Hypobromous Acid

HOBr

[13517-11-8]  · BrHO  · Hypobromous Acid  · (MW 96.91)

(preparation of bromohydrins5,8,12 by addition to alkenes; brominating reagent3 and oxidant4)

Solubility: sol H2O, H2O-DMSO, H2O-acetone, H2O-dioxane, H2O-DME.

Form Supplied in: stable only in solution;1,2 usually prepared in situ immediately before use.

Preparative Methods: traditional preparative methods2-4 are the addition of Bromine to aqueous mixtures of mercury or silver salts to precipitate the bromide ion formed as a byproduct. Newer methods employ a source of positive bromine such as N-Bromosuccinimide,5-7 N-Bromoacetamide,8,9 or 1,3-Dibromo-5,5-dimethylhydantoin (dibromantin)10 to generate the equivalent to HOBr in aqueous solution.

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

Bromohydrin Synthesis.

The title reagent (1) usually adds to unhindered alkenes following Markovnikov's rule, in which the initial electrophilic adduct is a bromonium ion (eqs 1 and 2).5,11 The resulting carbocation or bridged bromonium ion then reacts with hydroxide or water to yield the product bromohydrin.8 Reactions are generally run in water or solutions of water and DMSO, acetone, or dioxane at 0-25 °C, although aqueous DME at -20 °C has also been employed (eqs 1 and 2).7 Reactions run in moist DMSO generate bromohydrins in a regiospecific and stereospecific fashion with a minimum of rearrangement.12 The role of the solvent in the reaction has been demonstrated by radiolabeling.5

Participation by a neighboring functional group may influence the regioselectivity of HOBr addition.6,7,9 Oxime-assisted bromonium ion reaction has been invoked in the formation of a bromohydrin intermediate to the neurotoxin (±)-perhydrohistrionicotoxin (eq 3).7 Similarly, participation by the 7-acetoxy group results in a single bromohydrin product in the addition of HOBr to a cholestane derivative (eq 4).9

Oxidation and Bromination.

The title reagent has been employed in the oxidation of a thiazole thiourea to a thiazolo[3,2-b]thiadiazoline (eq 5).4 Reaction of HOBr with a variety of aryl methyl ketones yields ring-brominated products in a rapid reaction at rt.3

Related Reagents.

Hypochlorous Acid is utilized as an oxidant and for the preparation of chlorohydrins in a manner analogous to that of (1).


1. Cotton, F. A.; Wilkinson, G. Advanced Inorganic Chemistry, 5th ed.; Wiley: New York, 1988; pp 563-567.
2. Roedig, A. MOC 1960, V/4, 20.
3. Broxton, T. J.; Deady, L. W.; McCormack, J. D.; Kam, L. C.; Toh, S. H. JCS(P1) 1974, 1769.
4. Nagano, M.; Oshige, M.; Kinoshita, T.; Matsui, T.; Tobitsuka, J.; Oyamada, K. CPB 1973, 21, 2408.
5. Dalton, D. R.; Dutta, V. P.; Jones, D. C. JACS 1968, 90, 5498.
6. Morand, P.; Polakova-Paquet, A. CJC 1973, 51, 4098.
7. Corey, E. J.; Petrzilka, M.; Ueda, Y. TL 1975, 4343.
8. Marples, B. A.; Saint, C. G. SC 1982, 12, 545.
9. Kocovsky, P.; Stary, I.; Zajicek, J.; Turecek, F.; Vasickova, S. JCS(P1) 1988, 2297.
10. Kirby, G. W.; Mackinnon, J. W. M.; Elliot, S.; Uff, B. C. JCS(P1) 1979, 1298.
11. Erickson, K. L.; Kim, K. JOC 1971, 36, 2915.
12. Dalton, D. R.; Dutta, V. P. JCS(B) 1971, 85.

Paul C. Unangst

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



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