Sodium Hypochlorite1

NaOCl

[7681-52-9]  · ClNaO  · Sodium Hypochlorite  · (MW 74.44)

(versatile and easily handled oxidizing agent;1 can oxidize alcohols,2 aldehydes,3 electron deficient alkenes,4 amines,5 and transition metal catalysts;6 reagent for N-chlorination,7 oxidative coupling,8 and degradation reactions9)

Physical Data: most commonly used in aqueous solution; NaOCl.5H2O: mp 18 °C.

Solubility: pentahydrate: 293 g L-1 in H2O (0 °C).

Form Supplied in: commercially available as aqueous solutions with 5.25-12.5% available oxidant (w/v) (0.74-1.75 M). Concentration is expressed in % available chlorine, since half of the chlorine in bleach is present as NaCl. The pH of commercial bleach is typically 11-12.5, and it may be adjusted and buffered.6a

Analysis of Reagent Purity: active oxidant may be assayed by iodometric10 or potentiometric11 titration.

Preparative Methods: solutions may be generated in situ by passing Chlorine gas through aq Sodium Hydroxide solution,12 or electrochemically.13

Purification: commercial solutions are generally used without purification.

Handling, Storage, and Precautions: higher concentration sodium hypochlorite (12.5%), sometimes referred to as swimming pool chlorine, tends to decrease in concentration by 20% per month upon storage and therefore should be titrated prior to use.1b The concentration of oxidant in household bleach (5.25%) tends to remain constant upon prolonged storage; titration is generally not necessary with brand names (e.g. Clorox®). Solid NaOCl is explosive as the pentahydrate or the anhydride, and therefore it is very rarely employed in those forms. Aqueous solutions are very stable. Bleach is a household item, and it is quite easy and safe to handle. Still, it is a strong oxidant, and precaution should be taken to avoid prolonged skin exposure or inhalation.14 May react violently with NH3.

Composition of Aqueous Solution as a Function of pH.

The equilibrium composition of aqueous solutions of NaOCl is pH-dependent (eqs 1 and 2), and so pH control can be a critical consideration in many oxidation and chlorination reactions. Under strongly alkaline conditions (pH > 12), OCl- is the predominant form of positive chlorine. Because hypochlorite ion is insoluble in organic solvents, phase transfer catalysts are needed at this pH to effect oxidation reactions in biphasic media.15 In general, tetraalkylammonium salts have been the phase-transfer catalysts of choice for such applications. Below pH 11, the equilibrium amount of HOCl becomes significant,6a and this form of positive chlorine is soluble in polar organic solvents such as CH2Cl2. No phase-transfer catalyst is necessary to effect oxidation of substrates or catalysts dissolved in the organic phase of biphasic reactions in the pH range 10-11.6a Below pH 10, molecular chlorine becomes a significant component of aqueous bleach solutions, and the reactivity of these solutions can be attributed to that of Cl2.1b

Oxidation of Alcohols.

Oxidation of alcohols by NaOCl can be effected under a variety of conditions, and useful yields and selectivities are attainable for conversion of primary alcohols to aldehydes or carboxylic acids, or of secondary alcohols to ketones. The advantages of NaOCl oxidations over methods that employ stoichiometric CrVI include simplified waste disposal and lower toxicity and cost. The earliest application of NaOCl as a practical synthetic reagent for alcohol oxidation involved its use in a two-phase system with a phase-transfer catalyst,16 or in association with Ruthenium(VIII) Oxide.17 More recently, two improved methods for bleach-mediated oxidation of alcohols have been developed, one of which employs acetic acid as solvent in a monophasic system,18 and the other uses catalytic amounts of 2,2,6,6-Tetramethylpiperidin-1-oxyl (TEMPO) in a buffered biphasic medium.2b These variants are highly complementary and can offer significant advantages over alternative methods for alcohol oxidation.

Secondary alcohols are cleanly oxidized to ketones with NaOCl in acetic acid in the absence of added catalyst (eq 3).18 Either swimming pool chlorine or household laundry bleach can be used with similar success.19 Excess hypochlorite is quenched with sodium bisulfite, and essentially pure ketone is obtained simply by extraction of the product into dichloromethane or ether.

