDS, a product of disassociation of Frémy’s salt, is commonly used to examine the mechanism of oxidation and hydroxylation.^[2] Frémy’s salt is a commercially accessible dimer of NDS, it is also a relatively stable source of water-soluble nitroxyl radical that is used as an electronic spin resonance (ESR) standard for g-value determination and radical quantization it is also mainly used in oxidation reactions.^[3][4] Impurities, which may or may not be present in commercial samples, can catalyze the explosive decomposition reaction of this compound in the presence of oxygen.

Applications

The nitroso compound is a persistent radical like TEMPO. It is especially useful in oxidations of anilines and phenols to quinones.^[5][6]

Fremy's salt, being a long-lived free radical, is a useful reagent for electron paramagnetic resonance (EPR) work. The molecule gives an intense EPR spectrum dominated by three lines of equal intensity with a spacing of about 13 G (= 1.3 mT). For more details, see Wertz and Bolton (1972).^[7]

Fremy’s salt is commonly used in oxidation of aromatic amine and phenol structures.^[8][9] It can also be used as a model for peroxyl radicals in studies that examine the antioxidant mechanism of action in a wide range of natural products.^[10][11] Also are used in the synthesis of metabolites which are found to later bind with DNA.^[12] One of its few biological applications involves evaluation of radical scavenging activity and EPR kinetic studies.^[13] It is also a useful tool in understanding the reduction mechanism by ascorbic acid (AscH2).^[12]

Preparation

Fremy's salt is commercially available. It can be prepared by the addition of sodium nitrite, sodium bicarbonate, and sulfur dioxide to disodium hydroxylaminedisulfonate and carbon dioxide followed by one-electron oxidation by electrolysis in a basic solution.^[14] This reaction must be carried at 5˚C or lower with constant stirring.^[15]

Other Reactions:

HNO₂ + 2 HSO₃⁻ → HON(SO₃)₂²⁻ + H₂O

3 HON(SO₃)₂²⁻ + MnO₄⁻ + H⁺ → 3 ON(SO₃)₂²⁻ + MnO₂(s) + 2 H₂O

2 ON(SO₃)₂²⁻ + 4 K⁺ → K₄[ON(SO₃)₂]₂(s)

In the solid phase, potassium nitrodisulfonate has a bright yellowish-brown color, but it is bright violet in aqueous solutions.^[15] EPR measurements can be made to ensure the purity and paramagnetism of the compound.

