Hypochlorous Acid

HOCl

[7790-9-3]  · ClHO  · Hypochlorous Acid  · (MW 52.46)

(preparation of chlorohydrins6-9 and allylic chlorides5,11 by addition to alkenes; chlorinating reagent4 and oxidant12)

Solubility: sol H2O, Et2O, CH2Cl2.

Form Supplied in: stable only in solution;1,2 usually prepared in situ immediately before use. Most preparations are in water, water-acetone, or water-dioxane solutions under acidic conditions at 0-25 °C. The reagent can also be extracted into ether or other organic solvents for use under nonaqueous reaction conditions.

Analysis of Reagent Purity: standardized by iodometric titration.

Preparative Methods: traditionally prepared3 by addition of Chlorine to a cold aqueous solution of Sodium Hydroxide and Mercury(II) Chloride to generate NaOCl. Careful acidification then liberates HOCl. A more convenient procedure is the use of commercial bleach (stabilized 5.25% Sodium Hypochlorite solution)4 or 70% Calcium Hypochlorite.5 Reagents such as Chloramine-T,6 N-Chlorosuccinimide,7 and chlorourea8 serve as equivalents to HOCl by the production of a positive Cl species in aqueous solution.

Handling, Storage, and Precautions: strong oxidizing agent; use in a fume hood.

Chlorohydrin Synthesis.

The title reagent (1) usually adds to unhindered alkenes following Markovnikov's rule, in which the initial electrophilic adduct is a chloronium ion (eqs 1 and 2).7,8 The resulting carbocation or bridged chloronium ion then reacts with hydroxide or water to yield the product chlorohydrin. In some instances, anti-Markovnikov and dichloride side products are also observed.9 a,b-Unsaturated acids, esters, nitriles, aldehydes, and ketones with an unsubstituted a-hydrogen predominantly add Cl to the a-position and OH to the b-position.

Allylic Chloride Synthesis.

Reaction of (1) with highly substituted alkenes5 or conjugated ketones10 in a two-phase reaction mixture yields allylic chlorides rather than chlorohydrins (eq 3). Other functional groups, such as alcohols, aldehydes, epoxides, ethers, esters, ketones, and nitriles, are generally unaffected. In some cases, a mixture of allylic chloride and vinyl chloride products is obtained. This reaction has been applied to (+)-carvone and (+)-limonene in a synthetic route to various monocyclic sesquiterpenes.11

Oxidation and Chlorination.

The title reagent has been used to oxidize a cyclic acetal in the preparation of optically active a-amino acids (eq 4).12

Oxidation by hypochlorite solutions is used industrially on a large scale for bleaching and sterilization applications.

Aqueous (1) at 25 °C rapidly transforms cyclic oximes into a-chloronitroso derivatives, which are intermediates in the preparation of secondary nitro compounds (eq 5).4 Maintaining a pH of 5.5 in the chlorination medium was found to be critical in this reaction.

Related Reagents.

Hypobromous Acid is utilized as an oxidant for the preparation of bromohydrins in a manner analagous to that of (1). Direct chlorohydroxylation of alkenes can be achieved with t-Butyl Hydroperoxide or 1,1-Di-t-butyl Peroxide and Titanium(IV) Chloride,13 as well as with Chlorotrimethylsilane and 30% Hydrogen Peroxide.14 Since these peroxide reactions probably proceed through an epoxide intermediate, the resulting chlorohydrin is the opposite regioisomer from that obtained by addition of (1).


1. Cotton, F. A.; Wilkinson, G. Advanced Inorganic Chemistry, 5th ed.; Wiley: New York, 1988; pp 563-567.
2. Stroh, R. MOC 1962, V/3, 762.
3. Coleman, G. H.; Johnstone, H. F. OSC 1941, 1, 158.
4. Corey, E. J.; Estreicher, H. TL 1980, 21, 1117.
5. Hegde, S. G.; Vogel, M. K.; Saddler, J.; Hrinyo, T.; Rockwell, N.; Haynes, R.; Oliver, M.; Wolinsky, J. TL 1980, 21, 441.
6. Damin, B.; Garapon, J.; Sillion, B. S 1981, 362.
7. Kirby, G. W.; Tan, S. L.; Uff, B. C. JCS(P1) 1979, 266.
8. Donahoe, H. B.; Vanderwerf, C. A. OSC 1963, 4, 157.
9. Boguslavskaya, L. S. RCR 1972, 41, 740.
10. Hegde, S. G.; Wolinsky, J. TL 1981, 22, 5019.
11. Hegde, S. G.; Wolinsky, J. JOC 1982, 47, 3148.
12. Thiam, M.; Chastrette, F. TL 1990, 31, 1429.
13. Klunder, J. M.; Caron, M.; Uchiyama, M.; Sharpless, K. B. JOC 1985, 50, 912.
14. Ho, T.-L. SC 1979, 9, 37.

Paul C. Unangst

Parke-Davis Pharmaceutical Research, Ann Arbor, MI, USA



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