Hydrogen Peroxide-Iron(II) Sulfate1

H2O2-FeSO4.7H2O
(H2O2)

[7722-84-1]  · H2O2  · Hydrogen Peroxide-Iron(II) Sulfate  · (MW 34.02) (FeSO4.7H2O)

[7782-63-0]  · FeO4S  · Hydrogen Peroxide-Iron(II) Sulfate  · (MW 278.06)

(reagent for generation of organic radicals which undergo dimerization, oxidative insertion, dehydrogenation and hydroxylation; oxo-iron species formed in situ lead to oxo-transfer reactions)

Alternate Name: Fenton reagent.

Physical Data: FeSO4.7H2O; d 1.89 g cm-3; forms tetrahydrate at 56.6 °C and monohydrate at 65.0 °C; loses the last H2O at about 300 °C.

Solubility: FeSO4.7H2O: sol H2O, practically insol in alcohols.

Form Supplied in: FeSO4.7H2O: blue-green, monoclinic, orderless crystals or granules.

Handling, Storage, and Precautions: FeSO4.7H2O: oxidizes in moist air to form a basic iron(III) sulfate. Store in closed container. Wear rubber gloves when handling. See Hydrogen Peroxide and Iron(II) Sulfate.

General.1,2

The Fenton reagent, a combination of hydrogen peroxide and iron(II) sulfate, has been known since the 1890s.2 The mild oxidizing ability of H2O2 is considerably enhanced by FeII ion. The hydroxyl radical generated by the decomposition of H2O2 in the presence of FeII can produce organic radicals (eq 1) which undergo a variety of organic transformations, such as dimerization,3,4 oxidative insertion,5 hydroxylation,6 and dehydrogenation.7 Since the attack of HO&bdot; on aliphatic compounds is not highly selective, isomeric products are obtained in these reactions except in cases where symmetric reactants containing only equivalent hydrogen atoms are used.

FeII and FeIII ions in solution can be further oxidized by HO&bdot; to form FeIV=O or FeV=O species (eq 2).1c,8 The high oxidation state of FeIV=O (or FeV=O) leads to some interesting oxo-transfer reactions.9,10

Synthetic Applications.

2,5-Dimethyl-2,5-hexanediol is produced in 40-46% isolated yield by oxidative dimerization of t-butyl alcohol using Fenton reagent with 1 equiv of FeSO4.7H2O (eq 3).3 Analogous oxidative coupling has been accomplished with certain saturated lower, straight- and branched-chain aliphatic carboxylic acids, nitriles, amides, amines, alcohols, and ketones.4

Hydrocarbon derivatives can be converted to the corresponding carboxylic acids in low yields by Fenton reagents and carbon monoxide.5

Dehydrogenation of 2-amino-3,4-dihydroquinoxaline to 2-aminoquinoxaline is effected smoothly by H2O2 in the presence of trace amounts of FeII ions (eq 4).6 The reaction does not proceed without using the iron(II) catalyst. The procedure appears to be general and has been successfully applied to the synthesis of a number of alkyl-, halo-, and hydroxy-substituted 2-aminoquinoxalines.6

The Fenton reagent has also been employed to hydroxylate aromatic rings (eq 5).7 However, the yields are usually low, primarily due to the formation of biaryl products. The efficiency of this reaction is highly dependent on the concentrations of FeII and FeIII ions7 and can be improved by using phase-transfer catalysts.11

90% Stereoselectivity and 71% yield have been achieved in the synthesis of cis-1,3-cyclohexanediol by the reaction of cyclohexanol with Fenton reagent. A FeIV=O intermediate was proposed to account for the results.9

Oxidation of cholesterol with Fenton reagent in acetic acid gave dihydroxylation products as shown in eq 6.10 Evidently 5a,6a-epoxycholestan-3b-ol was formed via an oxo-transfer process in the early stages, and the subsequent epoxide opening by solvents provided trans-diol derivatives.


1. (a) Walling, C. ACR 1975, 8, 125. (b) Edwards, J. O.; Curci, R. Catal. Met. Complexes 1992, 9, 97. (c) Sheldon, R. A.; Kochi, J. K. Metal-Catalyzed Oxidations of Organic Compounds; Academic: New York, 1981; pp 33-38, 171-175. (d) Sosnovsky, G.; Rawlinson, D. J. In Organic Peroxides; Swern, D., Ed.; Wiley: New York, 1970; Vol. 2, pp 269-336.
2. Fenton, H. J. H. JCS 1894, 65, 899.
3. Jenner, E. L. OS 1960, 40, 90.
4. (a) Coffman, D. D.; Jenner, E. L.; Lipscomb, R. D. JACS 1958, 80, 2864. (b) Coffman, D. D.; Jenner, E. L. JACS 1958, 80, 2872. (c) Coffman, D. D.; Cripps, H. N. JACS 1958, 80, 2877, 2880.
5. Coffman, D. D.; Cramer, R.; Mochel, W. E. JACS 1958, 80, 2882.
6. Pfister, K., 3rd.; Sullivan, A. P., Jr.; Weijlard, J.; Tishler, M. JACS 1951, 73, 4955.
7. (a) Smith, J. R. L.; Norman, R. O. C. JCS 1963, 2897. (b) Tezuka, T.; Narita, N.; Ando, W.; Oae, S. JACS 1981, 103, 3045.
8. For the developments on oxo-iron chemistry, see: (a) Collman, J. P.; Zhang, X.; Lee, V. J.; Uffelman, E. S.; Brauman, J. I. Science 1993, 261, 1404 and references cited therein. (b) Groves, J. T.; McClusky, G. A. JACS 1976, 98, 859. (c) Groves, J. T.; Nemo, T. E.; Myers, R. S. JACS 1979, 101, 1032.
9. (a) Groves, J. T.; van der Puy, M. JACS 1974, 96, 5274. (b) Groves, J. T.; Swanson, W. W. TL 1975, 1953.
10. Kimura, M.; Tohma, M.; Tomita, T. CPB 1972, 20, 2185.
11. March, J. Advanced Organic Chemistry, 4th ed.; Wiley: New York, 1992; p 700.

Yaping Hong

Sepracor, Marlborough, MA, USA



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