Under these conditions, secondary alcohols can be oxidized in the presence of primary alcohols with essentially absolute selectivity (eq 4).20 No epimerization is observed in the oxidation of alcohols bearing b-stereocenters (eq 5). Kinetic studies have led to the proposal that molecular chlorine is the active oxidant under conditions of low pH such as those employed for these reactions.21

Primary and secondary alcohols can be oxidized by oxoammonium salts;22 hypochlorite oxidation of the reduced nitroxyl radical regenerates the active oxoammonium salt. Thus the nitroxyl radical agent TEMPO can be employed as an alcohol oxidation catalyst, with NaOCl as the stoichiometric oxidant.2b This protocol has rapidly achieved widespread use due to its selectivity, ease of application, and versatility. A biphasic system is employed consisting of CH2Cl2 or toluene as the organic phase, and commercial bleach buffered to pH ~9 with NaHCO3 and containing substoichiometric levels of KBr or NaBr (eq 6).23 Reaction times are longer in the absence of bromide salts, indicating that HOBr is the agent that oxidizes TEMPO to the nitrosonium ion. Without added phase transfer catalyst, primary alcohols are oxidized with excellent selectivity to the corresponding aldehydes.24 High stirring rates (>1000 rpm) help to minimize overoxidation to the carboxylic acid.23 The stereospecificity of TEMPO-catalyzed oxidations of primary alcohols bearing b-stereocenters has been investigated in detail, and it is absolute in all cases reported thus far (eqs 7-9).23,24

Although both primary and secondary alcohols are oxidized with this catalyst system, moderate-to-good selectivity for the primary position is obtained in oxidation of diols (eq 10).25 The diol must have nearly complete solubility in the organic phase for these oxidations to occur cleanly. This selectivity for primary alcohols is in direct contrast with monophasic NaOCl oxidations in acetic acid (see above). Thus, proper choice of reaction conditions allows selective oxidation by NaOCl of either or both the primary or the secondary carbinol in diols.

Molecular chlorine generated from NaOCl appears to have a detrimental effect on the oxidizing power of the N-oxoammonium salt in these reactions.26 A similar protocol to the one described above, but using Sodium Bromite (NaBrO2) in place of NaOCl may be superior in this context. Despite this caveat, there is ample precedent for the successful application of the NaOCl/TEMPO system with a variety of substrates, and the use of commercial bleach solutions has significant practical advantages.

For further discussion of this oxidizing system, see: 2,2,6,6-Tetramethylpiperidin-1-oxyl. See also Dimethyl Sulfoxide-Oxalyl Chloride, Pyridinium Chlorochromate, Pyridinium Dichromate, Potassium Permanganate, Dipyridine Chromium(VI) Oxide, and Tetra-n-propylammonium Perruthenate.

Oxidation of Primary Alcohols to Carboxylic Acids.

Simple incorporation of a tetraalkylammonium chloride phase-transfer catalyst (PTC) to the catalyst recipe outlined above for aldehyde synthesis leads to a useful protocol for oxidation of primary alcohols to the corresponding carboxylic acids (eq 11).2b Similar selectivity for primary alcohols over secondary alcohols is observed as in the absence of PTC.25 This has been exploited in the oxidation of unprotected monosaccharide derivatives to the corresponding uronic acids (eq 12).27

The mildness of the oxidizing medium in TEMPO-catalyzed oxidations by NaOCl is illustrated by the high yield oxidation of (2-hydroxyethyl)spiropentane to the corresponding acid (eq 13).28 Jones oxidation conditions lead to extensive decomposition of the spiropentane residue of the same substrate.

See also: Chromium(VI) Oxide, Potassium Dichromate, Potassium Permanganate, and Oxygen-Platinum Catalyst.

Oxidation of Aldehydes.

Sodium hypochlorite oxidizes aromatic aldehydes to the corresponding acids in the presence of a phase-transfer catalyst.3 Best results are obtained at pH 9-10 with Bu4NHSO4 as phase-transfer catalyst (eq 14). In this pH regime, HOCl is present in significant concentrations, and phase-transfer catalysts are generally not necessary.6a It has been suggested that in this system, however, the phase-transfer catalyst helps to solubilize HOCl in the organic phase through hydrogen bonding.3 Direct oxidation of aliphatic and aromatic aldehydes to the corresponding methyl esters is accomplished with methanol in acetic acid and 1-2 equiv of NaOCl.20 This reaction, which affords esters in moderate-to-good yield, probably proceeds via oxidation of equilibrium concentrations of methyl hemiacetals. Poor results are obtained with electron-rich aromatic aldehydes and unsaturated aldehydes, each of which undergo competitive chlorination.20

See also: Potassium Permanganate, Ozone, and N-Bromosuccinimide.

