Pyridinium perbromide

Under carefully controlled conditions the selective mono bromination of an electronically diverse range of acetophenone derivatives can be realized using the polymer-supported pyridinium perbromide reagent. The resultant a-bromoketone... 

The association between acetylcholine levels and Alzheimer s disease, as noted more than once previously, has led to the search for novel compounds that raise the level of that neurotransmitter by inhibiting acetylcholinesterase, the agent of its inactivation. The benzisoxazole icopezil (60-8) has undergone several trials against that debilitating disease as a result of selective chohnesterase inhibiting activity in the CNS. Friedel-Crafts acylation of the indolone (60-1) with acetyl chloride affords the methyl ketone (60-2). This is then converted to its oxime and that function acylated with acetic anhydride to yield (60-3). Treatment with pyridinium perbromide... 

Other highly regioselective brominating reagents are chlorotrimethylsilane/lith-ium bromide and hexamethyldisilane/pyridinium perbromide.88 An outline mechanism of the former reaction is formulated below and a preparative example is given in Expt 5.56. 

In an alternative methodology, 4- and 6-substituted-2-oxindoles, obtained from o-nitroarylmalonates, were converted to 3,3-dibromooxindoles by reaction with pyridinium perbromide. These intermediates were hydrolyzed to the corresponding isatins. This method, although limited to substrates with moderate to strongly electron withdrawing groups... 

The diene-Br2 complex is again in equilibrium with the reagents, and nucleophilic attack at carbon can be carried out either by the bromide of the ammonium bromide ion pair, formed at the moment of the electrophilic attack, or by the less nucleophilic pyridine added in excess in the reaction medium. It is noteworthy that this mechanism is characterized by a rate- and product-limiting nucleophilic step which should be quite insensitive to steric hindrance around the double bond. In agreement with a weak influence of the steric effects, pyridinium perbromide reacts in chloroform and tetrahydrofuran with substituted conjugated and non-conjugated dienes to give selectively (>95%) bromine addition to the more alkylated double bond (equation 44). 

Pyridine dibromide-HBr (pyridinium perbromide) can be used to mono-brominate polyhydric phenols such as pyrocatechol, pyrogallol, and also aryl ethers at or below room temperature.66-69,453 The solid reagent may be used (for preparation see page 112) alternatively glacial acetic acid containing a known amount of bromine is dropped into a mixture of the phenol or ether with pyridine hydrochloride (prepared by passing dry HC1 into an ethereal solution of pyridine) or with quinoline sulfate. 

An alternative reagent, namely pyridinium perbromide followed by butyllithium treatment has been used for this compound arising at an intermediate stage in a synthesis of the phytoalexin, orchinol. 2-(3,5-Dimethoxypheny0ethanol was converted with methyltriphenoxyphosphonium iodide in 93% yield to the iodide... 

On the other hand, pyridine is a weak base (p/Ta = 5.22) that can be protonated or can form salts with strong protonic acids. Some of the resulting pyridinium salts are commercial reagents. For instance, pyridinium perbromide is used as brominating agent, and pyridinium dichloromate... 

Azulenes are halocienated by jy-bromosuccinimide or iV-chlorosuccinimide [42,47], or by copper(II) bromide or chloride [94], to give mixtures of 1- and 1,3-substituted azulenes. Pyridinium perbromide produces the dibromo derivative [95]. Mono- and di-iodo derivatives have been obtained by reaction with iodine monochloride [95], T -iodosuccinimide [42] or iodine in the presence of copper(II) acetate [94]. Iodine in the presence of sodium iodide reacts with azulene at room temperature to give a good yield of 1-iodoazulene the kinetics of this reaction are comparable to those of a reactive benzene derivative such as aniline [96]. 

Phenyltrimethylammonium perbromide reacts like pyridinium perbromide but is easier to prepare and more stable. It dissolves easily in tetrahydrofuran, in which these reactions are performed. It monobromi-nates selectively ketones and cyclic ketals in a-posi-tion without affecting double bonds and reactive benzene rings.—E 2-Acetyl-6-methoxynaphthalene- 2-(co-bromoacetyl)-6-methoxynaphthalene. Y 80%. 

Pyridine bromide is a useful reagent for halogenation of alkenes and ketones, but both pyridine and bromine are noxious reagents, and the solid pyridinium perbromide complex is dangerous to handle. Poly(vinylpyridine perbromide) (21) quantitatively produces a-bromo ketones from cyclohexanone and propiophenone and is easy to handle. Bromination of (Z)-stilbene and ( )- and (Z)-1-phenylpropene gave 98-100% anti addition, as in equation (2), while bromine in solution yielded dibromophenylpropanes with 25-92% anti addition, depending upon the solvent. 

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