Frémy's salt explained

Frémy's salt is a chemical compound with the formula (K₄[ON(SO₃)₂]₂), sometimes written as (K₂[NO(SO₃)₂]). It is a bright yellowish-brown solid, but its aqueous solutions are bright violet. The related sodium salt, disodium nitrosodisulfonate (NDS, Na₂ON(SO₃)₂, CAS 29554-37-8) is also referred to as Frémy's salt.

Regardless of the cations, the salts are distinctive because aqueous solutions contain the radical [ON(SO₃)₂]²⁻.

Applications

Frémy's salt, being a long-lived free radical, is used as a standard in electron paramagnetic resonance (EPR) spectroscopy, e.g. for quantitation of radicals. Its intense EPR spectrum is dominated by three lines of equal intensity with a spacing of about 13 G (1.3 mT).^{[1] [2] [3]}

The inorganic aminoxyl group is a persistent radical, akin to TEMPO.

It has been used in some oxidation reactions, such as for oxidation of some anilines and phenols^{[4] [5] [6]} allowing polymerization and cross-linking of peptides and peptide-based hydrogels.^{[7] [8]}

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.^[9]

Preparation

Frémy's salt is prepared from hydroxylaminedisulfonic acid. Oxidation of the conjugate base gives the purple dianion:

HON(SO₃H)₂ → [HON(SO₃)₂]²⁻ + 2 H⁺

2 [HON(SO₃)₂]²⁻ + PbO₂ → 2 [ON(SO₃)₂]²⁻ + PbO + H₂O

The synthesis can be performed by combining nitrite and bisulfite to give the hydroxylaminedisulfonate. Oxidation is typically conducted at low-temperature, either chemically or by electrolysis.^{[10] [11]}

Other reactions:

HNO₂ + 2 → + H₂O

3 + + H⁺ → 3 + MnO₂ + 2 H₂O

2 + 4 K⁺ → K₄[ON(SO₃)₂]₂

History

Frémy's salt was discovered in 1845 by Edmond Frémy (1814–1894).^[12] Its use in organic synthesis was popularized by Hans Teuber, such that an oxidation using this salt is called the Teuber reaction.^{[13] [14]}

Further reading

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

Notes and References

1. Book: Wertz JE, Bolton JR . Electron Spin Resonance: Elementary Theory and Practical Applications . 1972 . McGraw-Hill . New York . 978-0-07-069454-5 . See page 463 for information on intensity measurements and page 86 for an EPR spectrum of Frémy's salt.
2. Colacicchi S, Carnicelli V, Gualtieri G, Di Giulio A . EPR study of Frémy's salt nitroxide reduction by ascorbic acid; influence of bulk pH values . Res. Chem. Intermed. . 26 . 9 . 885–896 . 2000 . 10.1163/156856700X00372. 98775951 .
3. Zielonka J, Zhao H, Xu Y, Kalyanaraman B . Mechanistic similarities between oxidation of hydroethidine by Frémy's salt and superoxide: stopped-flow optical and EPR studies . Free Radical Biology & Medicine . 39 . 7 . 853–863 . October 2005 . 10.1016/j.freeradbiomed.2005.05.001 . 16140206 .
4. Zimmer H, Lankin DC, Horgan SW . Oxidations with potassium nitrosodisulfonate (Frémy's radical). Teuber reaction. . Chemical Reviews . 1971 . 71 . 2 . 229–246 . 10.1021/cr60270a005 .
5. Islam I, Skibo EB, Dorr RT, Alberts DS . 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 . October 1991 . 1920349 . 10.1021/jm00114a003 .
6. Xue W, Warshawsky D, Rance M, Jayasimhulu K . A metabolic activation mechanism of 7H-dibenzo[''c'',''g'']carbozole via o-quinone. Part 1: synthesis of 7H-dibenzo[''c'',''g'']carbozole-3,4-dione and reactions with nucleophiles . Polycyclic Aromatic Compounds . 22 . 3–4 . 295–300 . 2002. 10.1080/10406630290026957 . 95507636 .
7. Wilchek M, Miron T . Mussel-inspired new approach for polymerization and cross-linking of peptides and proteins containing tyrosines by Frémy's salt oxidation . Bioconjugate Chemistry . 26 . 3 . 502–510 . March 2015 . 25692389 . 10.1021/bc5006152 .
8. Fichman G, Schneider JP . Utilizing Frémy's Salt to Increase the Mechanical Rigidity of Supramolecular Peptide-Based Gel Networks . English . Frontiers in Bioengineering and Biotechnology . 8 . 594258 . 2021 . 33469530 . 7813677 . 10.3389/fbioe.2020.594258 . free .
9. Liu ZL, Han ZX, Chen P, Liu YC . Stopped-flow ESR study on the reactivity of vitamin E, vitamin C and its lipophilic derivatives towards Frémy's salt in micellar systems . Chemistry and Physics of Lipids . 56 . 1 . 73–80 . November 1990 . 1965427 . 10.1016/0009-3084(90)90090-E .
10. Wehrli PA, Pigott F . Oxidation with the nitrosodisulfonate radical. I. Preparation and use of sodium nitrosodisulfonate: trimethyl-p-benzoquinone . Organic Syntheses . 10.15227/orgsyn.052.0083 . 83 . 52 . 1972 .
11. Web site: Synthesis and Characterization of Potassium Nitrosodisulfonate, Frémy's Salt . tripod.com .
12. 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 Frémy's sulphazotised salts of potassium," Journal of the Chemical Society, Transactions, 77 : 440-446. doi:10.1039/CT9007700440 Here, correct formulae for Frémy's salts are presented. On p. 445, the salt that Frémy called sulfazidate is identified as ON(SO₃K)₂.
13. Teuber HJ, Benz S . . Reaktionen mit Nitrosodisulfonat, XXXVI. Chinolin-chinone-(5.6) aus 5-Hydroxy-chinolinen . 100 . 2918–2929 . 9 . 1967 . 10.1002/cber.19671000916 . German .
14. Teuber HJ . Use of Dipotassium Nitrosodisulfonate (Frémy's Salt): 4,5-Dimethyl-o-Benzoquinone . 10.15227/orgsyn.052.0088. 52 . 88 . 1972. Org. Synth..