Epoxidation.

Sodium hypochlorite is an effective, although infrequently utilized, reagent for epoxidation of enones and polycyclic arenes. Careful control of pH is necessary for good yields in these reactions. Polycyclic aromatics can be oxidized to epoxides at pH 8-9 (eq 15).29 Phenanthridine is oxidized to the corresponding lactam, presumably via an oxaziridine intermediate (eq 16), without formation of N-oxide.29 The optimum pH for this reaction is 8-9, and phase transfer catalysts are required.

Enones,4,30 particularly chalcones,31 also react with sodium hypochlorite to form epoxides (eqs 17-19). These reactions generally exhibit a strong dependence on the pH of the aqueous phase; chlorination reactions can be competitive.30a The mechanism for these reactions has been proposed to involve production of the ClO. radical species; this proposal was made on the basis of data from the chlorination of hydrocarbons, selectivity of epoxidation reactions, and Hammett ρ values for the chlorination of toluene.32

See also: Sodium Hypochlorite-N,N-Bis(3,5-di-t-butylsalicylidene)-1,2-cyclohexanediaminomanganese(III) Chloride, Hydrogen Peroxide, t-Butyl Hydroperoxide, and Dimethyldioxirane.

Other Oxidation Reactions.

Several other substrate classes also undergo oxidation reactions with sodium hypochlorite. Diketones may be oxidatively cleaved to give the corresponding diacids (eq 20).33 Oxidation of hydroquinones and catechols34 and oxidative cyclization of phenols (eq 21)8 have also been realized.

Oxidative Degradation.

Treatment of carboxylic acids with sodium hypochlorite can lead to decarboxylation to afford aldehydes with one less carbon atom (eq 22).35 The mechanism of this reaction is likely to involve methylene oxidation to the chloride or the alcohol followed by decarboxylation and oxidation to the aldehyde. This method has primarily been applied to sugar degradation (eq 23).9,36

Reaction with Amines.

Reactions of sodium hypochlorite with amines can yield ketones, cyclization products, or, in the case of amino acids, degradation products. The mechanism of each of these processes involves initial N-chlorination.37 Chlorinated intermediates have been identified spectroscopically, and in some cases isolated, providing access to chlorination products as well. Treatment of aliphatic amines under phase transfer conditions yields ketones or nitriles.15,16a The initial product is the N-chloro imine, with the carbonyl being released upon hydrolytic workup (eq 24).

Reaction of a- or b-amino acids with NaOCl leads to the corresponding aldehyde or methyl ketone containing one less carbon.38 The mechanism postulated for this Strecker-type degradation of amino acids again involves N-chlorination, followed by decarboxylation to yield the imines. Aldehydes and ketones are released by hydrolysis (eq 25).39 This method has been applied to degradation of a-methyl DOPA (eq 26).40

Oxidative Cyclization of Amines.

Treatment of nitro anilines with sodium hypochlorite under alkaline conditions affords benzofuroxans as cyclization products (eq 27).41 Spectroscopic evidence suggests an initial chlorination of the amino group, followed by cyclization. In addition, chlorinated intermediates have been prepared independently and submitted to the reaction conditions to show that cyclization products are formed.37 The cyclization reaction requires addition of base, as azo products are formed at neutral pH. Oxadiazoles (eq 28)42 and chlorodiazirines (eq 29)43 are also formed by oxidative cyclization in moderate-to-good yields. The key intermediate for both of these reactions is also proposed to be an N-chloro imine.

Amine Coupling Reactions.

Hydrazines44 and alkylhydrazines (eq 30)45 are formed by the action of bleach and amines. Azoethanes are toxic, and therefore care should be taken in their production and handling.

Chlorination.

