Pyridinium Hydrobromide Perbromide1

[39416-48-3]  · C5H6Br3N  · Pyridinium Hydrobromide Perbromide  · (MW 319.86)

(selective brominating reagent for ketones,2 acetals,3 alkenes,4 activated phenols,5 anilines,6 and nitrogen heterocycles;7 mild oxidation/dehydrogenation reagent8)

Alternate Names: PHBP; pyridinium bromide perbromide; pyridinium perbromide; pyridinium tribromide.

Physical Data: mp 101-103 °C (39.7% Br), mp 132-134 °C (47% Br),7 135 °C (50% Br).9

Solubility: sol acetic acid, methanol, ethanol, n-butanol, THF, ether (wet); insol water, carbon tetrachloride, ethyl bromide, ether (anhydrous), benzene, toluene, ligroin, petroleum ether.9

Form Supplied in: red-orange solid, generally 90-97% pure; commercially available.

Analysis of Reagent Purity: iodometric titration.10

Preparative Method: from pyridine, 48% hydrobromic acid, and bromine.1,7 The bromine content varies depending on the method of preparation.7,11

Purification: recrystallization from ethanol.12 Recrystallization from acetic acid reduces the bromine content. Pure material can be obtained by adding bromine to impure material until a paste is produced. Excess bromine is allowed to evaporate, giving pure material, mp 135 °C (50% Br).9

Handling, Storage, and Precautions: protect from moisture, strong acids, and bases. This toxic reagent must be used in a fume hood.

Introduction.

Pyridinium hydrobromide perbromide is a solid complex of Pyridine with bromine that is used as a source of Bromine. It is more convenient to measure small amounts of active bromine with this stable reagent than with bromine itself. Its mild reactivity makes it ideal for selective brominations and dehydrogenations of sensitive molecules.1

a-Bromination of Ketones.

PHBP has been used to a-brominate steroid keto groups in good yields with high stereoselectivity.2,13 Flavinones react with PHBP giving a-brominated products.14 Tetrahydroindoles also react with PHBP (eq 1); however, better yields were obtained for this transformation with Copper(II) Bromide.15 PHBP reacts with cyclohexanones in Acetic Acid to give equatorially substituted a-bromocyclohexanones. In contrast, bromine in carbon tetrachloride gives mostly axial products.16 The cyclopentenone shown in eq 2 was successfully brominated with PHBP when an equivalent of pyridine was present.17 Phenyltrimethylammonium Perbromide is reported to give better yields of monobrominated ketones.18

a-Bromination of Acetals.

PHBP reacts with acetals to give good yields of their a-brominated derivatives.3 With chiral acetals, different ratios of stereoisomers can result when the solvent or the brominating agent are changed (eq 3).19

Phenyltrimethylammonium perbromide is a comparable acetal bromination reagent which has better solubility in THF at low temperatures.20 Acetals of benzophenone derivatives are more effectively brominated with Bromine-1,4-Dioxane rather than PHBP.21

Bromination of Alkenes.

PHBP readily adds in an anti fashion to carbon-carbon double bonds to give predominantly one stereoisomer.4 Studies of PHBP addition to cyclohexenes show that diaxial products are favored over diequatorial ones.22 There is a preference for 1,2- rather than 1,4-addition with conjugated dienes.23 Enones react with PHBP in methanol to give anti-Markovnikov addition products.24 Unlike bromine, this reagent adds to the double bond of unsaturated alcohols without brominating the alcohol.25 Alkenes can be protected by generating their dibromides with PHBP. Deprotection using controlled-potential electrolysis or cathodic debromination regenerates the alkenes.26

Bromination of Aromatic Compounds.

The reduced reactivity of PHBP is ideal for monobrominating activated aromatic ethers and phenols such as pyrogallol.5,27 A kinetic study of the reaction of phenols with PHBP has been reported.28 Anilines are selectively monobrominated with mostly para substitution in 75-95% yield.6 PHBP has been used for the analytical detection of phenols30 and anilines.31 Bromine-dioxane is a comparable reagent for brominating phenols. [18]Annulene has been monobrominated with PHBP in 44% yield.29

Heating PHBP to 230 °C affords 3-bromopyridine (37%) and 3,5-dibromopyridine (33%).7 In contrast, indoles,32 imidazoles,33 phenothiazines,34 and azathiabenzenes35 are readily monobrominated with PHBP at rt or at lower temperatures.

Dehydrogenations/Oxidations.

PHBP is a convenient reagent for conversion of cyclohexenones to phenols in steroids,8 tricyclic diterpenoids (eq 4),36 and other polycyclic compounds.37

Combination oxidation-brominations have been reported to occur using PHBP in conjunction with t-butyl alcohol (eq 5).38 Enediol silyl ethers are converted to 1,2-diones with PHBP (eq 6).39 Oxidations of phosphinic and phosphonic acids are reported to be first order in both the oxyacid and PHBP.40 Phosphites are oxidized to phosphates in the presence of alcohols and PHBP.41

Kinetic and mechanistic studies on the oxidation of primary alcohols by PHBP have been reported;10 however, many other more selective reagents are commonly used to oxidize alcohols (e.g. see Jones reagent (see Chromic Acid), Manganese Dioxide, Pyridinium Dichromate, etc.).

Bromination of Organometallic Compounds.

PHBP is an effective bromination reagent for compounds that are highly sensitive or prone to decomposition. If bromine is substituted for PHBP in eq 7, the nickel-cyclobutadiene complex decomposes.42 Good yields are obtained when bromine from PHBP displaces an aryl group from the bismuth compound of eq 8.43 Studies of brominations of metal chelates of b-diketones and b-keto esters have been described.44

Other Applications.

PHBP has been used to prepare alkyl bromides from alcohols.45 It is also effective in phase transfer nitrosation of amines.46 Thioacetals are oxidized in 78-91% yield to ketones and aldehydes with PHBP under phase transfer conditions.47 Dihydropyridines have been heated with PHBP to afford lactones via the postulated bromomethyl intermediate shown in eq 9.48 This intermediate is stable at low temperatures and can be reacted with nucleophiles to give varying yields of substituted dihydropyridines.49 PHBP has also been used to monobrominate active methylene groups.50


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M. P. Moon

DuPont Agricultural Products, Newark, DE, USA



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