Hydrogen Bromide1

HBr

[10035-10-6]  · BrH  · Hydrogen Bromide  · (MW 80.91)

(reagent for electrophilic5 and radical-mediated1b hydrobromination of alkenes and alkynes; cleaves epoxides1c and ethers;20 converts alcohols13 and chlorides32 to bromides; converts a-diazo ketones to a-bromomethyl ketones,28a and 1,4-cyclohexanediones to phenols29)

Alternate Name: Hydrobromic Acid

Solubility: sol most organic solvents.2

Form Supplied in: widely available as compressed gas; 30% solution in AcOH or EtCO2H; 48% aqueous solution.

Preparative Methods: can be generated in situ by treatment of refluxing tetrahydronaphthalene with Br2;3 treatment of Ph3PHBr with refluxing xylene.4

Handling, Storage, and Precautions: highly toxic and corrosive. This reagent should be handled in a fume hood.

Hydrobromination of Alkenes and Alkynes.

HBr undergoes addition readily to most alkenes and alkynes.1a However, radical and ionic addition usually compete, affording a mixture of products unless the system is symmetrically substituted (eq 1).5

Radical addition can be facilitated by light, peroxides, and other radical-generating systems.1b Limiting reaction to ionic addition is more challenging, requiring the rigorous absence of light, oxygen, and peroxide impurities, along with the use of a radical inhibitor.6 Ionic addition to alkenes without competing radical reaction can also be effected with aqueous HBr at 115 °C and a phase-transfer catalyst (eq 2).7

More conveniently, competing radical reaction can be avoided by conducting the addition in the presence of appropriately prepared silica gel or alumina, which also accelerates the rate of ionic addition.5,8 Addition is rendered even more convenient by the use of various inorganic and organic acid bromides that undergo reaction with silica gel or alumina to afford HBr in situ (eq 3).5

Surface-mediated hydrobromination of phenylalkynes initially affords the syn adducts, which undergo subsequent equilibration with the thermodynamically more stable (Z) isomers (eq 4).5 Thus either isomer can be obtained in high yield by the appropriate choice of reaction conditions. Surface-mediated hydrobromination of terminal alkylalkynes affords the corresponding 2-bromo-1-alkenes in good yield (eq 5).5 Several other methods had previously been developed for this difficult transformation.9

Cleavage of Epoxides to Bromohydrins.

The addition of HBr to epoxides to give bromohydrins proceeds readily with either 48% aqueous HBr or anhydrous HBr in a variety of organic solvents.1c,10 The stereoselectivity generally parallels that of HCl additions (see Hydrogen Chloride), and is similarly affected by changes in solvent and substitution. Typically, ring opening of unsymmetrical epoxides favors formation of the bromohydrin in which bromine is at the less highly substituted position. This preference is greater for HBr than HCl additions because of the greater size and nucleophilicity of the bromide ion.1c,11

Reaction with Alcohols.

The reaction of HBr with alcohols to form alkyl bromides is a general, high-yield reaction that can be effected under a variety of conditions. The conversion of primary and secondary alkyl alcohols to the corresponding bromides with anhydrous HBr requires elevated temperatures (100 °C),12 but benzylic and allylic alcohols are reactive in CHCl3 solution at 25 °C.13 Alcohols are also converted to alkyl bromides at elevated temperatures with 48% aqueous HBr.14 Alcohols resistant to substitution under these conditions are often reactive in the presence of H2SO4 as a catalyst.12,15 The use of phase-transfer catalysts has little effect on the rate of the reaction, but has been found to reduce significantly the extent of skeletal rearrangement that often accompanies substitution (eq 6).16 Tertiary bromides can be synthesized from the corresponding alcohols under especially mild conditions in the presence of Lithium Bromide.17

Vicinal diols, when treated with 48% aqueous HBr in AcOH, give 2-bromo acetates with good regio- and stereoselectivity (eq 7).18 In the absence of AcOH, some diols are dehydrated to give dienes.19

A series of bis(benzylic) diols has been converted to 2,3-disubstituted indenes with HBr in good yields (eq 8), whereas reactions with other hydrogen halides followed a different course.20 This method failed for the synthesis of monoalkyl indenes but was satisfactory for the synthesis of monoaryl systems.

Cleavage Reactions.

The cleavage of ethers by HBr is a synthetically useful method for the synthesis of alkyl bromides and for the deprotection of phenols.21 Dialkyl ethers are cleaved with 48% aqueous HBr at elevated temperatures in the presence of H2SO422 or a phase-transfer catalyst.23 Under these conditions, most dialkyl ethers give high yields (90-95%) of alkyl bromides, while alkyl aryl ethers give phenols (90%) and alkyl bromides (90%). Aryl methyl ethers are readily cleaved with the use of 48% aqueous HBr to give the phenol and MeBr.24 The cleavage of cyclic lactones by HBr, in a manner analogous to the cleavage of ethers, has also been reported.25 When triphenylphosphonium bromide is used as an in situ source of HBr, methyl, ethyl, and benzyl ethers are cleaved at elevated temperatures to give alkene products in good yield along with a tetrasubstituted phosphonium salt (eq 9).26 Similarly, aryl alkyl ethers are converted to phenols, and benzyl and methyl esters to carboxylic acids.

AcOH and CF3CO2H solutions of HBr efficiently cleave benzyloxycarbonyl groups from protected peptides.27 Anhydrous HBr selectively cleaves alkyl groups from aryl amines.28 Thus dialkyl-substituted anilines were converted to monoalkyl-substituted anilines at 150 °C, and monoalkyl anilines converted to aniline at 195 °C. This method is not useful for cleavage of trialkyl amines.

Synthesis of a-Bromo Ketones.

a-Diazo ketones are converted to a-bromomethyl ketones by either anhydrous HBr in Et2O or 48% aqueous HBr in various solvents (eq 10).29 This is a useful, high-yield, method for the regiospecific conversion of a carboxylic acid to the corresponding bromomethyl ketone, since the required a-diazo ketone is readily synthesized from reaction of the corresponding acid chloride with Diazomethane.

Reductions with HBr.

HBr has been used as a reagent for the reduction of 1,4-cyclohexanediones to phenols,30 as well as for the cyclization and aromatization of a variety of carbonyl-substituted arenes (eq 11).31

Although HBr generally reduces aryl sulfoxides, its uses are limited due to ensuing bromination of the aryl ring.32

Miscellaneous Reactions.

Alkyl chlorides, which are generally more readily available than alkyl bromides, are converted into the corresponding bromides by anhydrous HBr in the presence of catalytic amounts of FeBr3.33 Secondary, tertiary, and allylic bromides are formed in high yields from the corresponding chlorides, while primary systems undergo extensive cationic rearrangement. Alkyl iodides have been converted into the corresponding bromides with 42% HBr in the presence of HNO3.34

Several arylamines have been brominated at the ortho position by HBr in DMSO.35 Since removal of the amine functionality is possible in good yield, this provides a regiospecific method of arene bromination.

HBr reacts with aldehydes in the presence of arenes to give bromoalkylated products36 and in the presence of alcohols to give a-bromomethyl ethers in good yields (eq 12).37

Addition of anhydrous HBr to a,b-unsaturated aldehydes or ketones, followed by acetalization, readily affords b-bromoacetals (eq 13).38

Related Reagents.

Formaldehyde-Hydrogen Bromide; Hydrobromic Acid.


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Gary W. Breton & Paul J. Kropp

University of North Carolina, Chapel Hill, NC, USA



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