[7790-9-3] · ClHO · Hypochlorous Acid · (MW 52.46)
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.
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.
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
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.
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).
Paul C. Unangst
Parke-Davis Pharmaceutical Research, Ann Arbor, MI, USA