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Introduction to the Reactions of Enols and Enolates

α-Halogenation of CH-acidic Compounds

If enolizable carbonyl compounds are treated with iodine, bromine, or chlorine, halogenation of the α carbon occurs. Halogenation yields different products depending on whether the reaction conditions are acidic or basic.

Acid-catalyzed α-halogenation

Acid-catalyzed α-halogenation leads to the exchange of only one α hydrogen for a halogen even if the α carbon carries additional hydrogens. In the initial reaction step, the enol nucleophilically attacks the halogen molecule. As a result, the halogen molecule is heterolytically cleaved and a single bond between the α carbon and a halogen atom is formed. That is, the reaction step yields a halide anion, as well as a protonated and, thus, positively charged α-halocarbonyl compound. Deprotonation results in the formation of the α-halocarbonyl compound. Under acidic conditions, the enol is continually supplied through keto-enol tautomerism.

Fig.1
Acid-catalyzed α-halogenation.

Enolization, which supplies the nucleophile, is the rate-determining step of the reaction. Thus, the reaction rate does not depend on the halogen's concentration. However, in the reaction product, the α-halocarbonyl compound, the electron density of the carbonyl carbon is reduced by the electron-withdrawing effect of the halogen. As a result, protonation of the carbonyl carbon and, thus, enolization is considerably retarded. Consequently, under acidic conditions, the reaction rate of a second halogenation is much lower than that of the first halogenation. Therefore, halogenation of carbonyl compounds under acidic conditions yields monohalogenated α-halocarbonyl compounds.

Fig.2
Destabilization of protonated α-halocarbonyl compounds.

Due to the electron-withdrawing effect of the halogen atom, protonated α-halocarbonyl compounds are less stable than protonated carbonyl compounds. As a result, protonation of α-halocarbonyl compounds can proceed only very slowly.

Base-catalyzed α-halogenation

If halogenation is carried out under basic conditions with a halogen excess, all α hydrogens are exchanged for a halogen atom.

Fig.3
Base-catalyzed α-halogenation.

Under basic conditions, the halogen atom's electron-withdrawing effect promotes a second α deprotonation and, thus, the enolization, as the α hydrogen acidity has increased. As a result, all α hydrogens are exchanged for a halogen atom under basic conditions. If, for instance, methyl phenyl ketone is halogenated under basic conditions, trihalomethyl phenyl ketone is obtained. However, the trihalomethyl group is a good leaving group. Halogenation of methyl ketones under basic conditions is, therefore, usually followed by haloform reaction!

Fig.4
Promotion of enolization.

Due to the electron-withdrawing effect of the halogen atom, deprotonated α-halocarbonyl compounds are more stable than deprotonated carbonyl compounds. As a result, deprotonation of α-halocarbonyl compounds proceeds more rapidly than that of carbonyl compounds.

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