Several types of organic nucleophiles undergo reaction with sodium hypochlorite to afford chlorination products. N-Chlorination of primary and secondary amines is a representative and widely-used example of this reaction class (eq 31).46 Either mono- or dichlorinated products can be obtained selectively through control of the relative stoichiometry of the amine and NaOCl.47 A two-step chlorine-shuttle pathway for the selective chlorination of electron-rich aromatics has been developed which relies on initial N-chlorination with NaOCl.46 Intramolecular cyclization of amines via the Hofmann-Loffler reaction may also be accomplished by effecting the requisite N-halogenation with NaOCl (eq 32).48

Chlorination of indoles (eq 33),7,49 amides, and ureas50 occurs at the nitrogen center, while oximes51 are chlorinated at carbon. Selective chlorination of nicotinic acids (eq 34),52 chromones,53 and polymers54 has also been achieved. Substitution of chlorine for other halides occurs upon treatment of certain aromatic halides with sodium hypochlorite solution.55


1. (a) Chakrabartty, S. K. Oxidation in Organic Chemistry; Trahanovsky, W., Ed.; Academic: New York, 1976; Part C. (b) Mohrig, J. R.; Nienhuis, D. M.; Linck, C. F.; Van Zoeren, C.; Fox, B. G.; Mahaffy, R. G. J. Chem. Educ. 1985, 62, 519. (c) Skarzewski, J.; Siedlecka, R. OPP 1992, 24, 625.
2. (a) Procter, G. COS 1991, 7, 318. (b) Anelli, P. L.; Biffi, C.; Montanari, F.; Quici, S. JOC 1987, 52, 2559.
3. Abramovici, S.; Neumann, R.; Sasson, Y. J. Mol. Catal. 1985, 29, 291.
4. Marmor, S. JOC 1963, 28, 250.
5. Lee, G. A.; Freedman, H. H. TL 1976, 1641.
6. (a) Banfi, S.; Montanari, F.; Quici, S. JOC 1989, 54, 1850. (b) Balavoine, G.; Eskenazi, C.; Meunier, F. J. Mol. Catal. 1985, 30, 125.
7. De Rosa, M. CC 1975, 482.
8. Tsuge, O.; Watanabe, H.; Kanemasa, S. CL 1984, 1415.
9. Whistler, R. L.; Yagi, K. JOC 1964, 26, 1050.
10. Lolthoff, I. M.; Belcher, R. Volumetric Analysis; Interscience: New York, 1957; p 262.
11. Lieu, V. T.; Kalbus, G. E. J. Chem. Educ. 1988, 65, 184.
12. (a) Sanfourche, M.; Gardent, L. BSF 1924, 35, 1088. (b) Adams, R. A.; Brown, B. K. OSC 1932, 1, 309.
13. Robertson, P. M.; Oberlin, R.; Ibl, N. Electrochim. Acta 1981, 26, 941.
14. The Merck Index, 11th ed.; Budavari, S., Ed.; Merck: Rahway, NJ, 1989; p 1363.
15. Lee, G. A.; Freedman, H. H. Isr. J. Chem. 1988, 26, 229.
16. (a) Lee, G. A.; Freedman, H. H. TL 1976, 1641. (b) Regen, S. L. JOC 1977, 42, 875.
17. Wolfe, S.; Hasan, S. K.; Campbell, J. R. CC 1970, 1420.
18. Stevens, R. V.; Chapman, K. T.; Weller, H. N. JOC 1980, 45, 2030.
19. Perkins, R. A.; Chau, F. J. Chem. Educ. 1982, 59, 981.
20. Stevens, R. V.; Chapman, K. T.; Stubbs, C. A.; Tam, W. W.; Albizati, K. F. TL 1982, 23, 4647.
21. Kudesia, V. P.; Mukherjee, S. K. IJC(A) 1977, 15A, 513.
22. Yamaguchi, M.; Takata, T.; Endo, T. JOC 1990, 55, 1490.
23. Leanna, M. R.; Sowin, T. J.; Morton, H. E. TL 1992, 33, 5029.
