Halogenation, of enols and enolates

As m the acid catalyzed halogenation of aldehydes and ketones the reaction rate is mde pendent of the concentration of the halogen chlorination brommation and lodmation all occur at the same rate Formation of the enolate is rate determining and once formed the enolate ion reacts rapidly with the halogen... 

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... 

Rate coefficients (eqn 36) for the halogenation of enols, enol ethers and enolate ions in aqueous media at 25°C... 

Halogenation of enol ethers and enol esters, leading directly to a-halo ketones is realized by use of molecular halogen or halide salts and metal oxidants. Pyridinium chlorochromate (PCC)/l2, Cr03/TMS-Cl/l2, AgOAcfi2, T10Ac/l2. ° Pb(OAc)4 and metal halides and Cu(OAc)2/l2 are useful classes of reagents for this conversion, and some examples are listed in Table 1. 

Table 1 Halogenation of Enol Ethers and Esters with Metallic Reagents...

Halogenation of aldehydes and koUmes fiocura under boch baaic and conditions. As you naight cxpc ct, the base-promoted reaction occurs t1 an enolate ion intermediate. Even relatively weak bases such as hvdi ion are effective for halo nntion because it s not necessary to convert ketone completely into its enolate too. As soon as a. small amount of eoo late is generated, it reacts immediately with the halogen. 

A variety of methods are available for the halogenation of aldehydes and ketones, and rely on the ease of enolization of such compounds. Copper(II) chloride or bromide in ethyl acetate at reflux have been shown to be effective reagents and rely on the promotion of enolization by the copper ion prior to the transfer of halogen. Since these conditions tend to favor the thermodynanuc enol, unsymmetrical ketones preferentially halogenate at the more highly substituted a-carbon atom. Similar selectivity is observed withNBS. O- ... 

Halo acetals have been prepared by the action of alcohol on halo ketones and halo aldehydes.An indirect application of this reaction consists in the halogenation of enol acetates with subsequent reaction of the brominated products with alcohols to give the halo acetals. ... 

Base-promoted halogenation of aldehydes and ketones is little used ir, practice because it s difficult to stop the reaction at the monosubstituted product. An a-halogenated ketone is generally more acidic than the star jng, unsubstituted ketone because of the electron-withdrawing inductiv eflect of the halogen atom. Thus, monohaiogenated products are themselvi. rapidly turned into enolate ions and further halogcnated. 

Other synthetically useful reactions are allylic amination using TsN=Se=NTs and TsN=S=NTs/ photolysis of a/S-unsaturated ketones in the presence of U02Cl2-methanol [e.g. to give (6) cf. Vol. 6, p. 10], " halogenation of enol silyl ethers/ terminal double bond (e.g. geranyl cyanide, carvone) bromination with (7)... 

Aldehyde, Ketone, and Ester Enolates 867 Enolate Regiochemistry 872 The Aldol Condensation 873 Mixed Aldol Condensations 878 Chalcones From the Mulberry Tree to Cancer Chemotherapy 880 The Claisen Condensation 882 Intramolecular Claisen Condensation The Dieckmann Cyclization 884 Mixed Claisen Condensations 885 Acylation of Ketones with Esters 886 Alkylation of Enolates 887 The Acetoacetic Ester Synthesis 889 The Malonic Ester Synthesis 891 Alkylation of Chiral Enolates 893 Enolization and Enol Content 895 a Halogenation of Aldehydes and Ketones 900... 

Lapworth reasoned that an enol was a reactive intermediate, that its formation was ratedetermining, and that the halogen didn t participate until after the rate-determining step. These early studies provided the basis for the generally accepted mechanism for the a-halogenation of aldehydes and ketones. 

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