References

1. See:
   • Frémy, E. (1845) "Sur un nouvelle série d'acides formés d'oxygène, de soufre, d'hydrogène et de d'azote" (On a new series of acids formed from oxygen, sulfur, hydrogen, and nitrogen), Annales de Chimie et de Physique, 3rd series, 15 : 408-488. Frémy's salt appears on p. 447, where it's called "sulfazidate de potasse".
   • Frémy, E. (1845) "Sur un nouvelle série d'acides formés d'oxygène, de soufre, d'hydrogène et de d'azote" (On a new series of acids formed from oxygen, sulfur, hydrogen, and nitrogen), Comptes rendus, 21 : 218-226. This is a condensed version of the article that appeared in Annales de Chimie et de Physique.
   • "Séances académiques," L'Institut, no. 604, 23 July 1845, pp. 265-266.
   • "Séances académiques," L'Institut, no. 619, 12 November 1845, pp. 393. Here a committee of the French Academy of Sciences reviewed Frémy's findings.
   • Edward Divers and Tamemasa Haga (1900) "Identification and constitution of Fremy's sulphazotised salts of potassium," Journal of the Chemical Society, Transactions, 77 : 440-446. Here, correct formulae for Frémy's salts are presented. On p. 445, the salt that Frémy called sulfazidate is identified as ON(SO₃K)₂.
2. Zielonka, Jacek; et al. (2005). "Mechanistic similarities between oxidation of hydroethidine by Fremy’s salt and superoxide: Stopped-flow optical and EPR studies". Free Radical Biology & Medicine 39 (7): 853–863;. doi:10.1016/j.freeradbiomed.2005.05.001. PMID 16140206.
3. Weil, J. A.; Bolton, J. R.; Wertz, J. E. (1994). "Electron paramagnetic resonance: elementary theory and practical applications". Org. Synth.
4. Zielonka, Jacek; et al. (2005). "Mechanistic similarities between oxidation of hydroethidine by Fremy’s salt and superoxide: Stopped-flow optical and EPR studies". Free Radical Biology & Medicine 39 (7): 853–863;. doi:10.1016/j.freeradbiomed.2005.05.001. PMID 16140206.
5. See, for example, Islam, Imadul Islam; Skibo, Edward B.; Dorr, Robert T.; Alberts, David S. (1991). "Structure-activity studies of antitumor agents based on pyrrolo[1,2-a]benzimidazoles: new reductive alkylating DNA cleaving agents". Journal of Medicinal Chemistry 34 (10): 2954–2961. doi:10.1021/jm00114a003. PMID 1920349.
6. Teuber, Hans-J.; Benz, Siegfried (1967). "Reaktionen mit Nitrosodisulfonat, XXXVI. Chinolin-chinone-(5.6) aus 5-Hydroxy-chinolinen". Chem. Ber. 100 (9): 2918–29. doi:10.1002/cber.19671000916. Abstract (in German).
   Teuber, Hans-J. (1972). "Use of dipotassium nitrosodisulfonate (Fremy's salt): 4,5-dimethyl-o-benzoquinone". Org. Synth. 52: 88.; Coll. Vol. 6, p. 480
7. Wertz, J. E.; Bolton, J. R. (1972). Electron Spin Resonance: Elementary Theory and Practical Applications. New York: McGraw-Hill. ISBN 0-07-069454-0. - See page 463 for information on intensity measurements and page 86 for an EPR spectrum of Fremy's salt.
8. Zielonka, Jacek; et al. (2005). "Mechanistic similarities between oxidation of hydroethidine by Fremy’s salt and superoxide: Stopped-flow optical and EPR studies". Free Radical Biology & Medicine 39 (7): 853–863;. doi:10.1016/j.freeradbiomed.2005.05.001. PMID 16140206.
9. W. Xue; et al. (2002). "A metabolic activation mechanism of 7H-dibenzo[C,G]carbozole via 0-quinon. Part 1: synthesis of 7H-dibenzo[C,G]carbozole-3,4-dione and reactions with nucleophiles". Org. Synth. 22: 295–300.
10. Liu, Z.-L.; Han, Z.-X.; Chen, P.; Liu, Y.-C (1990). "Stopped-flow ESR study on the reactivity of vitamin E, vitamin C and its lipophilic derivatives towards Fremy’s salt in miceller systems". Chem. Phys. Lipids 56 (1): 73–80. doi:10.1016/0009-3084(90)90090-E. PMID 1965427.
11. Z.L., Liu, Z.X. Han, P. Chen and Y.C. Liu (1990). "Chem. Phys. Lipid" 56: 73.
12. W. Xue; et al. (2002). "A metabolic activation mechanism of 7H-dibenzo[C,G]carbozole via 0-quinon. Part 1: synthesis of 7H-dibenzo[C,G]carbozole-3,4-dione and reactions with nucleophiles". Polycyclic Aromatic Compounds 22 (3): 295–300. doi:10.1080/10406630213597.
13. Di Giulio; et al. (2000). "EPR study of Fremy’s salt nitroxide reduction by ascorbic acid; influence of bulk pH values". Res. Chem. Intermed 26 (9): 885–896. doi:10.1163/156856700X00372.
14. Wehrli, Pius A.; Pigott, Foster (1972). "Oxidation with the nitrosodisulfonate radical. I. Preparation and use of sodium nitrosodisulfonate: trimethyl-p-benzoquinone". Org. Synth. 52: 83.; Coll. Vol. 6, p. 1010
15. http://chemistris.tripod.com/science/synthesis_of_fremys_salt.pdf

Further reading

• Morey, J. (1988). "Undergraduate Experiments with a Long-Lived Radical (Fremy's salt): Synthesis of 1,4-Benzoquinones by Degradative Oxidation of p-Hydroxybenzyl Alcohols". J. Chem. Ed. 65 (7): 627–629. doi:10.1021/ed065p627.