24. Anelli, P. L.; Montanari, F.; Quici, S. OS 1991, 69, 212.
25. (a) Anelli, P. L.; Banfi, S.; Montanari, F.; Quici, S. JOC 1989, 54, 2970. (b) Siedlecka, R.; Skarzewski, J.; Mlochowski, J. TL 1990, 2177.
26. Inokuchi, T.; Matsumoto, S.; Nishiyama, T.; Torii, S. JOC 1990, 55, 462.
27. Davis, N. J.; Flitsch, S. L. TL 1993, 34, 1181.
28. Russo, J. M.; Price, W. A. JOC 1993, 58, 3589.
29. Krishnan, S.; Kuhn, D. G.; Hamilton, G. A. JACS 1977, 99, 8121.
30. (a) Wellman, G. R.; Lam, B.; Anderson, E. L.; White, V. E. S 1976, 547. (b) Jakubowski, A. A.; Guziec, F. S., Jr.; Tishler, M. TL 1977, 2399.
31. Arcoria, A.; Ballistreri, F. P.; Contone, A.; Musumarra, G.; Tripolone, M. G 1980, 110, 267.
32. Fonouni, H. E.; Krishnan, S.; Kuhn, D. G.; Hamilton, G. A. JACS 1983, 105, 7672.
33. (a) Corey, E. J.; Pearce, H. L. JACS 1979, 101, 5841. (b) Neiswender, D. D.; Moniz, W. B.; Dixon, J. A. JACS 1960, 82, 2876.
34. Ishii, F.; Kishi, K. S 1980, 706.
35. Kaberia, F.; Vickery, B. CC 1978, 459.
36. (a) Weerman, R. A. RTC 1917, 37, 16. (b) Whistler, R. L.; Schweiger, R. JACS 1959, 81, 5190.
37. Dyall, L. K. AJC 1984, 37, 2013.
38. (a) Langheld, K. CB 1909, 392. (b) Birkofer, L.; Brune, R. CB 1957, 90, 2536.
39. Schonberg, A.; Moubacher, R. CR 1952, 52, 281.
40. Fox, S. W.; Bullock, M. W. JACS 1951, 73, 2754.
41. (a) Green, A. G.; Rowe, F. JCS 1912, 101, 2443, 2452. (b) Mallory, F. B. OSC 1963, 4, 74. (c) Mallory, F. B.; Varimbi, S. P. JOC 1963, 28, 1656. (d) Mallory, F. B.; Wood, C. S.; Hurwitz, B. M. JOC 1964, 29, 2605.
42. Götz, N.; Zeeh, B. S 1976, 268.
43. (a) Graham, W. H. JACS 1965, 87, 4396. (b) Berneth, H.; Hünig, S. CB 1980, 113, 2040.
44. Boido, V.; Edwards, O. E. CJC 1971, 49, 2664.
45. Ohme, R.; Preleschhof, H.; Heyne, H.-U. OSC 1988, 6, 78.
46. Lindsay Smith, J. R.; McKeer, L. C.; Taylor, J. M. OS 1988, 67, 222.
47. (a) Kovacic, P.; Lowery, M. K.; Field, K. W. CRV 1970, 70, 639. (b) Gilchrist, T. L. COS 1991, 7, Chapter 6.1.
48. (a) Kerwin, J. F.; Wolff, M. E.; Owings, F. F.; Lewis, B. B.; Blank, B.; Magnani, A.; Karash, C.; Georgian, V. JOC 1962, 27, 3628. (b) Wolff, M. E. CRV 1963, 63, 55. (c) Stella, L. AG(E) 1983, 22, 337.
49. De Rosa, M.; Carbognani, L.; Febres, A. JOC 1981, 46, 2054.
50. Bachand, C.; Driguez, H.; Paton, J. M.; Touchard, D.; Lessard, J. JOC 1974, 39, 3136.
51. Coda, A. C.; Tacconi, G. G 1984, 114, 131.
52. Elliot, M. L.; Goddard, C. J. SC 1989, 19, 1505.
53. Nohara, A.; Ukawa, K.; Sanno, Y. TL 1973, 1999.
54. Jones, R. G.; Matsubayashi, Y. Polymer 1992, 33, 1069.
55. (a) Bayraktaroglu, T. O.; Gooding, M. A.; Khatib, S. F.; Lee, H.; Hourouma, M.; Landolt, R. G. JOC 1993, 58, 1264. (b) Arnold, J. T.; Bayraktaroglu, T. O.; Brown, R. G.; Heiermann, C. R.; Magnus, W. W.; Ohman, A. B.; Landolt, R. G. JOC 1992, 57, 391.

Jennifer M. Galvin

University of Illinois, Urbana, IL, USA

Eric N. Jacobsen

Harvard University, Cambridge, MA, USA



Copyright 1995-2000 by John Wiley & Sons, Ltd. All rights reserved.