Ketones, halogenation bromination

In spite of these rationali2ations, the stereochemistry of ketone halogenation retains some puzzling features. For example, the effect of a 2-methyl substituent on the direction of bromination at C-2 is unexpected. 

Bromination of the methyl group can be restricted to monosubstitution when the reaction is carried out in acidic media. The mechanism involves protonation of the carbonyl-oxygen, followed by proton loss to give the enol. After monobromination, protonation of the bromoketone is less favourable owing to the presence of the electron-withdrawing halogen atom. Further enolisation does not occur therefore and halogenation ceases (contrast the behaviour of methyl ketones on bromination under alkaline conditions, p. 667) the product is an aryl bromomethyl ketone or phenacyl bromide. 

The treatment of methyl ketones with bromine or chlorine in acidic aqueous medium in the presence of visible light leads to the formation of halogen methyl ketones (Fig. 19). Since some of our coenzyme analogues had... 

We recall that chlorine and bromine are deactivating groups in electrophilic aromatic substitution because they withdraw electron density by an inductive effect but are ineffective in the donation of electron density by resonance. The same features are important in controlling the rate of the second step of ketone halogenation. The bromine atom withdraws electron density from the carbonyl carbon atom, making the carbonyl oxygen atom less basic. Therefore, the enol forms more slowly in the second step. 

Rates of enolization can be measured in several wt s. One method involves determining the rate of halogenation of the ketone. In the presence of a sufficient concentration of bromine or iodine, halogenation is much faster than enolu ation or its reverse and can therefore serve to measure the rate of enolization ... 

Enolization is the rate-determining step in the halogenation of normal ketones. Where alternate directions for enolization exist, the preferred direction (and hence the position of kinetic bromination) depends on the substituents and stereochemistry. Furthermore, the orientation of the bromine introduced depends on stereochemical and stereoelectronic factors. 

A commonly used alternative to the direct bromination of ketones is the halogenation of enol acetates. This can be carried out under basic conditions if necessary. Sodium acetate, pyridine or an epoxide is usually added to buffer the reaction mixture. The direction of enolization is again dependent upon considerations of thermodynamic and kinetic control therefore, the proportion of enol acetates formed can vary markedly with the reaction conditions. Furthermore, halogenation via enol acetates does not necessarily give the same products as direct halogenation of ketones 3. 23... 

Bromination with A-bromosuccinimide generally gives the same result as bromination with free bromine or hypobromous acid. The reaction is considered to proceed with a small concentration of free bromine and does not generate an appreciable concentration of acid. Conditions are therefore mild. In addition, A-bromosuccinimide has been used to brominate the allylic position of a, -unsaturated ketones in the presence of free-radical promoters or with irradiation, and thus gives access to dienones by dehydro-halogenation, for exaraple " ... 

As in the acid-catalyzed halogenation of aldehydes and ketones, the reaction rate is independent of the concentration of the halogen chlorination, bromination, and iodination all occur at the same rate. Fomnation of the enolate is rate-detemnining, and, once fomned, the enolate ion reacts rapidly with the halogen. 

Methyl ketones 1, as well as acetaldehyde, are cleaved into a carboxylate anion 2 and a trihalomethane 3 (a haloform) by the Haloform reaction The respective halogen can be chlorine, bromine or iodine. 

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